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Mendeliome v1.231 OTULIN Zornitza Stark Phenotypes for gene: OTULIN were changed from Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099 to Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099; Susceptibility to infection with Staphylococcus aureus; Hereditary predisposition to infections, MONDO:0015979, OTULIN-related
Mendeliome v1.230 OTULIN Zornitza Stark Publications for gene: OTULIN were set to 27523608; 27559085
Mendeliome v1.229 OTULIN Zornitza Stark Mode of inheritance for gene: OTULIN was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.228 OTULIN Zornitza Stark changed review comment from: Autoinflammatory disorder presenting in the newborn period with recurrent fever, erythematous rash with painful nodules, painful joints, diarrhoea and lipodystrophy.; to: Bi-allelic variants: Autoinflammatory disorder presenting in the newborn period with recurrent fever, erythematous rash with painful nodules, painful joints, diarrhoea and lipodystrophy.
Mendeliome v1.228 OTULIN Zornitza Stark edited their review of gene: OTULIN: Added comment: PMID 35587511: Multiple individuals reported with haploinsufficiency of OTULIN and severe staphylococcal disease, with life-threatening skin or pulmonary necrosis. Functional data.; Changed publications: 27523608, 27559085, 35587511; Changed phenotypes: Autoinflammation, panniculitis, and dermatosis syndrome, MIM# 617099, Susceptibility to infection with Staphylococcus aureus, Hereditary predisposition to infections, MONDO:0015979, OTULIN-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phagocyte Defects v1.8 OTULIN Zornitza Stark Marked gene: OTULIN as ready
Phagocyte Defects v1.8 OTULIN Zornitza Stark Gene: otulin has been classified as Green List (High Evidence).
Phagocyte Defects v1.8 OTULIN Zornitza Stark Classified gene: OTULIN as Green List (high evidence)
Phagocyte Defects v1.8 OTULIN Zornitza Stark Gene: otulin has been classified as Green List (High Evidence).
Phagocyte Defects v1.7 OTULIN Zornitza Stark gene: OTULIN was added
gene: OTULIN was added to Phagocyte Defects. Sources: Literature
Mode of inheritance for gene: OTULIN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: OTULIN were set to 35587511
Phenotypes for gene: OTULIN were set to Susceptibility to infection with Staphylococcus aureus; Hereditary predisposition to infections, MONDO:0015979, OTULIN-related
Review for gene: OTULIN was set to GREEN
Added comment: Multiple individuals reported with haploinsufficiency of OTULIN and severe staphylococcal disease, with life-threatening skin or pulmonary necrosis. Functional data.

Note bi-allelic variants case early-onset autoinflammatory condition called OTULIN-related autoinflammatory syndrome (ORAS).
Sources: Literature
Mendeliome v1.228 NOX1 Zornitza Stark gene: NOX1 was added
gene: NOX1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NOX1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: NOX1 were set to 29091079; 32064493
Phenotypes for gene: NOX1 were set to Inflammatory bowel disease, MONDO:0005265, NOX1-related
Review for gene: NOX1 was set to AMBER
Added comment: 8 IBD patients with early onset of IBD with progressive and severe colonic disease, refractory to conventional therapy and functional studies suggesting variant-dependent loss of NOX1-mediated superoxide generation. However, high frequency of nonsynonymous mutations in NOX1 suggests that NOX1 is not a highly penetrant Mendelian disorder and that other genetic modifiers or environmental factors may contribute to disease pathogenesis.

The variant reported in PMID 32064493 is present in 6 hets in gnomad.
Sources: Literature
Inflammatory bowel disease v0.84 NOX1 Zornitza Stark Marked gene: NOX1 as ready
Inflammatory bowel disease v0.84 NOX1 Zornitza Stark Gene: nox1 has been classified as Amber List (Moderate Evidence).
Inflammatory bowel disease v0.84 NOX1 Zornitza Stark Phenotypes for gene: NOX1 were changed from Inflammatory bowel disease to Inflammatory bowel disease, MONDO:0005265, NOX1-related
Inflammatory bowel disease v0.83 NOX1 Zornitza Stark edited their review of gene: NOX1: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Inflammatory bowel disease v0.83 NOX1 Zornitza Stark Classified gene: NOX1 as Amber List (moderate evidence)
Inflammatory bowel disease v0.83 NOX1 Zornitza Stark Gene: nox1 has been classified as Amber List (Moderate Evidence).
Inflammatory bowel disease v0.83 NOX1 Zornitza Stark Classified gene: NOX1 as Amber List (moderate evidence)
Inflammatory bowel disease v0.83 NOX1 Zornitza Stark Gene: nox1 has been classified as Amber List (Moderate Evidence).
Inflammatory bowel disease v0.82 NOX1 Zornitza Stark reviewed gene: NOX1: Rating: AMBER; Mode of pathogenicity: None; Publications: 32064493; Phenotypes: Inflammatory bowel disease, MONDO:0005265, NOX1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.227 BICD2 Zornitza Stark Phenotypes for gene: BICD2 were changed from Spinal muscular atrophy, lower extremity-predominant, 2A, autosomal dominant, MIM# 615290; MONDO:0014121; Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, MIM# 618291 to Neurodevelopmental disorder (MONDO#0700092), BICD2-related; Spinal muscular atrophy, lower extremity-predominant, 2A, autosomal dominant, MIM# 615290; MONDO:0014121; Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, MIM# 618291
Mendeliome v1.226 BICD2 Zornitza Stark Publications for gene: BICD2 were set to 23664116; 23664119; 23664120; 27751653; 28635954; 30054298; 29528393
Mendeliome v1.225 BICD2 Zornitza Stark Mode of inheritance for gene: BICD2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4873 PSMC1 Zornitza Stark Marked gene: PSMC1 as ready
Intellectual disability syndromic and non-syndromic v0.4873 PSMC1 Zornitza Stark Gene: psmc1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.4873 PSMC1 Zornitza Stark Classified gene: PSMC1 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.4873 PSMC1 Zornitza Stark Gene: psmc1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.4872 PSMC1 Hazel Phillimore gene: PSMC1 was added
gene: PSMC1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PSMC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMC1 were set to PMID: 35861243
Phenotypes for gene: PSMC1 were set to spastic paraplegia; severe developmental delay; severe intellectual disability; hearing loss; micropenis; undescended testes; Syndromic disease MONDO:0002254, PSMC1-related
Review for gene: PSMC1 was set to RED
Added comment: Homozygosity mapping on one large consanguineous Bedouin kindred showed three affected children (out of the ten) to be homozygous for NM_002802.3:c.983T>C; p.(Ile328Thr).

Drosophila rescue experiments were carried out. Transgenic studies using drosophila with the silenced ortholog Rpt2 gene were rescued by the human wild-type PSMC1.

Three of the ten offspring of healthy consanguineous parents of Bedouin Israeli ancestry were affected with a similar phenotype of failure to thrive, developmental delay and severe intellectual disability, spastic tetraplegia with central hypotonia, chorea, as well as hearing loss. None of the three achieved verbal communication or ambulation (sitting / standing) at any age. They had mild dysmorphism of borderline dolichocephaly and microcephaly, prominent bushy eyebrows, flat midface, long nasal bridge and micrognathia. All three had micropenis with undescended testes. One of the affected (as a toddler) underwent thorough endocrinological analysis: testosterone and gonadotropin levels were low.
Sources: Literature
Anophthalmia_Microphthalmia_Coloboma v1.28 KIF15 Alison Yeung Marked gene: KIF15 as ready
Anophthalmia_Microphthalmia_Coloboma v1.28 KIF15 Alison Yeung Gene: kif15 has been classified as Red List (Low Evidence).
Anophthalmia_Microphthalmia_Coloboma v1.28 KIF15 Alison Yeung Phenotypes for gene: KIF15 were changed from ?Braddock-Carey syndrome 2 - MIM#619981 to Braddock-Carey syndrome 2 - MIM#619981
Anophthalmia_Microphthalmia_Coloboma v1.27 KIF15 Alison Yeung Classified gene: KIF15 as Red List (low evidence)
Anophthalmia_Microphthalmia_Coloboma v1.27 KIF15 Alison Yeung Gene: kif15 has been classified as Red List (Low Evidence).
Bleeding and Platelet Disorders v1.15 KIF15 Alison Yeung Marked gene: KIF15 as ready
Bleeding and Platelet Disorders v1.15 KIF15 Alison Yeung Gene: kif15 has been classified as Red List (Low Evidence).
Bleeding and Platelet Disorders v1.15 KIF15 Alison Yeung Phenotypes for gene: KIF15 were changed from ?Braddock-Carey syndrome 2 - MIM#619981 to Braddock-Carey syndrome 2 - MIM#619981
Bleeding and Platelet Disorders v1.14 KIF15 Alison Yeung Classified gene: KIF15 as Red List (low evidence)
Bleeding and Platelet Disorders v1.14 KIF15 Alison Yeung Gene: kif15 has been classified as Red List (Low Evidence).
Microcephaly v1.147 SARS Zornitza Stark Classified gene: SARS as Green List (high evidence)
Microcephaly v1.147 SARS Zornitza Stark Gene: sars has been classified as Green List (High Evidence).
Microcephaly v1.146 KIF15 Alison Yeung Marked gene: KIF15 as ready
Microcephaly v1.146 KIF15 Alison Yeung Gene: kif15 has been classified as Red List (Low Evidence).
Microcephaly v1.146 KIF15 Alison Yeung Phenotypes for gene: KIF15 were changed from ?Braddock-Carey syndrome 2 - MIM#619981 to Braddock-Carey syndrome 2 - MIM#619981
Microcephaly v1.145 KIF15 Alison Yeung Classified gene: KIF15 as Red List (low evidence)
Microcephaly v1.145 KIF15 Alison Yeung Gene: kif15 has been classified as Red List (Low Evidence).
Pierre Robin Sequence v0.43 KIF15 Alison Yeung Marked gene: KIF15 as ready
Pierre Robin Sequence v0.43 KIF15 Alison Yeung Gene: kif15 has been classified as Red List (Low Evidence).
Pierre Robin Sequence v0.43 KIF15 Alison Yeung Phenotypes for gene: KIF15 were changed from ?Braddock-Carey syndrome 2 - MIM#619981 to Braddock-Carey syndrome 2 - MIM#619981
Pierre Robin Sequence v0.42 KIF15 Alison Yeung Classified gene: KIF15 as Red List (low evidence)
Pierre Robin Sequence v0.42 KIF15 Alison Yeung Gene: kif15 has been classified as Red List (Low Evidence).
Mendeliome v1.224 KIF15 Alison Yeung Phenotypes for gene: KIF15 were changed from ?Braddock-Carey syndrome 2 - MIM#619981 to Braddock-Carey syndrome 2 - MIM#619981
Mendeliome v1.223 KIF15 Alison Yeung Marked gene: KIF15 as ready
Mendeliome v1.223 KIF15 Alison Yeung Gene: kif15 has been classified as Red List (Low Evidence).
Mendeliome v1.223 KIF15 Alison Yeung Classified gene: KIF15 as Red List (low evidence)
Mendeliome v1.223 KIF15 Alison Yeung Gene: kif15 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.4872 SARS Ain Roesley Phenotypes for gene: SARS were changed from Intellectual disability to neurodevelopmental disorder MONDO#070009, SARS1-related
Intellectual disability syndromic and non-syndromic v0.4872 SARS Ain Roesley Publications for gene: SARS were set to 28236339; 34570399
Microcephaly v1.142 SARS Ain Roesley gene: SARS was added
gene: SARS was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: SARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SARS were set to 35790048; 28236339; 34570399
Phenotypes for gene: SARS were set to neurodevelopmental disorder MONDO#070009, SARS1-related
Review for gene: SARS was set to GREEN
gene: SARS was marked as current diagnostic
Added comment: Total of 3 families
Sources: Literature
Microcephaly v1.142 SARS Ain Roesley Marked gene: SARS as ready
Microcephaly v1.142 SARS Ain Roesley Gene: sars has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.4872 SARS Ain Roesley Classified gene: SARS as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4872 SARS Ain Roesley Gene: sars has been classified as Green List (High Evidence).
Microcephaly v1.142 SARS Ain Roesley gene: SARS was added
gene: SARS was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: SARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SARS were set to 35790048; 28236339; 34570399
Phenotypes for gene: SARS were set to neurodevelopmental disorder MONDO#070009, SARS1-related
Review for gene: SARS was set to GREEN
gene: SARS was marked as current diagnostic
Added comment: Total of 3 families
Sources: Literature
Mendeliome v1.222 SARS Ain Roesley Publications for gene: SARS were set to 28236339; 34570399
Mendeliome v1.222 SARS Ain Roesley Classified gene: SARS as Green List (high evidence)
Mendeliome v1.222 SARS Ain Roesley Gene: sars has been classified as Green List (High Evidence).
Mendeliome v1.222 SARS Ain Roesley Phenotypes for gene: SARS were changed from Intellectual disability to neurodevelopmental disorder MONDO#070009, SARS1-related
Leukodystrophy - paediatric v0.274 WARS Seb Lunke Marked gene: WARS as ready
Leukodystrophy - paediatric v0.274 WARS Seb Lunke Gene: wars has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.274 WARS Seb Lunke Classified gene: WARS as Green List (high evidence)
Leukodystrophy - paediatric v0.274 WARS Seb Lunke Gene: wars has been classified as Green List (High Evidence).
Mendeliome v1.221 PSMC1 Zornitza Stark Marked gene: PSMC1 as ready
Mendeliome v1.221 PSMC1 Zornitza Stark Gene: psmc1 has been classified as Red List (Low Evidence).
Mendeliome v1.221 PSMC1 Zornitza Stark Phenotypes for gene: PSMC1 were changed from spastic paraplegia; severe developmental delay; severe intellectual disability; hearing loss; micropenis; undescended testes to 35861243; spastic paraplegia; severe developmental delay; severe intellectual disability; hearing loss; micropenis; undescended testes
Mendeliome v1.220 SARS Ain Roesley reviewed gene: SARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 35790048; Phenotypes: neurodevelopmental disorder MONDO#070009, SARS1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.4871 SARS Ain Roesley reviewed gene: SARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 35790048; Phenotypes: neurodevelopmental disorder MONDO#070009, SARS1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.220 PSMC1 Zornitza Stark Mode of pathogenicity for gene: PSMC1 was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to None
Mendeliome v1.219 PSMC1 Zornitza Stark Classified gene: PSMC1 as Red List (low evidence)
Mendeliome v1.219 PSMC1 Zornitza Stark Gene: psmc1 has been classified as Red List (Low Evidence).
Mendeliome v1.218 PSMC1 Zornitza Stark edited their review of gene: PSMC1: Changed phenotypes: Syndromic disease MONDO:0002254, PSMC1-related
Mendeliome v1.218 PSMC1 Zornitza Stark commented on gene: PSMC1: Single family only, homozygous missense variant.
Mendeliome v1.218 PSMC1 Zornitza Stark reviewed gene: PSMC1: Rating: RED; Mode of pathogenicity: None; Publications: 35861243; Phenotypes: Syndromic disease MONDO:0002254, PSMC1; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Lissencephaly and Band Heterotopia v1.10 BICD2 Zornitza Stark Marked gene: BICD2 as ready
Lissencephaly and Band Heterotopia v1.10 BICD2 Zornitza Stark Gene: bicd2 has been classified as Red List (Low Evidence).
Lissencephaly and Band Heterotopia v1.10 BICD2 Zornitza Stark Classified gene: BICD2 as Red List (low evidence)
Lissencephaly and Band Heterotopia v1.10 BICD2 Zornitza Stark Gene: bicd2 has been classified as Red List (Low Evidence).
Mendeliome v1.218 WARS Seb Lunke Publications for gene: WARS were set to PMID: 28369220; 31321409; 31069783.
Mendeliome v1.217 DOHH Zornitza Stark Marked gene: DOHH as ready
Mendeliome v1.217 DOHH Zornitza Stark Gene: dohh has been classified as Green List (High Evidence).
Mendeliome v1.217 WARS Seb Lunke Phenotypes for gene: WARS were changed from Neuronopathy, distal hereditary motor, type IX (OMIM:617721); juvenile to adult onset (15-23 years); distal wasting; distal weakness; length-dependent motor axonal degeneration to Neuronopathy, distal hereditary motor, type IX (OMIM:617721); juvenile to adult onset (15-23 years); Neurodevelopmental disorder (MONDO:0700092), WARS-related
Leukodystrophy - paediatric v0.273 WARS Anna Ritchie gene: WARS was added
gene: WARS was added to Leukodystrophy - paediatric. Sources: Literature
Mode of inheritance for gene: WARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WARS were set to PMID: 35815345 PMID: 35790048
Phenotypes for gene: WARS were set to Neurodevelopmental disorder (MONDO:0700092), WARS-related
Review for gene: WARS was set to GREEN
Added comment: Seven affected individuals from four families with biallelic variants, showing varying severities of developmental delay, intellectual disability and microcephaly. Hearing impairment and, as well as brain anomalies, skeletal system, movement/gait, and behaviour were variable features.
Sources: Literature
Anophthalmia_Microphthalmia_Coloboma v1.26 KIF15 Krithika Murali gene: KIF15 was added
gene: KIF15 was added to Anophthalmia_Microphthalmia_Coloboma. Sources: Literature
Mode of inheritance for gene: KIF15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF15 were set to 28150392
Phenotypes for gene: KIF15 were set to ?Braddock-Carey syndrome 2 - MIM#619981
Review for gene: KIF15 was set to AMBER
Added comment: PMID 28150392 Sleiman et al 2017 report one individual with homozygous R501* variant (NMD-predicted) from a consanguineous family. The child had thrombocytopenia, PRS, microcephaly -3SD by age 6, dysmorphic facies, bilateral external auditory canal atresia and deafness, microphthalmia, clinodactyly, short stature. Variant absent from gnomAD. Parents confirmed to be carriers and unaffected siblings were carriers/homozygous wild-type.

No other SNVs reported in ClinVar. Variant is absent from gnomAD. Authors note phenotypic similarities with Braddock-Carey syndrome (21q22 contiguous deletion also involving RUNX1).
Sources: Literature
Mendeliome v1.216 DOHH Zornitza Stark Classified gene: DOHH as Green List (high evidence)
Mendeliome v1.216 DOHH Zornitza Stark Gene: dohh has been classified as Green List (High Evidence).
Mendeliome v1.215 WARS Seb Lunke Mode of inheritance for gene: WARS was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.214 PPFIBP1 Zornitza Stark Publications for gene: PPFIBP1 were set to https://www.medrxiv.org/content/10.1101/2022.04.04.22273309v1
Intellectual disability syndromic and non-syndromic v0.4871 WARS Seb Lunke Marked gene: WARS as ready
Intellectual disability syndromic and non-syndromic v0.4871 WARS Seb Lunke Gene: wars has been classified as Green List (High Evidence).
Microcephaly v1.141 KIF15 Krithika Murali gene: KIF15 was added
gene: KIF15 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: KIF15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF15 were set to 28150392
Phenotypes for gene: KIF15 were set to ?Braddock-Carey syndrome 2 - MIM#619981
Review for gene: KIF15 was set to AMBER
Added comment: PMID 28150392 Sleiman et al 2017 report one individual with homozygous R501* variant (NMD-predicted) from a consanguineous family. The child had thrombocytopenia, PRS, microcephaly -3SD by age 6, dysmorphic facies, bilateral external auditory canal atresia and deafness, microphthalmia, clinodactyly, short stature. Variant absent from gnomAD. Parents confirmed to be carriers and unaffected siblings were carriers/homozygous wild-type.

No other SNVs reported in ClinVar. Variant is absent from gnomAD. Authors note phenotypic similarities with Braddock-Carey syndrome (21q22 contiguous deletion also involving RUNX1).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4871 WARS Seb Lunke Classified gene: WARS as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4871 WARS Seb Lunke Gene: wars has been classified as Green List (High Evidence).
Motor Neurone Disease v0.138 RNF13 Alison Yeung Marked gene: RNF13 as ready
Motor Neurone Disease v0.138 RNF13 Alison Yeung Gene: rnf13 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.213 SLITRK2 Zornitza Stark Marked gene: SLITRK2 as ready
Mendeliome v1.213 SLITRK2 Zornitza Stark Gene: slitrk2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1642 SLITRK2 Zornitza Stark Marked gene: SLITRK2 as ready
Genetic Epilepsy v0.1642 SLITRK2 Zornitza Stark Gene: slitrk2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1642 SLITRK2 Zornitza Stark Classified gene: SLITRK2 as Green List (high evidence)
Genetic Epilepsy v0.1642 SLITRK2 Zornitza Stark Gene: slitrk2 has been classified as Green List (High Evidence).
Mendeliome v1.213 BICD2 Lucy Spencer reviewed gene: BICD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 35896821; Phenotypes: Neurodevelopmental disorder (MONDO#0700092), BICD2-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Motor Neurone Disease v0.138 RNF13 Alison Yeung Classified gene: RNF13 as Amber List (moderate evidence)
Motor Neurone Disease v0.138 RNF13 Alison Yeung Gene: rnf13 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.213 KIF15 Krithika Murali reviewed gene: KIF15: Rating: AMBER; Mode of pathogenicity: None; Publications: 28150392; Phenotypes: ?Braddock-Carey syndrome 2 - MIM#619981; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.213 WARS Anna Ritchie reviewed gene: WARS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35815345, PMID: 35790048; Phenotypes: Neurodevelopmental disorder (MONDO:0700092), WARS-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Motor Neurone Disease v0.138 RNF13 Alison Yeung Classified gene: RNF13 as Amber List (moderate evidence)
Motor Neurone Disease v0.138 RNF13 Alison Yeung Gene: rnf13 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.213 SLITRK2 Zornitza Stark Classified gene: SLITRK2 as Green List (high evidence)
Mendeliome v1.213 SLITRK2 Zornitza Stark Gene: slitrk2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1641 RAC3 Zornitza Stark Marked gene: RAC3 as ready
Genetic Epilepsy v0.1641 RAC3 Zornitza Stark Gene: rac3 has been classified as Green List (High Evidence).
Mendeliome v1.212 KIF15 Krithika Murali Deleted their review
Congenital Heart Defect v0.259 DOHH Zornitza Stark Marked gene: DOHH as ready
Congenital Heart Defect v0.259 DOHH Zornitza Stark Gene: dohh has been classified as Green List (High Evidence).
Congenital Heart Defect v0.259 DOHH Zornitza Stark Classified gene: DOHH as Green List (high evidence)
Congenital Heart Defect v0.259 DOHH Zornitza Stark Gene: dohh has been classified as Green List (High Evidence).
Microcephaly v1.141 WARS Seb Lunke Marked gene: WARS as ready
Microcephaly v1.141 WARS Seb Lunke Gene: wars has been classified as Green List (High Evidence).
Mendeliome v1.212 PSMC1 Hazel Phillimore gene: PSMC1 was added
gene: PSMC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PSMC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMC1 were set to PMID: 35861243
Phenotypes for gene: PSMC1 were set to spastic paraplegia; severe developmental delay; severe intellectual disability; hearing loss; micropenis; undescended testes
Mode of pathogenicity for gene: PSMC1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: PSMC1 was set to AMBER
Added comment: Homozygosity mapping on one large consanguineous Bedouin kindred showed three affected children (out of the ten) to be homozygous for NM_002802.3:c.983T>C; p.(Ile328Thr).

Drosophila rescue experiments were carried out. Transgenic studies using drosophila with the silenced ortholog Rpt2 gene were rescued by the human wild-type PSMC1.

Three of the ten offspring of healthy consanguineous parents of Bedouin Israeli ancestry were affected with a similar phenotype of failure to thrive, developmental delay and severe intellectual disability, spastic tetraplegia with central hypotonia, chorea, as well as hearing loss. None of the three achieved verbal communication or ambulation (sitting / standing) at any age. They had mild dysmorphism of borderline dolichocephaly and microcephaly, prominent bushy eyebrows, flat midface, long nasal bridge and micrognathia. All three had micropenis with undescended testes. One of the affected (as a toddler) underwent thorough endocrinological analysis: testosterone and gonadotropin levels were low.
Sources: Literature
Mendeliome v1.212 KIF15 Krithika Murali gene: KIF15 was added
gene: KIF15 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIF15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF15 were set to 28150392
Phenotypes for gene: KIF15 were set to ?Braddock-Carey syndrome 2 - MIM#619981
Review for gene: KIF15 was set to GREEN
Added comment: PMID 28150392 Sleiman et al 2017 report one individual with homozygous R501* variant (NMD-predicted) from a consanguineous family. The child had thrombocytopenia, PRS, microcephaly -3SD by age 6, dysmorphic facies, bilateral external auditory canal atresia and deafness, microphthalmia, clinodactyly, short stature. Variant absent from gnomAD. Parents confirmed to be carriers and unaffected siblings were carriers/homozygous wild-type.

No other SNVs reported in ClinVar. Variant is absent from gnomAD. Authors note phenotypic similarities with Braddock-Carey syndrome (21q22 contiguous deletion also involving RUNX1).
Sources: Literature
Microcephaly v1.141 PPFIBP1 Zornitza Stark Publications for gene: PPFIBP1 were set to https://www.medrxiv.org/content/10.1101/2022.04.04.22273309v1
Intellectual disability syndromic and non-syndromic v0.4870 BICD2 Lucy Spencer reviewed gene: BICD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 35896821; Phenotypes: Neurodevelopmental disorder (MONDO#0700092), BICD2-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Pierre Robin Sequence v0.41 KIF15 Krithika Murali gene: KIF15 was added
gene: KIF15 was added to Pierre Robin Sequence. Sources: Literature
Mode of inheritance for gene: KIF15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF15 were set to 28150392
Phenotypes for gene: KIF15 were set to ?Braddock-Carey syndrome 2 - MIM#619981
Review for gene: KIF15 was set to AMBER
Added comment: PMID 28150392 Sleiman et al 2017 report one individual with homozygous R501* variant (NMD-predicted) from a consanguineous family. The child had thrombocytopenia, PRS, microcephaly -3SD by age 6, dysmorphic facies, bilateral external auditory canal atresia and deafness, microphthalmia, clinodactyly, short stature. Variant absent from gnomAD. Parents confirmed to be carriers and unaffected siblings were carriers/homozygous wild-type.

No other SNVs reported in ClinVar. Variant is absent from gnomAD. Authors note phenotypic similarities with Braddock-Carey syndrome (21q22 contiguous deletion also involving RUNX1).
Sources: Literature
Microcephaly v1.140 DOHH Zornitza Stark Marked gene: DOHH as ready
Microcephaly v1.140 DOHH Zornitza Stark Gene: dohh has been classified as Green List (High Evidence).
Microcephaly v1.140 DOHH Zornitza Stark Classified gene: DOHH as Green List (high evidence)
Microcephaly v1.140 DOHH Zornitza Stark Gene: dohh has been classified as Green List (High Evidence).
Motor Neurone Disease v0.137 RNF13 Melanie Marty changed review comment from: 3 x affected siblings with hom canonical splice variant. 2 x unaffected siblings het for the variant. RT-PCR showed expression of two mis-spliced forms of RNF13 mRNA (1 with a PTC and the other with an inframe del). Functional studies on patients cells showed an absence of protein.
Sources: Literature; to: 3 x affected siblings with hom canonical splice variant. 2 x unaffected siblings het for the variant. RT-PCR showed expression of two mis-spliced forms of RNF13 mRNA (1 with a PTC and the other with an inframe del). Functional studies showed an absence of protein.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4870 PPFIBP1 Zornitza Stark Publications for gene: PPFIBP1 were set to https://www.medrxiv.org/content/10.1101/2022.04.04.22273309v1
Bleeding and Platelet Disorders v1.13 KIF15 Krithika Murali gene: KIF15 was added
gene: KIF15 was added to Bleeding and Platelet Disorders. Sources: Literature
Mode of inheritance for gene: KIF15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF15 were set to 28150392
Phenotypes for gene: KIF15 were set to ?Braddock-Carey syndrome 2 - MIM#619981
Review for gene: KIF15 was set to AMBER
Added comment: PMID 28150392 Sleiman et al 2017 report one individual with homozygous R501* variant (NMD-predicted) from a consanguineous family. The child had thrombocytopenia, PRS, microcephaly <3 SD by age 6, dysmorphic facies, bilateral external auditory canal atresia and deafness, microphthalmia, clinodactyly, short stature. Variant absent from gnomAD. Parents confirmed to be carriers and unaffected siblings were carriers/homozygous wild-type.

No other SNVs reported in ClinVar. Variant is absent from gnomAD. Authors note phenotypic similarities with Braddock-Carey syndrome (21q22 contiguous deletion also involving RUNX1).
Sources: Literature
Microcephaly v1.139 WARS Seb Lunke Classified gene: WARS as Green List (high evidence)
Microcephaly v1.139 WARS Seb Lunke Gene: wars has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4869 C18orf32 Alison Yeung Marked gene: C18orf32 as ready
Intellectual disability syndromic and non-syndromic v0.4869 C18orf32 Alison Yeung Gene: c18orf32 has been classified as Red List (Low Evidence).
Congenital nystagmus v1.12 DOHH Zornitza Stark Marked gene: DOHH as ready
Congenital nystagmus v1.12 DOHH Zornitza Stark Gene: dohh has been classified as Green List (High Evidence).
Congenital nystagmus v1.12 DOHH Zornitza Stark Classified gene: DOHH as Green List (high evidence)
Congenital nystagmus v1.12 DOHH Zornitza Stark Gene: dohh has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4869 C18orf32 Alison Yeung Classified gene: C18orf32 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.4869 C18orf32 Alison Yeung Gene: c18orf32 has been classified as Red List (Low Evidence).
Mendeliome v1.212 BMP3 Seb Lunke Marked gene: BMP3 as ready
Mendeliome v1.212 BMP3 Seb Lunke Gene: bmp3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.212 BMP3 Seb Lunke Classified gene: BMP3 as Amber List (moderate evidence)
Mendeliome v1.212 BMP3 Seb Lunke Gene: bmp3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.211 BMP3 Seb Lunke gene: BMP3 was added
gene: BMP3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BMP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BMP3 were set to 35089417
Phenotypes for gene: BMP3 were set to coloboma, MONDO:0001476; microphthalmia, MONDO:0021129
Review for gene: BMP3 was set to AMBER
Added comment: Single missense variant identified segregating with disease following WES screen in a family with coloboma and/or microphthalmia in BMP3. Two additional unrelated patients identified with different missense in BMP3. Pathogenicity however largely on in-silicos, with one of the 3 missense having 29 hets in gnomAD. Additional functional work in bmp3 -/- zebra fish and some supporting evidence but not conclusive
Sources: Literature
Cerebellar and Pontocerebellar Hypoplasia v1.56 BICD2 Zornitza Stark Marked gene: BICD2 as ready
Cerebellar and Pontocerebellar Hypoplasia v1.56 BICD2 Zornitza Stark Gene: bicd2 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.56 BICD2 Zornitza Stark Classified gene: BICD2 as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v1.56 BICD2 Zornitza Stark Gene: bicd2 has been classified as Green List (High Evidence).
Mendeliome v1.210 C18orf32 Alison Yeung Marked gene: C18orf32 as ready
Mendeliome v1.210 C18orf32 Alison Yeung Gene: c18orf32 has been classified as Red List (Low Evidence).
Mendeliome v1.210 C18orf32 Alison Yeung Classified gene: C18orf32 as Red List (low evidence)
Mendeliome v1.210 C18orf32 Alison Yeung Gene: c18orf32 has been classified as Red List (Low Evidence).
Fetal anomalies v1.52 BMP3 Seb Lunke Marked gene: BMP3 as ready
Fetal anomalies v1.52 BMP3 Seb Lunke Gene: bmp3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v1.52 BMP3 Seb Lunke Classified gene: BMP3 as Amber List (moderate evidence)
Fetal anomalies v1.52 BMP3 Seb Lunke Gene: bmp3 has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.52 ALG5 Zornitza Stark Marked gene: ALG5 as ready
Renal Macrocystic Disease v0.52 ALG5 Zornitza Stark Gene: alg5 has been classified as Green List (High Evidence).
Mendeliome v1.209 ALG5 Zornitza Stark Marked gene: ALG5 as ready
Mendeliome v1.209 ALG5 Zornitza Stark Gene: alg5 has been classified as Green List (High Evidence).
Motor Neurone Disease v0.137 RNF13 Melanie Marty gene: RNF13 was added
gene: RNF13 was added to Motor Neurone Disease. Sources: Literature
Mode of inheritance for gene: RNF13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNF13 were set to PMID: 35879052
Phenotypes for gene: RNF13 were set to Amyotrophic lateral sclerosis
Review for gene: RNF13 was set to AMBER
Added comment: 3 x affected siblings with hom canonical splice variant. 2 x unaffected siblings het for the variant. RT-PCR showed expression of two mis-spliced forms of RNF13 mRNA (1 with a PTC and the other with an inframe del). Functional studies on patients cells showed an absence of protein.
Sources: Literature
Fetal anomalies v1.51 BMP3 Seb Lunke gene: BMP3 was added
gene: BMP3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: BMP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BMP3 were set to 35089417
Phenotypes for gene: BMP3 were set to coloboma, MONDO:0001476; microphthalmia, MONDO:0021129
Added comment: Single missense variant identified segregating with disease following WES screen in a family with coloboma and/or microphthalmia in BMP3. Two additional unrelated patients identified with different missense in BMP3. Pathogenicity however largely on in-silicos, with one of the 3 missense having 29 hets in gnomAD. Additional functional work in bmp3 -/- zebra fish and some supporting evidence but not conclusive.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4868 C18orf32 Naomi Baker gene: C18orf32 was added
gene: C18orf32 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: C18orf32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C18orf32 were set to PMID:35107634
Phenotypes for gene: C18orf32 were set to Neurodevelopmental disorder (MONDO:0700092), C18orf32-related
Review for gene: C18orf32 was set to RED
Added comment: Two siblings reported as affected, although sequencing only performed in one sibling, with homozygous loss-of-function variant identified. Clinical presentation included developmental delay, recurrent lower respiratory tract infections, sparse rough hair, roving eye movements, hypotonia, bilateral ankle contractures and inverted nipples.
Sources: Literature
Mendeliome v1.209 ALG5 Zornitza Stark Classified gene: ALG5 as Green List (high evidence)
Mendeliome v1.209 ALG5 Zornitza Stark Gene: alg5 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.52 ALG5 Zornitza Stark Phenotypes for gene: ALG5 were changed from Multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline to Cystic renal disease MONDO:0002473, ALG5-related; Multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline
Mendeliome v1.208 ALG5 Chern Lim edited their review of gene: ALG5: Changed phenotypes: Cystic renal disease MONDO:0002473, ALG5-related, Multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline, few or no liver cysts.
Anophthalmia_Microphthalmia_Coloboma v1.26 BMP3 Zornitza Stark Marked gene: BMP3 as ready
Anophthalmia_Microphthalmia_Coloboma v1.26 BMP3 Zornitza Stark Gene: bmp3 has been classified as Amber List (Moderate Evidence).
Anophthalmia_Microphthalmia_Coloboma v1.26 BMP3 Seb Lunke Marked gene: BMP3 as ready
Anophthalmia_Microphthalmia_Coloboma v1.26 BMP3 Seb Lunke Gene: bmp3 has been classified as Amber List (Moderate Evidence).
Anophthalmia_Microphthalmia_Coloboma v1.26 BMP3 Zornitza Stark Classified gene: BMP3 as Amber List (moderate evidence)
Anophthalmia_Microphthalmia_Coloboma v1.26 BMP3 Zornitza Stark Gene: bmp3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.208 ALG5 Chern Lim gene: ALG5 was added
gene: ALG5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ALG5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ALG5 were set to 35896117
Phenotypes for gene: ALG5 were set to Cystic renal disease MONDO:0002473, ALG5-related
Review for gene: ALG5 was set to GREEN
gene: ALG5 was marked as current diagnostic
Added comment: PMID:35896117:
- Five unrelated families, including 23 affected individuals with non-enlarged cystic kidneys and few or no liver cysts, 8 of them reached end-stage kidney disease from 62 to 91 years of age. Variant confirmed in all but one individual.
- Various variant types: frameshift, nonsense, two missense, splice.
- Functional studies showed haploinsufficiency is the disease mechanism.
Sources: Literature
Genetic Epilepsy v0.1641 RAC3 Zornitza Stark Classified gene: RAC3 as Green List (high evidence)
Genetic Epilepsy v0.1641 RAC3 Zornitza Stark Gene: rac3 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.55 BICD2 Lucy Spencer changed review comment from: Child with developmental delay, microcephaly, dysmorphic facial features, optic atrophy, lissencephaly, hypogenesis of the corpus callosum and cerebellar hypoplasia. Also short stature and underweight. Found to have a homozygous NMD predicted stop gain variant (consanguineous parents). This study reviewed previous patients and cerebellar hypoplasia seen in 3 other patients, and hypogenesis of the corpus callosum seen in 5 others but these individuals all had only 1 heterozygous variant, mostly missense.
Sources: Literature; to: Child with developmental delay, microcephaly, dysmorphic facial features, optic atrophy, lissencephaly, hypogenesis of the corpus callosum and cerebellar hypoplasia. Also short stature and underweight. Found to have a homozygous NMD predicted stop gain variant (consanguineous parents). This study reviewed previous patients and cerebellar hypoplasia seen in 3 other patients, and hypogenesis of the corpus callosum seen in 5 others but these individuals all had only 1 heterozygous variant, mostly missense. The patient in this paper appears to be a new mode of inheritance and mechanism associated with AR LOF variants (most previous variants are single heterozygous missense). This patient also appears to be the first report of lissencephaly.
Sources: Literature
Microcephaly v1.138 WARS Anna Ritchie gene: WARS was added
gene: WARS was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: WARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WARS were set to PMID: 35815345; 35790048
Phenotypes for gene: WARS were set to Neurodevelopmental disorder (MONDO:0700092), WARS-related
Review for gene: WARS was set to GREEN
Added comment: Seven affected individuals from four families with biallelic variants, showing varying
severities of developmental delay, intellectual disability and microcephaly. Hearing impairment and, as well as brain anomalies, skeletal system, movement/gait, and behaviour were variable features.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4868 SLITRK2 Zornitza Stark Marked gene: SLITRK2 as ready
Intellectual disability syndromic and non-syndromic v0.4868 SLITRK2 Zornitza Stark Gene: slitrk2 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.51 ALG5 Zornitza Stark Classified gene: ALG5 as Green List (high evidence)
Renal Macrocystic Disease v0.51 ALG5 Zornitza Stark Gene: alg5 has been classified as Green List (High Evidence).
Lissencephaly and Band Heterotopia v1.9 BICD2 Lucy Spencer gene: BICD2 was added
gene: BICD2 was added to Lissencephaly and Band Heterotopia. Sources: Literature
Mode of inheritance for gene: BICD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BICD2 were set to 35896821
Phenotypes for gene: BICD2 were set to Neurodevelopmental disorder (MONDO#0700092), BICD2-related
Review for gene: BICD2 was set to RED
Added comment: Child with developmental delay, microcephaly, dysmorphic facial features, optic atrophy, lissencephaly, hypogenesis of the corpus callosum and cerebellar hypoplasia. Also short stature and underweight. Found to have a homozygous NMD predicted stop gain variant (consanguineous parents). This paper reviews previous patients and found others with brain abnormalities including cerebellar hypoplasia but it looks like lissencephaly is a new phenotype in this individual associated with AR LOF variants (most previous variants are single heterozygous missense).
Sources: Literature
Genetic Epilepsy v0.1640 SLITRK2 Paul De Fazio edited their review of gene: SLITRK2: Changed rating: GREEN
Polycystic liver disease v1.3 ALG5 Zornitza Stark Marked gene: ALG5 as ready
Polycystic liver disease v1.3 ALG5 Zornitza Stark Gene: alg5 has been classified as Green List (High Evidence).
Mendeliome v1.208 DOHH Daniel Flanagan gene: DOHH was added
gene: DOHH was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: DOHH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DOHH were set to PMID: 35858628
Phenotypes for gene: DOHH were set to Neurodevelopmental disorder, DOHH-related (MONDO#0700092)
Review for gene: DOHH was set to GREEN
Added comment: Bi-allelic missense and truncating DOHH variants segregating with disease in five affected individuals from four unrelated families. Clinical features were developmental delay and/or intellectual disability (5/5), microcephaly (5/5), visual impairment (nystagmus (3/5), strabismus (3/5), and cortical visual impairment (1/5)) and congenital heart malformations (3/5 individuals).
Sources: Expert list
Polycystic liver disease v1.3 ALG5 Zornitza Stark Phenotypes for gene: ALG5 were changed from Multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline to Cystic renal disease MONDO:0002473, ALG5-related; Multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline
Genetic Epilepsy v0.1640 SLITRK2 Paul De Fazio gene: SLITRK2 was added
gene: SLITRK2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SLITRK2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: SLITRK2 were set to 35840571
Phenotypes for gene: SLITRK2 were set to Neurodevelopmental disorder, SLITRK2-related MONDO:0700092
gene: SLITRK2 was marked as current diagnostic
Added comment: 6 missense variants and 1 nonsense variant (NOT NMD-predicted, single-exon gene) reported in 7 males and 1 female with neurodevelopmental disorders. Phenotypes included dev delay, mild to severe ID, delayed or absent speech, seizures and brain MRI anomalies (in some patients).

The nonsense variant was identified in two affected brothers but not in the mother, suggesting it was de novo in the maternal germline. The variant in the one affected female was de novo. All other variants in hemizygous males were inherited from an unaffected mother. In one case, the variant was also identified in the unaffected grandmother.

Functional studies showed some but not all variants displayed impaired membrane transport and impaired excitatory synapse-promoting effects. Conditional knockout mice exhibited impaired long-term memory and abnormal gait.
Sources: Literature
Polycystic liver disease v1.2 ALG5 Zornitza Stark Mode of pathogenicity for gene: ALG5 was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to None
Mendeliome v1.208 PPFIBP1 Ee Ming Wong reviewed gene: PPFIBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35830857; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, PPFIBP1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Polycystic liver disease v1.1 ALG5 Zornitza Stark Classified gene: ALG5 as Green List (high evidence)
Polycystic liver disease v1.1 ALG5 Zornitza Stark Gene: alg5 has been classified as Green List (High Evidence).
Mendeliome v1.208 SLITRK2 Paul De Fazio gene: SLITRK2 was added
gene: SLITRK2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLITRK2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: SLITRK2 were set to 35840571
Phenotypes for gene: SLITRK2 were set to Neurodevelopmental disorder, SLITRK2-related MONDO:0700092
Review for gene: SLITRK2 was set to GREEN
gene: SLITRK2 was marked as current diagnostic
Added comment: 6 missense variants and 1 nonsense variant (NOT NMD-predicted, single-exon gene) reported in 7 males and 1 female with neurodevelopmental disorders. Phenotypes included dev delay, mild to severe ID, delayed or absent speech, seizures and brain MRI anomalies (in some patients).

The nonsense variant was identified in two affected brothers but not in the mother, suggesting it was de novo in the maternal germline. The variant in the one affected female was de novo. All other variants in hemizygous males were inherited from an unaffected mother. In one case, the variant was also identified in the unaffected grandmother.

Functional studies showed some but not all variants displayed impaired membrane transport and impaired excitatory synapse-promoting effects. Conditional knockout mice exhibited impaired long-term memory and abnormal gait.
Sources: Literature
Congenital Heart Defect v0.258 DOHH Daniel Flanagan gene: DOHH was added
gene: DOHH was added to Congenital Heart Defect. Sources: Expert list
Mode of inheritance for gene: DOHH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DOHH were set to PMID: 35858628
Phenotypes for gene: DOHH were set to Neurodevelopmental disorder, DOHH-related (MONDO#0700092)
Review for gene: DOHH was set to GREEN
Added comment: Bi-allelic missense and truncating DOHH variants segregating with disease in five affected individuals from four unrelated families. Clinical features were developmental delay and/or intellectual disability (5/5), microcephaly (5/5), visual impairment (nystagmus (3/5), strabismus (3/5), and cortical visual impairment (1/5)) and congenital heart malformations (3/5 individuals).
Sources: Expert list
Genetic Epilepsy v0.1640 RAC3 Alison Yeung gene: RAC3 was added
gene: RAC3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: RAC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAC3 were set to 35851598
Phenotypes for gene: RAC3 were set to Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies, MIM#618577
Review for gene: RAC3 was set to GREEN
Added comment: Sources: Literature
Anophthalmia_Microphthalmia_Coloboma v1.25 BMP3 Seb Lunke gene: BMP3 was added
gene: BMP3 was added to Anophthalmia_Microphthalmia_Coloboma. Sources: Literature
Mode of inheritance for gene: BMP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BMP3 were set to 35089417
Phenotypes for gene: BMP3 were set to coloboma, MONDO:0001476; microphthalmia, MONDO:0021129
Review for gene: BMP3 was set to AMBER
Added comment: Single missense variant identified segregating with disease following WES screen in a family with coloboma and/or microphthalmia in BMP3. Two additional unrelated patients identified with different missense in BMP3. Pathogenicity however largely on in-silicos, with one of the 3 missense having 29 hets in gnomAD.

Additional functional work in bmp3 -/- zebra fish and some supporting evidence but not conclusive.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4868 SLITRK2 Zornitza Stark Classified gene: SLITRK2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4868 SLITRK2 Zornitza Stark Gene: slitrk2 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.50 ALG5 Chern Lim edited their review of gene: ALG5: Changed phenotypes: Multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline, few or no liver cysts.
Microcephaly v1.138 PPFIBP1 Ee Ming Wong reviewed gene: PPFIBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35830857; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, PPFIBP1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.208 RFC1 Ain Roesley Publications for gene: RFC1 were set to 30926972
Mendeliome v1.208 RFC1 Ain Roesley Phenotypes for gene: RFC1 were changed from Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome OMIM 614575 to Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome MIM#614575
Polycystic liver disease v1.0 ALG5 Chern Lim edited their review of gene: ALG5: Changed phenotypes: Multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline, few or no liver cysts.
Mendeliome v1.207 RFC1 Ain Roesley Classified gene: RFC1 as Amber List (moderate evidence)
Mendeliome v1.207 RFC1 Ain Roesley Gene: rfc1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1640 RAC3 Alison Yeung gene: RAC3 was added
gene: RAC3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: RAC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAC3 were set to 35851598
Phenotypes for gene: RAC3 were set to Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies, MIM#618577
Review for gene: RAC3 was set to GREEN
Added comment: Sources: Literature
Microcephaly v1.138 DOHH Daniel Flanagan gene: DOHH was added
gene: DOHH was added to Microcephaly. Sources: Expert list
Mode of inheritance for gene: DOHH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DOHH were set to PMID: 35858628
Phenotypes for gene: DOHH were set to Neurodevelopmental disorder, DOHH-related (MONDO#0700092)
Review for gene: DOHH was set to GREEN
Added comment: Bi-allelic missense and truncating DOHH variants segregating with disease in five affected individuals from four unrelated families. Clinical features were developmental delay and/or intellectual disability (5/5), microcephaly (5/5), visual impairment (nystagmus (3/5), strabismus (3/5), and cortical visual impairment (1/5)) and congenital heart malformations (3/5 individuals).
Sources: Expert list
Mendeliome v1.206 C18orf32 Naomi Baker gene: C18orf32 was added
gene: C18orf32 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: C18orf32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C18orf32 were set to PMID:35107634
Phenotypes for gene: C18orf32 were set to Neurodevelopmental disorder (MONDO:0700092), C18orf32-related
Review for gene: C18orf32 was set to RED
Added comment: Two siblings reported as affected, although sequencing only performed in one sibling, with homozygous loss-of-function variant identified. Clinical presentation included developmental delay, recurrent lower respiratory tract infections, sparse rough hair, roving eye movements, hypotonia, bilateral ankle contractures and inverted nipples.
Sources: Literature
Ataxia - adult onset v0.169 RFC1 Ain Roesley Publications for gene: RFC1 were set to 30926972; 35883251
Ataxia - adult onset v0.168 RFC1 Ain Roesley Marked gene: RFC1 as ready
Ataxia - adult onset v0.168 RFC1 Ain Roesley Gene: rfc1 has been classified as Amber List (Moderate Evidence).
Ataxia - adult onset v0.168 RFC1 Ain Roesley Phenotypes for gene: RFC1 were changed from Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome, 614575; CANVAS to Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome MIM#614575
Intellectual disability syndromic and non-syndromic v0.4867 WARS Anna Ritchie gene: WARS was added
gene: WARS was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: WARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WARS were set to PMID: 35815345; 35790048
Phenotypes for gene: WARS were set to Neurodevelopmental disorder (MONDO:0700092), WARS-related
Review for gene: WARS was set to GREEN
Added comment: At least seven affected individuals from four families with biallelic variants, showing varying
severities of developmental delay, intellectual disability and microcephaly. Hearing impairment and, as well as brain anomalies, skeletal system, movement/gait, and behaviour were variable features.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4867 PPFIBP1 Ee Ming Wong reviewed gene: PPFIBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35830857; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, PPFIBP1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Ataxia - adult onset v0.168 RFC1 Ain Roesley Publications for gene: RFC1 were set to 30926972
Hereditary Neuropathy - complex v0.130 RFC1 Zornitza Stark Mode of pathogenicity for gene: RFC1 was changed from None to Other
Ataxia - adult onset v0.167 RFC1 Ain Roesley Classified gene: RFC1 as Amber List (moderate evidence)
Ataxia - adult onset v0.167 RFC1 Ain Roesley Gene: rfc1 has been classified as Amber List (Moderate Evidence).
Hereditary Neuropathy - complex v0.129 RFC1 Zornitza Stark Classified gene: RFC1 as Amber List (moderate evidence)
Hereditary Neuropathy - complex v0.129 RFC1 Zornitza Stark Gene: rfc1 has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.50 ALG5 Chern Lim gene: ALG5 was added
gene: ALG5 was added to Renal Macrocystic Disease. Sources: Literature
Mode of inheritance for gene: ALG5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ALG5 were set to 35896117
Phenotypes for gene: ALG5 were set to Multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline
Review for gene: ALG5 was set to GREEN
gene: ALG5 was marked as current diagnostic
Added comment: PMID:35896117:
- Five unrelated families, including 23 affected individuals with non-enlarged cystic kidneys and few or no liver cysts, 8 of them reached end-stage kidney disease from 62 to 91 years of age. Variant confirmed in all but one individual.
- Various variant types: frameshift, nonsense, two missense, splice.
- Functional studies showed haploinsufficiency is the disease mechanism.
Sources: Literature
Congenital nystagmus v1.11 DOHH Daniel Flanagan gene: DOHH was added
gene: DOHH was added to Congenital nystagmus. Sources: Expert list
Mode of inheritance for gene: DOHH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DOHH were set to PMID: 35858628
Phenotypes for gene: DOHH were set to Neurodevelopmental disorder, DOHH-related (MONDO#0700092)
Review for gene: DOHH was set to GREEN
Added comment: Bi-allelic missense and truncating DOHH variants segregating with disease in five affected individuals from four unrelated families. Clinical features were developmental delay and/or intellectual disability (5/5), microcephaly (5/5), visual impairment (nystagmus (3/5), strabismus (3/5), and cortical visual impairment (1/5)) and congenital heart malformations (3/5 individuals).
Sources: Expert list
Genetic Epilepsy v0.1639 PPFIBP1 Zornitza Stark Publications for gene: PPFIBP1 were set to https://www.medrxiv.org/content/10.1101/2022.04.04.22273309v1
Cerebellar and Pontocerebellar Hypoplasia v1.55 BICD2 Lucy Spencer gene: BICD2 was added
gene: BICD2 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Literature
Mode of inheritance for gene: BICD2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: BICD2 were set to 35896821
Phenotypes for gene: BICD2 were set to Neurodevelopmental disorder, BICD2-related (MONDO#0700092)
Review for gene: BICD2 was set to GREEN
Added comment: Child with developmental delay, microcephaly, dysmorphic facial features, optic atrophy, lissencephaly, hypogenesis of the corpus callosum and cerebellar hypoplasia. Also short stature and underweight. Found to have a homozygous NMD predicted stop gain variant (consanguineous parents). This study reviewed previous patients and cerebellar hypoplasia seen in 3 other patients, and hypogenesis of the corpus callosum seen in 5 others but these individuals all had only 1 heterozygous variant, mostly missense.
Sources: Literature
Polycystic liver disease v1.0 ALG5 Chern Lim gene: ALG5 was added
gene: ALG5 was added to Polycystic liver disease. Sources: Literature
Mode of inheritance for gene: ALG5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ALG5 were set to 35896117
Phenotypes for gene: ALG5 were set to Multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline
Mode of pathogenicity for gene: ALG5 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: ALG5 was set to GREEN
gene: ALG5 was marked as current diagnostic
Added comment: PMID:35896117:
- Five unrelated families, including 23 affected individuals with non-enlarged cystic kidneys and few or no liver cysts, 8 of them reached end-stage kidney disease from 62 to 91 years of age. Variant confirmed in all but one individual.
- Various variant types: frameshift, nonsense, two missense, splice.
- Functional studies showed haploinsufficiency is the disease mechanism.
Sources: Literature
Genetic Epilepsy v0.1638 ADGRL1 Elena Savva Classified gene: ADGRL1 as Amber List (moderate evidence)
Genetic Epilepsy v0.1638 ADGRL1 Elena Savva Gene: adgrl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.206 ADGRL1 Elena Savva Classified gene: ADGRL1 as Green List (high evidence)
Mendeliome v1.206 ADGRL1 Elena Savva Gene: adgrl1 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.178 RAC3 Alison Yeung Marked gene: RAC3 as ready
Polymicrogyria and Schizencephaly v0.178 RAC3 Alison Yeung Gene: rac3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4867 DOHH Zornitza Stark Marked gene: DOHH as ready
Intellectual disability syndromic and non-syndromic v0.4867 DOHH Zornitza Stark Gene: dohh has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4867 ADGRL1 Zornitza Stark Marked gene: ADGRL1 as ready
Intellectual disability syndromic and non-syndromic v0.4867 ADGRL1 Zornitza Stark Gene: adgrl1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4867 DOHH Zornitza Stark Classified gene: DOHH as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4867 DOHH Zornitza Stark Gene: dohh has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.178 RAC3 Alison Yeung Classified gene: RAC3 as Green List (high evidence)
Polymicrogyria and Schizencephaly v0.178 RAC3 Alison Yeung Gene: rac3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4867 SLITRK2 Paul De Fazio gene: SLITRK2 was added
gene: SLITRK2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SLITRK2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: SLITRK2 were set to 35840571
Phenotypes for gene: SLITRK2 were set to Neurodevelopmental disorder, SLITRK2-related MONDO:0700092
Review for gene: SLITRK2 was set to GREEN
gene: SLITRK2 was marked as current diagnostic
Added comment: 6 missense variants and 1 nonsense variant (NOT NMD-predicted, single-exon gene) reported in 7 males and 1 female with neurodevelopmental disorders. Phenotypes included dev delay, mild to severe ID, delayed or absent speech, seizures and brain MRI anomalies (in some patients).

The nonsense variant was identified in two affected brothers but not in the mother, suggesting it was de novo in the maternal germline. The variant in the one affected female was de novo. All other variants in hemizygous males were inherited from an unaffected mother. In one case, the variant was also identified in the unaffected grandmother.

Functional studies showed some but not all variants displayed impaired membrane transport and impaired excitatory synapse-promoting effects. Conditional knockout mice exhibited impaired long-term memory and abnormal gait.
Sources: Literature
Polymicrogyria and Schizencephaly v0.178 RAC3 Alison Yeung Classified gene: RAC3 as Green List (high evidence)
Polymicrogyria and Schizencephaly v0.178 RAC3 Alison Yeung Gene: rac3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4867 ADGRL1 Zornitza Stark Classified gene: ADGRL1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4867 ADGRL1 Zornitza Stark Gene: adgrl1 has been classified as Green List (High Evidence).
Mendeliome v1.205 RFC1 Ain Roesley reviewed gene: RFC1: Rating: AMBER; Mode of pathogenicity: None; Publications: 35883251; Phenotypes: Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome MIM#614575; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic Epilepsy v0.1637 ADGRL1 Elena Savva Classified gene: ADGRL1 as Amber List (moderate evidence)
Genetic Epilepsy v0.1637 ADGRL1 Elena Savva Gene: adgrl1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1637 ADGRL1 Elena Savva Classified gene: ADGRL1 as Amber List (moderate evidence)
Genetic Epilepsy v0.1637 ADGRL1 Elena Savva Gene: adgrl1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4866 ADGRL1 Elena Savva Marked gene: ADGRL1 as ready
Intellectual disability syndromic and non-syndromic v0.4866 ADGRL1 Elena Savva Gene: adgrl1 has been classified as Green List (High Evidence).
Mendeliome v1.205 ADGRL1 Elena Savva Classified gene: ADGRL1 as Green List (high evidence)
Mendeliome v1.205 ADGRL1 Elena Savva Gene: adgrl1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4866 ADGRL1 Zornitza Stark Classified gene: ADGRL1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4866 ADGRL1 Zornitza Stark Gene: adgrl1 has been classified as Green List (High Evidence).
Ataxia - adult onset v0.166 RFC1 Ain Roesley reviewed gene: RFC1: Rating: AMBER; Mode of pathogenicity: None; Publications: 35883251; Phenotypes: Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome MIM#614575; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.204 ADGRL1 Elena Savva Marked gene: ADGRL1 as ready
Mendeliome v1.204 ADGRL1 Elena Savva Gene: adgrl1 has been classified as Red List (Low Evidence).
Genetic Epilepsy v0.1636 ADGRL1 Elena Savva Marked gene: ADGRL1 as ready
Genetic Epilepsy v0.1636 ADGRL1 Elena Savva Gene: adgrl1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.4866 ADGRL1 Elena Savva Classified gene: ADGRL1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4866 ADGRL1 Elena Savva Gene: adgrl1 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.177 RAC3 Alison Yeung gene: RAC3 was added
gene: RAC3 was added to Polymicrogyria and Schizencephaly. Sources: Literature
Mode of inheritance for gene: RAC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAC3 were set to 35851598
Phenotypes for gene: RAC3 were set to Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies, MIM#618577
Review for gene: RAC3 was set to GREEN
Added comment: Polymicrogyria commonly reported in cohort of 10 patients
Sources: Literature
Hereditary Neuropathy - complex v0.128 RFC1 Ain Roesley reviewed gene: RFC1: Rating: AMBER; Mode of pathogenicity: None; Publications: 35883251; Phenotypes: Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome MIM#614575; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic Epilepsy v0.1636 PPFIBP1 Ee Ming Wong reviewed gene: PPFIBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35830857; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, PPFIBP1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic Epilepsy v0.1636 ADGRL1 Elena Savva gene: ADGRL1 was added
gene: ADGRL1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: ADGRL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ADGRL1 were set to PMID: 35907405
Phenotypes for gene: ADGRL1 were set to Neurodevelopmental disorder, ADGRL1-related (MONDO#0700092)
Review for gene: ADGRL1 was set to AMBER
Added comment: PMID: 35907405 - 9 patients, only had epilepsy (2/9).

Het null mouse model shows neurological and developmental abnormalities, with hom null mice non-viable.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4865 DOHH Daniel Flanagan gene: DOHH was added
gene: DOHH was added to Intellectual disability syndromic and non-syndromic. Sources: Expert list
Mode of inheritance for gene: DOHH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DOHH were set to PMID: 35858628
Phenotypes for gene: DOHH were set to Neurodevelopmental disorder, DOHH-related (MONDO#0700092)
Review for gene: DOHH was set to GREEN
Added comment: Bi-allelic missense and truncating DOHH variants segregating with disease in five affected individuals from four unrelated families. Clinical features were developmental delay and/or intellectual disability (5/5), microcephaly (5/5), visual impairment (nystagmus (3/5), strabismus (3/5), and cortical visual impairment (1/5)) and congenital heart malformations (3/5 individuals).
Sources: Expert list
Mendeliome v1.204 ADGRL1 Elena Savva gene: ADGRL1 was added
gene: ADGRL1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ADGRL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ADGRL1 were set to PMID: 35907405
Phenotypes for gene: ADGRL1 were set to Neurodevelopmental disorder, ADGRL1-related (MONDO#0700092)
Review for gene: ADGRL1 was set to GREEN
Added comment: PMID: 35907405 - 9 patients w/ ADHD (3/9), autism (4/9), mild-moderate ID (5/9) and epilepsy (2/9) and facial dysmorphism (7/9). Variants include missense (4) and PTCs (5), and were either de novo (7/9) or inherited from parents with learning difficulties/ID (2/9).

Functional studies on both PTCs and missense variants show significant reductions in calcium signalling and surface protein.

Het null mouse model shows neurological and developmental abnormalities, with hom null mice non-viable.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4865 ADGRL1 Elena Savva gene: ADGRL1 was added
gene: ADGRL1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ADGRL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ADGRL1 were set to PMID: 35907405
Phenotypes for gene: ADGRL1 were set to Neurodevelopmental disorder, ADGRL1-related (MONDO#0700092)
Review for gene: ADGRL1 was set to GREEN
Added comment: PMID: 35907405 - 9 patients w/ ADHD (3/9), autism (4/9), mild-moderate ID (5/9) and epilepsy (2/9) and facial dysmorphism (7/9). Variants include missense (4) and PTCs (5), and were either de novo (7/9) or inherited from parents with learning difficulties/ID (2/9).

Functional studies on both PTCs and missense variants show significant reductions in calcium signalling and surface protein.

Het null mouse model shows neurological and developmental abnormalities, with hom null mice non-viable.
Sources: Literature
Callosome v0.457 RAC3 Alison Yeung Marked gene: RAC3 as ready
Callosome v0.457 RAC3 Alison Yeung Gene: rac3 has been classified as Green List (High Evidence).
Callosome v0.457 RAC3 Alison Yeung Classified gene: RAC3 as Green List (high evidence)
Callosome v0.457 RAC3 Alison Yeung Gene: rac3 has been classified as Green List (High Evidence).
Callosome v0.456 RAC3 Alison Yeung gene: RAC3 was added
gene: RAC3 was added to Callosome. Sources: Literature
Mode of inheritance for gene: RAC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAC3 were set to 35851598
Phenotypes for gene: RAC3 were set to Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies, MIM#618577
Review for gene: RAC3 was set to GREEN
Added comment: Corpus callosal abnormalities reported in 100% of cohort of 10 patients
Sources: Literature
Congenital Heart Defect v0.258 DNAH9 Zornitza Stark Marked gene: DNAH9 as ready
Congenital Heart Defect v0.258 DNAH9 Zornitza Stark Gene: dnah9 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.258 DNAH9 Zornitza Stark Classified gene: DNAH9 as Green List (high evidence)
Congenital Heart Defect v0.258 DNAH9 Zornitza Stark Gene: dnah9 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.257 DNAH9 Zornitza Stark gene: DNAH9 was added
gene: DNAH9 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: DNAH9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAH9 were set to 35116053; 35050399; 30471717; 30471718
Phenotypes for gene: DNAH9 were set to Ciliary dyskinesia, primary, 40 618300; Heterotaxy
Review for gene: DNAH9 was set to GREEN
Added comment: Multiple families reported including with significant CHD.
Sources: Literature
Heterotaxy v1.20 DNAH9 Zornitza Stark reviewed gene: DNAH9: Rating: GREEN; Mode of pathogenicity: None; Publications: 35116053, 35050399; Phenotypes: Ciliary dyskinesia, primary, 40 618300, Heterotaxy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.203 EHHADH Zornitza Stark Classified gene: EHHADH as Amber List (moderate evidence)
Mendeliome v1.203 EHHADH Zornitza Stark Gene: ehhadh has been classified as Amber List (Moderate Evidence).
Mendeliome v1.202 EHHADH Zornitza Stark edited their review of gene: EHHADH: Added comment: https://clinmedjournals.org/articles/jcnrc/journal-of-clinical-nephrology-and-renal-care-jcnrc-3-027.pdf

Second case report, same variant, de novo. Also, experimental evidence. Assessed as MODERATE by ClinGen.; Changed rating: AMBER
Inflammatory bowel disease v0.82 NOX1 Peter McNaughton gene: NOX1 was added
gene: NOX1 was added to Inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: NOX1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: NOX1 were set to PMID: 29091079; 32064493
Phenotypes for gene: NOX1 were set to Inflammatory bowel disease
Review for gene: NOX1 was set to AMBER
Added comment: 8 IBD patients with early onset of IBD with progressive and severe colonic disease, refractory to conventional therapy and functional studies suggesting variant-dependent loss of NOX1-mediated superoxide generation. However, high frequency of nonsynonymous mutations in NOX1 suggests that NOX1 is not a highly penetrant Mendelian disorder and that other genetic modifiers or environmental factors may contribute to disease pathogenesis
Sources: Literature
Pulmonary Arterial Hypertension v1.13 SARS2 Zornitza Stark Marked gene: SARS2 as ready
Pulmonary Arterial Hypertension v1.13 SARS2 Zornitza Stark Gene: sars2 has been classified as Green List (High Evidence).
Mendeliome v1.202 DUOX2 Zornitza Stark Phenotypes for gene: DUOX2 were changed from Thyroid dyshormonogenesis 6 - MIM#607200 to Thyroid dyshormonogenesis 6 - MIM#607200; Inflammatory bowel disease, MONDO:0005265, DUOX2-related
Mendeliome v1.201 DUOX2 Zornitza Stark Publications for gene: DUOX2 were set to
Mendeliome v1.200 DUOX2 Zornitza Stark Mode of inheritance for gene: DUOX2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.199 DUOX2 Zornitza Stark Classified gene: DUOX2 as Amber List (moderate evidence)
Mendeliome v1.199 DUOX2 Zornitza Stark Gene: duox2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.198 DUOX2 Zornitza Stark reviewed gene: DUOX2: Rating: AMBER; Mode of pathogenicity: None; Publications: 35429653, 27373512, 26301257, 28683258; Phenotypes: Inflammatory bowel disease, MONDO:0005265, DUOX2-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Inflammatory bowel disease v0.82 DUOX2 Zornitza Stark Marked gene: DUOX2 as ready
Inflammatory bowel disease v0.82 DUOX2 Zornitza Stark Gene: duox2 has been classified as Amber List (Moderate Evidence).
Inflammatory bowel disease v0.82 DUOX2 Zornitza Stark Phenotypes for gene: DUOX2 were changed from Colitis to Inflammatory bowel disease, MONDO:0005265, DUOX2-related
Inflammatory bowel disease v0.81 DUOX2 Zornitza Stark Classified gene: DUOX2 as Amber List (moderate evidence)
Inflammatory bowel disease v0.81 DUOX2 Zornitza Stark Gene: duox2 has been classified as Amber List (Moderate Evidence).
Inflammatory bowel disease v0.80 DUOX2 Zornitza Stark reviewed gene: DUOX2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hydrocephalus_Ventriculomegaly v0.118 CWH43 Zornitza Stark Marked gene: CWH43 as ready
Hydrocephalus_Ventriculomegaly v0.118 CWH43 Zornitza Stark Gene: cwh43 has been classified as Red List (Low Evidence).
Hydrocephalus_Ventriculomegaly v0.118 CWH43 Zornitza Stark gene: CWH43 was added
gene: CWH43 was added to Hydrocephalus_Ventriculomegaly. Sources: Expert Review
cnv tags were added to gene: CWH43.
Mode of inheritance for gene: CWH43 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CWH43 were set to 33459505; 34380733
Phenotypes for gene: CWH43 were set to Hydrocephalus MONDO:0001150, CWH43-related
Review for gene: CWH43 was set to RED
Added comment: Two individuals with recurrent deletion reported.
Sources: Expert Review
Ataxia - adult onset v0.166 Zornitza Stark removed gene:CWH43 from the panel
Mendeliome v1.198 CWH43 Zornitza Stark Marked gene: CWH43 as ready
Mendeliome v1.198 CWH43 Zornitza Stark Gene: cwh43 has been classified as Red List (Low Evidence).
Mendeliome v1.198 CWH43 Zornitza Stark Phenotypes for gene: CWH43 were changed from normal pressure hydrocephalus to Hydrocephalus MONDO:0001150, CWH43-related
Mendeliome v1.197 CWH43 Zornitza Stark Classified gene: CWH43 as Red List (low evidence)
Mendeliome v1.197 CWH43 Zornitza Stark Gene: cwh43 has been classified as Red List (Low Evidence).
Mendeliome v1.196 CWH43 Zornitza Stark Tag cnv tag was added to gene: CWH43.
Mendeliome v1.196 CWH43 Zornitza Stark reviewed gene: CWH43: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hydrocephalus MONDO:0001150, CWH43-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary Arterial Hypertension v1.13 SARS2 Chirag Patel Classified gene: SARS2 as Green List (high evidence)
Pulmonary Arterial Hypertension v1.13 SARS2 Chirag Patel Gene: sars2 has been classified as Green List (High Evidence).
Pulmonary Arterial Hypertension v1.12 SARS2 Chirag Patel gene: SARS2 was added
gene: SARS2 was added to Pulmonary Arterial Hypertension. Sources: Literature
Mode of inheritance for gene: SARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SARS2 were set to 24034276; 21255763; 33751860
Phenotypes for gene: SARS2 were set to Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis, MIM#613845
Review for gene: SARS2 was set to GREEN
Added comment: HUPRA syndrome is a severe autosomal recessive multisystem disorder characterized by onset in infancy of progressive renal failure leading to electrolyte imbalances, metabolic alkalosis, pulmonary hypertension, hypotonia, and delayed development. Six patients from 4 unrelated families reported - only 1 patient did not have PAH.
Sources: Literature
Limb and Digital Malformations SuperPanel v0.28 Zornitza Stark Panel types changed to Superpanel; Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Inflammatory bowel disease v0.80 DUOX2 Peter McNaughton gene: DUOX2 was added
gene: DUOX2 was added to Inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: DUOX2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: DUOX2 were set to PMID: 35429653; 27373512; 26301257; 28683258
Phenotypes for gene: DUOX2 were set to Colitis
Review for gene: DUOX2 was set to AMBER
Added comment: 4 case reports of early onset colitis (1-4y) associated with monoallelic or biallelic variants in NOX2. Also reported in 15 members of the same Ashkenazi Jewish family with a high incidence of adult-onset CD.
Sources: Literature
Ataxia - adult onset v0.165 CWH43 Anna Le Fevre gene: CWH43 was added
gene: CWH43 was added to Ataxia - adult onset. Sources: Literature
Mode of inheritance for gene: CWH43 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CWH43 were set to PMID: 33459505; 34380733
Phenotypes for gene: CWH43 were set to normal pressure hydrocephalus
Penetrance for gene: CWH43 were set to Incomplete
Review for gene: CWH43 was set to AMBER
Added comment: Sources: Literature
Mendeliome v1.196 CWH43 Anna Le Fevre gene: CWH43 was added
gene: CWH43 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CWH43 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CWH43 were set to PMID: 33459505; 34380733
Phenotypes for gene: CWH43 were set to normal pressure hydrocephalus
Penetrance for gene: CWH43 were set to Incomplete
Review for gene: CWH43 was set to AMBER
Added comment: Sources: Literature
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.128 ADGRA3 Zornitza Stark Marked gene: ADGRA3 as ready
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.128 ADGRA3 Zornitza Stark Gene: adgra3 has been classified as Red List (Low Evidence).
Retinitis pigmentosa_Autosomal Recessive/X-linked v0.128 ADGRA3 Zornitza Stark Phenotypes for gene: ADGRA3 were changed from retinal dystrophy to Retinitis pigmentosa, MONDO:0019200, ADGRA3-related
Mendeliome v1.196 ADGRA3 Zornitza Stark Marked gene: ADGRA3 as ready
Mendeliome v1.196 ADGRA3 Zornitza Stark Gene: adgra3 has been classified as Red List (Low Evidence).
Mendeliome v1.196 ADGRA3 Zornitza Stark gene: ADGRA3 was added
gene: ADGRA3 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: ADGRA3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADGRA3 were set to 23105016
Phenotypes for gene: ADGRA3 were set to Retinitis pigmentosa, MONDO:0019200, ADGRA3-related
Review for gene: ADGRA3 was set to RED
Added comment: Only one report of a missense that is a VUS identified as a candidate through autozygome analysis (PMID: 23105016)
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.4864 TAF8 Zornitza Stark Phenotypes for gene: TAF8 were changed from Neurodevelopmental disorder, MONDO:0700092, TAF8-related to Neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy, MIM# 619972
Intellectual disability syndromic and non-syndromic v0.4863 TAF8 Zornitza Stark edited their review of gene: TAF8: Changed phenotypes: Neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy, MIM# 619972
Genetic Epilepsy v0.1635 TAF8 Zornitza Stark Phenotypes for gene: TAF8 were changed from Neurodevelopmental disorder, MONDO:0700092, TAF8-related to Neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy, MIM# 619972
Microcephaly v1.138 TAF8 Zornitza Stark Phenotypes for gene: TAF8 were changed from Neurodevelopmental disorder, MONDO:0700092, TAF8-related to Neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy, MIM# 619972
Genetic Epilepsy v0.1634 TAF8 Zornitza Stark edited their review of gene: TAF8: Changed phenotypes: Neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy, MIM# 619972
Microcephaly v1.137 TAF8 Zornitza Stark edited their review of gene: TAF8: Changed phenotypes: Neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy, MIM# 619972
Mendeliome v1.195 TAF8 Zornitza Stark Phenotypes for gene: TAF8 were changed from Neurodevelopmental disorder, MONDO:0700092, TAF8-related to Neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy, MIM# 619972
Mendeliome v1.194 TAF8 Zornitza Stark edited their review of gene: TAF8: Changed phenotypes: Neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy, MIM# 619972
Holoprosencephaly and septo-optic dysplasia v1.6 ARID1A Zornitza Stark Marked gene: ARID1A as ready
Holoprosencephaly and septo-optic dysplasia v1.6 ARID1A Zornitza Stark Gene: arid1a has been classified as Amber List (Moderate Evidence).
Holoprosencephaly and septo-optic dysplasia v1.6 ARID1A Zornitza Stark Classified gene: ARID1A as Amber List (moderate evidence)
Holoprosencephaly and septo-optic dysplasia v1.6 ARID1A Zornitza Stark Gene: arid1a has been classified as Amber List (Moderate Evidence).
Holoprosencephaly and septo-optic dysplasia v1.5 ARID1A Zornitza Stark reviewed gene: ARID1A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Coffin-Siris syndrome 2 #614607; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Holoprosencephaly and septo-optic dysplasia v1.5 SOX2 Zornitza Stark Marked gene: SOX2 as ready
Holoprosencephaly and septo-optic dysplasia v1.5 SOX2 Zornitza Stark Gene: sox2 has been classified as Amber List (Moderate Evidence).
Holoprosencephaly and septo-optic dysplasia v1.5 SOX2 Zornitza Stark Classified gene: SOX2 as Amber List (moderate evidence)
Holoprosencephaly and septo-optic dysplasia v1.5 SOX2 Zornitza Stark Gene: sox2 has been classified as Amber List (Moderate Evidence).
Holoprosencephaly and septo-optic dysplasia v1.4 SOX2 Zornitza Stark reviewed gene: SOX2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Optic nerve hypoplasia and abnormalities of the central nervous system #206900, Microphthalmia, syndromic 3 #206900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Holoprosencephaly and septo-optic dysplasia v1.4 ARID1A Di Milnes gene: ARID1A was added
gene: ARID1A was added to Holoprosencephaly and septo-optic dysplasia. Sources: Literature
Mode of inheritance for gene: ARID1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARID1A were set to 35885948
Phenotypes for gene: ARID1A were set to Coffin-Siris syndrome 2 #614607
Review for gene: ARID1A was set to AMBER
Added comment: single case SOD (absent septum pellucidum, absent corpus callosum, ventriculomegaly, aqueductal stenosis ONH), a ventricular septal defect and a patent foramen ovale, 13 pairs of ribs, bilateral clinodactyly, single palmar crease, broad large toe with hypoplastic nail, cleft palate, choanal atresia, seizures, apnoea, and dysmorphic facial features, including down-slanting palpebral fissures, long columella, low-set and posteriorly rotated ears, depressed nasal bridge, scant hair due to premature birth; he died at 6 weeks of age.
Mosaic truncating variant confirmed de novo Sanger sequencing (33% exome reads, lower peak on Sanger)
Sources: Literature
Holoprosencephaly and septo-optic dysplasia v1.4 SOX2 Di Milnes gene: SOX2 was added
gene: SOX2 was added to Holoprosencephaly and septo-optic dysplasia. Sources: Literature
Mode of inheritance for gene: SOX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX2 were set to 35885948
Phenotypes for gene: SOX2 were set to Optic nerve hypoplasia and abnormalities of the central nervous system #206900; Microphthalmia, syndromic 3 #206900
Review for gene: SOX2 was set to AMBER
Added comment: single case SOD (mild ONH, absent septum pellucidum, hypoplasia corpus callosum, dilated lateral ventricles de novo trio WES confirmed Sanger sequencing
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4863 POU3F3 Zornitza Stark Phenotypes for gene: POU3F3 were changed from Snijders Blok-Fisher syndrome MIM#618604 to Snijders Blok-Fisher syndrome MIM#618604
Intellectual disability syndromic and non-syndromic v0.4862 POU3F3 Zornitza Stark Phenotypes for gene: POU3F3 were changed from no OMIM number yet. to Snijders Blok-Fisher syndrome MIM#618604
Intellectual disability syndromic and non-syndromic v0.4861 POU3F3 Zornitza Stark reviewed gene: POU3F3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Snijders Blok-Fisher syndrome MIM#618604; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.194 POU3F3 Zornitza Stark Phenotypes for gene: POU3F3 were changed from Intellectual disability to Snijders Blok-Fisher syndrome MIM#618604
Mendeliome v1.193 POU3F3 Zornitza Stark edited their review of gene: POU3F3: Changed phenotypes: Snijders Blok-Fisher syndrome MIM#618604
Congenital Heart Defect v0.256 ROBO4 Zornitza Stark Phenotypes for gene: ROBO4 were changed from bicuspid aortic valve; ascending aortic aneurysm; ascending aorta dilatation to Aortic valve disease 8, MIM# 618496; bicuspid aortic valve; ascending aortic aneurysm; ascending aorta dilatation
Congenital Heart Defect v0.255 ROBO4 Zornitza Stark Classified gene: ROBO4 as Amber List (moderate evidence)
Congenital Heart Defect v0.255 ROBO4 Zornitza Stark Gene: robo4 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.254 ROBO4 Zornitza Stark Deleted their comment
Congenital Heart Defect v0.254 ROBO4 Zornitza Stark edited their review of gene: ROBO4: Added comment: LoF variants in this gene have high frequency in gnomad. Only two families reported. Functional data is not entirely convincing. May be a susceptibility factor to a relatively common phenotype (bicuspid aortic valve).; Changed rating: AMBER; Changed publications: 30455415; Changed phenotypes: Aortic valve disease 8, MIM# 618496, bicuspid aortic valve, ascending aortic aneurysm, ascending aorta dilatation; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Aortopathy_Connective Tissue Disorders v1.68 ROBO4 Zornitza Stark Classified gene: ROBO4 as Amber List (moderate evidence)
Aortopathy_Connective Tissue Disorders v1.68 ROBO4 Zornitza Stark Gene: robo4 has been classified as Amber List (Moderate Evidence).
Aortopathy_Connective Tissue Disorders v1.67 ROBO4 Zornitza Stark Deleted their comment
Aortopathy_Connective Tissue Disorders v1.67 ROBO4 Zornitza Stark edited their review of gene: ROBO4: Added comment: LoF variants in this gene have high frequency in gnomad.

Only two families reported. Functional data is not entirely convincing. May be a susceptibility factor to a relatively common phenotype (bicuspid aortic valve).; Changed rating: AMBER
Mendeliome v1.193 ROBO4 Zornitza Stark Phenotypes for gene: ROBO4 were changed from bicuspid aortic valve; ascending aortic aneurysm; ascending aorta dilatation to Aortic valve disease 8, MIM#618496; bicuspid aortic valve; ascending aortic aneurysm; ascending aorta dilatation
Mendeliome v1.192 ROBO4 Zornitza Stark Publications for gene: ROBO4 were set to 30455415
Mendeliome v1.191 ROBO4 Zornitza Stark Classified gene: ROBO4 as Amber List (moderate evidence)
Mendeliome v1.191 ROBO4 Zornitza Stark Gene: robo4 has been classified as Amber List (Moderate Evidence).
Monogenic Diabetes v0.30 EIF2B1 Zornitza Stark Marked gene: EIF2B1 as ready
Monogenic Diabetes v0.30 EIF2B1 Zornitza Stark Gene: eif2b1 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.30 EIF2B1 Zornitza Stark Classified gene: EIF2B1 as Green List (high evidence)
Monogenic Diabetes v0.30 EIF2B1 Zornitza Stark Gene: eif2b1 has been classified as Green List (High Evidence).
Monogenic Diabetes v0.29 EIF2B1 Zornitza Stark gene: EIF2B1 was added
gene: EIF2B1 was added to Monogenic Diabetes. Sources: Expert Review
Mode of inheritance for gene: EIF2B1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EIF2B1 were set to 31882561
Phenotypes for gene: EIF2B1 were set to Neonatal diabetes mellitus, MONDO:0016391, EIF2B1-related
Review for gene: EIF2B1 was set to GREEN
Added comment: PMID: 31882561: heterozygous de novo variants in 5 patients with permanent neonatal/early onset diabetes and transient liver dysfunction (4 missense, 1 stop-loss). No functional studies performed, missense clustered within a small region (p.Leu34-Ser77).
Sources: Expert Review
Mendeliome v1.190 EIF2B1 Zornitza Stark Phenotypes for gene: EIF2B1 were changed from leukoencephalopathy with vanishing white matter MONDO:0011380; ataxia; spasticity; optic atrophy to leukoencephalopathy with vanishing white matter MONDO:0011380; ataxia; spasticity; optic atrophy; Neonatal diabetes mellitus, MONDO:0016391, EIF2B1-related
Mendeliome v1.189 EIF2B1 Zornitza Stark Publications for gene: EIF2B1 were set to 11835386; 26285592; 15776425; 18263758; 25843247; 25761052; 30014503
Mendeliome v1.188 EIF2B1 Zornitza Stark Mode of inheritance for gene: EIF2B1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.187 EIF2B1 Zornitza Stark reviewed gene: EIF2B1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neonatal diabetes mellitus, MONDO:0016391, EIF2B1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardiomyopathy_Paediatric v0.133 MCM10 Zornitza Stark Classified gene: MCM10 as Amber List (moderate evidence)
Cardiomyopathy_Paediatric v0.133 MCM10 Zornitza Stark Gene: mcm10 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v0.132 MCM10 Zornitza Stark edited their review of gene: MCM10: Added comment: Upgraded due to functional evidence.; Changed rating: AMBER
Mendeliome v1.187 MCM10 Zornitza Stark Publications for gene: MCM10 were set to 32865517; 33712616
Mendeliome v1.186 MCM10 Zornitza Stark Classified gene: MCM10 as Amber List (moderate evidence)
Mendeliome v1.186 MCM10 Zornitza Stark Gene: mcm10 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.185 MCM10 Zornitza Stark edited their review of gene: MCM10: Added comment: PMID 33712616: further functional validation.; Changed rating: AMBER; Changed publications: 32865517, 33712616, 33712616
Susceptibility to Viral Infections v0.93 MCM10 Zornitza Stark Publications for gene: MCM10 were set to 32865517
Susceptibility to Viral Infections v0.92 MCM10 Zornitza Stark Classified gene: MCM10 as Amber List (moderate evidence)
Susceptibility to Viral Infections v0.92 MCM10 Zornitza Stark Gene: mcm10 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.35 ASXL3 Zornitza Stark Publications for gene: ASXL3 were set to
Cerebral Palsy v1.34 ASXL3 Zornitza Stark Classified gene: ASXL3 as Green List (high evidence)
Cerebral Palsy v1.34 ASXL3 Zornitza Stark Gene: asxl3 has been classified as Green List (High Evidence).
Autoinflammatory Disorders v0.163 CEBPE Zornitza Stark Marked gene: CEBPE as ready
Autoinflammatory Disorders v0.163 CEBPE Zornitza Stark Gene: cebpe has been classified as Amber List (Moderate Evidence).
Autoinflammatory Disorders v0.163 CEBPE Zornitza Stark Phenotypes for gene: CEBPE were changed from Autoinflammation to Autoinflammatory syndrome MONDO:0019751, CEBPE-related
Autoinflammatory Disorders v0.162 CEBPE Zornitza Stark Classified gene: CEBPE as Amber List (moderate evidence)
Autoinflammatory Disorders v0.162 CEBPE Zornitza Stark Gene: cebpe has been classified as Amber List (Moderate Evidence).
Autoinflammatory Disorders v0.161 CEBPE Zornitza Stark changed review comment from: Three individuals from a single family homozygous for a missense variant. Extensive functional data presented.; to: Three individuals from a single family homozygous for a missense variant. Extensive functional data presented. Gene already has an established role in immunological disorders.
Autoinflammatory Disorders v0.161 CEBPE Zornitza Stark reviewed gene: CEBPE: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.185 IKZF1 Zornitza Stark Phenotypes for gene: IKZF1 were changed from Immunodeficiency, common variable, 13 MIM# 616873; recurrent bacterial respiratory infections; Thrombocytopaenia; immunodeficiency; Hypogammaglobulinaemia; decrease B-cells; decrease B-cell differentiation; decrease memory B/T cells; Low Ig; pneumocystis early CID onset to Immunodeficiency, common variable, 13 MIM# 616873; recurrent bacterial respiratory infections; Thrombocytopaenia; immunodeficiency; Hypogammaglobulinaemia; decrease B-cells; decrease B-cell differentiation; decrease memory B/T cells; Low Ig; pneumocystis early CID onset; Immune dysregulation
Mendeliome v1.184 IKZF1 Zornitza Stark Publications for gene: IKZF1 were set to 21548011; 26981933; 29889099; 31057532; 7923373; 11805317
Mendeliome v1.183 IKZF1 Zornitza Stark edited their review of gene: IKZF1: Added comment: PMID 35333544: Eight individuals harboring heterozygous IKZF1R183H or IKZF1R183C variants associated with GOF effects reported. The clinical phenotypes and pathophysiology associated with IKZF1R183H/C differ from those of previously reported patients with IKZF1HI, IKZF1DN, and IKZF1DD and should therefore be considered as a novel IKAROS-associated disease entity. This condition is characterized by immune dysregulation manifestations including inflammation, autoimmunity, atopy, and polyclonal PC proliferation.; Changed publications: 21548011, 26981933, 29889099, 31057532, 7923373, 11805317, 35333544; Changed phenotypes: Immunodeficiency, common variable, 13 MIM# 616873, recurrent bacterial respiratory infections, Thrombocytopaenia, immunodeficiency, Hypogammaglobulinaemia, decrease B-cells, decrease B-cell differentiation, decrease memory B/T cells, Low Ig, pneumocystis early CID onset, Immune dysregulation
Autoinflammatory Disorders v0.161 TBK1 Zornitza Stark Phenotypes for gene: TBK1 were changed from Autoinflammation to Immunodeficiency, MONDO:0021094, TBK1-related, AR; Autoinflammation
Mendeliome v1.183 IKZF2 Zornitza Stark Phenotypes for gene: IKZF2 were changed from Immune dysregulation to Immunodeficiency, MONDO:0021094, IKZF2-related; Immune dysregulation
Mendeliome v1.182 IKZF2 Zornitza Stark Publications for gene: IKZF2 were set to 34920454
Mendeliome v1.181 IKZF2 Zornitza Stark Mode of inheritance for gene: IKZF2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.180 IKZF2 Zornitza Stark edited their review of gene: IKZF2: Added comment: Iranian male with homozygous missense variant with recurrent infection, hypogammaglobulinaemia. Extends inheritance to AR. Supportive functional data.; Changed publications: 34920454, 34826259; Changed phenotypes: Immunodeficiency, MONDO:0021094, IKZF2-related, Immune dysregulation; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Disorders of immune dysregulation v0.151 IKZF2 Zornitza Stark Phenotypes for gene: IKZF2 were changed from Immune dysregulation to Immunodeficiency, MONDO:0021094, IKZF2-related; Immune dysregulation
Disorders of immune dysregulation v0.150 IKZF2 Zornitza Stark Publications for gene: IKZF2 were set to 34920454
Disorders of immune dysregulation v0.149 IKZF2 Zornitza Stark Mode of inheritance for gene: IKZF2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary Spastic Paraplegia - paediatric v1.40 TMEM63C Zornitza Stark Phenotypes for gene: TMEM63C were changed from Hereditary spastic paraplegia, MONDO:0019064, TMEM63C-related to Spastic paraplegia 87, autosomal recessive, MIM# 619966
Hereditary Spastic Paraplegia - paediatric v1.39 TMEM63C Zornitza Stark reviewed gene: TMEM63C: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 87, autosomal recessive, MIM# 619966; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4861 TMEM63C Zornitza Stark Phenotypes for gene: TMEM63C were changed from Hereditary spastic paraplegia, MONDO:0019064, TMEM63C-related to Spastic paraplegia 87, autosomal recessive, MIM# 619966
Intellectual disability syndromic and non-syndromic v0.4860 TMEM63C Zornitza Stark reviewed gene: TMEM63C: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 87, autosomal recessive, MIM# 619966; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.180 TMEM63C Zornitza Stark Marked gene: TMEM63C as ready
Mendeliome v1.180 TMEM63C Zornitza Stark Gene: tmem63c has been classified as Green List (High Evidence).
Mendeliome v1.180 TMEM63C Zornitza Stark Phenotypes for gene: TMEM63C were changed from Hereditary spastic paraplegia, MONDO:0019064, TMEM63C-related to Spastic paraplegia 87, autosomal recessive, MIM# 619966
Mendeliome v1.179 TMEM63C Zornitza Stark reviewed gene: TMEM63C: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 87, autosomal recessive, MIM# 619966; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.95 WNT10A Zornitza Stark Marked gene: WNT10A as ready
Prepair 1000+ v0.95 WNT10A Zornitza Stark Gene: wnt10a has been classified as Red List (Low Evidence).
Prepair 1000+ v0.95 WNT10A Zornitza Stark Classified gene: WNT10A as Red List (low evidence)
Prepair 1000+ v0.95 WNT10A Zornitza Stark Gene: wnt10a has been classified as Red List (Low Evidence).
Prepair 1000+ v0.94 TFR2 Zornitza Stark Tag for review tag was added to gene: TFR2.
Prepair 1000+ v0.94 TECPR2 Zornitza Stark Marked gene: TECPR2 as ready
Prepair 1000+ v0.94 TECPR2 Zornitza Stark Gene: tecpr2 has been classified as Green List (High Evidence).
Prepair 1000+ v0.94 TECPR2 Zornitza Stark Classified gene: TECPR2 as Green List (high evidence)
Prepair 1000+ v0.94 TECPR2 Zornitza Stark Gene: tecpr2 has been classified as Green List (High Evidence).
Prepair 1000+ v0.93 TECPR2 Zornitza Stark reviewed gene: TECPR2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neuropathy, hereditary sensory and autonomic, type IX, with developmental delay, MIM#615031; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.93 TAT Zornitza Stark Tag for review tag was added to gene: TAT.
Prepair 1000+ v0.93 SLC4A11 Zornitza Stark Tag for review tag was added to gene: SLC4A11.
Prepair 1000+ v0.93 SLC26A4 Zornitza Stark Marked gene: SLC26A4 as ready
Prepair 1000+ v0.93 SLC26A4 Zornitza Stark Gene: slc26a4 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.93 SLC26A4 Zornitza Stark Classified gene: SLC26A4 as Red List (low evidence)
Prepair 1000+ v0.93 SLC26A4 Zornitza Stark Gene: slc26a4 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.92 SLC26A4 Zornitza Stark reviewed gene: SLC26A4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 4, with enlarged vestibular aqueduct (MIM#600791), Pendred syndrome (MIM#274600); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.92 SLC12A3 Zornitza Stark Tag for review tag was added to gene: SLC12A3.
Prepair 1000+ v0.92 RS1 Zornitza Stark Tag for review tag was added to gene: RS1.
Prepair 1000+ v0.92 PYGM Zornitza Stark Tag for review tag was added to gene: PYGM.
Prepair 1000+ v0.92 OAT Zornitza Stark Tag for review tag was added to gene: OAT.
Prepair 1000+ v0.92 NR2E3 Zornitza Stark Tag for review tag was added to gene: NR2E3.
Prepair 1000+ v0.92 MEFV Zornitza Stark Tag for review tag was added to gene: MEFV.
Prepair 1000+ v0.92 MCCC2 Zornitza Stark Marked gene: MCCC2 as ready
Prepair 1000+ v0.92 MCCC2 Zornitza Stark Gene: mccc2 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.92 MCCC2 Zornitza Stark Classified gene: MCCC2 as Red List (low evidence)
Prepair 1000+ v0.92 MCCC2 Zornitza Stark Gene: mccc2 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.91 MCCC1 Zornitza Stark reviewed gene: MCCC1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: 3-Methylcrotonyl-CoA carboxylase 1 deficiency (MIM#210200); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.91 MCCC1 Zornitza Stark Marked gene: MCCC1 as ready
Prepair 1000+ v0.91 MCCC1 Zornitza Stark Gene: mccc1 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.91 MCCC1 Zornitza Stark Classified gene: MCCC1 as Red List (low evidence)
Prepair 1000+ v0.91 MCCC1 Zornitza Stark Gene: mccc1 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.90 LOXHD1 Zornitza Stark Marked gene: LOXHD1 as ready
Prepair 1000+ v0.90 LOXHD1 Zornitza Stark Gene: loxhd1 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.90 LOXHD1 Zornitza Stark Classified gene: LOXHD1 as Red List (low evidence)
Prepair 1000+ v0.90 LOXHD1 Zornitza Stark Gene: loxhd1 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.89 LOXHD1 Zornitza Stark reviewed gene: LOXHD1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal recessive 77 (MIM#613079); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Autoinflammatory Disorders v0.160 ALPK1 Zornitza Stark Publications for gene: ALPK1 were set to 31053777
Autoinflammatory Disorders v0.159 ALPK1 Zornitza Stark Phenotypes for gene: ALPK1 were changed from Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome to Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache (ROSAH) syndrome, MIM#614979; Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome
Autoinflammatory Disorders v0.158 ALPK1 Zornitza Stark Classified gene: ALPK1 as Green List (high evidence)
Autoinflammatory Disorders v0.158 ALPK1 Zornitza Stark Gene: alpk1 has been classified as Green List (High Evidence).
Mendeliome v1.179 ROBO4 Elena Savva reviewed gene: ROBO4: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID:30455415, 32748548; Phenotypes: Aortic valve disease 8 MIM#618496; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v1.179 EIF2B1 Elena Savva reviewed gene: EIF2B1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31882561; Phenotypes: Leukoencephalopathy with vanishing white matter MIM#603896, permanent neonatal/early onset diabetes and transient liver dysfunction; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Disorders of immune dysregulation v0.148 IKZF1 Bryony Thompson Marked gene: IKZF1 as ready
Disorders of immune dysregulation v0.148 IKZF1 Bryony Thompson Gene: ikzf1 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.148 IKZF1 Bryony Thompson Classified gene: IKZF1 as Green List (high evidence)
Disorders of immune dysregulation v0.148 IKZF1 Bryony Thompson Gene: ikzf1 has been classified as Green List (High Evidence).
Autoinflammatory Disorders v0.157 TBK1 Bryony Thompson Marked gene: TBK1 as ready
Autoinflammatory Disorders v0.157 TBK1 Bryony Thompson Gene: tbk1 has been classified as Green List (High Evidence).
Autoinflammatory Disorders v0.157 TBK1 Bryony Thompson Classified gene: TBK1 as Green List (high evidence)
Autoinflammatory Disorders v0.157 TBK1 Bryony Thompson Gene: tbk1 has been classified as Green List (High Evidence).
Photosensitivity Syndromes v1.2 RECQL Bryony Thompson Marked gene: RECQL as ready
Photosensitivity Syndromes v1.2 RECQL Bryony Thompson Gene: recql has been classified as Amber List (Moderate Evidence).
Photosensitivity Syndromes v1.2 RECQL Bryony Thompson Classified gene: RECQL as Amber List (moderate evidence)
Photosensitivity Syndromes v1.2 RECQL Bryony Thompson Gene: recql has been classified as Amber List (Moderate Evidence).
Photosensitivity Syndromes v1.1 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Susceptibility to Viral Infections v0.91 MCM10 Peter McNaughton reviewed gene: MCM10: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 33712616; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.33 ASXL3 Clare van Eyk reviewed gene: ASXL3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35863334, 33528536; Phenotypes: Bainbridge-Ropers syndrome (MIM #615485); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4860 ARFGEF1 Zornitza Stark Phenotypes for gene: ARFGEF1 were changed from Intellectual disability; Epilepsy to Developmental delay, impaired speech, and behavioral abnormalities, MIM# 619964
Intellectual disability syndromic and non-syndromic v0.4859 ARFGEF1 Zornitza Stark edited their review of gene: ARFGEF1: Changed phenotypes: Developmental delay, impaired speech, and behavioral abnormalities, MIM# 619964
Autoinflammatory Disorders v0.156 CEBPE Peter McNaughton gene: CEBPE was added
gene: CEBPE was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: CEBPE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEBPE were set to PMID: 31201888
Phenotypes for gene: CEBPE were set to Autoinflammation
Mode of pathogenicity for gene: CEBPE was set to Other
Review for gene: CEBPE was set to AMBER
Added comment: Single family presenting with autoinflammatory syndrome - recurrent attacks of abdominal pain, aseptic fever, and systemic inflammation lasting 4 to 5 days. These were accompanied by an acute-phase response and occasionally by nailbed, tongue, submandibular and gluteal abscesses; intra-abdominal granulomas; pyoderma gangrenosum; and buccal ulcerations
Sources: Literature
Genetic Epilepsy v0.1634 ARFGEF1 Zornitza Stark Phenotypes for gene: ARFGEF1 were changed from Intellectual disability; Epilepsy to Developmental delay, impaired speech, and behavioral abnormalities, MIM# 619964
Genetic Epilepsy v0.1633 ARFGEF1 Zornitza Stark edited their review of gene: ARFGEF1: Changed phenotypes: Developmental delay, impaired speech, and behavioral abnormalities, MIM# 619964
Mendeliome v1.179 ARFGEF1 Zornitza Stark Phenotypes for gene: ARFGEF1 were changed from Intellectual disability; Epilepsy to Developmental delay, impaired speech, and behavioral abnormalities, MIM# 619964
Mendeliome v1.178 ARFGEF1 Zornitza Stark edited their review of gene: ARFGEF1: Changed phenotypes: Developmental delay, impaired speech, and behavioral abnormalities, MIM# 619964
Mendeliome v1.178 PAK2 Zornitza Stark Phenotypes for gene: PAK2 were changed from Knobloch 2 syndrome to Knobloch 2 syndrome, MIM#618458
Mendeliome v1.177 INPP5E Zornitza Stark Publications for gene: INPP5E were set to 19668216; 32139166; 29230161; 29052317; 27998989; 27401686; 19668215
Mendeliome v1.176 INPP5E Zornitza Stark edited their review of gene: INPP5E: Added comment: Additional MORM family reported in PMID 34211432, hmz LoF.; Changed publications: 19668216, 32139166, 29230161, 29052317, 27998989, 27401686, 19668215, 34211432
Disorders of immune dysregulation v0.147 IKZF1 Peter McNaughton gene: IKZF1 was added
gene: IKZF1 was added to Disorders of immune dysregulation. Sources: Literature
Mode of inheritance for gene: IKZF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IKZF1 were set to PMID: 35333544
Phenotypes for gene: IKZF1 were set to Immune dysregulation
Mode of pathogenicity for gene: IKZF1 was set to Other
Review for gene: IKZF1 was set to GREEN
Added comment: Eight individuals harboring heterozygous IKZF1R183H or IKZF1R183C variants associated with GOF effects. The clinical phenotypes and pathophysiology associated with IKZF1R183H/C differ from those of previously reported patients with IKZF1HI, IKZF1DN, and IKZF1DD and should therefore be considered as a novel IKAROS-associated disease entity. This condition is characterized by immune dysregulation manifestations including inflammation, autoimmunity, atopy, and polyclonal PC proliferation.
Sources: Literature
Autoinflammatory Disorders v0.156 TBK1 Peter McNaughton gene: TBK1 was added
gene: TBK1 was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: TBK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBK1 were set to PMID: 34363755
Phenotypes for gene: TBK1 were set to Autoinflammation
Review for gene: TBK1 was set to GREEN
Added comment: 4 individuals from 3 unrelated families with biallelic LOF mutations with early onset autoinflammatory syndrome without susceptibility to viral infection.
Sources: Literature
Disorders of immune dysregulation v0.147 IKZF2 Peter McNaughton reviewed gene: IKZF2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34826259; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Prepair 1000+ v0.89 HYAL1 Zornitza Stark Marked gene: HYAL1 as ready
Prepair 1000+ v0.89 HYAL1 Zornitza Stark Gene: hyal1 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.89 HYAL1 Zornitza Stark Classified gene: HYAL1 as Red List (low evidence)
Prepair 1000+ v0.89 HYAL1 Zornitza Stark Gene: hyal1 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.88 HOGA1 Zornitza Stark Tag for review tag was added to gene: HOGA1.
Prepair 1000+ v0.88 HGD Zornitza Stark Marked gene: HGD as ready
Prepair 1000+ v0.88 HGD Zornitza Stark Gene: hgd has been classified as Red List (Low Evidence).
Prepair 1000+ v0.88 HGD Zornitza Stark Classified gene: HGD as Red List (low evidence)
Prepair 1000+ v0.88 HGD Zornitza Stark Gene: hgd has been classified as Red List (Low Evidence).
Prepair 1000+ v0.87 HFE Zornitza Stark Marked gene: HFE as ready
Prepair 1000+ v0.87 HFE Zornitza Stark Gene: hfe has been classified as Red List (Low Evidence).
Prepair 1000+ v0.87 HFE Zornitza Stark Classified gene: HFE as Red List (low evidence)
Prepair 1000+ v0.87 HFE Zornitza Stark Gene: hfe has been classified as Red List (Low Evidence).
Prepair 1000+ v0.86 HBA2 Zornitza Stark Tag for review tag was added to gene: HBA2.
Prepair 1000+ v0.86 HBA1 Zornitza Stark Tag for review tag was added to gene: HBA1.
Prepair 1000+ v0.86 GRHPR Zornitza Stark Tag for review tag was added to gene: GRHPR.
Prepair 1000+ v0.86 GP9 Zornitza Stark Tag for review tag was added to gene: GP9.
Prepair 1000+ v0.86 GP1BA Zornitza Stark Tag for review tag was added to gene: GP1BA.
Prepair 1000+ v0.86 GJB2 Zornitza Stark Marked gene: GJB2 as ready
Prepair 1000+ v0.86 GJB2 Zornitza Stark Gene: gjb2 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.86 GJB2 Zornitza Stark Classified gene: GJB2 as Red List (low evidence)
Prepair 1000+ v0.86 GJB2 Zornitza Stark Gene: gjb2 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.85 GJB2 Zornitza Stark reviewed gene: GJB2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Prepair 1000+ v0.85 GJB1 Zornitza Stark Tag for review tag was added to gene: GJB1.
Prepair 1000+ v0.85 GALK1 Zornitza Stark Tag for review tag was added to gene: GALK1.
Prepair 1000+ v0.85 G6PD Zornitza Stark Tag for review tag was added to gene: G6PD.
Prepair 1000+ v0.85 F11 Zornitza Stark Tag for review tag was added to gene: F11.
Susceptibility to Fungal Infections v1.6 CLEC7A Zornitza Stark Marked gene: CLEC7A as ready
Susceptibility to Fungal Infections v1.6 CLEC7A Zornitza Stark Gene: clec7a has been classified as Red List (Low Evidence).
Susceptibility to Fungal Infections v1.6 CLEC7A Zornitza Stark Phenotypes for gene: CLEC7A were changed from Mucocutaneous candidiasis to Candidiasis, familial, 4, autosomal recessive MIM#613108; {Aspergillosis, susceptibility to} , MIM#614079; Mucocutaneous candidiasis
Susceptibility to Fungal Infections v1.5 CLEC7A Zornitza Stark Classified gene: CLEC7A as Red List (low evidence)
Susceptibility to Fungal Infections v1.5 CLEC7A Zornitza Stark Gene: clec7a has been classified as Red List (Low Evidence).
Susceptibility to Fungal Infections v1.4 CLEC7A Zornitza Stark reviewed gene: CLEC7A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Candidiasis, familial, 4, autosomal recessive MIM#613108; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Susceptibility to Fungal Infections v1.4 STAT3 Zornitza Stark Marked gene: STAT3 as ready
Susceptibility to Fungal Infections v1.4 STAT3 Zornitza Stark Gene: stat3 has been classified as Green List (High Evidence).
Susceptibility to Fungal Infections v1.4 STAT3 Zornitza Stark Phenotypes for gene: STAT3 were changed from Mucocutaneous candidiasis to Hyper-IgE recurrent infection syndrome , MIM#147060; Mucocutaneous candidiasis
Susceptibility to Fungal Infections v1.3 STAT3 Zornitza Stark Classified gene: STAT3 as Green List (high evidence)
Susceptibility to Fungal Infections v1.3 STAT3 Zornitza Stark Gene: stat3 has been classified as Green List (High Evidence).
Susceptibility to Fungal Infections v1.2 STAT3 Zornitza Stark reviewed gene: STAT3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hyper-IgE recurrent infection syndrome , MIM#147060; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Susceptibility to Fungal Infections v1.2 AIRE Zornitza Stark Marked gene: AIRE as ready
Susceptibility to Fungal Infections v1.2 AIRE Zornitza Stark Gene: aire has been classified as Green List (High Evidence).
Susceptibility to Fungal Infections v1.2 AIRE Zornitza Stark Phenotypes for gene: AIRE were changed from to Autoimmune polyendocrinopathy syndrome , type I, with or without reversible metaphyseal dysplasia, MIM# 240300
Susceptibility to Fungal Infections v1.1 AIRE Zornitza Stark Classified gene: AIRE as Green List (high evidence)
Susceptibility to Fungal Infections v1.1 AIRE Zornitza Stark Gene: aire has been classified as Green List (High Evidence).
Hydrops fetalis v0.290 SPTA1 Zornitza Stark Marked gene: SPTA1 as ready
Hydrops fetalis v0.290 SPTA1 Zornitza Stark Gene: spta1 has been classified as Green List (High Evidence).
Hydrops fetalis v0.290 SPTA1 Zornitza Stark Publications for gene: SPTA1 were set to 34132406; 35483216; 31333484; 29594000
Fetal anomalies v1.50 SPTA1 Zornitza Stark Marked gene: SPTA1 as ready
Fetal anomalies v1.50 SPTA1 Zornitza Stark Gene: spta1 has been classified as Green List (High Evidence).
Fetal anomalies v1.50 SPTA1 Zornitza Stark Classified gene: SPTA1 as Green List (high evidence)
Fetal anomalies v1.50 SPTA1 Zornitza Stark Gene: spta1 has been classified as Green List (High Evidence).
Hydrops fetalis v0.289 SPTA1 Zornitza Stark Publications for gene: SPTA1 were set to 34132406
Fetal anomalies v1.49 SPTA1 Zornitza Stark gene: SPTA1 was added
gene: SPTA1 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: SPTA1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SPTA1 were set to 34132406; 35483216; 31333484; 29594000
Phenotypes for gene: SPTA1 were set to Spherocytosis type 3 #270970; Elliptocytosis-2 #130600; pyropoikilocytosis #266140
Review for gene: SPTA1 was set to GREEN
Added comment: Severe presentations with hydrops reported.
Sources: Expert Review
Hydrops fetalis v0.289 SPTA1 Zornitza Stark Mode of inheritance for gene: SPTA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hydrops fetalis v0.288 SPTA1 Zornitza Stark Classified gene: SPTA1 as Green List (high evidence)
Hydrops fetalis v0.288 SPTA1 Zornitza Stark Gene: spta1 has been classified as Green List (High Evidence).
Hydrops fetalis v0.287 SPTA1 Zornitza Stark reviewed gene: SPTA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35483216, 31333484, 29594000; Phenotypes: Spherocytosis type 3 #270970, Elliptocytosis-2 #130600, Pyropoikilocytosis #266140; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hydrops fetalis v0.287 GLDN Zornitza Stark Marked gene: GLDN as ready
Hydrops fetalis v0.287 GLDN Zornitza Stark Gene: gldn has been classified as Amber List (Moderate Evidence).
Hydrops fetalis v0.287 GLDN Zornitza Stark Classified gene: GLDN as Amber List (moderate evidence)
Hydrops fetalis v0.287 GLDN Zornitza Stark Gene: gldn has been classified as Amber List (Moderate Evidence).
Hydrops fetalis v0.286 GLDN Zornitza Stark reviewed gene: GLDN: Rating: AMBER; Mode of pathogenicity: None; Publications: 35806855; Phenotypes: Lethal congenital contracture syndrome 11, MIM# 617194; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.85 EYS Zornitza Stark Tag for review tag was added to gene: EYS.
Hydrops fetalis v0.286 DOK7 Zornitza Stark Publications for gene: DOK7 were set to 31880392; 19261599
Hydrops fetalis v0.285 DOK7 Zornitza Stark Classified gene: DOK7 as Green List (high evidence)
Hydrops fetalis v0.285 DOK7 Zornitza Stark Gene: dok7 has been classified as Green List (High Evidence).
Hydrops fetalis v0.284 DOK7 Zornitza Stark edited their review of gene: DOK7: Added comment: Upgrade to Green with additional families published (founder variant).; Changed rating: GREEN; Changed publications: 31880392, 19261599, 34132406
Prepair 1000+ v0.85 CYP21A2 Zornitza Stark Tag for review tag was added to gene: CYP21A2.
Early-onset Parkinson disease v0.230 ATXN1_CAG Zornitza Stark Marked STR: ATXN1_CAG as ready
Early-onset Parkinson disease v0.230 ATXN1_CAG Zornitza Stark Str: atxn1_cag has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.230 ATXN1_CAG Zornitza Stark Classified STR: ATXN1_CAG as Green List (high evidence)
Early-onset Parkinson disease v0.230 ATXN1_CAG Zornitza Stark Str: atxn1_cag has been classified as Green List (High Evidence).
Congenital Heart Defect v0.254 KYNU Zornitza Stark Marked gene: KYNU as ready
Congenital Heart Defect v0.254 KYNU Zornitza Stark Gene: kynu has been classified as Green List (High Evidence).
Congenital Heart Defect v0.254 KYNU Zornitza Stark Phenotypes for gene: KYNU were changed from MIM# 617661 Vertebral, cardiac, renal, and limb defects syndrome 2 to Vertebral, cardiac, renal, and limb defects syndrome 2, MIM# 617661
Congenital Heart Defect v0.253 KYNU Zornitza Stark Classified gene: KYNU as Green List (high evidence)
Congenital Heart Defect v0.253 KYNU Zornitza Stark Gene: kynu has been classified as Green List (High Evidence).
Congenital Heart Defect v0.252 KDR Zornitza Stark Marked gene: KDR as ready
Congenital Heart Defect v0.252 KDR Zornitza Stark Gene: kdr has been classified as Red List (Low Evidence).
Congenital Heart Defect v0.252 KDR Zornitza Stark Phenotypes for gene: KDR were changed from Tetralogy of Fallot to Tetralogy of Fallot, MONDO:0008542
Congenital Heart Defect v0.251 KDR Zornitza Stark Mode of inheritance for gene: KDR was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.250 KDR Zornitza Stark Classified gene: KDR as Red List (low evidence)
Congenital Heart Defect v0.250 KDR Zornitza Stark Gene: kdr has been classified as Red List (Low Evidence).
Congenital Heart Defect v0.249 KDR Zornitza Stark reviewed gene: KDR: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Tetralogy of Fallot, MONDO:0008542; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.249 HDAC8 Zornitza Stark Marked gene: HDAC8 as ready
Congenital Heart Defect v0.249 HDAC8 Zornitza Stark Gene: hdac8 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.249 HDAC8 Zornitza Stark Phenotypes for gene: HDAC8 were changed from MIM# 300882 Cornelia de Lange syndrome 5 to Cornelia de Lange syndrome 5, MIM# 300882
Congenital Heart Defect v0.248 HDAC8 Zornitza Stark Mode of inheritance for gene: HDAC8 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Congenital Heart Defect v0.247 HDAC8 Zornitza Stark reviewed gene: HDAC8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cornelia de Lange syndrome 5, MIM# 300882; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Congenital Heart Defect v0.247 HDAC8 Zornitza Stark Classified gene: HDAC8 as Green List (high evidence)
Congenital Heart Defect v0.247 HDAC8 Zornitza Stark Gene: hdac8 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.246 HAAO Zornitza Stark Marked gene: HAAO as ready
Congenital Heart Defect v0.246 HAAO Zornitza Stark Gene: haao has been classified as Green List (High Evidence).
Congenital Heart Defect v0.246 HAAO Zornitza Stark Phenotypes for gene: HAAO were changed from Atrial septal defect; Hypoplastic left heart syndrome; Aortic stenosis; Mitral stenosis; Tetralogy of fallot with complete atriventricular canal and pulmonary stenosis; Lsvc and left pulmonary artery arising from the ductus arteriosus; Shone syndrome with aortic coarctation to Vertebral, cardiac, renal, and limb defects syndrome 1, MIM# 617660; Atrial septal defect; Hypoplastic left heart syndrome; Aortic stenosis; Mitral stenosis; Tetralogy of fallot with complete atriventricular canal and pulmonary stenosis; Lsvc and left pulmonary artery arising from the ductus arteriosus; Shone syndrome with aortic coarctation
Congenital Heart Defect v0.245 HAAO Zornitza Stark Classified gene: HAAO as Green List (high evidence)
Congenital Heart Defect v0.245 HAAO Zornitza Stark Gene: haao has been classified as Green List (High Evidence).
Congenital Heart Defect v0.244 GLI3 Zornitza Stark Marked gene: GLI3 as ready
Congenital Heart Defect v0.244 GLI3 Zornitza Stark Gene: gli3 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.244 GLI3 Zornitza Stark Phenotypes for gene: GLI3 were changed from ASD, VSD, AVSD, aortic arch anomaly, PDA to Pallister-Hall syndrome, MIM# 146510; ASD, VSD, AVSD, aortic arch anomaly, PDA
Congenital Heart Defect v0.243 GLI3 Zornitza Stark Mode of pathogenicity for gene: GLI3 was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Other
Congenital Heart Defect v0.242 GLI3 Zornitza Stark Classified gene: GLI3 as Green List (high evidence)
Congenital Heart Defect v0.242 GLI3 Zornitza Stark Gene: gli3 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.241 GLI3 Zornitza Stark reviewed gene: GLI3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pallister-Hall syndrome, MIM# 146510; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.241 FOXP1 Zornitza Stark Marked gene: FOXP1 as ready
Congenital Heart Defect v0.241 FOXP1 Zornitza Stark Gene: foxp1 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.241 FOXP1 Zornitza Stark Phenotypes for gene: FOXP1 were changed from Atrial septal defect; Atrioventricular septal defect; Patent ductus arteriosus; Pulmonic stenosis; Hypoplastic left heart syndrome to Intellectual developmental disorder with language impairment with or without autistic features, MIM# 613670; Atrial septal defect; Atrioventricular septal defect; Patent ductus arteriosus; Pulmonic stenosis; Hypoplastic left heart syndrome
Congenital Heart Defect v0.240 FOXP1 Zornitza Stark Classified gene: FOXP1 as Amber List (moderate evidence)
Congenital Heart Defect v0.240 FOXP1 Zornitza Stark Gene: foxp1 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.239 FOXP1 Zornitza Stark reviewed gene: FOXP1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder with language impairment with or without autistic features, MIM# 613670; Mode of inheritance: None
Prepair 1000+ v0.85 CYP19A1 Zornitza Stark Tag for review tag was added to gene: CYP19A1.
Early-onset Parkinson disease v0.229 MT-ND6 Zornitza Stark Tag mtDNA tag was added to gene: MT-ND6.
Prepair 1000+ v0.85 WNT10A Crystle Lee gene: WNT10A was added
gene: WNT10A was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: WNT10A was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: WNT10A were set to 19559398; 30426266
Phenotypes for gene: WNT10A were set to Odontoonychodermal dysplasia 257980 AR; Schopf-Schulz-Passarge syndrome 224750 AR; Tooth agenesis, selective, 4 150400 AR, AD
Penetrance for gene: WNT10A were set to Incomplete
Review for gene: WNT10A was set to RED
Added comment: Well established gene disease association.

Genotype-phenotype correlation is unclear. The same variant has been associated with all 3 phenotypes and both AR and AD inheritance. Variable expressivity, however milder phenotypes seem to be associated with AD (PMID: 19559398; 30426266)
Sources: Literature
Prepair 1000+ v0.85 TFR2 Crystle Lee gene: TFR2 was added
gene: TFR2 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: TFR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TFR2 were set to 29743178
Phenotypes for gene: TFR2 were set to Hemochromatosis, type 3, MIM#604250
Review for gene: TFR2 was set to AMBER
Added comment: Age of onset in individuals with TFR2-HHC is earlier than in individuals with HFE-associated hereditary hemochromatosis (Gene Reviews)

PMID: 29743178: Mean age at diagnosis for TFR2 HH (32 years) was significantly higher than for HJV HH
Sources: Literature
Early-onset Parkinson disease v0.229 WASL Zornitza Stark Marked gene: WASL as ready
Early-onset Parkinson disease v0.229 WASL Zornitza Stark Gene: wasl has been classified as Red List (Low Evidence).
Prepair 1000+ v0.85 TECPR2 Crystle Lee gene: TECPR2 was added
gene: TECPR2 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: TECPR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TECPR2 were set to 23176824; 26542466; 35130874
Phenotypes for gene: TECPR2 were set to Neuropathy, hereditary sensory and autonomic, type IX, with developmental delay, MIM#615031
Review for gene: TECPR2 was set to GREEN
Added comment: SPG49 is an autosomal recessive complicated form of spastic paraplegia. PMID 23176824 reported 4 Jewish Bukharian individuals homozygous for same founder variant and delayed psychomotor development, intellectual disability, and onset of spastic paraplegia in the first decade. Affected individuals also had dysmorphic features, thin corpus callosum on brain imaging, and episodes of central apnea, some of which were fatal. Three additional patients from unrelated non-Bukharian families reported in PMID 26542466, harboring two novel variants (c.1319delT, c.C566T) in this gene. In addition to intellectual disability and evolving spasticity, autonomic-sensory neuropathy accompanied by chronic respiratory disease and paroxysmal autonomic events were prominent
Sources: Literature
Prepair 1000+ v0.85 TAT Crystle Lee gene: TAT was added
gene: TAT was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: TAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAT were set to 16574453
Phenotypes for gene: TAT were set to Tyrosinemia, type II (MIM#276600)
Review for gene: TAT was set to AMBER
Added comment: Well established gene-disease association. Also known as Richner-Hanhart syndrome, the clinical hallmarks consist of a triad of painful palmoplantar keratoderma, keratitis with photophobia and variable mental impairment.

RHS shows inter and intrafamilial phenotypic variability. Phenotype variability observed even among individuals sharing the same pathogenic variant.
Sources: Literature
Mendeliome v1.176 WASL Zornitza Stark Marked gene: WASL as ready
Mendeliome v1.176 WASL Zornitza Stark Gene: wasl has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.229 WASL Zornitza Stark Phenotypes for gene: WASL were changed from Early onset parkinsonism to Parkinson's disease, MONDO:0005180, WASL-related
Mendeliome v1.176 WASL Zornitza Stark gene: WASL was added
gene: WASL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WASL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WASL were set to 33571872
Phenotypes for gene: WASL were set to Parkinson's disease, MONDO:0005180, WASL-related
Review for gene: WASL was set to RED
Added comment: Single family reported, where bi-allelic variants segregated with PD in three affected individuals.
Sources: Literature
Early-onset Parkinson disease v0.228 WASL Zornitza Stark Classified gene: WASL as Red List (low evidence)
Early-onset Parkinson disease v0.228 WASL Zornitza Stark Gene: wasl has been classified as Red List (Low Evidence).
Prepair 1000+ v0.85 SLC4A11 Crystle Lee gene: SLC4A11 was added
gene: SLC4A11 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: SLC4A11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC4A11 were set to 26451371; 20118786; 21203343
Phenotypes for gene: SLC4A11 were set to Corneal dystrophy, Fuchs endothelial, 4, MIM# 613268; Corneal endothelial dystrophy and perceptive deafness, MIM# 217400; Corneal endothelial dystrophy, autosomal recessive, MIM# 217700
Review for gene: SLC4A11 was set to AMBER
Added comment: Well established gene-disease association. Inter- and intra-familial variability and no genotype-phenotype correlation
Sources: Literature
Early-onset Parkinson disease v0.227 WASL Zornitza Stark reviewed gene: WASL: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Parkinson's disease, MONDO:0005180, WASL-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.227 KMT2B Zornitza Stark Marked gene: KMT2B as ready
Early-onset Parkinson disease v0.227 KMT2B Zornitza Stark Gene: kmt2b has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.227 KMT2B Zornitza Stark Phenotypes for gene: KMT2B were changed from DYT28; Childhood‐onset and progressive dystonia; Dysarthria; Dysphagia; Developmental delay; Dysmorphic features; Parkinsonism; OMIM 617284 to Dystonia 28, childhood-onset , MIM#617284
Early-onset Parkinson disease v0.226 KMT2B Zornitza Stark Mode of inheritance for gene: KMT2B was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.225 KMT2B Zornitza Stark Classified gene: KMT2B as Green List (high evidence)
Early-onset Parkinson disease v0.225 KMT2B Zornitza Stark Gene: kmt2b has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.224 KMT2B Zornitza Stark reviewed gene: KMT2B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dystonia 28, childhood-onset , MIM#617284; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.224 GBA Zornitza Stark Marked gene: GBA as ready
Early-onset Parkinson disease v0.224 GBA Zornitza Stark Gene: gba has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.224 GBA Zornitza Stark Phenotypes for gene: GBA were changed from Gaucher Disease Type 1; Early onset parkinsonism; Bone lesions; Hepatosplenomegaly; Hematologic disorders; OMIM 230800 to Parkinson's disease, MONDO:0005180, GBA-related
Prepair 1000+ v0.85 SLC26A4 Crystle Lee gene: SLC26A4 was added
gene: SLC26A4 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: SLC26A4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC26A4 were set to 24599119
Phenotypes for gene: SLC26A4 were set to Deafness, autosomal recessive 4, with enlarged vestibular aqueduct (MIM#600791); Pendred syndrome (MIM#274600)
Review for gene: SLC26A4 was set to AMBER
Added comment: PDS and NSEVA are considered a disease spectrum and are distinguishable based on the presence of thyroid dysfunction in PDS (GeneReviews).

In relation to severity of hearing, there's no correlation between missense vs PTCs. There was great variation in hearing loss severity with the same mutations. Phenotype cannot be predicted from the genotype (PMID: 24599119)
Sources: Literature
Early-onset Parkinson disease v0.223 GBA Zornitza Stark Publications for gene: GBA were set to PMID: 12809640
Early-onset Parkinson disease v0.222 GBA Zornitza Stark Mode of inheritance for gene: GBA was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.221 GBA Zornitza Stark Classified gene: GBA as Green List (high evidence)
Early-onset Parkinson disease v0.221 GBA Zornitza Stark Gene: gba has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.220 GBA Zornitza Stark reviewed gene: GBA: Rating: GREEN; Mode of pathogenicity: None; Publications: 35639160; Phenotypes: Parkinson's disease, MONDO:0005180, GBA-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.220 FRRS1L Zornitza Stark Marked gene: FRRS1L as ready
Early-onset Parkinson disease v0.220 FRRS1L Zornitza Stark Gene: frrs1l has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.220 FRRS1L Zornitza Stark Phenotypes for gene: FRRS1L were changed from Developmental and epileptic dyskinetic encephalopathy; Seizures; Chorea; Parkinsonism; Developmental delay; OMIM 616981 to Developmental and epileptic encephalopathy 37, MIM# 616981; Seizures; Chorea; Parkinsonism; Developmental delay
Early-onset Parkinson disease v0.219 FRRS1L Zornitza Stark Classified gene: FRRS1L as Green List (high evidence)
Early-onset Parkinson disease v0.219 FRRS1L Zornitza Stark Gene: frrs1l has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.218 FRRS1L Zornitza Stark reviewed gene: FRRS1L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 37, MIM# 616981; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.85 SLC12A3 Crystle Lee gene: SLC12A3 was added
gene: SLC12A3 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: SLC12A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC12A3 were set to 8528245; 11102542
Phenotypes for gene: SLC12A3 were set to Gitelman syndrome (MIM#263800)
Review for gene: SLC12A3 was set to AMBER
Added comment: Gitelman syndrome is an autosomal recessive renal tubular salt-wasting disorder characterized by hypokalemic metabolic alkalosis with hypomagnesemia and hypocalciuria. It is the most common renal tubular disorder among Caucasians (prevalence of 1 in 40,000). Most individuals have onset of symptoms as adults, but some can present in childhood. Clinical features include transient periods of muscle weakness and tetany, abdominal pains, and chondrocalcinosis.

Well established gene-disease association.
Sources: Literature
Prepair 1000+ v0.85 CYP11B1 Zornitza Stark Tag for review tag was added to gene: CYP11B1.
Prepair 1000+ v0.85 RS1 Crystle Lee gene: RS1 was added
gene: RS1 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: RS1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: RS1 were set to 15932525; 23453514; 23847049
Phenotypes for gene: RS1 were set to Retinoschisis (MIM#312700)
Review for gene: RS1 was set to AMBER
Added comment: - This gene is known to be associated with X-linked recessive disease, however, some affected females have been reported (OMIM).
- May not clinically manifest until middle life (OMIM)
- Many PTCs and missense reported. All result in same XLRS phenotype (although expression can be variable). Also a knockout mouse with similar phenotype.
- PTCs and missense involving cysteines tend to result in a more severe phenotype, whereas other missense can vary widely in severity (PMID: 23847049).
Sources: Literature
Prepair 1000+ v0.85 PYGM Crystle Lee gene: PYGM was added
gene: PYGM was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: PYGM was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PYGM were set to McArdle disease (MIM#232600)
Review for gene: PYGM was set to AMBER
Added comment: Gene-disease association for bi-allelic variants is well established.

McCardle disease: glycogen storage disease type V (GSD5), characterized by onset of exercise intolerance and muscle cramps in childhood or adolescence. Transient myoglobinuria may occur after exercise, due to rhabdomyolysis. Severe myoglobinuria may lead to acute renal failure. Patients may report muscle weakness, myalgia, and lack of endurance since childhood or adolescence. Later in adult life, there is persistent and progressive muscle weakness and atrophy with fatty replacement. McArdle disease is a relatively benign disorder, except for possible renal failure as a complication of myoglobinuria

Clinical heterogeneity exists; about 10% of all affected individuals have mild manifestations (e.g., fatigue or poor stamina without contractures) and remain virtually asymptomatic during daily activities of living(Gene Reviews)
Sources: Literature
Prepair 1000+ v0.85 OAT Crystle Lee gene: OAT was added
gene: OAT was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: OAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OAT were set to 33463379; 34340878
Phenotypes for gene: OAT were set to Gyrate atrophy of choroid and retina with or without ornithinemia (MIM#258870)
Review for gene: OAT was set to AMBER
Added comment: Biallelic variants associated with deficiency of mitochondrial enzyme ornithine aminotransferase and elevation of plasma ornithine levels without elevation of ammonia. Characterized by ocular anomalies; however, neurological and muscular features may also be present.

There is evidence of intra-familial variability.
Sources: Literature
Prepair 1000+ v0.85 NR2E3 Crystle Lee gene: NR2E3 was added
gene: NR2E3 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: NR2E3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: NR2E3 were set to 32679203; 33138239; 19139342; 26910043
Phenotypes for gene: NR2E3 were set to Enhanced S-cone syndrome (MIM#268100); Retinitis pigmentosa 37 (MIM#611131)
Review for gene: NR2E3 was set to AMBER
Added comment: Both biallelic and monoallelic variants associated with a range of phenotypes including retinitis pigments (NR2E3-related retinal dystrophy). Highly variable phenotype.

PMID: 26910043: Single variant associated with a wide range of phenotypic characteristics
Sources: Literature
Prepair 1000+ v0.85 MEFV Crystle Lee gene: MEFV was added
gene: MEFV was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: MEFV was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: MEFV were set to Familial Mediterranean fever, AR (MIM#249100)
Penetrance for gene: MEFV were set to Incomplete
Review for gene: MEFV was set to AMBER
Added comment: Well established association. Predominantly bi-allelic, though a limited range of heterozygous variants have been associated with disease.
Sources: Literature
Prepair 1000+ v0.85 MCCC2 Crystle Lee gene: MCCC2 was added
gene: MCCC2 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: MCCC2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MCCC2 were set to 3-Methylcrotonyl-CoA carboxylase 2 deficiency (MIM#210210)
Review for gene: MCCC2 was set to RED
Added comment: Variants in this gene cause a biochemical defect. Relationship to clinical features is less certain.

Variants in this gene have been reported in multiple individuals with ID/regression/neurological phenotypes. However, ascertainment through NBS programs indicates most individuals remain asymptomatic and therefore caution should be applied in interpreting the clinical significance of variants in this gene (though they undoubtedly cause a biochemical phenotype).
Sources: Literature
Early-onset Parkinson disease v0.218 ALPL Zornitza Stark Marked gene: ALPL as ready
Early-onset Parkinson disease v0.218 ALPL Zornitza Stark Gene: alpl has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.218 ALPL Zornitza Stark Phenotypes for gene: ALPL were changed from Hypophosphatasia; Osteomalacia; Parkinsonism; OMIM 146300 to Hypophosphatasia, adult, MIM# 146300; Osteomalacia; Parkinsonism
Early-onset Parkinson disease v0.217 ALPL Zornitza Stark Classified gene: ALPL as Red List (low evidence)
Early-onset Parkinson disease v0.217 ALPL Zornitza Stark Gene: alpl has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.216 ALPL Zornitza Stark reviewed gene: ALPL: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hypophosphatasia, adult, MIM# 146300; Mode of inheritance: None
Prepair 1000+ v0.85 CERKL Zornitza Stark Tag for review tag was added to gene: CERKL.
Early-onset Parkinson disease v0.216 ADAR Zornitza Stark Marked gene: ADAR as ready
Early-onset Parkinson disease v0.216 ADAR Zornitza Stark Gene: adar has been classified as Green List (High Evidence).
Prepair 1000+ v0.85 MCCC1 Crystle Lee gene: MCCC1 was added
gene: MCCC1 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: MCCC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCCC1 were set to 31730530
Phenotypes for gene: MCCC1 were set to 3-Methylcrotonyl-CoA carboxylase 1 deficiency (MIM#210200)
Review for gene: MCCC1 was set to RED
Added comment: Highly variable phenotype. May present in infancy but also be present in asymptomatic adults (OMIM)

Variants in this gene cause a biochemical defect. The relationship to clinical phenotype has been questioned by NBS programs, PMID 31730530.
Sources: Literature
Early-onset Parkinson disease v0.216 ADAR Zornitza Stark Classified gene: ADAR as Green List (high evidence)
Early-onset Parkinson disease v0.216 ADAR Zornitza Stark Gene: adar has been classified as Green List (High Evidence).
Prepair 1000+ v0.85 BTD Zornitza Stark Tag for review tag was added to gene: BTD.
Deafness_Isolated v1.34 TRRAP Zornitza Stark Marked gene: TRRAP as ready
Deafness_Isolated v1.34 TRRAP Zornitza Stark Gene: trrap has been classified as Red List (Low Evidence).
Deafness_Isolated v1.34 TRRAP Zornitza Stark Phenotypes for gene: TRRAP were changed from ?Deafness, autosomal dominant 75 MIM#618778 to Deafness, autosomal dominant 75 MIM#618778
Prepair 1000+ v0.85 AIRE Zornitza Stark Tag for review tag was added to gene: AIRE.
Prepair 1000+ v0.85 KCNE1 Zornitza Stark Marked gene: KCNE1 as ready
Prepair 1000+ v0.85 KCNE1 Zornitza Stark Gene: kcne1 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.85 KCNE1 Zornitza Stark Phenotypes for gene: KCNE1 were changed from Jervell and Lange-Nielsen syndrome 2, 612347 (3) to Jervell and Lange-Nielsen syndrome 2, MIM# 612347
Prepair 1000+ v0.84 KCNE1 Zornitza Stark Classified gene: KCNE1 as Red List (low evidence)
Prepair 1000+ v0.84 KCNE1 Zornitza Stark Gene: kcne1 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.83 KCNE1 Zornitza Stark reviewed gene: KCNE1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Prepair 1000+ v0.83 VPS13A Zornitza Stark Tag for review tag was added to gene: VPS13A.
Prepair 1000+ v0.83 TH Zornitza Stark Marked gene: TH as ready
Prepair 1000+ v0.83 TH Zornitza Stark Gene: th has been classified as Green List (High Evidence).
Prepair 1000+ v0.83 TH Zornitza Stark Phenotypes for gene: TH were changed from Segawa syndrome, recessive, 605407 (3) to Segawa syndrome, recessive, MIM# 605407
Prepair 1000+ v0.82 SPG11 Zornitza Stark Marked gene: SPG11 as ready
Prepair 1000+ v0.82 SPG11 Zornitza Stark Gene: spg11 has been classified as Green List (High Evidence).
Prepair 1000+ v0.82 SPG11 Zornitza Stark Phenotypes for gene: SPG11 were changed from Spastic paraplegia 11, autosomal recessive, 604360 (3) to Spastic paraplegia 11, autosomal recessive, MIM# 604360
Prepair 1000+ v0.81 SPG11 Zornitza Stark Publications for gene: SPG11 were set to
Prepair 1000+ v0.80 SPART Zornitza Stark Marked gene: SPART as ready
Prepair 1000+ v0.80 SPART Zornitza Stark Gene: spart has been classified as Green List (High Evidence).
Prepair 1000+ v0.80 SPART Zornitza Stark Phenotypes for gene: SPART were changed from Troyer syndrome, 275900 (3) to Troyer syndrome (MIM#275900); SPG20; MONDO:0010156
Prepair 1000+ v0.79 SPART Zornitza Stark Publications for gene: SPART were set to
Prepair 1000+ v0.78 SETX Zornitza Stark Marked gene: SETX as ready
Prepair 1000+ v0.78 SETX Zornitza Stark Gene: setx has been classified as Green List (High Evidence).
Prepair 1000+ v0.78 SETX Zornitza Stark Phenotypes for gene: SETX were changed from Spinocerebellar ataxia, autosomal recessive 1, 606002 (3) to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 (MIM#606002)
Prepair 1000+ v0.77 SETX Zornitza Stark Publications for gene: SETX were set to
Prepair 1000+ v0.76 PLA2G6 Zornitza Stark Marked gene: PLA2G6 as ready
Prepair 1000+ v0.76 PLA2G6 Zornitza Stark Gene: pla2g6 has been classified as Green List (High Evidence).
Prepair 1000+ v0.76 PLA2G6 Zornitza Stark Phenotypes for gene: PLA2G6 were changed from Neurodegeneration with brain iron accumulation 2B, 610217 (3) to Infantile neuroaxonal dystrophy 1 MIM#256600; Neurodegeneration with brain iron accumulation 2B MIM#610217
Prepair 1000+ v0.75 PLA2G6 Zornitza Stark Publications for gene: PLA2G6 were set to
Prepair 1000+ v0.74 PANK2 Zornitza Stark Marked gene: PANK2 as ready
Prepair 1000+ v0.74 PANK2 Zornitza Stark Gene: pank2 has been classified as Green List (High Evidence).
Prepair 1000+ v0.74 PANK2 Zornitza Stark Phenotypes for gene: PANK2 were changed from Neurodegeneration with brain iron accumulation 1, 234200 (3) to Neurodegeneration with brain iron accumulation 1, MIM#234200
Prepair 1000+ v0.73 PANK2 Zornitza Stark Publications for gene: PANK2 were set to
Prepair 1000+ v0.72 NPC2 Zornitza Stark Marked gene: NPC2 as ready
Prepair 1000+ v0.72 NPC2 Zornitza Stark Gene: npc2 has been classified as Green List (High Evidence).
Prepair 1000+ v0.72 NPC2 Zornitza Stark Phenotypes for gene: NPC2 were changed from Niemann-pick disease, type C2, 607625 (3) to Niemann-pick disease, type C2, MIM#607625
Prepair 1000+ v0.71 NPC2 Zornitza Stark Publications for gene: NPC2 were set to
Prepair 1000+ v0.70 NPC1 Zornitza Stark Marked gene: NPC1 as ready
Prepair 1000+ v0.70 NPC1 Zornitza Stark Gene: npc1 has been classified as Green List (High Evidence).
Prepair 1000+ v0.70 NPC1 Zornitza Stark Phenotypes for gene: NPC1 were changed from Niemann-Pick disease, type C1, 257220 (3) to Niemann-Pick disease, type C1, MIM#257220
Prepair 1000+ v0.69 NPC1 Zornitza Stark Publications for gene: NPC1 were set to
Prepair 1000+ v0.68 LMNA Zornitza Stark reviewed gene: LMNA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Restrictive dermopathy, lethal, MIM#275210; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.68 LMNA Zornitza Stark Marked gene: LMNA as ready
Prepair 1000+ v0.68 LMNA Zornitza Stark Gene: lmna has been classified as Green List (High Evidence).
Prepair 1000+ v0.68 LMNA Zornitza Stark Publications for gene: LMNA were set to
Prepair 1000+ v0.67 LDLR Zornitza Stark Tag for review tag was added to gene: LDLR.
Prepair 1000+ v0.67 FIG4 Zornitza Stark Marked gene: FIG4 as ready
Prepair 1000+ v0.67 FIG4 Zornitza Stark Gene: fig4 has been classified as Green List (High Evidence).
Prepair 1000+ v0.67 FIG4 Zornitza Stark Phenotypes for gene: FIG4 were changed from Yunis-Varon syndrome, 216340 (3) to Yunis-Varon syndrome, MIM#216340
Prepair 1000+ v0.66 FIG4 Zornitza Stark Publications for gene: FIG4 were set to
Hyperinsulinism v0.32 PMM2 Zornitza Stark edited their review of gene: PMM2: Added comment: Cabezas et al (2017) reported co-occurrence of hyperinsulinaemic hypoglycaemia and polycystic kidney disease (HIPKD in 17 children from 11 unrelated families. Patients presented with hyperinsulinaemic hypoglycaemia in infancy and enlarged kidneys with multiple kidney cysts. Some progressed to ESKD and some had liver cysts. Whole-genome linkage analysis in 5 informative families identified a single significant locus on chromosome 16p13.2. Sequencing of the coding regions of all linked genes failed to identify biallelic mutations. Instead, they found in all patients a promoter mutation (c.-167G>T) in PMM2, either homozygous or in trans with PMM2 coding mutations. They found deglycosylation in cultured pancreatic β cells altered insulin secretion. In vitro, the PMM2 promoter mutation associated with decreased transcriptional activity in patient kidney cells and impaired binding of the transcription factor ZNF143. In silico analysis suggested an important role of ZNF143 for the formation of a chromatin loop including PMM2. They proposed that the PMM2 promoter mutation alters tissue-specific chromatin loop formation, with consequent organ-specific deficiency of PMM2 leading to the restricted phenotype of HIPKD.

None of the patients exhibited the typical clinical or diagnostic features of CDG1A. Serum transferrin glycosylation was normal in 11 patients who had assessment.; Changed phenotypes: Hyperinsulinaemic Hypoglycaemia and Polycystic Kidney Disease (HIPKD), MONDO:0020642, PMM2-related; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Macrocystic Disease v0.50 PMM2 Zornitza Stark Marked gene: PMM2 as ready
Renal Macrocystic Disease v0.50 PMM2 Zornitza Stark Gene: pmm2 has been classified as Green List (High Evidence).
Hyperinsulinism v0.32 PMM2 Zornitza Stark reviewed gene: PMM2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v1.175 PMM2 Zornitza Stark Phenotypes for gene: PMM2 were changed from Congenital disorder of glycosylation, type Ia (MIM#212065) to Congenital disorder of glycosylation, type Ia (MIM#212065); Hyperinsulinaemic Hypoglycaemia and Polycystic Kidney Disease (HIPKD), MONDO:0020642, PMM2-related
Mendeliome v1.174 PMM2 Zornitza Stark Publications for gene: PMM2 were set to 28108845
Mendeliome v1.173 PMM2 Zornitza Stark changed review comment from: Well established gene-disease association.; to: CDG: Well established gene-disease association.
Mendeliome v1.173 PMM2 Zornitza Stark edited their review of gene: PMM2: Added comment: Association with HIPKD:
Cabezas et al (2017) reported co-occurrence of hyperinsulinaemic hypoglycaemia and polycystic kidney disease (HIPKD in 17 children from 11 unrelated families. Patients presented with hyperinsulinaemic hypoglycaemia in infancy and enlarged kidneys with multiple kidney cysts. Some progressed to ESKD and some had liver cysts. Whole-genome linkage analysis in 5 informative families identified a single significant locus on chromosome 16p13.2. Sequencing of the coding regions of all linked genes failed to identify biallelic mutations. Instead, they found in all patients a promoter mutation (c.-167G>T) in PMM2, either homozygous or in trans with PMM2 coding mutations. They found deglycosylation in cultured pancreatic β cells altered insulin secretion. In vitro, the PMM2 promoter mutation associated with decreased transcriptional activity in patient kidney cells and impaired binding of the transcription factor ZNF143. In silico analysis suggested an important role of ZNF143 for the formation of a chromatin loop including PMM2. They proposed that the PMM2 promoter mutation alters tissue-specific chromatin loop formation, with consequent organ-specific deficiency of PMM2 leading to the restricted phenotype of HIPKD. None of the patients exhibited the typical clinical or diagnostic features of CDG1A. Serum transferrin glycosylation was normal in 11 patients who had assessment.; Changed publications: 28108845, 28373276, 32595772; Changed phenotypes: Congenital disorder of glycosylation, type Ia (MIM#212065), Hyperinsulinaemic Hypoglycaemia and Polycystic Kidney Disease (HIPKD), MONDO:0020642, PMM2-related
Renal Macrocystic Disease v0.50 PMM2 Zornitza Stark Publications for gene: PMM2 were set to PMID: 28373276, 32595772
Renal Macrocystic Disease v0.49 PMM2 Zornitza Stark Phenotypes for gene: PMM2 were changed from Hyperinsulinaemic Hypoglycaemia and Polycystic Kidney Disease (HIPKD) to Hyperinsulinaemic Hypoglycaemia and Polycystic Kidney Disease (HIPKD), MONDO:0020642, PMM2-related
Prepair 1000+ v0.65 LOXHD1 Crystle Lee gene: LOXHD1 was added
gene: LOXHD1 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: LOXHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LOXHD1 were set to 31547530
Phenotypes for gene: LOXHD1 were set to Deafness, autosomal recessive 77 (MIM#613079)
Review for gene: LOXHD1 was set to AMBER
Added comment: Well established gene disease association with non-syndromic hearing loss.
Sources: Literature
Renal Macrocystic Disease v0.48 PMM2 Zornitza Stark Tag 5'UTR tag was added to gene: PMM2.
Prepair 1000+ v0.65 IGHM Zornitza Stark Tag for review tag was added to gene: IGHM.
Prepair 1000+ v0.65 DOCK2 Zornitza Stark Marked gene: DOCK2 as ready
Prepair 1000+ v0.65 DOCK2 Zornitza Stark Gene: dock2 has been classified as Green List (High Evidence).
Prepair 1000+ v0.65 DOCK2 Zornitza Stark Publications for gene: DOCK2 were set to
Prepair 1000+ v0.64 PRKRA Zornitza Stark Tag for review tag was added to gene: PRKRA.
Mendeliome v1.173 SLCO2A1 Zornitza Stark Phenotypes for gene: SLCO2A1 were changed from Hypertrophic osteoarthropathy, primary, autosomal dominant, MIM# 167100; Hypertrophic osteoarthropathy, primary, autosomal recessive 2, MIM# 614441 to Hypertrophic osteoarthropathy, primary, autosomal dominant, MIM# 167100; Hypertrophic osteoarthropathy, primary, autosomal recessive 2, MIM# 614441; Inflammatory bowel disease, MONDO:0005265, SLCO2A1-related
Mendeliome v1.172 SLCO2A1 Zornitza Stark Publications for gene: SLCO2A1 were set to 23509104; 27134495; 33852188; 22331663; 27134495
Mendeliome v1.171 SLCO2A1 Zornitza Stark edited their review of gene: SLCO2A1: Added comment: PMID 29313109: Over 40 Japanese individuals reported with bi-allelic variants in this gene and multiple small intestinal ulcers of nonspecific histology. Some overlap with the hypertrophic osteoarthropathy also associated with bi-allelic variants in this gene. Mild digital clubbing or periostosis was found in 13 patients (28%), with five male patients fulfilling the major diagnostic criteria of PHO.; Changed publications: 23509104, 27134495, 33852188, 22331663, 27134495, 29313109; Changed phenotypes: Hypertrophic osteoarthropathy, primary, autosomal dominant, MIM# 167100, Hypertrophic osteoarthropathy, primary, autosomal recessive 2, MIM# 614441, Inflammatory bowel disease, MONDO:0005265, SLCO2A1-related
Autoinflammatory Disorders v0.156 ALPK1 Peter McNaughton reviewed gene: ALPK1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35868845; Phenotypes: retinal dystrophy, optic nerve oedema, splenomegaly, anhidrosis, headache; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Inflammatory bowel disease v0.80 SLCO2A1 Zornitza Stark Marked gene: SLCO2A1 as ready
Inflammatory bowel disease v0.80 SLCO2A1 Zornitza Stark Gene: slco2a1 has been classified as Green List (High Evidence).
Inflammatory bowel disease v0.80 SLCO2A1 Zornitza Stark Phenotypes for gene: SLCO2A1 were changed from Enteropathy to Inflammatory bowel disease, MONDO:0005265, SLCO2A1-related; Enteropathy
Inflammatory bowel disease v0.79 SLCO2A1 Zornitza Stark Classified gene: SLCO2A1 as Green List (high evidence)
Inflammatory bowel disease v0.79 SLCO2A1 Zornitza Stark Gene: slco2a1 has been classified as Green List (High Evidence).
Inflammatory bowel disease v0.78 SLCO2A1 Zornitza Stark changed review comment from: Over 40 Japanese individuals reported with bi-allelic variants in this gene and multiple small intestinal ulcers of nonspecific histology.

This is distinct from the hypertrophic osteoarthropathy also associated with bi-allelic variants in this gene.; to: Over 40 Japanese individuals reported with bi-allelic variants in this gene and multiple small intestinal ulcers of nonspecific histology.

Some overlap with the hypertrophic osteoarthropathy also associated with bi-allelic variants in this gene. Mild digital clubbing or periostosis was found in 13 patients (28%), with five male patients fulfilling the major diagnostic criteria of PHO.
Inflammatory bowel disease v0.78 SLCO2A1 Zornitza Stark changed review comment from: Over 40 Japanese individuals reported with bi-allelic variants in this gene and multiple small intestinal ulcers of nonspecific histology.

This distinct from the hypertrophic osteoarthropathy also associated with bi-allelic variants in this gene.; to: Over 40 Japanese individuals reported with bi-allelic variants in this gene and multiple small intestinal ulcers of nonspecific histology.

This is distinct from the hypertrophic osteoarthropathy also associated with bi-allelic variants in this gene.
Inflammatory bowel disease v0.78 SLCO2A1 Zornitza Stark reviewed gene: SLCO2A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Inflammatory bowel disease, MONDO:0005265, SLCO2A1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.64 KCNQ1 Zornitza Stark Tag for review tag was added to gene: KCNQ1.
Prepair 1000+ v0.64 GLA Zornitza Stark Marked gene: GLA as ready
Prepair 1000+ v0.64 GLA Zornitza Stark Gene: gla has been classified as Green List (High Evidence).
Prepair 1000+ v0.64 GLA Zornitza Stark Phenotypes for gene: GLA were changed from Fabry disease, 301500 (3) to Fabry disease, MIM#301500
Prepair 1000+ v0.63 GLA Zornitza Stark Publications for gene: GLA were set to
Prepair 1000+ v0.62 FA2H Zornitza Stark Marked gene: FA2H as ready
Prepair 1000+ v0.62 FA2H Zornitza Stark Gene: fa2h has been classified as Green List (High Evidence).
Prepair 1000+ v0.62 FA2H Zornitza Stark Publications for gene: FA2H were set to
Prepair 1000+ v0.61 HYAL1 Crystle Lee gene: HYAL1 was added
gene: HYAL1 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: HYAL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HYAL1 were set to 10339581; 18344557; 21559944
Phenotypes for gene: HYAL1 were set to Mucopolysaccharidosis type IX (MIM#601492)
Review for gene: HYAL1 was set to RED
Added comment: Two families reported: in one, multiple soft tissue masses were the predominant clinical manifestation, and in the second, juvenile arthritis. Mouse model.

>15 pLoF variants reported as pathogenic in ClinVar. All submitted by a single lab and evidence suggests that the variant has not been previously reported.

Insufficient gene disease association. Not suitable for inclusion in a carrier screening panel
Sources: Literature
Prepair 1000+ v0.61 HOGA1 Crystle Lee gene: HOGA1 was added
gene: HOGA1 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: HOGA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HOGA1 were set to 31123811
Phenotypes for gene: HOGA1 were set to Hyperoxaluria, primary, type III (MIM#613616)
Review for gene: HOGA1 was set to AMBER
Added comment: Well-established association with primary hyperoxaluria type III (PH3). Variable phenotype

Three distinct genetic forms of PH have been defined: PH1–3. PH3 might be the least severe form with a milder phenotype with good preservation of kidney function in most patients. It does not develop ESRD generally
Sources: Literature
Prepair 1000+ v0.61 HGD Crystle Lee gene: HGD was added
gene: HGD was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: HGD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HGD were set to 25804398
Phenotypes for gene: HGD were set to Alkaptonuria (MIM#203500)
Review for gene: HGD was set to RED
Added comment: Well established gene disease association. Symptoms occur in adulthood.

Ochronosis generally occurs after age 30 years; arthritis often begins in the third decade. (Gene Reviews)
Sources: Literature
Hydrops fetalis v0.284 SPTA1 Di Milnes Deleted their comment
Hydrops fetalis v0.284 SPTA1 Di Milnes edited their review of gene: SPTA1: Added comment: single case fetus consanguineous parents
severe anaemia with NIHF
homozygous variant NM_003126.4:c.83G>A; Changed phenotypes: Spherocytosis type 3 #270970, Elliptocytosis-2 #130600, Pyropoikilocytosis #266140
Cancer Predisposition_Paediatric v0.126 TRIM37 Zornitza Stark Marked gene: TRIM37 as ready
Cancer Predisposition_Paediatric v0.126 TRIM37 Zornitza Stark Gene: trim37 has been classified as Green List (High Evidence).
Cancer Predisposition_Paediatric v0.126 TRIM37 Zornitza Stark Classified gene: TRIM37 as Green List (high evidence)
Cancer Predisposition_Paediatric v0.126 TRIM37 Zornitza Stark Gene: trim37 has been classified as Green List (High Evidence).
Cancer Predisposition_Paediatric v0.125 TRIM37 Zornitza Stark gene: TRIM37 was added
gene: TRIM37 was added to Cancer Predisposition_Paediatric. Sources: Expert Review
Mode of inheritance for gene: TRIM37 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIM37 were set to 34309235; 19334051; 17100991
Phenotypes for gene: TRIM37 were set to Mulibrey nanism, MIM# 253250
Review for gene: TRIM37 was set to GREEN
Added comment: Multiple reports of WT with mulibrey nanism.
Sources: Expert Review
Hydrops fetalis v0.284 SPTA1 Di Milnes reviewed gene: SPTA1: Rating: AMBER; Mode of pathogenicity: None; Publications: 34132406; Phenotypes: Spherocytosis type 3 #270970, Elliptocytosis-2 #130600, pyropoikilocytosis #266140; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hydrops fetalis v0.284 SPTA1 Di Milnes Deleted their review
Hydrops fetalis v0.284 DOK7 Di Milnes reviewed gene: DOK7: Rating: AMBER; Mode of pathogenicity: None; Publications: 34132406; Phenotypes: Fetal akinesia deformation sequence 3, MIM# 618389; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hydrops fetalis v0.284 DOK7 Di Milnes Deleted their review
Prepair 1000+ v0.61 HFE Crystle Lee gene: HFE was added
gene: HFE was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: HFE was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: HFE were set to Hemochromatosis (MIM#235200)
Penetrance for gene: HFE were set to Incomplete
Review for gene: HFE was set to RED
Added comment: Well established gene disease association. HFE hemochromatosis is an adult-onset, treatable disorder with low clinical penetrance (Gene Reviews).

Not suitable for population carrier screening.
Sources: Literature
Cancer Predisposition_Paediatric v0.124 TRIM28 Zornitza Stark Marked gene: TRIM28 as ready
Cancer Predisposition_Paediatric v0.124 TRIM28 Zornitza Stark Gene: trim28 has been classified as Green List (High Evidence).
Cancer Predisposition_Paediatric v0.124 TRIM28 Zornitza Stark Classified gene: TRIM28 as Green List (high evidence)
Cancer Predisposition_Paediatric v0.124 TRIM28 Zornitza Stark Gene: trim28 has been classified as Green List (High Evidence).
Cancer Predisposition_Paediatric v0.123 TRIM28 Zornitza Stark gene: TRIM28 was added
gene: TRIM28 was added to Cancer Predisposition_Paediatric. Sources: Expert Review
Mode of inheritance for gene: TRIM28 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRIM28 were set to 30694527
Phenotypes for gene: TRIM28 were set to Wilms tumour, MONDO:0006058, TRIM28-related
Review for gene: TRIM28 was set to GREEN
Added comment: Eleven individuals with germline variants identified; plus one somatic. Exome sequencing on eight tumor DNA samples from six individuals showed loss-of-heterozygosity (LOH) of the TRIM28-locus by mitotic recombination in seven tumors, suggesting that TRIM28 functions as a tumor suppressor gene in Wilms tumor development.
Sources: Expert Review
Prepair 1000+ v0.61 HBA2 Crystle Lee gene: HBA2 was added
gene: HBA2 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: HBA2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: HBA2 were set to Erythrocytosis 7, MIM# 617981; Heinz body anaemia, MIM# 140700; Haemoglobin H disease, deletional and nondeletional, MIM# 613978; Thalassaemia, alpha-, MIM# 604131
Review for gene: HBA2 was set to RED
Added comment: Haemoglobinopathies of alpha-globin can result from variants at either of the 2 alpha-globin loci, HBA1 or HBA2.

Note deletions are common.
Sources: Literature
Prepair 1000+ v0.61 HBA1 Crystle Lee gene: HBA1 was added
gene: HBA1 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: HBA1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: HBA1 were set to Erythrocytosis 7, MIM# 617981; Heinz body anemias, alpha-, MIM# 140700; Methemoglobinemia, alpha type , MIM#617973; Thalassemias, alpha-, MIM# 604131; Hemoglobin H disease, nondeletional, MIM# 613978
Review for gene: HBA1 was set to RED
Added comment: Well established gene-disease associations. Haemoglobinopathies of alpha-globin can result from variants at either of the 2 alpha-globin loci, HBA1 or HBA2.

Note deletions are common.
Sources: Literature
Prepair 1000+ v0.61 GRHPR Crystle Lee gene: GRHPR was added
gene: GRHPR was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: GRHPR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRHPR were set to 28569194; 10484776; 10484776; 24116921
Phenotypes for gene: GRHPR were set to Hyperoxaluria, primary, type II (MIM#260000)
Review for gene: GRHPR was set to AMBER
Added comment: Well established gene-disease association, more than 10 families reported.
Onset usually in infancy or early childhood, variable severity and some patients may be asymptomatic (OMIM; Gene Reviews)
Sources: Literature
Prepair 1000+ v0.61 GP9 Crystle Lee gene: GP9 was added
gene: GP9 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: GP9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GP9 were set to 8049428; 33553065; 32030720; 31484196
Phenotypes for gene: GP9 were set to Bernard-Soulier syndrome, type C (MIM#231200)
Review for gene: GP9 was set to AMBER
Added comment: Bernard-Soulier syndrome is a bleeding disorder caused by a defect in or deficiency of the platelet membrane von Willebrand factor receptor complex, glycoprotein Ib (GP Ib). GP Ib is composed of 4 subunits encoded by 4 separate genes: GP1BA, GP1BB, GP9, and GP5.

At least 3 unrelated families reported, animal model.
Sources: Literature
Cancer Predisposition_Paediatric v0.122 REST Zornitza Stark Marked gene: REST as ready
Cancer Predisposition_Paediatric v0.122 REST Zornitza Stark Gene: rest has been classified as Green List (High Evidence).
Cancer Predisposition_Paediatric v0.122 REST Zornitza Stark Classified gene: REST as Green List (high evidence)
Cancer Predisposition_Paediatric v0.122 REST Zornitza Stark Gene: rest has been classified as Green List (High Evidence).
Cancer Predisposition_Paediatric v0.121 REST Zornitza Stark gene: REST was added
gene: REST was added to Cancer Predisposition_Paediatric. Sources: Expert Review
Mode of inheritance for gene: REST was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: REST were set to 26551668; 34308104
Phenotypes for gene: REST were set to {Wilms tumor 6, susceptibility to}, MIM# 616806
Review for gene: REST was set to GREEN
Added comment: More than 10 families reported.
Sources: Expert Review
Prepair 1000+ v0.61 GP1BA Crystle Lee gene: GP1BA was added
gene: GP1BA was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: GP1BA was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: GP1BA were set to 21173099; 24934643; 18081445
Phenotypes for gene: GP1BA were set to Bernard-Soulier syndrome, type A1 (recessive), (MIM#231200), AR (AR BSS); von Willebrand disease, platelet-type, (MIM#177820), AD (VWD); MONDO:0008332; Bernard-Soulier syndrome, type A2 (dominant), (MIM#153670) (AD BSS); MONDO:0007930
Review for gene: GP1BA was set to AMBER
Added comment: Bernard-Soulier syndrome is usually transmitted as a recessive trait with giant platelets and severe bleeding tendency.
Sources: Literature
Cancer Predisposition_Paediatric v0.120 PIK3CA Zornitza Stark Marked gene: PIK3CA as ready
Cancer Predisposition_Paediatric v0.120 PIK3CA Zornitza Stark Gene: pik3ca has been classified as Green List (High Evidence).
Cancer Predisposition_Paediatric v0.120 PIK3CA Zornitza Stark Classified gene: PIK3CA as Green List (high evidence)
Cancer Predisposition_Paediatric v0.120 PIK3CA Zornitza Stark Gene: pik3ca has been classified as Green List (High Evidence).
Cancer Predisposition_Paediatric v0.119 PIK3CA Zornitza Stark gene: PIK3CA was added
gene: PIK3CA was added to Cancer Predisposition_Paediatric. Sources: Expert Review
somatic tags were added to gene: PIK3CA.
Mode of inheritance for gene: PIK3CA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PIK3CA were set to Megalencephaly-capillary malformation-polymicrogyria syndrome, somatic, MIM# 602501
Review for gene: PIK3CA was set to GREEN
Added comment: MCAP syndrome is associated with increased risk of Wilm's tumour, and other neoplasms (leukaemia, meningioma).
Sources: Expert Review
Cancer Predisposition_Paediatric v0.118 GPC3 Zornitza Stark Marked gene: GPC3 as ready
Cancer Predisposition_Paediatric v0.118 GPC3 Zornitza Stark Gene: gpc3 has been classified as Green List (High Evidence).
Prepair 1000+ v0.61 GJB2 Crystle Lee gene: GJB2 was added
gene: GJB2 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: GJB2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: GJB2 were set to Bart-Pumphrey syndrome, MIM#149200; Deafness, autosomal dominant 3A, MIM#601544; Deafness, autosomal recessive 1A, MIM#220290; Hystrix-like ichthyosis with deafness, MIM#602540; Keratitis-ichthyosis-deafness syndrome, MIM#148210; Keratoderma, palmoplantar, with deafness, MIM#148350; Vohwinkel syndrome, MIM# 124500
Review for gene: GJB2 was set to AMBER
Added comment: Well established gene disease association. AR deafness MIM#220290 is associated with biallelic variants or digenic dominant with large deletion in GJB6
Sources: Literature
Prepair 1000+ v0.61 GJB1 Crystle Lee gene: GJB1 was added
gene: GJB1 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: GJB1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: GJB1 were set to Charcot-Marie-Tooth neuropathy, X-linked dominant, 1 (MIM#302800)
Review for gene: GJB1 was set to AMBER
Added comment: CMTX has both demyelinating and axonal features. Well established gene-disease association, over 100 families reported. Variable phenotype with incomplete penetrance (OMIM)

PMID 31842800: Three unrelated males with GJB1 variants and recurrent episodes of reversible posterior leukoencephalopathy reported.
Sources: Literature
Prepair 1000+ v0.61 GALK1 Crystle Lee gene: GALK1 was added
gene: GALK1 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: GALK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GALK1 were set to 32807972
Phenotypes for gene: GALK1 were set to Galactokinase deficiency with cataracts (MIM#230200)
Review for gene: GALK1 was set to AMBER
Added comment: Well established gene disease association. Galactokinase (GALK1) deficiency is a rare hereditary galactose metabolism disorder. Beyond cataract, the phenotypic spectrum is questionable
Sources: Literature
Prepair 1000+ v0.61 G6PD Crystle Lee gene: G6PD was added
gene: G6PD was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: G6PD was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: G6PD were set to Hemolytic anemia, G6PD deficient (favism) (MIM#300908)
Review for gene: G6PD was set to AMBER
Added comment: Well established gene disease association. Most G6PD-deficient patients are asymptomatic throughout their life, but G6PD deficiency can be life-threatening

Note: OMIM states this is XLD, however it is males that a repeatedly reported affected and just carrier females; females are affected when HOMOZYGOUS, meaning this is primarily an XLR condition
Sources: Literature
Prepair 1000+ v0.61 F11 Crystle Lee gene: F11 was added
gene: F11 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: F11 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: F11 were set to 18446632; 15026311; 27723456
Phenotypes for gene: F11 were set to Factor XI deficiency, autosomal dominant (MIM#612416); Factor XI deficiency, autosomal recessive, (MIM#612416)
Review for gene: F11 was set to AMBER
Added comment: Recessive cases are more severe than heterozygous carriers, who may be asymptomatic despite having FXI deficiency (PMID:18446632). Dominant negative missense tend to have dominant inheritance patterns (PMID:15026311), while PTCs are generally recessive, though symptomatic carriers have been reported (OMIM).

PMID: 27723456 - "Bleeding due to FXI deficiency is variable and does not correlate with the plasma FXI level or FXI coagulant activity1"
Sources: Literature
Susceptibility to Fungal Infections v1.0 CLEC7A Peter McNaughton gene: CLEC7A was added
gene: CLEC7A was added to Susceptibility to Fungal Infections. Sources: Literature
Mode of inheritance for gene: CLEC7A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CLEC7A were set to PMID: 19864674
Phenotypes for gene: CLEC7A were set to Mucocutaneous candidiasis
Review for gene: CLEC7A was set to RED
Added comment: Single kindred with mucocutaneous candida.
Sources: Literature
Susceptibility to Fungal Infections v1.0 STAT3 Peter McNaughton gene: STAT3 was added
gene: STAT3 was added to Susceptibility to Fungal Infections. Sources: Literature
Mode of inheritance for gene: STAT3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: STAT3 were set to PMID: 30185668; PMID: 22751495
Phenotypes for gene: STAT3 were set to Mucocutaneous candidiasis
Mode of pathogenicity for gene: STAT3 was set to Other
Added comment: Mucocutaneous candida in 85% of STAT3-LOF
Sources: Literature
Susceptibility to Fungal Infections v1.0 AIRE Peter McNaughton gene: AIRE was added
gene: AIRE was added to Susceptibility to Fungal Infections. Sources: Literature
Mode of inheritance for gene: AIRE was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: AIRE were set to PMID: 30510552
Review for gene: AIRE was set to GREEN
Added comment: CMC is the most common infection occurring in APECED patients (77–100%), CMC is also the most common first clinical manifestation of APECED syndrome (40–93%)
Sources: Literature
Hydrops fetalis v0.284 SPTA1 Di Milnes gene: SPTA1 was added
gene: SPTA1 was added to Hydrops fetalis. Sources: Literature
Mode of inheritance for gene: SPTA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPTA1 were set to 34132406
Phenotypes for gene: SPTA1 were set to Spherocytosis type 3 #270970; Elliptocytosis-2 #130600; pyropoikilocytosis #266140
Review for gene: SPTA1 was set to AMBER
Added comment: single case fetus consanguineous parents
severe anaemia with NIHF
homozygous variant NM_003126.4:c.83G>A
Sources: Literature
Hydrops fetalis v0.284 DOK7 Di Milnes changed review comment from: Homozygous pathogenic variant NM_173660.5:c.439delG
recurrent NIHF in four consanguineous families
NIHF as part of the presentation of FADS; to: Homozygous pathogenic variant NM_173660.5:c.439delG
recurrent NIHF in four consanguineous families
NIHF as part of the presentation of FADS
PMID didn't save the last digit - 34132406
Hydrops fetalis v0.284 GLDN Di Milnes gene: GLDN was added
gene: GLDN was added to Hydrops fetalis. Sources: Literature
Mode of inheritance for gene: GLDN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLDN were set to 34132406
Phenotypes for gene: GLDN were set to Lethal congenital contracture syndrome 11, MIM# 617194
Review for gene: GLDN was set to AMBER
Added comment: Homozygous pathogenic variant in two of three recurrent NIHF in consanguineous couple (no DNA from the 3rd fetus available - two prior pregnancies and current pregnancy NIHF), segregated in parents
NM_181789.4:c.385_392delTGCAACAG
Sources: Literature
Prepair 1000+ v0.61 EYS Crystle Lee gene: EYS was added
gene: EYS was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: EYS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EYS were set to 31074760
Phenotypes for gene: EYS were set to Retinitis pigmentosa 25 (MIM#602772)
Review for gene: EYS was set to AMBER
Added comment: Well established gene disease association. Highly variable age of onset of retinal disease
Sources: Literature
Hydrops fetalis v0.284 DOK7 Di Milnes reviewed gene: DOK7: Rating: AMBER; Mode of pathogenicity: None; Publications: 3413240; Phenotypes: Fetal akinesia deformation sequence 3, MIM# 618389; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.61 CYP21A2 Crystle Lee gene: CYP21A2 was added
gene: CYP21A2 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: CYP21A2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CYP21A2 were set to Adrenal hyperplasia, congenital, due to 21-hydroxylase deficiency (MIM#201910)
Review for gene: CYP21A2 was set to RED
Added comment: Well established gene-disease association.

Pseudogene and structural variants make NGS data difficult to interpret. Not suitable for inclusion in a carrier screening panel due to technical reasons
Sources: Literature
Early-onset Parkinson disease v0.215 ATXN1_CAG SHEKEEB MOHAMMAD STR: ATXN1_CAG was added
STR: ATXN1_CAG was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for STR: ATXN1_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: ATXN1_CAG were set to • PMID: 24602359
Phenotypes for STR: ATXN1_CAG were set to Spinocerebellar Ataxia type 1; Parkinsonism; OMIM 164400
Review for STR: ATXN1_CAG was set to GREEN
Added comment: Sources: Literature
Congenital Heart Defect v0.239 KYNU Chloe Stutterd gene: KYNU was added
gene: KYNU was added to Congenital Heart Defect. Sources: Literature,Expert list
Mode of inheritance for gene: KYNU was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KYNU were set to 28792876; 33942433
Phenotypes for gene: KYNU were set to MIM# 617661 Vertebral, cardiac, renal, and limb defects syndrome 2
Review for gene: KYNU was set to GREEN
gene: KYNU was marked as current diagnostic
Added comment: Biallelic, inactivating variants in three genes encoding enzymes of the NAD biosynthesis pathway (KYNU, HAAO, and NADSYN1) disrupt NAD synthesis and have been identified in patients with multiple malformations of the heart, kidney, vertebrae, and limbs; these patients have Congenital NAD Deficiency Disorder (PMID: 33942433)
Sources: Literature, Expert list
Congenital Heart Defect v0.239 KDR Chloe Stutterd gene: KDR was added
gene: KDR was added to Congenital Heart Defect. Sources: Literature,Expert list
Mode of inheritance for gene: KDR was set to Unknown
Publications for gene: KDR were set to 34113005; 34328347; 30232381
Phenotypes for gene: KDR were set to Tetralogy of Fallot
Review for gene: KDR was set to RED
gene: KDR was marked as current diagnostic
Added comment: Rare variants associated with ToF but lacking evidence for causality and pathogenesis.

PMID 34113005 (2021): Exome sequencing in a family with two siblings affected by TOF revealed biallelic missense variants in KDR. Studies in knock-in mice and in HEK 293T cells identified embryonic lethality for one variant when occurring in the homozygous state, and a significantly reduced VEGFR2 phosphorylation for both variants. Rare variant burden analysis conducted in a set of 1,569 patients of European descent with TOF identified a 46-fold enrichment of protein-truncating variants (PTVs) in TOF cases compared to controls (P = 7 × 10-11).

PMID 34328347 (2021): exome sequencing data from 811 probands with ToF, four patients had novel LoF variants in KDR demonstrating enrichment in ToF compared with controls. Segregation data not available.

PMID: 30232381 (2019): KDR variants identified in four patients (two stopgain and two nonsynonymous variants) with other VUS identified in one patient. Segregation data not available.
Sources: Literature, Expert list
Congenital Heart Defect v0.239 HDAC8 Chloe Stutterd gene: HDAC8 was added
gene: HDAC8 was added to Congenital Heart Defect. Sources: Literature,Expert list
Mode of inheritance for gene: HDAC8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HDAC8 were set to 24403048
Phenotypes for gene: HDAC8 were set to MIM# 300882 Cornelia de Lange syndrome 5
Review for gene: HDAC8 was set to GREEN
gene: HDAC8 was marked as current diagnostic
Added comment: PMID:24403048: 11/30 individuals with HDAC8-related CdLS identified with CHD (ASD, VSD, ToF, valve dysplasia, PDA)(Supp table).
Sources: Literature, Expert list
Cancer Predisposition_Paediatric v0.118 GPC3 Zornitza Stark Classified gene: GPC3 as Green List (high evidence)
Cancer Predisposition_Paediatric v0.118 GPC3 Zornitza Stark Gene: gpc3 has been classified as Green List (High Evidence).
Cancer Predisposition_Paediatric v0.117 GPC3 Zornitza Stark gene: GPC3 was added
gene: GPC3 was added to Cancer Predisposition_Paediatric. Sources: Expert Review
Mode of inheritance for gene: GPC3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: GPC3 were set to Simpson-Golabi-Behmel syndrome, type 1, MIM# 312870
Review for gene: GPC3 was set to GREEN
Added comment: Increased risk of Wilms tumour and embryonal tumours is a feature of Simpson-Golabi-Behmel syndrome.
Sources: Expert Review
Congenital Heart Defect v0.239 HAAO Chloe Stutterd edited their review of gene: HAAO: Added comment: CHD reported: Atrial septal defect; Hypoplastic left heart syndrome; Aortic stenosis; Mitral stenosis; Tetralogy of fallot with complete atriventricular canal and pulmonary stenosis; Lsvc and left pulmonary artery arising from the ductus arteriosus; Shone syndrome with aortic coarctation; Changed phenotypes: MIM#617660 Vertebral, cardiac, renal, and limb defects syndrome 1
Congenital Heart Defect v0.239 HAAO Chloe Stutterd gene: HAAO was added
gene: HAAO was added to Congenital Heart Defect. Sources: Literature,Expert list
Mode of inheritance for gene: HAAO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HAAO were set to 28792876; 33942433
Phenotypes for gene: HAAO were set to Atrial septal defect; Hypoplastic left heart syndrome; Aortic stenosis; Mitral stenosis; Tetralogy of fallot with complete atriventricular canal and pulmonary stenosis; Lsvc and left pulmonary artery arising from the ductus arteriosus; Shone syndrome with aortic coarctation
Review for gene: HAAO was set to GREEN
gene: HAAO was marked as current diagnostic
Added comment: MIM#617660 phenotype is called 'Vertebral, cardiac, renal, and limb defects syndrome type 1' and is a form of Congenital NAD Deficiency Disorder.

Biallelic, inactivating variants in three genes encoding enzymes of the NAD biosynthesis pathway (KYNU, HAAO, and NADSYN1) disrupt NAD synthesis and have been identified in patients with multiple malformations of the heart, kidney, vertebrae, and limbs; these patients have Congenital NAD Deficiency Disorder (PMID: 33942433).
Sources: Literature, Expert list
Congenital Heart Defect v0.239 GLI3 Chloe Stutterd gene: GLI3 was added
gene: GLI3 was added to Congenital Heart Defect. Sources: Literature,Expert list
Mode of inheritance for gene: GLI3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GLI3 were set to 24736735; 7211952
Phenotypes for gene: GLI3 were set to ASD, VSD, AVSD, aortic arch anomaly, PDA
Mode of pathogenicity for gene: GLI3 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: GLI3 was set to GREEN
gene: GLI3 was marked as current diagnostic
Added comment: Syndromic CHD associated with the Pallister-Hall syndrome (PHS) phenotype which is caused by truncating mutations in the middle third of the gene that produce a truncated functional repressor protein.

OMIM #146510 (Pallister-Hall syndrome; PHS) phenotype includes ventricular septal defect, aortic coarctation and patent ductus arteriosus based on original clinical description of syndrome in 1980 in patients without molecular confirmation of diagnosis (PubMed 7211952)

PMID 24736735 (2015): French cohort of 76 individuals from 55 families carrying a GLI3 molecular defect. CHD identified in 5/21 unrelated patients with PHS (septal defects, aortic arch anomaly).
Sources: Literature, Expert list
Congenital Heart Defect v0.239 FOXP1 Chloe Stutterd gene: FOXP1 was added
gene: FOXP1 was added to Congenital Heart Defect. Sources: Literature,Expert list
Mode of inheritance for gene: FOXP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXP1 were set to 29090079; 23766104
Phenotypes for gene: FOXP1 were set to Atrial septal defect; Atrioventricular septal defect; Patent ductus arteriosus; Pulmonic stenosis; Hypoplastic left heart syndrome
Review for gene: FOXP1 was set to AMBER
gene: FOXP1 was marked as current diagnostic
Added comment: Best evidence of association with CHD comes from PMID:29090079 but only for two patients and one with very mild CHD only. Study is a prospective investigation of nine children with FOXP1 syndrome using a battery of standardized clinical assessments, two had CHD (one with pulmonary stenosis, the other with self-resolving PDA). Authors recommend cardiac screening for patients with FOXP1 neurodevelopmental syndrome.

PMID:23766104: Single patient with CHD (AVSD, hypoplastic left ventricle and aortic arch, left atrioventricular valve stenosis, bilateral superior vena cavae, transposed great vessels) and cryptorchidism and a novel 3p14 microdeletion involving first 4 exons of FOXP1, inherited from an unaffected mother. FOXP1 sequenced in 82 patients with AVSD or HLHS: 2/82 patients had FOXP1 variant c.1702C>T;p.(Pro568Ser), inheritance unknown, variant present gnomAD in 153 hets, benign/likely benign in ClinVar .

PMID: 25908055; 22290856: CHD associated with 3p14 contiguous gene deletion syndrome involving FOXP1 and up to 30 other genes.

Homozygous null mice have CHD (MGI ID:1914004; PMID: 15342473).
Sources: Literature, Expert list
Mendeliome v1.171 CTR9 Zornitza Stark Phenotypes for gene: CTR9 were changed from Neurodevelopmental disorder (MONDO:0700092), CTR9 related to Neurodevelopmental disorder (MONDO:0700092), CTR9 related; Familial Wilms tumour, MONDO:0006058, CTR9-related
Mendeliome v1.170 CTR9 Zornitza Stark Publications for gene: CTR9 were set to PMID: 35499524
Mendeliome v1.169 CTR9 Zornitza Stark reviewed gene: CTR9: Rating: GREEN; Mode of pathogenicity: None; Publications: 25099282, 29292210; Phenotypes: Familial Wilms tumour, MONDO:0006058, CTR9-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cancer Predisposition_Paediatric v0.116 CTR9 Zornitza Stark Marked gene: CTR9 as ready
Cancer Predisposition_Paediatric v0.116 CTR9 Zornitza Stark Gene: ctr9 has been classified as Green List (High Evidence).
Cancer Predisposition_Paediatric v0.116 CTR9 Zornitza Stark Classified gene: CTR9 as Green List (high evidence)
Cancer Predisposition_Paediatric v0.116 CTR9 Zornitza Stark Gene: ctr9 has been classified as Green List (High Evidence).
Cancer Predisposition_Paediatric v0.115 CTR9 Zornitza Stark gene: CTR9 was added
gene: CTR9 was added to Cancer Predisposition_Paediatric. Sources: Expert Review
Mode of inheritance for gene: CTR9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTR9 were set to 25099282; 29292210
Phenotypes for gene: CTR9 were set to Familial Wilms tumour, MONDO:0006058, CTR9-related
Review for gene: CTR9 was set to GREEN
Added comment: Four unrelated families reported, where germline variants segregated with disease. Postulated to be a tumour suppressor gene.

Note variants in this gene have also been associated with a neurodevelopmental disorder.
Sources: Expert Review
Prepair 1000+ v0.61 CERKL Crystle Lee edited their review of gene: CERKL: Changed rating: AMBER
Prepair 1000+ v0.61 CYP19A1 Crystle Lee gene: CYP19A1 was added
gene: CYP19A1 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: CYP19A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP19A1 were set to 29553041; 17164303; 25264451
Phenotypes for gene: CYP19A1 were set to Aromatase deficiency (MIM#613546)
Review for gene: CYP19A1 was set to AMBER
Added comment: Aromatase deficiency is a rare disease characterized by a decrease in estrogen synthesis. Clinical characteristics of patients with aromatase deficiency vary depending on gender, age and enzymatic activity

CYP19A1 loss-of-function because of biallelic mutations leads to aromatase deficiency, whereas CYP19A1 overexpression because of genomic rearrangements results in aromatase excess syndrome (https://doi.org/10.1016/j.coemr.2020.03.002)
Sources: Literature
Early-onset Parkinson disease v0.215 MT-ND6 SHEKEEB MOHAMMAD gene: MT-ND6 was added
gene: MT-ND6 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene gene: MT-ND6 was set to MITOCHONDRIAL
Publications for gene: MT-ND6 were set to PMID: 33109474
Phenotypes for gene: MT-ND6 were set to Leber Optic Atrophy; Parkinsonism; OMIM 516006
Review for gene: MT-ND6 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.215 WASL SHEKEEB MOHAMMAD gene: WASL was added
gene: WASL was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: WASL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WASL were set to PMID: 33571872
Phenotypes for gene: WASL were set to Early onset parkinsonism
Review for gene: WASL was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.215 KMT2B SHEKEEB MOHAMMAD gene: KMT2B was added
gene: KMT2B was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: KMT2B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KMT2B were set to PMID: 33816656
Phenotypes for gene: KMT2B were set to DYT28; Childhood‐onset and progressive dystonia; Dysarthria; Dysphagia; Developmental delay; Dysmorphic features; Parkinsonism; OMIM 617284
Review for gene: KMT2B was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.215 GBA SHEKEEB MOHAMMAD gene: GBA was added
gene: GBA was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: GBA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GBA were set to PMID: 12809640
Phenotypes for gene: GBA were set to Gaucher Disease Type 1; Early onset parkinsonism; Bone lesions; Hepatosplenomegaly; Hematologic disorders; OMIM 230800
Review for gene: GBA was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.215 FRRS1L SHEKEEB MOHAMMAD gene: FRRS1L was added
gene: FRRS1L was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: FRRS1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FRRS1L were set to PMID: 29086067
Phenotypes for gene: FRRS1L were set to Developmental and epileptic dyskinetic encephalopathy; Seizures; Chorea; Parkinsonism; Developmental delay; OMIM 616981
Review for gene: FRRS1L was set to GREEN
Added comment: Sources: Literature
Prepair 1000+ v0.61 CYP11B1 Crystle Lee gene: CYP11B1 was added
gene: CYP11B1 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: CYP11B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP11B1 were set to 8768848
Phenotypes for gene: CYP11B1 were set to Adrenal hyperplasia, congenital, due to 11-beta-hydroxylase deficiency (MIM#202010)
Review for gene: CYP11B1 was set to AMBER
Added comment: CAH due to 11-beta-hydroxylase deficiency is an autosomal recessive disorder of corticosteroid biosynthesis resulting in androgen excess, virilization, and hypertension.

Well established gene-disease association.
Sources: Literature
Early-onset Parkinson disease v0.215 ALPL SHEKEEB MOHAMMAD gene: ALPL was added
gene: ALPL was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: ALPL was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: ALPL were set to PMID: 32956941
Phenotypes for gene: ALPL were set to Hypophosphatasia; Osteomalacia; Parkinsonism; OMIM 146300
Review for gene: ALPL was set to GREEN
Added comment: Sources: Literature
Prepair 1000+ v0.61 CERKL Crystle Lee edited their review of gene: CERKL: Changed publications: 33322828, 32036094
Prepair 1000+ v0.61 CERKL Crystle Lee changed review comment from: More than 20 families reported, though some variants are recurrent (founder). This gene causes nonsyndromic retinal disease. Highly variable age of onset (7-45 years) and severity. There is also evidence of phenotypic intra- and inter-familial variability between patients with the same genotype.
Sources: Literature; to: More than 20 families reported, though some variants are recurrent (founder). This gene causes nonsyndromic retinal disease. Highly variable age of onset (7-45 years) and severity. There is also evidence of phenotypic intra- and inter-familial variability between patients with the same genotype.
Sources: Literature
Prepair 1000+ v0.61 CERKL Crystle Lee gene: CERKL was added
gene: CERKL was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: CERKL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CERKL were set to 33322828
Phenotypes for gene: CERKL were set to Retinitis pigmentosa 26 (MIM#608380)
Review for gene: CERKL was set to RED
Added comment: More than 20 families reported, though some variants are recurrent (founder). This gene causes nonsyndromic retinal disease. Highly variable age of onset (7-45 years) and severity. There is also evidence of phenotypic intra- and inter-familial variability between patients with the same genotype.
Sources: Literature
Early-onset Parkinson disease v0.215 ADAR SHEKEEB MOHAMMAD gene: ADAR was added
gene: ADAR was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: ADAR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAR were set to PMID: 32911246
Phenotypes for gene: ADAR were set to Aicardi-Goutieres syndrome 6; neuroinflammatory disorder with cerebral calcification; progressive loss of cognition; spasticity; dystonia; parkinsonism; OMIM 615010
Review for gene: ADAR was set to GREEN
Added comment: Sources: Literature
Prepair 1000+ v0.61 BTD Crystle Lee gene: BTD was added
gene: BTD was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: BTD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BTD were set to 16435182; 20301497; 32440248
Phenotypes for gene: BTD were set to Biotinidase deficiency (MIM#253260)
Review for gene: BTD was set to RED
Added comment: Well-established gene disease association. Genotype/phenotype correlations in biotinidase deficiency are not well established, decisions regarding treatment should be based on the results of enzyme activity rather than molecular genetic testing.

May be challenging to predict phenotypic outcome in a carrier screening context.
Sources: Literature
Deafness_Isolated v1.33 TRRAP Elena Savva gene: TRRAP was added
gene: TRRAP was added to Deafness_Isolated. Sources: Literature
Mode of inheritance for gene: TRRAP was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TRRAP were set to PMID: 31231791
Phenotypes for gene: TRRAP were set to ?Deafness, autosomal dominant 75 MIM#618778
Review for gene: TRRAP was set to RED
Added comment: PMID: 31231791: missense variant, no functional performed
- 4 members of a 3-generation Chinese family with adult-onset autosomal dominant nonsyndromic moderate to severe deafness, but 8 hets in gnomAD
- Knockdown or knockout of TRRAP resulted in significant defects in the inner ear of zebrafish
Sources: Literature
Prepair 1000+ v0.61 AIRE Crystle Lee gene: AIRE was added
gene: AIRE was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: AIRE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AIRE were set to 35521792; 28323927
Phenotypes for gene: AIRE were set to Autoimmune polyendocrinopathy syndrome , type I, with or without reversible metaphyseal dysplasia (MIM#240300)
Review for gene: AIRE was set to AMBER
Added comment: Well established gene disease association. Onset in childhood however phenotype can vary even between siblings with the same genotype. Therefore, it may be difficult (?impossible) to predict the severity/age of onset from the genotype

Most reported individuals have bi-allelic variants. AD inheritance has been reported in a single family (OMIM) p.G228W has been shown to have a dominant-negative effect by binding to WT AIRE (OMIM)
Sources: Literature
Prepair 1000+ v0.61 KCNE1 Crystle Lee reviewed gene: KCNE1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Long QT syndrome 5, MIM# 613695, Jervell and Lange-Nielsen syndrome 2, MIM# 612347, Acquired LQTS; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.61 VPS13A Crystle Lee reviewed gene: VPS13A: Rating: AMBER; Mode of pathogenicity: None; Publications: 28446873; Phenotypes: Choreoacanthocytosis (MIM#200150); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.61 TH Crystle Lee reviewed gene: TH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Segawa syndrome, recessive (MIM#605407); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.61 SPG11 Crystle Lee reviewed gene: SPG11: Rating: GREEN; Mode of pathogenicity: None; Publications: 33581793; Phenotypes: Spastic paraplegia 11, autosomal recessive (MIM#604360); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.61 SPART Crystle Lee reviewed gene: SPART: Rating: GREEN; Mode of pathogenicity: None; Publications: 31535723, 28875386, 28679690; Phenotypes: Troyer syndrome (MIM#275900), SPG20, MONDO:0010156; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.61 SETX Crystle Lee reviewed gene: SETX: Rating: GREEN; Mode of pathogenicity: None; Publications: 23129421; Phenotypes: Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 (MIM#606002); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.61 PLA2G6 Crystle Lee reviewed gene: PLA2G6: Rating: GREEN; Mode of pathogenicity: None; Publications: 35803092; Phenotypes: Infantile neuroaxonal dystrophy 1 MIM#256600, Neurodegeneration with brain iron accumulation 2B MIM#610217; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.61 PANK2 Crystle Lee reviewed gene: PANK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 15911822; Phenotypes: HARP syndrome (MIM#607236), Neurodegeneration with brain iron accumulation 1 (MIM#234200); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.61 NPC2 Crystle Lee reviewed gene: NPC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29625568, 17470133; Phenotypes: Niemann-pick disease, type C2 (MIM#607625); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.61 NPC1 Crystle Lee reviewed gene: NPC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11333381, 26910362; Phenotypes: Niemann-Pick disease, type C1 (MIM#257220); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.61 LMNA Crystle Lee reviewed gene: LMNA: Rating: GREEN; Mode of pathogenicity: None; Publications: 18551513, 15148145, 17377071; Phenotypes: Emery-Dreifuss muscular dystrophy 3, autosomal recessive (MIM#616516), Mandibuloacral dysplasia (MIM#248370); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Prepair 1000+ v0.61 LDLR Crystle Lee reviewed gene: LDLR: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: LDL cholesterol level QTL2/Hypercholesterolemia, familial, 1 (MIM#143890); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Prepair 1000+ v0.61 FIG4 Crystle Lee reviewed gene: FIG4: Rating: GREEN; Mode of pathogenicity: None; Publications: 30740813, 23623387, 17572665, 24878229; Phenotypes: Yunis-Varon syndrome (MIM#216340); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Macrocystic Disease v0.48 PMM2 Chirag Patel Classified gene: PMM2 as Green List (high evidence)
Renal Macrocystic Disease v0.48 PMM2 Chirag Patel Gene: pmm2 has been classified as Green List (High Evidence).
Renal Macrocystic Disease v0.47 PMM2 Chirag Patel gene: PMM2 was added
gene: PMM2 was added to Renal Macrocystic Disease. Sources: Literature
Mode of inheritance for gene: PMM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PMM2 were set to PMID: 28373276, 32595772
Phenotypes for gene: PMM2 were set to Hyperinsulinaemic Hypoglycaemia and Polycystic Kidney Disease (HIPKD)
Review for gene: PMM2 was set to GREEN
gene: PMM2 was marked as current diagnostic
Added comment: Cabezas et al (2017) reported co-occurrence of hyperinsulinaemic hypoglycaemia and polycystic kidney disease (HIPKD in 17 children from 11 unrelated families. Patients presented with hyperinsulinaemic hypoglycaemia in infancy and enlarged kidneys with multiple kidney cysts. Some progressed to ESKD and some had liver cysts.

Whole-genome linkage analysis in 5 informative families identified a single significant locus on chromosome 16p13.2. Sequencing of the coding regions of all linked genes failed to identify biallelic mutations. Instead, they found in all patients a promoter mutation (c.-167G>T) in PMM2, either homozygous or in trans with PMM2 coding mutations. They found deglycosylation in cultured pancreatic β cells altered insulin secretion. In vitro, the PMM2 promoter mutation associated with decreased transcriptional activity in patient kidney cells and impaired binding of the transcription factor ZNF143. In silico analysis suggested an important role of ZNF143 for the formation of a chromatin loop including PMM2. They proposed that the PMM2 promoter mutation alters tissue-specific chromatin loop formation, with consequent organ-specific deficiency of PMM2 leading to the restricted phenotype of HIPKD.

None of the patients exhibited the typical clinical or diagnostic features of CDG1A. Serum transferrin glycosylation was normal in 11 patients who had assessment.
Sources: Literature
Prepair 1000+ v0.61 IGHM Crystle Lee reviewed gene: IGHM: Rating: AMBER; Mode of pathogenicity: None; Publications: 12370281, 8890099; Phenotypes: Agammaglobulinemia 1 (MIM#601495); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.61 DOCK2 Crystle Lee reviewed gene: DOCK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26083206, 29204803, 33928462, 30826364; Phenotypes: Immunodeficiency 40 (MIM#616433); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.61 PRKRA Crystle Lee reviewed gene: PRKRA: Rating: AMBER; Mode of pathogenicity: None; Publications: 35844281, 18243799, 25142429, 35844287; Phenotypes: Dystonia 16 (MIM#612067); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Inflammatory bowel disease v0.78 SLCO2A1 Peter McNaughton gene: SLCO2A1 was added
gene: SLCO2A1 was added to Inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: SLCO2A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLCO2A1 were set to PMID: 29313109
Phenotypes for gene: SLCO2A1 were set to Enteropathy
Review for gene: SLCO2A1 was set to GREEN
Added comment: Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4859 C20orf24 Zornitza Stark Marked gene: C20orf24 as ready
Intellectual disability syndromic and non-syndromic v0.4859 C20orf24 Zornitza Stark Gene: c20orf24 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.4859 C20orf24 Zornitza Stark gene: C20orf24 was added
gene: C20orf24 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
new gene name tags were added to gene: C20orf24.
Mode of inheritance for gene: C20orf24 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C20orf24 were set to 35614220; 24194475
Phenotypes for gene: C20orf24 were set to Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome 2, MIM# 616994
Review for gene: C20orf24 was set to RED
Added comment: Bi-allelic LoF variant identified in patient originally reported in PMID 24194475. HGNC approved name is RAB5IF.
Sources: Literature
Mendeliome v1.169 C20orf24 Zornitza Stark Tag new gene name tag was added to gene: C20orf24.
Mendeliome v1.169 C20orf24 Zornitza Stark Marked gene: C20orf24 as ready
Mendeliome v1.169 C20orf24 Zornitza Stark Gene: c20orf24 has been classified as Red List (Low Evidence).
Mendeliome v1.169 C20orf24 Zornitza Stark gene: C20orf24 was added
gene: C20orf24 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: C20orf24 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C20orf24 were set to 35614220; 24194475
Phenotypes for gene: C20orf24 were set to Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome 2, MIM# 616994
Review for gene: C20orf24 was set to RED
Added comment: Bi-allelic LoF variant identified in patient originally reported in PMID 24194475.

HGNC approved name is RAB5IF.
Sources: Literature
Prepair 1000+ v0.61 KCNQ1 Crystle Lee reviewed gene: KCNQ1: Rating: AMBER; Mode of pathogenicity: None; Publications: 29033053, 28438721; Phenotypes: Jervell and Lange-Nielsen syndrome (MIM#220400); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.61 GLA Crystle Lee reviewed gene: GLA: Rating: GREEN; Mode of pathogenicity: None; Publications: 29649853, 20301469; Phenotypes: Fabry disease (MIM#301500); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v0.61 DSP Zornitza Stark Marked gene: DSP as ready
Prepair 1000+ v0.61 DSP Zornitza Stark Gene: dsp has been classified as Green List (High Evidence).
Prepair 1000+ v0.61 DSP Zornitza Stark Phenotypes for gene: DSP were changed from Cardiomyopathy, dilated, with woolly hair and keratoderma, 605676 (3) to Cardiomyopathy, dilated, with woolly hair and keratoderma (MIM#605676); Epidermolysis bullosa, lethal acantholytic (MIM#609638)
Prepair 1000+ v0.60 DSP Zornitza Stark Publications for gene: DSP were set to
Prepair 1000+ v0.59 CASQ2 Zornitza Stark Tag for review tag was added to gene: CASQ2.
Prepair 1000+ v0.59 ATP7B Zornitza Stark Marked gene: ATP7B as ready
Prepair 1000+ v0.59 ATP7B Zornitza Stark Gene: atp7b has been classified as Green List (High Evidence).
Prepair 1000+ v0.59 ATP7B Zornitza Stark Publications for gene: ATP7B were set to
Prepair 1000+ v0.58 ATP13A2 Zornitza Stark Tag for review tag was added to gene: ATP13A2.
Prepair 1000+ v0.58 BGN Zornitza Stark Tag for review tag was added to gene: BGN.
Prepair 1000+ v0.58 C8B Zornitza Stark Tag for review tag was added to gene: C8B.
Prepair 1000+ v0.58 C7 Zornitza Stark Tag for review tag was added to gene: C7.
Prepair 1000+ v0.58 C6 Zornitza Stark Tag for review tag was added to gene: C6.
Mendeliome v1.168 IL23R Zornitza Stark edited their review of gene: IL23R: Changed phenotypes: Immunodeficiency disease, MONDO:0021094, Susceptibility to mycobacteria and Salmonella Edit
Mendeliome v1.168 IL23R Zornitza Stark edited their review of gene: IL23R: Changed phenotypes: Immunodeficiency disease, MONDO:0021094
Mendeliome v1.168 IL23R Zornitza Stark Phenotypes for gene: IL23R were changed from Susceptibility to mycobacteria and Salmonella to Immunodeficiency disease, MONDO:0021094; Susceptibility to mycobacteria and Salmonella
Mendeliome v1.167 IL23R Zornitza Stark Publications for gene: IL23R were set to 30578351
Mendeliome v1.166 IL23R Zornitza Stark Classified gene: IL23R as Amber List (moderate evidence)
Mendeliome v1.166 IL23R Zornitza Stark Gene: il23r has been classified as Amber List (Moderate Evidence).
Mendeliome v1.165 IL23R Zornitza Stark edited their review of gene: IL23R: Added comment: PMID 35829840: 48yo male with disseminated NTM homozygous (p.R381X) with supportive functional data.; Changed rating: AMBER; Changed publications: 30578351, 35829840
Defects of intrinsic and innate immunity v0.117 IL23R Zornitza Stark Phenotypes for gene: IL23R were changed from Susceptibility to mycobacteria and Salmonella to Immunodeficiency disease, MONDO:0021094; Susceptibility to mycobacteria and Salmonella
Defects of intrinsic and innate immunity v0.116 IL23R Zornitza Stark Publications for gene: IL23R were set to 30578351
Defects of intrinsic and innate immunity v0.115 IL23R Zornitza Stark Classified gene: IL23R as Green List (high evidence)
Defects of intrinsic and innate immunity v0.115 IL23R Zornitza Stark Gene: il23r has been classified as Green List (High Evidence).
Prepair 1000+ v0.58 FA2H Crystle Lee reviewed gene: FA2H: Rating: GREEN; Mode of pathogenicity: None; Publications: 31135052, 31837835, 22146942, 19068277; Phenotypes: Spastic paraplegia 35, autosomal recessive (MIM#612319); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Phagocyte Defects v1.6 HYOU1 Zornitza Stark edited their review of gene: HYOU1: Changed rating: AMBER; Changed phenotypes: Immunodeficiency 59 and hypoglycemia, MIM# 233600
Prepair 1000+ v0.58 DSP Crystle Lee reviewed gene: DSP: Rating: GREEN; Mode of pathogenicity: None; Publications: 22795705, 16175511, 20302578, 20613772, 16467215; Phenotypes: Cardiomyopathy, dilated, with woolly hair and keratoderma (MIM#605676), Epidermolysis bullosa, lethal acantholytic (MIM#609638); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.165 HYOU1 Zornitza Stark Classified gene: HYOU1 as Amber List (moderate evidence)
Mendeliome v1.165 HYOU1 Zornitza Stark Gene: hyou1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.164 HYOU1 Zornitza Stark edited their review of gene: HYOU1: Added comment: Second individual reported in PMID: 35822684 with severe neutropenia.; Changed rating: AMBER; Changed publications: 27913302, 35822684; Changed phenotypes: Immunodeficiency 59 and hypoglycemia, MIM# 233600
Phagocyte Defects v1.6 HYOU1 Zornitza Stark Marked gene: HYOU1 as ready
Phagocyte Defects v1.6 HYOU1 Zornitza Stark Added comment: Comment when marking as ready: Promoted to Amber as two individuals now reported.
Phagocyte Defects v1.6 HYOU1 Zornitza Stark Gene: hyou1 has been classified as Amber List (Moderate Evidence).
Phagocyte Defects v1.6 HYOU1 Zornitza Stark Publications for gene: HYOU1 were set to 27913302
Phagocyte Defects v1.5 HYOU1 Zornitza Stark Classified gene: HYOU1 as Amber List (moderate evidence)
Phagocyte Defects v1.5 HYOU1 Zornitza Stark Gene: hyou1 has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v0.58 PGK1 Zornitza Stark Tag for review tag was added to gene: PGK1.
Prepair 1000+ v0.58 GK Zornitza Stark Tag for review tag was added to gene: GK.
Prepair 1000+ v0.58 CASQ2 Crystle Lee reviewed gene: CASQ2: Rating: AMBER; Mode of pathogenicity: None; Publications: 34012068; Phenotypes: Ventricular tachycardia, catecholaminergic polymorphic, 2 (MIM#611938); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.58 ATP7B Crystle Lee reviewed gene: ATP7B: Rating: GREEN; Mode of pathogenicity: None; Publications: 28433102; Phenotypes: Wilson disease (MIM#277900); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.58 ATP13A2 Crystle Lee reviewed gene: ATP13A2: Rating: RED; Mode of pathogenicity: None; Publications: 28137957, 30746398; Phenotypes: Kufor-Rakeb syndrome (MIM#606693), Spastic paraplegia 78, autosomal recessive (MIM#617225); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.58 BGN Crystle Lee reviewed gene: BGN: Rating: AMBER; Mode of pathogenicity: None; Publications: 27632686, 17502576, 27236923; Phenotypes: Meester-Loeys syndrome (MIM#300989), Spondyloepimetaphyseal dysplasia, X-linked (MIM#300106); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v0.58 C8B Crystle Lee reviewed gene: C8B: Rating: AMBER; Mode of pathogenicity: None; Publications: 8098723, 33563058, 27183977, 9476133, 19434484, 31440263; Phenotypes: C8 deficiency, type II (MIM#613789); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.58 C7 Crystle Lee reviewed gene: C7: Rating: AMBER; Mode of pathogenicity: None; Publications: 22206826, 20591074, 17407100, 16771861; Phenotypes: C7 deficiency (MIM#610102); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.58 C6 Crystle Lee reviewed gene: C6: Rating: AMBER; Mode of pathogenicity: None; Publications: 31440263, 23537992, 17257682, 22668955, 32670577; Phenotypes: C6 deficiency (MIM#612446); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Complement Deficiencies v0.72 C5 Crystle Lee reviewed gene: C5: Rating: AMBER; Mode of pathogenicity: None; Publications: 31440263, 23743184, 15488949, 15778377, 23371790; Phenotypes: C5 deficiency (MIM#609536); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Defects of intrinsic and innate immunity v0.114 IL23R Peter McNaughton reviewed gene: IL23R: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35829840; Phenotypes: Susceptibility to mycobacterial disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Phagocyte Defects v1.4 HYOU1 Peter McNaughton reviewed gene: HYOU1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 35822684; Phenotypes: Severe congenital neutropaenia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.58 PGK1 Crystle Lee reviewed gene: PGK1: Rating: ; Mode of pathogenicity: None; Publications: 16567715, 30887539, 22348148, 28580215; Phenotypes: Phosphoglycerate kinase 1 deficiency (MIM#300653); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v0.58 GK Crystle Lee reviewed gene: GK: Rating: AMBER; Mode of pathogenicity: None; Publications: 33212314, 16549535, 10851254, 9719371, 8651297; Phenotypes: Glycerol kinase deficiency (MIM#307030); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hydrops fetalis v0.284 UROS Zornitza Stark Publications for gene: UROS were set to 24027798
Hydrops fetalis v0.283 UROS Zornitza Stark Classified gene: UROS as Green List (high evidence)
Hydrops fetalis v0.283 UROS Zornitza Stark Gene: uros has been classified as Green List (High Evidence).
Hydrops fetalis v0.282 UROS Chern Lim reviewed gene: UROS: Rating: GREEN; Mode of pathogenicity: None; Publications: 30685241, 34828434, 15065102, 11254675; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v0.58 HERC2 Zornitza Stark Tag for review tag was added to gene: HERC2.
Prepair 1000+ v0.58 GBA Zornitza Stark Tag for review tag was added to gene: GBA.
Prepair 1000+ v0.58 SAMD9 Zornitza Stark Marked gene: SAMD9 as ready
Prepair 1000+ v0.58 SAMD9 Zornitza Stark Gene: samd9 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.58 SAMD9 Zornitza Stark Publications for gene: SAMD9 were set to
Prepair 1000+ v0.57 SAMD9 Zornitza Stark Classified gene: SAMD9 as Red List (low evidence)
Prepair 1000+ v0.57 SAMD9 Zornitza Stark Gene: samd9 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.56 FTCD Zornitza Stark Tag for review tag was added to gene: FTCD.
Prepair 1000+ v0.56 KRT85 Zornitza Stark Marked gene: KRT85 as ready
Prepair 1000+ v0.56 KRT85 Zornitza Stark Gene: krt85 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.56 KRT85 Zornitza Stark Classified gene: KRT85 as Red List (low evidence)
Prepair 1000+ v0.56 KRT85 Zornitza Stark Gene: krt85 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.55 KRT85 Zornitza Stark reviewed gene: KRT85: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ectodermal dysplasia 4, hair/nail type (MIM#602032); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.55 RAG2 Zornitza Stark Marked gene: RAG2 as ready
Prepair 1000+ v0.55 RAG2 Zornitza Stark Gene: rag2 has been classified as Green List (High Evidence).
Prepair 1000+ v0.55 RAG2 Zornitza Stark Publications for gene: RAG2 were set to
Cardiomyopathy_Paediatric v0.132 PPP1R13L Zornitza Stark Phenotypes for gene: PPP1R13L were changed from Dilated cardiomyopathy, onset in infancy to Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042 - PPP1R13L-related; Dilated cardiomyopathy, onset in infancy
Mendeliome v1.164 PPP1R13L Zornitza Stark Phenotypes for gene: PPP1R13L were changed from Dilated cardiomyopathy, onset in infancy to Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042 - PPP1R13L-related; Dilated cardiomyopathy, onset in infancy
Clefting disorders v0.183 PPP1R13L Zornitza Stark Phenotypes for gene: PPP1R13L were changed from Dilated cardiomyopathy, onset in infancy; Cleft lip and palate to Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042 - PPP1R13L-related; Dilated cardiomyopathy, onset in infancy; Cleft lip and palate
Fetal anomalies v1.48 PPP1R13L Zornitza Stark Phenotypes for gene: PPP1R13L were changed from Dilated cardiomyopathy, onset in infancy; Cleft lip and palate to Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042 - PPP1R13L-related; Dilated cardiomyopathy, onset in infancy; Cleft lip and palate
Prepair 1000+ v0.54 CARD9 Zornitza Stark Tag for review tag was added to gene: CARD9.
Prepair 1000+ v0.54 PLG Zornitza Stark Tag for review tag was added to gene: PLG.
Prepair 1000+ v0.54 GYS2 Zornitza Stark Tag for review tag was added to gene: GYS2.
Prepair 1000+ v0.54 MPZ Zornitza Stark Tag for review tag was added to gene: MPZ.
Early-onset Parkinson disease v0.215 KIAA1161 Zornitza Stark Tag new gene name tag was added to gene: KIAA1161.
Prepair 1000+ v0.54 HERC2 Crystle Lee reviewed gene: HERC2: Rating: AMBER; Mode of pathogenicity: None; Publications: 31124564, 11896453; Phenotypes: Intellectual developmental disorder, autosomal recessive 38 (MIM#615516); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.54 GBA Crystle Lee reviewed gene: GBA: Rating: AMBER; Mode of pathogenicity: None; Publications: 28727984; Phenotypes: Gaucher disease, perinatal lethal (MIM#608013); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.215 KIAA1161 Zornitza Stark Marked gene: KIAA1161 as ready
Early-onset Parkinson disease v0.215 KIAA1161 Zornitza Stark Gene: kiaa1161 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.215 KIAA1161 Zornitza Stark Phenotypes for gene: KIAA1161 were changed from Primary familial brain calcification; Atypical parkinsonism; Supranuclear gaze palsy; OMIM 618317 to Basal ganglia calcification, idiopathic, 7, autosomal recessive, OMIM #618317; Primary familial brain calcification; Atypical parkinsonism; Supranuclear gaze palsy
Early-onset Parkinson disease v0.214 KIAA1161 Zornitza Stark Publications for gene: KIAA1161 were set to PMID: 32211515
Early-onset Parkinson disease v0.213 KIAA1161 Zornitza Stark Classified gene: KIAA1161 as Green List (high evidence)
Early-onset Parkinson disease v0.213 KIAA1161 Zornitza Stark Gene: kiaa1161 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.212 KIAA1161 Zornitza Stark reviewed gene: KIAA1161: Rating: GREEN; Mode of pathogenicity: None; Publications: 30656188, 30649222, 30460687, 29910000, 31951047; Phenotypes: Basal ganglia calcification, idiopathic, 7, autosomal recessive, OMIM #618317; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.212 NHLRC1 Zornitza Stark Marked gene: NHLRC1 as ready
Early-onset Parkinson disease v0.212 NHLRC1 Zornitza Stark Gene: nhlrc1 has been classified as Amber List (Moderate Evidence).
Early-onset Parkinson disease v0.212 NHLRC1 Zornitza Stark Phenotypes for gene: NHLRC1 were changed from Lafora disease; Progressive Myoclonic Epilepsy; Parkinsonism; OMIM 254780 to Epilepsy, progressive myoclonic 2B (Lafora), MIM# 254780; Lafora disease; Progressive Myoclonic Epilepsy; Parkinsonism
Early-onset Parkinson disease v0.211 NHLRC1 Zornitza Stark Classified gene: NHLRC1 as Amber List (moderate evidence)
Early-onset Parkinson disease v0.211 NHLRC1 Zornitza Stark Gene: nhlrc1 has been classified as Amber List (Moderate Evidence).
Early-onset Parkinson disease v0.210 NHLRC1 Zornitza Stark reviewed gene: NHLRC1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Epilepsy, progressive myoclonic 2B (Lafora), MIM# 254780; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.210 C9orf3 Zornitza Stark Tag new gene name tag was added to gene: C9orf3.
Early-onset Parkinson disease v0.210 C9orf3 Zornitza Stark Marked gene: C9orf3 as ready
Early-onset Parkinson disease v0.210 C9orf3 Zornitza Stark Gene: c9orf3 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.210 C9orf3 Zornitza Stark Phenotypes for gene: C9orf3 were changed from Dystonia-31; Childhood/Adolescence onset generalised dystonia; Dystonia parkinsonism; Zech-Boesch Syndrome; OMIM 619565 to Dystonia 31, MIM# 619565; Childhood/Adolescence onset generalised dystonia; Dystonia parkinsonism; Zech-Boesch Syndrome
Early-onset Parkinson disease v0.209 C9orf3 Zornitza Stark Classified gene: C9orf3 as Green List (high evidence)
Early-onset Parkinson disease v0.209 C9orf3 Zornitza Stark Gene: c9orf3 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.208 C9orf3 Zornitza Stark reviewed gene: C9orf3: Rating: GREEN; Mode of pathogenicity: None; Publications: 35306330; Phenotypes: Dystonia 31, MIM# 619565; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.54 NCF1 Zornitza Stark Tag for review tag was added to gene: NCF1.
Prepair 1000+ v0.54 NEB Zornitza Stark Tag for review tag was added to gene: NEB.
Prepair 1000+ v0.54 HYDIN Zornitza Stark Tag for review tag was added to gene: HYDIN.
Prepair 1000+ v0.54 SNORD118 Zornitza Stark Marked gene: SNORD118 as ready
Prepair 1000+ v0.54 SNORD118 Zornitza Stark Gene: snord118 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.54 SNORD118 Zornitza Stark Publications for gene: SNORD118 were set to
Prepair 1000+ v0.53 SNORD118 Zornitza Stark Classified gene: SNORD118 as Red List (low evidence)
Prepair 1000+ v0.53 SNORD118 Zornitza Stark Gene: snord118 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.52 SNORD118 Zornitza Stark reviewed gene: SNORD118: Rating: RED; Mode of pathogenicity: None; Publications: 32361877, 33029936; Phenotypes: Leukoencephalopathy, brain calcifications, and cysts, MIM#614561; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.52 UBA1 Zornitza Stark Marked gene: UBA1 as ready
Prepair 1000+ v0.52 UBA1 Zornitza Stark Gene: uba1 has been classified as Green List (High Evidence).
Prepair 1000+ v0.52 UBA1 Zornitza Stark Publications for gene: UBA1 were set to
Prepair 1000+ v0.51 CHM Zornitza Stark Tag for review tag was added to gene: CHM.
Prepair 1000+ v0.51 PROC Zornitza Stark Tag for review tag was added to gene: PROC.
Prepair 1000+ v0.51 IKBKG Zornitza Stark Marked gene: IKBKG as ready
Prepair 1000+ v0.51 IKBKG Zornitza Stark Gene: ikbkg has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v0.51 IKBKG Zornitza Stark Classified gene: IKBKG as Amber List (moderate evidence)
Prepair 1000+ v0.51 IKBKG Zornitza Stark Gene: ikbkg has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v0.50 IKBKG Zornitza Stark reviewed gene: IKBKG: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early-onset Parkinson disease v0.208 ATXN10 Zornitza Stark Marked gene: ATXN10 as ready
Early-onset Parkinson disease v0.208 ATXN10 Zornitza Stark Gene: atxn10 has been removed from the panel.
Early-onset Parkinson disease v0.208 ATXN10 Zornitza Stark Tag STR tag was added to gene: ATXN10.
Early-onset Parkinson disease v0.208 ATXN10 Zornitza Stark commented on gene: ATXN10
Early-onset Parkinson disease v0.208 ATXN2 Zornitza Stark Marked gene: ATXN2 as ready
Early-onset Parkinson disease v0.208 ATXN2 Zornitza Stark Gene: atxn2 has been removed from the panel.
Early-onset Parkinson disease v0.208 ATXN2 Zornitza Stark Publications for gene: ATXN2 were set to PMID: 11761482, 17923635
Early-onset Parkinson disease v0.207 ATXN2 Zornitza Stark Tag STR tag was added to gene: ATXN2.
Early-onset Parkinson disease v0.207 ATXN2 Zornitza Stark commented on gene: ATXN2
Early-onset Parkinson disease v0.207 ATXN3 Zornitza Stark Tag STR tag was added to gene: ATXN3.
Early-onset Parkinson disease v0.207 ATXN3 Zornitza Stark Marked gene: ATXN3 as ready
Early-onset Parkinson disease v0.207 ATXN3 Zornitza Stark Gene: atxn3 has been removed from the panel.
Early-onset Parkinson disease v0.207 ATXN3 Zornitza Stark commented on gene: ATXN3
Early-onset Parkinson disease v0.207 ATXN8 Zornitza Stark Marked gene: ATXN8 as ready
Early-onset Parkinson disease v0.207 ATXN8 Zornitza Stark Gene: atxn8 has been removed from the panel.
Early-onset Parkinson disease v0.207 ATXN8 Zornitza Stark Tag STR tag was added to gene: ATXN8.
Early-onset Parkinson disease v0.207 ATXN8 Zornitza Stark commented on gene: ATXN8
Early-onset Parkinson disease v0.207 TPP1 Zornitza Stark Marked gene: TPP1 as ready
Early-onset Parkinson disease v0.207 TPP1 Zornitza Stark Gene: tpp1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.207 TPP1 Zornitza Stark Phenotypes for gene: TPP1 were changed from Late Infantile NCL; Parkinsonism; OMIM 204500 to Ceroid lipofuscinosis, neuronal, 2, MIM# 204500; Parkinsonism
Early-onset Parkinson disease v0.206 TPP1 Zornitza Stark Classified gene: TPP1 as Green List (high evidence)
Early-onset Parkinson disease v0.206 TPP1 Zornitza Stark Gene: tpp1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.205 TPP1 Zornitza Stark reviewed gene: TPP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ceroid lipofuscinosis, neuronal, 2, MIM# 204500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.205 CYP27A1 Zornitza Stark Marked gene: CYP27A1 as ready
Early-onset Parkinson disease v0.205 CYP27A1 Zornitza Stark Gene: cyp27a1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.205 CYP27A1 Zornitza Stark Phenotypes for gene: CYP27A1 were changed from Cerebrotendinous xanthomatosis, infantile-onset diarrhoea, juvenile-onset cataract, young adult-onset tendon xanthomas; Epilepsy; Parkinsonism; Ataxia; Peripheral neuropathy; OMIM 213700 to Cerebrotendinous xanthomatosis, MIM# 213700; Cerebrotendinous xanthomatosis, infantile-onset diarrhoea, juvenile-onset cataract, young adult-onset tendon xanthomas; Epilepsy; Parkinsonism; Ataxia; Peripheral neuropathy
Early-onset Parkinson disease v0.204 CYP27A1 Zornitza Stark Classified gene: CYP27A1 as Green List (high evidence)
Early-onset Parkinson disease v0.204 CYP27A1 Zornitza Stark Gene: cyp27a1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.203 DDC Zornitza Stark Marked gene: DDC as ready
Early-onset Parkinson disease v0.203 DDC Zornitza Stark Gene: ddc has been classified as Amber List (Moderate Evidence).
Early-onset Parkinson disease v0.203 DDC Zornitza Stark Phenotypes for gene: DDC were changed from Aromatic L-amino acid decarboxylase deficiency (DYT-DDC); Infantile-onset parkinsonism & dystonia; Bulbar dysfunction; Oculogyric crisis; Autonomic dysfunction; Intellectual disability; OMIM 608603 to Aromatic L-amino acid decarboxylase deficiency, MIM# 608643; Infantile-onset parkinsonism & dystonia; Bulbar dysfunction; Oculogyric crisis; Autonomic dysfunction; Intellectual disability
Early-onset Parkinson disease v0.202 DDC Zornitza Stark Classified gene: DDC as Amber List (moderate evidence)
Early-onset Parkinson disease v0.202 DDC Zornitza Stark Gene: ddc has been classified as Amber List (Moderate Evidence).
Early-onset Parkinson disease v0.201 DDC Zornitza Stark reviewed gene: DDC: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Aromatic L-amino acid decarboxylase deficiency, MIM# 608643; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.50 SAMD9 Crystle Lee reviewed gene: SAMD9: Rating: RED; Mode of pathogenicity: None; Publications: 16960814, 18094730; Phenotypes: MIRAGE syndrome (MIM#617053), Monosomy 7 myelodysplasia and leukemia syndrome 2 (MIM#619041), Tumoral calcinosis, familial, normophosphatemic (MIM#610455); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Prepair 1000+ v0.50 FTCD Crystle Lee reviewed gene: FTCD: Rating: AMBER; Mode of pathogenicity: None; Publications: 29178637, 30740726, 12815595; Phenotypes: Glutamate formiminotransferase deficiency (MIM#229100); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.50 KRT85 Crystle Lee reviewed gene: KRT85: Rating: AMBER; Mode of pathogenicity: None; Publications: 16525032, 19865094, 31273852; Phenotypes: Ectodermal dysplasia 4, hair/nail type (MIM#602032); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.163 CHD5 Elena Savva Phenotypes for gene: CHD5 were changed from Intellectual disability; Epilepsy to Parenti-Mignot neurodevelopmental syndrome MIM#619873
Mendeliome v1.162 CHD5 Elena Savva reviewed gene: CHD5: Rating: GREEN; Mode of pathogenicity: None; Publications: 33944996; Phenotypes: Parenti-Mignot neurodevelopmental syndrome MIM#619873; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Prepair 1000+ v0.50 RAG2 Crystle Lee reviewed gene: RAG2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26996199, 30046960; Phenotypes: Combined cellular and humoral immune defects with granulomas (MIM#233650), Omenn syndrome (MIM#603554), Severe combined immunodeficiency, B cell-negative (MIM#601457); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.162 PPP1R13L Krithika Murali reviewed gene: PPP1R13L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042 - PPP1R13L-related disorder; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Clefting disorders v0.182 PPP1R13L Krithika Murali reviewed gene: PPP1R13L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042 - PPP1R13L-related disorder; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cardiomyopathy_Paediatric v0.131 PPP1R13L Krithika Murali reviewed gene: PPP1R13L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042 - PPP1R13L-related disorder; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.47 PPP1R13L Krithika Murali edited their review of gene: PPP1R13L: Changed phenotypes: Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042 - PPP1R13L-related disorder, Dilated cardiomyopathy, onset in infancy, Cleft lip and palate
Early-onset Parkinson disease v0.201 DHDDS Zornitza Stark Marked gene: DHDDS as ready
Early-onset Parkinson disease v0.201 DHDDS Zornitza Stark Gene: dhdds has been classified as Amber List (Moderate Evidence).
Early-onset Parkinson disease v0.201 DHDDS Zornitza Stark Phenotypes for gene: DHDDS were changed from Myoclonic Epilepsy; Parkinsonism; Ataxia; Intellectual disability; OMIM 617836 to Developmental delay and seizures with or without movement abnormalities, MIM# 617836; Myoclonic Epilepsy; Parkinsonism; Ataxia; Intellectual disability
Early-onset Parkinson disease v0.200 DHDDS Zornitza Stark Publications for gene: DHDDS were set to PMID: 34837344, 29100083
Early-onset Parkinson disease v0.199 DHDDS Zornitza Stark Classified gene: DHDDS as Amber List (moderate evidence)
Early-onset Parkinson disease v0.199 DHDDS Zornitza Stark Gene: dhdds has been classified as Amber List (Moderate Evidence).
Early-onset Parkinson disease v0.198 DHDDS Zornitza Stark reviewed gene: DHDDS: Rating: AMBER; Mode of pathogenicity: None; Publications: 34837344; Phenotypes: Developmental delay and seizures with or without movement abnormalities, MIM# 617836; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.198 EIF2AK2 Zornitza Stark Marked gene: EIF2AK2 as ready
Early-onset Parkinson disease v0.198 EIF2AK2 Zornitza Stark Gene: eif2ak2 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.198 EIF2AK2 Zornitza Stark Phenotypes for gene: EIF2AK2 were changed from Neurodevelopmental Syndrome; Developmental delays; Ataxia; Parkinsonism; White matter alterations; OMIM 618877 to Leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome, MIM# 618877; Neurodevelopmental Syndrome; Developmental delays; Ataxia; Parkinsonism; White matter alterations
Early-onset Parkinson disease v0.197 EIF2AK2 Zornitza Stark Mode of inheritance for gene: EIF2AK2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.196 EIF2AK2 Zornitza Stark Classified gene: EIF2AK2 as Green List (high evidence)
Early-onset Parkinson disease v0.196 EIF2AK2 Zornitza Stark Gene: eif2ak2 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.195 EIF2AK2 Zornitza Stark reviewed gene: EIF2AK2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome, MIM# 618877; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.195 EPM2A Zornitza Stark Marked gene: EPM2A as ready
Early-onset Parkinson disease v0.195 EPM2A Zornitza Stark Gene: epm2a has been classified as Amber List (Moderate Evidence).
Early-onset Parkinson disease v0.195 EPM2A Zornitza Stark Phenotypes for gene: EPM2A were changed from Lafora disease; Progressive Myoclonic Epilepsy; Parkinsonism; OMIM 254780 to Epilepsy, progressive myoclonic 2A (Lafora), MIM# 254780; Progressive Myoclonic Epilepsy; Parkinsonism
Early-onset Parkinson disease v0.194 EPM2A Zornitza Stark Classified gene: EPM2A as Amber List (moderate evidence)
Early-onset Parkinson disease v0.194 EPM2A Zornitza Stark Gene: epm2a has been classified as Amber List (Moderate Evidence).
Early-onset Parkinson disease v0.193 EPM2A Zornitza Stark reviewed gene: EPM2A: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Epilepsy, progressive myoclonic 2A (Lafora), MIM# 254780; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.193 FOXG1 Zornitza Stark Classified gene: FOXG1 as Green List (high evidence)
Early-onset Parkinson disease v0.193 FOXG1 Zornitza Stark Gene: foxg1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.192 FOXG1 Zornitza Stark Marked gene: FOXG1 as ready
Early-onset Parkinson disease v0.192 FOXG1 Zornitza Stark Gene: foxg1 has been removed from the panel.
Early-onset Parkinson disease v0.192 FOXG1 Zornitza Stark Phenotypes for gene: FOXG1 were changed from Developmental and Epileptic Encephalopathy; Dystonia,; Athetosis; Parkinsonism; Stereotypies; OMIM 613454 to Rett syndrome, congenital variant, MIM# 613454; Developmental and Epileptic Encephalopathy; Dystonia,; Athetosis; Parkinsonism; Stereotypies
Early-onset Parkinson disease v0.191 GLB1 Zornitza Stark changed review comment from: Reported in Type 3.; to: Parkinsonism reported in Type 3.
Early-onset Parkinson disease v0.191 GLB1 Zornitza Stark Marked gene: GLB1 as ready
Early-onset Parkinson disease v0.191 GLB1 Zornitza Stark Gene: glb1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.191 GLB1 Zornitza Stark Phenotypes for gene: GLB1 were changed from GM1 Gangliosidosis; Parkinsonism; OMIM 230650 to GM1-gangliosidosis, type III , MIM#230650; Parkinsonism
Early-onset Parkinson disease v0.190 GLB1 Zornitza Stark Classified gene: GLB1 as Green List (high evidence)
Early-onset Parkinson disease v0.190 GLB1 Zornitza Stark Gene: glb1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.189 GLB1 Zornitza Stark reviewed gene: GLB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: GM1-gangliosidosis, type III , MIM#230650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v0.181 GINS3 Zornitza Stark Marked gene: GINS3 as ready
Skeletal dysplasia v0.181 GINS3 Zornitza Stark Gene: gins3 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.181 GINS3 Zornitza Stark Classified gene: GINS3 as Green List (high evidence)
Skeletal dysplasia v0.181 GINS3 Zornitza Stark Gene: gins3 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.180 GINS3 Zornitza Stark gene: GINS3 was added
gene: GINS3 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: GINS3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GINS3 were set to 35603789
Phenotypes for gene: GINS3 were set to Meier-Gorlin syndrome, MONDO:0016817, GINS3-related
Review for gene: GINS3 was set to GREEN
Added comment: 7 individuals from 5 families reported, presenting with prenatal and postnatal growth deficiency as well as other features. Three unique missense variants identified, two affecting p.Asp24. These variants are thought to be hypomorphic. Supportive mouse model.
Sources: Literature
Prepair 1000+ v0.50 CARD9 Crystle Lee reviewed gene: CARD9: Rating: AMBER; Mode of pathogenicity: None; Publications: 30136218; Phenotypes: Immunodeficiency 103, susceptibility to fungal infection (MIM#212050); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.137 GINS3 Zornitza Stark Marked gene: GINS3 as ready
Microcephaly v1.137 GINS3 Zornitza Stark Gene: gins3 has been classified as Green List (High Evidence).
Microcephaly v1.137 GINS3 Zornitza Stark Classified gene: GINS3 as Green List (high evidence)
Microcephaly v1.137 GINS3 Zornitza Stark Gene: gins3 has been classified as Green List (High Evidence).
Microcephaly v1.136 GINS3 Zornitza Stark gene: GINS3 was added
gene: GINS3 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: GINS3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GINS3 were set to 35603789
Phenotypes for gene: GINS3 were set to Meier-Gorlin syndrome, MONDO:0016817, GINS3-related
Review for gene: GINS3 was set to GREEN
Added comment: 7 individuals from 5 families reported, presenting with prenatal and postnatal growth deficiency as well as other features. Three unique missense variants identified, two affecting p.Asp24. These variants are thought to be hypomorphic. Supportive mouse model.
Sources: Literature
Fetal anomalies v1.47 GINS3 Zornitza Stark gene: GINS3 was added
gene: GINS3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: GINS3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GINS3 were set to 35603789
Phenotypes for gene: GINS3 were set to Meier-Gorlin syndrome, MONDO:0016817, GINS3-related
Review for gene: GINS3 was set to GREEN
Added comment: 7 individuals from 5 families reported, presenting with prenatal and postnatal growth deficiency as well as other features. Three unique missense variants identified, two affecting p.Asp24. These variants are thought to be hypomorphic. Supportive mouse model.
Sources: Literature
Growth failure v1.44 GINS3 Zornitza Stark Marked gene: GINS3 as ready
Growth failure v1.44 GINS3 Zornitza Stark Gene: gins3 has been classified as Green List (High Evidence).
Growth failure v1.44 GINS3 Zornitza Stark Classified gene: GINS3 as Green List (high evidence)
Growth failure v1.44 GINS3 Zornitza Stark Gene: gins3 has been classified as Green List (High Evidence).
Growth failure v1.43 GINS3 Zornitza Stark gene: GINS3 was added
gene: GINS3 was added to Growth failure. Sources: Literature
Mode of inheritance for gene: GINS3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GINS3 were set to 35603789
Phenotypes for gene: GINS3 were set to Meier-Gorlin syndrome, MONDO:0016817, GINS3-related
Review for gene: GINS3 was set to GREEN
Added comment: 7 individuals from 5 families reported, presenting with prenatal and postnatal growth deficiency as well as other features. Three unique missense variants identified, two affecting p.Asp24. These variants are thought to be hypomorphic. Supportive mouse model.
Sources: Literature
Mendeliome v1.162 GINS3 Zornitza Stark Marked gene: GINS3 as ready
Mendeliome v1.162 GINS3 Zornitza Stark Gene: gins3 has been classified as Green List (High Evidence).
Mendeliome v1.162 GINS3 Zornitza Stark Classified gene: GINS3 as Green List (high evidence)
Mendeliome v1.162 GINS3 Zornitza Stark Gene: gins3 has been classified as Green List (High Evidence).
Mendeliome v1.161 GINS3 Zornitza Stark gene: GINS3 was added
gene: GINS3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GINS3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GINS3 were set to 35603789
Phenotypes for gene: GINS3 were set to Meier-Gorlin syndrome, MONDO:0016817, GINS3-related
Review for gene: GINS3 was set to GREEN
Added comment: 7 individuals from 5 families reported, presenting with prenatal and postnatal growth deficiency as well as other features. Three unique missense variants identified, two affecting p.Asp24. These variants are thought to be hypomorphic. Supportive mouse model.
Sources: Literature
Prepair 1000+ v0.50 PLG Crystle Lee changed review comment from: 2 AR conditions associated with PLG; Type I plasminogen deficiency and type II plasminogen deficiency, also known as 'dysplasminogenemia'. Patients with type II deficiency are usually asymptomatic (OMIM). The most common clinical manifestation is ligneous conjunctivitis. Other neurological manifestations such as hydrocephalus and Dandy Walker malformation can also be present in some patients

PMID: 21174000: Phenotype shows inter- and intra- familial variability. Residual PLG activity does not always correlate with clinical severity

AR condition can be associated with severe, early onset presentation; to: 2 AR conditions associated with PLG; Type I plasminogen deficiency and type II plasminogen deficiency, also known as 'dysplasminogenemia'. Patients with type II deficiency are usually asymptomatic (OMIM). The most common clinical manifestation is ligneous conjunctivitis. Other neurological manifestations such as hydrocephalus and Dandy Walker malformation can also be present in some patients

PMID: 21174000: Phenotype shows inter- and intra- familial variability. Residual PLG activity does not always correlate with clinical severity

AR condition can be associated with severe, early onset presentation
Prepair 1000+ v0.50 PLG Crystle Lee reviewed gene: PLG: Rating: AMBER; Mode of pathogenicity: None; Publications: 9242524, 35244080; Phenotypes: Angioedema, hereditary, 4 (MIM#619360), Dysplasminogenemia (MIM#217090), Plasminogen deficiency, type I (MIM#217090); Mode of inheritance: None
Prepair 1000+ v0.50 GYS2 Crystle Lee reviewed gene: GYS2: Rating: AMBER; Mode of pathogenicity: None; Publications: 18341095, 32395408; Phenotypes: Glycogen storage disease 0, liver (MIM#240600); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.50 MPZ Crystle Lee reviewed gene: MPZ: Rating: AMBER; Mode of pathogenicity: None; Publications: 30239779, 8816708, 12845552, 16488608, 26310628, 8630052; Phenotypes: Charcot-Marie-Tooth disease, dominant intermediate D (MIM#607791), Charcot-Marie-Tooth disease, type 1B (MIM#118200), Charcot-Marie-Tooth disease, type 2I (MIM#607677), Charcot-Marie-Tooth disease, type 2J (MIM#607736), Dejerine-Sottas disease (MIM#145900), Hypomyelinating neuropathy, congenital, 2 (MIM#618184), Roussy-Levy syndrome (MIM#180800); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Early-onset Parkinson disease v0.189 KIAA1161 SHEKEEB MOHAMMAD gene: KIAA1161 was added
gene: KIAA1161 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: KIAA1161 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA1161 were set to PMID: 32211515
Phenotypes for gene: KIAA1161 were set to Primary familial brain calcification; Atypical parkinsonism; Supranuclear gaze palsy; OMIM 618317
Review for gene: KIAA1161 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.189 C9orf3 SHEKEEB MOHAMMAD reviewed gene: C9orf3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Early-onset Parkinson disease v0.189 NHLRC1 SHEKEEB MOHAMMAD gene: NHLRC1 was added
gene: NHLRC1 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: NHLRC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NHLRC1 were set to PMID: 22425593
Phenotypes for gene: NHLRC1 were set to Lafora disease; Progressive Myoclonic Epilepsy; Parkinsonism; OMIM 254780
Review for gene: NHLRC1 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.189 C9orf3 SHEKEEB MOHAMMAD gene: C9orf3 was added
gene: C9orf3 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: C9orf3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C9orf3 were set to PMID: 35306330
Phenotypes for gene: C9orf3 were set to Dystonia-31; Childhood/Adolescence onset generalised dystonia; Dystonia parkinsonism; Zech-Boesch Syndrome; OMIM 619565
Early-onset Parkinson disease v0.189 HEXA Zornitza Stark edited their review of gene: HEXA: Changed rating: RED; Changed phenotypes: Tay-Sachs disease, MIM# 272800; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.189 HEXA Zornitza Stark Marked gene: HEXA as ready
Early-onset Parkinson disease v0.189 HEXA Zornitza Stark Gene: hexa has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.189 HEXA Zornitza Stark Classified gene: HEXA as Red List (low evidence)
Early-onset Parkinson disease v0.189 HEXA Zornitza Stark Gene: hexa has been classified as Red List (Low Evidence).
Early-onset Parkinson disease v0.188 HEXA Zornitza Stark Classified gene: HEXA as Amber List (moderate evidence)
Early-onset Parkinson disease v0.188 HEXA Zornitza Stark Gene: hexa has been classified as Amber List (Moderate Evidence).
Early-onset Parkinson disease v0.187 HEXA Zornitza Stark reviewed gene: HEXA: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Early-onset Parkinson disease v0.187 JPH3 Zornitza Stark Marked gene: JPH3 as ready
Early-onset Parkinson disease v0.187 JPH3 Zornitza Stark Gene: jph3 has been removed from the panel.
Early-onset Parkinson disease v0.187 JPH3 Zornitza Stark Tag STR tag was added to gene: JPH3.
Early-onset Parkinson disease v0.187 JPH3 Zornitza Stark commented on gene: JPH3
Early-onset Parkinson disease v0.187 NPC2 Zornitza Stark Marked gene: NPC2 as ready
Early-onset Parkinson disease v0.187 NPC2 Zornitza Stark Gene: npc2 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.187 NPC2 Zornitza Stark Phenotypes for gene: NPC2 were changed from Niemann Pick C2; Parkinsonism; OMIM 607625 to Niemann Pick C2, OMIM 607625; Parkinsonism
Early-onset Parkinson disease v0.186 NPC2 Zornitza Stark Classified gene: NPC2 as Green List (high evidence)
Early-onset Parkinson disease v0.186 NPC2 Zornitza Stark Gene: npc2 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.185 NPC1 Zornitza Stark Marked gene: NPC1 as ready
Early-onset Parkinson disease v0.185 NPC1 Zornitza Stark Gene: npc1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.185 NPC1 Zornitza Stark Phenotypes for gene: NPC1 were changed from Niemann Pick C1; Parkinsonism; OMIM 257220 to Niemann-Pick disease, MIM# 257220; Parkinsonism
Early-onset Parkinson disease v0.184 NPC1 Zornitza Stark Publications for gene: NPC1 were set to PMID: 24035292
Early-onset Parkinson disease v0.183 NPC1 Zornitza Stark Mode of inheritance for gene: NPC1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.182 NPC1 Zornitza Stark Classified gene: NPC1 as Green List (high evidence)
Early-onset Parkinson disease v0.182 NPC1 Zornitza Stark Gene: npc1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.181 NPC1 Zornitza Stark reviewed gene: NPC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Niemann-Pick disease, MIM# 257220; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.181 NUS1 Zornitza Stark Marked gene: NUS1 as ready
Early-onset Parkinson disease v0.181 NUS1 Zornitza Stark Gene: nus1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.181 NUS1 Zornitza Stark Phenotypes for gene: NUS1 were changed from Mental retardation 55 with seizures (MRD55); Parkinsonism; Developmental delay; Intellectual disability; Ataxia; Myoclonus; OMIM 617831 to Intellectual developmental disorder, autosomal dominant 55, with seizures, MIM# 617831; Parkinsonism; Developmental delay; Intellectual disability; Ataxia; Myoclonus
Early-onset Parkinson disease v0.180 NUS1 Zornitza Stark Mode of inheritance for gene: NUS1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.179 NUS1 Zornitza Stark Classified gene: NUS1 as Green List (high evidence)
Early-onset Parkinson disease v0.179 NUS1 Zornitza Stark Gene: nus1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.178 PGK1 Zornitza Stark Marked gene: PGK1 as ready
Early-onset Parkinson disease v0.178 PGK1 Zornitza Stark Gene: pgk1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.178 PGK1 Zornitza Stark Phenotypes for gene: PGK1 were changed from Haemolytic anaemia; Rhabdomyolysis; Myopathy; Juvenile Parkinsonism; OMIM 300653 to Phosphoglycerate kinase 1 deficiency, MIM# 300653; Haemolytic anaemia; Rhabdomyolysis; Myopathy; Juvenile Parkinsonism; OMIM 300653
Early-onset Parkinson disease v0.177 PGK1 Zornitza Stark Classified gene: PGK1 as Green List (high evidence)
Early-onset Parkinson disease v0.177 PGK1 Zornitza Stark Gene: pgk1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.176 PGK1 Zornitza Stark reviewed gene: PGK1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Phosphoglycerate kinase 1 deficiency, MIM# 300653; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early-onset Parkinson disease v0.176 POLR3A Zornitza Stark Marked gene: POLR3A as ready
Early-onset Parkinson disease v0.176 POLR3A Zornitza Stark Gene: polr3a has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.176 POLR3A Zornitza Stark Phenotypes for gene: POLR3A were changed from POLR3A Leukoencephalopathy; Parkinsonism; Ocular and dental abnormality; Hypogonadism, OMIM 607694 to Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism, MIM# 607694; POLR3A Leukoencephalopathy; Parkinsonism; Ocular and dental abnormality; Hypogonadism
Early-onset Parkinson disease v0.175 POLR3A Zornitza Stark Classified gene: POLR3A as Green List (high evidence)
Early-onset Parkinson disease v0.175 POLR3A Zornitza Stark Gene: polr3a has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.174 POLR3A Zornitza Stark reviewed gene: POLR3A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism, MIM# 607694; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.174 PPP2R2B Zornitza Stark Marked gene: PPP2R2B as ready
Early-onset Parkinson disease v0.174 PPP2R2B Zornitza Stark Gene: ppp2r2b has been removed from the panel.
Early-onset Parkinson disease v0.174 PPP2R2B Zornitza Stark Tag STR tag was added to gene: PPP2R2B.
Early-onset Parkinson disease v0.174 PPP2R2B Zornitza Stark commented on gene: PPP2R2B
Early-onset Parkinson disease v0.174 PRKCG Zornitza Stark Marked gene: PRKCG as ready
Early-onset Parkinson disease v0.174 PRKCG Zornitza Stark Gene: prkcg has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.174 PRKCG Zornitza Stark Phenotypes for gene: PRKCG were changed from Spinocerebellar ataxia 14; Myoclonus; Parkinsonism; OMIM 605361 to Spinocerebellar ataxia 14, MIM# 605361; Myoclonus; Parkinsonism
Early-onset Parkinson disease v0.173 PRKCG Zornitza Stark Mode of inheritance for gene: PRKCG was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.172 PRKCG Zornitza Stark Classified gene: PRKCG as Green List (high evidence)
Early-onset Parkinson disease v0.172 PRKCG Zornitza Stark Gene: prkcg has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.171 PRKCG Zornitza Stark reviewed gene: PRKCG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinocerebellar ataxia 14, MIM# 605361; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.171 QDPR Zornitza Stark Marked gene: QDPR as ready
Early-onset Parkinson disease v0.171 QDPR Zornitza Stark Gene: qdpr has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.171 QDPR Zornitza Stark Phenotypes for gene: QDPR were changed from Dehydropteridin reductase deficiency, Infantile-onset dystonia; Parkinsonism; Epilepsy; Autonomic dysfunction; Hyperphenylalaninemia; OMIM 261360 to Hyperphenylalaninemia, BH4-deficient, C, MIM#261630; Dehydropteridin reductase deficiency, Infantile-onset dystonia; Parkinsonism; Epilepsy; Autonomic dysfunction; Hyperphenylalaninemia
Early-onset Parkinson disease v0.170 QDPR Zornitza Stark Classified gene: QDPR as Green List (high evidence)
Early-onset Parkinson disease v0.170 QDPR Zornitza Stark Gene: qdpr has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.169 QDPR Zornitza Stark reviewed gene: QDPR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hyperphenylalaninemia, BH4-deficient, C, MIM#261630; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.169 SCN1A Zornitza Stark Marked gene: SCN1A as ready
Early-onset Parkinson disease v0.169 SCN1A Zornitza Stark Gene: scn1a has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.169 SCN1A Zornitza Stark Phenotypes for gene: SCN1A were changed from Dravet syndrome; Epilepsy, Paekinsonism; OMIM 607208 to Dravet syndrome, MIM# 607208; Epilepsy, Paekinsonism
Early-onset Parkinson disease v0.168 SCN1A Zornitza Stark Mode of inheritance for gene: SCN1A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.167 SCN1A Zornitza Stark Classified gene: SCN1A as Green List (high evidence)
Early-onset Parkinson disease v0.167 SCN1A Zornitza Stark Gene: scn1a has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.166 SCN1A Zornitza Stark reviewed gene: SCN1A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dravet syndrome, MIM# 607208; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.166 SERAC1 Zornitza Stark Marked gene: SERAC1 as ready
Early-onset Parkinson disease v0.166 SERAC1 Zornitza Stark Gene: serac1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.166 SERAC1 Zornitza Stark Phenotypes for gene: SERAC1 were changed from MEGDEL Syndrome; Parkinsonism to 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, MIM# 614739; Parkinsonism
Early-onset Parkinson disease v0.165 SERAC1 Zornitza Stark Classified gene: SERAC1 as Green List (high evidence)
Early-onset Parkinson disease v0.165 SERAC1 Zornitza Stark Gene: serac1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.164 SERAC1 Zornitza Stark reviewed gene: SERAC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, MIM# 614739; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.164 SLC19A3 Zornitza Stark Marked gene: SLC19A3 as ready
Early-onset Parkinson disease v0.164 SLC19A3 Zornitza Stark Gene: slc19a3 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.164 SLC19A3 Zornitza Stark Phenotypes for gene: SLC19A3 were changed from Biotin-Thiamine Responsive Basal Ganglia disease; Childhood onset Dystonia and Parkinsonism; OMIM 607483 to Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2), MIM# 607483; Childhood onset Dystonia and Parkinsonism
Early-onset Parkinson disease v0.163 SLC19A3 Zornitza Stark Classified gene: SLC19A3 as Green List (high evidence)
Early-onset Parkinson disease v0.163 SLC19A3 Zornitza Stark Gene: slc19a3 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.162 SLC19A3 Zornitza Stark reviewed gene: SLC19A3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2), MIM# 607483; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.162 SLC18A2 Zornitza Stark Marked gene: SLC18A2 as ready
Early-onset Parkinson disease v0.162 SLC18A2 Zornitza Stark Gene: slc18a2 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.162 SLC18A2 Zornitza Stark Phenotypes for gene: SLC18A2 were changed from Brain dopamine-serotonin transport disease, Childhood-onset parkinsonism, OMIM 618049 to Parkinsonism-dystonia, infantile, 2 , MIM# 618049; Brain dopamine-serotonin transport disease, Childhood-onset parkinsonism
Early-onset Parkinson disease v0.161 SLC18A2 Zornitza Stark Publications for gene: SLC18A2 were set to PMID: 23363473, 33983693
Early-onset Parkinson disease v0.160 SLC18A2 Zornitza Stark Classified gene: SLC18A2 as Green List (high evidence)
Early-onset Parkinson disease v0.160 SLC18A2 Zornitza Stark Gene: slc18a2 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.159 SLC18A2 Zornitza Stark reviewed gene: SLC18A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23363473, 31240161, 26497564; Phenotypes: Parkinsonism-dystonia, infantile, 2 , MIM# 618049; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.159 SOX6 Zornitza Stark Marked gene: SOX6 as ready
Early-onset Parkinson disease v0.159 SOX6 Zornitza Stark Gene: sox6 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.159 SOX6 Zornitza Stark Publications for gene: SOX6 were set to PMID: 24453155, 25127144
Early-onset Parkinson disease v0.158 SOX6 Zornitza Stark Phenotypes for gene: SOX6 were changed from Tolchin-Le Caignec syndrome; Developmental delay; ID; ASD; ADHD; Parkinsonism; Syringomyelia, OMIM 618971 to Tolchin-Le Caignec syndrome, MIM# 618971; Developmental delay; ID; ASD; ADHD; Parkinsonism; Syringomyelia
Early-onset Parkinson disease v0.157 SOX6 Zornitza Stark Mode of inheritance for gene: SOX6 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.156 SOX6 Zornitza Stark Classified gene: SOX6 as Green List (high evidence)
Early-onset Parkinson disease v0.156 SOX6 Zornitza Stark Gene: sox6 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.155 SPG7 Zornitza Stark Marked gene: SPG7 as ready
Early-onset Parkinson disease v0.155 SPG7 Zornitza Stark Gene: spg7 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.155 SPG7 Zornitza Stark Phenotypes for gene: SPG7 were changed from Hereditary Spastic Paraplegia 7; Ataxia; Progressive external opthalmoplegia; Parkinsonism; OMIM 607259 to Spastic paraplegia 7, autosomal recessive, MIM# 607259; Ataxia; Progressive external opthalmoplegia; Parkinsonism
Early-onset Parkinson disease v0.154 SPG7 Zornitza Stark Classified gene: SPG7 as Green List (high evidence)
Early-onset Parkinson disease v0.154 SPG7 Zornitza Stark Gene: spg7 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.153 STUB1 Zornitza Stark Marked gene: STUB1 as ready
Early-onset Parkinson disease v0.153 STUB1 Zornitza Stark Gene: stub1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.153 STUB1 Zornitza Stark Phenotypes for gene: STUB1 were changed from Spinocerebellar Ataxia 48; Parkinsonism, OMIM 618093 to Spinocerebellar Ataxia 48, OMIM 618093; Parkinsonism
Early-onset Parkinson disease v0.152 STUB1 Zornitza Stark Publications for gene: STUB1 were set to PubMed: 30381368; 32285148, 32337344
Early-onset Parkinson disease v0.152 STUB1 Zornitza Stark Mode of inheritance for gene: STUB1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.151 STUB1 Zornitza Stark Mode of inheritance for gene: STUB1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.151 STUB1 Zornitza Stark Classified gene: STUB1 as Green List (high evidence)
Early-onset Parkinson disease v0.151 STUB1 Zornitza Stark Gene: stub1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.150 STXBP1 Zornitza Stark Marked gene: STXBP1 as ready
Early-onset Parkinson disease v0.150 STXBP1 Zornitza Stark Gene: stxbp1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.150 STXBP1 Zornitza Stark Phenotypes for gene: STXBP1 were changed from Developmental and epileptic encephalopathy 4; Juvenile onset Parkinsonism; OMIM 612164 to Developmental and epileptic encephalopathy 4, MIM# 612164; Juvenile onset Parkinsonism
Early-onset Parkinson disease v0.149 STXBP1 Zornitza Stark Publications for gene: STXBP1 were set to PMID: 25418441, 32643187, 29929108
Early-onset Parkinson disease v0.148 STXBP1 Zornitza Stark Mode of inheritance for gene: STXBP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.147 STXBP1 Zornitza Stark Classified gene: STXBP1 as Green List (high evidence)
Early-onset Parkinson disease v0.147 STXBP1 Zornitza Stark Gene: stxbp1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.146 STXBP1 Zornitza Stark reviewed gene: STXBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 4, MIM# 612164; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.146 TBC1D24 Zornitza Stark Marked gene: TBC1D24 as ready
Early-onset Parkinson disease v0.146 TBC1D24 Zornitza Stark Gene: tbc1d24 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.146 TBC1D24 Zornitza Stark Phenotypes for gene: TBC1D24 were changed from Developmental and epileptic encephalopathy 16; Intellectual disability; Parkinsonism; Seizures; Psychosis; OMIM 615338 to Developmental and epileptic encephalopathy 16, MIM# 615338; Intellectual disability; Parkinsonism; Seizures; Psychosis
Early-onset Parkinson disease v0.145 TBC1D24 Zornitza Stark Classified gene: TBC1D24 as Green List (high evidence)
Early-onset Parkinson disease v0.145 TBC1D24 Zornitza Stark Gene: tbc1d24 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.144 TBC1D24 Zornitza Stark reviewed gene: TBC1D24: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 16, MIM# 615338; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.144 TBP Zornitza Stark Marked gene: TBP as ready
Early-onset Parkinson disease v0.144 TBP Zornitza Stark Gene: tbp has been removed from the panel.
Early-onset Parkinson disease v0.144 TBP Zornitza Stark Tag STR tag was added to gene: TBP.
Early-onset Parkinson disease v0.144 TBP Zornitza Stark commented on gene: TBP
Early-onset Parkinson disease v0.144 UBTF Zornitza Stark Marked gene: UBTF as ready
Early-onset Parkinson disease v0.144 UBTF Zornitza Stark Gene: ubtf has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.144 UBTF Zornitza Stark Phenotypes for gene: UBTF were changed from Neurodegeneration, childhood-onset; Parkinsonism; Dystonia; Chorea; Brain atrophy to Neurodegeneration, childhood-onset, with brain atrophy, MIM# 617672; Parkinsonism; Dystonia; Chorea; Brain atrophy
Early-onset Parkinson disease v0.143 UBTF Zornitza Stark Mode of inheritance for gene: UBTF was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.142 UBTF Zornitza Stark Classified gene: UBTF as Green List (high evidence)
Early-onset Parkinson disease v0.142 UBTF Zornitza Stark Gene: ubtf has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.141 UBTF Zornitza Stark reviewed gene: UBTF: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodegeneration, childhood-onset, with brain atrophy, MIM# 617672; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Parkinson disease v0.141 VAC14 Zornitza Stark Marked gene: VAC14 as ready
Early-onset Parkinson disease v0.141 VAC14 Zornitza Stark Gene: vac14 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.141 VAC14 Zornitza Stark Phenotypes for gene: VAC14 were changed from Childhood onset Striatonigral degeneration; Dystonia; Parkinsonism; OMIM 617054 to Striatonigral degeneration, childhood-onset, MIM# 617054; Dystonia; Parkinsonism
Early-onset Parkinson disease v0.140 VAC14 Zornitza Stark Classified gene: VAC14 as Green List (high evidence)
Early-onset Parkinson disease v0.140 VAC14 Zornitza Stark Gene: vac14 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.139 VAC14 Zornitza Stark reviewed gene: VAC14: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Striatonigral degeneration, childhood-onset, MIM# 617054; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.50 NCF1 Crystle Lee reviewed gene: NCF1: Rating: AMBER; Mode of pathogenicity: None; Publications: 30651282, 23688784; Phenotypes: Chronic granulomatous disease 1, autosomal recessive (MIM#233700); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.50 NEB Crystle Lee reviewed gene: NEB: Rating: AMBER; Mode of pathogenicity: None; Publications: 27228465; Phenotypes: Arthrogryposis multiplex congenita 6 (MIM#619334), Nemaline myopathy 2, autosomal recessive (MIM#256030); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.50 HYDIN Crystle Lee reviewed gene: HYDIN: Rating: AMBER; Mode of pathogenicity: None; Publications: 23022101, 28441829, 31116566; Phenotypes: Ciliary dyskinesia, primary, 5 (MIM#608647); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.50 SNORD118 Crystle Lee reviewed gene: SNORD118: Rating: AMBER; Mode of pathogenicity: None; Publications: 33029936; Phenotypes: Leukoencephalopathy, brain calcifications, and cysts (MIM#614561); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.50 UBA1 Crystle Lee reviewed gene: UBA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18179898, 32181232, 31932168, 29034082, 23518311, 26028276; Phenotypes: Spinal muscular atrophy, X-linked 2, infantile (MIM#301830); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Familial hypoparathyroidism v1.1 Bryony Thompson Panel status changed from internal to public
Familial hypoparathyroidism v1.0 Bryony Thompson promoted panel to version 1.0
Familial hypoparathyroidism v0.26 TBCE Bryony Thompson Marked gene: TBCE as ready
Familial hypoparathyroidism v0.26 TBCE Bryony Thompson Gene: tbce has been classified as Green List (High Evidence).
Familial hypoparathyroidism v0.26 TBCE Bryony Thompson Publications for gene: TBCE were set to
Familial hypoparathyroidism v0.25 TBCE Bryony Thompson Classified gene: TBCE as Green List (high evidence)
Familial hypoparathyroidism v0.25 TBCE Bryony Thompson Gene: tbce has been classified as Green List (High Evidence).
Familial hypoparathyroidism v0.24 TBCE Bryony Thompson Deleted their review
Familial hypoparathyroidism v0.24 PTH Bryony Thompson Marked gene: PTH as ready
Familial hypoparathyroidism v0.24 PTH Bryony Thompson Gene: pth has been classified as Green List (High Evidence).
Familial hypoparathyroidism v0.24 PTH Bryony Thompson Publications for gene: PTH were set to
Familial hypoparathyroidism v0.23 PTH Bryony Thompson Classified gene: PTH as Green List (high evidence)
Familial hypoparathyroidism v0.23 PTH Bryony Thompson Gene: pth has been classified as Green List (High Evidence).
Familial hypoparathyroidism v0.22 PTH Bryony Thompson Deleted their review
Familial hypoparathyroidism v0.22 PTH Bryony Thompson Deleted their comment
Familial hypoparathyroidism v0.22 GNA11 Bryony Thompson Marked gene: GNA11 as ready
Familial hypoparathyroidism v0.22 GNA11 Bryony Thompson Gene: gna11 has been classified as Green List (High Evidence).
Familial hypoparathyroidism v0.22 GNA11 Bryony Thompson Publications for gene: GNA11 were set to
Familial hypoparathyroidism v0.21 GNA11 Bryony Thompson Mode of pathogenicity for gene: GNA11 was changed from None to Other
Familial hypoparathyroidism v0.20 GNA11 Bryony Thompson Classified gene: GNA11 as Green List (high evidence)
Familial hypoparathyroidism v0.20 GNA11 Bryony Thompson Gene: gna11 has been classified as Green List (High Evidence).
Familial hypoparathyroidism v0.19 GNA11 Bryony Thompson Deleted their review
Familial hypoparathyroidism v0.19 GCM2 Bryony Thompson Marked gene: GCM2 as ready
Familial hypoparathyroidism v0.19 GCM2 Bryony Thompson Gene: gcm2 has been classified as Green List (High Evidence).
Familial hypoparathyroidism v0.19 GCM2 Bryony Thompson Publications for gene: GCM2 were set to
Familial hypoparathyroidism v0.18 GCM2 Bryony Thompson Mode of pathogenicity for gene: GCM2 was changed from None to Other
Familial hypoparathyroidism v0.17 GCM2 Bryony Thompson Mode of inheritance for gene: GCM2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Familial hypoparathyroidism v0.16 GCM2 Bryony Thompson Classified gene: GCM2 as Green List (high evidence)
Familial hypoparathyroidism v0.16 GCM2 Bryony Thompson Gene: gcm2 has been classified as Green List (High Evidence).
Familial hypoparathyroidism v0.15 GCM2 Bryony Thompson Deleted their review
Familial hypoparathyroidism v0.15 GCM2 Bryony Thompson Deleted their comment
Familial hypoparathyroidism v0.15 GATA3 Bryony Thompson Marked gene: GATA3 as ready
Familial hypoparathyroidism v0.15 GATA3 Bryony Thompson Gene: gata3 has been classified as Green List (High Evidence).
Familial hypoparathyroidism v0.15 GATA3 Bryony Thompson Publications for gene: GATA3 were set to
Familial hypoparathyroidism v0.14 GATA3 Bryony Thompson Classified gene: GATA3 as Green List (high evidence)
Familial hypoparathyroidism v0.14 GATA3 Bryony Thompson Gene: gata3 has been classified as Green List (High Evidence).
Familial hypoparathyroidism v0.13 GATA3 Bryony Thompson Deleted their review
Familial hypoparathyroidism v0.13 CASR Bryony Thompson Marked gene: CASR as ready
Familial hypoparathyroidism v0.13 CASR Bryony Thompson Gene: casr has been classified as Green List (High Evidence).
Familial hypoparathyroidism v0.13 CASR Bryony Thompson Publications for gene: CASR were set to
Familial hypoparathyroidism v0.12 CASR Bryony Thompson Mode of inheritance for gene: CASR was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Familial hypoparathyroidism v0.11 CASR Bryony Thompson Classified gene: CASR as Green List (high evidence)
Familial hypoparathyroidism v0.11 CASR Bryony Thompson Gene: casr has been classified as Green List (High Evidence).
Familial hypoparathyroidism v0.10 CASR Bryony Thompson Deleted their review
Familial hypoparathyroidism v0.10 CASR Bryony Thompson Deleted their comment
Familial hypoparathyroidism v0.10 AIRE Bryony Thompson Marked gene: AIRE as ready
Familial hypoparathyroidism v0.10 AIRE Bryony Thompson Gene: aire has been classified as Green List (High Evidence).
Familial hypoparathyroidism v0.10 AIRE Bryony Thompson Mode of inheritance for gene: AIRE was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Familial hypoparathyroidism v0.9 AIRE Bryony Thompson Classified gene: AIRE as Green List (high evidence)
Familial hypoparathyroidism v0.9 AIRE Bryony Thompson Gene: aire has been classified as Green List (High Evidence).
Familial hypoparathyroidism v0.8 AIRE Bryony Thompson Deleted their review
Familial hypoparathyroidism v0.8 AIRE Bryony Thompson Deleted their comment
Clefting disorders v0.182 RYR1 Zornitza Stark Marked gene: RYR1 as ready
Clefting disorders v0.182 RYR1 Zornitza Stark Gene: ryr1 has been classified as Red List (Low Evidence).
Clefting disorders v0.182 RYR1 Zornitza Stark Phenotypes for gene: RYR1 were changed from CCD; CENTRAL CORE DISEASE OF MUSCLE to RYR1-related myopathy - MONDO:0100150
Clefting disorders v0.181 RYR1 Zornitza Stark Classified gene: RYR1 as Red List (low evidence)
Clefting disorders v0.181 RYR1 Zornitza Stark Gene: ryr1 has been classified as Red List (Low Evidence).
Familial hypoparathyroidism v0.7 TBCE Bryony Thompson gene: TBCE was added
gene: TBCE was added to Familial hypoparathyroidism. Sources: NHS GMS
Mode of inheritance for gene: TBCE was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TBCE were set to hypoparathyroidism-retardation-dysmorphism syndrome MONDO:0009426
Review for gene: TBCE was set to GREEN
Added comment: Sources: NHS GMS
Familial hypoparathyroidism v0.6 PTH Bryony Thompson gene: PTH was added
gene: PTH was added to Familial hypoparathyroidism. Sources: NHS GMS
Mode of inheritance for gene: PTH was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: PTH were set to familial isolated hypoparathyroidism due to impaired PTH secretion MONDO:0016000
Review for gene: PTH was set to GREEN
Added comment: Sources: NHS GMS
Familial hypoparathyroidism v0.5 GNA11 Bryony Thompson gene: GNA11 was added
gene: GNA11 was added to Familial hypoparathyroidism. Sources: NHS GMS
Mode of inheritance for gene: GNA11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: GNA11 were set to autosomal dominant hypocalcemia MONDO:0018543
Review for gene: GNA11 was set to GREEN
Added comment: Sources: NHS GMS
Familial hypoparathyroidism v0.4 GCM2 Bryony Thompson gene: GCM2 was added
gene: GCM2 was added to Familial hypoparathyroidism. Sources: NHS GMS
Mode of inheritance for gene: GCM2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: GCM2 were set to Familial isolated hyperparathyroidism MONDO:0015027
Review for gene: GCM2 was set to GREEN
Added comment: Sources: NHS GMS
Familial hypoparathyroidism v0.3 GATA3 Bryony Thompson gene: GATA3 was added
gene: GATA3 was added to Familial hypoparathyroidism. Sources: NHS GMS
Mode of inheritance for gene: GATA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: GATA3 were set to Hypoparathyroidism-deafness-renal disease syndrome MONDO:0007797
Review for gene: GATA3 was set to GREEN
Added comment: Sources: NHS GMS
Familial hypoparathyroidism v0.2 CASR Bryony Thompson gene: CASR was added
gene: CASR was added to Familial hypoparathyroidism. Sources: NHS GMS
Mode of inheritance for gene: CASR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: CASR were set to autosomal dominant hypocalcemia 1 MONDO:0011013
Review for gene: CASR was set to GREEN
Added comment: Sources: NHS GMS
Familial hypoparathyroidism v0.1 AIRE Bryony Thompson gene: AIRE was added
gene: AIRE was added to Familial hypoparathyroidism. Sources: NHS GMS
Mode of inheritance for gene: AIRE was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: AIRE were set to Autoimmune polyendocrine syndrome type 1 MONDO:0009411
Review for gene: AIRE was set to GREEN
Added comment: Sources: NHS GMS
Familial hypoparathyroidism v0.0 Bryony Thompson Added Panel Familial hypoparathyroidism
Set panel types to: Royal Melbourne Hospital; Rare Disease
Clefting disorders v0.180 RYR1 Krithika Murali reviewed gene: RYR1: Rating: RED; Mode of pathogenicity: None; Publications: 23553484; Phenotypes: RYR1-related myopathy - MONDO:0100150; Mode of inheritance: None
Prepair 1000+ v0.50 CHM Crystle Lee reviewed gene: CHM: Rating: AMBER; Mode of pathogenicity: None; Publications: 33110609, 27820636; Phenotypes: Choroideremia (MIM#303100); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v0.50 PROC Crystle Lee reviewed gene: PROC: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Thrombophilia 3 due to protein C deficiency, autosomal recessive (MIM#612304), Thrombophilia 3 due to protein C deficiency, autosomal dominant (MIM#176860); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Prepair 1000+ v0.50 PROC Crystle Lee Deleted their review
Prepair 1000+ v0.50 PROC Crystle Lee changed review comment from: Gene is associated AD and AR thrombophilia 3 due to protein C deficiency

AR form of condition is associated with variable severity and occasional late-onset of symptoms with homozygosity

Heterozygous 'carriers' of pathogenic variants in the PROC gene are said to have mild protein C deficiency which is often asymptomatic, but may involve recurrent venous thrombosis.

Difficult to define penetrance as represents risk factor for thrombophilia.

Challenge in interpretation and reporting in a carrier screening context; to: Gene is associated AD and AR thrombophilia 3 due to protein C deficiency

AR form of condition is associated with variable severity and occasional late-onset of symptoms with homozygosity

Heterozygous 'carriers' of pathogenic variants in the PROC gene are said to have mild protein C deficiency which is often asymptomatic, but may involve recurrent venous thrombosis.

Difficult to define penetrance as represents risk factor for thrombophilia.

Challenge in interpretation and reporting in a carrier screening context
Prepair 1000+ v0.50 PROC Crystle Lee reviewed gene: PROC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thrombophilia 3 due to protein C deficiency, autosomal recessive (MIM#612304), Thrombophilia 3 due to protein C deficiency, autosomal dominant (MIM#176860); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Prepair 1000+ v0.50 IKBKG Crystle Lee reviewed gene: IKBKG: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Ectodermal dysplasia and immunodeficiency 1, MIM# 300291, Immunodeficiency 33 , MIM#300636, Incontinentia pigmenti, MIM# 308300, Autoinflammatory disease, systemic, X-linked, MIM# 301081; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early-onset Parkinson disease v0.139 WARS2 Zornitza Stark Marked gene: WARS2 as ready
Early-onset Parkinson disease v0.139 WARS2 Zornitza Stark Gene: wars2 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.139 WARS2 Zornitza Stark Phenotypes for gene: WARS2 were changed from Parkinsonism-dystonia 3, childhood-onset, MIM# 619738 to Parkinsonism-dystonia 3, childhood-onset, MIM# 619738
Early-onset Parkinson disease v0.139 WARS2 Zornitza Stark Phenotypes for gene: WARS2 were changed from Childhood onset parkinsonism dystonia-3; Myoclonus ataxia; OMIM 619738 to Parkinsonism-dystonia 3, childhood-onset, MIM# 619738
Early-onset Parkinson disease v0.138 WARS2 Zornitza Stark Publications for gene: WARS2 were set to PMID: 29120065; 34890876
Early-onset Parkinson disease v0.137 WARS2 Zornitza Stark Classified gene: WARS2 as Green List (high evidence)
Early-onset Parkinson disease v0.137 WARS2 Zornitza Stark Gene: wars2 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.136 WARS2 Zornitza Stark reviewed gene: WARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34890876, 31970218, 29120065; Phenotypes: Parkinsonism-dystonia 3, childhood-onset, MIM# 619738; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v0.136 ZFYVE26 Zornitza Stark Marked gene: ZFYVE26 as ready
Early-onset Parkinson disease v0.136 ZFYVE26 Zornitza Stark Gene: zfyve26 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.136 ZFYVE26 Zornitza Stark Phenotypes for gene: ZFYVE26 were changed from Spastic paraplegia and retinal degeneration; Kjellin syndrome; Parkinsonism; OMIM 270700 to Spastic paraplegia 15, autosomal recessive, MIM# 270700; Spastic paraplegia and retinal degeneration; Kjellin syndrome; Parkinsonism
Early-onset Parkinson disease v0.135 ZFYVE26 Zornitza Stark Classified gene: ZFYVE26 as Green List (high evidence)
Early-onset Parkinson disease v0.135 ZFYVE26 Zornitza Stark Gene: zfyve26 has been classified as Green List (High Evidence).
Aortopathy_Connective Tissue Disorders v1.67 COL11A1 Zornitza Stark Marked gene: COL11A1 as ready
Aortopathy_Connective Tissue Disorders v1.67 COL11A1 Zornitza Stark Gene: col11a1 has been classified as Green List (High Evidence).
Early-onset Parkinson disease v0.134 ATXN10 SHEKEEB MOHAMMAD gene: ATXN10 was added
gene: ATXN10 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: ATXN10 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ATXN10 were set to PMID: 28890930
Phenotypes for gene: ATXN10 were set to Spinocerebellar Ataxia 10; Parkinsonism; OMIM 603516
Review for gene: ATXN10 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 ATXN2 SHEKEEB MOHAMMAD gene: ATXN2 was added
gene: ATXN2 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: ATXN2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ATXN2 were set to PMID: 11761482, 17923635
Phenotypes for gene: ATXN2 were set to Spinocerebellar Ataxia 2; Parkinsonism; Myoclonus; OMIM 183090
Review for gene: ATXN2 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 ATXN3 SHEKEEB MOHAMMAD gene: ATXN3 was added
gene: ATXN3 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: ATXN3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ATXN3 were set to PMID: 11176969; 7574470
Phenotypes for gene: ATXN3 were set to Spinocerebellar 3; Machado Joseph disease; Ataxia; Parkinsonism; OMIM 109150
Review for gene: ATXN3 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 ATXN8 SHEKEEB MOHAMMAD gene: ATXN8 was added
gene: ATXN8 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: ATXN8 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ATXN8 were set to PMID: 24285970
Phenotypes for gene: ATXN8 were set to Spinocerebellar 8; Parkinsonism; OMIM 608768
Review for gene: ATXN8 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 TPP1 SHEKEEB MOHAMMAD gene: TPP1 was added
gene: TPP1 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: TPP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TPP1 were set to PMID: 21940688
Phenotypes for gene: TPP1 were set to Late Infantile NCL; Parkinsonism; OMIM 204500
Review for gene: TPP1 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 CYP27A1 SHEKEEB MOHAMMAD gene: CYP27A1 was added
gene: CYP27A1 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: CYP27A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP27A1 were set to PMID: 30054180
Phenotypes for gene: CYP27A1 were set to Cerebrotendinous xanthomatosis, infantile-onset diarrhoea, juvenile-onset cataract, young adult-onset tendon xanthomas; Epilepsy; Parkinsonism; Ataxia; Peripheral neuropathy; OMIM 213700
Review for gene: CYP27A1 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 DDC SHEKEEB MOHAMMAD gene: DDC was added
gene: DDC was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: DDC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DDC were set to PMID: 33983693
Phenotypes for gene: DDC were set to Aromatic L-amino acid decarboxylase deficiency (DYT-DDC); Infantile-onset parkinsonism & dystonia; Bulbar dysfunction; Oculogyric crisis; Autonomic dysfunction; Intellectual disability; OMIM 608603
Review for gene: DDC was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 DHDDS SHEKEEB MOHAMMAD gene: DHDDS was added
gene: DHDDS was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: DHDDS was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DHDDS were set to PMID: 34837344, 29100083
Phenotypes for gene: DHDDS were set to Myoclonic Epilepsy; Parkinsonism; Ataxia; Intellectual disability; OMIM 617836
Review for gene: DHDDS was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 EIF2AK2 SHEKEEB MOHAMMAD gene: EIF2AK2 was added
gene: EIF2AK2 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: EIF2AK2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: EIF2AK2 were set to PMID: 32197074
Phenotypes for gene: EIF2AK2 were set to Neurodevelopmental Syndrome; Developmental delays; Ataxia; Parkinsonism; White matter alterations; OMIM 618877
Review for gene: EIF2AK2 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 EPM2A SHEKEEB MOHAMMAD gene: EPM2A was added
gene: EPM2A was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: EPM2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EPM2A were set to PMID: 27574708
Phenotypes for gene: EPM2A were set to Lafora disease; Progressive Myoclonic Epilepsy; Parkinsonism; OMIM 254780
Review for gene: EPM2A was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 FOXG1 SHEKEEB MOHAMMAD gene: FOXG1 was added
gene: FOXG1 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: FOXG1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FOXG1 were set to PMID: 21953941
Phenotypes for gene: FOXG1 were set to Developmental and Epileptic Encephalopathy; Dystonia,; Athetosis; Parkinsonism; Stereotypies; OMIM 613454
Review for gene: FOXG1 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 GLB1 SHEKEEB MOHAMMAD gene: GLB1 was added
gene: GLB1 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: GLB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLB1 were set to PMID: 34514040
Phenotypes for gene: GLB1 were set to GM1 Gangliosidosis; Parkinsonism; OMIM 230650
Review for gene: GLB1 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 HEXA SHEKEEB MOHAMMAD gene: HEXA was added
gene: HEXA was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: HEXA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HEXA were set to PMID: 33069254
Phenotypes for gene: HEXA were set to GM2 Gangliosidosis; Tay-Sachs disease; Parkinsonism; OMIM 272800
Review for gene: HEXA was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 JPH3 SHEKEEB MOHAMMAD gene: JPH3 was added
gene: JPH3 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: JPH3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: JPH3 were set to PMID: 28131164
Phenotypes for gene: JPH3 were set to Huntington Disease Like 2 (HDL2); Parkinsonism; Severe Dementia; OMIM 606438
Review for gene: JPH3 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 NPC2 SHEKEEB MOHAMMAD gene: NPC2 was added
gene: NPC2 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: NPC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NPC2 were set to PMID: 35695805
Phenotypes for gene: NPC2 were set to Niemann Pick C2; Parkinsonism; OMIM 607625
Review for gene: NPC2 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 NPC1 SHEKEEB MOHAMMAD edited their review of gene: NPC1: Changed publications: PMID: 24035292, 30369906
Early-onset Parkinson disease v0.134 NPC1 SHEKEEB MOHAMMAD gene: NPC1 was added
gene: NPC1 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: NPC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NPC1 were set to PMID: 24035292
Phenotypes for gene: NPC1 were set to Niemann Pick C1; Parkinsonism; OMIM 257220
Review for gene: NPC1 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 NUS1 SHEKEEB MOHAMMAD gene: NUS1 was added
gene: NUS1 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: NUS1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NUS1 were set to PMID: 32485575; 30348779
Phenotypes for gene: NUS1 were set to Mental retardation 55 with seizures (MRD55); Parkinsonism; Developmental delay; Intellectual disability; Ataxia; Myoclonus; OMIM 617831
Review for gene: NUS1 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 PGK1 SHEKEEB MOHAMMAD gene: PGK1 was added
gene: PGK1 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: PGK1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PGK1 were set to PMID: 30975619
Phenotypes for gene: PGK1 were set to Haemolytic anaemia; Rhabdomyolysis; Myopathy; Juvenile Parkinsonism; OMIM 300653
Review for gene: PGK1 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 POLR3A SHEKEEB MOHAMMAD gene: POLR3A was added
gene: POLR3A was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: POLR3A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3A were set to PMID: 33652360
Phenotypes for gene: POLR3A were set to POLR3A Leukoencephalopathy; Parkinsonism; Ocular and dental abnormality; Hypogonadism, OMIM 607694
Review for gene: POLR3A was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 PPP2R2B SHEKEEB MOHAMMAD gene: PPP2R2B was added
gene: PPP2R2B was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: PPP2R2B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PPP2R2B were set to PMID: 31286011
Phenotypes for gene: PPP2R2B were set to Spinocerebellar ataxia 12; Parkinsonism; OMIM 604326
Review for gene: PPP2R2B was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 PRKCG SHEKEEB MOHAMMAD gene: PRKCG was added
gene: PRKCG was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: PRKCG was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRKCG were set to PMID: 29603387
Phenotypes for gene: PRKCG were set to Spinocerebellar ataxia 14; Myoclonus; Parkinsonism; OMIM 605361
Review for gene: PRKCG was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 QDPR SHEKEEB MOHAMMAD gene: QDPR was added
gene: QDPR was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: QDPR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: QDPR were set to PMID: 28413401
Phenotypes for gene: QDPR were set to Dehydropteridin reductase deficiency, Infantile-onset dystonia; Parkinsonism; Epilepsy; Autonomic dysfunction; Hyperphenylalaninemia; OMIM 261360
Review for gene: QDPR was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 SCN1A SHEKEEB MOHAMMAD gene: SCN1A was added
gene: SCN1A was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: SCN1A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SCN1A were set to PMID: 28186331; 24850485
Phenotypes for gene: SCN1A were set to Dravet syndrome; Epilepsy, Paekinsonism; OMIM 607208
Review for gene: SCN1A was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 SERAC1 SHEKEEB MOHAMMAD gene: SERAC1 was added
gene: SERAC1 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: SERAC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SERAC1 were set to PMID: 29332177; 16527507
Phenotypes for gene: SERAC1 were set to MEGDEL Syndrome; Parkinsonism
Review for gene: SERAC1 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 SLC19A3 SHEKEEB MOHAMMAD gene: SLC19A3 was added
gene: SLC19A3 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: SLC19A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC19A3 were set to PMID: 24260777
Phenotypes for gene: SLC19A3 were set to Biotin-Thiamine Responsive Basal Ganglia disease; Childhood onset Dystonia and Parkinsonism; OMIM 607483
Review for gene: SLC19A3 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 SLC18A2 SHEKEEB MOHAMMAD gene: SLC18A2 was added
gene: SLC18A2 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: SLC18A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC18A2 were set to PMID: 23363473, 33983693
Phenotypes for gene: SLC18A2 were set to Brain dopamine-serotonin transport disease, Childhood-onset parkinsonism, OMIM 618049
Review for gene: SLC18A2 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 SOX6 SHEKEEB MOHAMMAD gene: SOX6 was added
gene: SOX6 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: SOX6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SOX6 were set to PMID: 24453155, 25127144
Phenotypes for gene: SOX6 were set to Tolchin-Le Caignec syndrome; Developmental delay; ID; ASD; ADHD; Parkinsonism; Syringomyelia, OMIM 618971
Review for gene: SOX6 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 SPG7 SHEKEEB MOHAMMAD gene: SPG7 was added
gene: SPG7 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: SPG7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPG7 were set to PMID: 31433872
Phenotypes for gene: SPG7 were set to Hereditary Spastic Paraplegia 7; Ataxia; Progressive external opthalmoplegia; Parkinsonism; OMIM 607259
Review for gene: SPG7 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 STUB1 SHEKEEB MOHAMMAD gene: STUB1 was added
gene: STUB1 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: STUB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: STUB1 were set to PubMed: 30381368; 32285148, 32337344
Phenotypes for gene: STUB1 were set to Spinocerebellar Ataxia 48; Parkinsonism, OMIM 618093
Review for gene: STUB1 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 STXBP1 SHEKEEB MOHAMMAD gene: STXBP1 was added
gene: STXBP1 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: STXBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: STXBP1 were set to PMID: 25418441, 32643187, 29929108
Phenotypes for gene: STXBP1 were set to Developmental and epileptic encephalopathy 4; Juvenile onset Parkinsonism; OMIM 612164
Review for gene: STXBP1 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 TBC1D24 SHEKEEB MOHAMMAD gene: TBC1D24 was added
gene: TBC1D24 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: TBC1D24 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBC1D24 were set to PMID: 28663785; 21087195
Phenotypes for gene: TBC1D24 were set to Developmental and epileptic encephalopathy 16; Intellectual disability; Parkinsonism; Seizures; Psychosis; OMIM 615338
Review for gene: TBC1D24 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 TBP SHEKEEB MOHAMMAD gene: TBP was added
gene: TBP was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: TBP was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TBP were set to PMID: 27172828; 14638975; 11313753; 11914409
Phenotypes for gene: TBP were set to Spinocerebellar Ataxia 17; Parkinsonism; Chorea; Seizures; Psychosis; Dementia; OMIM 607136
Review for gene: TBP was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 UBTF SHEKEEB MOHAMMAD gene: UBTF was added
gene: UBTF was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: UBTF was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: UBTF were set to PubMed: 28777933; 29300972
Phenotypes for gene: UBTF were set to Neurodegeneration, childhood-onset; Parkinsonism; Dystonia; Chorea; Brain atrophy
Review for gene: UBTF was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 VAC14 SHEKEEB MOHAMMAD gene: VAC14 was added
gene: VAC14 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: VAC14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VAC14 were set to PMID: 31392254; 28502045
Phenotypes for gene: VAC14 were set to Childhood onset Striatonigral degeneration; Dystonia; Parkinsonism; OMIM 617054
Review for gene: VAC14 was set to GREEN
Added comment: Sources: Literature
Early-onset Parkinson disease v0.134 WARS2 SHEKEEB MOHAMMAD reviewed gene: WARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Early-onset Parkinson disease v0.134 WARS2 SHEKEEB MOHAMMAD gene: WARS2 was added
gene: WARS2 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: WARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WARS2 were set to PMID: 29120065; 34890876
Phenotypes for gene: WARS2 were set to Childhood onset parkinsonism dystonia-3; Myoclonus ataxia; OMIM 619738
Early-onset Parkinson disease v0.134 ZFYVE26 SHEKEEB MOHAMMAD gene: ZFYVE26 was added
gene: ZFYVE26 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: ZFYVE26 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZFYVE26 were set to PMID: 33033739; 21462267
Phenotypes for gene: ZFYVE26 were set to Spastic paraplegia and retinal degeneration; Kjellin syndrome; Parkinsonism; OMIM 270700
Review for gene: ZFYVE26 was set to GREEN
Added comment: Sources: Literature
Hand and foot malformations v0.58 UBA2 Zornitza Stark Marked gene: UBA2 as ready
Hand and foot malformations v0.58 UBA2 Zornitza Stark Gene: uba2 has been classified as Green List (High Evidence).
Hand and foot malformations v0.58 UBA2 Zornitza Stark Classified gene: UBA2 as Green List (high evidence)
Hand and foot malformations v0.58 UBA2 Zornitza Stark Gene: uba2 has been classified as Green List (High Evidence).
Hand and foot malformations v0.57 UBA2 Zornitza Stark gene: UBA2 was added
gene: UBA2 was added to Hand and foot malformations. Sources: Expert Review
Mode of inheritance for gene: UBA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UBA2 were set to 31332306; 31587267; 34159400
Phenotypes for gene: UBA2 were set to ACCES syndrome, MIM# 619959; Split-Hand/Foot Malformation; Aplasia Cutis Congenita; Ectrodactyly
Review for gene: UBA2 was set to GREEN
Added comment: 2x unrelated probands with isolated split hand malformation. fs variants - 1x de novo and 1x inherited from apparent unaffected mother (no radiographs of her hand available)

1x proband with unilateral split-hand malformation (missense). Her daughter and grandson reported to have ectrofactyly but were unavailable for testing
Sources: Expert Review
Skeletal dysplasia v0.179 UBA2 Zornitza Stark Publications for gene: UBA2 were set to 31332306; 31587267
Fetal anomalies v1.46 UBA2 Zornitza Stark Phenotypes for gene: UBA2 were changed from Split-Hand/Foot Malformation; Aplasia Cutis Congenita; Ectrodactyly to ACCES syndrome, MIM# 619959; Split-Hand/Foot Malformation; Aplasia Cutis Congenita; Ectrodactyly
Fetal anomalies v1.45 UBA2 Zornitza Stark Publications for gene: UBA2 were set to PMID: 31332306; 31587267
Skeletal dysplasia v0.178 UBA2 Zornitza Stark Phenotypes for gene: UBA2 were changed from Split-Hand/Foot Malformation; Aplasia Cutis Congenita; Ectrodactyly to ACCES syndrome, MIM# 619959; Split-Hand/Foot Malformation; Aplasia Cutis Congenita; Ectrodactyly
Mendeliome v1.160 UBA2 Zornitza Stark Phenotypes for gene: UBA2 were changed from Split-Hand/Foot Malformation; Aplasia Cutis Congenita; Ectrodactyly to ACCES syndrome, MIM# 619959; Split-Hand/Foot Malformation; Aplasia Cutis Congenita; Ectrodactyly
Mendeliome v1.159 UBA2 Zornitza Stark reviewed gene: UBA2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ACCES syndrome, MIM# 619959; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.239 ANKRD11 Zornitza Stark Marked gene: ANKRD11 as ready
Congenital Heart Defect v0.239 ANKRD11 Zornitza Stark Gene: ankrd11 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.239 ANKRD11 Zornitza Stark Phenotypes for gene: ANKRD11 were changed from to KBG syndrome, MIM# 148050
Congenital Heart Defect v0.238 ANKRD11 Zornitza Stark Publications for gene: ANKRD11 were set to
Congenital Heart Defect v0.237 ANKRD11 Zornitza Stark Mode of inheritance for gene: ANKRD11 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.236 ANKRD11 Zornitza Stark reviewed gene: ANKRD11: Rating: GREEN; Mode of pathogenicity: None; Publications: 27605097; Phenotypes: KBG syndrome 148050; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.236 ADAMTS10 Zornitza Stark Marked gene: ADAMTS10 as ready
Congenital Heart Defect v0.236 ADAMTS10 Zornitza Stark Gene: adamts10 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.236 ADAMTS10 Zornitza Stark Phenotypes for gene: ADAMTS10 were changed from to Weill-Marchesani syndrome 1, recessive, MIM# 277600
Congenital Heart Defect v0.235 ADAMTS10 Zornitza Stark Publications for gene: ADAMTS10 were set to
Congenital Heart Defect v0.234 ADAMTS10 Zornitza Stark Mode of inheritance for gene: ADAMTS10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.233 ADAMTS10 Zornitza Stark reviewed gene: ADAMTS10: Rating: GREEN; Mode of pathogenicity: None; Publications: 15368195, 18567016, 19836009; Phenotypes: Weill-Marchesani syndrome 1, recessive, MIM# 277600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.233 ACVR1 Zornitza Stark Marked gene: ACVR1 as ready
Congenital Heart Defect v0.233 ACVR1 Zornitza Stark Gene: acvr1 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.233 ACVR1 Zornitza Stark Phenotypes for gene: ACVR1 were changed from to Congenital heart disease, MONDO:0005453
Congenital Heart Defect v0.232 ACVR1 Zornitza Stark Publications for gene: ACVR1 were set to
Congenital Heart Defect v0.231 ACVR1 Zornitza Stark Mode of inheritance for gene: ACVR1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.230 ACVR1 Zornitza Stark reviewed gene: ACVR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29089047, 19506109, 21248739; Phenotypes: Congenital heart disease, MONDO:0005453; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.33 ASXL1 Zornitza Stark Marked gene: ASXL1 as ready
Cerebral Palsy v1.33 ASXL1 Zornitza Stark Gene: asxl1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.33 ASXL1 Zornitza Stark Classified gene: ASXL1 as Green List (high evidence)
Cerebral Palsy v1.33 ASXL1 Zornitza Stark Gene: asxl1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.32 ASXL1 Clare van Eyk gene: ASXL1 was added
gene: ASXL1 was added to Cerebral Palsy. Sources: Literature,Expert Review
Mode of inheritance for gene: ASXL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ASXL1 were set to 33528536; 30542205
Phenotypes for gene: ASXL1 were set to Bohring-Opitz syndrome (MIM 605039)
Review for gene: ASXL1 was set to GREEN
Added comment: 3 individuals with de novo loss of function variants identified in a retrospective CP cohort analysis (PMID 33528536) . One additional individual reported in PMID 30542205 with "atypical cerebral palsy".

Truncal hypotonia with spasticity of the extremities are sometimes reported in BOS (but are not characteristic of the disorder), along with multiple developmental abnormalities of varying severity.
Sources: Literature, Expert Review
Cerebral Palsy v1.32 ATP1A3 Zornitza Stark Classified gene: ATP1A3 as Green List (high evidence)
Cerebral Palsy v1.32 ATP1A3 Zornitza Stark Gene: atp1a3 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.230 ESCO2 Zornitza Stark Marked gene: ESCO2 as ready
Congenital Heart Defect v0.230 ESCO2 Zornitza Stark Gene: esco2 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.230 ESCO2 Zornitza Stark Phenotypes for gene: ESCO2 were changed from Atrial septal defect; Ventricular septal defect; Pulmonic stenosis; tricuspid regurgitation to Roberts-SC phocomelia syndrome, MIM# 268300; Atrial septal defect; Ventricular septal defect; Pulmonic stenosis; tricuspid regurgitation
Congenital Heart Defect v0.229 ESCO2 Zornitza Stark Classified gene: ESCO2 as Green List (high evidence)
Congenital Heart Defect v0.229 ESCO2 Zornitza Stark Gene: esco2 has been classified as Green List (High Evidence).
Prepair 1000+ v0.50 RYR1 Zornitza Stark Tag for review tag was added to gene: RYR1.
Congenital Heart Defect v0.228 EP300 Zornitza Stark Marked gene: EP300 as ready
Congenital Heart Defect v0.228 EP300 Zornitza Stark Gene: ep300 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.228 EP300 Zornitza Stark Marked gene: EP300 as ready
Congenital Heart Defect v0.228 EP300 Zornitza Stark Gene: ep300 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.228 EP300 Zornitza Stark Phenotypes for gene: EP300 were changed from Ventricular septal defect; Patent foramen ovale; Patent ductus arteriosus; mild valve dysplasia to Rubinstein-Taybi syndrome 2, MIM# 613684
Congenital Heart Defect v0.227 EP300 Zornitza Stark Classified gene: EP300 as Green List (high evidence)
Congenital Heart Defect v0.227 EP300 Zornitza Stark Gene: ep300 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.226 EP300 Zornitza Stark reviewed gene: EP300: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Rubinstein-Taybi syndrome 2, MIM# 613684; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.226 DNAH5 Zornitza Stark Marked gene: DNAH5 as ready
Congenital Heart Defect v0.226 DNAH5 Zornitza Stark Gene: dnah5 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.226 DNAH5 Zornitza Stark Phenotypes for gene: DNAH5 were changed from Atrial septal defect; Ventricular septal defect; Atrioventricular septal defect; Transposition of the great arteries to Ciliary dyskinesia, primary, 3, with or without situs inversus, MIM# 608644
Congenital Heart Defect v0.225 DNAH5 Zornitza Stark Classified gene: DNAH5 as Green List (high evidence)
Congenital Heart Defect v0.225 DNAH5 Zornitza Stark Gene: dnah5 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.224 DNAH5 Zornitza Stark reviewed gene: DNAH5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 3, with or without situs inversus, MIM# 608644; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.224 CHST14 Zornitza Stark Marked gene: CHST14 as ready
Congenital Heart Defect v0.224 CHST14 Zornitza Stark Gene: chst14 has been classified as Red List (Low Evidence).
Congenital Heart Defect v0.224 CHST14 Zornitza Stark Phenotypes for gene: CHST14 were changed from Atrial septal defect; Coarctation of the aorta to Ehlers-Danlos syndrome, musculocontractural type 1, MIM# 601776
Congenital Heart Defect v0.223 CHST14 Zornitza Stark Classified gene: CHST14 as Red List (low evidence)
Congenital Heart Defect v0.223 CHST14 Zornitza Stark Gene: chst14 has been classified as Red List (Low Evidence).
Congenital Heart Defect v0.222 CHST14 Zornitza Stark reviewed gene: CHST14: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ehlers-Danlos syndrome, musculocontractural type 1, MIM# 601776; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.222 CFC1 Zornitza Stark Marked gene: CFC1 as ready
Congenital Heart Defect v0.222 CFC1 Zornitza Stark Gene: cfc1 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.222 CFC1 Zornitza Stark Phenotypes for gene: CFC1 were changed from Atrioventricular septal defect; Interrupted aortic arch; Tetralogy of fallot; Transposition of the great arteries; Truncus arteriosus; Double outlet right ventricle; Heterotaxy to Heterotaxy, visceral, 2, MIM# 605376
Congenital Heart Defect v0.221 CFC1 Zornitza Stark Publications for gene: CFC1 were set to
Congenital Heart Defect v0.220 CFC1 Zornitza Stark Classified gene: CFC1 as Green List (high evidence)
Congenital Heart Defect v0.220 CFC1 Zornitza Stark Gene: cfc1 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.219 CFC1 Zornitza Stark reviewed gene: CFC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31633655, 18162845, 25423076, 11062482; Phenotypes: Heterotaxy, visceral, 2, MIM# 605376; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v0.50 CNGA3 Zornitza Stark Tag for review tag was added to gene: CNGA3.
Prepair 1000+ v0.50 F2 Zornitza Stark Tag for review tag was added to gene: F2.
Prepair 1000+ v0.50 F5 Zornitza Stark Tag for review tag was added to gene: F5.
Prepair 1000+ v0.50 F9 Zornitza Stark Tag for review tag was added to gene: F9.
Prepair 1000+ v0.50 ITGA6 Zornitza Stark Marked gene: ITGA6 as ready
Prepair 1000+ v0.50 ITGA6 Zornitza Stark Gene: itga6 has been classified as Green List (High Evidence).
Prepair 1000+ v0.50 ITGA6 Zornitza Stark Publications for gene: ITGA6 were set to
Prepair 1000+ v0.49 PDHA1 Zornitza Stark Tag for review tag was added to gene: PDHA1.
Cerebral Palsy v1.31 ATP1A3 Clare van Eyk reviewed gene: ATP1A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 33528536, 30542205; Phenotypes: Developmental and epileptic encephalopathy 99 (MIM# 619606); Mode of inheritance: None
Congenital Heart Defect v0.219 ESCO2 Chloe Stutterd gene: ESCO2 was added
gene: ESCO2 was added to Congenital Heart Defect. Sources: Expert list,Literature
Mode of inheritance for gene: ESCO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ESCO2 were set to 19574259; 31976146
Phenotypes for gene: ESCO2 were set to Atrial septal defect; Ventricular septal defect; Pulmonic stenosis; tricuspid regurgitation
Penetrance for gene: ESCO2 were set to Complete
Review for gene: ESCO2 was set to GREEN
gene: ESCO2 was marked as current diagnostic
Added comment: CHD reported in 8/31 patients with molecularly-confirmed Roberts syndrome (PMID 19574259). Septal defect and tricuspid regurgitation reported in one patient with molecularly-confirmed Roberts syndrome (PMID:31976146).
Sources: Expert list, Literature
Prepair 1000+ v0.49 RYR1 Crystle Lee reviewed gene: RYR1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Central core disease (MIM#117000), Minicore myopathy with external ophthalmoplegia (MIM#255320), Neuromuscular disease, congenital, with uniform type 1 fiber (MIM#117000); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Congenital Heart Defect v0.219 EP300 Chloe Stutterd gene: EP300 was added
gene: EP300 was added to Congenital Heart Defect. Sources: Expert list,Literature
Mode of inheritance for gene: EP300 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EP300 were set to 24352918; 24476420
Phenotypes for gene: EP300 were set to Ventricular septal defect; Patent foramen ovale; Patent ductus arteriosus; mild valve dysplasia
Penetrance for gene: EP300 were set to unknown
Review for gene: EP300 was set to AMBER
gene: EP300 was marked as current diagnostic
Added comment: Included in Victor Chang CHD gene list. Mice homozygotes for targeted null mutations have CHD (MGI ID: 1276116). Five patients reported with with CHD (VSD, PFO, PDA, valve dysplasia), all with extra-cardiac features of Rubinstein–Taybi syndrome (24352918; 24476420).
Sources: Expert list, Literature
Congenital Heart Defect v0.219 DNAH5 Chloe Stutterd gene: DNAH5 was added
gene: DNAH5 was added to Congenital Heart Defect. Sources: Expert list,Literature
Mode of inheritance for gene: DNAH5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAH5 were set to 31638833
Phenotypes for gene: DNAH5 were set to Atrial septal defect; Ventricular septal defect; Atrioventricular septal defect; Transposition of the great arteries
Penetrance for gene: DNAH5 were set to unknown
Review for gene: DNAH5 was set to AMBER
gene: DNAH5 was marked as current diagnostic
Added comment: Gene included in Victor Chang CHD gene list but all references to CHD are in association with heterotaxy. PMID 31638833: 8/132 (6.1%) patients with DNAH5-associated primary ciliary dyskinesia presented with CHD (septal defects with or without valve and vessel defects) and all had heterotaxy (three with situs solitus and five had situs inversus).
Sources: Expert list, Literature
Congenital Heart Defect v0.219 CHST14 Chloe Stutterd gene: CHST14 was added
gene: CHST14 was added to Congenital Heart Defect. Sources: Expert list,Literature
Mode of inheritance for gene: CHST14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHST14 were set to 20503305
Phenotypes for gene: CHST14 were set to Atrial septal defect; Coarctation of the aorta
Penetrance for gene: CHST14 were set to unknown
Review for gene: CHST14 was set to RED
Added comment: Gene included in Victor Chang CHD gene list however evidence does not exist for causality of significant or isolated CHD and only reported in association with the EDS phenotype. PMID 20503305 reports one patient with EDS and moderate tricuspid valve regurgitation, prolapse of the tricuspid and mitral valves, and left-to-right shunt via a small atrial septal defect, and two patients with valvular regurgitation diagnosed in adulthood in association with the EDS phenotype.
Sources: Expert list, Literature
Congenital Heart Defect v0.219 CFC1 Chloe Stutterd gene: CFC1 was added
gene: CFC1 was added to Congenital Heart Defect. Sources: Expert list,Literature
Mode of inheritance for gene: CFC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CFC1 were set to Atrioventricular septal defect; Interrupted aortic arch; Tetralogy of fallot; Transposition of the great arteries; Truncus arteriosus; Double outlet right ventricle; Heterotaxy
Penetrance for gene: CFC1 were set to unknown
Review for gene: CFC1 was set to RED
Added comment: Strong evidence for causality of heterotaxy syndromes with congenital cardiac malformations (11062482), however investigation of CFC1 as a cause of isolated CHD identified only the polymorphism R78W or the A145T variant which was also present in controls (11799476; 17072672).
Sources: Expert list, Literature
Prepair 1000+ v0.49 CNGA3 Crystle Lee reviewed gene: CNGA3: Rating: RED; Mode of pathogenicity: None; Publications: 11536077, 35332618; Phenotypes: Achromatopsia 2 (MIM#216900); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.49 F2 Crystle Lee reviewed gene: F2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Dysprothrombinemia (MIM#613679), Hypoprothrombinemia (MIM#613679); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.49 F5 Crystle Lee reviewed gene: F5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Factor V deficiency (MIM#227400); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v0.49 F9 Crystle Lee reviewed gene: F9: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hemophilia B (MIM#306900); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.159 C9orf84 Zornitza Stark Marked gene: C9orf84 as ready
Mendeliome v1.159 C9orf84 Zornitza Stark Gene: c9orf84 has been classified as Green List (High Evidence).
Mendeliome v1.159 C9orf84 Zornitza Stark Classified gene: C9orf84 as Green List (high evidence)
Mendeliome v1.159 C9orf84 Zornitza Stark Gene: c9orf84 has been classified as Green List (High Evidence).
Mendeliome v1.158 C9orf84 Zornitza Stark Tag new gene name tag was added to gene: C9orf84.
Mendeliome v1.158 C9orf84 Zornitza Stark changed review comment from: 8 families reported with bi-allelic variants in this gene and spermatogenic failure.
Sources: Literature; to: 8 families reported with bi-allelic variants in this gene and spermatogenic failure. A male germ cell-specific Shoc1 knockout mouse model recapitulates the phenotype (germline knockout: early lethality).

HGNC approved name is SHOC1.

Sources: Literature
Mendeliome v1.158 C9orf84 Zornitza Stark gene: C9orf84 was added
gene: C9orf84 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: C9orf84 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C9orf84 were set to 32741963; 32900840; 35485979
Phenotypes for gene: C9orf84 were set to Spermatogenic failure 75, MIM# 619949
Review for gene: C9orf84 was set to GREEN
Added comment: 8 families reported with bi-allelic variants in this gene and spermatogenic failure.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4858 HIST1H4E Zornitza Stark Phenotypes for gene: HIST1H4E were changed from Neurodevelopmental disorder, HIST1H4E-related MONDO:0700092 to Tessadori-van Haaften neurodevelopmental syndrome 3, MIM# 619950
Intellectual disability syndromic and non-syndromic v0.4857 HIST1H4E Zornitza Stark Mode of inheritance for gene: HIST1H4E was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4856 HIST1H4E Zornitza Stark reviewed gene: HIST1H4E: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Tessadori-van Haaften neurodevelopmental syndrome 3, MIM# 619950; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v1.135 HIST1H4E Zornitza Stark Marked gene: HIST1H4E as ready
Microcephaly v1.135 HIST1H4E Zornitza Stark Gene: hist1h4e has been classified as Green List (High Evidence).
Microcephaly v1.135 HIST1H4E Zornitza Stark Phenotypes for gene: HIST1H4E were changed from Neurodevelopmental disorder, HIST1H4E-related MONDO:0700092 to Tessadori-van Haaften neurodevelopmental syndrome 3, MIM# 619950
Microcephaly v1.134 HIST1H4E Zornitza Stark Mode of inheritance for gene: HIST1H4E was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v1.133 HIST1H4E Zornitza Stark Classified gene: HIST1H4E as Green List (high evidence)
Microcephaly v1.133 HIST1H4E Zornitza Stark Gene: hist1h4e has been classified as Green List (High Evidence).
Microcephaly v1.132 HIST1H4E Zornitza Stark Tag new gene name tag was added to gene: HIST1H4E.
Microcephaly v1.132 HIST1H4E Zornitza Stark reviewed gene: HIST1H4E: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Tessadori-van Haaften neurodevelopmental syndrome 3, MIM# 619950; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.157 HIST1H4E Zornitza Stark Phenotypes for gene: HIST1H4E were changed from Neurodevelopmental disorder, HIST1H4E-related MONDO:0700092 to Tessadori-van Haaften neurodevelopmental syndrome 3, MIM# 619950
Mendeliome v1.156 HIST1H4E Zornitza Stark Tag new gene name tag was added to gene: HIST1H4E.
Mendeliome v1.156 HIST1H4E Zornitza Stark reviewed gene: HIST1H4E: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Tessadori-van Haaften neurodevelopmental syndrome 3, MIM# 619950; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4856 KMT2B Zornitza Stark Phenotypes for gene: KMT2B were changed from Dystonia 28, childhood-onset, MIM#617284 to Dystonia 28, childhood-onset 617284; MONDO:0015004; Intellectual developmental disorder, autosomal dominant 68, MIM# 619934
Intellectual disability syndromic and non-syndromic v0.4855 KMT2B Zornitza Stark Publications for gene: KMT2B were set to
Intellectual disability syndromic and non-syndromic v0.4854 KMT2B Zornitza Stark changed review comment from: ID described as part of the phenotype in some patients.; to: Childhood-onset dystonia: ID described as part of the phenotype in some patients.
Intellectual disability syndromic and non-syndromic v0.4854 KMT2B Zornitza Stark edited their review of gene: KMT2B: Added comment: Nine individuals reported in PMID 33150406 with heterozygous variants in this gene and intellectual disability, speech delay, microcephaly, growth delay, feeding problems, and dysmorphic features, including epicanthic folds, posteriorly rotated ears, syndactyly/clinodactyly of toes, and fifth finger clinodactyly, normal MRIs and NO dystonia.; Changed publications: 33150406; Changed phenotypes: Dystonia 28, childhood-onset 617284, MONDO:0015004, Intellectual developmental disorder, autosomal dominant 68, MIM# 619934
Mendeliome v1.156 KMT2B Zornitza Stark Publications for gene: KMT2B were set to 27839873; 27992417
Mendeliome v1.155 KMT2B Zornitza Stark edited their review of gene: KMT2B: Added comment: Nine individuals reported in PMID 33150406 with heterozygous variants in this gene and intellectual disability, speech delay, microcephaly, growth delay, feeding problems, and dysmorphic features, including epicanthic folds, posteriorly rotated ears, syndactyly/clinodactyly of toes, and fifth finger clinodactyly, normal MRIs and NO dystonia.; Changed publications: 27839873, 27992417, 33150406; Changed phenotypes: Dystonia 28, childhood-onset 617284, MONDO:0015004, Intellectual developmental disorder, autosomal dominant 68, MIM# 619934
Intellectual disability syndromic and non-syndromic v0.4854 LMAN2L Zornitza Stark Phenotypes for gene: LMAN2L were changed from ?Mental retardation, autosomal recessive, 52; OMIM #616887 to Mental retardation, autosomal recessive, 52 OMIM #616887; Intellectual developmental disorder, autosomal dominant 69 , MIM# 617863
Intellectual disability syndromic and non-syndromic v0.4853 LMAN2L Zornitza Stark reviewed gene: LMAN2L: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, autosomal recessive, 52 OMIM #616887, Intellectual developmental disorder, autosomal dominant 69 , MIM# 617863; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.155 LMAN2L Zornitza Stark Phenotypes for gene: LMAN2L were changed from Mental retardation, autosomal recessive, 52; OMIM #616887 to Mental retardation, autosomal recessive, 52 OMIM #616887; Intellectual developmental disorder, autosomal dominant 69 , MIM# 617863
Mendeliome v1.154 LMAN2L Zornitza Stark edited their review of gene: LMAN2L: Changed phenotypes: Mental retardation, autosomal recessive, 52 OMIM #616887, Intellectual developmental disorder, autosomal dominant 69 , MIM# 617863
Mendeliome v1.154 CDH2 Zornitza Stark edited their review of gene: CDH2: Changed phenotypes: Intellectual disability, corpus callosum abnormalities, congenital abnormalities, Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929, Attention deficit-hyperactivity disorder 8 , MIM# 619957
Mendeliome v1.154 CDH2 Zornitza Stark Phenotypes for gene: CDH2 were changed from Intellectual disability; corpus callosum abnormalities; congenital abnormalities; Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929 to Intellectual disability; corpus callosum abnormalities; congenital abnormalities; Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929; Attention deficit-hyperactivity disorder 8 , MIM# 619957
Mendeliome v1.153 CDH2 Zornitza Stark Mode of inheritance for gene: CDH2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.152 CDH2 Zornitza Stark edited their review of gene: CDH2: Added comment: PMID 34702855: three sibs with homozygous missense and strikingly severe ADHD. Mouse model of same variant recapitulated the phenotype. AMBER for bi-allelic association (segregation and functional data).; Changed publications: 31585109, 34702855; Changed phenotypes: Intellectual disability, corpus callosum abnormalities, congenital abnormalities, Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM# 618929:Attention deficit-hyperactivity disorder 8 , MIM# 619957; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4853 PLXNA1 Zornitza Stark reviewed gene: PLXNA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dworschak-Punetha neurodevelopmental syndrome, MIM# 619955; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4853 PLXNA1 Zornitza Stark Phenotypes for gene: PLXNA1 were changed from Neurodevelopmental disorder with cerebral and eye anomalies to Dworschak-Punetha neurodevelopmental syndrome, MIM# 619955
Genetic Epilepsy v0.1633 PLXNA1 Zornitza Stark Phenotypes for gene: PLXNA1 were changed from Neurodevelopmental disorder with cerebral and eye anomalies to Dworschak-Punetha neurodevelopmental syndrome, MIM# 619955
Genetic Epilepsy v0.1632 PLXNA1 Zornitza Stark edited their review of gene: PLXNA1: Changed phenotypes: Dworschak-Punetha neurodevelopmental syndrome, MIM# 619955
Mendeliome v1.152 PLXNA1 Zornitza Stark Phenotypes for gene: PLXNA1 were changed from Neurodevelopmental disorder with cerebral and eye anomalies to Dworschak-Punetha neurodevelopmental syndrome, MIM# 619955
Mendeliome v1.151 PLXNA1 Zornitza Stark edited their review of gene: PLXNA1: Changed phenotypes: Dworschak-Punetha neurodevelopmental syndrome, MIM# 619955
Mendeliome v1.151 TBP Zornitza Stark Tag STR tag was added to gene: TBP.
Prepair 1000+ v0.49 ITGA6 Crystle Lee reviewed gene: ITGA6: Rating: GREEN; Mode of pathogenicity: None; Publications: 31502654, 27607025, 9158140, 34525201, 20301336; Phenotypes: Epidermolysis bullosa, junctional 6, with pyloric atresia (MIM#619817); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.49 PDHA1 Crystle Lee reviewed gene: PDHA1: Rating: AMBER; Mode of pathogenicity: None; Publications: 28584645, 22142326; Phenotypes: Pyruvate dehydrogenase E1-alpha deficiency (MIM#312170); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v1.31 ADAT3 Zornitza Stark Marked gene: ADAT3 as ready
Cerebral Palsy v1.31 ADAT3 Zornitza Stark Gene: adat3 has been classified as Green List (High Evidence).
Cerebral Palsy v1.31 ADAT3 Zornitza Stark Phenotypes for gene: ADAT3 were changed from MIM #615286 to Neurodevelopmental disorder with brain abnormalities, poor growth, and dysmorphic facies, MIM# 615286
Cerebral Palsy v1.30 ADAT3 Zornitza Stark Classified gene: ADAT3 as Green List (high evidence)
Cerebral Palsy v1.30 ADAT3 Zornitza Stark Gene: adat3 has been classified as Green List (High Evidence).
Prepair 1000+ v0.49 TTN Zornitza Stark Marked gene: TTN as ready
Prepair 1000+ v0.49 TTN Zornitza Stark Gene: ttn has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v0.49 TTN Zornitza Stark Classified gene: TTN as Amber List (moderate evidence)
Prepair 1000+ v0.49 TTN Zornitza Stark Gene: ttn has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v0.48 VWF Zornitza Stark Marked gene: VWF as ready
Prepair 1000+ v0.48 VWF Zornitza Stark Gene: vwf has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v0.48 VWF Zornitza Stark Classified gene: VWF as Amber List (moderate evidence)
Prepair 1000+ v0.48 VWF Zornitza Stark Gene: vwf has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v0.47 SHOX Zornitza Stark Marked gene: SHOX as ready
Prepair 1000+ v0.47 SHOX Zornitza Stark Gene: shox has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v0.47 SHOX Zornitza Stark Mode of inheritance for gene: SHOX was changed from BIALLELIC, autosomal or pseudoautosomal to Other
Prepair 1000+ v0.46 SHOX Zornitza Stark Classified gene: SHOX as Amber List (moderate evidence)
Prepair 1000+ v0.46 SHOX Zornitza Stark Gene: shox has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v0.45 SHOX Zornitza Stark Tag SV/CNV tag was added to gene: SHOX.
Prepair 1000+ v0.45 EFNB1 Zornitza Stark Tag for review tag was added to gene: EFNB1.
Prepair 1000+ v0.45 VPS11 Zornitza Stark Marked gene: VPS11 as ready
Prepair 1000+ v0.45 VPS11 Zornitza Stark Gene: vps11 has been classified as Green List (High Evidence).
Prepair 1000+ v0.45 VPS11 Zornitza Stark Publications for gene: VPS11 were set to
Prepair 1000+ v0.44 TNFRSF13B Zornitza Stark Marked gene: TNFRSF13B as ready
Prepair 1000+ v0.44 TNFRSF13B Zornitza Stark Gene: tnfrsf13b has been classified as Red List (Low Evidence).
Prepair 1000+ v0.44 TNFRSF13B Zornitza Stark Publications for gene: TNFRSF13B were set to
Prepair 1000+ v0.43 TNFRSF13B Zornitza Stark Classified gene: TNFRSF13B as Red List (low evidence)
Prepair 1000+ v0.43 TNFRSF13B Zornitza Stark Gene: tnfrsf13b has been classified as Red List (Low Evidence).
Prepair 1000+ v0.42 RPL10 Zornitza Stark Tag for review tag was added to gene: RPL10.
Prepair 1000+ v0.42 SERPINA1 Zornitza Stark Marked gene: SERPINA1 as ready
Prepair 1000+ v0.42 SERPINA1 Zornitza Stark Gene: serpina1 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.42 SERPINA1 Zornitza Stark Classified gene: SERPINA1 as Red List (low evidence)
Prepair 1000+ v0.42 SERPINA1 Zornitza Stark Gene: serpina1 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.41 TRAC Zornitza Stark Tag for review tag was added to gene: TRAC.
Prepair 1000+ v0.41 OCA2 Zornitza Stark Tag for review tag was added to gene: OCA2.
Prepair 1000+ v0.41 F8 Zornitza Stark Marked gene: F8 as ready
Prepair 1000+ v0.41 F8 Zornitza Stark Gene: f8 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.41 F8 Zornitza Stark Tag SV/CNV tag was added to gene: F8.
Prepair 1000+ v0.41 F8 Zornitza Stark Classified gene: F8 as Red List (low evidence)
Prepair 1000+ v0.41 F8 Zornitza Stark Gene: f8 has been classified as Red List (Low Evidence).
Mendeliome v1.151 KITLG Zornitza Stark Phenotypes for gene: KITLG were changed from Deafness, autosomal dominant 69, unilateral or asymmetric, MIM# 616697 to Deafness, autosomal dominant 69, unilateral or asymmetric, MIM# 616697; deafness; heterochromia iridis; hypopigmentation of the skin; hyperpigmentation of the skin; Waardenburg syndrome,MONDO:0018094, KITLG-related
Mendeliome v1.150 KITLG Zornitza Stark Publications for gene: KITLG were set to 26522471
Mendeliome v1.149 KITLG Zornitza Stark Classified gene: KITLG as Green List (high evidence)
Mendeliome v1.149 KITLG Zornitza Stark Gene: kitlg has been classified as Green List (High Evidence).
Brain Calcification v1.14 CLDN5 Zornitza Stark Marked gene: CLDN5 as ready
Brain Calcification v1.14 CLDN5 Zornitza Stark Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Brain Calcification v1.14 CLDN5 Zornitza Stark Classified gene: CLDN5 as Amber List (moderate evidence)
Brain Calcification v1.14 CLDN5 Zornitza Stark Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Brain Calcification v1.13 CLDN5 Zornitza Stark gene: CLDN5 was added
gene: CLDN5 was added to Brain Calcification. Sources: Literature
Mode of inheritance for gene: CLDN5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CLDN5 were set to 35714222
Phenotypes for gene: CLDN5 were set to alternating hemiplegia, MONDO:0016210, CLDN5-related
Mode of pathogenicity for gene: CLDN5 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: CLDN5 was set to AMBER
Added comment: PMID: 35714222; Hashimoto, Y. et al. (2022): Two unrelated cases (early-onset) with alternating hemiplegia with microcephaly were shown to have the same de novo variant, NM_001363066.2:c.178G>A, p.(Gly60Arg).

One with Jewish / Tunisian ancestry: Onset was at 8 months, three episodes of febrile tonic-clonic 1 seizures of the four limbs, with eye rolling, loss of consciousness, transient left and right post-2 ictal hemiparesis and vomiting. The other with Asian / European ancestry: Onset was at 30 months with three iterative episodes of febrile and non-febrile hemiplegia and loss of 18 consciousness. The recurrent episodes alternatively involved the left-and 19 right-hand side, then generalised and were followed by post ictal hemiparesis.

CT scans of both showed brain calcifications and aberrant blood flow patterns. Transfected cell lines with this variant, c178G>A, showed higher chloride ion permeability and lower sodium ion permeability when compared to wildtype.
Sources: Literature
Mendeliome v1.148 CLDN5 Zornitza Stark Marked gene: CLDN5 as ready
Mendeliome v1.148 CLDN5 Zornitza Stark Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.148 CLDN5 Zornitza Stark Classified gene: CLDN5 as Amber List (moderate evidence)
Mendeliome v1.148 CLDN5 Zornitza Stark Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.147 CLDN5 Zornitza Stark gene: CLDN5 was added
gene: CLDN5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CLDN5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CLDN5 were set to 35714222
Phenotypes for gene: CLDN5 were set to alternating hemiplegia, MONDO:0016210, CLDN5-related
Mode of pathogenicity for gene: CLDN5 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: CLDN5 was set to AMBER
Added comment: PMID: 35714222; Hashimoto, Y. et al. (2022): Two unrelated cases (early-onset) with alternating hemiplegia with microcephaly were shown to have the same de novo variant, NM_001363066.2:c.178G>A, p.(Gly60Arg).

One with Jewish / Tunisian ancestry: Onset was at 8 months, three episodes of febrile tonic-clonic 1 seizures of the four limbs, with eye rolling, loss of consciousness, transient left and right post-2 ictal hemiparesis and vomiting. The other with Asian / European ancestry: Onset was at 30 months with three iterative episodes of febrile and non-febrile hemiplegia and loss of 18 consciousness. The recurrent episodes alternatively involved the left-and 19 right-hand side, then generalised and were followed by post ictal hemiparesis.

CT scans of both showed brain calcifications and aberrant blood flow patterns. Transfected cell lines with this variant, c178G>A, showed higher chloride ion permeability and lower sodium ion permeability when compared to wildtype.
Sources: Literature
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.304 CCDC155 Zornitza Stark Marked gene: CCDC155 as ready
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.304 CCDC155 Zornitza Stark Gene: ccdc155 has been classified as Green List (High Evidence).
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.304 CCDC155 Zornitza Stark Phenotypes for gene: CCDC155 were changed from Non-obstructive azoospermia; Premature ovarian insufficiency; Infertility disorder, MONDO:0005047, CCDC155-related to Premature ovarian insufficiency; Infertility disorder, MONDO:0005047, CCDC155-related
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.303 CCDC155 Zornitza Stark Classified gene: CCDC155 as Green List (high evidence)
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.303 CCDC155 Zornitza Stark Gene: ccdc155 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.273 Zornitza Stark removed gene:MAK from the panel
Mendeliome v1.146 PSMB9 Zornitza Stark Publications for gene: PSMB9 were set to 26524591
Mendeliome v1.145 PSMB9 Zornitza Stark Mode of inheritance for gene: PSMB9 was changed from Other to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.144 PSMB9 Zornitza Stark Classified gene: PSMB9 as Green List (high evidence)
Mendeliome v1.144 PSMB9 Zornitza Stark Gene: psmb9 has been classified as Green List (High Evidence).
Mendeliome v1.143 PSMB9 Zornitza Stark edited their review of gene: PSMB9: Added comment: Two additional individuals with neonatal onset autoinflammatory syndrome and a mouse model. De novo recurrent missense G156D.; Changed rating: GREEN; Changed publications: 26524591, 34819510; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autoinflammatory Disorders v0.156 PSMB9 Zornitza Stark Publications for gene: PSMB9 were set to 26524591
Autoinflammatory Disorders v0.155 PSMB9 Zornitza Stark Mode of pathogenicity for gene: PSMB9 was changed from to Other
Autoinflammatory Disorders v0.154 PSMB9 Zornitza Stark Mode of inheritance for gene: PSMB9 was changed from Other to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autoinflammatory Disorders v0.153 PSMB9 Zornitza Stark Classified gene: PSMB9 as Green List (high evidence)
Autoinflammatory Disorders v0.153 PSMB9 Zornitza Stark Gene: psmb9 has been classified as Green List (High Evidence).
Mendeliome v1.143 HCK Zornitza Stark Marked gene: HCK as ready
Mendeliome v1.143 HCK Zornitza Stark Gene: hck has been classified as Amber List (Moderate Evidence).
Mendeliome v1.143 HCK Zornitza Stark Classified gene: HCK as Amber List (moderate evidence)
Mendeliome v1.143 HCK Zornitza Stark Gene: hck has been classified as Amber List (Moderate Evidence).
Mendeliome v1.142 HCK Zornitza Stark gene: HCK was added
gene: HCK was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HCK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HCK were set to 34536415
Phenotypes for gene: HCK were set to Autoinflammatory syndrome, MONDO:0019751, HCK-related
Mode of pathogenicity for gene: HCK was set to Other
Review for gene: HCK was set to AMBER
Added comment: Single patient with supportive functional data.
Sources: Literature
Autoinflammatory Disorders v0.152 HCK Zornitza Stark Marked gene: HCK as ready
Autoinflammatory Disorders v0.152 HCK Zornitza Stark Gene: hck has been classified as Amber List (Moderate Evidence).
Autoinflammatory Disorders v0.152 HCK Zornitza Stark Phenotypes for gene: HCK were changed from Autoinflammation to Autoinflammatory syndrome, MONDO:0019751, HCK-related
Autoinflammatory Disorders v0.151 HCK Zornitza Stark Classified gene: HCK as Amber List (moderate evidence)
Autoinflammatory Disorders v0.151 HCK Zornitza Stark Gene: hck has been classified as Amber List (Moderate Evidence).
Mendeliome v1.141 TBX21 Zornitza Stark Classified gene: TBX21 as Amber List (moderate evidence)
Mendeliome v1.141 TBX21 Zornitza Stark Gene: tbx21 has been classified as Amber List (Moderate Evidence).
Defects of intrinsic and innate immunity v0.114 TBX21 Zornitza Stark Marked gene: TBX21 as ready
Defects of intrinsic and innate immunity v0.114 TBX21 Zornitza Stark Gene: tbx21 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.140 TBX21 Zornitza Stark changed review comment from: Single individual reported with disseminated disease following BCG vaccination, who subsequently developed severe persistent reactive airway disease and eosinophilia that responded to steroid treatment. Homozygous variant identified.

Association with asthma and nasal polyps pertains to promoter SNPs.; to: Single individual reported with disseminated disease following BCG vaccination, who subsequently developed severe persistent reactive airway disease and eosinophilia that responded to steroid treatment. Homozygous variant identified. Functional data.

Association with asthma and nasal polyps pertains to promoter SNPs.
Mendeliome v1.140 TBX21 Zornitza Stark edited their review of gene: TBX21: Changed rating: AMBER
Defects of intrinsic and innate immunity v0.114 TBX21 Zornitza Stark Classified gene: TBX21 as Amber List (moderate evidence)
Defects of intrinsic and innate immunity v0.114 TBX21 Zornitza Stark Gene: tbx21 has been classified as Amber List (Moderate Evidence).
Defects of intrinsic and innate immunity v0.113 TBX21 Zornitza Stark Phenotypes for gene: TBX21 were changed from Susceptibility to mycobacterial disease to Immunodeficiency 88, MIM# 619630; Susceptibility to mycobacterial disease
Fetal anomalies v1.44 TTC25 Zornitza Stark Publications for gene: TTC25 were set to 27486780
Fetal anomalies v1.43 TTC25 Zornitza Stark Classified gene: TTC25 as Green List (high evidence)
Fetal anomalies v1.43 TTC25 Zornitza Stark Gene: ttc25 has been classified as Green List (High Evidence).
Fetal anomalies v1.42 TTC25 Zornitza Stark edited their review of gene: TTC25: Added comment: At least 7 families reported now.; Changed rating: GREEN; Changed publications: 27486780, 31765523, 33715250, 33746037, 34215651
Heterotaxy v1.20 TTC25 Zornitza Stark Publications for gene: TTC25 were set to 27486780
Heterotaxy v1.19 TTC25 Zornitza Stark Classified gene: TTC25 as Green List (high evidence)
Heterotaxy v1.19 TTC25 Zornitza Stark Gene: ttc25 has been classified as Green List (High Evidence).
Heterotaxy v1.18 TTC25 Zornitza Stark edited their review of gene: TTC25: Added comment: At least 7 families reported now.; Changed rating: GREEN; Changed publications: 27486780, 31765523, 33715250, 33746037, 34215651
Ciliary Dyskinesia v1.20 TTC25 Zornitza Stark Publications for gene: TTC25 were set to 27486780
Ciliary Dyskinesia v1.19 TTC25 Zornitza Stark Classified gene: TTC25 as Green List (high evidence)
Ciliary Dyskinesia v1.19 TTC25 Zornitza Stark Gene: ttc25 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v1.18 TTC25 Zornitza Stark reviewed gene: TTC25: Rating: GREEN; Mode of pathogenicity: None; Publications: 27486780, 31765523, 33715250, 33746037, 34215651; Phenotypes: Ciliary dyskinesia, primary, 35, OMIM:617092; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.140 TTC25 Zornitza Stark Publications for gene: TTC25 were set to 27486780
Mendeliome v1.139 TTC25 Zornitza Stark Classified gene: TTC25 as Green List (high evidence)
Mendeliome v1.139 TTC25 Zornitza Stark Gene: ttc25 has been classified as Green List (High Evidence).
Cerebral Palsy v1.29 ADAT3 Clare van Eyk changed review comment from: Homozygous founder variant in ADAT3 (p.V144M) reported in two cohort studies of children diagnosed with cerebral palsy (PMIDs 35076175; 34321325).

Tone abnormalities, including spasticity and hypotonia, are frequently reported in individuals from additional families with the same variant (PMID 26842963, 11 families, variant also called V128M) and are variable within families. Intellectual disability/developmental delay are always present and the majority with strabismus and growth failure.
Sources: Literature; to: Homozygous founder variant in ADAT3 (p.V144M) reported in two cohort studies of children diagnosed with cerebral palsy (PMIDs 35076175; 34321325).

Tone abnormalities, including spasticity and hypotonia, are frequently reported in individuals from additional families with the same variant (PMID 26842963, 11 families, variant also called V128M) and are variable within families. Intellectual disability/developmental delay are always present and the majority with strabismus and growth failure.
Sources: Literature
Cerebral Palsy v1.29 ADAT3 Clare van Eyk gene: ADAT3 was added
gene: ADAT3 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ADAT3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAT3 were set to 35076175; 34321325
Phenotypes for gene: ADAT3 were set to MIM #615286
Review for gene: ADAT3 was set to GREEN
Added comment: Homozygous founder variant in ADAT3 (p.V144M) reported in two cohort studies of children diagnosed with cerebral palsy (PMIDs 35076175; 34321325).

Tone abnormalities, including spasticity and hypotonia, are frequently reported in individuals from additional families with the same variant (PMID 26842963, 11 families, variant also called V128M) and are variable within families. Intellectual disability/developmental delay are always present and the majority with strabismus and growth failure.
Sources: Literature
Prepair 1000+ v0.40 TTN Crystle Lee reviewed gene: TTN: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardiomyopathy, dilated, 1G (MIM#604145), Cardiomyopathy, familial hypertrophic, 9 (MIM#613765), Muscular dystrophy, limb-girdle, autosomal recessive 10 (MIM#608807), Myopathy, myofibrillar, 9, with early respiratory failure (MIM#603689), Salih myopathy (MIM#611705), Tibial muscular dystrophy, tardive (MIM#600334); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Prepair 1000+ v0.40 VWF Crystle Lee reviewed gene: VWF: Rating: AMBER; Mode of pathogenicity: Other; Publications: ; Phenotypes: von Willebrand disease, type 1 (MIM#193400), von Willebrand disease, type 3 (MIM#277480), von Willebrand disease, types 2A, 2B, 2M, and 2N (MIM#613554); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Prepair 1000+ v0.40 SHOX Crystle Lee reviewed gene: SHOX: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Langer mesomelic dysplasia (MIM#249700), Leri-Weill dyschondrosteosis (MIM#127300), Short stature, idiopathic familial (MIM#300582); Mode of inheritance: Other
Prepair 1000+ v0.40 EFNB1 Crystle Lee reviewed gene: EFNB1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Craniofrontonasal dysplasia (MIM#304110); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v0.40 VPS11 Crystle Lee reviewed gene: VPS11: Rating: GREEN; Mode of pathogenicity: None; Publications: 27120463, 26307567, 27473128; Phenotypes: Leukodystrophy, hypomyelinating, 12 (MIM#616683); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.40 TNFRSF13B Crystle Lee reviewed gene: TNFRSF13B: Rating: RED; Mode of pathogenicity: None; Publications: 31681265; Phenotypes: Immunodeficiency, common variable, 2 (MIM#240500); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Prepair 1000+ v0.40 RPL10 Crystle Lee reviewed gene: RPL10: Rating: AMBER; Mode of pathogenicity: None; Publications: 25316788, 26290468, 25846674, 29066376; Phenotypes: Intellectual developmental disorder, X-linked, syndromic, 35, MIM300998; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v0.40 SERPINA1 Crystle Lee reviewed gene: SERPINA1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Emphysema due to AAT deficiency (MIM#613490), Emphysema-cirrhosis, due to AAT deficiency (MIM#613490), Hemorrhagic diathesis due to antithrombin Pittsburgh (MIM#613490); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.40 TRAC Crystle Lee reviewed gene: TRAC: Rating: RED; Mode of pathogenicity: None; Publications: 33909184, 21206088; Phenotypes: Immunodeficiency 7, TCR-alpha/beta deficient (MIM#615387); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.40 OCA2 Crystle Lee reviewed gene: OCA2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Albinism, brown oculocutaneous (MIM#203200), Albinism, oculocutaneous, type II (MIM#203200); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.40 F8 Crystle Lee reviewed gene: F8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Hemophilia A (MIM#306700); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Alternating Hemiplegia and Hemiplegic Migraine v0.53 CLDN5 Hazel Phillimore changed review comment from: PMID: 35714222; Hashimoto, Y. et al. (2022): Two unrelated cases (early-onset) with alternating hemiplegia with microcephaly were shown to have the same de novo variant, NM_001363066.2:c.178G>A, p.(Gly60Arg).
One with Jewish / Tunisian ancestry: Onset was at 8 months, three episodes of febrile tonic-clonic 1 seizures of the four limbs, with eye rolling, loss of consciousness, transient left and right post-2 ictal hemiparesis and vomiting.
The other with Asian / European ancestry: Onset was at 30 months with three iterative episodes of febrile and non-febrile hemiplegia and loss of 18 consciousness. The recurrent episodes alternatively involved the left-and 19 right-hand side, then generalised and were followed by post ictal hemiparesis.
CT scans of both showed brain calcifications and aberrant blood flow patterns.
Transfected HEK cell lines with this variant, c178G>A, showed higher chloride ion permeability and lower sodium ion permeability of the blood brain barrier when compared to wildtype.
Sources: Literature; to: PMID: 35714222; Hashimoto, Y. et al. (2022): Two unrelated cases (early-onset) with alternating hemiplegia with microcephaly were shown to have the same de novo variant, NM_001363066.2:c.178G>A, p.(Gly60Arg).
One with Jewish / Tunisian ancestry: Onset was at 8 months, three episodes of febrile tonic-clonic 1 seizures of the four limbs, with eye rolling, loss of consciousness, transient left and right post-2 ictal hemiparesis and vomiting.
The other with Asian / European ancestry: Onset was at 30 months with three iterative episodes of febrile and non-febrile hemiplegia and loss of 18 consciousness. The recurrent episodes alternatively involved the left-and 19 right-hand side, then generalised and were followed by post ictal hemiparesis.
CT scans of both showed brain calcifications and aberrant blood flow patterns.
Transfected cell lines with this variant, c178G>A, showed higher chloride ion permeability and lower sodium ion permeability when compared to wildtype.
Sources: Literature
Alternating Hemiplegia and Hemiplegic Migraine v0.53 CLDN5 Hazel Phillimore changed review comment from: PMID: 35714222; Hashimoto, Y et al (2022): Two unrelated cases (early-onset) with alternating hemiplegia with microcephaly were shown to have the same de novo variant, c.178G>A, p.(Gly60Arg).
One with Jewish / Tunisian ancestry: Onset was at 8 months, three episodes of febrile tonic-clonic 1 seizures of the four limbs, with eye rolling, loss of consciousness, transient left and right post-2 ictal hemiparesis and vomiting.
The other with Asian / European ancestry: Onset was at 30 months with three iterative episodes of febrile and non-febrile hemiplegia and loss of 18 consciousness. The recurrent episodes alternatively involved the left-and 19 right-hand side, then generalised and were followed by post ictal hemiparesis.
CT scans of both showed brain calcifications and aberrant blood flow patterns.
Transfected HEK cell lines with this variant, c178G>A, showed higher chloride ion permeability and lower sodium ion permeability of the blood brain barrier when compared to wildtype.
Sources: Literature; to: PMID: 35714222; Hashimoto, Y. et al. (2022): Two unrelated cases (early-onset) with alternating hemiplegia with microcephaly were shown to have the same de novo variant, NM_001363066.2:c.178G>A, p.(Gly60Arg).
One with Jewish / Tunisian ancestry: Onset was at 8 months, three episodes of febrile tonic-clonic 1 seizures of the four limbs, with eye rolling, loss of consciousness, transient left and right post-2 ictal hemiparesis and vomiting.
The other with Asian / European ancestry: Onset was at 30 months with three iterative episodes of febrile and non-febrile hemiplegia and loss of 18 consciousness. The recurrent episodes alternatively involved the left-and 19 right-hand side, then generalised and were followed by post ictal hemiparesis.
CT scans of both showed brain calcifications and aberrant blood flow patterns.
Transfected HEK cell lines with this variant, c178G>A, showed higher chloride ion permeability and lower sodium ion permeability of the blood brain barrier when compared to wildtype.
Sources: Literature
Mendeliome v1.138 KITLG Dean Phelan reviewed gene: KITLG: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 35543077, 28504826, 19375057, 21368769; Phenotypes: deafness, heterochromia iridis, hypopigmentation of the skin, hyperpigmentation of the skin, Waardenburg syndrome,MONDO:0018094, KITLG-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.42 WNT7B Zornitza Stark Marked gene: WNT7B as ready
Fetal anomalies v1.42 WNT7B Zornitza Stark Gene: wnt7b has been classified as Green List (High Evidence).
Microcephaly v1.132 AUTS2 Elena Savva Marked gene: AUTS2 as ready
Microcephaly v1.132 AUTS2 Elena Savva Gene: auts2 has been classified as Green List (High Evidence).
Microcephaly v1.132 AUTS2 Elena Savva Classified gene: AUTS2 as Green List (high evidence)
Microcephaly v1.132 AUTS2 Elena Savva Gene: auts2 has been classified as Green List (High Evidence).
Microcephaly v1.131 AUTS2 Elena Savva gene: AUTS2 was added
gene: AUTS2 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: AUTS2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: AUTS2 were set to PMID: 35802027; 34573342
Phenotypes for gene: AUTS2 were set to Intellectual developmental disorder, autosomal dominant 26 MIM#615834
Review for gene: AUTS2 was set to GREEN
Added comment: PMID: 35802027 - human cerebral organoid model used to illustrate functionality of de novo missense variants.
Describes rat model who lacked a microcephaly presentation.
Proband has profound ID, microcephaly, epilepsy, cerebellar hypoplasia and dysmorphic features.

PMID: 34573342 - microcephaly as a feature in 3/5 patients in an internal cohort. Review of the literature found 65% freq of microcephaly (34/52 patients)
Sources: Literature
Skeletal dysplasia v0.177 NFATC2 Zornitza Stark Marked gene: NFATC2 as ready
Skeletal dysplasia v0.177 NFATC2 Zornitza Stark Gene: nfatc2 has been classified as Red List (Low Evidence).
Skeletal dysplasia v0.177 NFATC2 Zornitza Stark Classified gene: NFATC2 as Red List (low evidence)
Skeletal dysplasia v0.177 NFATC2 Zornitza Stark Gene: nfatc2 has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.140 KITLG Zornitza Stark Phenotypes for gene: KITLG were changed from Deafness, autosomal dominant 69, unilateral or asymmetric, MIM# 616697 to Waardenburg syndrome, MONDO:0018094, KITLG-related; Deafness, autosomal dominant 69, unilateral or asymmetric, MIM# 616697
Mendeliome v1.138 NFATC2 Zornitza Stark Marked gene: NFATC2 as ready
Mendeliome v1.138 NFATC2 Zornitza Stark Gene: nfatc2 has been classified as Red List (Low Evidence).
Deafness_IsolatedAndComplex v1.139 KITLG Zornitza Stark Mode of inheritance for gene: KITLG was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.138 KITLG Zornitza Stark Classified gene: KITLG as Green List (high evidence)
Deafness_IsolatedAndComplex v1.138 KITLG Zornitza Stark Gene: kitlg has been classified as Green List (High Evidence).
Mendeliome v1.138 NFATC2 Zornitza Stark Classified gene: NFATC2 as Red List (low evidence)
Mendeliome v1.138 NFATC2 Zornitza Stark Gene: nfatc2 has been classified as Red List (Low Evidence).
Arthrogryposis v0.349 NFATC2 Zornitza Stark Marked gene: NFATC2 as ready
Arthrogryposis v0.349 NFATC2 Zornitza Stark Gene: nfatc2 has been classified as Red List (Low Evidence).
Arthrogryposis v0.349 NFATC2 Zornitza Stark Classified gene: NFATC2 as Red List (low evidence)
Arthrogryposis v0.349 NFATC2 Zornitza Stark Gene: nfatc2 has been classified as Red List (Low Evidence).
Skeletal dysplasia v0.176 NFATC2 Paul De Fazio gene: NFATC2 was added
gene: NFATC2 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: NFATC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NFATC2 were set to 35789258
Phenotypes for gene: NFATC2 were set to Skeletal system disorder MONDO:0005172
Review for gene: NFATC2 was set to RED
gene: NFATC2 was marked as current diagnostic
Added comment: Patient born to consanguineous parents homozygous for a frameshift variant. No other (unaffected) members of the family were homozygous. Family history of recurrent childhood deaths.

After a healthy birth the patient developed painless decreased range of motion at 1.5yrs leading to difficulty with ambulation at 3yrs. Formal orthopedic assessment at age 15 years
demonstrated a neurodevelopmentally normal young man with marked bilateral fixed flexion contractures of knees, hips, and ankles. The main musculoskeletal findings were painless contractures of the large and small joints of the upper and lower limbs, osteochondromas, and osteopenia. Patient was diagnosed with B-cell lymphoma at age 18.

Patient CD8+ T-cells show impaired polyfunctionality, and the patient had an accumulation of non-functional memory CD4+ T-cells. TFH cell function was also impaired.
Sources: Literature
Alternating Hemiplegia and Hemiplegic Migraine v0.53 CLDN5 Zornitza Stark Marked gene: CLDN5 as ready
Alternating Hemiplegia and Hemiplegic Migraine v0.53 CLDN5 Zornitza Stark Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Alternating Hemiplegia and Hemiplegic Migraine v0.53 CLDN5 Zornitza Stark Phenotypes for gene: CLDN5 were changed from alternating hemiplegia with microcephaly to alternating hemiplegia, MONDO:0016210, CLDN5-related
Arthrogryposis v0.348 NFATC2 Paul De Fazio gene: NFATC2 was added
gene: NFATC2 was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: NFATC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NFATC2 were set to 35789258
Phenotypes for gene: NFATC2 were set to Skeletal system disorder MONDO:0005172
Review for gene: NFATC2 was set to RED
gene: NFATC2 was marked as current diagnostic
Added comment: Patient born to consanguineous parents homozygous for a frameshift variant. No other (unaffected) members of the family were homozygous. Family history of recurrent childhood deaths.

After a healthy birth the patient developed painless decreased range of motion at 1.5yrs leading to difficulty with ambulation at 3yrs. Formal orthopedic assessment at age 15 years
demonstrated a neurodevelopmentally normal young man with marked bilateral fixed flexion contractures of knees, hips, and ankles. The main musculoskeletal findings were painless contractures of the large and small joints of the upper and lower limbs, osteochondromas, and osteopenia. Patient was diagnosed with B-cell lymphoma at age 18.

Patient CD8+ T-cells show impaired polyfunctionality, and the patient had an accumulation of non-functional memory CD4+ T-cells. TFH cell function was also impaired.
Sources: Literature
Deafness_IsolatedAndComplex v1.137 KITLG Dean Phelan reviewed gene: KITLG: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 35543077, 28504826, 19375057, 21368769; Phenotypes: deafness, heterochromia iridis, hypopigmentation of the skin, hyperpigmentation of the skin, Waardenburg syndrome; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Alternating Hemiplegia and Hemiplegic Migraine v0.52 CLDN5 Zornitza Stark Classified gene: CLDN5 as Amber List (moderate evidence)
Alternating Hemiplegia and Hemiplegic Migraine v0.52 CLDN5 Zornitza Stark Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.137 NFATC2 Paul De Fazio gene: NFATC2 was added
gene: NFATC2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NFATC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NFATC2 were set to 35789258
Phenotypes for gene: NFATC2 were set to Skeletal system disorder MONDO:0005172
Review for gene: NFATC2 was set to RED
gene: NFATC2 was marked as current diagnostic
Added comment: Patient born to consanguineous parents homozygous for a frameshift variant. No other (unaffected) members of the family were homozygous. Family history of recurrent childhood deaths.

After a healthy birth the patient developed painless decreased range of motion at 1.5yrs leading to difficulty with ambulation at 3yrs. Formal orthopedic assessment at age 15 years
demonstrated a neurodevelopmentally normal young man with marked bilateral fixed flexion contractures of knees, hips, and ankles. The main musculoskeletal findings were painless contractures of the large and small joints of the upper and lower limbs, osteochondromas, and osteopenia. Patient was diagnosed with B-cell lymphoma at age 18.

Patient CD8+ T-cells show impaired polyfunctionality, and the patient had an accumulation of non-functional memory CD4+ T-cells. TFH cell function was also impaired.
Sources: Literature
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.302 CCDC155 Melanie Marty gene: CCDC155 was added
gene: CCDC155 was added to Primary Ovarian Insufficiency_Premature Ovarian Failure. Sources: Literature
Mode of inheritance for gene: CCDC155 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC155 were set to 35674372; 35708642; 29790874; 35587281
Phenotypes for gene: CCDC155 were set to Non-obstructive azoospermia; Premature ovarian insufficiency; Infertility disorder, MONDO:0005047, CCDC155-related
Review for gene: CCDC155 was set to GREEN
Added comment: Current HGNC name is KASH5

Summary: 4 families reported with non-obstructive azoospermia or premature ovarian insufficiency. Functional studies have been performed and mouse models recapitulate the phenotype.

PMID: 35674372 CNV and frameshift variants in KASH5 were identified in a non-obstructive azoospermia affected patient and in his infertile sister by whole-exome sequencing and CNV array. Kash5 knockout mouse displayed similar phenotypes, including a meiotic arrest at a zygotene-like stage and impaired pairing and synapsis.

PMID: 35708642 Hom splice identified in KASH5 in 2 sisters with premature ovarian insufficiency. In vitro studies found the variant disturbed the nuclear membrane localization of KASH5 and its binding with SUN1. Moreover, the Kash5 C-terminal deleted mice revealed defective meiotic homolog pairing and accelerated depletion of oocytes.

PMID: 29790874 2 brothers with non-obstructive azoospermia with hom missense in CCDC155

PMID: 35587281 2 siblings with hom missense in CCDC155 non-obstructive azoospermia and premature ovarian insufficiency.
Sources: Literature
Alternating Hemiplegia and Hemiplegic Migraine v0.51 CLDN5 Hazel Phillimore gene: CLDN5 was added
gene: CLDN5 was added to Alternating Hemiplegia and Hemiplegic Migraine. Sources: Literature
Mode of inheritance for gene: CLDN5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CLDN5 were set to PMID: 35714222
Phenotypes for gene: CLDN5 were set to alternating hemiplegia with microcephaly
Mode of pathogenicity for gene: CLDN5 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: CLDN5 was set to AMBER
Added comment: PMID: 35714222; Hashimoto, Y et al (2022): Two unrelated cases (early-onset) with alternating hemiplegia with microcephaly were shown to have the same de novo variant, c.178G>A, p.(Gly60Arg).
One with Jewish / Tunisian ancestry: Onset was at 8 months, three episodes of febrile tonic-clonic 1 seizures of the four limbs, with eye rolling, loss of consciousness, transient left and right post-2 ictal hemiparesis and vomiting.
The other with Asian / European ancestry: Onset was at 30 months with three iterative episodes of febrile and non-febrile hemiplegia and loss of 18 consciousness. The recurrent episodes alternatively involved the left-and 19 right-hand side, then generalised and were followed by post ictal hemiparesis.
CT scans of both showed brain calcifications and aberrant blood flow patterns.
Transfected HEK cell lines with this variant, c178G>A, showed higher chloride ion permeability and lower sodium ion permeability of the blood brain barrier when compared to wildtype.
Sources: Literature
Mendeliome v1.137 PIK3C2B Zornitza Stark Marked gene: PIK3C2B as ready
Mendeliome v1.137 PIK3C2B Zornitza Stark Gene: pik3c2b has been classified as Amber List (Moderate Evidence).
Mendeliome v1.137 PIK3C2B Zornitza Stark Classified gene: PIK3C2B as Amber List (moderate evidence)
Mendeliome v1.137 PIK3C2B Zornitza Stark Gene: pik3c2b has been classified as Amber List (Moderate Evidence).
Mendeliome v1.136 CCDC155 Zornitza Stark Marked gene: CCDC155 as ready
Mendeliome v1.136 CCDC155 Zornitza Stark Gene: ccdc155 has been classified as Green List (High Evidence).
Mendeliome v1.136 CCDC155 Zornitza Stark Phenotypes for gene: CCDC155 were changed from Non-obstructive azoospermia; Premature ovarian insufficiency to Non-obstructive azoospermia; Premature ovarian insufficiency; Infertility disorder, MONDO:0005047, CCDC155-related
Mendeliome v1.135 CCDC155 Zornitza Stark Classified gene: CCDC155 as Green List (high evidence)
Mendeliome v1.135 CCDC155 Zornitza Stark Gene: ccdc155 has been classified as Green List (High Evidence).
Mendeliome v1.134 PIK3C2B Krithika Murali gene: PIK3C2B was added
gene: PIK3C2B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PIK3C2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PIK3C2B were set to PMID:35786744
Phenotypes for gene: PIK3C2B were set to familial partial epilepsy - MONDO#0017704
Review for gene: PIK3C2B was set to AMBER
Added comment: No OMIM gene disease association.

Gozzelino et al.(2022) Brain - report enrichment of ultra-rare PIK3C2B variants in focal epilepsy cohorts, including one variant shown to be de novo (G1294Q). Segregation data not provided for all cases. The p.G1345S variant was inherited from an affected father. The p.K584* variant was inherited from an unaffected father suggesting incomplete penetrance. Functional studies supported a LoF mechanism and mouse model studies suggestive of mTORC1 pathway hyperactivation.
Sources: Literature
Mendeliome v1.134 CCDC155 Zornitza Stark Tag new gene name tag was added to gene: CCDC155.
Mendeliome v1.134 CCDC155 Melanie Marty gene: CCDC155 was added
gene: CCDC155 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CCDC155 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC155 were set to 35674372; 35708642; 29790874; 35587281
Phenotypes for gene: CCDC155 were set to Non-obstructive azoospermia; Premature ovarian insufficiency
Review for gene: CCDC155 was set to GREEN
Added comment: Current HGNC name is KASH5

Summary: 4 families reported with non-obstructive azoospermia or premature ovarian insufficiency. Functional studies have been performed and mouse models recapitulate the phenotype.

PMID: 35674372 CNV and frameshift variants in KASH5 were identified in a non-obstructive azoospermia affected patient and in his infertile sister by whole-exome sequencing and CNV array. Kash5 knockout mouse displayed similar phenotypes, including a meiotic arrest at a zygotene-like stage and impaired pairing and synapsis.

PMID: 35708642 Hom splice identified in KASH5 in 2 sisters with premature ovarian insufficiency. In vitro studies found the variant disturbed the nuclear membrane localization of KASH5 and its binding with SUN1. Moreover, the Kash5 C-terminal deleted mice revealed defective meiotic homolog pairing and accelerated depletion of oocytes.

PMID: 29790874 2 brothers with non-obstructive azoospermia with hom missense in CCDC155

35587281 2 siblings with hom missense in CCDC155 non-obstructive azoospermia and premature ovarian insufficiency.
Sources: Literature
Polydactyly v0.257 SLC30A7 Alison Yeung Classified gene: SLC30A7 as Amber List (moderate evidence)
Polydactyly v0.257 SLC30A7 Alison Yeung Gene: slc30a7 has been classified as Amber List (Moderate Evidence).
Polydactyly v0.257 SLC30A7 Alison Yeung Marked gene: SLC30A7 as ready
Polydactyly v0.257 SLC30A7 Alison Yeung Gene: slc30a7 has been classified as Amber List (Moderate Evidence).
Polydactyly v0.257 SLC30A7 Alison Yeung Classified gene: SLC30A7 as Amber List (moderate evidence)
Polydactyly v0.257 SLC30A7 Alison Yeung Gene: slc30a7 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.134 SLC30A7 Alison Yeung Marked gene: SLC30A7 as ready
Mendeliome v1.134 SLC30A7 Alison Yeung Gene: slc30a7 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.134 SLC30A7 Alison Yeung Classified gene: SLC30A7 as Amber List (moderate evidence)
Mendeliome v1.134 SLC30A7 Alison Yeung Gene: slc30a7 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1632 PIK3C2B Zornitza Stark Marked gene: PIK3C2B as ready
Genetic Epilepsy v0.1632 PIK3C2B Zornitza Stark Gene: pik3c2b has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1632 PIK3C2B Zornitza Stark Classified gene: PIK3C2B as Amber List (moderate evidence)
Genetic Epilepsy v0.1632 PIK3C2B Zornitza Stark Gene: pik3c2b has been classified as Amber List (Moderate Evidence).
Ciliopathies v1.32 SLC30A7 Alison Yeung Marked gene: SLC30A7 as ready
Ciliopathies v1.32 SLC30A7 Alison Yeung Gene: slc30a7 has been classified as Amber List (Moderate Evidence).
Ciliopathies v1.32 SLC30A7 Alison Yeung Classified gene: SLC30A7 as Amber List (moderate evidence)
Ciliopathies v1.32 SLC30A7 Alison Yeung Gene: slc30a7 has been classified as Amber List (Moderate Evidence).
Polydactyly v0.256 SLC30A7 Naomi Baker gene: SLC30A7 was added
gene: SLC30A7 was added to Polydactyly. Sources: Literature
Mode of inheritance for gene: SLC30A7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC30A7 were set to PMID: 35751429
Phenotypes for gene: SLC30A7 were set to Joubert syndrome (MONDO:0018772), SLC30A7-related
Review for gene: SLC30A7 was set to AMBER
Added comment: PMID: 35751429: Two individuals reported with de novo variants, one missense and one delins resulting in missense. The first individual is a female with history of unilateral postaxial polydactyly, classic molar tooth sign on MRI, macrocephaly, ataxia, ocular motor apraxia, neurodevelopmental delay, and precocious puberty. The second individual had bilateral postaxial polydactyly, molar tooth sign, macrocephaly, developmental delay, and an extra oral frenulum. No functional studies reported.
Sources: Literature
Joubert syndrome and other neurological ciliopathies v1.23 SLC30A7 Alison Yeung Marked gene: SLC30A7 as ready
Joubert syndrome and other neurological ciliopathies v1.23 SLC30A7 Alison Yeung Gene: slc30a7 has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v1.23 SLC30A7 Alison Yeung Classified gene: SLC30A7 as Amber List (moderate evidence)
Joubert syndrome and other neurological ciliopathies v1.23 SLC30A7 Alison Yeung Gene: slc30a7 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.130 WNK3 Zornitza Stark Marked gene: WNK3 as ready
Microcephaly v1.130 WNK3 Zornitza Stark Gene: wnk3 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.130 WNK3 Zornitza Stark Classified gene: WNK3 as Amber List (moderate evidence)
Microcephaly v1.130 WNK3 Zornitza Stark Gene: wnk3 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1631 PIK3C2B Krithika Murali gene: PIK3C2B was added
gene: PIK3C2B was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PIK3C2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PIK3C2B were set to PMID: 35786744
Phenotypes for gene: PIK3C2B were set to familial partial epilepsy - MONDO#0017704
Review for gene: PIK3C2B was set to AMBER
Added comment: No OMIM gene disease association.

Gozzelino et al.(2022) Brain - report enrichment of ultra-rare PIK3C2B variants in focal epilepsy cohorts, including one variant shown to be de novo (G1294Q). Segregation data not provided for all cases. The p.G1345S variant was inherited from an affected father. The p.K584* variant was inherited from an unaffected father suggesting incomplete penetrance. Functional studies supported a LoF mechanism and mouse model studies suggestive of mTORC1 pathway hyperactivation.
Sources: Literature
Genetic Epilepsy v0.1631 WNK3 Zornitza Stark Marked gene: WNK3 as ready
Genetic Epilepsy v0.1631 WNK3 Zornitza Stark Gene: wnk3 has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v0.116 Zornitza Stark removed gene:SLC30A7 from the panel
Genetic Epilepsy v0.1631 WNK3 Zornitza Stark Classified gene: WNK3 as Green List (high evidence)
Genetic Epilepsy v0.1631 WNK3 Zornitza Stark Gene: wnk3 has been classified as Green List (High Evidence).
Malignant Hyperthermia Susceptibility v1.6 ASPH Zornitza Stark Phenotypes for gene: ASPH were changed from Exertional heat illness; malignant hyperthermia susceptibility HP:0002047, ASPH-related to Exertional heat illness; malignant hyperthermia susceptibility, MONDO:0018493, ASPH-related
Mendeliome v1.133 ASPH Zornitza Stark Phenotypes for gene: ASPH were changed from Traboulsi syndrome , MIM#601552 to Traboulsi syndrome , MIM#601552; Exertional heat illness; malignant hyperthermia susceptibility, MONDO:0018493, ASPH-related
Rhabdomyolysis and Metabolic Myopathy v0.90 ASPH Zornitza Stark Marked gene: ASPH as ready
Rhabdomyolysis and Metabolic Myopathy v0.90 ASPH Zornitza Stark Gene: asph has been classified as Amber List (Moderate Evidence).
Mendeliome v1.132 ASPH Zornitza Stark Publications for gene: ASPH were set to 24768550; 30194805; 34018898
Mendeliome v1.131 ASPH Zornitza Stark Mode of inheritance for gene: ASPH was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rhabdomyolysis and Metabolic Myopathy v0.90 ASPH Zornitza Stark Phenotypes for gene: ASPH were changed from Exertional heat illness; malignant hyperthermia susceptibility to Exertional heat illness; malignant hyperthermia susceptibility, MONDO:0018493, ASPH-related
Peroxisomal Disorders v0.42 ACOX1 Alison Yeung Phenotypes for gene: ACOX1 were changed from Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470 to Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470
Rhabdomyolysis and Metabolic Myopathy v0.89 ASPH Zornitza Stark Classified gene: ASPH as Amber List (moderate evidence)
Rhabdomyolysis and Metabolic Myopathy v0.89 ASPH Zornitza Stark Gene: asph has been classified as Amber List (Moderate Evidence).
Peroxisomal Disorders v0.42 ACOX1 Alison Yeung Marked gene: ACOX1 as ready
Peroxisomal Disorders v0.42 ACOX1 Alison Yeung Gene: acox1 has been classified as Green List (High Evidence).
Peroxisomal Disorders v0.42 ACOX1 Alison Yeung Phenotypes for gene: ACOX1 were changed from Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470 to Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470
Peroxisomal Disorders v0.41 ACOX1 Alison Yeung Phenotypes for gene: ACOX1 were changed from Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470; Mitchell syndrome, MIM# 618960 to Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470
Malignant Hyperthermia Susceptibility v1.5 ASPH Zornitza Stark Marked gene: ASPH as ready
Malignant Hyperthermia Susceptibility v1.5 ASPH Zornitza Stark Gene: asph has been classified as Amber List (Moderate Evidence).
Malignant Hyperthermia Susceptibility v1.5 ASPH Zornitza Stark Phenotypes for gene: ASPH were changed from Exertional heat illness; malignant hyperthermia susceptibility to Exertional heat illness; malignant hyperthermia susceptibility HP:0002047, ASPH-related
Peroxisomal Disorders v0.41 ACOX1 Alison Yeung Phenotypes for gene: ACOX1 were changed from to Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470; Mitchell syndrome, MIM# 618960
Malignant Hyperthermia Susceptibility v1.4 ASPH Zornitza Stark Classified gene: ASPH as Amber List (moderate evidence)
Malignant Hyperthermia Susceptibility v1.4 ASPH Zornitza Stark Gene: asph has been classified as Amber List (Moderate Evidence).
Peroxisomal Disorders v0.40 ACOX1 Alison Yeung Mode of inheritance for gene: ACOX1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Peroxisomal Disorders v0.40 ACOX1 Alison Yeung Mode of inheritance for gene: ACOX1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.130 SLC30A7 Naomi Baker gene: SLC30A7 was added
gene: SLC30A7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC30A7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC30A7 were set to PMID: 35751429
Phenotypes for gene: SLC30A7 were set to Joubert syndrome (MONDO:0018772), SLC30A7-related
Review for gene: SLC30A7 was set to AMBER
Added comment: PMID: 35751429: Two individuals reported with de novo variants, one missense and one delins resulting in missense. The first individual is a female with history of unilateral postaxial polydactyly, classic molar tooth sign on MRI, macrocephaly, ataxia, ocular motor apraxia, neurodevelopmental delay, and precocious puberty. The second individual had bilateral postaxial polydactyly, molar tooth sign, macrocephaly, developmental delay, and an extra oral frenulum. No functional studies reported.
Sources: Literature
Regression v0.489 ACOX1 Alison Yeung Marked gene: ACOX1 as ready
Regression v0.489 ACOX1 Alison Yeung Gene: acox1 has been classified as Green List (High Evidence).
Regression v0.489 ACOX1 Alison Yeung Classified gene: ACOX1 as Green List (high evidence)
Regression v0.489 ACOX1 Alison Yeung Gene: acox1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4852 CHMP3 Zornitza Stark Marked gene: CHMP3 as ready
Intellectual disability syndromic and non-syndromic v0.4852 CHMP3 Zornitza Stark Gene: chmp3 has been classified as Amber List (Moderate Evidence).
Regression v0.488 ACOX1 Alison Yeung gene: ACOX1 was added
gene: ACOX1 was added to Regression. Sources: Literature
Mode of inheritance for gene: ACOX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ACOX1 were set to 32169171; 35715200
Phenotypes for gene: ACOX1 were set to Mitchell syndrome, MIM# 618960
Review for gene: ACOX1 was set to GREEN
Added comment: Mono-allelic variants (recurrent de novo missense, N237S) associated with Mitchell syndrome (MITCH): a progressive disorder characterised by episodic demyelination, sensorimotor polyneuropathy, and hearing loss. Bi-allelic variants cause a peroxisomal disorder characterised by neonatal hypotonia, seizures, apneic spells, delayed psychomotor development, and neurologic regression.
Sources: Literature
Macrocephaly_Megalencephaly v0.115 SLC30A7 Naomi Baker gene: SLC30A7 was added
gene: SLC30A7 was added to Macrocephaly_Megalencephaly. Sources: Literature
Mode of inheritance for gene: SLC30A7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC30A7 were set to PMID: 35751429
Phenotypes for gene: SLC30A7 were set to Joubert syndrome (MONDO:0018772), SLC30A7-related
Review for gene: SLC30A7 was set to AMBER
Added comment: PMID: 35751429: Two individuals reported with de novo variants, one missense and one delins resulting in missense. The first individual is a female with history of unilateral postaxial polydactyly, classic molar tooth sign on MRI, macrocephaly, ataxia, ocular motor apraxia, neurodevelopmental delay, and precocious puberty. The second individual had bilateral postaxial polydactyly, molar tooth sign, macrocephaly, developmental delay, and an extra oral frenulum. No functional studies reported.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4852 CHMP3 Zornitza Stark Classified gene: CHMP3 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.4852 CHMP3 Zornitza Stark Gene: chmp3 has been classified as Amber List (Moderate Evidence).
Regression v0.487 CHMP3 Zornitza Stark Marked gene: CHMP3 as ready
Regression v0.487 CHMP3 Zornitza Stark Gene: chmp3 has been classified as Amber List (Moderate Evidence).
Regression v0.487 CHMP3 Zornitza Stark Classified gene: CHMP3 as Amber List (moderate evidence)
Regression v0.487 CHMP3 Zornitza Stark Gene: chmp3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4851 PABPC1 Elena Savva Classified gene: PABPC1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4851 PABPC1 Elena Savva Gene: pabpc1 has been classified as Green List (High Evidence).
Mendeliome v1.130 ASPH Paul De Fazio reviewed gene: ASPH: Rating: AMBER; Mode of pathogenicity: None; Publications: 35697689; Phenotypes: Exertional heat illness, malignant hyperthermia susceptibility; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Genetic Epilepsy v0.1630 WNK3 Lucy Spencer gene: WNK3 was added
gene: WNK3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: WNK3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: WNK3 were set to 35678782
Phenotypes for gene: WNK3 were set to Neurodevelopmental disorder, WNK3-related (MONDO#0700092)
Review for gene: WNK3 was set to GREEN
Added comment: 6 maternally inherited hemizygous variants, 3 missense and 3 LOF. Seen in 14 individuals from 6 families. The variants cosegregated with disease in 3 families with multiple affected individuals. Phenotype described as intellectual disability, with the variable presence of seizures and structural brain defects. One family previously had a clinical diagnosis of X-linked Prieto syndrome.
Sources: Literature
Mendeliome v1.130 CHMP3 Zornitza Stark Marked gene: CHMP3 as ready
Mendeliome v1.130 CHMP3 Zornitza Stark Gene: chmp3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.130 CHMP3 Zornitza Stark Classified gene: CHMP3 as Amber List (moderate evidence)
Mendeliome v1.130 CHMP3 Zornitza Stark Gene: chmp3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4850 PABPC1 Elena Savva Classified gene: PABPC1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4850 PABPC1 Elena Savva Gene: pabpc1 has been classified as Green List (High Evidence).
Ciliopathies v1.31 SLC30A7 Naomi Baker gene: SLC30A7 was added
gene: SLC30A7 was added to Ciliopathies. Sources: Literature
Mode of inheritance for gene: SLC30A7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC30A7 were set to PMID: 35751429
Phenotypes for gene: SLC30A7 were set to Joubert syndrome (MONDO:0018772), SLC30A7-related
Review for gene: SLC30A7 was set to AMBER
Added comment: PMID: 35751429: Two individuals reported with de novo variants, one missense and one delins resulting in missense. The first individual is a female with history of unilateral postaxial polydactyly, classic molar tooth sign on MRI, macrocephaly, ataxia, ocular motor apraxia, neurodevelopmental delay, and precocious puberty. The second individual had bilateral postaxial polydactyly, molar tooth sign, macrocephaly, developmental delay, and an extra oral frenulum. No functional studies reported.
Sources: Literature
Hereditary Spastic Paraplegia - paediatric v1.39 CHMP3 Zornitza Stark Marked gene: CHMP3 as ready
Hereditary Spastic Paraplegia - paediatric v1.39 CHMP3 Zornitza Stark Gene: chmp3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4850 PABPC1 Elena Savva Classified gene: PABPC1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4850 PABPC1 Elena Savva Gene: pabpc1 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v1.39 CHMP3 Zornitza Stark Classified gene: CHMP3 as Amber List (moderate evidence)
Hereditary Spastic Paraplegia - paediatric v1.39 CHMP3 Zornitza Stark Gene: chmp3 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4849 PABPC1 Elena Savva Marked gene: PABPC1 as ready
Intellectual disability syndromic and non-syndromic v0.4849 PABPC1 Elena Savva Gene: pabpc1 has been classified as Red List (Low Evidence).
Mendeliome v1.129 PABPC1 Elena Savva Marked gene: PABPC1 as ready
Mendeliome v1.129 PABPC1 Elena Savva Gene: pabpc1 has been classified as Green List (High Evidence).
Mendeliome v1.129 PABPC1 Elena Savva Classified gene: PABPC1 as Green List (high evidence)
Mendeliome v1.129 PABPC1 Elena Savva Gene: pabpc1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4849 PABPC1 Elena Savva gene: PABPC1 was added
gene: PABPC1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PABPC1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PABPC1 were set to PMID: 35511136
Phenotypes for gene: PABPC1 were set to Neurodevelopmental disorder, PABPC1-related (MONDO#0700092)
Review for gene: PABPC1 was set to GREEN
Added comment: PMID: 35511136 - 4 probands with an overlapping phenotype of DD, expressive speech delay, and autistic features and heterozygous de novo variants that cluster in the PABP domain of PABPC1.
Electroporation of mouse embryo brains showed that Pabpc1 knockdown decreases the proliferation of neural progenitor cells. Wild-type Pabpc1 could rescue this disturbance, whereas 3 of the 4 variants did not.
Sources: Literature
Microcephaly v1.129 WNK3 Lucy Spencer gene: WNK3 was added
gene: WNK3 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: WNK3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: WNK3 were set to 35678782
Phenotypes for gene: WNK3 were set to Neurodevelopmental disorder, WNK3-related (MONDO#0700092)
Added comment: 6 individuals with microcephaly all at -2 to -2.4SD so leaving as amber for now. Individuals also had ID and other features
Sources: Literature
Mendeliome v1.128 PABPC1 Elena Savva gene: PABPC1 was added
gene: PABPC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PABPC1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PABPC1 were set to PMID: 35511136
Phenotypes for gene: PABPC1 were set to Neurodevelopmental disorder, PABPC1-related (MONDO#0700092)
Review for gene: PABPC1 was set to GREEN
Added comment: PMID: 35511136 - 4 probands with an overlapping phenotype of DD, expressive speech delay, and autistic features and heterozygous de novo variants that cluster in the PABP domain of PABPC1.
Electroporation of mouse embryo brains showed that Pabpc1 knockdown decreases the proliferation of neural progenitor cells. Wild-type Pabpc1 could rescue this disturbance, whereas 3 of the 4 variants did not.
Sources: Literature
Joubert syndrome and other neurological ciliopathies v1.22 SLC30A7 Naomi Baker gene: SLC30A7 was added
gene: SLC30A7 was added to Joubert syndrome and other neurological ciliopathies. Sources: Literature
Mode of inheritance for gene: SLC30A7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC30A7 were set to PMID: 35751429
Phenotypes for gene: SLC30A7 were set to Joubert syndrome (MONDO:0018772), SLC30A7-related
Review for gene: SLC30A7 was set to AMBER
Added comment: PMID: 35751429: Two individuals reported with de novo variants, one missense and one delins resulting in missense. The first individual is a female with history of unilateral postaxial polydactyly, classic molar tooth sign on MRI, macrocephaly, ataxia, ocular motor apraxia, neurodevelopmental delay, and precocious puberty. The second individual had bilateral postaxial polydactyly, molar tooth sign, macrocephaly, developmental delay, and an extra oral frenulum. No functional studies reported.
Sources: Literature
Leukodystrophy - paediatric v0.272 ACOX1 Alison Yeung Marked gene: ACOX1 as ready
Leukodystrophy - paediatric v0.272 ACOX1 Alison Yeung Gene: acox1 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.272 ACOX1 Alison Yeung Added comment: Comment on phenotypes: Mono-allelic variants (recurrent de novo missense, N237S) associated with Mitchell syndrome (MITCH): a progressive disorder characterised by episodic demyelination, sensorimotor polyneuropathy, and hearing loss. Bi-allelic variants cause a peroxisomal disorder characterised by neonatal hypotonia, seizures, apneic spells, delayed psychomotor development, and neurologic regression.
Leukodystrophy - paediatric v0.272 ACOX1 Alison Yeung Phenotypes for gene: ACOX1 were changed from Peroxisomal acyl-CoA oxidase deficiency 264470; General Leukodystrophy & Mitochondrial Leukoencephalopathy to Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470; Mitchell syndrome, MIM# 618960
Mendeliome v1.127 WNK3 Zornitza Stark Marked gene: WNK3 as ready
Mendeliome v1.127 WNK3 Zornitza Stark Gene: wnk3 has been classified as Green List (High Evidence).
Mendeliome v1.127 WNK3 Zornitza Stark reviewed gene: WNK3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.127 WNK3 Zornitza Stark Classified gene: WNK3 as Green List (high evidence)
Mendeliome v1.127 WNK3 Zornitza Stark Gene: wnk3 has been classified as Green List (High Evidence).
Mendeliome v1.126 CHMP3 Chern Lim gene: CHMP3 was added
gene: CHMP3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CHMP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHMP3 were set to PMID: 35710109
Phenotypes for gene: CHMP3 were set to Hereditary spastic paraplegia (MONDO:0019064), CHMP3-related
Review for gene: CHMP3 was set to AMBER
gene: CHMP3 was marked as current diagnostic
Added comment: PMID: 35710109
- Single large family with consanguinity, homozygous missense variant in 5 affected individuals with intellectual and progressive motor disabilities, seizures and spastic quadriplegia.
- Functional studies showed reduced CHMP3 protein in patient's fibroblasts, lenti-rescue study showed improved cellular phenotypes associated with impaired autophagy.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4848 WNK3 Zornitza Stark Marked gene: WNK3 as ready
Intellectual disability syndromic and non-syndromic v0.4848 WNK3 Zornitza Stark Gene: wnk3 has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.271 ACOX1 Alison Yeung Mode of inheritance for gene: ACOX1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rhabdomyolysis and Metabolic Myopathy v0.88 ASPH Paul De Fazio gene: ASPH was added
gene: ASPH was added to Rhabdomyolysis. Sources: Literature
Mode of inheritance for gene: ASPH was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ASPH were set to 35697689
Phenotypes for gene: ASPH were set to Exertional heat illness; malignant hyperthermia susceptibility
Review for gene: ASPH was set to AMBER
gene: ASPH was marked as current diagnostic
Added comment: In a study of 103 individuals (63 affected from 34 families, plus 40 sporadic cases) who had either a sentinel event of EHI or MH, or else a positive CHCT and a first degree releative with EHI/MH, and where RYR1 and CACNA1S Sanger sequencing was negative, the following variants in ASPH were identified in unrelated individuals:

- c.161T > C in 2 members of a family with myalgias exacerbated by heat/exercise. One had elevated CK. Both had positive CHCT. An unaffected sibling did not have the variant. 27 hets in gnomad v2 / 17 hets in gnomad v3.
- c.445G>C in a patient with MH, myalgias and muscle cramps worsened by heat and exercise. 4 hets in gnomad v2 / 3 hets in gnomad v3. Non-coding in the MANE transcript.
- c.263A > C in a patient with EHI, diagnosed as MHN by in vitro contracture test. Absent from gnomad but non-coding in the MANE transcript.
- c.605A > G in a patient with EHI, diagnosed as MHN by in vitro contracture test. 223 hets in gnomad v2 / 120 hets in gnomad v3; no homs. Non-coding in the MANE transcript.

A zebrafish model and cell line functional studies supported pathogenicity of the c.161T > C and c.263A > C variants.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4848 WNK3 Zornitza Stark Classified gene: WNK3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4848 WNK3 Zornitza Stark Gene: wnk3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4847 ACOX1 Alison Yeung Phenotypes for gene: ACOX1 were changed from Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470; Mitchell syndrome, MIM# 618960 to Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470; Mitchell syndrome, MIM# 618960
Regression v0.486 CHMP3 Chern Lim gene: CHMP3 was added
gene: CHMP3 was added to Regression. Sources: Literature
Mode of inheritance for gene: CHMP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHMP3 were set to PMID: 35710109
Phenotypes for gene: CHMP3 were set to Hereditary spastic paraplegia (MONDO:0019064), CHMP3-related
Review for gene: CHMP3 was set to AMBER
gene: CHMP3 was marked as current diagnostic
Added comment: PMID: 35710109
- Single large family with consanguinity, homozygous missense variant in 5 affected individuals with intellectual and progressive motor disabilities, seizures and spastic quadriplegia.
- Functional studies showed reduced CHMP3 protein in patient's fibroblasts, lenti-rescue study showed improved cellular phenotypes associated with impaired autophagy.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4847 ACOX1 Alison Yeung Phenotypes for gene: ACOX1 were changed from Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470; Mitchell syndrome, MIM# 618960 to Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470; Mitchell syndrome, MIM# 618960
Intellectual disability syndromic and non-syndromic v0.4846 ACOX1 Alison Yeung Phenotypes for gene: ACOX1 were changed from Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470; Mitchell syndrome, MIM# 618960 to Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470; Mitchell syndrome, MIM# 618960
Intellectual disability syndromic and non-syndromic v0.4846 CHMP3 Chern Lim gene: CHMP3 was added
gene: CHMP3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: CHMP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHMP3 were set to PMID: 35710109
Phenotypes for gene: CHMP3 were set to Hereditary spastic paraplegia (MONDO:0019064), CHMP3-related
Review for gene: CHMP3 was set to AMBER
gene: CHMP3 was marked as current diagnostic
Added comment: PMID: 35710109
- Single large family with consanguinity, homozygous missense variant in 5 affected individuals with intellectual and progressive motor disabilities, seizures and spastic quadriplegia.
- Functional studies showed reduced CHMP3 protein in patient's fibroblasts, lenti-rescue study showed improved cellular phenotypes associated with impaired autophagy.
Sources: Literature
Mendeliome v1.126 WNK3 Lucy Spencer gene: WNK3 was added
gene: WNK3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WNK3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: WNK3 were set to 35678782
Phenotypes for gene: WNK3 were set to Neurodevelopmental disorder, WNK3-related (MONDO#0700092)
Added comment: 6 maternally inherited hemizygous variants, 3 missense, 2 canonical splice, and a nonsense. Seen in 14 individuals from 6 families, all 14 are male who inherited hemizygous variants from their unaffected heterozygous mothers. The variants cosegregated with disease in 3 families with multiple affected individuals. All 14 patients have ID, 11 have speech delay, 10 have facial abnormalities, 5 have seizures, 6 with microcephaly and 7 with anomalies in brain imaging.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4846 ACOX1 Alison Yeung Publications for gene: ACOX1 were set to 32169171; 17458872
Malignant Hyperthermia Susceptibility v1.3 ASPH Paul De Fazio gene: ASPH was added
gene: ASPH was added to Malignant Hyperthermia Susceptibility. Sources: Literature
Mode of inheritance for gene: ASPH was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ASPH were set to 35697689
Phenotypes for gene: ASPH were set to Exertional heat illness; malignant hyperthermia susceptibility
Review for gene: ASPH was set to AMBER
gene: ASPH was marked as current diagnostic
Added comment: In a study of 103 individuals (63 affected from 34 families, plus 40 sporadic cases) who had either a sentinel event of EHI or MH, or else a positive CHCT and a first degree releative with EHI/MH, and where RYR1 and CACNA1S Sanger sequencing was negative, the following variants in ASPH were identified in unrelated individuals:

- c.161T > C in 2 members of a family with myalgias exacerbated by heat/exercise. One had elevated CK. Both had positive CHCT. An unaffected sibling did not have the variant. 27 hets in gnomad v2 / 17 hets in gnomad v3.
- c.445G>C in a patient with MH, myalgias and muscle cramps worsened by heat and exercise. 4 hets in gnomad v2 / 3 hets in gnomad v3. Non-coding in the MANE transcript.
- c.263A > C in a patient with EHI, diagnosed as MHN by in vitro contracture test. Absent from gnomad but non-coding in the MANE transcript.
- c.605A > G in a patient with EHI, diagnosed as MHN by in vitro contracture test. 223 hets in gnomad v2 / 120 hets in gnomad v3; no homs. Non-coding in the MANE transcript.

A zebrafish model and cell line functional studies supported pathogenicity of the c.161T > C and c.263A > C variants.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4845 ACOX1 Alison Yeung Phenotypes for gene: ACOX1 were changed from to Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470; Mitchell syndrome, MIM# 618960
Intellectual disability syndromic and non-syndromic v0.4845 ACOX1 Alison Yeung Marked gene: ACOX1 as ready
Intellectual disability syndromic and non-syndromic v0.4845 ACOX1 Alison Yeung Gene: acox1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4845 ACOX1 Alison Yeung Publications for gene: ACOX1 were set to
Hereditary Spastic Paraplegia - paediatric v1.38 CHMP3 Chern Lim gene: CHMP3 was added
gene: CHMP3 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Literature
Mode of inheritance for gene: CHMP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHMP3 were set to PMID: 35710109
Phenotypes for gene: CHMP3 were set to Hereditary spastic paraplegia (MONDO:0019064), CHMP3-related
Review for gene: CHMP3 was set to AMBER
gene: CHMP3 was marked as current diagnostic
Added comment: PMID: 35710109
- Single large family with consanguinity, homozygous missense variant in 5 affected individuals with intellectual and progressive motor disabilities, seizures and spastic quadriplegia.
- Functional studies showed reduced CHMP3 protein in patient's fibroblasts, lenti-rescue study showed improved cellular phenotypes associated with impaired autophagy.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4844 ACOX1 Alison Yeung Mode of inheritance for gene: ACOX1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.126 WNT7B Zornitza Stark Marked gene: WNT7B as ready
Mendeliome v1.126 WNT7B Zornitza Stark Gene: wnt7b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4843 ACOX1 Alison Yeung reviewed gene: ACOX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32169171, 17458872; Phenotypes: Peroxisomal acyl-CoA oxidase deficiency, MIM# 264470, Mitchell syndrome, MIM# 618960; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.126 WNT7B Zornitza Stark Classified gene: WNT7B as Green List (high evidence)
Mendeliome v1.126 WNT7B Zornitza Stark Gene: wnt7b has been classified as Green List (High Evidence).
Mendeliome v1.125 WNT7B Zornitza Stark gene: WNT7B was added
gene: WNT7B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WNT7B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WNT7B were set to 35790350
Phenotypes for gene: WNT7B were set to Pulmonary hypoplasia, Diaphragmatic anomalies, Anophthalmia/microphthalmia and Cardiac defects syndrome; Multiple congenital anomalies/dysmorphic features syndrome MONDO:0043005, WNT7B-related
Review for gene: WNT7B was set to GREEN
Added comment: Three families reported with fetuses with multiple congenital anomalies and bi-allelic LoF variants. Two of the families had at the same variant. Supportive zebrafish model.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4843 WNK3 Lucy Spencer gene: WNK3 was added
gene: WNK3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: WNK3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: WNK3 were set to 35678782
Phenotypes for gene: WNK3 were set to Neurodevelopmental disorder, WNK3-related (MONDO#0700092)
Review for gene: WNK3 was set to GREEN
Added comment: 6 maternally inherited hemizygous variants, 3 missense, 2 canonical splice, and a nonsense. Seen in 14 individuals from 6 families, all 14 are male who inherited hemizygous variants from their unaffected heterozygous mothers. The variants cosegregated with disease in 3 families with multiple affected individuals. All 14 patients have ID, 11 have speech delay, 10 have facial abnormalities, 5 have seizures, 6 with microcephaly and 7 with anomalies in brain imaging.
Sources: Literature
Anophthalmia_Microphthalmia_Coloboma v1.24 WNT7B Zornitza Stark Marked gene: WNT7B as ready
Anophthalmia_Microphthalmia_Coloboma v1.24 WNT7B Zornitza Stark Gene: wnt7b has been classified as Amber List (Moderate Evidence).
Anophthalmia_Microphthalmia_Coloboma v1.24 WNT7B Zornitza Stark Classified gene: WNT7B as Amber List (moderate evidence)
Anophthalmia_Microphthalmia_Coloboma v1.24 WNT7B Zornitza Stark Gene: wnt7b has been classified as Amber List (Moderate Evidence).
Anophthalmia_Microphthalmia_Coloboma v1.23 WNT7B Zornitza Stark gene: WNT7B was added
gene: WNT7B was added to Anophthalmia_Microphthalmia_Coloboma. Sources: Literature
Mode of inheritance for gene: WNT7B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WNT7B were set to 35790350
Phenotypes for gene: WNT7B were set to Pulmonary hypoplasia, Diaphragmatic anomalies, Anophthalmia/microphthalmia and Cardiac defects syndrome; Multiple congenital anomalies/dysmorphic features syndrome MONDO:0043005, WNT7B-related
Review for gene: WNT7B was set to AMBER
Added comment: Three families reported with fetuses with multiple congenital anomalies and bi-allelic LoF variants. Two of the families had at the same variant. Supportive zebrafish model. Uncertain if all had anophthalmia/microphthalmia.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4843 MAL Zornitza Stark Marked gene: MAL as ready
Intellectual disability syndromic and non-syndromic v0.4843 MAL Zornitza Stark Gene: mal has been classified as Amber List (Moderate Evidence).
Mendeliome v1.124 TMEM63C Elena Savva Classified gene: TMEM63C as Green List (high evidence)
Mendeliome v1.124 TMEM63C Elena Savva Gene: tmem63c has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4843 TMEM63C Elena Savva Classified gene: TMEM63C as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4843 TMEM63C Elena Savva Gene: tmem63c has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4843 MAL Zornitza Stark Classified gene: MAL as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.4843 MAL Zornitza Stark Gene: mal has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4842 TMEM63C Elena Savva Classified gene: TMEM63C as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4842 TMEM63C Elena Savva Gene: tmem63c has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4842 TMEM63C Elena Savva Classified gene: TMEM63C as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4842 TMEM63C Elena Savva Gene: tmem63c has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v1.38 TMEM63C Elena Savva Classified gene: TMEM63C as Green List (high evidence)
Hereditary Spastic Paraplegia - paediatric v1.38 TMEM63C Elena Savva Gene: tmem63c has been classified as Green List (High Evidence).
Congenital diaphragmatic hernia v1.8 WNT7B Zornitza Stark Marked gene: WNT7B as ready
Congenital diaphragmatic hernia v1.8 WNT7B Zornitza Stark Gene: wnt7b has been classified as Green List (High Evidence).
Congenital diaphragmatic hernia v1.8 WNT7B Zornitza Stark Classified gene: WNT7B as Green List (high evidence)
Congenital diaphragmatic hernia v1.8 WNT7B Zornitza Stark Gene: wnt7b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4841 TMEM63C Elena Savva Marked gene: TMEM63C as ready
Intellectual disability syndromic and non-syndromic v0.4841 TMEM63C Elena Savva Gene: tmem63c has been classified as Red List (Low Evidence).
Hereditary Spastic Paraplegia - paediatric v1.37 TMEM63C Elena Savva Classified gene: TMEM63C as Green List (high evidence)
Hereditary Spastic Paraplegia - paediatric v1.37 TMEM63C Elena Savva Gene: tmem63c has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v1.36 TMEM63C Elena Savva Marked gene: TMEM63C as ready
Hereditary Spastic Paraplegia - paediatric v1.36 TMEM63C Elena Savva Gene: tmem63c has been classified as Red List (Low Evidence).
Mendeliome v1.123 TMEM63C Elena Savva gene: TMEM63C was added
gene: TMEM63C was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TMEM63C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM63C were set to PMID: 35718349
Phenotypes for gene: TMEM63C were set to Hereditary spastic paraplegia, MONDO:0019064, TMEM63C-related
Review for gene: TMEM63C was set to GREEN
Added comment: PMID: 35718349 - Four NMD PTCs observed in at least 3 unrelated patients. Two segregated strongly in highly consanguineous families.
Common clinical details include mild ID, spastic paraplegia, hypereflexia, spasticity, delayed motor development. Single patient was microcephalic
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4841 TMEM63C Elena Savva gene: TMEM63C was added
gene: TMEM63C was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: TMEM63C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM63C were set to PMID: 35718349
Phenotypes for gene: TMEM63C were set to Hereditary spastic paraplegia, MONDO:0019064, TMEM63C-related
Review for gene: TMEM63C was set to GREEN
Added comment: PMID: 35718349 - Four NMD PTCs observed in at least 3 unrelated patients. Two segregated strongly in highly consanguineous families.
Common clinical details include mild ID, spastic paraplegia, hypereflexia, spasticity, delayed motor development.
Sources: Literature
Hereditary Spastic Paraplegia - paediatric v1.36 TMEM63C Elena Savva gene: TMEM63C was added
gene: TMEM63C was added to Hereditary Spastic Paraplegia - paediatric. Sources: Literature
Mode of inheritance for gene: TMEM63C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM63C were set to PMID: 35718349
Phenotypes for gene: TMEM63C were set to Hereditary spastic paraplegia, MONDO:0019064, TMEM63C-related
Review for gene: TMEM63C was set to GREEN
Added comment: PMID: 35718349 - Four NMD PTCs observed in at least 3 unrelated patients. Two segregated strongly in highly consanguineous families.
Common clinical details include mild ID, spastic paraplegia, hypereflexia, spasticity, delayed motor development.
Sources: Literature
Congenital diaphragmatic hernia v1.7 WNT7B Zornitza Stark gene: WNT7B was added
gene: WNT7B was added to Congenital diaphragmatic hernia. Sources: Literature
Mode of inheritance for gene: WNT7B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WNT7B were set to 35790350
Phenotypes for gene: WNT7B were set to Pulmonary hypoplasia, Diaphragmatic anomalies, Anophthalmia/microphthalmia and Cardiac defects syndrome; Multiple congenital anomalies/dysmorphic features syndrome MONDO:0043005, WNT7B-related
Review for gene: WNT7B was set to GREEN
Added comment: Three families reported with fetuses with multiple congenital anomalies and bi-allelic LoF variants. Two of the families had at the same variant. Supportive zebrafish model.
Sources: Literature
Fetal anomalies v1.42 WNT7B Zornitza Stark Classified gene: WNT7B as Green List (high evidence)
Fetal anomalies v1.42 WNT7B Zornitza Stark Gene: wnt7b has been classified as Green List (High Evidence).
Fetal anomalies v1.41 WNT7B Zornitza Stark gene: WNT7B was added
gene: WNT7B was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: WNT7B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WNT7B were set to 35790350
Phenotypes for gene: WNT7B were set to Pulmonary hypoplasia, Diaphragmatic anomalies, Anophthalmia/microphthalmia and Cardiac defects syndrome; Multiple congenital anomalies/dysmorphic features syndrome MONDO:0043005, WNT7B-related
Review for gene: WNT7B was set to GREEN
Added comment: Three families reported with fetuses with multiple congenital anomalies and bi-allelic LoF variants. Two of the families had at the same variant. Supportive zebrafish model.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4840 MAL Zornitza Stark gene: MAL was added
gene: MAL was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: MAL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAL were set to 35217805
Phenotypes for gene: MAL were set to Leukodystrophy MONDO:0019046, MAL-related
Review for gene: MAL was set to AMBER
Added comment: Single family with two affected siblings reported, with homozygous missense variant, some functional data.
Sources: Literature
Mendeliome v1.122 MAL Zornitza Stark Marked gene: MAL as ready
Mendeliome v1.122 MAL Zornitza Stark Gene: mal has been classified as Amber List (Moderate Evidence).
Mendeliome v1.122 MAL Zornitza Stark Classified gene: MAL as Amber List (moderate evidence)
Mendeliome v1.122 MAL Zornitza Stark Gene: mal has been classified as Amber List (Moderate Evidence).
Mendeliome v1.121 MAL Zornitza Stark gene: MAL was added
gene: MAL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MAL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAL were set to 35217805
Phenotypes for gene: MAL were set to Leukodystrophy MONDO:0019046, MAL-related
Review for gene: MAL was set to AMBER
Added comment: Single family with two affected siblings reported, with homozygous missense variant, some functional data.
Sources: Literature
Leukodystrophy - paediatric v0.270 MAL Zornitza Stark Marked gene: MAL as ready
Leukodystrophy - paediatric v0.270 MAL Zornitza Stark Gene: mal has been classified as Amber List (Moderate Evidence).
Leukodystrophy - paediatric v0.270 MAL Zornitza Stark Classified gene: MAL as Amber List (moderate evidence)
Leukodystrophy - paediatric v0.270 MAL Zornitza Stark Gene: mal has been classified as Amber List (Moderate Evidence).
Leukodystrophy - paediatric v0.269 MAL Zornitza Stark gene: MAL was added
gene: MAL was added to Leukodystrophy - paediatric. Sources: Literature
Mode of inheritance for gene: MAL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAL were set to 35217805
Phenotypes for gene: MAL were set to Leukodystrophy MONDO:0019046, MAL-related
Review for gene: MAL was set to AMBER
Added comment: Single family with two affected siblings reported, with homozygous missense variant, some functional data.
Sources: Literature
Leukodystrophy - paediatric v0.268 MAK Zornitza Stark Marked gene: MAK as ready
Leukodystrophy - paediatric v0.268 MAK Zornitza Stark Gene: mak has been classified as Amber List (Moderate Evidence).
Leukodystrophy - paediatric v0.268 MAK Zornitza Stark Classified gene: MAK as Amber List (moderate evidence)
Leukodystrophy - paediatric v0.268 MAK Zornitza Stark Gene: mak has been classified as Amber List (Moderate Evidence).
Leukodystrophy - paediatric v0.267 MAK Zornitza Stark gene: MAK was added
gene: MAK was added to Leukodystrophy - paediatric. Sources: Literature
Mode of inheritance for gene: MAK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAK were set to 35217805
Phenotypes for gene: MAK were set to Leukodystrophy MONDO:0019046, MAL-related
Review for gene: MAK was set to AMBER
Added comment: Single family with two affected siblings reported, with homozygous missense variant, some functional data.
Sources: Literature
Cerebellar and Pontocerebellar Hypoplasia v1.55 RELN Zornitza Stark Publications for gene: RELN were set to 27000652
Cerebellar and Pontocerebellar Hypoplasia v1.54 RELN Zornitza Stark Classified gene: RELN as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v1.54 RELN Zornitza Stark Gene: reln has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.53 RELN Zornitza Stark edited their review of gene: RELN: Added comment: Additional families with bi-allelic variants reported. Cerebellar hypoplasia is a feature.; Changed rating: GREEN; Changed publications: 27000652, 35769015
Mendeliome v1.120 RELN Zornitza Stark Publications for gene: RELN were set to 32001840
Mendeliome v1.119 RELN Zornitza Stark edited their review of gene: RELN: Added comment: PMID 35769015: 13 individuals from seven families with monoallelic (heterozygous) variants of RELN and frontotemporal or temporal-predominant lissencephaly variant. Some individuals with monoallelic variants had moderate frontotemporal lissencephaly, but with normal cerebellar structure and intellectual disability with severe behavioural dysfunction. However, one adult had abnormal MRI with normal intelligence and neurological profile. Additional 7 individuals from 4 families with bi-allelic variants.; Changed publications: 35769015
Lissencephaly and Band Heterotopia v1.9 RELN Zornitza Stark Publications for gene: RELN were set to 10973257; 29671837; 31805691
Lissencephaly and Band Heterotopia v1.8 RELN Zornitza Stark Mode of inheritance for gene: RELN was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Lissencephaly and Band Heterotopia v1.7 RELN Zornitza Stark changed review comment from: PMID 35769015: 13 individuals from seven families with monoallelic (heterozygous) variants of RELN and frontotemporal or temporal-predominant lissencephaly variant. Some individuals with monoallelic variants had moderate frontotemporal lissencephaly, but with normal cerebellar structure and intellectual disability with severe behavioural dysfunction. However, one adult had abnormal MRI with normal intelligence and neurological profile.; to: PMID 35769015: 13 individuals from seven families with monoallelic (heterozygous) variants of RELN and frontotemporal or temporal-predominant lissencephaly variant. Some individuals with monoallelic variants had moderate frontotemporal lissencephaly, but with normal cerebellar structure and intellectual disability with severe behavioural dysfunction. However, one adult had abnormal MRI with normal intelligence and neurological profile.

Additional 7 individuals from 4 families with bi-allelic variants.
Lissencephaly and Band Heterotopia v1.7 RELN Zornitza Stark edited their review of gene: RELN: Added comment: PMID 35769015: 13 individuals from seven families with monoallelic (heterozygous) variants of RELN and frontotemporal or temporal-predominant lissencephaly variant. Some individuals with monoallelic variants had moderate frontotemporal lissencephaly, but with normal cerebellar structure and intellectual disability with severe behavioural dysfunction. However, one adult had abnormal MRI with normal intelligence and neurological profile.; Changed publications: 10973257, 29671837, 31805691, 35769015; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4839 TAF8 Zornitza Stark changed review comment from: Further 7 individuals reported from 4 families, three of which were consanguineous.

Clinical features included severe psychomotor retardation with almost absent development, feeding problems, microcephaly, growth retardation, spasticity and epilepsy.

Five had the previously reported c.781-1G > A variant in homozygous state. This is likely to be a founder variant.

One family with different compound heterozygous variants.; to: Further 7 individuals reported from 4 families, three of which were consanguineous.

Clinical features included severe psychomotor retardation with almost absent development, feeding problems, microcephaly, growth retardation, spasticity and epilepsy.

Five had the previously reported c.781-1G > A variant in homozygous state. Unclear if this is a founder variant, families of different ethnicities.

One family with different compound heterozygous variants.
Intellectual disability syndromic and non-syndromic v0.4839 TAF8 Zornitza Stark Tag founder was removed from gene: TAF8.
Mendeliome v1.119 TAF8 Zornitza Stark changed review comment from: 8 individuals reported from 5 families, four of which were consanguineous. Clinical features included severe psychomotor retardation with almost absent development, feeding problems, microcephaly, growth retardation, spasticity and epilepsy. Six had the c.781-1G > A variant in homozygous state. This is likely to be a founder variant. One family with different compound heterozygous variants.
Sources: Literature; to: 8 individuals reported from 5 families, four of which were consanguineous. Clinical features included severe psychomotor retardation with almost absent development, feeding problems, microcephaly, growth retardation, spasticity and epilepsy. Six had the c.781-1G > A variant in homozygous state. Unclear if this is a founder variant, families of different ethnicities. One family with different compound heterozygous variants.
Sources: Literature
Microcephaly v1.129 TAF8 Zornitza Stark changed review comment from: 8 individuals reported from 5 families, four of which were consanguineous. Clinical features included severe psychomotor retardation with almost absent development, feeding problems, microcephaly, growth retardation, spasticity and epilepsy. Six had the c.781-1G > A variant in homozygous state. This is likely to be a founder variant. One family with different compound heterozygous variants.
Sources: Literature; to: 8 individuals reported from 5 families, four of which were consanguineous. Clinical features included severe psychomotor retardation with almost absent development, feeding problems, microcephaly, growth retardation, spasticity and epilepsy. Six had the c.781-1G > A variant in homozygous state. Unclear if this is a founder variant, families of different ethnicities. One family with different compound heterozygous variants.
Sources: Literature
Genetic Epilepsy v0.1630 TAF8 Zornitza Stark changed review comment from: 8 individuals reported from 5 families, four of which were consanguineous. Clinical features included severe psychomotor retardation with almost absent development, feeding problems, microcephaly, growth retardation, spasticity and epilepsy. Six had the c.781-1G > A variant in homozygous state. This is likely to be a founder variant. One family with different compound heterozygous variants.
Sources: Literature; to: 8 individuals reported from 5 families, four of which were consanguineous. Clinical features included severe psychomotor retardation with almost absent development, feeding problems, microcephaly, growth retardation, spasticity and epilepsy. Six had the c.781-1G > A variant in homozygous state. Unclear if this is a founder variant, families were of different ethnicities. One family with different compound heterozygous variants.
Sources: Literature
Genetic Epilepsy v0.1630 TAF8 Zornitza Stark Tag founder was removed from gene: TAF8.
Mendeliome v1.119 TAF8 Zornitza Stark Tag founder was removed from gene: TAF8.
Microcephaly v1.129 TAF8 Zornitza Stark Tag founder was removed from gene: TAF8.
Microcephaly v1.129 TAF8 Zornitza Stark Marked gene: TAF8 as ready
Microcephaly v1.129 TAF8 Zornitza Stark Gene: taf8 has been classified as Green List (High Evidence).
Microcephaly v1.129 TAF8 Zornitza Stark Classified gene: TAF8 as Green List (high evidence)
Microcephaly v1.129 TAF8 Zornitza Stark Gene: taf8 has been classified as Green List (High Evidence).
Microcephaly v1.128 TAF8 Zornitza Stark gene: TAF8 was added
gene: TAF8 was added to Microcephaly. Sources: Literature
founder tags were added to gene: TAF8.
Mode of inheritance for gene: TAF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAF8 were set to 29648665; 35759269
Phenotypes for gene: TAF8 were set to Neurodevelopmental disorder, MONDO:0700092, TAF8-related
Review for gene: TAF8 was set to GREEN
Added comment: 8 individuals reported from 5 families, four of which were consanguineous. Clinical features included severe psychomotor retardation with almost absent development, feeding problems, microcephaly, growth retardation, spasticity and epilepsy. Six had the c.781-1G > A variant in homozygous state. This is likely to be a founder variant. One family with different compound heterozygous variants.
Sources: Literature
Genetic Epilepsy v0.1630 TAF8 Zornitza Stark Marked gene: TAF8 as ready
Genetic Epilepsy v0.1630 TAF8 Zornitza Stark Gene: taf8 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1630 TAF8 Zornitza Stark Classified gene: TAF8 as Green List (high evidence)
Genetic Epilepsy v0.1630 TAF8 Zornitza Stark Gene: taf8 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1629 TAF8 Zornitza Stark gene: TAF8 was added
gene: TAF8 was added to Genetic Epilepsy. Sources: Literature
founder tags were added to gene: TAF8.
Mode of inheritance for gene: TAF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAF8 were set to 29648665; 35759269
Phenotypes for gene: TAF8 were set to Neurodevelopmental disorder, MONDO:0700092, TAF8-related
Review for gene: TAF8 was set to GREEN
Added comment: 8 individuals reported from 5 families, four of which were consanguineous. Clinical features included severe psychomotor retardation with almost absent development, feeding problems, microcephaly, growth retardation, spasticity and epilepsy. Six had the c.781-1G > A variant in homozygous state. This is likely to be a founder variant. One family with different compound heterozygous variants.
Sources: Literature
Mendeliome v1.119 TAF8 Zornitza Stark Marked gene: TAF8 as ready
Mendeliome v1.119 TAF8 Zornitza Stark Gene: taf8 has been classified as Green List (High Evidence).
Mendeliome v1.119 TAF8 Zornitza Stark Classified gene: TAF8 as Green List (high evidence)
Mendeliome v1.119 TAF8 Zornitza Stark Gene: taf8 has been classified as Green List (High Evidence).
Mendeliome v1.118 TAF8 Zornitza Stark gene: TAF8 was added
gene: TAF8 was added to Mendeliome. Sources: Literature
founder tags were added to gene: TAF8.
Mode of inheritance for gene: TAF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAF8 were set to 29648665; 35759269
Phenotypes for gene: TAF8 were set to Neurodevelopmental disorder, MONDO:0700092, TAF8-related
Review for gene: TAF8 was set to GREEN
Added comment: 8 individuals reported from 5 families, four of which were consanguineous. Clinical features included severe psychomotor retardation with almost absent development, feeding problems, microcephaly, growth retardation, spasticity and epilepsy. Six had the c.781-1G > A variant in homozygous state. This is likely to be a founder variant. One family with different compound heterozygous variants.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4839 TAF8 Zornitza Stark Tag founder tag was added to gene: TAF8.
Intellectual disability syndromic and non-syndromic v0.4839 TAF8 Zornitza Stark Phenotypes for gene: TAF8 were changed from Neurodevelopmental disorder, MONDO:0700092, TAF8-related to Neurodevelopmental disorder, MONDO:0700092, TAF8-related
Intellectual disability syndromic and non-syndromic v0.4838 TAF8 Zornitza Stark Phenotypes for gene: TAF8 were changed from to Neurodevelopmental disorder, MONDO:0700092, TAF8-related
Intellectual disability syndromic and non-syndromic v0.4837 TAF8 Zornitza Stark Publications for gene: TAF8 were set to PMID: 29648665
Intellectual disability syndromic and non-syndromic v0.4836 TAF8 Zornitza Stark Classified gene: TAF8 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4836 TAF8 Zornitza Stark Gene: taf8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4835 TAF8 Zornitza Stark edited their review of gene: TAF8: Changed publications: 35759269
Intellectual disability syndromic and non-syndromic v0.4835 TAF8 Zornitza Stark reviewed gene: TAF8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, TAF8-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4835 KCNK9 Zornitza Stark Publications for gene: KCNK9 were set to 28333430; 27151206; 24980697; 18678320
Intellectual disability syndromic and non-syndromic v0.4834 KCNK9 Zornitza Stark edited their review of gene: KCNK9: Added comment: Additional 47 individuals reported with 15 variants, including another hotspot at p.Arg131.; Changed publications: 28333430, 27151206, 24980697, 18678320, 35698242
Mendeliome v1.117 PNPT1 Zornitza Stark Phenotypes for gene: PNPT1 were changed from Combined oxidative phosphorylation deficiency 13 (MIM#614932); Deafness, autosomal recessive 70 (MIM#614934) to Combined oxidative phosphorylation deficiency 13 (MIM#614932); Deafness, autosomal recessive 70 (MIM#614934); Spinocerebellar ataxia 25, MIM# 608703
Mendeliome v1.116 PNPT1 Zornitza Stark Publications for gene: PNPT1 were set to 31752325; 30244537; 28594066; 28645153; 33199448
Mendeliome v1.115 PNPT1 Zornitza Stark Mode of inheritance for gene: PNPT1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.114 PNPT1 Zornitza Stark edited their review of gene: PNPT1: Added comment: Three families reported with heterozygous variants and SCA25. Incomplete penetrance in one of the families. In the third family, the variant was inherited from an asymptomatic 80+ year old. Note bi-allelic variants in this gene cause a mitochondrial disorder. Exact mechanism through which mono-allelic variants cause SCA25 not elucidated: authors speculate abnormal accumulation of mitochondrial RNA with subsequent leakage into the cytosol that may trigger a type 1 interferon response leading to neuroinflammation with neuronal dysfunction or neuronal loss.; Changed rating: AMBER; Changed publications: 35411967; Changed phenotypes: Spinocerebellar ataxia 25, MIM# 608703; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia - adult onset v0.165 PNPT1 Zornitza Stark Marked gene: PNPT1 as ready
Ataxia - adult onset v0.165 PNPT1 Zornitza Stark Gene: pnpt1 has been classified as Amber List (Moderate Evidence).
Ataxia - adult onset v0.165 PNPT1 Zornitza Stark Classified gene: PNPT1 as Amber List (moderate evidence)
Ataxia - adult onset v0.165 PNPT1 Zornitza Stark Gene: pnpt1 has been classified as Amber List (Moderate Evidence).
Ataxia - adult onset v0.164 PNPT1 Zornitza Stark gene: PNPT1 was added
gene: PNPT1 was added to Ataxia - adult onset. Sources: Literature
Mode of inheritance for gene: PNPT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PNPT1 were set to 35411967
Phenotypes for gene: PNPT1 were set to Spinocerebellar ataxia 25, MIM# 608703
Review for gene: PNPT1 was set to AMBER
Added comment: Three families reported with heterozygous variants and SCA25. Incomplete penetrance in one of the families. In the third family, the variant was inherited from an asymptomatic 80+ year old.

Note bi-allelic variants in this gene cause a mitochondrial disorder. Exact mechanism through which mono-allelic variants cause SCA25 not elucidated: authors speculate abnormal accumulation of mitochondrial RNA with subsequent leakage into the cytosol that may trigger a type 1 interferon response leading to neuroinflammation with neuronal dysfunction or neuronal loss.
Sources: Literature
Autoinflammatory Disorders v0.150 PSMB9 Peter McNaughton reviewed gene: PSMB9: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 34819510; Phenotypes: Autoinflammation; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autoinflammatory Disorders v0.150 HCK Peter McNaughton gene: HCK was added
gene: HCK was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Literature
Mode of inheritance for gene: HCK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HCK were set to PMID: 34536415
Phenotypes for gene: HCK were set to Autoinflammation
Mode of pathogenicity for gene: HCK was set to Other
Review for gene: HCK was set to AMBER
Added comment: Single patient with supportive functional data.
Sources: Literature
Defects of intrinsic and innate immunity v0.112 TBX21 Peter McNaughton gene: TBX21 was added
gene: TBX21 was added to Defects of innate immunity. Sources: Literature
Mode of inheritance for gene: TBX21 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBX21 were set to PMID: 33296702; PMID: 34160550
Phenotypes for gene: TBX21 were set to Susceptibility to mycobacterial disease
Review for gene: TBX21 was set to AMBER
Added comment: Single patient with strong functional validation
Sources: Literature
Mendeliome v1.114 TTC25 Arina Puzriakova reviewed gene: TTC25: Rating: GREEN; Mode of pathogenicity: None; Publications: 27486780, 31765523, 33715250, 33746037, 34215651; Phenotypes: Ciliary dyskinesia, primary, 35, OMIM:617092; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Macrocephaly_Megalencephaly v0.115 CTR9 Zornitza Stark Classified gene: CTR9 as Green List (high evidence)
Macrocephaly_Megalencephaly v0.115 CTR9 Zornitza Stark Gene: ctr9 has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v0.114 CTR9 Zornitza Stark gene: CTR9 was added
gene: CTR9 was added to Macrocephaly_Megalencephaly. Sources: Literature
Mode of inheritance for gene: CTR9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTR9 were set to 35499524; 35717577
Phenotypes for gene: CTR9 were set to Neurodevelopmental disorder (MONDO:0700092), CTR9 related; Macrocephaly
Review for gene: CTR9 was set to GREEN
Added comment: Additional two individuals reported who had macrocephaly in addition to ID.
Sources: Literature
Mendeliome v1.114 CXCR2 Zornitza Stark Classified gene: CXCR2 as Green List (high evidence)
Mendeliome v1.114 CXCR2 Zornitza Stark Gene: cxcr2 has been classified as Green List (High Evidence).
Mendeliome v1.113 CXCR2 Zornitza Stark edited their review of gene: CXCR2: Added comment: 4 unrelated patients with neutropaenia reported.; Changed rating: GREEN; Changed publications: 24777453, 34854278; Changed phenotypes: WHIM syndrome 2, MIM#619407
Phagocyte Defects v1.4 CXCR2 Zornitza Stark Classified gene: CXCR2 as Green List (high evidence)
Phagocyte Defects v1.4 CXCR2 Zornitza Stark Gene: cxcr2 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.147 PDCD1 Zornitza Stark Marked gene: PDCD1 as ready
Disorders of immune dysregulation v0.147 PDCD1 Zornitza Stark Gene: pdcd1 has been classified as Red List (Low Evidence).
Disorders of immune dysregulation v0.147 PDCD1 Zornitza Stark Phenotypes for gene: PDCD1 were changed from Complex Autoimmunity to Complex Autoimmunity; Inborn errors of immunity, MONDO:0003778
Disorders of immune dysregulation v0.146 PDCD1 Zornitza Stark Classified gene: PDCD1 as Red List (low evidence)
Disorders of immune dysregulation v0.146 PDCD1 Zornitza Stark Gene: pdcd1 has been classified as Red List (Low Evidence).
Mendeliome v1.113 RHOG Zornitza Stark Marked gene: RHOG as ready
Mendeliome v1.113 RHOG Zornitza Stark Gene: rhog has been classified as Amber List (Moderate Evidence).
Mendeliome v1.113 RHOG Zornitza Stark Classified gene: RHOG as Amber List (moderate evidence)
Mendeliome v1.113 RHOG Zornitza Stark Gene: rhog has been classified as Amber List (Moderate Evidence).
Mendeliome v1.112 RHOG Zornitza Stark gene: RHOG was added
gene: RHOG was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RHOG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RHOG were set to 33513601
Phenotypes for gene: RHOG were set to Genetic HLH, MONDO:0015541, RHOG-related
Review for gene: RHOG was set to AMBER
Added comment: Single individual reported, extensive functional data supports gene-disease association.
Sources: Literature
Disorders of immune dysregulation v0.145 RHOG Zornitza Stark Marked gene: RHOG as ready
Disorders of immune dysregulation v0.145 RHOG Zornitza Stark Gene: rhog has been classified as Amber List (Moderate Evidence).
Disorders of immune dysregulation v0.145 RHOG Zornitza Stark Phenotypes for gene: RHOG were changed from HLH to Genetic HLH, MONDO:0015541, RHOG-related
Disorders of immune dysregulation v0.144 RHOG Zornitza Stark Classified gene: RHOG as Amber List (moderate evidence)
Disorders of immune dysregulation v0.144 RHOG Zornitza Stark Gene: rhog has been classified as Amber List (Moderate Evidence).
Disorders of immune dysregulation v0.143 RHOG Zornitza Stark reviewed gene: RHOG: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Genetic HLH, MONDO:0015541, RHOG-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.111 TNFSF13 Zornitza Stark Marked gene: TNFSF13 as ready
Mendeliome v1.111 TNFSF13 Zornitza Stark Gene: tnfsf13 has been classified as Red List (Low Evidence).
Mendeliome v1.111 TNFSF13 Zornitza Stark gene: TNFSF13 was added
gene: TNFSF13 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TNFSF13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TNFSF13 were set to 32298700
Phenotypes for gene: TNFSF13 were set to Hypogammaglobulinaemia, MONDO:0015977, TNSF13-related
Review for gene: TNFSF13 was set to RED
Added comment: Single individual, consanguineous parents.
Sources: Literature
Predominantly Antibody Deficiency v0.116 TNFSF13 Zornitza Stark Marked gene: TNFSF13 as ready
Predominantly Antibody Deficiency v0.116 TNFSF13 Zornitza Stark Gene: tnfsf13 has been classified as Red List (Low Evidence).
Predominantly Antibody Deficiency v0.116 TNFSF13 Zornitza Stark Phenotypes for gene: TNFSF13 were changed from Hypogammaglobulinaemia to Hypogammaglobulinaemia, MONDO:0015977, TNSF13-related
Predominantly Antibody Deficiency v0.115 TNFSF13 Zornitza Stark Classified gene: TNFSF13 as Red List (low evidence)
Predominantly Antibody Deficiency v0.115 TNFSF13 Zornitza Stark Gene: tnfsf13 has been classified as Red List (Low Evidence).
Mendeliome v1.110 POU2AF1 Zornitza Stark Marked gene: POU2AF1 as ready
Mendeliome v1.110 POU2AF1 Zornitza Stark Gene: pou2af1 has been classified as Red List (Low Evidence).
Mendeliome v1.110 POU2AF1 Zornitza Stark gene: POU2AF1 was added
gene: POU2AF1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: POU2AF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POU2AF1 were set to 33571536
Phenotypes for gene: POU2AF1 were set to Agammaglobulinaemia, MONDO:0015977, POU2AF1-related
Review for gene: POU2AF1 was set to RED
Added comment: Single individual from consanguineous parents lacking immunoglobulins despite normal total B-cell numbers.
Sources: Expert Review
Predominantly Antibody Deficiency v0.114 POU2AF1 Zornitza Stark Marked gene: POU2AF1 as ready
Predominantly Antibody Deficiency v0.114 POU2AF1 Zornitza Stark Gene: pou2af1 has been classified as Red List (Low Evidence).
Predominantly Antibody Deficiency v0.114 POU2AF1 Zornitza Stark Phenotypes for gene: POU2AF1 were changed from Agammaglobulinaemia to Agammaglobulinaemia, MONDO:0015977, POU2AF1-related
Predominantly Antibody Deficiency v0.113 POU2AF1 Zornitza Stark Classified gene: POU2AF1 as Red List (low evidence)
Predominantly Antibody Deficiency v0.113 POU2AF1 Zornitza Stark Gene: pou2af1 has been classified as Red List (Low Evidence).
Predominantly Antibody Deficiency v0.112 PIK3CG Zornitza Stark Marked gene: PIK3CG as ready
Predominantly Antibody Deficiency v0.112 PIK3CG Zornitza Stark Gene: pik3cg has been classified as Amber List (Moderate Evidence).
Predominantly Antibody Deficiency v0.112 PIK3CG Zornitza Stark Phenotypes for gene: PIK3CG were changed from Humoral deficiency; Immune dysregulation; HLH to Immunodeficiency 97 with autoinflammation, MIM# 619802; Humoral deficiency; Immune dysregulation; HLH
Predominantly Antibody Deficiency v0.111 PIK3CG Zornitza Stark Classified gene: PIK3CG as Amber List (moderate evidence)
Predominantly Antibody Deficiency v0.111 PIK3CG Zornitza Stark Gene: pik3cg has been classified as Amber List (Moderate Evidence).
Predominantly Antibody Deficiency v0.110 PIK3CG Zornitza Stark reviewed gene: PIK3CG: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency 97 with autoinflammation, MIM# 619802; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v1.25 DIAPH1 Zornitza Stark Marked gene: DIAPH1 as ready
Combined Immunodeficiency v1.25 DIAPH1 Zornitza Stark Gene: diaph1 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.25 DIAPH1 Zornitza Stark Phenotypes for gene: DIAPH1 were changed from Combined Immune deficiency to Seizures, cortical blindness, microcephaly syndrome, MIM# 616632; Combined Immune deficiency
Combined Immunodeficiency v1.24 DIAPH1 Zornitza Stark Classified gene: DIAPH1 as Green List (high evidence)
Combined Immunodeficiency v1.24 DIAPH1 Zornitza Stark Gene: diaph1 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.23 DIAPH1 Zornitza Stark reviewed gene: DIAPH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Seizures, cortical blindness, microcephaly syndrome, MIM# 616632; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.109 CD28 Zornitza Stark Marked gene: CD28 as ready
Mendeliome v1.109 CD28 Zornitza Stark Gene: cd28 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.109 CD28 Zornitza Stark Classified gene: CD28 as Amber List (moderate evidence)
Mendeliome v1.109 CD28 Zornitza Stark Gene: cd28 has been classified as Amber List (Moderate Evidence).
Susceptibility to Viral Infections v0.91 CD28 Zornitza Stark Marked gene: CD28 as ready
Susceptibility to Viral Infections v0.91 CD28 Zornitza Stark Gene: cd28 has been classified as Amber List (Moderate Evidence).
Susceptibility to Viral Infections v0.91 CD28 Zornitza Stark Classified gene: CD28 as Amber List (moderate evidence)
Susceptibility to Viral Infections v0.91 CD28 Zornitza Stark Gene: cd28 has been classified as Amber List (Moderate Evidence).
Susceptibility to Viral Infections v0.90 CD28 Zornitza Stark reviewed gene: CD28: Rating: AMBER; Mode of pathogenicity: None; Publications: 34214472; Phenotypes: Hereditary predisposition to infections, MONDO:0015979, CD28-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.108 CD28 Zornitza Stark edited their review of gene: CD28: Changed rating: AMBER
Mendeliome v1.108 CD28 Zornitza Stark changed review comment from: Rare homozygous CD28 variant segregates with severe verrucosis in three relatives and supportive functional data.
Sources: Expert Review; to: Rare homozygous CD28 variant segregates with severe verrucosis in three relatives and supportive functional data. CD28-deficient mice are susceptible to cutaneous infections with the mouse papillomavirus MmuPV1.
Sources: Expert Review
Mendeliome v1.108 CD28 Zornitza Stark gene: CD28 was added
gene: CD28 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: CD28 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD28 were set to 34214472
Phenotypes for gene: CD28 were set to Hereditary predisposition to infections, MONDO:0015979, CD28-related; isolated susceptibility to cutaneous α- and γ-HPVs
Review for gene: CD28 was set to RED
Added comment: Rare homozygous CD28 variant segregates with severe verrucosis in three relatives and supportive functional data.
Sources: Expert Review
Susceptibility to Viral Infections v0.90 CD28 Zornitza Stark Phenotypes for gene: CD28 were changed from Hereditary predisposition to infections, MONDO:0015979, CD28-related; isolated susceptibility to cutaneous α- and γ-HPVs to Hereditary predisposition to infections, MONDO:0015979, CD28-related; isolated susceptibility to cutaneous α- and γ-HPVs
Susceptibility to Viral Infections v0.89 CD28 Zornitza Stark Phenotypes for gene: CD28 were changed from isolated susceptibility to cutaneous α- and γ-HPVs to Hereditary predisposition to infections, MONDO:0015979, CD28-related; isolated susceptibility to cutaneous α- and γ-HPVs
Susceptibility to Viral Infections v0.88 CD28 Zornitza Stark Classified gene: CD28 as Red List (low evidence)
Susceptibility to Viral Infections v0.88 CD28 Zornitza Stark Gene: cd28 has been classified as Red List (Low Evidence).
Mendeliome v1.107 IKZF3 Zornitza Stark Classified gene: IKZF3 as Green List (high evidence)
Mendeliome v1.107 IKZF3 Zornitza Stark Gene: ikzf3 has been classified as Green List (High Evidence).
Mendeliome v1.106 IKZF3 Zornitza Stark edited their review of gene: IKZF3: Added comment: Additional multigenerational family where novel missense variant segregated with disease in 4 individuals.; Changed rating: GREEN; Changed publications: 34155405, 34694366
Combined Immunodeficiency v1.23 IKZF3 Zornitza Stark Publications for gene: IKZF3 were set to 34155405
Combined Immunodeficiency v1.22 IKZF3 Zornitza Stark Marked gene: IKZF3 as ready
Combined Immunodeficiency v1.22 IKZF3 Zornitza Stark Added comment: Comment when marking as ready: Additional family with good segregation data: two families and mouse model, so upgrade to Green.
Combined Immunodeficiency v1.22 IKZF3 Zornitza Stark Gene: ikzf3 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.22 IKZF3 Zornitza Stark Classified gene: IKZF3 as Green List (high evidence)
Combined Immunodeficiency v1.22 IKZF3 Zornitza Stark Gene: ikzf3 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.22 IKZF3 Zornitza Stark Classified gene: IKZF3 as Green List (high evidence)
Combined Immunodeficiency v1.22 IKZF3 Zornitza Stark Gene: ikzf3 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.21 COPG1 Zornitza Stark Classified gene: COPG1 as Amber List (moderate evidence)
Combined Immunodeficiency v1.21 COPG1 Zornitza Stark Gene: copg1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.106 COPG1 Zornitza Stark Marked gene: COPG1 as ready
Mendeliome v1.106 COPG1 Zornitza Stark Gene: copg1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.106 COPG1 Zornitza Stark Classified gene: COPG1 as Amber List (moderate evidence)
Mendeliome v1.106 COPG1 Zornitza Stark Gene: copg1 has been classified as Amber List (Moderate Evidence).
Combined Immunodeficiency v1.20 COPG1 Zornitza Stark reviewed gene: COPG1: Rating: AMBER; Mode of pathogenicity: None; Publications: 33529166; Phenotypes: Combined immunodeficiency MONDO:0015131, COPG1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.105 COPG1 Zornitza Stark edited their review of gene: COPG1: Changed rating: AMBER
Mendeliome v1.105 COPG1 Zornitza Stark gene: COPG1 was added
gene: COPG1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: COPG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COPG1 were set to 33529166
Phenotypes for gene: COPG1 were set to Combined immunodeficiency MONDO:0015131, COPG1-related
Review for gene: COPG1 was set to RED
Added comment: Five Omani siblings, born to consanguineous parents, homozygous missense.

Homozygous Copg1K652E mice had increased ER stress in activated T and B cells, poor antibody responses, and normal numbers of T cells that proliferated normally, but underwent increased apoptosis upon activation. Exposure of the mutants to pet store mice caused weight loss, lymphopenia, and defective T cell proliferation that recapitulated the findings in the patients. The ER stress-relieving agent tauroursodeoxycholic acid corrected the immune defects of the mutants and reversed the phenotype they acquired following exposure to pet store mice.
Sources: Expert Review
Combined Immunodeficiency v1.20 COPG1 Zornitza Stark Marked gene: COPG1 as ready
Combined Immunodeficiency v1.20 COPG1 Zornitza Stark Gene: copg1 has been classified as Red List (Low Evidence).
Combined Immunodeficiency v1.20 COPG1 Zornitza Stark Phenotypes for gene: COPG1 were changed from Combined immunodeficiency MONDO:0015131, COPG1-related to Combined immunodeficiency MONDO:0015131, COPG1-related
Combined Immunodeficiency v1.19 COPG1 Zornitza Stark Phenotypes for gene: COPG1 were changed from Combined Immune deficiency to Combined immunodeficiency MONDO:0015131, COPG1-related
Combined Immunodeficiency v1.18 COPG1 Zornitza Stark Classified gene: COPG1 as Red List (low evidence)
Combined Immunodeficiency v1.18 COPG1 Zornitza Stark Gene: copg1 has been classified as Red List (Low Evidence).
Combined Immunodeficiency v1.17 MAN2B2 Zornitza Stark Marked gene: MAN2B2 as ready
Combined Immunodeficiency v1.17 MAN2B2 Zornitza Stark Gene: man2b2 has been classified as Red List (Low Evidence).
Combined Immunodeficiency v1.17 MAN2B2 Zornitza Stark Phenotypes for gene: MAN2B2 were changed from Combined Immune deficiency to Congenital disorder of glycosylation, MONDO:0015286, MAN2B2-related; Combined Immune deficiency
Combined Immunodeficiency v1.16 MAN2B2 Zornitza Stark Classified gene: MAN2B2 as Red List (low evidence)
Combined Immunodeficiency v1.16 MAN2B2 Zornitza Stark Gene: man2b2 has been classified as Red List (Low Evidence).
Combined Immunodeficiency v1.15 MAN2B2 Zornitza Stark reviewed gene: MAN2B2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, MONDO:0015286, MAN2B2-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.40 VPS37A Zornitza Stark Marked gene: VPS37A as ready
Prepair 1000+ v0.40 VPS37A Zornitza Stark Gene: vps37a has been classified as Red List (Low Evidence).
Prepair 1000+ v0.40 VPS37A Zornitza Stark Publications for gene: VPS37A were set to
Prepair 1000+ v0.39 VPS37A Zornitza Stark Classified gene: VPS37A as Red List (low evidence)
Prepair 1000+ v0.39 VPS37A Zornitza Stark Gene: vps37a has been classified as Red List (Low Evidence).
Prepair 1000+ v0.38 UQCRQ Zornitza Stark Marked gene: UQCRQ as ready
Prepair 1000+ v0.38 UQCRQ Zornitza Stark Gene: uqcrq has been classified as Red List (Low Evidence).
Prepair 1000+ v0.38 UQCRQ Zornitza Stark Publications for gene: UQCRQ were set to
Prepair 1000+ v0.37 UQCRQ Zornitza Stark Classified gene: UQCRQ as Red List (low evidence)
Prepair 1000+ v0.37 UQCRQ Zornitza Stark Gene: uqcrq has been classified as Red List (Low Evidence).
Prepair 1000+ v0.36 SGO1 Zornitza Stark Marked gene: SGO1 as ready
Prepair 1000+ v0.36 SGO1 Zornitza Stark Gene: sgo1 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.36 SGO1 Zornitza Stark Publications for gene: SGO1 were set to
Prepair 1000+ v0.35 SGO1 Zornitza Stark Classified gene: SGO1 as Red List (low evidence)
Prepair 1000+ v0.35 SGO1 Zornitza Stark Gene: sgo1 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.34 SGO1 Zornitza Stark Tag founder tag was added to gene: SGO1.
Prepair 1000+ v0.34 TSPAN7 Zornitza Stark Marked gene: TSPAN7 as ready
Prepair 1000+ v0.34 TSPAN7 Zornitza Stark Gene: tspan7 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.34 TSPAN7 Zornitza Stark Phenotypes for gene: TSPAN7 were changed from Mental retardation, X-linked 58, 300210 (3) to Intellectual developmental disorder, X-linked 58, MIM #300210, MONDO:0010266
Prepair 1000+ v0.33 TSPAN7 Zornitza Stark Publications for gene: TSPAN7 were set to
Prepair 1000+ v0.32 TSPAN7 Zornitza Stark reviewed gene: TSPAN7: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.4834 TSPAN7 Zornitza Stark Classified gene: TSPAN7 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.4834 TSPAN7 Zornitza Stark Gene: tspan7 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4833 TSPAN7 Zornitza Stark Tag disputed was removed from gene: TSPAN7.
Intellectual disability syndromic and non-syndromic v0.4833 TSPAN7 Zornitza Stark edited their review of gene: TSPAN7: Added comment: Two families reported with LoF variants and ID: Abidi FE et al. 2002 Jun (PMID:12070254); Zemni R et al. 2000 Feb (PMID:10655063) Assessed as MODERATE by ClinGen.; Changed rating: AMBER
Mendeliome v1.104 TSPAN7 Zornitza Stark Tag disputed was removed from gene: TSPAN7.
Mendeliome v1.104 TSPAN7 Zornitza Stark edited their review of gene: TSPAN7: Added comment: Two families reported with LoF variants and ID: Abidi FE et al. 2002 Jun (PMID:12070254); Zemni R et al. 2000 Feb (PMID:10655063)

Assessed as MODERATE by ClinGen.; Changed rating: AMBER; Changed publications: 12070254, 10655063
Mendeliome v1.104 TSPAN7 Zornitza Stark Tag disputed tag was added to gene: TSPAN7.
Mendeliome v1.104 TSPAN7 Zornitza Stark edited their review of gene: TSPAN7: Changed rating: RED
Intellectual disability syndromic and non-syndromic v0.4833 TSPAN7 Zornitza Stark Classified gene: TSPAN7 as Red List (low evidence)
Intellectual disability syndromic and non-syndromic v0.4833 TSPAN7 Zornitza Stark Gene: tspan7 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.4832 TSPAN7 Zornitza Stark Tag disputed tag was added to gene: TSPAN7.
Intellectual disability syndromic and non-syndromic v0.4832 TSPAN7 Zornitza Stark edited their review of gene: TSPAN7: Changed rating: RED
Prepair 1000+ v0.32 TSPAN7 Zornitza Stark Classified gene: TSPAN7 as Red List (low evidence)
Prepair 1000+ v0.32 TSPAN7 Zornitza Stark Gene: tspan7 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.31 TSPAN7 Zornitza Stark Tag disputed tag was added to gene: TSPAN7.
Mendeliome v1.104 IFNAR2 Zornitza Stark Publications for gene: IFNAR2 were set to 26424569
Mendeliome v1.103 IFNAR2 Zornitza Stark Classified gene: IFNAR2 as Green List (high evidence)
Mendeliome v1.103 IFNAR2 Zornitza Stark Gene: ifnar2 has been classified as Green List (High Evidence).
Mendeliome v1.102 IFNAR2 Zornitza Stark edited their review of gene: IFNAR2: Added comment: Five children from Greenland, Canada, and Alaska presenting with viral diseases, including life-threatening COVID-19 or influenza, in addition to meningoencephalitis and/or hemophagocytic lymphohistiocytosis following live-attenuated viral vaccination; Changed rating: GREEN; Changed publications: 26424569, 35442417
Susceptibility to Viral Infections v0.87 IFNAR2 Zornitza Stark Publications for gene: IFNAR2 were set to 26424569
Susceptibility to Viral Infections v0.86 IFNAR2 Zornitza Stark Classified gene: IFNAR2 as Green List (high evidence)
Susceptibility to Viral Infections v0.86 IFNAR2 Zornitza Stark Gene: ifnar2 has been classified as Green List (High Evidence).
Mendeliome v1.102 IFNAR1 Zornitza Stark Phenotypes for gene: IFNAR1 were changed from Severe disease caused by Yellow Fever vaccine and Measles vaccine to Immunodeficiency 106, susceptibility to viral infections, MIM# 619935; Severe disease caused by Yellow Fever vaccine and Measles vaccine
Mendeliome v1.101 IFNAR1 Zornitza Stark Publications for gene: IFNAR1 were set to 31270247
Mendeliome v1.100 IFNAR1 Zornitza Stark Classified gene: IFNAR1 as Green List (high evidence)
Mendeliome v1.100 IFNAR1 Zornitza Stark Gene: ifnar1 has been classified as Green List (High Evidence).
Mendeliome v1.99 IFNAR1 Zornitza Stark edited their review of gene: IFNAR1: Changed rating: GREEN
Mendeliome v1.99 IFNAR1 Zornitza Stark edited their review of gene: IFNAR1: Added comment: Seven children from five unrelated kindreds; Changed publications: 31270247, 35442418; Changed phenotypes: Immunodeficiency 106, susceptibility to viral infections, MIM# 619935, Severe disease caused by Yellow Fever vaccine and Measles vaccine
Susceptibility to Viral Infections v0.85 IFNAR1 Zornitza Stark Phenotypes for gene: IFNAR1 were changed from Severe disease caused by Yellow Fever vaccine and Measles vaccine to Immunodeficiency 106, susceptibility to viral infections, MIM# 619935; Severe disease caused by Yellow Fever vaccine and Measles vaccine
Susceptibility to Viral Infections v0.84 IFNAR1 Zornitza Stark Classified gene: IFNAR1 as Green List (high evidence)
Susceptibility to Viral Infections v0.84 IFNAR1 Zornitza Stark Gene: ifnar1 has been classified as Green List (High Evidence).
Mendeliome v1.99 SLC26A1 Zornitza Stark Tag disputed tag was added to gene: SLC26A1.
Mendeliome v1.99 SLC26A1 Zornitza Stark Classified gene: SLC26A1 as Red List (low evidence)
Mendeliome v1.99 SLC26A1 Zornitza Stark Gene: slc26a1 has been classified as Red List (Low Evidence).
Mendeliome v1.98 NEK8 Zornitza Stark Phenotypes for gene: NEK8 were changed from Renal-hepatic-pancreatic dysplasia 2, MIM# 615415; MONDO:0014174 to Renal-hepatic-pancreatic dysplasia 2, MIM# 615415; MONDO:0014174; Familial renal cystic disease MONDO:0019741, NEK8-related, dominant
Mendeliome v1.97 NEK8 Zornitza Stark Mode of inheritance for gene: NEK8 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.96 NEK8 Zornitza Stark edited their review of gene: NEK8: Added comment: ESHG 2022: 12 families with paediatric renal cystic disease (enlarged kidneys, kidney cysts, ESKF <20yrs) -3 recurrent HTZ variants in NEK8 kinase domain (Arg45Trp, Ile150Met, Lys157Gln) -suspected dominant negative effect -patient fibroblasts show normal ciliogenesis and normal localisation and expression of NEK8 (Note carriers of AR-NEK8 disease do not show renal manifestations, as variants are LOF); Changed phenotypes: Renal-hepatic-pancreatic dysplasia 2, MIM# 615415, MONDO:0014174, Familial renal cystic disease MONDO:0019741, NEK8-related, dominant; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ciliopathies v1.31 NEK8 Zornitza Stark Phenotypes for gene: NEK8 were changed from Renal-hepatic-pancreatic dysplasia 2, MIM# 615415; MONDO:0014174 to Renal-hepatic-pancreatic dysplasia 2, MIM# 615415; MONDO:0014174; Familial renal cystic disease MONDO:0019741, NEK8-related, dominant
Ciliopathies v1.30 NEK8 Zornitza Stark Mode of inheritance for gene: NEK8 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ciliopathies v1.29 NEK8 Zornitza Stark edited their review of gene: NEK8: Added comment: ESHG 2022:
12 families with paediatric renal cystic disease (enlarged kidneys, kidney cysts, ESKF <20yrs) -3 recurrent HTZ variants in NEK8 kinase domain (Arg45Trp, Ile150Met, Lys157Gln) -suspected dominant negative effect -patient fibroblasts show normal ciliogenesis and normal localisation and expression of NEK8 (Note carriers of AR-NEK8 disease do not show renal manifestations, as variants are LOF); Changed phenotypes: Renal-hepatic-pancreatic dysplasia 2, MIM# 615415, MONDO:0014174, Familial renal cystic disease MONDO:0019741, NEK8-related, dominant; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Renal Macrocystic Disease v0.46 NEK8 Zornitza Stark Marked gene: NEK8 as ready
Renal Macrocystic Disease v0.46 NEK8 Zornitza Stark Gene: nek8 has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.46 NEK8 Zornitza Stark Phenotypes for gene: NEK8 were changed from Renal cystic disease to Familial renal cystic disease MONDO:0019741, NEK8-related, dominant
Renal Ciliopathies and Nephronophthisis v1.13 NEK8 Zornitza Stark Phenotypes for gene: NEK8 were changed from Renal-hepatic-pancreatic dysplasia 2, MIM# 615415; MONDO:0014174 to Renal-hepatic-pancreatic dysplasia 2, MIM# 615415; MONDO:0014174; Familial renal cystic disease MONDO:0019741, NEK8-related, dominant
Renal Ciliopathies and Nephronophthisis v1.12 NEK8 Zornitza Stark Mode of inheritance for gene: NEK8 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Liver Failure_Paediatric v1.15 SKIV2L Zornitza Stark Marked gene: SKIV2L as ready
Liver Failure_Paediatric v1.15 SKIV2L Zornitza Stark Gene: skiv2l has been classified as Green List (High Evidence).
Liver Failure_Paediatric v1.15 SKIV2L Zornitza Stark Publications for gene: SKIV2L were set to PMID: 22444670, 33114497, 30397475, 29527791, 29484573
Liver Failure_Paediatric v1.14 TULP3 Zornitza Stark Marked gene: TULP3 as ready
Liver Failure_Paediatric v1.14 TULP3 Zornitza Stark Gene: tulp3 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v1.14 TULP3 Zornitza Stark Phenotypes for gene: TULP3 were changed from progressive degenerative liver fibrosis with variable fibrocystic kidney disease; hypertrophic cardiomyopathy MONDO:0005045 to Hepatorenocardiac degenerative fibrosis, MIM# 619902
Liver Failure_Paediatric v1.13 TULP3 Zornitza Stark reviewed gene: TULP3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hepatorenocardiac degenerative fibrosis, MIM# 619902; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Regression v0.486 DRD2 Zornitza Stark Marked gene: DRD2 as ready
Regression v0.486 DRD2 Zornitza Stark Gene: drd2 has been classified as Red List (Low Evidence).
Regression v0.486 DRD2 Zornitza Stark Phenotypes for gene: DRD2 were changed from to Combined dystonia, MONDO:0020065, DRD2-related
Regression v0.485 DRD2 Zornitza Stark Publications for gene: DRD2 were set to
Regression v0.484 DRD2 Zornitza Stark Mode of pathogenicity for gene: DRD2 was changed from to Other
Regression v0.483 DRD2 Zornitza Stark Mode of inheritance for gene: DRD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Regression v0.482 DRD2 Zornitza Stark Classified gene: DRD2 as Red List (low evidence)
Regression v0.482 DRD2 Zornitza Stark Gene: drd2 has been classified as Red List (Low Evidence).
Regression v0.481 DRD2 Zornitza Stark reviewed gene: DRD2: Rating: RED; Mode of pathogenicity: Other; Publications: 33200438; Phenotypes: Combined dystonia, MONDO:0020065, DRD2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.96 DRD2 Zornitza Stark Phenotypes for gene: DRD2 were changed from to Combined dystonia, MONDO:0020065, DRD2-related; dystonia; chorea; anxiety; ataxia; orofacial dyskinesia; tremor; memory problems
Mendeliome v1.95 DRD2 Zornitza Stark Mode of pathogenicity for gene: DRD2 was changed from to Other
Mendeliome v1.94 DRD2 Zornitza Stark Mode of inheritance for gene: DRD2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dystonia - isolated/combined v1.24 DRD2 Zornitza Stark Marked gene: DRD2 as ready
Dystonia - isolated/combined v1.24 DRD2 Zornitza Stark Gene: drd2 has been classified as Red List (Low Evidence).
Mendeliome v1.93 DRD2 Zornitza Stark reviewed gene: DRD2: Rating: RED; Mode of pathogenicity: Other; Publications: 33200438; Phenotypes: Combined dystonia, MONDO:0020065, DRD2-related, dystonia, chorea, anxiety, ataxia, orofacial dyskinesia, tremor, memory problems; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dystonia - isolated/combined v1.24 DRD2 Zornitza Stark Phenotypes for gene: DRD2 were changed from dystonia; chorea; anxiety; ataxia; orofacial dyskinesia; tremor; memory problems to Combined dystonia, MONDO:0020065, DRD2-related; dystonia; chorea; anxiety; ataxia; orofacial dyskinesia; tremor; memory problems
Cerebral Palsy v1.29 ADAR Zornitza Stark Publications for gene: ADAR were set to 33528536
Cerebral Palsy v1.28 ADAR Zornitza Stark Mode of inheritance for gene: ADAR was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cerebral Palsy v1.27 ELOVL1 Zornitza Stark Marked gene: ELOVL1 as ready
Cerebral Palsy v1.27 ELOVL1 Zornitza Stark Gene: elovl1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.27 ELOVL1 Zornitza Stark Phenotypes for gene: ELOVL1 were changed from MIM 618527 to Ichthyotic keratoderma, spasticity, hypomyelination, and dysmorphic facies, MIM# 618527
Cerebral Palsy v1.26 ELOVL1 Zornitza Stark Publications for gene: ELOVL1 were set to (PMID: 35379526; 30487246; 29496980)
Cerebral Palsy v1.25 ELOVL1 Zornitza Stark Classified gene: ELOVL1 as Green List (high evidence)
Cerebral Palsy v1.25 ELOVL1 Zornitza Stark Gene: elovl1 has been classified as Green List (High Evidence).
Cerebral Palsy v1.24 ELOVL1 Zornitza Stark reviewed gene: ELOVL1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ichthyotic keratoderma, spasticity, hypomyelination, and dysmorphic facies, MIM# 618527; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.93 THSD1 Zornitza Stark Phenotypes for gene: THSD1 were changed from Aneurysm, intracranial berry, 12 , MIM# 618734 to Aneurysm, intracranial berry, 12 , MIM# 618734; Hydrops fetalis MONDO:0015193, THSD1-related
Mendeliome v1.92 THSD1 Zornitza Stark Publications for gene: THSD1 were set to 27895300
Mendeliome v1.91 THSD1 Zornitza Stark Classified gene: THSD1 as Green List (high evidence)
Mendeliome v1.91 THSD1 Zornitza Stark Gene: thsd1 has been classified as Green List (High Evidence).
Mendeliome v1.91 THSD1 Zornitza Stark Classified gene: THSD1 as Green List (high evidence)
Mendeliome v1.91 THSD1 Zornitza Stark Gene: thsd1 has been classified as Green List (High Evidence).
Hydrops fetalis v0.282 THSD1 Zornitza Stark Classified gene: THSD1 as Green List (high evidence)
Hydrops fetalis v0.282 THSD1 Zornitza Stark Gene: thsd1 has been classified as Green List (High Evidence).
Hydrops fetalis v0.281 THSD1 Zornitza Stark Marked gene: THSD1 as ready
Hydrops fetalis v0.281 THSD1 Zornitza Stark Gene: thsd1 has been classified as Amber List (Moderate Evidence).
Hydrops fetalis v0.281 THSD1 Zornitza Stark Phenotypes for gene: THSD1 were changed from nonimmune hydrops fetalis to Hydrops fetalis MONDO:0015193, THSD1-related
Phagocyte Defects v1.3 CXCR2 Peter McNaughton reviewed gene: CXCR2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34854278; Phenotypes: Neutropaenia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Disorders of immune dysregulation v0.143 PDCD1 Peter McNaughton gene: PDCD1 was added
gene: PDCD1 was added to Disorders of immune dysregulation. Sources: Literature
Mode of inheritance for gene: PDCD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDCD1 were set to PMID: 34183838
Phenotypes for gene: PDCD1 were set to Complex Autoimmunity
Review for gene: PDCD1 was set to RED
Added comment: Single patient born to consanguineous parents presenting with type 1 diabetes (T1D), hypothyroidism, and juvenile idiopathic arthritis (JIA)
Sources: Literature
Disorders of immune dysregulation v0.143 RHOG Peter McNaughton gene: RHOG was added
gene: RHOG was added to Disorders of immune dysregulation. Sources: Literature
Mode of inheritance for gene: RHOG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RHOG were set to PMID: 33513601
Phenotypes for gene: RHOG were set to HLH
Review for gene: RHOG was set to RED
Added comment: Single patient with supportive functional data.
Sources: Literature
Predominantly Antibody Deficiency v0.110 TNFSF13 Peter McNaughton gene: TNFSF13 was added
gene: TNFSF13 was added to Predominantly Antibody Deficiency. Sources: Literature
Mode of inheritance for gene: TNFSF13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TNFSF13 were set to PMID: 32298700
Phenotypes for gene: TNFSF13 were set to Hypogammaglobulinaemia
Review for gene: TNFSF13 was set to RED
Added comment: Single patient born to consanguineous parents
Sources: Literature
Predominantly Antibody Deficiency v0.110 POU2AF1 Peter McNaughton gene: POU2AF1 was added
gene: POU2AF1 was added to Predominantly Antibody Deficiency. Sources: Literature
Mode of inheritance for gene: POU2AF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POU2AF1 were set to PMID: 33571536
Phenotypes for gene: POU2AF1 were set to Agammaglobulinaemia
Review for gene: POU2AF1 was set to RED
Added comment: Single patient from consanguineous parents lacking immunoglobulins despite normal total B-cell numbers.
Sources: Literature
Predominantly Antibody Deficiency v0.110 PIK3CG Peter McNaughton gene: PIK3CG was added
gene: PIK3CG was added to Predominantly Antibody Deficiency. Sources: Literature
Mode of inheritance for gene: PIK3CG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIK3CG were set to PMID: 31554793; PMID: 33054089
Phenotypes for gene: PIK3CG were set to Humoral deficiency; Immune dysregulation; HLH
Review for gene: PIK3CG was set to AMBER
Added comment: Included in IUIS 2022 update predominantly antibody deficiency.
PMID: 31554793 female patient presented with haemolytic anaemia, pulmonary impairment and hypogammaglobulinaemia.
Sources: Literature
Combined Immunodeficiency v1.15 DIAPH1 Peter McNaughton gene: DIAPH1 was added
gene: DIAPH1 was added to Combined Immunodeficiency. Sources: Literature
Mode of inheritance for gene: DIAPH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DIAPH1 were set to PMID: 33662367
Phenotypes for gene: DIAPH1 were set to Combined Immune deficiency
Review for gene: DIAPH1 was set to GREEN
Added comment: 5 Finnish and 2 Omani patients with B and T cell defects
Sources: Literature
Susceptibility to Viral Infections v0.83 CD28 Peter McNaughton gene: CD28 was added
gene: CD28 was added to Susceptibility to Viral Infections. Sources: Literature
Mode of inheritance for gene: CD28 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD28 were set to PMID: 34214472
Phenotypes for gene: CD28 were set to isolated susceptibility to cutaneous α- and γ-HPVs
Review for gene: CD28 was set to RED
Added comment: Rare homozygous CD28 variant segregates with severe verrucosis in three relatives and supportive functional data.
Sources: Literature
Combined Immunodeficiency v1.15 IKZF3 Peter McNaughton reviewed gene: IKZF3: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 34694366; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Combined Immunodeficiency v1.15 COPG1 Peter McNaughton gene: COPG1 was added
gene: COPG1 was added to Combined Immunodeficiency. Sources: Literature
Mode of inheritance for gene: COPG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COPG1 were set to PMID: 33529166
Phenotypes for gene: COPG1 were set to Combined Immune deficiency
Review for gene: COPG1 was set to RED
Added comment: Five Omani siblings, born to consanguineous parents
Sources: Literature
Combined Immunodeficiency v1.15 MAN2B2 Peter McNaughton gene: MAN2B2 was added
gene: MAN2B2 was added to Combined Immunodeficiency. Sources: Literature
Mode of inheritance for gene: MAN2B2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAN2B2 were set to PMID: 31775018
Phenotypes for gene: MAN2B2 were set to Combined Immune deficiency
Review for gene: MAN2B2 was set to RED
Added comment: Single syndromic patient with combined immune deficiency
Sources: Literature
Genetic Epilepsy v0.1628 TRPM3 Zornitza Stark Phenotypes for gene: TRPM3 were changed from Intellectual disability; epilepsy to Neurodevelopmental disorder, MONDO:0700092, TRPM3-related
Mendeliome v1.90 TRPM3 Zornitza Stark Phenotypes for gene: TRPM3 were changed from Intellectual disability; epilepsy to Neurodevelopmental disorder, MONDO:0700092, TRPM3-related
Intellectual disability syndromic and non-syndromic v0.4832 TRPM3 Zornitza Stark Phenotypes for gene: TRPM3 were changed from Intellectual disability; epilepsy to Neurodevelopmental disorder, MONDO:0700092, TRPM3-related
Prepair 1000+ v0.31 VPS37A Crystle Lee reviewed gene: VPS37A: Rating: RED; Mode of pathogenicity: None; Publications: 22717650, 29473047; Phenotypes: Spastic paraplegia 53, autosomal recessive (MIM#614898); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.31 UQCRQ Crystle Lee reviewed gene: UQCRQ: Rating: RED; Mode of pathogenicity: None; Publications: 18439546; Phenotypes: Mitochondrial complex III deficiency, nuclear type 4 (MIM#615159); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.31 SGO1 Crystle Lee reviewed gene: SGO1: Rating: RED; Mode of pathogenicity: None; Publications: 25282101; Phenotypes: Chronic atrial and intestinal dysrhythmia, MIM# 616201; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.31 TSPAN7 Crystle Lee reviewed gene: TSPAN7: Rating: RED; Mode of pathogenicity: None; Publications: 10449641, 12070254, 10655063, 25081361; Phenotypes: Intellectual developmental disorder, X-linked 58, MIM #300210, MONDO:0010266; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.31 ALG2 Crystle Lee commented on gene: ALG2: One additional variant reported in association with CDG on top of the previously reviewed patients reported with CDG/congenital myasthenia

PMID: 33644825: R251L reported in 3 probands from 2 families with CDG (same patients in PMID: 30397276)
Mackenzie's Mission_Reproductive Carrier Screening v0.108 IGFBP7 Crystle Lee reviewed gene: IGFBP7: Rating: RED; Mode of pathogenicity: None; Publications: 34519236, 31730227, 32429784; Phenotypes: Retinal arterial macroaneurysm with supravalvular pulmonic stenosis (MIM#614224); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.108 ALG2 Crystle Lee changed review comment from: One additional variant reported in association with CDG on top of the previous patients reported with CDG/congenital myasthenia

PMID: 33644825: R251L reported in 3 probands from 2 families with CDG (same patients in PMID: 30397276)

Association with myasthenia: Two families reported, same, likely founder variant.

Association with CDG: one individual with multisystemic disorder with ID, seizures, coloboma of the iris, hypomyelination, hepatomegaly, and coagulation abnormalities reported in PMID 12684507. Fibroblasts showed severely reduced enzymatic activity.; to: One additional variant reported in association with CDG on top of the previously reviewed patients reported with CDG/congenital myasthenia

PMID: 33644825: R251L reported in 3 probands from 2 families with CDG (same patients in PMID: 30397276)

Association with myasthenia: Two families reported, same, likely founder variant.

Association with CDG: one individual with multisystemic disorder with ID, seizures, coloboma of the iris, hypomyelination, hepatomegaly, and coagulation abnormalities reported in PMID 12684507. Fibroblasts showed severely reduced enzymatic activity.
Mackenzie's Mission_Reproductive Carrier Screening v0.108 ALG2 Crystle Lee reviewed gene: ALG2: Rating: AMBER; Mode of pathogenicity: None; Publications: 33644825, 23404334, 24461433, 12684507, 30397276; Phenotypes: Congenital disorder of glycosylation, type Ii (MIM#607906), Myasthenic syndrome, congenital, 14, with tubular aggregates (MIM#616228); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.108 TSPAN7 Crystle Lee reviewed gene: TSPAN7: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mackenzie's Mission_Reproductive Carrier Screening v0.108 SGO1 Crystle Lee reviewed gene: SGO1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Chronic atrial and intestinal dysrhythmia (MIM#616201); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.108 VPS37A Crystle Lee reviewed gene: VPS37A: Rating: RED; Mode of pathogenicity: None; Publications: 22717650, 29473047; Phenotypes: Spastic paraplegia 53, autosomal recessive (MIM#614898); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Susceptibility to Viral Infections v0.83 IFNAR2 Peter McNaughton reviewed gene: IFNAR2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35442417; Phenotypes: Severe viral disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Susceptibility to Viral Infections v0.83 IFNAR1 Peter McNaughton reviewed gene: IFNAR1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35442418; Phenotypes: Severe Viral disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mackenzie's Mission_Reproductive Carrier Screening v0.108 UQCRQ Crystle Lee reviewed gene: UQCRQ: Rating: RED; Mode of pathogenicity: None; Publications: 18439546; Phenotypes: Mitochondrial complex III deficiency, nuclear type 4 (MIM#615159); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.89 SLC26A1 Krithika Murali reviewed gene: SLC26A1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ?Nephrolithiasis, calcium oxalate - MIM#167030; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Macrocystic Disease v0.45 NEK8 Chirag Patel Classified gene: NEK8 as Amber List (moderate evidence)
Renal Macrocystic Disease v0.45 NEK8 Chirag Patel Gene: nek8 has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.44 NEK8 Chirag Patel Classified gene: NEK8 as Amber List (moderate evidence)
Renal Macrocystic Disease v0.44 NEK8 Chirag Patel Gene: nek8 has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.44 NEK8 Chirag Patel Classified gene: NEK8 as Amber List (moderate evidence)
Renal Macrocystic Disease v0.44 NEK8 Chirag Patel Gene: nek8 has been classified as Amber List (Moderate Evidence).
Renal Macrocystic Disease v0.43 NEK8 Chirag Patel gene: NEK8 was added
gene: NEK8 was added to Renal Macrocystic Disease. Sources: Other
Mode of inheritance for gene: NEK8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NEK8 were set to Unpublished ESHG presentation
Phenotypes for gene: NEK8 were set to Renal cystic disease
Mode of pathogenicity for gene: NEK8 was set to Other
Review for gene: NEK8 was set to AMBER
Added comment: 12 families with paediatric renal cystic disease (enlarged kidneys, kidney cysts, ESKF <20yrs)
-3 recurrent HTZ variants in NEK8 kinase domain (Arg45Trp, Ile150Met, Lys157Gln)
-suspected dominant negative effect
-patient fibroblasts show normal ciliogenesis and normal localisation and expression of NEK8
(Note carriers of AR-NEK8 disease do not show renal manifestations, as variants are LOF)
Sources: Other
Renal Ciliopathies and Nephronophthisis v1.11 NEK8 Chirag Patel reviewed gene: NEK8: Rating: GREEN; Mode of pathogenicity: None; Publications: Unpublished ESHG presentation; Phenotypes: Renal cystic disease; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Liver Failure_Paediatric v1.13 SKIV2L Chirag Patel Classified gene: SKIV2L as Green List (high evidence)
Liver Failure_Paediatric v1.13 SKIV2L Chirag Patel Gene: skiv2l has been classified as Green List (High Evidence).
Liver Failure_Paediatric v1.12 SKIV2L Chirag Patel gene: SKIV2L was added
gene: SKIV2L was added to Liver Failure_Paediatric. Sources: Literature
Mode of inheritance for gene: SKIV2L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SKIV2L were set to PMID: 22444670, 33114497, 30397475, 29527791, 29484573
Phenotypes for gene: SKIV2L were set to Trichohepatoenteric syndrome 2, MIM# 614602; Respiratory infections; IUGR; Facial dysmorphic features; Wooly hair; Early-onset intractable diarrhoea; Liver cirrhosis; Platelet abnormalities
Review for gene: SKIV2L was set to GREEN
gene: SKIV2L was marked as current diagnostic
Added comment: Numerous families reported.
Sources: Literature
Liver Failure_Paediatric v1.11 TULP3 Chirag Patel Classified gene: TULP3 as Green List (high evidence)
Liver Failure_Paediatric v1.11 TULP3 Chirag Patel Gene: tulp3 has been classified as Green List (High Evidence).
Liver Failure_Paediatric v1.10 TULP3 Chirag Patel gene: TULP3 was added
gene: TULP3 was added to Liver Failure_Paediatric. Sources: Literature
Mode of inheritance for gene: TULP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TULP3 were set to PMID: 35397207
Phenotypes for gene: TULP3 were set to progressive degenerative liver fibrosis with variable fibrocystic kidney disease; hypertrophic cardiomyopathy MONDO:0005045
Review for gene: TULP3 was set to GREEN
gene: TULP3 was marked as current diagnostic
Added comment: 15 individuals from eight unrelated families with bi-allelic variants in TULP3 were detected. The affected individuals reported are mostly adults, in the 3rd through 7th decades of life, and presented with progressive degenerative liver fibrosis, then variable fibrocystic kidney disease and then hypertrophic cardiomyopathy. The human phenotype was recapitulated in adult zebrafish and confirmed disruption of critical ciliary cargo composition in several primary cell lines derived from affected individuals. Some G-P correlation with 2 x PTV leading to childhood disease (<10yrs), and 2 x missense variants leading to adult onset disease (>20yrs).
Sources: Literature
Cerebral Palsy v1.24 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital; Rare Disease
Dystonia - isolated/combined v1.23 DRD2 Chirag Patel Classified gene: DRD2 as Red List (low evidence)
Dystonia - isolated/combined v1.23 DRD2 Chirag Patel Added comment: Comment on list classification: Single family only
Dystonia - isolated/combined v1.23 DRD2 Chirag Patel Gene: drd2 has been classified as Red List (Low Evidence).
Dystonia - isolated/combined v1.22 DRD2 Shekeeb Mohammad edited their review of gene: DRD2: Changed rating: GREEN; Set current diagnostic: yes
Dystonia - isolated/combined v1.22 DRD2 Shekeeb Mohammad gene: DRD2 was added
gene: DRD2 was added to Dystonia - isolated/combined. Sources: Literature
Mode of inheritance for gene: DRD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DRD2 were set to 33200438
Phenotypes for gene: DRD2 were set to dystonia; chorea; anxiety; ataxia; orofacial dyskinesia; tremor; memory problems
Penetrance for gene: DRD2 were set to Complete
Mode of pathogenicity for gene: DRD2 was set to Other
Added comment: Gain of Function variants reported with disease in a single multigenerational family doi: 10.1002/mds.28385
Sources: Literature
Ciliopathies v1.29 ZNF423 Zornitza Stark Phenotypes for gene: ZNF423 were changed from Joubert syndrome 19, OMIM# 614844 to Joubert syndrome 19, OMIM# 614844; Nephronophthisis 14, OMIM:614844
Mendeliome v1.89 DDR2 Zornitza Stark changed review comment from: Bi-allelic variants in this gene are associated with a severe perinatal skeletal dysplasia.

Mono-allelic variants cause Warburg-Cinotti syndrome, which is characterized by progressive corneal neovascularization, keloid formation, chronic skin ulcers, wasting of subcutaneous tissue, flexion contractures of the fingers, and acroosteolysis. Four unrelated families reported with missense variants, which were activating.; to: Bi-allelic variants in this gene are associated with a severe perinatal skeletal dysplasia. LoF.

Mono-allelic variants cause Warburg-Cinotti syndrome, which is characterized by progressive corneal neovascularization, keloid formation, chronic skin ulcers, wasting of subcutaneous tissue, flexion contractures of the fingers, and acroosteolysis. Four unrelated families reported with missense variants, which were activating. GoF.
Cerebral Palsy v1.23 ELOVL1 Clare van Eyk changed review comment from: Same novel heterozygous missense variant reported in 2 families (p.Ser165Phe, described twice in the literature, PMIDs 30487246 and 29496980) de novo in one family, unknown inheritance in a second) with similar phenotype which included icthyotic keratoderma, spasticity, hypomyelination and some dysmorphism. Fatty acid profile was altered in HEK293 cells transfected with mutant construct.

An additional 2 members of a consanguineous family both with cerebral palsy were described with a novel homozygous variant affecting splicing of ELOVL1 and similar clinical phenotype with earlier onset and more severe phenotype (PMID 35379526) . Heterozygous parents are unaffected. Patient skin samples show defects in very long chain fatty acid synthesis.
Sources: Literature; to: Same novel heterozygous missense variant reported in 2 families (p.Ser165Phe, described twice in the literature, PMIDs 30487246 and 29496980) de novo in one family, unknown inheritance in a second) with similar phenotype which included icthyotic keratoderma, spasticity, hypomyelination and some dysmorphism. Fatty acid profile was altered in HEK293 cells transfected with mutant construct.

An additional 2 members of a consanguineous family both with cerebral palsy were described with a novel homozygous variant affecting splicing of ELOVL1 and similar clinical phenotype with earlier onset and more severe phenotype (PMID 35379526) . Heterozygous parents are unaffected. Patient skin samples show defects in very long chain fatty acid synthesis.
Sources: Literature
Cerebral Palsy v1.23 ADAR Clare van Eyk reviewed gene: ADAR: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34702576; Phenotypes: Aicardi-Goutieres syndrome 6, MIM#615010; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cerebral Palsy v1.23 ELOVL1 Clare van Eyk gene: ELOVL1 was added
gene: ELOVL1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ELOVL1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: ELOVL1 were set to (PMID: 35379526; 30487246; 29496980)
Phenotypes for gene: ELOVL1 were set to MIM 618527
Review for gene: ELOVL1 was set to GREEN
Added comment: Same novel heterozygous missense variant reported in 2 families (p.Ser165Phe, described twice in the literature, PMIDs 30487246 and 29496980) de novo in one family, unknown inheritance in a second) with similar phenotype which included icthyotic keratoderma, spasticity, hypomyelination and some dysmorphism. Fatty acid profile was altered in HEK293 cells transfected with mutant construct.

An additional 2 members of a consanguineous family both with cerebral palsy were described with a novel homozygous variant affecting splicing of ELOVL1 and similar clinical phenotype with earlier onset and more severe phenotype (PMID 35379526) . Heterozygous parents are unaffected. Patient skin samples show defects in very long chain fatty acid synthesis.
Sources: Literature
Hydrops fetalis v0.280 THSD1 Elena Savva Classified gene: THSD1 as Amber List (moderate evidence)
Hydrops fetalis v0.280 THSD1 Elena Savva Gene: thsd1 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.265 PBX1 Bryony Thompson Phenotypes for gene: PBX1 were changed from 46, XY gonadal dysgenesis to 46, XY gonadal dysgenesis; congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay MONDO:0060549
Differences of Sex Development v0.264 PBX1 Bryony Thompson Publications for gene: PBX1 were set to 31302614; 31058389
Differences of Sex Development v0.263 PBX1 Bryony Thompson Classified gene: PBX1 as Green List (high evidence)
Differences of Sex Development v0.263 PBX1 Bryony Thompson Gene: pbx1 has been classified as Green List (High Evidence).
Differences of Sex Development v0.262 PBX1 Bryony Thompson reviewed gene: PBX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35451537, 31302614, 31058389, 32141698; Phenotypes: congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay MONDO:0060549; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.89 TNNT1 Bryony Thompson Phenotypes for gene: TNNT1 were changed from Nemaline myopathy 5, Amish type, MIM# 605355 to Nemaline myopathy 5, Amish type, MIM# 605355; nemaline myopathy MONDO:0018958
Mendeliome v1.88 TNNT1 Bryony Thompson Publications for gene: TNNT1 were set to
Mendeliome v1.87 TNNT1 Bryony Thompson Added comment: Comment on mode of inheritance: There is emerging evidence for monoallelic mode of inheritance
Mendeliome v1.87 TNNT1 Bryony Thompson Mode of inheritance for gene: TNNT1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.86 TNNT1 Bryony Thompson Mode of inheritance for gene: TNNT1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.85 TNNT1 Bryony Thompson reviewed gene: TNNT1: Rating: AMBER; Mode of pathogenicity: Other; Publications: 29178646, 35510366; Phenotypes: nemaline myopathy MONDO:0018958; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.85 EPHA2 Elena Savva reviewed gene: EPHA2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34638995, 19005574, 19649315, 19306328, 33671840; Phenotypes: Early-Onset Cataract, cataract 6 multiple types MONDO:0007288; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.85 GRIA1 Zornitza Stark edited their review of gene: GRIA1: Changed phenotypes: Intellectual developmental disorder, autosomal dominant 67, MIM# 619927, Intellectual developmental disorder, autosomal recessive 76, MIM# 619931
Mendeliome v1.85 GRIA1 Zornitza Stark Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, MIM# 619927 to Intellectual developmental disorder, autosomal dominant 67, MIM# 619927; Intellectual developmental disorder, autosomal recessive 76, MIM# 619931
Mendeliome v1.84 GRIA1 Zornitza Stark Publications for gene: GRIA1 were set to 28628100; 23033978; 26350204; 24896178
Mendeliome v1.83 GRIA1 Zornitza Stark Mode of inheritance for gene: GRIA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.82 GRIA1 Zornitza Stark edited their review of gene: GRIA1: Added comment: Single individual reported with bi-allelic LoF variant. RED/AMBER for bi-allelic variants.; Changed publications: 28628100, 23033978, 26350204, 24896178, 35675825; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4831 GRIA1 Zornitza Stark changed review comment from: Single individual reported with bi-allelic LoF variant.; to: Single individual reported with bi-allelic LoF variant. RED/AMBER for bi-allelic variants.
Intellectual disability syndromic and non-syndromic v0.4831 GRIA1 Zornitza Stark Mode of inheritance for gene: GRIA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4830 GRIA1 Zornitza Stark Phenotypes for gene: GRIA1 were changed from Intellectual developmental disorder, autosomal dominant 67, MIM# 619927 to Intellectual developmental disorder, autosomal dominant 67, MIM# 619927; Intellectual developmental disorder, autosomal recessive 76, MIM# 619931
Intellectual disability syndromic and non-syndromic v0.4829 GRIA1 Zornitza Stark edited their review of gene: GRIA1: Added comment: Single individual reported with bi-allelic LoF variant.; Changed publications: 35675825; Changed phenotypes: Intellectual developmental disorder, autosomal recessive 76, MIM# 619931
Intellectual disability syndromic and non-syndromic v0.4829 GRIA1 Zornitza Stark Phenotypes for gene: GRIA1 were changed from Intellectual disability; autism to Intellectual developmental disorder, autosomal dominant 67, MIM# 619927
Intellectual disability syndromic and non-syndromic v0.4828 GRIA1 Zornitza Stark edited their review of gene: GRIA1: Changed phenotypes: Intellectual developmental disorder, autosomal dominant 67, MIM# 619927
Mendeliome v1.82 GRIA1 Zornitza Stark Phenotypes for gene: GRIA1 were changed from Intellectual disability; autism to Intellectual developmental disorder, autosomal dominant 67, MIM# 619927
Mendeliome v1.81 GRIA1 Zornitza Stark edited their review of gene: GRIA1: Changed phenotypes: Intellectual developmental disorder, autosomal dominant 67, MIM# 619927
Arrhythmia_SuperPanel v3.1 Bryony Thompson Panel types changed to Superpanel; Victorian Clinical Genetics Services; Rare Disease; Royal Melbourne Hospital
Primary Ovarian Insufficiency_Premature Ovarian Failure v0.302 MSH5 Zornitza Stark Mode of inheritance for gene: MSH5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.81 MSH5 Zornitza Stark Phenotypes for gene: MSH5 were changed from Premature ovarian failure 13, MIM#617442; Premature ovarian failure 13, MIM#617442 to Spermatogenic failure 74, MIM# 619937; Premature ovarian failure 13, MIM#617442
Mendeliome v1.80 MSH5 Zornitza Stark reviewed gene: MSH5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spermatogenic failure 74, MIM# 619937; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.80 MSH5 Zornitza Stark Phenotypes for gene: MSH5 were changed from Premature ovarian failure 13 MIM#617442 to Premature ovarian failure 13, MIM#617442; Premature ovarian failure 13, MIM#617442
Congenital Heart Defect v0.219 AFF4 Zornitza Stark Marked gene: AFF4 as ready
Congenital Heart Defect v0.219 AFF4 Zornitza Stark Gene: aff4 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.219 AFF4 Zornitza Stark Phenotypes for gene: AFF4 were changed from ventricular septal defect; patent ductus arteriosus; patent foramen ovale to CHOPS syndrome, MIM# 616368; ventricular septal defect; patent ductus arteriosus; patent foramen ovale
Congenital Heart Defect v0.218 AFF4 Zornitza Stark Classified gene: AFF4 as Green List (high evidence)
Congenital Heart Defect v0.218 AFF4 Zornitza Stark Gene: aff4 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.217 ACTC1 Zornitza Stark commented on gene: ACTC1: E101K is multiply reported as pathogenic/likely pathogenic for HCM rather than CHD in ClinVar.

The 17bp deletion was inherited from a parent, with a very questionable affected status (posteriorly deviated interventricular septum).
Congenital Heart Defect v0.217 AFF4 Chloe Stutterd gene: AFF4 was added
gene: AFF4 was added to Congenital Heart Defect. Sources: Literature,Expert Review
Mode of inheritance for gene: AFF4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AFF4 were set to 25730767; 31058441
Phenotypes for gene: AFF4 were set to ventricular septal defect; patent ductus arteriosus; patent foramen ovale
Review for gene: AFF4 was set to GREEN
Added comment: At least 15 unrelated individuals reported. CdL-like, clinically recognisable phenotype, characterised by cognitive impairment, coarse facies, heart defects, obesity, pulmonary involvement, short stature, and skeletal dysplasia. CHD include VSD, PDA, PFO.
Sources: Literature, Expert Review
Congenital Heart Defect v0.217 ACTC1 Chloe Stutterd reviewed gene: ACTC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17611253, 17947298; Phenotypes: Atrial septal defect, Ventricular septal defect; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hydrops fetalis v0.279 THSD1 Elena Savva gene: THSD1 was added
gene: THSD1 was added to Hydrops fetalis. Sources: Literature
Mode of inheritance for gene: THSD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: THSD1 were set to PMID: 33569873; 27895300
Phenotypes for gene: THSD1 were set to nonimmune hydrops fetalis
Review for gene: THSD1 was set to GREEN
Added comment: PMID: 33569873 - 1 fetus with a homozygous PTC and nonimmune hydrops fetalis (NIHF), congenital heart disease and hemangiomas. Mother described as having Crohns disease but nothing else unusual, no comments on the father. Fx of 1/3 triplets with severe hydrops fetalis, not sequenced.
- Paper reviews previous NIHF cases and reports another homozygous PTC in two families (4, 2 affected) and a recurring homozygous missense (p.Cys206Tyr) in three families (6, 4, 3 affected).
- No mention of clinically affected heterozygotes.

PMID: 27895300- Mouse model has hydrocephaly with poor perfusion.
Sources: Literature
Mendeliome v1.79 THSD1 Elena Savva reviewed gene: THSD1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33569873, 27895300; Phenotypes: Aneurysm, intracranial berry, 12 MIM# 618734, nonimmune hydrops fetalis; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cataract v0.344 GLS Chern Lim changed review comment from: PMID: 30239721:
A de novo Ser482Cys gain-of-function variant in GLS, associated with profound developmental delay and
infantile cataract.
Functional analysis demonstrated that this variant causes hyperactivity and compensatory downregulation of GLS expression combined with upregulation of the counteracting enzyme GS, supporting pathogenicity.; to: PMID: 30239721:
A de novo Ser482Cys gain-of-function variant in GLS, associated with profound developmental delay and infantile cataract.
Functional analysis demonstrated that this variant causes hyperactivity and compensatory downregulation of GLS expression combined with upregulation of the counteracting enzyme GS, supporting pathogenicity.
Cataract v0.344 GLS Chern Lim reviewed gene: GLS: Rating: AMBER; Mode of pathogenicity: Other; Publications: ; Phenotypes: Infantile cataract; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Polycystic liver disease v1.0 Bryony Thompson promoted panel to version 1.0
Polycystic liver disease v0.28 Bryony Thompson Panel types changed to Victorian Clinical Genetics Services; Genetic Health Queensland; Royal Melbourne Hospital; Rare Disease
Hereditary Spastic Paraplegia - paediatric v1.35 GCH1 Elena Savva Classified gene: GCH1 as Green List (high evidence)
Hereditary Spastic Paraplegia - paediatric v1.35 GCH1 Elena Savva Gene: gch1 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v1.34 GCH1 Elena Savva Classified gene: GCH1 as Amber List (moderate evidence)
Hereditary Spastic Paraplegia - paediatric v1.34 GCH1 Elena Savva Gene: gch1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.79 GCH1 Zornitza Stark Phenotypes for gene: GCH1 were changed from Hyperphenylalaninemia, BH4-deficient, B, MIM# 233910; Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, MIM# 128230 to Hyperphenylalaninemia, BH4-deficient, B, MIM# 233910; Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, MIM# 128230; Hereditary spastic paraplegia MONDO:0019064, GCH1-related
Mendeliome v1.78 GCH1 Zornitza Stark Publications for gene: GCH1 were set to 7874165; 11113234; 15753436; 9667588; 10987649; 32170445; 32278297; 32746945; 30314816
Mendeliome v1.77 GCH1 Zornitza Stark reviewed gene: GCH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21935284, 24509643, 33713342; Phenotypes: Hereditary spastic paraplegia MONDO:0019064, GCH1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Spastic Paraplegia - paediatric v1.33 GCH1 Zornitza Stark Publications for gene: GCH1 were set to 21935284; 24509643
Hereditary Spastic Paraplegia - paediatric v1.32 GCH1 Zornitza Stark Phenotypes for gene: GCH1 were changed from Dystonia; progressive spastic paraplegia; Spastic paraplegia; Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, 128230 to Hereditary spastic paraplegia MONDO:0019064, GCH1-related
Hereditary Spastic Paraplegia - paediatric v1.31 GCH1 Zornitza Stark Classified gene: GCH1 as Green List (high evidence)
Hereditary Spastic Paraplegia - paediatric v1.31 GCH1 Zornitza Stark Gene: gch1 has been classified as Green List (High Evidence).
Mendeliome v1.77 IL6ST Zornitza Stark edited their review of gene: IL6ST: Changed phenotypes: Hyper-IgE recurrent infection syndrome 4A, autosomal dominant , MIM#619752, Hyper-IgE recurrent infection syndrome 4B, autosomal recessive, MIM# 618523, Stuve-Wiedemann syndrome 2, MIM# 619751: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response, Hyper-IgE syndrome, autosomal dominant, Immunodeficiency 94 with autoinflammation and dysmorphic facies, MIM# 619750
Hereditary Spastic Paraplegia - paediatric v1.30 GCH1 Elena Savva changed review comment from: PMID: 33713342 - additional three patients (2 families) with heterozygous variants and HSP, all had onset in childhood; to: PMID: 33713342 - additional three patients (2 families) with heterozygous variants and HSP, all had onset in childhood
Hereditary Spastic Paraplegia - paediatric v1.30 GCH1 Elena Savva reviewed gene: GCH1: Rating: ; Mode of pathogenicity: None; Publications: PMID: 33713342, 24509643, 21935284; Phenotypes: Hereditary spastic paraplegia; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Dystonia - isolated/combined v1.22 SHQ1 Zornitza Stark Phenotypes for gene: SHQ1 were changed from Dystonia to Dystonia 35, childhood-onset , MIM# 619921
Dystonia - isolated/combined v1.21 SHQ1 Zornitza Stark edited their review of gene: SHQ1: Changed phenotypes: Dystonia 35, childhood-onset , MIM# 619921
Dystonia - complex v0.215 SHQ1 Zornitza Stark Phenotypes for gene: SHQ1 were changed from Dystonia; Neurodegeneration to Dystonia 35, childhood-onset , MIM# 619921; Neurodevelopmental disorder with dystonia and seizures, MIM# 619922
Dystonia - complex v0.214 SHQ1 Zornitza Stark edited their review of gene: SHQ1: Changed phenotypes: Dystonia 35, childhood-onset , MIM# 619921, Neurodevelopmental disorder with dystonia and seizures, MIM# 619922
Regression v0.481 SHQ1 Zornitza Stark Phenotypes for gene: SHQ1 were changed from Dystonia; Neurodegeneration to Neurodevelopmental disorder with dystonia and seizures, MIM# 619922
Regression v0.480 SHQ1 Zornitza Stark edited their review of gene: SHQ1: Changed phenotypes: Neurodevelopmental disorder with dystonia and seizures, MIM# 619922
Mendeliome v1.77 SHQ1 Zornitza Stark Phenotypes for gene: SHQ1 were changed from Dystonia; Neurodegeneration to Dystonia 35, childhood-onset , MIM# 619921; Neurodevelopmental disorder with dystonia and seizures, MIM# 619922
Mendeliome v1.76 SHQ1 Zornitza Stark edited their review of gene: SHQ1: Changed phenotypes: Dystonia 35, childhood-onset , MIM# 619921, Neurodevelopmental disorder with dystonia and seizures, MIM# 619922
Mendeliome v1.76 KCNA5 Zornitza Stark Classified gene: KCNA5 as Amber List (moderate evidence)
Mendeliome v1.76 KCNA5 Zornitza Stark Gene: kcna5 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.75 KCNA5 Zornitza Stark edited their review of gene: KCNA5: Added comment: Multiple families reported. At least one with LoF variant, rest missense. The missense variants are present in the population, ranging from 2 to 40 individuals in gnomad, which raises doubt about their pathogenicity.; Changed rating: AMBER
Deafness_IsolatedAndComplex v1.137 GREB1L Zornitza Stark Marked gene: GREB1L as ready
Deafness_IsolatedAndComplex v1.137 GREB1L Zornitza Stark Gene: greb1l has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.137 GREB1L Zornitza Stark Classified gene: GREB1L as Green List (high evidence)
Deafness_IsolatedAndComplex v1.137 GREB1L Zornitza Stark Gene: greb1l has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.136 GREB1L Manny Jacobs gene: GREB1L was added
gene: GREB1L was added to Deafness_IsolatedAndComplex. Sources: Literature
Mode of inheritance for gene: GREB1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GREB1L were set to PMID: 29100091; 29955957; 32585897; 35012281
Phenotypes for gene: GREB1L were set to Renal hypodysplasia/aplasia 3, OMIM# 617805; Deafness, autosomal dominant 80, MIM# 619274
Review for gene: GREB1L was set to GREEN
Added comment: 7 unrelated families reported for non syndromic AD deafness

Multiple unrelated families reported with CAKUT
Sources: Literature
Prepair 1000+ v0.31 SEMA4A Zornitza Stark Marked gene: SEMA4A as ready
Prepair 1000+ v0.31 SEMA4A Zornitza Stark Gene: sema4a has been classified as Red List (Low Evidence).
Prepair 1000+ v0.31 SEMA4A Zornitza Stark Phenotypes for gene: SEMA4A were changed from Cone-rod dystrophy 10, 610283 (3) to Cone-rod dystrophy 10, 610283; Retinitis pigmentosa 35, 610282
Prepair 1000+ v0.30 SEMA4A Zornitza Stark Publications for gene: SEMA4A were set to
Prepair 1000+ v0.29 SEMA4A Zornitza Stark Classified gene: SEMA4A as Red List (low evidence)
Prepair 1000+ v0.29 SEMA4A Zornitza Stark Gene: sema4a has been classified as Red List (Low Evidence).
Prepair 1000+ v0.28 SEMA4A Zornitza Stark reviewed gene: SEMA4A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Prepair 1000+ v0.28 SEC23A Zornitza Stark Marked gene: SEC23A as ready
Prepair 1000+ v0.28 SEC23A Zornitza Stark Gene: sec23a has been classified as Red List (Low Evidence).
Prepair 1000+ v0.28 SEC23A Zornitza Stark Phenotypes for gene: SEC23A were changed from Craniolenticulosutural dysplasia, 607812 (3) to Craniolenticulosutural dysplasia (MIM# 607812)
Prepair 1000+ v0.27 SEC23A Zornitza Stark Publications for gene: SEC23A were set to
Prepair 1000+ v0.26 SEC23A Zornitza Stark Classified gene: SEC23A as Red List (low evidence)
Prepair 1000+ v0.26 SEC23A Zornitza Stark Gene: sec23a has been classified as Red List (Low Evidence).
Prepair 1000+ v0.25 SEC23A Zornitza Stark reviewed gene: SEC23A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Prepair 1000+ v0.25 NUP62 Zornitza Stark Marked gene: NUP62 as ready
Prepair 1000+ v0.25 NUP62 Zornitza Stark Gene: nup62 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.25 NUP62 Zornitza Stark Phenotypes for gene: NUP62 were changed from Striatonigral degeneration, infantile, 271930 (3) to Striatonigral degeneration, infantile - MIM#271930
Prepair 1000+ v0.24 NUP62 Zornitza Stark Publications for gene: NUP62 were set to
Prepair 1000+ v0.23 NUP62 Zornitza Stark Classified gene: NUP62 as Red List (low evidence)
Prepair 1000+ v0.23 NUP62 Zornitza Stark Gene: nup62 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.22 NUP62 Zornitza Stark reviewed gene: NUP62: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Prepair 1000+ v0.22 NLGN4X Zornitza Stark Marked gene: NLGN4X as ready
Prepair 1000+ v0.22 NLGN4X Zornitza Stark Gene: nlgn4x has been classified as Red List (Low Evidence).
Prepair 1000+ v0.22 NLGN4X Zornitza Stark Phenotypes for gene: NLGN4X were changed from Mental retardation, X-linked, 300495 (3) to Intellectual developmental disorder, X-linked (MIM#300495)
Prepair 1000+ v0.21 NLGN4X Zornitza Stark Publications for gene: NLGN4X were set to
Prepair 1000+ v0.20 NLGN4X Zornitza Stark Classified gene: NLGN4X as Red List (low evidence)
Prepair 1000+ v0.20 NLGN4X Zornitza Stark Gene: nlgn4x has been classified as Red List (Low Evidence).
Prepair 1000+ v0.19 NDUFA11 Zornitza Stark Marked gene: NDUFA11 as ready
Prepair 1000+ v0.19 NDUFA11 Zornitza Stark Gene: ndufa11 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.19 NDUFA11 Zornitza Stark Phenotypes for gene: NDUFA11 were changed from Mitochondrial complex I deficiency, 252010 (3) to Mitochondrial complex I deficiency, nuclear type 14, MIM#618236
Prepair 1000+ v0.18 NDUFA11 Zornitza Stark Publications for gene: NDUFA11 were set to
Prepair 1000+ v0.17 NDUFA11 Zornitza Stark Classified gene: NDUFA11 as Red List (low evidence)
Prepair 1000+ v0.17 NDUFA11 Zornitza Stark Gene: ndufa11 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.16 NDUFA11 Zornitza Stark reviewed gene: NDUFA11: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Prepair 1000+ v0.16 MCM4 Zornitza Stark Marked gene: MCM4 as ready
Prepair 1000+ v0.16 MCM4 Zornitza Stark Gene: mcm4 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.16 MCM4 Zornitza Stark Phenotypes for gene: MCM4 were changed from Natural killer cell and glucocorticoid deficiency with DNA repair defect, 609981 (3) to Immunodeficiency 54, MIM# 609981
Prepair 1000+ v0.15 MCM4 Zornitza Stark Publications for gene: MCM4 were set to
Prepair 1000+ v0.14 MCM4 Zornitza Stark Classified gene: MCM4 as Red List (low evidence)
Prepair 1000+ v0.14 MCM4 Zornitza Stark Gene: mcm4 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.13 MCM4 Zornitza Stark reviewed gene: MCM4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Prepair 1000+ v0.13 LDHB Zornitza Stark Marked gene: LDHB as ready
Prepair 1000+ v0.13 LDHB Zornitza Stark Gene: ldhb has been classified as Red List (Low Evidence).
Prepair 1000+ v0.13 LDHB Zornitza Stark Classified gene: LDHB as Red List (low evidence)
Prepair 1000+ v0.13 LDHB Zornitza Stark Gene: ldhb has been classified as Red List (Low Evidence).
Prepair 1000+ v0.12 IGFBP7 Zornitza Stark Marked gene: IGFBP7 as ready
Prepair 1000+ v0.12 IGFBP7 Zornitza Stark Gene: igfbp7 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.12 IGFBP7 Zornitza Stark Phenotypes for gene: IGFBP7 were changed from Retinal arterial macroaneurysm with supravalvular pulmonic stenosis, 614224 (3) to Retinal arterial macroaneurysm with supravalvular pulmonic stenosis, MIM#614224
Prepair 1000+ v0.11 IGFBP7 Zornitza Stark Publications for gene: IGFBP7 were set to
Prepair 1000+ v0.10 IGFBP7 Zornitza Stark Classified gene: IGFBP7 as Red List (low evidence)
Prepair 1000+ v0.10 IGFBP7 Zornitza Stark Gene: igfbp7 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.9 IGFBP7 Zornitza Stark reviewed gene: IGFBP7: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Prepair 1000+ v0.9 EMG1 Zornitza Stark Marked gene: EMG1 as ready
Prepair 1000+ v0.9 EMG1 Zornitza Stark Gene: emg1 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.9 EMG1 Zornitza Stark Publications for gene: EMG1 were set to
Prepair 1000+ v0.8 EMG1 Zornitza Stark Classified gene: EMG1 as Red List (low evidence)
Prepair 1000+ v0.8 EMG1 Zornitza Stark Gene: emg1 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.7 EMG1 Zornitza Stark reviewed gene: EMG1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Prepair 1000+ v0.7 DSTYK Zornitza Stark Marked gene: DSTYK as ready
Prepair 1000+ v0.7 DSTYK Zornitza Stark Gene: dstyk has been classified as Red List (Low Evidence).
Prepair 1000+ v0.7 DSTYK Zornitza Stark Phenotypes for gene: DSTYK were changed from Spastic paraplegia 23, 270750 (3), Autosomal recessive to Spastic paraplegia 23, MIM# 270750
Prepair 1000+ v0.6 DSTYK Zornitza Stark Publications for gene: DSTYK were set to
Prepair 1000+ v0.5 DSTYK Zornitza Stark Classified gene: DSTYK as Red List (low evidence)
Prepair 1000+ v0.5 DSTYK Zornitza Stark Gene: dstyk has been classified as Red List (Low Evidence).
Prepair 1000+ v0.4 DSTYK Zornitza Stark reviewed gene: DSTYK: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Prepair 1000+ v0.4 ALG2 Zornitza Stark Marked gene: ALG2 as ready
Prepair 1000+ v0.4 ALG2 Zornitza Stark Gene: alg2 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.4 ALG2 Zornitza Stark Phenotypes for gene: ALG2 were changed from Myasthenic syndrome, congenital, 14, with tubular aggregates, 616228 (3) to Myasthenic syndrome, congenital, 14, with tubular aggregates, MIM# 616228; Congenital disorder of glycosylation, type Ii, MIM# 607906
Prepair 1000+ v0.3 ALG2 Zornitza Stark Publications for gene: ALG2 were set to
Prepair 1000+ v0.2 ALG2 Zornitza Stark Classified gene: ALG2 as Red List (low evidence)
Prepair 1000+ v0.2 ALG2 Zornitza Stark Gene: alg2 has been classified as Red List (Low Evidence).
Prepair 1000+ v0.1 ALG2 Zornitza Stark reviewed gene: ALG2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Prepair 1000+ v0.1 PIBF1 Zornitza Stark Marked gene: PIBF1 as ready
Prepair 1000+ v0.1 PIBF1 Zornitza Stark Gene: pibf1 has been classified as Green List (High Evidence).
Prepair 1000+ v0.1 PIBF1 Zornitza Stark Classified gene: PIBF1 as Green List (high evidence)
Prepair 1000+ v0.1 PIBF1 Zornitza Stark Gene: pibf1 has been classified as Green List (High Evidence).
Prepair 1000+ v0.0 PIBF1 Zornitza Stark reviewed gene: PIBF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Joubert syndrome 33 (MIM#617767); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuria v0.208 APOL1 Bryony Thompson Mode of inheritance for gene: APOL1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Proteinuria v0.207 APOL1 Bryony Thompson Mode of pathogenicity for gene: APOL1 was changed from to Other
Proteinuria v0.206 APOL1 Bryony Thompson Publications for gene: APOL1 were set to 20647424; 24206458; 20635188
Proteinuria v0.205 APOL1 Bryony Thompson Classified gene: APOL1 as Amber List (moderate evidence)
Proteinuria v0.205 APOL1 Bryony Thompson Added comment: Comment on list classification: Assigning amber status, because this is a susceptibility allele
Proteinuria v0.205 APOL1 Bryony Thompson Gene: apol1 has been classified as Amber List (Moderate Evidence).
Proteinuria v0.204 APOL1 Bryony Thompson reviewed gene: APOL1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 20647424, 25993319, 34350953; Phenotypes: focal segmental glomerulosclerosis 4, susceptibility to MONDO:0012931; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Red cell disorders v1.18 GATA1 Zornitza Stark Phenotypes for gene: GATA1 were changed from Thrombocytopaenia, X-linked, with or without dyserythropoietic anaemia, MIM# 300367 to Thrombocytopenia, X-linked, with or without dyserythropoietic anaemia, MIM# 300367; Haemolytic anaemia due to elevated adenosine deaminase, MIM# 301083
Red cell disorders v1.17 GATA1 Zornitza Stark edited their review of gene: GATA1: Changed phenotypes: Thrombocytopenia, X-linked, with or without dyserythropoietic anaemia, MIM# 300367, Haemolytic anaemia due to elevated adenosine deaminase 301083
Mendeliome v1.75 GATA1 Zornitza Stark Phenotypes for gene: GATA1 were changed from Thrombocytopaenia, X-linked, with or without dyserythropoietic anaemia, MIM# 300367 to Thrombocytopaenia, X-linked, with or without dyserythropoietic anaemia, MIM# 300367; Haemolytic anaemia due to elevated adenosine deaminase, MIM# 301083; Anemia, X-linked, with/without neutropenia and/or platelet abnormalities, MIM# 300835
Mendeliome v1.74 GATA1 Zornitza Stark Deleted their comment
Mendeliome v1.74 GATA1 Zornitza Stark edited their review of gene: GATA1: Added comment: Variants in GATA1 are associated with a number of haematological disorders, which probably represent a spectrum rather than distinct entities.; Changed phenotypes: Thrombocytopaenia, X-linked, with or without dyserythropoietic anaemia, MIM# 300367, Haemolytic anaemia due to elevated adenosine deaminase, MIM# 301083, Anemia, X-linked, with/without neutropenia and/or platelet abnormalities, MIM# 300835
Bone Marrow Failure v1.18 GATA1 Zornitza Stark edited their review of gene: GATA1: Changed phenotypes: Thrombocytopaenia, X-linked, with or without dyserythropoietic anaemia, MIM# 300367
Bone Marrow Failure v1.18 GATA1 Zornitza Stark edited their review of gene: GATA1: Changed phenotypes: Thrombocytopenia, X-linked, with or without dyserythropoietic anemia, MIM# 300367, Haemolytic anemia due to elevated adenosine deaminase 301083
Dystonia - complex v0.214 NR4A2 Zornitza Stark Phenotypes for gene: NR4A2 were changed from Intellectual Disability; Dystonia and Early-onset Parkinson to Intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism, MIM# 619911
Genetic Epilepsy v0.1627 NR4A2 Zornitza Stark Phenotypes for gene: NR4A2 were changed from Generalized hypotonia, Global developmental delay, Intellectual disability, Seizures, Behavioral abnormality, Abnormality of movement, Joint hypermobility to Intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism, MIM# 619911
Genetic Epilepsy v0.1626 NR4A2 Zornitza Stark edited their review of gene: NR4A2: Changed phenotypes: Intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism, MIM# 619911
Early-onset Parkinson disease v0.134 NR4A2 Zornitza Stark Phenotypes for gene: NR4A2 were changed from Intellectual Disability; Dystonia and Early-onset Parkinson to Intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism, MIM# 619911
Mendeliome v1.74 NR4A2 Zornitza Stark Phenotypes for gene: NR4A2 were changed from Intellectual disability; epilepsy to Intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism, MIM# 619911
Mendeliome v1.73 NR4A2 Zornitza Stark edited their review of gene: NR4A2: Changed phenotypes: Intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism, MIM# 619911
Intellectual disability syndromic and non-syndromic v0.4828 NR4A2 Zornitza Stark Phenotypes for gene: NR4A2 were changed from Intellectual disability; rolandic epilepsy; autism to Intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism, MIM# 619911
Mendeliome v1.73 KCNA5 Chern Lim reviewed gene: KCNA5: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.4827 KCNC2 Zornitza Stark Marked gene: KCNC2 as ready
Intellectual disability syndromic and non-syndromic v0.4827 KCNC2 Zornitza Stark Gene: kcnc2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4827 KCNC2 Zornitza Stark Classified gene: KCNC2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4827 KCNC2 Zornitza Stark Gene: kcnc2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4826 KCNC2 Zornitza Stark gene: KCNC2 was added
gene: KCNC2 was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review
Mode of inheritance for gene: KCNC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNC2 were set to 32392612; 31972370; 35314505
Phenotypes for gene: KCNC2 were set to Developmental and epileptic encephalopathy 103, MIM# 619913
Review for gene: KCNC2 was set to GREEN
Added comment: More than 10 unrelated families reported. ID ranges from mild to severe.
Sources: Expert Review
Genetic Epilepsy v0.1626 KCNC2 Zornitza Stark Phenotypes for gene: KCNC2 were changed from Developmental and epileptic encephalopathy 103, MIM# 619913 to Developmental and epileptic encephalopathy 103, MIM# 619913
Genetic Epilepsy v0.1625 KCNC2 Zornitza Stark Phenotypes for gene: KCNC2 were changed from epileptic encephalopathy; spastic tetraplegia; opisthotonos attacks; intellectual disability; West syndrome to Developmental and epileptic encephalopathy 103, MIM# 619913
Genetic Epilepsy v0.1624 KCNC2 Zornitza Stark Publications for gene: KCNC2 were set to PMID:32392612; 31972370
Genetic Epilepsy v0.1623 KCNC2 Zornitza Stark Classified gene: KCNC2 as Green List (high evidence)
Genetic Epilepsy v0.1623 KCNC2 Zornitza Stark Gene: kcnc2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1622 KCNC2 Zornitza Stark reviewed gene: KCNC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 35314505; Phenotypes: Developmental and epileptic encephalopathy 103, MIM# 619913; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.73 KCNC2 Zornitza Stark Phenotypes for gene: KCNC2 were changed from epileptic encephalopathy; spastic tetraplegia; opisthotonos attacks; intellectual disability; West syndrome to Developmental and epileptic encephalopathy 103, MIM# 619913
Mendeliome v1.72 KCNC2 Zornitza Stark Publications for gene: KCNC2 were set to 32392612; 31972370
Mendeliome v1.71 KCNC2 Zornitza Stark Classified gene: KCNC2 as Green List (high evidence)
Mendeliome v1.71 KCNC2 Zornitza Stark Gene: kcnc2 has been classified as Green List (High Evidence).
Mendeliome v1.70 KCNC2 Zornitza Stark reviewed gene: KCNC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 35314505; Phenotypes: Developmental and epileptic encephalopathy 103, MIM# 619913; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.70 KCNJ1 Zornitza Stark Publications for gene: KCNJ1 were set to 28630040
Mendeliome v1.69 KCNJ1 Zornitza Stark reviewed gene: KCNJ1: Rating: GREEN; Mode of pathogenicity: None; Publications: 8841184, 19096086, 7635463, 12086641, 9580661, 12122007; Phenotypes: Bartter syndrome, type 2, MIM#241200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral vascular malformations v0.31 COL4A1 Zornitza Stark Marked gene: COL4A1 as ready
Cerebral vascular malformations v0.31 COL4A1 Zornitza Stark Gene: col4a1 has been classified as Green List (High Evidence).
Cerebral vascular malformations v0.31 COL4A1 Zornitza Stark Phenotypes for gene: COL4A1 were changed from {Hemorrhage, intracerebral, susceptibility to}, 614519; Brain small vessel disease with or without ocular anomalies; Brain Small Vessel Disease with Hemorrhage; {Hemorrhage, intracerebral, susceptibility to} to Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps, MIM# 611773; Brain small vessel disease with or without ocular anomalies, MIM# 175780
Cerebral vascular malformations v0.30 COL4A1 Zornitza Stark Publications for gene: COL4A1 were set to
Cerebral vascular malformations v0.29 COL4A1 Zornitza Stark Mode of inheritance for gene: COL4A1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral vascular malformations v0.28 COL4A1 Zornitza Stark Classified gene: COL4A1 as Green List (high evidence)
Cerebral vascular malformations v0.28 COL4A1 Zornitza Stark Gene: col4a1 has been classified as Green List (High Evidence).
Cerebral vascular malformations v0.27 COL4A1 Zornitza Stark reviewed gene: COL4A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps, MIM# 611773, Brain small vessel disease with or without ocular anomalies, MIM# 175780; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4825 ATP2B1 Zornitza Stark Phenotypes for gene: ATP2B1 were changed from Neurodevelopmental disorder, MONDO:0700092, ATP2B1-related to Intellectual developmental disorder, autosomal dominant 66, MIM# 619910
Intellectual disability syndromic and non-syndromic v0.4824 ATP2B1 Zornitza Stark reviewed gene: ATP2B1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal dominant 66, MIM# 619910; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1622 ATP2B1 Zornitza Stark Phenotypes for gene: ATP2B1 were changed from Neurodevelopmental disorder, MONDO:0700092, ATP2B1-related to Intellectual developmental disorder, autosomal dominant 66, MIM# 619910
Genetic Epilepsy v0.1621 ATP2B1 Zornitza Stark reviewed gene: ATP2B1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal dominant 66, MIM# 619910; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.69 ATP2B1 Zornitza Stark Phenotypes for gene: ATP2B1 were changed from Neurodevelopmental disorder, MONDO:0700092, ATP2B1-related to Intellectual developmental disorder, autosomal dominant 66, MIM# 619910
Mendeliome v1.68 ATP2B1 Zornitza Stark reviewed gene: ATP2B1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal dominant 66, MIM# 619910; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4824 PRDM13 Zornitza Stark Phenotypes for gene: PRDM13 were changed from Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, MIM# 619761 to Pontocerebellar hypoplasia, type 17, MIM# 619909; Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, MIM# 619761
Intellectual disability syndromic and non-syndromic v0.4823 PRDM13 Zornitza Stark edited their review of gene: PRDM13: Added comment: Note only single family reported with MIM#619761. The two disorders likely represent a continuum of severity.; Changed phenotypes: Pontocerebellar hypoplasia, type 17, MIM# 619909, Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, MIM# 619761
Mendeliome v1.68 PRDM13 Zornitza Stark Phenotypes for gene: PRDM13 were changed from Chorioretinal atrophy, progressive bifocal, MIM# 600790; Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, MIM# 619761 to Chorioretinal atrophy, progressive bifocal, MIM# 600790; Pontocerebellar hypoplasia, type 17, MIM# 619909; Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, MIM# 61976
Mendeliome v1.67 PRDM13 Zornitza Stark Publications for gene: PRDM13 were set to 30710461; 34730112; 35390279
Mendeliome v1.66 PRDM13 Zornitza Stark edited their review of gene: PRDM13: Added comment: Note only single family reported with Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, MIM# 61976 -- this likely lies on the same spectrum as Pontocerebellar hypoplasia, type 17, MIM# 619909 rather than being a distinct disorder.; Changed publications: 30710461, 34730112; Changed phenotypes: Retinal dystrophy, Chorioretinal atrophy, progressive bifocal, MIM# 600790, Pontocerebellar hypoplasia, type 17, MIM# 619909, Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, MIM# 61976; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cerebellar and Pontocerebellar Hypoplasia v1.53 PRDM13 Zornitza Stark Publications for gene: PRDM13 were set to PMID: 35390279
Cerebellar and Pontocerebellar Hypoplasia v1.52 PRDM13 Zornitza Stark Phenotypes for gene: PRDM13 were changed from Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, MIM# 619761 to Pontocerebellar hypoplasia, type 17, MIM# 619909; Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, MIM# 619761
Cerebellar and Pontocerebellar Hypoplasia v1.51 PRDM13 Zornitza Stark edited their review of gene: PRDM13: Added comment: Note only single family reported with MIM#619761. The two disorders likely represent a continuum of severity.; Changed publications: 34730112; Changed phenotypes: Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, MIM# 619761, Pontocerebellar hypoplasia, type 17, MIM# 619909
Intellectual disability syndromic and non-syndromic v0.4823 TIAM1 Zornitza Stark Phenotypes for gene: TIAM1 were changed from Neurodevelopmental disorder, TIAM1-related, MONDO:0700092 to Neurodevelopmental disorder with language delay and seizures, MIM# 619908
Genetic Epilepsy v0.1621 TIAM1 Zornitza Stark Phenotypes for gene: TIAM1 were changed from Neurodevelopmental disorder, TIAM1-related, MONDO:0700092 to Neurodevelopmental disorder with language delay and seizures, MIM# 619908
Mendeliome v1.66 TIAM1 Zornitza Stark Phenotypes for gene: TIAM1 were changed from Neurodevelopmental disorder, TIAM1-related, MONDO:0700092 to Neurodevelopmental disorder with language delay and seizures, MIM# 619908
Mendeliome v1.65 RBFOX2 Chern Lim changed review comment from: - PMID: 26785492: Analysed CHD (1213 congenital heart disease trios) and control (autism spectrum disorder) trios for de novo mutations. Found RBFOX2 gene had significantly more damaging de novo variants than expected: 3 de novo LoF variants (eg. nonsense, frameshift, or canonical splice disruptions). All 3 probands have hypoplastic left heart syndrome (HLHS). No further patient-specific clinical or variant info were available. Same cohort later included in PMID: 32368696, listed 4 de novo variants in this gene, in patients with left ventricular outflow tract obstruction (LVOTO) or conotruncal defects (CTDs).

- PMID: 27670201: RNA expression study showed the silenced allele harbours a nonsense RBFOX2 variant (Arg287*), CHD patient heart tissue sample, same patient published in PMID: 26785492.
- PMID: 27485310: Functional studies using heart tissue sample from HLHS patient with NM_001031695.2:c.859C>T p.(Arg287*) showed subcellular mislocalisation, impacting its nuclear function in RNA splicing.

- PMID: 25205790: De novo 111.3kb del chr22:36038076-36149338 (hg19) which includes APOL5,APOL6,RBFOX2, in a patient with HLHS.

- PMID: 35137168: Rbfox2 conditional knockout mouse model recapitulated several molecular and phenotypic features of HLHS.; to: - PMID: 26785492: Analysed CHD (1213 congenital heart disease trios) and control (autism spectrum disorder) trios for de novo mutations. Found RBFOX2 gene had significantly more damaging de novo variants than expected: 3 de novo LoF variants (1x nonsense, 1x frameshift, 1x canonical splice variants). All 3 probands have hypoplastic left heart syndrome (HLHS) and no extra-cardiac features. Same cohort later included in PMID: 32368696, listed one additional de novo variant in this gene (missense variant) in a patient with conotruncal defects (CTDs).

- PMID: 27670201: RNA expression study showed the silenced allele harbours a nonsense RBFOX2 variant (Arg287*), CHD patient heart tissue sample, same patient published in PMID: 26785492.
- PMID: 27485310: Functional studies using heart tissue sample from HLHS patient with NM_001031695.2:c.859C>T p.(Arg287*) showed subcellular mislocalisation, impacting its nuclear function in RNA splicing.

- PMID: 25205790: De novo 111.3kb del chr22:36038076-36149338 (hg19) which includes APOL5,APOL6,RBFOX2, in a patient with HLHS.

- PMID: 35137168: Rbfox2 conditional knockout mouse model recapitulated several molecular and phenotypic features of HLHS.
Cerebral vascular malformations v0.27 COL4A1 Nicola Fearn reviewed gene: COL4A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27794444, PMID 25719457, OMIM 120130; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1620 DLG4 Zornitza Stark Marked gene: DLG4 as ready
Genetic Epilepsy v0.1620 DLG4 Zornitza Stark Gene: dlg4 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1620 DLG4 Zornitza Stark Mode of inheritance for gene: DLG4 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1619 DLG4 Zornitza Stark Classified gene: DLG4 as Green List (high evidence)
Genetic Epilepsy v0.1619 DLG4 Zornitza Stark Gene: dlg4 has been classified as Green List (High Evidence).
Vasculitis v0.71 TGFBR1 Sue White commented on gene: TGFBR1
Prepair 1000+ v0.0 SEMA4A Crystle Lee reviewed gene: SEMA4A: Rating: RED; Mode of pathogenicity: None; Publications: 16199541, 28805479; Phenotypes: Cone-rod dystrophy 10, 610283, Retinitis pigmentosa 35, 610282; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Prepair 1000+ v0.0 SEC23A Crystle Lee changed review comment from: Amber in Mendeliome. Insufficient evidence for inclusion.

There is only one family reported with convincing evidence for gene-disease association, and we have downgraded this gene on other panels.; to: Amber in Mendeliome. Insufficient evidence for inclusion.

There is only one family reported with convincing evidence for gene-disease association, and we have downgraded this gene on other panels.
Prepair 1000+ v0.0 SEC23A Crystle Lee reviewed gene: SEC23A: Rating: ; Mode of pathogenicity: None; Publications: 16980979, 21039434, 16980978, 27148587; Phenotypes: Craniolenticulosutural dysplasia (MIM# 607812); Mode of inheritance: None
Prepair 1000+ v0.0 NUP62 Crystle Lee reviewed gene: NUP62: Rating: RED; Mode of pathogenicity: None; Publications: 16786527; Phenotypes: Striatonigral degeneration, infantile - MIM#271930; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.0 NLGN4X Crystle Lee reviewed gene: NLGN4X: Rating: RED; Mode of pathogenicity: None; Publications: 12669065, 18231125, 10071191, 29428674; Phenotypes: Intellectual developmental disorder, X-linked (MIM#300495); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v0.0 NDUFA11 Crystle Lee reviewed gene: NDUFA11: Rating: RED; Mode of pathogenicity: None; Publications: 18306244, 31074871; Phenotypes: Mitochondrial complex I deficiency, nuclear type 14, MIM#618236; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.65 CSNK2B Bryony Thompson Phenotypes for gene: CSNK2B were changed from Poirier-Bienvenu neurodevelopmental syndrome , MIM#618732 to Poirier-Bienvenu neurodevelopmental syndrome , MIM#618732; Craniodigital syndrome-intellectual disability syndrome MONDO:0015463
Mendeliome v1.64 CSNK2B Bryony Thompson Publications for gene: CSNK2B were set to 28585349; 28762608
Prepair 1000+ v0.0 MCM4 Crystle Lee reviewed gene: MCM4: Rating: RED; Mode of pathogenicity: None; Publications: 22354167, 22354170, 22499342; Phenotypes: Immunodeficiency 54, MIM# 609981; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.0 LDHB Crystle Lee reviewed gene: LDHB: Rating: RED; Mode of pathogenicity: None; Publications: 6383647; Phenotypes: Lactate dehydrogenase-B deficiency, MIM# 614128; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.0 IGFBP7 Crystle Lee reviewed gene: IGFBP7: Rating: RED; Mode of pathogenicity: None; Publications: 34519236, 31730227, 32429784; Phenotypes: Retinal arterial macroaneurysm with supravalvular pulmonic stenosiS, MIM#614224; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.0 EMG1 Crystle Lee reviewed gene: EMG1: Rating: RED; Mode of pathogenicity: None; Publications: 19463982; Phenotypes: Bowen-Conradi syndrome MIM #2111180; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.0 DSTYK Crystle Lee reviewed gene: DSTYK: Rating: RED; Mode of pathogenicity: None; Publications: 28157540, 23862974; Phenotypes: Spastic paraplegia 23, MIM# 270750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v0.0 ALG2 Crystle Lee reviewed gene: ALG2: Rating: AMBER; Mode of pathogenicity: None; Publications: 23404334, 24461433, 12684507; Phenotypes: Myasthenic syndrome, congenital, 14, with tubular aggregates, MIM# 616228, Congenital disorder of glycosylation, type Ii, MIM# 607906; Mode of inheritance: None
Mendeliome v1.63 CSNK2B Bryony Thompson reviewed gene: CSNK2B: Rating: GREEN; Mode of pathogenicity: Other; Publications: 35571680; Phenotypes: Craniodigital syndrome-intellectual disability syndrome MONDO:0015463; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1618 DLG4 Lucy Spencer gene: DLG4 was added
gene: DLG4 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: DLG4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DLG4 were set to 33597769
Phenotypes for gene: DLG4 were set to Intellectual developmental disorder, autosomal dominant 62 MIM#618793
Review for gene: DLG4 was set to GREEN
Added comment: PMID: 33597769- A cohort of 53 individuals with DLG4 variants 24 of whom had epilepsy or some form of seizures including focal or febrile seizures along with ID and other features.
Sources: Literature
Hereditary Neuropathy - complex v0.128 SLC5A6 Zornitza Stark Phenotypes for gene: SLC5A6 were changed from Neurodegeneration, infantile-onset, biotin-responsive, MIM# 618973 to Peripheral motor neuropathy, childhood-onset, biotin-responsive, MIM# 619903
Hereditary Neuropathy - complex v0.127 SLC5A6 Zornitza Stark edited their review of gene: SLC5A6: Changed phenotypes: Peripheral motor neuropathy, childhood-onset, biotin-responsive, MIM# 619903
Mendeliome v1.63 SLC5A6 Zornitza Stark Phenotypes for gene: SLC5A6 were changed from Developmental delay; epilepsy; neurodegeneration; Neurodegeneration, infantile-onset, biotin-responsive, MIM# 618973 to Peripheral motor neuropathy, childhood-onset, biotin-responsive, MIM# 619903; Neurodegeneration, infantile-onset, biotin-responsive, MIM# 618973
Mendeliome v1.62 SLC5A6 Zornitza Stark Publications for gene: SLC5A6 were set to 31754459; 27904971
Mendeliome v1.61 SLC5A6 Zornitza Stark changed review comment from: Two unrelated families reported, functional data and some evidence of response to treatment.
Sources: Literature; to: Complex neurodegenerative disorder: Two unrelated families reported, functional data and some evidence of response to treatment.
Sources: Literature
Mendeliome v1.61 SLC5A6 Zornitza Stark edited their review of gene: SLC5A6: Added comment: PMID 35013551: 5 individuals from 3 unrelated families reported with predominantly neuropathy phenotype.; Changed publications: 31754459, 27904971, 35013551; Changed phenotypes: Peripheral motor neuropathy, childhood-onset, biotin-responsive, MIM# 619903, Neurodegeneration, infantile-onset, biotin-responsive, MIM# 618973
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.69 DNMT3B Bryony Thompson Marked gene: DNMT3B as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.69 DNMT3B Bryony Thompson Gene: dnmt3b has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.69 DNMT3B Bryony Thompson Classified gene: DNMT3B as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.69 DNMT3B Bryony Thompson Gene: dnmt3b has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.68 DNMT3B Bryony Thompson gene: DNMT3B was added
gene: DNMT3B was added to Limb Girdle Muscular Dystrophy. Sources: Literature
Mode of inheritance for gene: DNMT3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DNMT3B were set to 27153398; 33004076
Phenotypes for gene: DNMT3B were set to Facioscapulohumeral muscular dystrophy MONDO:0001347
Review for gene: DNMT3B was set to AMBER
Added comment: FSHD shares some features with LGMD.
Two families reported with FSHD2. In one family carriers of the heterozygous DNMT3B missense variant (c.1579T>C) had reduced DNA methylation levels at the D4Z4 repeat array and were more likely to develop FSHD in comparison to other family members carrying an identical permissive 4qA allele of 9 D4Z4 units. In the other family, digenic inheritance of a heterozygous DNMT3B missense variant (c.2072C>T) and a permissive 4qA allele of 13 D4Z4 units induced hypomethylation at the D4Z4 repeat array but only one of the two family members was diagnosed with FSHD. A mouse model with an in-frame deletion (similar to the reported missense variants) does not induce a skeletal muscle pathology nor does it increase the extremely low DUX4 transcript levels in skeletal muscles of a FSHD transgenic mouse. The mouse model also suggested that Smchd1 may have a more potent role in DUX4 derepression than Dnmt3b.
Sources: Literature
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.67 LRIF1 Bryony Thompson Marked gene: LRIF1 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.67 LRIF1 Bryony Thompson Gene: lrif1 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.67 LRIF1 Bryony Thompson Classified gene: LRIF1 as Amber List (moderate evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.67 LRIF1 Bryony Thompson Gene: lrif1 has been classified as Amber List (Moderate Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.66 LRIF1 Bryony Thompson gene: LRIF1 was added
gene: LRIF1 was added to Limb Girdle Muscular Dystrophy. Sources: Literature
Mode of inheritance for gene: LRIF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRIF1 were set to 32467133
Phenotypes for gene: LRIF1 were set to Facioscapulohumeral muscular dystrophy MONDO:0001347
Review for gene: LRIF1 was set to AMBER
Added comment: FSHD shares some similar features with LGMD.
A single consanguineous case with a homozygous truncating variant, and D4Z4 repeat of 13 units on a 4qA haplotype (permissive haplotype). DZ4Z hypomethylation and increased DUX expression was present in patient cells. siRNA-mediated depletion of LRIF1L in immortalized myoblasts derepressed the DUX4 locus.
Sources: Literature
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.65 SMCHD1 Bryony Thompson Marked gene: SMCHD1 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.65 SMCHD1 Bryony Thompson Gene: smchd1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.65 SMCHD1 Bryony Thompson Classified gene: SMCHD1 as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.65 SMCHD1 Bryony Thompson Gene: smchd1 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v0.64 SMCHD1 Bryony Thompson gene: SMCHD1 was added
gene: SMCHD1 was added to Limb Girdle Muscular Dystrophy. Sources: Expert list
Mode of inheritance for gene: SMCHD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMCHD1 were set to 20301616
Phenotypes for gene: SMCHD1 were set to Facioscapulohumeral muscular dystrophy MONDO:0001347
Review for gene: SMCHD1 was set to GREEN
gene: SMCHD1 was marked as current diagnostic
Added comment: FSHD can have overlapping features with LGMD
Sources: Expert list
Prepair 1000+ v0.0 PIBF1 Crystle Lee gene: PIBF1 was added
gene: PIBF1 was added to Reproductive Carrier Screen_VCGS. Sources: Literature
Mode of inheritance for gene: PIBF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIBF1 were set to 26167768; 30858804; 29695797; 33004012
Phenotypes for gene: PIBF1 were set to Joubert syndrome 33 (MIM#617767)
Review for gene: PIBF1 was set to AMBER
Added comment: Green gene to be considered for inclusion

Three unrelated families plus three Hutterite families reported with bi-allelic variants in this gene.
Sources: Literature
Muscular dystrophy and myopathy_Paediatric v0.119 DAG1 Zornitza Stark Marked gene: DAG1 as ready
Muscular dystrophy and myopathy_Paediatric v0.119 DAG1 Zornitza Stark Gene: dag1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.119 DAG1 Zornitza Stark Phenotypes for gene: DAG1 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 9; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 9, 613818; Walker-Warburg syndrome and tectocerebellar dysgraphia
Muscular dystrophy and myopathy_Paediatric v0.118 DAG1 Zornitza Stark Publications for gene: DAG1 were set to
Muscular dystrophy and myopathy_Paediatric v0.117 DAG1 Zornitza Stark Mode of inheritance for gene: DAG1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.832 RMND1 Zornitza Stark Marked gene: RMND1 as ready
Mitochondrial disease v0.832 RMND1 Zornitza Stark Gene: rmnd1 has been classified as Green List (High Evidence).
Mitochondrial disease v0.832 RMND1 Zornitza Stark Phenotypes for gene: RMND1 were changed from to Combined oxidative phosphorylation deficiency 11 MIM#614922
Mitochondrial disease v0.831 RMND1 Zornitza Stark Publications for gene: RMND1 were set to
Mitochondrial disease v0.830 RMND1 Zornitza Stark Mode of inheritance for gene: RMND1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1618 RMND1 Zornitza Stark Marked gene: RMND1 as ready
Genetic Epilepsy v0.1618 RMND1 Zornitza Stark Gene: rmnd1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1618 RMND1 Zornitza Stark Phenotypes for gene: RMND1 were changed from to Combined oxidative phosphorylation deficiency 11 MIM#614922
Genetic Epilepsy v0.1617 RMND1 Zornitza Stark Publications for gene: RMND1 were set to
Genetic Epilepsy v0.1616 RMND1 Zornitza Stark Mode of inheritance for gene: RMND1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.116 COL6A1 Zornitza Stark Marked gene: COL6A1 as ready
Muscular dystrophy and myopathy_Paediatric v0.116 COL6A1 Zornitza Stark Gene: col6a1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.116 COL6A1 Zornitza Stark Phenotypes for gene: COL6A1 were changed from to Bethlem myopathy MIM#158810; Ullrich congenital muscular dystrophy MIM#254090
Muscular dystrophy and myopathy_Paediatric v0.115 COL6A1 Zornitza Stark Publications for gene: COL6A1 were set to
Muscular dystrophy and myopathy_Paediatric v0.114 COL6A1 Zornitza Stark Mode of inheritance for gene: COL6A1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.113 COL6A1 Zornitza Stark reviewed gene: COL6A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Combined Immunodeficiency v1.15 SASH3 Zornitza Stark Phenotypes for gene: SASH3 were changed from Combined immunodeficiency; immune dysregulation to Immunodeficiency 102, MIM# 301082
Disorders of immune dysregulation v0.143 SASH3 Zornitza Stark Phenotypes for gene: SASH3 were changed from Combined immunodeficiency; immune dysregulation to Immunodeficiency 102, MIM# 301082
Disorders of immune dysregulation v0.142 SASH3 Zornitza Stark edited their review of gene: SASH3: Changed phenotypes: Immunodeficiency 102, MIM# 301082
Combined Immunodeficiency v1.14 SASH3 Zornitza Stark edited their review of gene: SASH3: Changed phenotypes: Immunodeficiency 102, MIM# 301082
Mendeliome v1.61 SASH3 Zornitza Stark Phenotypes for gene: SASH3 were changed from Combined immunodeficiency; immune dysregulation to Immunodeficiency 102, MIM# 301082
Mendeliome v1.60 SASH3 Zornitza Stark edited their review of gene: SASH3: Changed phenotypes: Immunodeficiency 102, MIM# 301082
Mitochondrial disease v0.829 RMND1 Belinda Chong reviewed gene: RMND1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18835491, 23022099, 23022098, 25604853, 26395190; Phenotypes: Combined oxidative phosphorylation deficiency 11 MIM#614922; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic Epilepsy v0.1615 RMND1 Belinda Chong reviewed gene: RMND1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23022098, 25604853, 26395190; Phenotypes: Combined oxidative phosphorylation deficiency 11 MIM#614922; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.60 BUB1 Elena Savva Classified gene: BUB1 as Amber List (moderate evidence)
Mendeliome v1.60 BUB1 Elena Savva Gene: bub1 has been classified as Amber List (Moderate Evidence).
Callosome v0.455 RMND1 Zornitza Stark Marked gene: RMND1 as ready
Callosome v0.455 RMND1 Zornitza Stark Gene: rmnd1 has been classified as Green List (High Evidence).
Callosome v0.455 RMND1 Zornitza Stark Phenotypes for gene: RMND1 were changed from to Combined oxidative phosphorylation deficiency 11 MIM#614922
Callosome v0.454 RMND1 Zornitza Stark Publications for gene: RMND1 were set to
Callosome v0.453 RMND1 Zornitza Stark Mode of inheritance for gene: RMND1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Callosome v0.452 RMND1 Zornitza Stark reviewed gene: RMND1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined oxidative phosphorylation deficiency 11 MIM#614922; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebellar and Pontocerebellar Hypoplasia v1.51 ATOH1 Zornitza Stark Marked gene: ATOH1 as ready
Cerebellar and Pontocerebellar Hypoplasia v1.51 ATOH1 Zornitza Stark Gene: atoh1 has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.51 ATOH1 Zornitza Stark Classified gene: ATOH1 as Amber List (moderate evidence)
Cerebellar and Pontocerebellar Hypoplasia v1.51 ATOH1 Zornitza Stark Gene: atoh1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.59 BUB1 Zornitza Stark reviewed gene: BUB1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, BUB1-related MONDO:0700092; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.59 BUB1 Zornitza Stark Classified gene: BUB1 as Amber List (moderate evidence)
Mendeliome v1.59 BUB1 Zornitza Stark Gene: bub1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4822 SEMA6B Zornitza Stark Marked gene: SEMA6B as ready
Intellectual disability syndromic and non-syndromic v0.4822 SEMA6B Zornitza Stark Gene: sema6b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4822 SEMA6B Zornitza Stark Classified gene: SEMA6B as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4822 SEMA6B Zornitza Stark Gene: sema6b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4821 IREB2 Zornitza Stark Publications for gene: IREB2 were set to 30915432; 31243445; 11175792
Intellectual disability syndromic and non-syndromic v0.4820 IREB2 Zornitza Stark edited their review of gene: IREB2: Added comment: Additional individual reported in PMID 35602653; Changed publications: 30915432, 31243445, 11175792, 35602653
Regression v0.480 IREB2 Zornitza Stark Publications for gene: IREB2 were set to 30915432; 31243445; 11175792
Regression v0.479 IREB2 Zornitza Stark edited their review of gene: IREB2: Added comment: Additional individual reported PMID 35602653; Changed publications: 30915432, 31243445, 11175792, 35602653
Mendeliome v1.58 IREB2 Zornitza Stark Publications for gene: IREB2 were set to 30915432; 31243445; 11175792
Disorders of immune dysregulation v0.142 GIMAP6 Zornitza Stark Phenotypes for gene: GIMAP6 were changed from Autophagy, immune competence and inflammation to Autoinflammatory syndrome MONDO:0019751, GIMAP6-related
Mendeliome v1.57 GIMAP6 Zornitza Stark Phenotypes for gene: GIMAP6 were changed from Autophagy, immune competence and inflammation to Autoinflammatory syndrome MONDO:0019751, GIMAP6-related
Mendeliome v1.56 GIMAP6 Zornitza Stark reviewed gene: GIMAP6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Autoinflammatory syndrome MONDO:0019751, GIMAP6-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bone Marrow Failure v1.18 PTPN13 Zornitza Stark Marked gene: PTPN13 as ready
Bone Marrow Failure v1.18 PTPN13 Zornitza Stark Gene: ptpn13 has been classified as Amber List (Moderate Evidence).
Bone Marrow Failure v1.18 PTPN13 Zornitza Stark Classified gene: PTPN13 as Amber List (moderate evidence)
Bone Marrow Failure v1.18 PTPN13 Zornitza Stark Gene: ptpn13 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.56 BUB1 Elena Savva Classified gene: BUB1 as Red List (low evidence)
Mendeliome v1.56 BUB1 Elena Savva Gene: bub1 has been classified as Red List (Low Evidence).
Fetal anomalies v1.40 PAN2 Zornitza Stark Marked gene: PAN2 as ready
Fetal anomalies v1.40 PAN2 Zornitza Stark Gene: pan2 has been classified as Green List (High Evidence).
Fetal anomalies v1.40 PAN2 Zornitza Stark Classified gene: PAN2 as Green List (high evidence)
Fetal anomalies v1.40 PAN2 Zornitza Stark Gene: pan2 has been classified as Green List (High Evidence).
Fetal anomalies v1.39 PAN2 Zornitza Stark reviewed gene: PAN2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Syndromic disease MONDO:0002254; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4820 PAN2 Zornitza Stark Marked gene: PAN2 as ready
Intellectual disability syndromic and non-syndromic v0.4820 PAN2 Zornitza Stark Gene: pan2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4820 PAN2 Zornitza Stark Classified gene: PAN2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4820 PAN2 Zornitza Stark Gene: pan2 has been classified as Green List (High Evidence).
Mendeliome v1.55 PAN2 Zornitza Stark Phenotypes for gene: PAN2 were changed from Neurodevelopmental disorder, MONDO:0700092, PAN2-related to Syndromic disease MONDO:0002254, PAN2-related
Mendeliome v1.54 PAN2 Zornitza Stark reviewed gene: PAN2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Syndromic disease MONDO:0002254; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.114 PAN2 Zornitza Stark Marked gene: PAN2 as ready
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.114 PAN2 Zornitza Stark Gene: pan2 has been classified as Green List (High Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.114 PAN2 Zornitza Stark Classified gene: PAN2 as Green List (high evidence)
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.114 PAN2 Zornitza Stark Gene: pan2 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.217 PAN2 Zornitza Stark Marked gene: PAN2 as ready
Congenital Heart Defect v0.217 PAN2 Zornitza Stark Gene: pan2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1615 PRPF8 Zornitza Stark Marked gene: PRPF8 as ready
Genetic Epilepsy v0.1615 PRPF8 Zornitza Stark Gene: prpf8 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1615 PRPF8 Zornitza Stark Phenotypes for gene: PRPF8 were changed from Neurodevelopmental disorder MONDO:0700092, PRPF8-related; Retinitis pigmentosa 13 - MIM#600059 to Neurodevelopmental disorder MONDO:0700092, PRPF8-related; Retinitis pigmentosa 13 - MIM#600059
Mendeliome v1.54 PRPF8 Zornitza Stark Phenotypes for gene: PRPF8 were changed from Retinitis pigmentosa 13, MIM#600059 to Retinitis pigmentosa 13, MIM#600059; Neurodevelopmental disorder MONDO:0700092, PRPF8-related
Genetic Epilepsy v0.1614 PRPF8 Zornitza Stark Phenotypes for gene: PRPF8 were changed from urodevelopmental disorder MONDO:0700092, PRPF8-related; Retinitis pigmentosa 13 - MIM#600059 to Neurodevelopmental disorder MONDO:0700092, PRPF8-related; Retinitis pigmentosa 13 - MIM#600059
Congenital Heart Defect v0.217 PAN2 Seb Lunke Classified gene: PAN2 as Green List (high evidence)
Congenital Heart Defect v0.217 PAN2 Seb Lunke Gene: pan2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1614 PRPF8 Zornitza Stark Phenotypes for gene: PRPF8 were changed from urodevelopmental disorder MONDO:0700092, PRPF8-related; Retinitis pigmentosa 13 - MIM#600059 to urodevelopmental disorder MONDO:0700092, PRPF8-related; Retinitis pigmentosa 13 - MIM#600059
Callosome v0.452 RMND1 Belinda Chong reviewed gene: RMND1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23022098; Phenotypes: Combined oxidative phosphorylation deficiency 11 MIM#614922; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Congenital Heart Defect v0.216 PAN2 Seb Lunke Classified gene: PAN2 as Green List (high evidence)
Congenital Heart Defect v0.216 PAN2 Seb Lunke Gene: pan2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1614 PRPF8 Zornitza Stark Phenotypes for gene: PRPF8 were changed from Epilepsy; intellectual disability; Retinitis pigmentosa 13 - MIM#600059 to urodevelopmental disorder MONDO:0700092, PRPF8-related; Retinitis pigmentosa 13 - MIM#600059
Microcephaly v1.127 BUB1 Zornitza Stark Marked gene: BUB1 as ready
Microcephaly v1.127 BUB1 Zornitza Stark Gene: bub1 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.216 PAN2 Seb Lunke Classified gene: PAN2 as Green List (high evidence)
Congenital Heart Defect v0.216 PAN2 Seb Lunke Gene: pan2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4819 RMND1 Belinda Chong reviewed gene: RMND1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26395190; Phenotypes: Combined oxidative phosphorylation deficiency 11 MIM#614922; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.53 BUB1 Elena Savva Classified gene: BUB1 as Amber List (moderate evidence)
Mendeliome v1.53 BUB1 Elena Savva Gene: bub1 has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v0.829 RRM1 Seb Lunke Marked gene: RRM1 as ready
Mitochondrial disease v0.829 RRM1 Seb Lunke Gene: rrm1 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.215 PAN2 Naomi Baker gene: PAN2 was added
gene: PAN2 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: PAN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PAN2 were set to PMID:35304602; 29620724
Phenotypes for gene: PAN2 were set to Syndromic disease MONDO:0002254
Review for gene: PAN2 was set to GREEN
Added comment: PMID:35304602 reports five individuals from 3 families with biallelic (homozygous) loss-of-function variants. Clinical presentation incudes mild-moderate intellectual disability, hypotonia, sensorineural hearing loss, EEG abnormalities, congenital heart defects (tetralogy of Fallot, septal defects, dilated aortic root), urinary tract malformations, ophthalmological anomalies, short stature with other skeletal anomalies, and craniofacial features including flat occiput, ptosis, long philtrum, and short neck.

PMID:29620724 reports one individual with biallelic (homozygous) loss-of-function variant who presented with global developmental delay, mild hypotonia, craniosynostosis, severe early-onset scoliosis, imperforate anus, and double urinary collecting system.
Sources: Literature
Mitochondrial disease v0.829 RRM1 Seb Lunke Classified gene: RRM1 as Amber List (moderate evidence)
Mitochondrial disease v0.829 RRM1 Seb Lunke Gene: rrm1 has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v0.828 RRM1 Seb Lunke Classified gene: RRM1 as Amber List (moderate evidence)
Mitochondrial disease v0.828 RRM1 Seb Lunke Gene: rrm1 has been classified as Amber List (Moderate Evidence).
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.113 PAN2 Naomi Baker gene: PAN2 was added
gene: PAN2 was added to Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic. Sources: Literature
Mode of inheritance for gene: PAN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PAN2 were set to PMID:35304602; 29620724
Phenotypes for gene: PAN2 were set to Syndromic disease MONDO:0002254
Review for gene: PAN2 was set to GREEN
Added comment: PMID:35304602 reports five individuals from 3 families with biallelic (homozygous) loss-of-function variants. Clinical presentation incudes mild-moderate intellectual disability, hypotonia, sensorineural hearing loss, EEG abnormalities, congenital heart defects (tetralogy of Fallot, septal defects, dilated aortic root), urinary tract malformations, ophthalmological anomalies, short stature with other skeletal anomalies, and craniofacial features including flat occiput, ptosis, long philtrum, and short neck.

PMID:29620724 reports one individual with biallelic (homozygous) loss-of-function variant who presented with global developmental delay, mild hypotonia, craniosynostosis, severe early-onset scoliosis, imperforate anus, and double urinary collecting system.
Sources: Literature
Microcephaly v1.127 BUB1 Zornitza Stark Classified gene: BUB1 as Amber List (moderate evidence)
Microcephaly v1.127 BUB1 Zornitza Stark Gene: bub1 has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v0.827 RRM1 Daniel Flanagan gene: RRM1 was added
gene: RRM1 was added to Mitochondrial disease. Sources: Expert list
Mode of inheritance for gene: RRM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RRM1 were set to PMID: 35617047
Phenotypes for gene: RRM1 were set to Multiple mitochondrial DNA deletion syndrome (MONDO:0016797)
Review for gene: RRM1 was set to AMBER
Added comment: Homozygous missense were identified in 4 four probands (p.Arg381Cys or p.Arg381His) from three families, who presented with ptosis and ophthalmoplegia, plus other manifestations and multiple mtDNA deletions in muscle. Heterozygous carriers were unaffected. An additional proband was heterozygous for a different RRM1 missense (p.Asn427Lys), another variant not identified.
Sources: Expert list
Microcephaly v1.127 BUB1 Zornitza Stark Classified gene: BUB1 as Amber List (moderate evidence)
Microcephaly v1.127 BUB1 Zornitza Stark Gene: bub1 has been classified as Amber List (Moderate Evidence).
Cardiomyopathy_Paediatric v0.131 LMOD2 Seb Lunke Marked gene: LMOD2 as ready
Cardiomyopathy_Paediatric v0.131 LMOD2 Seb Lunke Gene: lmod2 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.131 LMOD2 Seb Lunke Classified gene: LMOD2 as Green List (high evidence)
Cardiomyopathy_Paediatric v0.131 LMOD2 Seb Lunke Gene: lmod2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1613 PRPF8 Zornitza Stark Classified gene: PRPF8 as Green List (high evidence)
Genetic Epilepsy v0.1613 PRPF8 Zornitza Stark Gene: prpf8 has been classified as Green List (High Evidence).
Mendeliome v1.52 RRM1 Seb Lunke Marked gene: RRM1 as ready
Mendeliome v1.52 RRM1 Seb Lunke Gene: rrm1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4819 PRPF8 Zornitza Stark Marked gene: PRPF8 as ready
Intellectual disability syndromic and non-syndromic v0.4819 PRPF8 Zornitza Stark Gene: prpf8 has been classified as Green List (High Evidence).
Mendeliome v1.52 BUB1 Zornitza Stark Marked gene: BUB1 as ready
Mendeliome v1.52 BUB1 Zornitza Stark Gene: bub1 has been classified as Green List (High Evidence).
Mendeliome v1.52 RRM1 Seb Lunke Classified gene: RRM1 as Amber List (moderate evidence)
Mendeliome v1.52 RRM1 Seb Lunke Added comment: Comment on list classification: 3 families but only 2 Hom variants, not convinced they are definitely unrelated. 4th probed inconclusive.
Mendeliome v1.52 RRM1 Seb Lunke Gene: rrm1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.52 BUB1 Zornitza Stark Phenotypes for gene: BUB1 were changed from Intellectual disability and microcephaly to Neurodevelopmental disorder, BUB1-related MONDO:0700092
Mendeliome v1.51 BUB1 Zornitza Stark Classified gene: BUB1 as Green List (high evidence)
Mendeliome v1.51 BUB1 Zornitza Stark Gene: bub1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4819 PRPF8 Zornitza Stark Phenotypes for gene: PRPF8 were changed from Intellectual disability; epilepsy; Retinitis pigmentosa 13 - MIM#600059 to Neurodevelopmental disorder MONDO:0700092, PRPF8-related; Retinitis pigmentosa 13 - MIM#600059
Fetal anomalies v1.39 PAN2 Naomi Baker gene: PAN2 was added
gene: PAN2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PAN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PAN2 were set to PMID:35304602; 29620724
Phenotypes for gene: PAN2 were set to Syndromic disease MONDO:0002254
Added comment: PMID:35304602 reports five individuals from 3 families with biallelic (homozygous) loss-of-function variants. Clinical presentation incudes mild-moderate intellectual disability, hypotonia, sensorineural hearing loss, EEG abnormalities, congenital heart defects (tetralogy of Fallot, septal defects, dilated aortic root), urinary tract malformations, ophthalmological anomalies, short stature with other skeletal anomalies, and craniofacial features including flat occiput, ptosis, long philtrum, and short neck.

PMID:29620724 reports one individual with biallelic (homozygous) loss-of-function variant who presented with global developmental delay, mild hypotonia, craniosynostosis, severe early-onset scoliosis, imperforate anus, and double urinary collecting system.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4818 BUB1 Zornitza Stark Marked gene: BUB1 as ready
Intellectual disability syndromic and non-syndromic v0.4818 BUB1 Zornitza Stark Gene: bub1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4818 PAN2 Naomi Baker gene: PAN2 was added
gene: PAN2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PAN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PAN2 were set to PMID:35304602; 29620724
Phenotypes for gene: PAN2 were set to Syndromic disease MONDO:0002254
Review for gene: PAN2 was set to GREEN
Added comment: PMID:35304602 reports five individuals from 3 families with biallelic (homozygous) loss-of-function variants. Clinical presentation incudes mild-moderate intellectual disability, hypotonia, sensorineural hearing loss, EEG abnormalities, congenital heart defects (tetralogy of Fallot, septal defects, dilated aortic root), urinary tract malformations, ophthalmological anomalies, short stature with other skeletal anomalies, and craniofacial features including flat occiput, ptosis, long philtrum, and short neck.

PMID:29620724 reports one individual with biallelic (homozygous) loss-of-function variant who presented with global developmental delay, mild hypotonia, craniosynostosis, severe early-onset scoliosis, imperforate anus, and double urinary collecting system.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4818 PRPF8 Zornitza Stark Classified gene: PRPF8 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4818 PRPF8 Zornitza Stark Gene: prpf8 has been classified as Green List (High Evidence).
Cardiomyopathy_Paediatric v0.130 LMOD2 Melanie Marty gene: LMOD2 was added
gene: LMOD2 was added to Cardiomyopathy_Paediatric. Sources: Literature
Mode of inheritance for gene: LMOD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LMOD2 were set to 31517052; 34888509; 5082396; 35188328; 26487682
Phenotypes for gene: LMOD2 were set to Dilated cardiomyopathy MONDO:0005021
Review for gene: LMOD2 was set to GREEN
Added comment: 4 unrelated families with early onset dilated cardiomyopathy, autosomal recessive inheritance, functional studies showing loss of protein and a mouse model reported.

PMID: 31517052 1 x neonate with DCM, homozygous nonsense variant identified.

PMID: 34888509 2 x neonatal deaths (from 1 family) related to dilated cardiomyopathy (DCM), compound heterozygous loss-of-function variants identified.

PMID:35082396 2 x siblings with DCM who died shortly after birth due to heart failure, homozygous canonical splice variant identified. Functional studies show loss of donor site and loss of protein.

PMID: 35188328 1 x child (9 months) with DCM, with homozygous frameshift variant. Functional studies showed absence of LMOD2 protein (western blot).

PMID: 26487682 Lmod2 null (knockout) mice present with short cardiac thin filaments and die at ~3 weeks due to dysfunctional, dilated hearts
Sources: Literature
Genetic Epilepsy v0.1612 PRPF8 Krithika Murali changed review comment from: PMID 35543142 O'Grady et al 2022 report 14 unrelated individuals with heterozygous PRPF8 variants and ID, dymorphic features and epilepsy (7/14). Short stature, abnormal gait and cardiac anomalies also reported. 11 variants identified were de novo, 1 variant - maternal mosaicism, 1 variant - duo sequencing (not identified in mother, father could not be sequenced). 1 individual did not have parental testing. Cardiac anomalies varied and included benign cardiac tumour, dilated cardiomyopathy, dilated aortic root (COL5A2 VUS also identified), bicuspid aortic valve, cardiac arrest, self-resolving ASD/VSD.

Heterozygous PRPF8 variants previously associated with retinitis pigmentosa. 1 out of the 14 individuals in this cohort had a diagnosis of RP. RP variants noted to cluster in the C'terminal MPN domain. The individual with RP in this paper had a variant in the preceding RNAase H homology domain near the C-terminus. Not all of the individuals in this paper had formal ophthalmological examination.
Sources: Literature; to: PMID 35543142 O'Grady et al 2022 report 14 unrelated individuals with heterozygous PRPF8 variants and ID, dev delay, dymorphic features and epilepsy (7/14). Short stature, abnormal gait and cardiac anomalies also reported. 11 variants identified were de novo, 1 variant - maternal mosaicism, 1 variant - duo sequencing (not identified in mother, father could not be sequenced). 1 individual did not have parental testing. Cardiac anomalies varied and included benign cardiac tumour, dilated cardiomyopathy, dilated aortic root (COL5A2 VUS also identified), bicuspid aortic valve, cardiac arrest, self-resolving ASD/VSD.

Heterozygous PRPF8 variants previously associated with retinitis pigmentosa. 1 out of the 14 individuals in this cohort had a diagnosis of RP. RP variants noted to cluster in the C'terminal MPN domain. The individual with RP in this paper had a variant in the preceding RNAase H homology domain near the C-terminus. Not all of the individuals in this paper had formal ophthalmological examination.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4817 BUB1 Zornitza Stark Classified gene: BUB1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.4817 BUB1 Zornitza Stark Gene: bub1 has been classified as Amber List (Moderate Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.50 ATOH1 Chloe Stutterd gene: ATOH1 was added
gene: ATOH1 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Literature,Expert Review
Mode of inheritance for gene: ATOH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATOH1 were set to 35518571
Phenotypes for gene: ATOH1 were set to Pontocerebellar hypoplasia MONDO:0020135, ATOH1-related
Penetrance for gene: ATOH1 were set to unknown
Review for gene: ATOH1 was set to AMBER
Added comment: Single report of novel homozygous variant in functional domain in two affected siblings with pontocerebellar hypoplasia, developmental delay and hearing loss. Similar phenotype previously reported in animal model with bi-allelic missense variant in same functional domain.
Sources: Literature, Expert Review
Mendeliome v1.50 PAN2 Zornitza Stark Marked gene: PAN2 as ready
Mendeliome v1.50 PAN2 Zornitza Stark Gene: pan2 has been classified as Green List (High Evidence).
Mendeliome v1.50 PAN2 Zornitza Stark Classified gene: PAN2 as Green List (high evidence)
Mendeliome v1.50 PAN2 Zornitza Stark Gene: pan2 has been classified as Green List (High Evidence).
Mendeliome v1.49 RRM1 Daniel Flanagan gene: RRM1 was added
gene: RRM1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: RRM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RRM1 were set to 35617047
Phenotypes for gene: RRM1 were set to Multiple mitochondrial DNA deletion syndrome (MONDO:0016797)
Review for gene: RRM1 was set to GREEN
Added comment: Homozygous missense were identified in 4 four probands (p.Arg381Cys or p.Arg381His) from three families, who presented with ptosis and ophthalmoplegia, plus other manifestations and multiple mtDNA deletions in muscle. Heterozygous carriers were unaffected. An additional proband was heterozygous for a different RRM1 missense (p.Asn427Lys), another variant not identified.
Sources: Expert list
Intellectual disability syndromic and non-syndromic v0.4816 BUB1 Zornitza Stark Classified gene: BUB1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.4816 BUB1 Zornitza Stark Gene: bub1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1612 PRPF8 Krithika Murali gene: PRPF8 was added
gene: PRPF8 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: PRPF8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRPF8 were set to 35543142
Phenotypes for gene: PRPF8 were set to Epilepsy; intellectual disability; Retinitis pigmentosa 13 - MIM#600059
Review for gene: PRPF8 was set to GREEN
Added comment: PMID 35543142 O'Grady et al 2022 report 14 unrelated individuals with heterozygous PRPF8 variants and ID, dymorphic features and epilepsy (7/14). Short stature, abnormal gait and cardiac anomalies also reported. 11 variants identified were de novo, 1 variant - maternal mosaicism, 1 variant - duo sequencing (not identified in mother, father could not be sequenced). 1 individual did not have parental testing. Cardiac anomalies varied and included benign cardiac tumour, dilated cardiomyopathy, dilated aortic root (COL5A2 VUS also identified), bicuspid aortic valve, cardiac arrest, self-resolving ASD/VSD.

Heterozygous PRPF8 variants previously associated with retinitis pigmentosa. 1 out of the 14 individuals in this cohort had a diagnosis of RP. RP variants noted to cluster in the C'terminal MPN domain. The individual with RP in this paper had a variant in the preceding RNAase H homology domain near the C-terminus. Not all of the individuals in this paper had formal ophthalmological examination.
Sources: Literature
Mendeliome v1.49 LMOD2 Seb Lunke Marked gene: LMOD2 as ready
Mendeliome v1.49 LMOD2 Seb Lunke Gene: lmod2 has been classified as Green List (High Evidence).
Microcephaly v1.126 BUB1 Paul De Fazio gene: BUB1 was added
gene: BUB1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: BUB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BUB1 were set to 35044816; 19772675; 19117986; 23209306
Phenotypes for gene: BUB1 were set to Neurodevelopmental disorder, BUB1-related MONDO:0700092; Intellectual disability and microcephaly
Review for gene: BUB1 was set to AMBER
gene: BUB1 was marked as current diagnostic
Added comment: 2 unrelated patients with ID, microcephaly, short stature, dysmorphic features reported with biallelic variants:

P1 (3yo male): homozygous start-loss variant (2 hets and 0 hom in gnomAD). Functional testing showed a small amount of full-length protein was translated, and BUB1 recruitment to kinetochores was nearly undetectable.
P2 (16yo female): compound heterozygous for a canonical splice variant (1 het and no hom in gnomAD) and an NMD-predicted frameshift variant (absent from gnomAD). The splice variant was shown to result in an in-frame deletion of 54 amino acids in the kinase domain. P2 cells have reduced protein levels but essentially no kinase activity.

BUB1 patient cells have impaired mitotic fidelity.

Homozygous Bub1 disruption in mice is embryonic lethal (PMID:19772675). A hypomorphic mouse is viable with increased tumourigenesis with ageing and aneuploidy (PMID:19117986). A kinase-dead mouse does not show increased tumourigenesis but does have a high frequency of aneuploid cells (PMID:23209306)
Sources: Literature
Mendeliome v1.49 LMOD2 Seb Lunke Phenotypes for gene: LMOD2 were changed from Dilated cardiomyopathy to Dilated cardiomyopathy, MONDO:0005021
Intellectual disability syndromic and non-syndromic v0.4815 BUB1 Zornitza Stark Classified gene: BUB1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.4815 BUB1 Zornitza Stark Gene: bub1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.48 ATOH1 Zornitza Stark Marked gene: ATOH1 as ready
Mendeliome v1.48 ATOH1 Zornitza Stark Gene: atoh1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.48 LMOD2 Seb Lunke Classified gene: LMOD2 as Green List (high evidence)
Mendeliome v1.48 LMOD2 Seb Lunke Gene: lmod2 has been classified as Green List (High Evidence).
Mendeliome v1.47 PAN2 Naomi Baker gene: PAN2 was added
gene: PAN2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PAN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PAN2 were set to PMID:35304602; 29620724
Phenotypes for gene: PAN2 were set to Neurodevelopmental disorder, MONDO:0700092, PAN2-related
Review for gene: PAN2 was set to GREEN
Added comment: PMID:35304602 reports five individuals from 3 families with biallelic (homozygous) loss-of-function variants. Clinical presentation incudes mild-moderate intellectual disability, hypotonia, sensorineural hearing loss, EEG abnormalities, congenital heart defects (tetralogy of Fallot, septal defects, dilated aortic root), urinary tract malformations, ophthalmological anomalies, short stature with other skeletal anomalies, and craniofacial features including flat occiput, ptosis, long philtrum, and short neck.

PMID:29620724 reports one individual with biallelic (homozygous) loss-of-function variant who presented with global developmental delay, mild hypotonia, craniosynostosis, severe early-onset scoliosis, imperforate anus, and double urinary collecting system.
Sources: Literature
Disorders of immune dysregulation v0.141 GIMAP6 Elena Savva Classified gene: GIMAP6 as Green List (high evidence)
Disorders of immune dysregulation v0.141 GIMAP6 Elena Savva Gene: gimap6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4814 PRPF8 Krithika Murali gene: PRPF8 was added
gene: PRPF8 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PRPF8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRPF8 were set to 35543142
Phenotypes for gene: PRPF8 were set to Intellectual disability; epilepsy; Retinitis pigmentosa 13 - MIM#600059
Review for gene: PRPF8 was set to GREEN
Added comment: PMID 35543142 O'Grady et al 2022 report 14 unrelated individuals with heterozygous PRPF8 variants and ID, dymorphic features and epilepsy (7/14). Short stature, abnormal gait and cardiac anomalies also reported. 11 variants identified were de novo, 1 variant - maternal mosaicism, 1 variant - duo sequencing (not identified in mother, father could not be sequenced). 1 individual did not have parental testing. Cardiac anomalies varied and included benign cardiac tumour, dilated cardiomyopathy, dilated aortic root (COL5A2 VUS also identified), bicuspid aortic valve, cardiac arrest, self-resolving ASD/VSD.

Heterozygous PRPF8 variants previously associated with retinitis pigmentosa. 1 out of the 14 individuals in this cohort had a diagnosis of RP. RP variants noted to cluster in the C'terminal MPN domain. The individual with RP in this paper had a variant in the preceding RNAase H homology domain near the C-terminus. Not all of the individuals in this paper had formal ophthalmological examination
Sources: Literature
Disorders of immune dysregulation v0.141 GIMAP6 Elena Savva Classified gene: GIMAP6 as Green List (high evidence)
Disorders of immune dysregulation v0.141 GIMAP6 Elena Savva Gene: gimap6 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.140 GIMAP6 Elena Savva Classified gene: GIMAP6 as Green List (high evidence)
Disorders of immune dysregulation v0.140 GIMAP6 Elena Savva Gene: gimap6 has been classified as Green List (High Evidence).
Disorders of immune dysregulation v0.140 GIMAP6 Elena Savva Classified gene: GIMAP6 as Green List (high evidence)
Disorders of immune dysregulation v0.140 GIMAP6 Elena Savva Gene: gimap6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4814 BUB1 Paul De Fazio gene: BUB1 was added
gene: BUB1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: BUB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BUB1 were set to 35044816; 19772675; 19117986; 23209306
Phenotypes for gene: BUB1 were set to Neurodevelopmental disorder, BUB1-related MONDO:0700092; Intellectual disability and microcephaly
Review for gene: BUB1 was set to GREEN
gene: BUB1 was marked as current diagnostic
Added comment: 2 unrelated patients with ID, microcephaly, short stature, dysmorphic features reported with biallelic variants:

P1 (3yo male): homozygous start-loss variant (2 hets and 0 hom in gnomAD). Functional testing showed a small amount of full-length protein was translated, and BUB1 recruitment to kinetochores was nearly undetectable.
P2 (16yo female): compound heterozygous for a canonical splice variant (1 het and no hom in gnomAD) and an NMD-predicted frameshift variant (absent from gnomAD). The splice variant was shown to result in an in-frame deletion of 54 amino acids in the kinase domain. P2 cells have reduced protein levels but essentially no kinase activity.

BUB1 patient cells have impaired mitotic fidelity.

Homozygous Bub1 disruption in mice is embryonic lethal (PMID:19772675). A hypomorphic mouse is viable with increased tumourigenesis with ageing and aneuploidy (PMID:19117986). A kinase-dead mouse does not show increased tumourigenesis but does have a high frequency of aneuploid cells (PMID:23209306)
Sources: Literature
Disorders of immune dysregulation v0.140 GIMAP6 Elena Savva Classified gene: GIMAP6 as Green List (high evidence)
Disorders of immune dysregulation v0.140 GIMAP6 Elena Savva Gene: gimap6 has been classified as Green List (High Evidence).
Mendeliome v1.47 PRPF8 Krithika Murali reviewed gene: PRPF8: Rating: GREEN; Mode of pathogenicity: None; Publications: 35543142; Phenotypes: Intellectual disability, epilepsy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.47 ATOH1 Zornitza Stark Phenotypes for gene: ATOH1 were changed from Pontocerebellar hypoplasia; developmental delay; hearing loss to Pontocerebellar hypoplasia MONDO:0020135, ATOH1-related
Mendeliome v1.46 ATOH1 Zornitza Stark Classified gene: ATOH1 as Amber List (moderate evidence)
Mendeliome v1.46 ATOH1 Zornitza Stark Gene: atoh1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.46 PTPN13 Ain Roesley Marked gene: PTPN13 as ready
Mendeliome v1.46 PTPN13 Ain Roesley Gene: ptpn13 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.46 PTPN13 Ain Roesley Classified gene: PTPN13 as Amber List (moderate evidence)
Mendeliome v1.46 PTPN13 Ain Roesley Gene: ptpn13 has been classified as Amber List (Moderate Evidence).
Disorders of immune dysregulation v0.139 GIMAP6 Elena Savva Marked gene: GIMAP6 as ready
Disorders of immune dysregulation v0.139 GIMAP6 Elena Savva Gene: gimap6 has been classified as Red List (Low Evidence).
Mendeliome v1.45 PTPN13 Ain Roesley gene: PTPN13 was added
gene: PTPN13 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PTPN13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTPN13 were set to 35643866
Phenotypes for gene: PTPN13 were set to bone marrow failure syndrome MONDO#0000159, PTPN13-related
Review for gene: PTPN13 was set to AMBER
gene: PTPN13 was marked as current diagnostic
Added comment: 2 families

Family A: 3 affecteds only 2 sequenced. Hom for a missense
3/3 Anaemia, 1x thrombocytopaenia, 1x severe neutropaenia, bone marrow with pure red cell aplasia
noted that the sibling who wasn't sequenced had normal bone marrow morphology

Family B: Chet for a missense and inframe del of 1 amino acid
Persistent hypogammaglobulinemia after transplant (at least 14 months after) with normal blood counts and Pre-B ALL with MLL rearrangement

In vitro studies of individual variants were LoF, including defective erythroid and megakaryocytic differentiation, consistent with anaemia and thrombocytopaenia reported in family A
Sources: Literature
Disorders of immune dysregulation v0.139 GIMAP6 Elena Savva gene: GIMAP6 was added
gene: GIMAP6 was added to Disorders of immune dysregulation. Sources: Literature
Mode of inheritance for gene: GIMAP6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GIMAP6 were set to PMID: 35551368; 33328581
Phenotypes for gene: GIMAP6 were set to Autophagy, immune competence and inflammation
Review for gene: GIMAP6 was set to GREEN
Added comment: PMID: 35551368, PMID: 33328581
- K/O mice show autophagy, redox regulation, and polyunsaturated fatty acid (PUFA)–containing lipids and die prematurely from microangiopathic glomerulosclerosis with immunodeficiency.
- 2 unrelated families (3 patients) w/ a homozygous missense (p.Gly153Val) and nonsense (p.Trp86*). All unaffected siblings were heterozygous.
Patient 1 (missense) presented with Coombs-positive hemolytic anemia, hepatosplenomegaly, Cranial MRI showed bilateral effusions, sulcal hyperintensity, and lateral parietal subcortical acute focal ischemic lesions.
Patient 2 (nonsense) presented with recurrent purulent otitis media and a chronic wet cough, persistent jaundice, recurrent chest and ear infections, lingular consolidation, mild bronchiectasis, bibasilar bronchial wall thickening, right peribronchial consolidation, right lower lobe bronchiectasis, bilateral axillary lymphadenopathy, and splenomegaly.
Patient 3 (nonsense) presented with suffered headaches, abdomen pain, mouth ulcers, and recurrent infections

- Functional studies show patient 1 (missense) with reduced protein expression on western blot, and patient 2/3 (nonsense) with no protein expression. T cells of Pt 1 were similar to mouse K/O model (elevated basal LC3-II, reduced autophagic flux).

gnomAD: 0 homozygous PTCs, but a very common canonical splice which is present in the non-canonical transcript Sources: Literature
Sources: Literature
Mendeliome v1.44 BUB1 Paul De Fazio edited their review of gene: BUB1: Changed phenotypes: Neurodevelopmental disorder, BUB1-related MONDO:0700092, Intellectual disability and microcephaly
Growth failure v1.42 HEATR3 Zornitza Stark Marked gene: HEATR3 as ready
Growth failure v1.42 HEATR3 Zornitza Stark Gene: heatr3 has been classified as Green List (High Evidence).
Mendeliome v1.44 ATOH1 Chloe Stutterd gene: ATOH1 was added
gene: ATOH1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATOH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATOH1 were set to 35518571
Phenotypes for gene: ATOH1 were set to Pontocerebellar hypoplasia; developmental delay; hearing loss
Penetrance for gene: ATOH1 were set to unknown
Review for gene: ATOH1 was set to AMBER
Added comment: Single report of novel homozygous missense variant in functional domain segregating with disease in two affected siblings with pontocerebellar hypoplasia, developmental delay and hearing loss. Similar phenotype previously reported in animal model with biallelic missense variant affecting same functional domain. Homology modelling predicts this missense variant affects binding capability of the bHLH domain to the DNA. Gene encodes a core transcription factor in developing cerebellum, brainstem, dorsal spinal cord and ear.
Sources: Literature
Diamond Blackfan anaemia v1.3 HEATR3 Zornitza Stark Marked gene: HEATR3 as ready
Diamond Blackfan anaemia v1.3 HEATR3 Zornitza Stark Gene: heatr3 has been classified as Green List (High Evidence).
Growth failure v1.42 HEATR3 Zornitza Stark Classified gene: HEATR3 as Green List (high evidence)
Growth failure v1.42 HEATR3 Zornitza Stark Gene: heatr3 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.17 HEATR3 Zornitza Stark Marked gene: HEATR3 as ready
Bone Marrow Failure v1.17 HEATR3 Zornitza Stark Gene: heatr3 has been classified as Green List (High Evidence).
Diamond Blackfan anaemia v1.3 HEATR3 Zornitza Stark Classified gene: HEATR3 as Green List (high evidence)
Diamond Blackfan anaemia v1.3 HEATR3 Zornitza Stark Gene: heatr3 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.17 HEATR3 Zornitza Stark Phenotypes for gene: HEATR3 were changed from Bone marrow failure, short stature, facial and acromelic dysmorphic features, and mild intellectual disability to Diamond Blackfan anaemia MONDO:0015253, HEATR3 related
Bone Marrow Failure v1.16 HEATR3 Zornitza Stark Classified gene: HEATR3 as Green List (high evidence)
Bone Marrow Failure v1.16 HEATR3 Zornitza Stark Gene: heatr3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4814 SEMA6B Dean Phelan gene: SEMA6B was added
gene: SEMA6B was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SEMA6B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SEMA6B were set to PMID: 35604360
Phenotypes for gene: SEMA6B were set to Intellectual disability, MONDO:0001071, SEMA6B related
Penetrance for gene: SEMA6B were set to Complete
Review for gene: SEMA6B was set to GREEN
Added comment: PMID: 35604360
- 14 heterozygous variants were observed in 16 unrelated individuals referred for intellectual disability. Majority of the variants 9/14 were PTCs in the last exon and predicted to escape NMD. Functional studies of selected variants and shRNA knock down studies showed mislocalisation and abnormal protein function.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4814 HEATR3 Zornitza Stark Marked gene: HEATR3 as ready
Intellectual disability syndromic and non-syndromic v0.4814 HEATR3 Zornitza Stark Gene: heatr3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.44 BUB1 Paul De Fazio gene: BUB1 was added
gene: BUB1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BUB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BUB1 were set to 35044816; 19772675; 19117986; 23209306
Phenotypes for gene: BUB1 were set to Intellectual disability and microcephaly
Review for gene: BUB1 was set to GREEN
gene: BUB1 was marked as current diagnostic
Added comment: 2 unrelated patients with ID, microcephaly, short stature, dysmorphic features reported with biallelic variants:

P1 (3yo male): homozygous start-loss variant (2 hets and 0 hom in gnomAD). Functional testing showed a small amount of full-length protein was translated, and BUB1 recruitment to kinetochores was nearly undetectable.
P2 (16yo female): compound heterozygous for a canonical splice variant (1 het and no hom in gnomAD) and an NMD-predicted frameshift variant (absent from gnomAD). The splice variant was shown to result in an in-frame deletion of 54 amino acids in the kinase domain. P2 cells have reduced protein levels but essentially no kinase activity.

BUB1 patient cells have impaired mitotic fidelity.

Homozygous Bub1 disruption in mice is embryonic lethal (PMID:19772675). A hypomorphic mouse is viable with increased tumourigenesis with ageing and aneuploidy (PMID:19117986). A kinase-dead mouse does not show increased tumourigenesis but does have a high frequency of aneuploid cells (PMID:23209306)
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4814 HEATR3 Zornitza Stark Classified gene: HEATR3 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.4814 HEATR3 Zornitza Stark Gene: heatr3 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.44 LMOD2 Melanie Marty gene: LMOD2 was added
gene: LMOD2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LMOD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LMOD2 were set to PMID: 31517052; PMID: 34888509; PMID: 35082396; PMID: 35188328; PMID: 26487682
Phenotypes for gene: LMOD2 were set to Dilated cardiomyopathy
Review for gene: LMOD2 was set to GREEN
Added comment: 4 unrelated families with early onset dilated cardiomyopathy, autosomal recessive inheritance, functional studies showing loss of protein and a mouse model reported.

PMID: 31517052 1 x neonate with DCM, homozygous nonsense variant identified.

PMID: 34888509 2 x neonatal deaths (from 1 family) related to dilated cardiomyopathy (DCM), compound heterozygous loss-of-function variants identified.

PMID:35082396 2 x siblings with DCM who died shortly after birth due to heart failure, homozygous canonical splice variant identified. Functional studies show loss of donor site and loss of protein.

PMID: 35188328 1 x child (9 months) with DCM, with homozygous frameshift variant. Functional studies showed absence of LMOD2 protein (western blot).

PMID: 26487682 Lmod2 null (knockout) mice present with short cardiac thin filaments and die at ~3 weeks due to dysfunctional, dilated hearts
Sources: Literature
Mendeliome v1.44 SEMA6B Zornitza Stark Phenotypes for gene: SEMA6B were changed from Progressive myoclonic epilepsy to Progressive myoclonic epilepsy; Intellectual disability, MONDO:0001071, SEMA6B related
Mendeliome v1.43 SRRM2 Zornitza Stark Phenotypes for gene: SRRM2 were changed from Developmental disorders to Neurodevelopmental disorder MONDO:0700092 SRRM2-related
Mendeliome v1.42 SEMA6B Zornitza Stark Publications for gene: SEMA6B were set to 32169168
Growth failure v1.41 HEATR3 Chern Lim changed review comment from: PMID: 35213692:
- 4 unrelated individuals with biallelic HEATR3 variants (missense and splice site variants), exhibiting bone marrow failure, short stature, facial and acromelic dysmorphic features, and mild intellectual disability.
- Functional analysis showed HEATR3 variants destabilised the protein, resulting in a reduction of nuclear uL18 and impaired ribosome biogenesis.

Bone marrow failure, short stature, facial and acromelic dysmorphic features, and mild intellectual disability
Sources: Literature; to: PMID: 35213692:
- 4 unrelated individuals with biallelic HEATR3 variants (missense and splice site variants), exhibiting bone marrow failure, short stature, facial and acromelic dysmorphic features, and mild intellectual disability.
- Functional analysis showed HEATR3 variants destabilised the protein, resulting in a reduction of nuclear uL18 and impaired ribosome biogenesis.
Genetic Epilepsy v0.1612 NOVA2 Seb Lunke Publications for gene: NOVA2 were set to 32197073
Diamond Blackfan anaemia v1.2 HEATR3 Chern Lim gene: HEATR3 was added
gene: HEATR3 was added to Diamond Blackfan anaemia. Sources: Literature
Mode of inheritance for gene: HEATR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HEATR3 were set to PMID: 35213692
Phenotypes for gene: HEATR3 were set to Bone marrow failure, short stature, facial and acromelic dysmorphic features, and mild intellectual disability; Diamond Blackfan anaemia MONDO:0015253, HEATR3 related
Review for gene: HEATR3 was set to GREEN
gene: HEATR3 was marked as current diagnostic
Added comment: PMID: 35213692:
- 4 unrelated individuals with biallelic HEATR3 variants (missense and splice site variants), exhibiting bone marrow failure, short stature, facial and acromelic dysmorphic features, and mild intellectual disability.
- Functional analysis showed HEATR3 variants destabilised the protein, resulting in a reduction of nuclear uL18 and impaired ribosome biogenesis.
Sources: Literature
Genetic Epilepsy v0.1611 NOVA2 Seb Lunke Classified gene: NOVA2 as Green List (high evidence)
Genetic Epilepsy v0.1611 NOVA2 Seb Lunke Gene: nova2 has been classified as Green List (High Evidence).
Mendeliome v1.41 SEMA6B Dean Phelan Deleted their comment
Growth failure v1.41 HEATR3 Chern Lim gene: HEATR3 was added
gene: HEATR3 was added to Growth failure. Sources: Literature
Mode of inheritance for gene: HEATR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HEATR3 were set to PMID: 35213692
Phenotypes for gene: HEATR3 were set to Bone marrow failure, short stature, facial and acromelic dysmorphic features, and mild intellectual disability; Diamond Blackfan anaemia MONDO:0015253, HEATR3 related
Review for gene: HEATR3 was set to GREEN
gene: HEATR3 was marked as current diagnostic
Added comment: PMID: 35213692:
- 4 unrelated individuals with biallelic HEATR3 variants (missense and splice site variants), exhibiting bone marrow failure, short stature, facial and acromelic dysmorphic features, and mild intellectual disability.
- Functional analysis showed HEATR3 variants destabilised the protein, resulting in a reduction of nuclear uL18 and impaired ribosome biogenesis.

Bone marrow failure, short stature, facial and acromelic dysmorphic features, and mild intellectual disability
Sources: Literature
Genetic Epilepsy v0.1610 NOVA2 Seb Lunke reviewed gene: NOVA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 35607920; Phenotypes: Neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities, MIM# 618859; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v1.41 SRRM2 Zornitza Stark Classified gene: SRRM2 as Green List (high evidence)
Mendeliome v1.41 SRRM2 Zornitza Stark Gene: srrm2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4813 HEATR3 Chern Lim gene: HEATR3 was added
gene: HEATR3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: HEATR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HEATR3 were set to PMID: 35213692
Phenotypes for gene: HEATR3 were set to Bone marrow failure, short stature, facial and acromelic dysmorphic features, and mild intellectual disability; Diamond Blackfan anaemia MONDO:0015253, HEATR3 related
Review for gene: HEATR3 was set to AMBER
gene: HEATR3 was marked as current diagnostic
Added comment: PMID: 35213692:
- 4 unrelated individuals with biallelic HEATR3 variants (missense and splice site variants), exhibiting bone marrow failure, short stature, facial and acromelic dysmorphic features, and mild intellectual disability.
- Functional analysis showed HEATR3 variants destabilised the protein, resulting in a reduction of nuclear uL18 and impaired ribosome biogenesis.
Sources: Literature
Mendeliome v1.40 SEMA6B Dean Phelan commented on gene: SEMA6B: PMID: 35604360
- 14 heterozygous variants were observed in 16 unrelated individuals referred for intellectual disability. Majority of the variants 9/14 were PTCs in the last exon and predicted to escape NMD. Functional studies of selected variants and shRNA knock down studies showed mislocalisation and abnormal protein function.
Mendeliome v1.40 SEMA6B Dean Phelan reviewed gene: SEMA6B: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35604360; Phenotypes: Intellectual disability, MONDO:0001071, SEMA6B related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.40 GIMAP6 Elena Savva Marked gene: GIMAP6 as ready
Mendeliome v1.40 GIMAP6 Elena Savva Gene: gimap6 has been classified as Green List (High Evidence).
Mendeliome v1.40 GIMAP6 Elena Savva Classified gene: GIMAP6 as Green List (high evidence)
Mendeliome v1.40 GIMAP6 Elena Savva Gene: gimap6 has been classified as Green List (High Evidence).
Mendeliome v1.39 HEATR3 Zornitza Stark Phenotypes for gene: HEATR3 were changed from Diamond Blackfan anaemia, MONDO:0015253, HEATR3 related to Diamond Blackfan anaemia, MONDO:0015253, HEATR3 related
Mendeliome v1.38 HEATR3 Zornitza Stark Marked gene: HEATR3 as ready
Mendeliome v1.38 HEATR3 Zornitza Stark Gene: heatr3 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.15 PTPN13 Ain Roesley gene: PTPN13 was added
gene: PTPN13 was added to Bone Marrow Failure. Sources: Literature
Mode of inheritance for gene: PTPN13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTPN13 were set to 35643866
Phenotypes for gene: PTPN13 were set to bone marrow failure syndrome MONDO#0000159, PTPN13-related
Review for gene: PTPN13 was set to AMBER
gene: PTPN13 was marked as current diagnostic
Added comment: 2 families

Family A: 3 affecteds only 2 sequenced. Hom for a missense
3/3 Anaemia, 1x thrombocytopaenia, 1x severe neutropaenia, bone marrow with pure red cell aplasia
noted that the sibling who wasn't sequenced had normal bone marrow morphology

Family B: Chet for a missense and inframe del of 1 amino acid
Persistent hypogammaglobulinemia after transplant (at least 14 months after) with normal blood counts and Pre-B ALL with MLL rearrangement

In vitro studies of individual variants were LoF, including defective erythroid and megakaryocytic differentiation, consistent with anaemia and thrombocytopaenia reported in family A
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4813 SRRM2 Zornitza Stark Phenotypes for gene: SRRM2 were changed from Developmental disorders to neurodevelopmental disorder MONDO:0700092 SRRM2-related
Bone Marrow Failure v1.15 PTPN13 Ain Roesley gene: PTPN13 was added
gene: PTPN13 was added to Bone Marrow Failure. Sources: Literature
Mode of inheritance for gene: PTPN13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTPN13 were set to 35643866
Phenotypes for gene: PTPN13 were set to bone marrow failure syndrome MONDO#0000159, PTPN13-related
Review for gene: PTPN13 was set to AMBER
gene: PTPN13 was marked as current diagnostic
Added comment: 2 families

Family A: 3 affecteds only 2 sequenced. Hom for a missense
3/3 Anaemia, 1x thrombocytopaenia, 1x severe neutropaenia, bone marrow with pure red cell aplasia
noted that the sibling who wasn't sequenced had normal bone marrow morphology

Family B: Chet for a missense and inframe del of 1 amino acid
Persistent hypogammaglobulinemia after transplant (at least 14 months after) with normal blood counts and Pre-B ALL with MLL rearrangement

In vitro studies of individual variants were LoF, including defective erythroid and megakaryocytic differentiation, consistent with anaemia and thrombocytopaenia reported in family A
Sources: Literature
Mendeliome v1.38 HEATR3 Zornitza Stark Phenotypes for gene: HEATR3 were changed from DiMONDO:0015253 to Diamond Blackfan anaemia, MONDO:0015253, HEATR3 related
Mendeliome v1.37 IREB2 Lucy Spencer reviewed gene: IREB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 35602653; Phenotypes: Neurodegeneration, early-onset, with choreoathetoid movements and microcytic anemia, MIM#618451; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.37 HEATR3 Zornitza Stark Phenotypes for gene: HEATR3 were changed from Bone marrow failure, short stature, facial and acromelic dysmorphic features, and mild intellectual disability to DiMONDO:0015253
Mendeliome v1.36 SRRM2 Michelle Torres reviewed gene: SRRM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 35567594; Phenotypes: neurodevelopmental disorder MONDO:0700092 SRRM2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v1.36 HEATR3 Zornitza Stark Classified gene: HEATR3 as Green List (high evidence)
Mendeliome v1.36 HEATR3 Zornitza Stark Gene: heatr3 has been classified as Green List (High Evidence).
Mendeliome v1.35 GIMAP6 Elena Savva gene: GIMAP6 was added
gene: GIMAP6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GIMAP6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GIMAP6 were set to PMID: 35551368; 33328581
Phenotypes for gene: GIMAP6 were set to Autophagy, immune competence and inflammation
Review for gene: GIMAP6 was set to AMBER
Added comment: PMID: 35551368, PMID: 33328581
- K/O mice show autophagy, redox regulation, and polyunsaturated fatty acid (PUFA)–containing lipids and die prematurely from microangiopathic glomerulosclerosis with immunodeficiency.
- 2 unrelated families (3 patients) w/ a homozygous missense (p.Gly153Val) and nonsense (p.Trp86*). All unaffected siblings were heterozygous.
Patient 1 (missense) presented with Coombs-positive hemolytic anemia, hepatosplenomegaly, Cranial MRI showed bilateral effusions, sulcal hyperintensity, and lateral parietal subcortical acute focal ischemic lesions.
Patient 2 (nonsense) presented with recurrent purulent otitis media and a chronic wet cough, persistent jaundice, recurrent chest and ear infections, lingular consolidation, mild bronchiectasis, bibasilar bronchial wall thickening, right peribronchial consolidation, right lower lobe bronchiectasis, bilateral axillary lymphadenopathy, and splenomegaly.
Patient 3 (nonsense) presented with suffered headaches, abdomen pain, mouth ulcers, and recurrent infections

- Functional studies show patient 1 (missense) with reduced protein expression on western blot, and patient 2/3 (nonsense) with no protein expression. T cells of Pt 1 were similar to mouse K/O model (elevated basal LC3-II, reduced autophagic flux).

gnomAD: 0 homozygous PTCs, but a very common canonical splice which is present in the non-canonical transcript
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4812 SRRM2 Zornitza Stark Classified gene: SRRM2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4812 SRRM2 Zornitza Stark Gene: srrm2 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.14 HEATR3 Chern Lim gene: HEATR3 was added
gene: HEATR3 was added to Bone Marrow Failure. Sources: Literature
Mode of inheritance for gene: HEATR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HEATR3 were set to PMID: 35213692
Phenotypes for gene: HEATR3 were set to Bone marrow failure, short stature, facial and acromelic dysmorphic features, and mild intellectual disability
Review for gene: HEATR3 was set to GREEN
gene: HEATR3 was marked as current diagnostic
Added comment: PMID: 35213692:
- 4 unrelated individuals with biallelic HEATR3 variants (missense and splice site variants), exhibiting bone marrow failure, short stature, facial and acromelic dysmorphic features, and mild intellectual disability.
- Functional analysis showed HEATR3 variants destabilised the protein, resulting in a reduction of nuclear uL18 and impaired ribosome biogenesis.
Sources: Literature
Mendeliome v1.34 HEATR3 Chern Lim gene: HEATR3 was added
gene: HEATR3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HEATR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HEATR3 were set to PMID: 35213692
Phenotypes for gene: HEATR3 were set to Bone marrow failure, short stature, facial and acromelic dysmorphic features, and mild intellectual disability
Review for gene: HEATR3 was set to GREEN
gene: HEATR3 was marked as current diagnostic
Added comment: PMID: 35213692:
- 4 unrelated individuals with biallelic HEATR3 variants (missense and splice site variants), exhibiting bone marrow failure, short stature, facial and acromelic dysmorphic features, and mild intellectual disability.
- Functional analysis showed HEATR3 variants destabilised the protein, resulting in a reduction of nuclear uL18 and impaired ribosome biogenesis.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4811 SRRM2 Michelle Torres reviewed gene: SRRM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 35567594; Phenotypes: neurodevelopmental disorder MONDO:0700092 SRRM2-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.34 TRIM47 Zornitza Stark Marked gene: TRIM47 as ready
Mendeliome v1.34 TRIM47 Zornitza Stark Gene: trim47 has been classified as Red List (Low Evidence).
Mendeliome v1.34 TRIM47 Zornitza Stark gene: TRIM47 was added
gene: TRIM47 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TRIM47 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRIM47 were set to 35511193
Phenotypes for gene: TRIM47 were set to Genetic cerebral small vessel disease MONDO:0018787
Review for gene: TRIM47 was set to RED
Added comment: GWAS data: Combined evidence from summary-based Mendelian randomization studies and profiling of human loss-of-function allele carriers showed an inverse relation between TRIM47 expression in the brain and blood vessels and extensive small vessel disease severity. Observed significant enrichment of Trim47 in isolated brain vessel preparations compared to total brain fraction in mice, in line with the literature showing Trim47 enrichment in brain endothelial cells at single cell level. Functional evaluation of TRIM47 by small interfering RNAs-mediated knockdown in human brain endothelial cells showed increased endothelial permeability, an important hallmark of cerebral small vessel disease pathology.
Sources: Literature
Stroke v1.7 TRIM47 Zornitza Stark Marked gene: TRIM47 as ready
Stroke v1.7 TRIM47 Zornitza Stark Gene: trim47 has been classified as Red List (Low Evidence).
Stroke v1.7 TRIM47 Zornitza Stark gene: TRIM47 was added
gene: TRIM47 was added to Stroke. Sources: Literature
Mode of inheritance for gene: TRIM47 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRIM47 were set to 35511193
Phenotypes for gene: TRIM47 were set to Genetic cerebral small vessel disease MONDO:0018787
Review for gene: TRIM47 was set to RED
Added comment: GWAS data:

Combined evidence from summary-based Mendelian randomization studies and profiling of human loss-of-function allele carriers showed an inverse relation between TRIM47 expression in the brain and blood vessels and extensive small vessel disease severity. Observed significant enrichment of Trim47 in isolated brain vessel preparations compared to total brain fraction in mice, in line with the literature showing Trim47 enrichment in brain endothelial cells at single cell level. Functional evaluation of TRIM47 by small interfering RNAs-mediated knockdown in human brain endothelial cells showed increased endothelial permeability, an important hallmark of cerebral small vessel disease pathology.
Sources: Literature
Calcium and Phosphate disorders v0.38 SLC34A3 Zornitza Stark Marked gene: SLC34A3 as ready
Calcium and Phosphate disorders v0.38 SLC34A3 Zornitza Stark Gene: slc34a3 has been classified as Green List (High Evidence).
Calcium and Phosphate disorders v0.38 SLC34A3 Zornitza Stark Phenotypes for gene: SLC34A3 were changed from to Hypophosphataemic rickets with hypercalciuria, (MIM#241530)
Calcium and Phosphate disorders v0.37 SLC34A3 Zornitza Stark Publications for gene: SLC34A3 were set to
Calcium and Phosphate disorders v0.36 SLC34A3 Zornitza Stark Mode of inheritance for gene: SLC34A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Calcium and Phosphate disorders v0.35 SLC34A3 Zornitza Stark reviewed gene: SLC34A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 32524022; Phenotypes: Hypophosphataemic rickets with hypercalciuria, (MIM#241530); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.113 COL12A1 Zornitza Stark Marked gene: COL12A1 as ready
Muscular dystrophy and myopathy_Paediatric v0.113 COL12A1 Zornitza Stark Gene: col12a1 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v0.113 COL12A1 Zornitza Stark Phenotypes for gene: COL12A1 were changed from to Ullrich congenital muscular dystrophy 2 , MIM# 616470
Muscular dystrophy and myopathy_Paediatric v0.112 COL12A1 Zornitza Stark Publications for gene: COL12A1 were set to
Muscular dystrophy and myopathy_Paediatric v0.111 COL12A1 Zornitza Stark Mode of inheritance for gene: COL12A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.110 COL12A1 Zornitza Stark Classified gene: COL12A1 as Amber List (moderate evidence)
Muscular dystrophy and myopathy_Paediatric v0.110 COL12A1 Zornitza Stark Gene: col12a1 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v0.109 COL12A1 Zornitza Stark reviewed gene: COL12A1: Rating: AMBER; Mode of pathogenicity: None; Publications: 24334604; Phenotypes: Ullrich congenital muscular dystrophy 2 , MIM# 616470; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.109 CHKB Zornitza Stark Marked gene: CHKB as ready
Muscular dystrophy and myopathy_Paediatric v0.109 CHKB Zornitza Stark Gene: chkb has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.109 CHKB Zornitza Stark Phenotypes for gene: CHKB were changed from to Muscular dystrophy, congenital, megaconial type, MIM# 602541
Muscular dystrophy and myopathy_Paediatric v0.108 CHKB Zornitza Stark Publications for gene: CHKB were set to
Muscular dystrophy and myopathy_Paediatric v0.107 CHKB Zornitza Stark Mode of inheritance for gene: CHKB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.106 ACTA1 Zornitza Stark Marked gene: ACTA1 as ready
Muscular dystrophy and myopathy_Paediatric v0.106 ACTA1 Zornitza Stark Gene: acta1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v0.106 ACTA1 Zornitza Stark Phenotypes for gene: ACTA1 were changed from to Nemaline myopathy 3, autosomal dominant or recessive, MIM# 161800
Muscular dystrophy and myopathy_Paediatric v0.105 ACTA1 Zornitza Stark Publications for gene: ACTA1 were set to
Muscular dystrophy and myopathy_Paediatric v0.104 ACTA1 Zornitza Stark Mode of inheritance for gene: ACTA1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Muscular dystrophy and myopathy_Paediatric v0.103 ACTA1 Zornitza Stark reviewed gene: ACTA1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Nemaline myopathy 3, autosomal dominant or recessive, MIM# 161800; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4811 TCTN2 Zornitza Stark Marked gene: TCTN2 as ready
Intellectual disability syndromic and non-syndromic v0.4811 TCTN2 Zornitza Stark Gene: tctn2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4811 TCTN2 Zornitza Stark Phenotypes for gene: TCTN2 were changed from to Joubert syndrome 24, MIM# 616654 MONDO:0014724
Intellectual disability syndromic and non-syndromic v0.4810 TCTN2 Zornitza Stark Publications for gene: TCTN2 were set to
Intellectual disability syndromic and non-syndromic v0.4809 TCTN2 Zornitza Stark Mode of inheritance for gene: TCTN2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4808 TCTN2 Zornitza Stark reviewed gene: TCTN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21565611, 25118024; Phenotypes: Joubert syndrome 24, MIM# 616654 MONDO:0014724; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Polydactyly v0.256 TCTN2 Zornitza Stark Marked gene: TCTN2 as ready
Polydactyly v0.256 TCTN2 Zornitza Stark Gene: tctn2 has been classified as Green List (High Evidence).
Polydactyly v0.256 TCTN2 Zornitza Stark Phenotypes for gene: TCTN2 were changed from to Joubert syndrome 24, MIM# 616654; MONDO:0014724; Meckel syndrome 8, MIM# 613885; MONDO:0013482
Polydactyly v0.255 TCTN2 Zornitza Stark Publications for gene: TCTN2 were set to
Polydactyly v0.254 TCTN2 Zornitza Stark reviewed gene: TCTN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21462283, 21565611, 25118024, 21725307, 32139166, 25118024, 32655147, 33590725; Phenotypes: Joubert syndrome 24, MIM# 616654, MONDO:0014724, Meckel syndrome 8, MIM# 613885, MONDO:0013482; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Desmosomal disorders v0.31 PKP1 Zornitza Stark Marked gene: PKP1 as ready
Desmosomal disorders v0.31 PKP1 Zornitza Stark Gene: pkp1 has been classified as Green List (High Evidence).
Desmosomal disorders v0.31 PKP1 Zornitza Stark Phenotypes for gene: PKP1 were changed from to Ectodermal dysplasia/skin fragility syndrome, MIM# 604536
Desmosomal disorders v0.30 PKP1 Zornitza Stark Publications for gene: PKP1 were set to
Desmosomal disorders v0.29 PKP1 Zornitza Stark Mode of inheritance for gene: PKP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Desmosomal disorders v0.28 PKP1 Zornitza Stark reviewed gene: PKP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24073657, 16781314, 11994137, 10951270, 32346906; Phenotypes: Ectodermal dysplasia/skin fragility syndrome, MIM# 604536; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Desmosomal disorders v0.28 DSG4 Zornitza Stark Marked gene: DSG4 as ready
Desmosomal disorders v0.28 DSG4 Zornitza Stark Gene: dsg4 has been classified as Green List (High Evidence).
Desmosomal disorders v0.28 DSG4 Zornitza Stark Phenotypes for gene: DSG4 were changed from to Hypotrichosis 6, MIM#607903
Desmosomal disorders v0.27 DSG4 Zornitza Stark Publications for gene: DSG4 were set to
Desmosomal disorders v0.26 DSG4 Zornitza Stark Mode of inheritance for gene: DSG4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Desmosomal disorders v0.25 DSG4 Zornitza Stark reviewed gene: DSG4: Rating: GREEN; Mode of pathogenicity: None; Publications: 12705872, 16439973, 16543896, 16575393, 17392831; Phenotypes: Hypotrichosis 6, MIM#607903; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Desmosomal disorders v0.25 ATP2A2 Zornitza Stark Marked gene: ATP2A2 as ready
Desmosomal disorders v0.25 ATP2A2 Zornitza Stark Added comment: Comment when marking as ready: Multiple reports of somatic mosaicism.
Desmosomal disorders v0.25 ATP2A2 Zornitza Stark Gene: atp2a2 has been classified as Green List (High Evidence).
Desmosomal disorders v0.25 ATP2A2 Zornitza Stark Tag somatic tag was added to gene: ATP2A2.
Desmosomal disorders v0.25 ATP2A2 Zornitza Stark Phenotypes for gene: ATP2A2 were changed from to Darier disease, MIM# 124200; Acrokeratosis verruciformis, MIM# 101900
Desmosomal disorders v0.24 ATP2A2 Zornitza Stark Publications for gene: ATP2A2 were set to
Desmosomal disorders v0.23 ATP2A2 Zornitza Stark Mode of inheritance for gene: ATP2A2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Desmosomal disorders v0.22 ATP2A2 Zornitza Stark Mode of inheritance for gene: ATP2A2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Desmosomal disorders v0.21 ATP2A2 Zornitza Stark reviewed gene: ATP2A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 10441325, 12072062, 10970890, 11389134; Phenotypes: Darier disease, MIM# 124200, Acrokeratosis verruciformis, MIM# 101900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Atrial Fibrillation v1.0 Zornitza Stark promoted panel to version 1.0
Atrial Fibrillation v0.20 KCNA5 Zornitza Stark Marked gene: KCNA5 as ready
Atrial Fibrillation v0.20 KCNA5 Zornitza Stark Gene: kcna5 has been classified as Amber List (Moderate Evidence).
Atrial Fibrillation v0.20 KCNA5 Zornitza Stark Phenotypes for gene: KCNA5 were changed from to Atrial fibrillation, familial, 7, MIM# 612240
Atrial Fibrillation v0.19 KCNA5 Zornitza Stark Publications for gene: KCNA5 were set to
Atrial Fibrillation v0.18 KCNA5 Zornitza Stark Mode of inheritance for gene: KCNA5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Atrial Fibrillation v0.17 KCNA5 Zornitza Stark Classified gene: KCNA5 as Amber List (moderate evidence)
Atrial Fibrillation v0.17 KCNA5 Zornitza Stark Gene: kcna5 has been classified as Amber List (Moderate Evidence).
Atrial Fibrillation v0.16 KCNA5 Zornitza Stark reviewed gene: KCNA5: Rating: AMBER; Mode of pathogenicity: None; Publications: 16772329, 19343045, 23264583; Phenotypes: Atrial fibrillation, familial, 7, MIM# 612240; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early-onset Dementia v0.155 APOE Zornitza Stark Classified gene: APOE as Amber List (moderate evidence)
Early-onset Dementia v0.155 APOE Zornitza Stark Gene: apoe has been classified as Amber List (Moderate Evidence).
Early-onset Dementia v0.154 APOE Zornitza Stark changed review comment from: E4 allele association with late-onset AD.; to: E4 allele association with late-onset AD. Susceptibility allele.
Early-onset Dementia v0.154 APOE Zornitza Stark edited their review of gene: APOE: Changed rating: AMBER
Intellectual disability syndromic and non-syndromic v0.4808 PRDM13 Zornitza Stark Phenotypes for gene: PRDM13 were changed from intellectual disability, MONDO:0001071, PRDM13-associated; Pontocerebellar hypoplasia (MONDO:0020135), PRDM13 related; congenital hypogonadotropic hypogonadism, MONDO:0015770 to Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, MIM# 619761
Intellectual disability syndromic and non-syndromic v0.4807 PRDM13 Zornitza Stark reviewed gene: PRDM13: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, MIM# 619761; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.33 PRDM13 Zornitza Stark Phenotypes for gene: PRDM13 were changed from Retinal dystrophy; Chorioretinal atrophy, progressive bifocal, MIM# 600790; intellectual disability, MONDO:0001071, PRDM13-associated; ataxia with cerebellar hypoplasia, MONDO:0016054, PRDM13-associated; congenital hypogonadotropic hypogonadism, MONDO:0015770 to Chorioretinal atrophy, progressive bifocal, MIM# 600790; Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, MIM# 619761
Differences of Sex Development v0.262 PRDM13 Zornitza Stark Phenotypes for gene: PRDM13 were changed from congenital hypogonadotropic hypogonadism, MONDO:0015770 to Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, MIM# 619761
Differences of Sex Development v0.261 PRDM13 Zornitza Stark edited their review of gene: PRDM13: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Differences of Sex Development v0.261 PRDM13 Zornitza Stark reviewed gene: PRDM13: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, MIM# 619761; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebellar and Pontocerebellar Hypoplasia v1.50 PRDM13 Zornitza Stark Phenotypes for gene: PRDM13 were changed from Pontocerebellar hypoplasia (MONDO:0020135), PRDM13 related; Intellectual disability (MONDO:0001071) to Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, MIM# 619761
Cerebellar and Pontocerebellar Hypoplasia v1.49 PRDM13 Zornitza Stark reviewed gene: PRDM13: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, MIM# 619761; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4807 HIST1H4J Zornitza Stark Phenotypes for gene: HIST1H4J were changed from microcephaly; intellectual disability; dysmorphic features to Tessadori-van Haaften neurodevelopmental syndrome 2 , MIM# 619759
Intellectual disability syndromic and non-syndromic v0.4806 HIST1H4J Zornitza Stark reviewed gene: HIST1H4J: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Tessadori-van Haaften neurodevelopmental syndrome 2 , MIM# 619759; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.32 HIST1H4J Zornitza Stark Phenotypes for gene: HIST1H4J were changed from microcephaly; intellectual disability; dysmorphic features to Tessadori-van Haaften neurodevelopmental syndrome 2 , MIM# 619759
Mendeliome v1.31 HIST1H4J Zornitza Stark edited their review of gene: HIST1H4J: Changed phenotypes: Tessadori-van Haaften neurodevelopmental syndrome 2 , MIM# 619759
Fetal anomalies v1.39 HIST1H4C Zornitza Stark Phenotypes for gene: HIST1H4C were changed from Growth delay, microcephaly and intellectual disability to Tessadori-van Haaften neurodevelopmental syndrome 1 MIM#619758
Fetal anomalies v1.38 HIST1H4C Zornitza Stark edited their review of gene: HIST1H4C: Changed phenotypes: Tessadori-van Haaften neurodevelopmental syndrome 1 MIM#619758
Microcephaly v1.126 HIST1H4C Zornitza Stark Phenotypes for gene: HIST1H4C were changed from Growth delay, microcephaly and intellectual disability to Tessadori-van Haaften neurodevelopmental syndrome 1 MIM#619758
Microcephaly v1.125 HIST1H4C Zornitza Stark edited their review of gene: HIST1H4C: Changed phenotypes: Tessadori-van Haaften neurodevelopmental syndrome 1 MIM#619758
Prepair 1000+ v0.0 ZNF469 Zornitza Stark gene: ZNF469 was added
gene: ZNF469 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Red
Mode of inheritance for gene: ZNF469 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ZNF469 were set to Brittle cornea syndrome 1, MIM #229200
Prepair 1000+ v0.0 YIF1B Zornitza Stark gene: YIF1B was added
gene: YIF1B was added to Reproductive Carrier Screen_VCGS. Sources: Expert Review
Mode of inheritance for gene: YIF1B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YIF1B were set to 32006098; 26077767
Phenotypes for gene: YIF1B were set to Abnormality of movement; Seizures; Failure to thrive; Spasticity; Central hypotonia; Intellectual disability; Global developmental delay; Microcephaly
Prepair 1000+ v0.0 UQCRC2 Zornitza Stark gene: UQCRC2 was added
gene: UQCRC2 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Red
Mode of inheritance for gene: UQCRC2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UQCRC2 were set to Mitochondrial complex III deficiency, nuclear type 5, 615160 (3)
Prepair 1000+ v0.0 UPB1 Zornitza Stark gene: UPB1 was added
gene: UPB1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Red
Mode of inheritance for gene: UPB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UPB1 were set to 24526388
Phenotypes for gene: UPB1 were set to Beta-ureidopropionase deficiency, MIM #613161
Prepair 1000+ v0.0 TUBA8 Zornitza Stark gene: TUBA8 was added
gene: TUBA8 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Red
Mode of inheritance for gene: TUBA8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TUBA8 were set to Polymicrogyria with optic nerve hypoplasia, 613180 (3)
Prepair 1000+ v0.0 TSPYL1 Zornitza Stark gene: TSPYL1 was added
gene: TSPYL1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Red
Mode of inheritance for gene: TSPYL1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TSPYL1 were set to Sudden infant death with dysgenesis of the testes syndrome, 608800 (3)
Prepair 1000+ v0.0 TRAPPC6B Zornitza Stark gene: TRAPPC6B was added
gene: TRAPPC6B was added to Reproductive Carrier Screen_VCGS. Sources: Expert Review
Mode of inheritance for gene: TRAPPC6B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRAPPC6B were set to 28397838; 28626029; 31687267
Phenotypes for gene: TRAPPC6B were set to Neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy, MIM# 617862
Prepair 1000+ v0.0 TRAPPC12 Zornitza Stark gene: TRAPPC12 was added
gene: TRAPPC12 was added to Reproductive Carrier Screen_VCGS. Sources: Expert Review
Mode of inheritance for gene: TRAPPC12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRAPPC12 were set to 32369837; 28777934
Phenotypes for gene: TRAPPC12 were set to Encephalopathy, progressive, early-onset, with brain atrophy and spasticity, MIM# 617669
Prepair 1000+ v0.0 TPRKB Zornitza Stark gene: TPRKB was added
gene: TPRKB was added to Reproductive Carrier Screen_VCGS. Sources: Expert Review
Mode of inheritance for gene: TPRKB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TPRKB were set to 30053862; 28805828
Phenotypes for gene: TPRKB were set to Galloway-Mowat syndrome 5, MIM# 617731
Prepair 1000+ v0.0 TP53RK Zornitza Stark gene: TP53RK was added
gene: TP53RK was added to Reproductive Carrier Screen_VCGS. Sources: Expert Review
Mode of inheritance for gene: TP53RK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TP53RK were set to 30053862; 28805828
Phenotypes for gene: TP53RK were set to Galloway-Mowat syndrome 4, MIM# 617730
Prepair 1000+ v0.0 TBX22 Zornitza Stark gene: TBX22 was added
gene: TBX22 was added to Reproductive Carrier Screen_VCGS. Sources: Expert Review,Expert Review Red
Mode of inheritance for gene: TBX22 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: TBX22 were set to Cleft palate with ankyloglossia, MIM #303400
Prepair 1000+ v0.0 TBC1D20 Zornitza Stark gene: TBC1D20 was added
gene: TBC1D20 was added to Reproductive Carrier Screen_VCGS. Sources: Expert list
Mode of inheritance for gene: TBC1D20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBC1D20 were set to 32162791; 24239381; 32740904
Phenotypes for gene: TBC1D20 were set to Martsolf syndrome; Warburg micro syndrome 4, MIM# 615663
Prepair 1000+ v0.0 PUS7 Zornitza Stark gene: PUS7 was added
gene: PUS7 was added to Reproductive Carrier Screen_VCGS. Sources: Expert list
Mode of inheritance for gene: PUS7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PUS7 were set to 30526862; 31583274; 30778726
Phenotypes for gene: PUS7 were set to OMIM #618342; Intellectual developmental disorder with abnormal behavior, microcephaly, and short stature
Prepair 1000+ v0.0 PTPN23 Zornitza Stark gene: PTPN23 was added
gene: PTPN23 was added to Reproductive Carrier Screen_VCGS. Sources: Expert list
Mode of inheritance for gene: PTPN23 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTPN23 were set to 25558065; 31395947; 27848944; 29899372; 29090338
Phenotypes for gene: PTPN23 were set to Neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity, MIM# 618890
Prepair 1000+ v0.0 PIP5K1C Zornitza Stark gene: PIP5K1C was added
gene: PIP5K1C was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Red
Mode of inheritance for gene: PIP5K1C was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PIP5K1C were set to Lethal congenital contractural syndrome 3, 611369 (3)
Prepair 1000+ v0.0 PDE6B Zornitza Stark gene: PDE6B was added
gene: PDE6B was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Red
Mode of inheritance for gene: PDE6B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PDE6B were set to Retinitis pigmentosa-40, MIM #613801
Prepair 1000+ v0.0 OPN1LW Zornitza Stark gene: OPN1LW was added
gene: OPN1LW was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Red
Mode of inheritance for gene: OPN1LW was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: OPN1LW were set to Blue cone monochromacy, MIM#303700; Colorblindness, protan, MIM#303900
Prepair 1000+ v0.0 KRT8 Zornitza Stark gene: KRT8 was added
gene: KRT8 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Red
Mode of inheritance for gene: KRT8 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KRT8 were set to 12724528; 11372009; 15235035
Phenotypes for gene: KRT8 were set to CIRRHOSIS, FAMILIAL, MIM #215600
Prepair 1000+ v0.0 ITGA3 Zornitza Stark gene: ITGA3 was added
gene: ITGA3 was added to Reproductive Carrier Screen_VCGS. Sources: Expert Review
Mode of inheritance for gene: ITGA3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ITGA3 were set to 27717396; 22512483; 26854491; 32198874; 25810266
Phenotypes for gene: ITGA3 were set to Interstitial lung disease, nephrotic syndrome, and epidermolysis bullosa, congenital, MIM# 614748
Prepair 1000+ v0.0 ISCA1 Zornitza Stark gene: ISCA1 was added
gene: ISCA1 was added to Reproductive Carrier Screen_VCGS. Sources: Expert Review
Mode of inheritance for gene: ISCA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ISCA1 were set to 32092383; 30113620; 30105122; 31016283; 28356563
Phenotypes for gene: ISCA1 were set to Multiple mitochondrial dysfunctions syndrome 5, MIM# 617613
Prepair 1000+ v0.0 IMPG2 Zornitza Stark gene: IMPG2 was added
gene: IMPG2 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Red
Mode of inheritance for gene: IMPG2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IMPG2 were set to Retinitis pigmentosa 56, MIM #613801
Prepair 1000+ v0.0 GTPBP2 Zornitza Stark gene: GTPBP2 was added
gene: GTPBP2 was added to Reproductive Carrier Screen_VCGS. Sources: Expert Review
Mode of inheritance for gene: GTPBP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTPBP2 were set to 30790272; 26675814; 29449720
Phenotypes for gene: GTPBP2 were set to Jaberi-Elahi syndrome, MIM#617988
Prepair 1000+ v0.0 FITM2 Zornitza Stark gene: FITM2 was added
gene: FITM2 was added to Reproductive Carrier Screen_VCGS. Sources: Expert list,Expert Review Red
Mode of inheritance for gene: FITM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FITM2 were set to 30214770; 28067622; 30288795
Phenotypes for gene: FITM2 were set to Siddiqi syndrome MIM#618635
Prepair 1000+ v0.0 FAM161A Zornitza Stark gene: FAM161A was added
gene: FAM161A was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Red
Mode of inheritance for gene: FAM161A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FAM161A were set to Retinitis pigmentosa 28, MIM #606068
Prepair 1000+ v0.0 COG5 Zornitza Stark gene: COG5 was added
gene: COG5 was added to Reproductive Carrier Screen_VCGS. Sources: Expert Review
Mode of inheritance for gene: COG5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COG5 were set to 32174980; 31572517; 23228021
Phenotypes for gene: COG5 were set to Congenital disorder of glycosylation, type IIi, MIM# 613612
Prepair 1000+ v0.0 CIB2 Zornitza Stark gene: CIB2 was added
gene: CIB2 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Red
Mode of inheritance for gene: CIB2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CIB2 were set to Usher syndrome, type IJ, 614869 (3)
Prepair 1000+ v0.0 CD81 Zornitza Stark gene: CD81 was added
gene: CD81 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Red
Mode of inheritance for gene: CD81 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CD81 were set to 20237408
Phenotypes for gene: CD81 were set to Immunodeficiency, common variable, 6, 613496 (3)
Prepair 1000+ v0.0 CBS Zornitza Stark gene: CBS was added
gene: CBS was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Red
Mode of inheritance for gene: CBS was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CBS were set to Homocystinuria, B6-responsive and nonresponsive types, 236200 (3)
Prepair 1000+ v0.0 BCAP31 Zornitza Stark gene: BCAP31 was added
gene: BCAP31 was added to Reproductive Carrier Screen_VCGS. Sources: Expert Review
Mode of inheritance for gene: BCAP31 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: BCAP31 were set to 31330203; 24011989; 33603160
Phenotypes for gene: BCAP31 were set to Deafness, dystonia, and cerebral hypomyelination, MIM# 300475
Prepair 1000+ v0.0 AFF2 Zornitza Stark gene: AFF2 was added
gene: AFF2 was added to Reproductive Carrier Screen_VCGS. Sources: Expert Review,Expert Review Red
Mode of inheritance for gene: AFF2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: AFF2 were set to Mental retardation, X-linked, FRAXE type, #309548
Prepair 1000+ v0.0 ADPRHL2 Zornitza Stark gene: ADPRHL2 was added
gene: ADPRHL2 was added to Reproductive Carrier Screen_VCGS. Sources: Expert Review
Mode of inheritance for gene: ADPRHL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADPRHL2 were set to 30401461; 30100084
Phenotypes for gene: ADPRHL2 were set to Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, MIM#618170
Prepair 1000+ v0.0 ACY1 Zornitza Stark gene: ACY1 was added
gene: ACY1 was added to Reproductive Carrier Screen_VCGS. Sources: Expert Review
Mode of inheritance for gene: ACY1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACY1 were set to 24117009; 16465618; 16274666; 17562838
Phenotypes for gene: ACY1 were set to Aminoacylase 1 deficiency, MIM# 609924
Prepair 1000+ v0.0 ACSF3 Zornitza Stark gene: ACSF3 was added
gene: ACSF3 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Red
Mode of inheritance for gene: ACSF3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ACSF3 were set to Combined malonic and methylmalonic aciduria, MIM#614265
Prepair 1000+ v0.0 ABCC6 Zornitza Stark gene: ABCC6 was added
gene: ABCC6 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Red
Mode of inheritance for gene: ABCC6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ABCC6 were set to Pseudoxanthoma elasticum MIM#264800; Arterial calcification, generalized, of infancy, 2 MIM#614473
Prepair 1000+ v0.0 ABCA4 Zornitza Stark gene: ABCA4 was added
gene: ABCA4 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Red
Mode of inheritance for gene: ABCA4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ABCA4 were set to Cone-rod dystrophy 3 MIM#604116; Stargardt disease 1 MIM#248200; Retinal dystrophy, early-onset severe MIM#248200
Prepair 1000+ v0.0 XPNPEP3 Zornitza Stark gene: XPNPEP3 was added
gene: XPNPEP3 was added to Reproductive Carrier Screen_VCGS. Sources: Expert Review Amber,Mackenzie's Mission
Mode of inheritance for gene: XPNPEP3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: XPNPEP3 were set to Nephronophthisis-like nephropathy 1, 613159 (3)
Prepair 1000+ v0.0 TRAC Zornitza Stark gene: TRAC was added
gene: TRAC was added to Reproductive Carrier Screen_VCGS. Sources: Expert Review Amber,Mackenzie's Mission
Mode of inheritance for gene: TRAC was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRAC were set to Immunodeficiency 7, TCR-alpha/beta deficient, 615387 (3)
Prepair 1000+ v0.0 TMEM94 Zornitza Stark gene: TMEM94 was added
gene: TMEM94 was added to Reproductive Carrier Screen_VCGS. Sources: Expert Review Amber,Expert list
Mode of inheritance for gene: TMEM94 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM94 were set to 30526868
Phenotypes for gene: TMEM94 were set to Intellectual developmental disorder with cardiac defects and dysmorphic facies, MIM#618316
Prepair 1000+ v0.0 RPL10 Zornitza Stark gene: RPL10 was added
gene: RPL10 was added to Reproductive Carrier Screen_VCGS. Sources: Expert Review Amber,Mackenzie's Mission
Mode of inheritance for gene: RPL10 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: RPL10 were set to Mental retardation, X-linked, syndromic, 35 (MIM#300998)
Prepair 1000+ v0.0 POLA1 Zornitza Stark gene: POLA1 was added
gene: POLA1 was added to Reproductive Carrier Screen_VCGS. Sources: Expert Review Amber,Mackenzie's Mission
Mode of inheritance for gene: POLA1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: POLA1 were set to Pigmentary disorder, reticulate, with systemic manifestations, X-linked, MIM#301220; Van Esch-O'Driscoll syndrome, MIM #301030
Prepair 1000+ v0.0 NTNG2 Zornitza Stark gene: NTNG2 was added
gene: NTNG2 was added to Reproductive Carrier Screen_VCGS. Sources: Expert Review Amber,Expert Review
Mode of inheritance for gene: NTNG2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NTNG2 were set to 31692205; 31668703
Phenotypes for gene: NTNG2 were set to Neurodevelopmental disorder with behavioral abnormalities, absent speech, and hypotonia, MIM# 618718
Prepair 1000+ v0.0 MOGS Zornitza Stark gene: MOGS was added
gene: MOGS was added to Reproductive Carrier Screen_VCGS. Sources: Expert Review Amber,Expert Review
Mode of inheritance for gene: MOGS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MOGS were set to 30587846; 33058492; 31925597
Phenotypes for gene: MOGS were set to Congenital disorder of glycosylation, type IIb, MIM# 606056
Prepair 1000+ v0.0 MBTPS1 Zornitza Stark gene: MBTPS1 was added
gene: MBTPS1 was added to Reproductive Carrier Screen_VCGS. Sources: Expert Review Amber,Literature,Expert Review
Mode of inheritance for gene: MBTPS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MBTPS1 were set to 32857899; 30046013; 32420688
Phenotypes for gene: MBTPS1 were set to ?Spondyloepiphyseal dysplasia, Kondo-Fu type, MIM #618392
Prepair 1000+ v0.0 KCNE1 Zornitza Stark gene: KCNE1 was added
gene: KCNE1 was added to Reproductive Carrier Screen_VCGS. Sources: Expert Review Amber,Mackenzie's Mission
Mode of inheritance for gene: KCNE1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: KCNE1 were set to Jervell and Lange-Nielsen syndrome 2, 612347 (3)
Prepair 1000+ v0.0 ERBB3 Zornitza Stark gene: ERBB3 was added
gene: ERBB3 was added to Reproductive Carrier Screen_VCGS. Sources: Expert Review Amber,Mackenzie's Mission
Mode of inheritance for gene: ERBB3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ERBB3 were set to Lethal congenital contractural syndrome 2, 607598 (3)
Prepair 1000+ v0.0 DYNC1I2 Zornitza Stark gene: DYNC1I2 was added
gene: DYNC1I2 was added to Reproductive Carrier Screen_VCGS. Sources: Expert Review Amber,Expert Review
Mode of inheritance for gene: DYNC1I2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DYNC1I2 were set to 31079899
Phenotypes for gene: DYNC1I2 were set to Neurodevelopmental disorder with microcephaly and structural brain anomalies , MIM#618492
Prepair 1000+ v0.0 COL2A1 Zornitza Stark gene: COL2A1 was added
gene: COL2A1 was added to Reproductive Carrier Screen_VCGS. Sources: Expert Review Amber,Mackenzie's Mission
Mode of inheritance for gene: COL2A1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: COL2A1 were set to 32896647; 31755234
Phenotypes for gene: COL2A1 were set to Spondyloperipheral dysplasia, MIM #271700
Prepair 1000+ v0.0 B9D1 Zornitza Stark gene: B9D1 was added
gene: B9D1 was added to Reproductive Carrier Screen_VCGS. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: B9D1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B9D1 were set to 21493627; 24886560; 25920555
Phenotypes for gene: B9D1 were set to Joubert syndrome 27, MIM# 617120; Meckel syndrome 9, MIM# 614209
Prepair 1000+ v0.0 ZNHIT3 Zornitza Stark gene: ZNHIT3 was added
gene: ZNHIT3 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: ZNHIT3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ZNHIT3 were set to PEHO syndrome, 260565 (3), Autosomal recessive
Prepair 1000+ v0.0 ZNF711 Zornitza Stark gene: ZNF711 was added
gene: ZNF711 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: ZNF711 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: ZNF711 were set to Mental retardation, X-linked 97, 300803 (3)
Prepair 1000+ v0.0 ZNF335 Zornitza Stark gene: ZNF335 was added
gene: ZNF335 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: ZNF335 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ZNF335 were set to Microcephaly 10, primary, autosomal recessive
Prepair 1000+ v0.0 ZMYND10 Zornitza Stark gene: ZMYND10 was added
gene: ZMYND10 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: ZMYND10 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ZMYND10 were set to Ciliary dyskinesia, primary, 22, 615444 (3)
Prepair 1000+ v0.0 ZMPSTE24 Zornitza Stark gene: ZMPSTE24 was added
gene: ZMPSTE24 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: ZMPSTE24 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ZMPSTE24 were set to Restrictive dermopathy, lethal, 275210 (3)
Prepair 1000+ v0.0 ZIC3 Zornitza Stark gene: ZIC3 was added
gene: ZIC3 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: ZIC3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: ZIC3 were set to Congenital heart defects, nonsyndromic, 1, X-linked, 306955 (3)
Prepair 1000+ v0.0 ZFYVE26 Zornitza Stark gene: ZFYVE26 was added
gene: ZFYVE26 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: ZFYVE26 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ZFYVE26 were set to Spastic paraplegia 15, autosomal recessive, 270700 (3)
Prepair 1000+ v0.0 ZDHHC9 Zornitza Stark gene: ZDHHC9 was added
gene: ZDHHC9 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: ZDHHC9 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: ZDHHC9 were set to Mental retardation, X-linked syndromic, Raymond type, 300799 (3)
Prepair 1000+ v0.0 ZC4H2 Zornitza Stark gene: ZC4H2 was added
gene: ZC4H2 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: ZC4H2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: ZC4H2 were set to Wieacker-Wolff syndrome, 314580 (3)
Prepair 1000+ v0.0 ZBTB24 Zornitza Stark gene: ZBTB24 was added
gene: ZBTB24 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: ZBTB24 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ZBTB24 were set to Immunodeficiency-centromeric instability-facial anomalies syndrome-2, 614069 (3)
Prepair 1000+ v0.0 ZAP70 Zornitza Stark gene: ZAP70 was added
gene: ZAP70 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: ZAP70 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ZAP70 were set to Selective T-cell defect, 269840 (3)
Prepair 1000+ v0.0 YARS2 Zornitza Stark gene: YARS2 was added
gene: YARS2 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: YARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: YARS2 were set to Myopathy, lactic acidosis, and sideroblastic anemia 2, 613561 (3)
Prepair 1000+ v0.0 XYLT2 Zornitza Stark gene: XYLT2 was added
gene: XYLT2 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: XYLT2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: XYLT2 were set to Spondyloocular syndrome, 605822 (3), Autosomal recessive
Prepair 1000+ v0.0 XYLT1 Zornitza Stark gene: XYLT1 was added
gene: XYLT1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: XYLT1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: XYLT1 were set to Desbuquois dysplasia 2, 615777 (3)
Prepair 1000+ v0.0 XRCC4 Zornitza Stark gene: XRCC4 was added
gene: XRCC4 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: XRCC4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: XRCC4 were set to Short stature, microcephaly, and endocrine dysfunction, 616541 (3), Autosomal recessive
Prepair 1000+ v0.0 XPC Zornitza Stark gene: XPC was added
gene: XPC was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: XPC was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: XPC were set to Xeroderma pigmentosum, group C, 278720 (3)
Prepair 1000+ v0.0 XPA Zornitza Stark gene: XPA was added
gene: XPA was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: XPA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: XPA were set to Xeroderma pigmentosum, group A, 278700 (3)
Prepair 1000+ v0.0 XIAP Zornitza Stark gene: XIAP was added
gene: XIAP was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: XIAP was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: XIAP were set to Lymphoproliferative syndrome, X-linked, 2, 300635 (3)
Prepair 1000+ v0.0 WWOX Zornitza Stark gene: WWOX was added
gene: WWOX was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: WWOX was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WWOX were set to Epileptic encephalopathy, early infantile, 28, 616211 (3)
Prepair 1000+ v0.0 WRN Zornitza Stark gene: WRN was added
gene: WRN was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: WRN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WRN were set to Werner syndrome, 277700 (3)
Prepair 1000+ v0.0 WRAP53 Zornitza Stark gene: WRAP53 was added
gene: WRAP53 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: WRAP53 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WRAP53 were set to Dyskeratosis congenita, autosomal recessive 3, 613988 (3)
Prepair 1000+ v0.0 WNT7A Zornitza Stark gene: WNT7A was added
gene: WNT7A was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: WNT7A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WNT7A were set to Ulna and fibula, absence of, with severe limb deficiency, 276820 (3)
Prepair 1000+ v0.0 WNT10B Zornitza Stark gene: WNT10B was added
gene: WNT10B was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: WNT10B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WNT10B were set to Split-hand/foot malformation 6, 225300 (3)
Prepair 1000+ v0.0 WNT1 Zornitza Stark gene: WNT1 was added
gene: WNT1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: WNT1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WNT1 were set to Osteogenesis imperfecta, type XV, 615220 (3)
Prepair 1000+ v0.0 WNK1 Zornitza Stark gene: WNK1 was added
gene: WNK1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: WNK1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WNK1 were set to Neuropathy, hereditary sensory and autonomic, type II, 201300 (3)
Prepair 1000+ v0.0 WISP3 Zornitza Stark gene: WISP3 was added
gene: WISP3 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: WISP3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WISP3 were set to Arthropathy, progressive pseudorheumatoid, of childhood, 208230 (3)
Prepair 1000+ v0.0 WHRN Zornitza Stark gene: WHRN was added
gene: WHRN was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: WHRN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WHRN were set to Usher syndrome, type 2D, 611383 (3)
Prepair 1000+ v0.0 WFS1 Zornitza Stark gene: WFS1 was added
gene: WFS1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: WFS1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WFS1 were set to Wolfram syndrome, 222300 (3)
Prepair 1000+ v0.0 WDR81 Zornitza Stark gene: WDR81 was added
gene: WDR81 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: WDR81 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WDR81 were set to Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 2, 610185 (3)
Prepair 1000+ v0.0 WDR73 Zornitza Stark gene: WDR73 was added
gene: WDR73 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: WDR73 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WDR73 were set to Galloway-Mowat syndrome, 251300 (3)
Prepair 1000+ v0.0 WDR62 Zornitza Stark gene: WDR62 was added
gene: WDR62 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: WDR62 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WDR62 were set to Microcephaly 2, primary, autosomal recessive, with or without cortical malformations, 604317 (3)
Prepair 1000+ v0.0 WDR60 Zornitza Stark gene: WDR60 was added
gene: WDR60 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: WDR60 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WDR60 were set to Short-rib thoracic dysplasia 8 with or without polydactyly, 615503 (3)
Prepair 1000+ v0.0 WDR45B Zornitza Stark gene: WDR45B was added
gene: WDR45B was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: WDR45B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WDR45B were set to Neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizures, 617977 (3), Autosomal recessive
Prepair 1000+ v0.0 WDR35 Zornitza Stark gene: WDR35 was added
gene: WDR35 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: WDR35 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WDR35 were set to Short-rib thoracic dysplasia 7 with or without polydactyly, 614091 (3)
Prepair 1000+ v0.0 WDR34 Zornitza Stark gene: WDR34 was added
gene: WDR34 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: WDR34 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WDR34 were set to Short-rib thoracic dysplasia 11 with or without polydactyly, 615633 (3)
Prepair 1000+ v0.0 WDR19 Zornitza Stark gene: WDR19 was added
gene: WDR19 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: WDR19 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WDR19 were set to Senior-Loken syndrome 8, 616307 (3)
Prepair 1000+ v0.0 WAS Zornitza Stark gene: WAS was added
gene: WAS was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: WAS was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: WAS were set to Wiskott-Aldrich syndrome, 301000 (3)
Prepair 1000+ v0.0 WARS2 Zornitza Stark gene: WARS2 was added
gene: WARS2 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: WARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WARS2 were set to Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures, 617710 (3), Autosomal recessive
Prepair 1000+ v0.0 VWF Zornitza Stark gene: VWF was added
gene: VWF was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: VWF was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VWF were set to von Willebrand disease, types 2A, 2B, 2M, and 2N, 613554 (3)
Prepair 1000+ v0.0 VSX2 Zornitza Stark gene: VSX2 was added
gene: VSX2 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: VSX2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VSX2 were set to Microphthalmia with coloboma 3, 610092 (3)
Prepair 1000+ v0.0 VRK1 Zornitza Stark gene: VRK1 was added
gene: VRK1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: VRK1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VRK1 were set to Pontocerebellar hypoplasia type 1A, 607596 (3)
Prepair 1000+ v0.0 VPS53 Zornitza Stark gene: VPS53 was added
gene: VPS53 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: VPS53 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VPS53 were set to Pontocerebellar hypoplasia, type 2E, 615851 (3)
Prepair 1000+ v0.0 VPS45 Zornitza Stark gene: VPS45 was added
gene: VPS45 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: VPS45 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VPS45 were set to Neutropenia, severe congenital, 5, autosomal recessive, 615285 (3)
Prepair 1000+ v0.0 VPS37A Zornitza Stark gene: VPS37A was added
gene: VPS37A was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: VPS37A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VPS37A were set to Spastic paraplegia 53, autosomal recessive, 614898 (3)
Prepair 1000+ v0.0 VPS33B Zornitza Stark gene: VPS33B was added
gene: VPS33B was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: VPS33B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VPS33B were set to Arthrogryposis, renal dysfunction, and cholestasis 1, 208085 (3)
Prepair 1000+ v0.0 VPS13B Zornitza Stark gene: VPS13B was added
gene: VPS13B was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: VPS13B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VPS13B were set to Cohen syndrome, 216550 (3)
Prepair 1000+ v0.0 VPS13A Zornitza Stark gene: VPS13A was added
gene: VPS13A was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: VPS13A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VPS13A were set to Choreoacanthocytosis, 200150 (3)
Prepair 1000+ v0.0 VPS11 Zornitza Stark gene: VPS11 was added
gene: VPS11 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: VPS11 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VPS11 were set to Leukodystrophy, hypomyelinating, 12, 616683 (3), Autosomal recessive
Prepair 1000+ v0.0 VMA21 Zornitza Stark gene: VMA21 was added
gene: VMA21 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: VMA21 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: VMA21 were set to Myopathy, X-linked, with excessive autophagy, 310440 (3), X-linked recessive
Prepair 1000+ v0.0 VLDLR Zornitza Stark gene: VLDLR was added
gene: VLDLR was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: VLDLR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VLDLR were set to Cerebellar hypoplasia and mental retardation with or without quadrupedal locomotion 1, 224050 (3)
Prepair 1000+ v0.0 VKORC1 Zornitza Stark gene: VKORC1 was added
gene: VKORC1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: VKORC1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VKORC1 were set to Vitamin K-dependent clotting factors, combined deficiency of, 2, 607473 (3)
Prepair 1000+ v0.0 VIPAS39 Zornitza Stark gene: VIPAS39 was added
gene: VIPAS39 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: VIPAS39 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VIPAS39 were set to Arthrogryposis, renal dysfunction, and cholestasis 2, 613404 (3)
Prepair 1000+ v0.0 VARS2 Zornitza Stark gene: VARS2 was added
gene: VARS2 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: VARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VARS2 were set to Combined oxidative phosphorylation deficiency 20, 615917 (3)
Prepair 1000+ v0.0 VARS Zornitza Stark gene: VARS was added
gene: VARS was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: VARS was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VARS were set to Neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy, 617802 (3), Autosomal recessive
Prepair 1000+ v0.0 USP9X Zornitza Stark gene: USP9X was added
gene: USP9X was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: USP9X was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: USP9X were set to Mental retardation, X-linked 99, 300919 (3)
Prepair 1000+ v0.0 USH2A Zornitza Stark gene: USH2A was added
gene: USH2A was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: USH2A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: USH2A were set to Usher syndrome, type 2A, 276901 (3)
Prepair 1000+ v0.0 USH1G Zornitza Stark gene: USH1G was added
gene: USH1G was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: USH1G was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: USH1G were set to Usher syndrome, type 1G, 606943 (3)
Prepair 1000+ v0.0 USH1C Zornitza Stark gene: USH1C was added
gene: USH1C was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: USH1C was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: USH1C were set to Usher syndrome, type 1C, 276904 (3)
Prepair 1000+ v0.0 USB1 Zornitza Stark gene: USB1 was added
gene: USB1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: USB1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: USB1 were set to Poikiloderma with neutropenia, 604173 (3)
Prepair 1000+ v0.0 UROS Zornitza Stark gene: UROS was added
gene: UROS was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: UROS was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UROS were set to Porphyria, congenital erythropoietic, 263700 (3)
Prepair 1000+ v0.0 UQCRQ Zornitza Stark gene: UQCRQ was added
gene: UQCRQ was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: UQCRQ was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UQCRQ were set to Mitochondrial complex III deficiency, nuclear type 4, 615159 (3)
Prepair 1000+ v0.0 UPF3B Zornitza Stark gene: UPF3B was added
gene: UPF3B was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: UPF3B was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: UPF3B were set to Mental retardation, X-linked, syndromic 14, 300676 (3)
Prepair 1000+ v0.0 UNC80 Zornitza Stark gene: UNC80 was added
gene: UNC80 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: UNC80 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UNC80 were set to Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, 616801 (3), Autosomal recessive
Prepair 1000+ v0.0 UNC13D Zornitza Stark gene: UNC13D was added
gene: UNC13D was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: UNC13D was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UNC13D were set to Hemophagocytic lymphohistiocytosis, familial, 3, 608898 (3)
Prepair 1000+ v0.0 UMPS Zornitza Stark gene: UMPS was added
gene: UMPS was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: UMPS was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UMPS were set to Orotic aciduria, 258900 (3)
Prepair 1000+ v0.0 UGT1A1 Zornitza Stark gene: UGT1A1 was added
gene: UGT1A1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: UGT1A1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UGT1A1 were set to Crigler-Najjar syndrome, type I, 218800 (3)
Prepair 1000+ v0.0 UFM1 Zornitza Stark gene: UFM1 was added
gene: UFM1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: UFM1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UFM1 were set to Leukodystrophy, hypomyelinating, 14, 617899 (3), Autosomal recessive
Prepair 1000+ v0.0 UBR1 Zornitza Stark gene: UBR1 was added
gene: UBR1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: UBR1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UBR1 were set to Johanson-Blizzard syndrome, 243800 (3)
Prepair 1000+ v0.0 UBE3B Zornitza Stark gene: UBE3B was added
gene: UBE3B was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: UBE3B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UBE3B were set to Kaufman oculocerebrofacial syndrome, 244450 (3)
Prepair 1000+ v0.0 UBE2T Zornitza Stark gene: UBE2T was added
gene: UBE2T was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: UBE2T was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UBE2T were set to Fanconi anemia, complementation group T, 616435 (3)
Prepair 1000+ v0.0 UBE2A Zornitza Stark gene: UBE2A was added
gene: UBE2A was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: UBE2A was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: UBE2A were set to Mental retardation, X-linked syndromic, Nascimento-type, 300860 (3)
Prepair 1000+ v0.0 UBA5 Zornitza Stark gene: UBA5 was added
gene: UBA5 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: UBA5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UBA5 were set to Epileptic encephalopathy, early infantile, 44, 617132 (3), Autosomal recessive
Prepair 1000+ v0.0 UBA1 Zornitza Stark gene: UBA1 was added
gene: UBA1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: UBA1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: UBA1 were set to Spinal muscular atrophy, X-linked 2, infantile, 301830 (3)
Prepair 1000+ v0.0 TYRP1 Zornitza Stark gene: TYRP1 was added
gene: TYRP1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TYRP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TYRP1 were set to Albinism, oculocutaneous, type III, 203290 (3)
Prepair 1000+ v0.0 TYR Zornitza Stark gene: TYR was added
gene: TYR was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TYR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TYR were set to Albinism, oculocutaneous, type IA, 203100 (3)
Prepair 1000+ v0.0 TYMP Zornitza Stark gene: TYMP was added
gene: TYMP was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TYMP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TYMP were set to Mitochondrial DNA depletion syndrome 1 (MNGIE type), 603041 (3)
Prepair 1000+ v0.0 TYK2 Zornitza Stark gene: TYK2 was added
gene: TYK2 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TYK2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TYK2 were set to Immunodeficiency 35, 611521 (3)
Prepair 1000+ v0.0 TXNL4A Zornitza Stark gene: TXNL4A was added
gene: TXNL4A was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TXNL4A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TXNL4A were set to Burn-McKeown syndrome, 608572 (3)
Prepair 1000+ v0.0 TWNK Zornitza Stark gene: TWNK was added
gene: TWNK was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TWNK was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TWNK were set to Mitochondrial DNA depletion syndrome 7 (hepatocerebral type), 271245 (3)
Prepair 1000+ v0.0 TUSC3 Zornitza Stark gene: TUSC3 was added
gene: TUSC3 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TUSC3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TUSC3 were set to Mental retardation, autosomal recessive 7, 611093 (3)
Prepair 1000+ v0.0 TULP1 Zornitza Stark gene: TULP1 was added
gene: TULP1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TULP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TULP1 were set to Retinitis pigmentosa 14, 600132 (3)
Prepair 1000+ v0.0 TUFM Zornitza Stark gene: TUFM was added
gene: TUFM was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TUFM was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TUFM were set to Combined oxidative phosphorylation deficiency 4, 610678 (3)
Prepair 1000+ v0.0 TUBGCP6 Zornitza Stark gene: TUBGCP6 was added
gene: TUBGCP6 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TUBGCP6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TUBGCP6 were set to Microcephaly and chorioretinopathy, autosomal recessive, 1, 251270 (3)
Prepair 1000+ v0.0 TUBGCP4 Zornitza Stark gene: TUBGCP4 was added
gene: TUBGCP4 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TUBGCP4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TUBGCP4 were set to Microcephaly and chorioretinopathy, autosomal recessive, 3, 616335 (3)
Prepair 1000+ v0.0 TTPA Zornitza Stark gene: TTPA was added
gene: TTPA was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TTPA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TTPA were set to Ataxia with isolated vitamin E deficiency, 277460 (3)
Prepair 1000+ v0.0 TTN Zornitza Stark gene: TTN was added
gene: TTN was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TTN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TTN were set to Myopathy, early-onset, with fatal cardiomyopathy, 611705 (3)
Prepair 1000+ v0.0 TTI2 Zornitza Stark gene: TTI2 was added
gene: TTI2 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TTI2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TTI2 were set to Mental retardation, autosomal recessive 39, 615541 (3)
Prepair 1000+ v0.0 TTC8 Zornitza Stark gene: TTC8 was added
gene: TTC8 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TTC8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TTC8 were set to Bardet-Biedl syndrome 8, 615985 (3)
Prepair 1000+ v0.0 TTC7A Zornitza Stark gene: TTC7A was added
gene: TTC7A was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TTC7A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TTC7A were set to Gastrointestinal defects and immunodeficiency syndrome, 243150 (3)
Prepair 1000+ v0.0 TTC37 Zornitza Stark gene: TTC37 was added
gene: TTC37 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TTC37 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TTC37 were set to Trichohepatoenteric syndrome 1, 222470 (3)
Prepair 1000+ v0.0 TTC21B Zornitza Stark gene: TTC21B was added
gene: TTC21B was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TTC21B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TTC21B were set to Short-rib thoracic dysplasia 4 with or without polydactyly, 613819 (3)
Prepair 1000+ v0.0 TTC19 Zornitza Stark gene: TTC19 was added
gene: TTC19 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TTC19 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TTC19 were set to Mitochondrial complex III deficiency, nuclear type 2, 615157 (3)
Prepair 1000+ v0.0 TSPAN7 Zornitza Stark gene: TSPAN7 was added
gene: TSPAN7 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TSPAN7 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: TSPAN7 were set to Mental retardation, X-linked 58, 300210 (3)
Prepair 1000+ v0.0 TSHB Zornitza Stark gene: TSHB was added
gene: TSHB was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TSHB was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TSHB were set to Hypothryoidism, congenital, nongoitrous 4, 275100 (3)
Prepair 1000+ v0.0 TSFM Zornitza Stark gene: TSFM was added
gene: TSFM was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TSFM was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TSFM were set to Combined oxidative phosphorylation deficiency 3, 610505 (3)
Prepair 1000+ v0.0 TSEN54 Zornitza Stark gene: TSEN54 was added
gene: TSEN54 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TSEN54 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TSEN54 were set to Pontocerebellar hypoplasia type 2A, 277470 (3)
Prepair 1000+ v0.0 TSEN2 Zornitza Stark gene: TSEN2 was added
gene: TSEN2 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TSEN2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TSEN2 were set to Pontocerebellar hypoplasia type 2B, 612389 (3)
Prepair 1000+ v0.0 TRPM6 Zornitza Stark gene: TRPM6 was added
gene: TRPM6 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TRPM6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRPM6 were set to Hypomagnesemia 1, intestinal, 602014 (3)
Prepair 1000+ v0.0 TRNT1 Zornitza Stark gene: TRNT1 was added
gene: TRNT1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TRNT1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRNT1 were set to Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay, 616084 (3)
Prepair 1000+ v0.0 TRMU Zornitza Stark gene: TRMU was added
gene: TRMU was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TRMU was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRMU were set to Liver failure, transient infantile, 613070 (3)
Prepair 1000+ v0.0 TRMT10A Zornitza Stark gene: TRMT10A was added
gene: TRMT10A was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TRMT10A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRMT10A were set to Microcephaly, short stature, and impaired glucose metabolism, 616033 (3)
Prepair 1000+ v0.0 TRIT1 Zornitza Stark gene: TRIT1 was added
gene: TRIT1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TRIT1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRIT1 were set to Combined oxidative phosphorylation deficiency 35, 617873 (3), Autosomal recessive
Prepair 1000+ v0.0 TRIP11 Zornitza Stark gene: TRIP11 was added
gene: TRIP11 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TRIP11 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRIP11 were set to Achondrogenesis, type IA, 200600 (3)
Prepair 1000+ v0.0 TRIM37 Zornitza Stark gene: TRIM37 was added
gene: TRIM37 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TRIM37 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRIM37 were set to Mulibrey nanism, 253250 (3)
Prepair 1000+ v0.0 TRIM32 Zornitza Stark gene: TRIM32 was added
gene: TRIM32 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TRIM32 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRIM32 were set to Muscular dystrophy, limb-girdle, type 2H, 254110 (3)
Prepair 1000+ v0.0 TREX1 Zornitza Stark gene: TREX1 was added
gene: TREX1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TREX1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TREX1 were set to Aicardi-Goutieres syndrome 1, dominant and recessive, 225750 (3)
Prepair 1000+ v0.0 TRDN Zornitza Stark gene: TRDN was added
gene: TRDN was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TRDN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRDN were set to Ventricular tachycardia, catecholaminergic polymorphic, 5, with or without muscle weakness, 615441 (3)
Prepair 1000+ v0.0 TRAPPC9 Zornitza Stark gene: TRAPPC9 was added
gene: TRAPPC9 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TRAPPC9 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRAPPC9 were set to Mental retardation, autosomal recessive 13, 613192 (3)
Prepair 1000+ v0.0 TRAPPC11 Zornitza Stark gene: TRAPPC11 was added
gene: TRAPPC11 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TRAPPC11 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRAPPC11 were set to Muscular dystrophy, limb-girdle, type 2S, 615356 (3)
Prepair 1000+ v0.0 TPP1 Zornitza Stark gene: TPP1 was added
gene: TPP1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TPP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TPP1 were set to Ceroid lipofuscinosis, neuronal, 2, 204500 (3)
Prepair 1000+ v0.0 TPM3 Zornitza Stark gene: TPM3 was added
gene: TPM3 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TPM3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TPM3 were set to Nemaline myopathy 1, autosomal dominant or recessive, 609284 (3)
Prepair 1000+ v0.0 TPK1 Zornitza Stark gene: TPK1 was added
gene: TPK1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TPK1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TPK1 were set to Thiamine metabolism dysfunction syndrome 5 (episodic encephalopathy type), 614458 (3)
Prepair 1000+ v0.0 TPI1 Zornitza Stark gene: TPI1 was added
gene: TPI1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TPI1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TPI1 were set to Hemolytic anemia due to triosephosphate isomerase deficiency, 615512 (3)
Prepair 1000+ v0.0 TOE1 Zornitza Stark gene: TOE1 was added
gene: TOE1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TOE1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TOE1 were set to Pontocerebellar hypoplasia, type 7, 614969 (3), Autosomal recessive
Prepair 1000+ v0.0 TNNT1 Zornitza Stark gene: TNNT1 was added
gene: TNNT1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TNNT1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TNNT1 were set to Nemaline myopathy 5, Amish type, 605355 (3)
Prepair 1000+ v0.0 TNFSF11 Zornitza Stark gene: TNFSF11 was added
gene: TNFSF11 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TNFSF11 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TNFSF11 were set to Osteopetrosis, autosomal recessive 2, 259710 (3)
Prepair 1000+ v0.0 TNFRSF13B Zornitza Stark gene: TNFRSF13B was added
gene: TNFRSF13B was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TNFRSF13B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TNFRSF13B were set to Immunodeficiency, common variable, 2, 240500 (3)
Prepair 1000+ v0.0 TNFRSF11B Zornitza Stark gene: TNFRSF11B was added
gene: TNFRSF11B was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TNFRSF11B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TNFRSF11B were set to Paget disease of bone 5, juvenile-onset, 239000 (3)
Prepair 1000+ v0.0 TNFRSF11A Zornitza Stark gene: TNFRSF11A was added
gene: TNFRSF11A was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TNFRSF11A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TNFRSF11A were set to Osteopetrosis, autosomal recessive 7, 612301 (3)
Prepair 1000+ v0.0 TMTC3 Zornitza Stark gene: TMTC3 was added
gene: TMTC3 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TMTC3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TMTC3 were set to Lissencephaly 8, 617255 (3), Autosomal recessive
Prepair 1000+ v0.0 TMEM70 Zornitza Stark gene: TMEM70 was added
gene: TMEM70 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TMEM70 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TMEM70 were set to Mitochondrial complex V (ATP synthase) deficiency, nuclear type 2, 614052 (3)
Prepair 1000+ v0.0 TMEM67 Zornitza Stark gene: TMEM67 was added
gene: TMEM67 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TMEM67 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TMEM67 were set to Joubert syndrome 6, 610688 (3)
Prepair 1000+ v0.0 TMEM5 Zornitza Stark gene: TMEM5 was added
gene: TMEM5 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TMEM5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TMEM5 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 10, 615041 (3)
Prepair 1000+ v0.0 TMEM237 Zornitza Stark gene: TMEM237 was added
gene: TMEM237 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TMEM237 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TMEM237 were set to Joubert syndrome 14, 614424 (3)
Prepair 1000+ v0.0 TMEM231 Zornitza Stark gene: TMEM231 was added
gene: TMEM231 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TMEM231 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TMEM231 were set to Joubert syndrome 20, 614970 (3)
Prepair 1000+ v0.0 TMEM216 Zornitza Stark gene: TMEM216 was added
gene: TMEM216 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TMEM216 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TMEM216 were set to Joubert syndrome 2, 608091 (3)
Prepair 1000+ v0.0 TMEM165 Zornitza Stark gene: TMEM165 was added
gene: TMEM165 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TMEM165 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TMEM165 were set to Congenital disorder of glycosylation, type IIk, 614727 (3)
Prepair 1000+ v0.0 TMEM138 Zornitza Stark gene: TMEM138 was added
gene: TMEM138 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TMEM138 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TMEM138 were set to Joubert syndrome 16, 614465 (3)
Prepair 1000+ v0.0 TMEM126A Zornitza Stark gene: TMEM126A was added
gene: TMEM126A was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TMEM126A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TMEM126A were set to Optic atrophy 7, 612989 (3)
Prepair 1000+ v0.0 TMEM107 Zornitza Stark gene: TMEM107 was added
gene: TMEM107 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TMEM107 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TMEM107 were set to Orofaciodigital syndrome XVI, 617563 (3), Autosomal recessive
Prepair 1000+ v0.0 TMCO1 Zornitza Stark gene: TMCO1 was added
gene: TMCO1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TMCO1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TMCO1 were set to Craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome, 213980 (3)
Prepair 1000+ v0.0 TK2 Zornitza Stark gene: TK2 was added
gene: TK2 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TK2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TK2 were set to Mitochondrial DNA depletion syndrome 2 (myopathic type), 609560 (3)
Prepair 1000+ v0.0 TJP2 Zornitza Stark gene: TJP2 was added
gene: TJP2 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TJP2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TJP2 were set to Cholestasis, progressive familial intrahepatic 4, 615878 (3)
Prepair 1000+ v0.0 TIMM8A Zornitza Stark gene: TIMM8A was added
gene: TIMM8A was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TIMM8A was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: TIMM8A were set to Jensen syndrome, 311150 (3)
Prepair 1000+ v0.0 THOC2 Zornitza Stark gene: THOC2 was added
gene: THOC2 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: THOC2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: THOC2 were set to Mental retardation, X-linked 12/35, 300957 (3), X-linked recessive
Prepair 1000+ v0.0 TH Zornitza Stark gene: TH was added
gene: TH was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TH was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TH were set to Segawa syndrome, recessive, 605407 (3)
Prepair 1000+ v0.0 TGM1 Zornitza Stark gene: TGM1 was added
gene: TGM1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TGM1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TGM1 were set to Ichthyosis, congenital, autosomal recessive 1, 242300 (3)
Prepair 1000+ v0.0 TF Zornitza Stark gene: TF was added
gene: TF was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TF was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TF were set to Atransferrinemia, 209300 (3)
Prepair 1000+ v0.0 TELO2 Zornitza Stark gene: TELO2 was added
gene: TELO2 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TELO2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TELO2 were set to You-Hoover-Fong syndrome, 616954 (3), Autosomal recessive
Prepair 1000+ v0.0 TDRD7 Zornitza Stark gene: TDRD7 was added
gene: TDRD7 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TDRD7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TDRD7 were set to Cataract 36, 613887 (3)
Prepair 1000+ v0.0 TCTN3 Zornitza Stark gene: TCTN3 was added
gene: TCTN3 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TCTN3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TCTN3 were set to Joubert syndrome 18, 614815 (3)
Prepair 1000+ v0.0 TCTN2 Zornitza Stark gene: TCTN2 was added
gene: TCTN2 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TCTN2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TCTN2 were set to Joubert syndrome 24
Prepair 1000+ v0.0 TCN2 Zornitza Stark gene: TCN2 was added
gene: TCN2 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TCN2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TCN2 were set to Transcobalamin II deficiency, 275350 (3)
Prepair 1000+ v0.0 TCIRG1 Zornitza Stark gene: TCIRG1 was added
gene: TCIRG1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TCIRG1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TCIRG1 were set to Osteopetrosis, autosomal recessive 1, 259700 (3)
Prepair 1000+ v0.0 TCAP Zornitza Stark gene: TCAP was added
gene: TCAP was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TCAP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TCAP were set to Muscular dystrophy, limb-girdle, type 2G, 601954 (3)
Prepair 1000+ v0.0 TBX19 Zornitza Stark gene: TBX19 was added
gene: TBX19 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TBX19 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TBX19 were set to Adrenocorticotropic hormone deficiency, 201400 (3)
Prepair 1000+ v0.0 TBCK Zornitza Stark gene: TBCK was added
gene: TBCK was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TBCK was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TBCK were set to Hypotonia, infantile, with psychomotor retardation and characteristic facies 3, 616900 (3), Autosomal recessive
Prepair 1000+ v0.0 TBCE Zornitza Stark gene: TBCE was added
gene: TBCE was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TBCE was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TBCE were set to Kenny-Caffey syndrome-1, 244460 (3)
Prepair 1000+ v0.0 TBCD Zornitza Stark gene: TBCD was added
gene: TBCD was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TBCD was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TBCD were set to Encephalopathy, progressive, early-onset, with brain atrophy and thin corpus callosum, 617193 (3), Autosomal recessive
Prepair 1000+ v0.0 TBC1D24 Zornitza Stark gene: TBC1D24 was added
gene: TBC1D24 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TBC1D24 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TBC1D24 were set to Epileptic encephalopathy, early infantile, 16, 615338 (3)
Prepair 1000+ v0.0 TBC1D23 Zornitza Stark gene: TBC1D23 was added
gene: TBC1D23 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TBC1D23 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TBC1D23 were set to Pontocerebellar hypoplasia, type 11, 617695 (3), Autosomal recessive
Prepair 1000+ v0.0 TAZ Zornitza Stark gene: TAZ was added
gene: TAZ was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TAZ was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: TAZ were set to Barth syndrome, 302060 (3)
Prepair 1000+ v0.0 TAP1 Zornitza Stark gene: TAP1 was added
gene: TAP1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TAP1 were set to Bare lymphocyte syndrome, type I, 604571 (3)
Prepair 1000+ v0.0 TANGO2 Zornitza Stark gene: TANGO2 was added
gene: TANGO2 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TANGO2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TANGO2 were set to Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration
Prepair 1000+ v0.0 TALDO1 Zornitza Stark gene: TALDO1 was added
gene: TALDO1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: TALDO1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TALDO1 were set to Transaldolase deficiency, 606003 (3)
Prepair 1000+ v0.0 SYP Zornitza Stark gene: SYP was added
gene: SYP was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SYP was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: SYP were set to Mental retardation, X-linked 96, 300802 (3)
Prepair 1000+ v0.0 SYN1 Zornitza Stark gene: SYN1 was added
gene: SYN1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SYN1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: SYN1 were set to Epilepsy, X-linked, with variable learning disabilities and behavior disorders, 300491 (3)
Prepair 1000+ v0.0 SURF1 Zornitza Stark gene: SURF1 was added
gene: SURF1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SURF1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SURF1 were set to Leigh syndrome, due to COX deficiency, 256000 (3)
Prepair 1000+ v0.0 SUOX Zornitza Stark gene: SUOX was added
gene: SUOX was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SUOX was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SUOX were set to Sulfite oxidase deficiency, 272300 (3)
Prepair 1000+ v0.0 SUMF1 Zornitza Stark gene: SUMF1 was added
gene: SUMF1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SUMF1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SUMF1 were set to Multiple sulfatase deficiency, 272200 (3)
Prepair 1000+ v0.0 SUCLG1 Zornitza Stark gene: SUCLG1 was added
gene: SUCLG1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SUCLG1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SUCLG1 were set to Mitochondrial DNA depletion syndrome 9 (encephalomyopathic type with methylmalonic aciduria), 245400 (3)
Prepair 1000+ v0.0 SUCLA2 Zornitza Stark gene: SUCLA2 was added
gene: SUCLA2 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SUCLA2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SUCLA2 were set to Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), 612073 (3)
Prepair 1000+ v0.0 STXBP2 Zornitza Stark gene: STXBP2 was added
gene: STXBP2 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: STXBP2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: STXBP2 were set to Hemophagocytic lymphohistiocytosis, familial, 5, 613101 (3)
Prepair 1000+ v0.0 STX11 Zornitza Stark gene: STX11 was added
gene: STX11 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: STX11 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: STX11 were set to Hemophagocytic lymphohistiocytosis, familial, 4, 603552 (3)
Prepair 1000+ v0.0 STUB1 Zornitza Stark gene: STUB1 was added
gene: STUB1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: STUB1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: STUB1 were set to Spinocerebellar ataxia, autosomal recessive 16, 615768 (3)
Prepair 1000+ v0.0 STRADA Zornitza Stark gene: STRADA was added
gene: STRADA was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: STRADA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: STRADA were set to Polyhydramnios, megalencephaly, and symptomatic epilepsy, 611087 (3), Autosomal recessive
Prepair 1000+ v0.0 STRA6 Zornitza Stark gene: STRA6 was added
gene: STRA6 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: STRA6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: STRA6 were set to Microphthalmia, isolated, with coloboma 8, 601186 (3)
Prepair 1000+ v0.0 STIM1 Zornitza Stark gene: STIM1 was added
gene: STIM1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: STIM1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: STIM1 were set to Immunodeficiency 10, 612783 (3)
Prepair 1000+ v0.0 STIL Zornitza Stark gene: STIL was added
gene: STIL was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: STIL was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: STIL were set to Microcephaly 7, primary, autosomal recessive, 612703 (3)
Prepair 1000+ v0.0 STAT1 Zornitza Stark gene: STAT1 was added
gene: STAT1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: STAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: STAT1 were set to Immunodeficiency 31B, mycobacterial and viral infections, autosomal recessive, 613796 (3)
Prepair 1000+ v0.0 STAR Zornitza Stark gene: STAR was added
gene: STAR was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: STAR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: STAR were set to Lipoid adrenal hyperplasia, 201710 (3)
Prepair 1000+ v0.0 STAMBP Zornitza Stark gene: STAMBP was added
gene: STAMBP was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: STAMBP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: STAMBP were set to Microcephaly-capillary malformation syndrome, 614261 (3)
Prepair 1000+ v0.0 ST3GAL5 Zornitza Stark gene: ST3GAL5 was added
gene: ST3GAL5 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: ST3GAL5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ST3GAL5 were set to Salt and pepper developmental regression syndrome, 609056 (3), Autosomal recessive
Prepair 1000+ v0.0 SSR4 Zornitza Stark gene: SSR4 was added
gene: SSR4 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SSR4 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: SSR4 were set to Congenital disorder of glycosylation, type Iy, 300934 (3), X-linked recessive
Prepair 1000+ v0.0 SRD5A3 Zornitza Stark gene: SRD5A3 was added
gene: SRD5A3 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SRD5A3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SRD5A3 were set to Congenital disorder of glycosylation, type Iq, 612379 (3)
Prepair 1000+ v0.0 SQSTM1 Zornitza Stark gene: SQSTM1 was added
gene: SQSTM1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SQSTM1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SQSTM1 were set to Neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset, 617145 (3), Autosomal recessive
Prepair 1000+ v0.0 SPR Zornitza Stark gene: SPR was added
gene: SPR was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SPR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SPR were set to Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, 612716 (3)
Prepair 1000+ v0.0 SPINT2 Zornitza Stark gene: SPINT2 was added
gene: SPINT2 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SPINT2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SPINT2 were set to Diarrhea 3, secretory sodium, congenital, syndromic, 270420 (3)
Prepair 1000+ v0.0 SPINK5 Zornitza Stark gene: SPINK5 was added
gene: SPINK5 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SPINK5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SPINK5 were set to Netherton syndrome, 256500 (3)
Prepair 1000+ v0.0 SPG11 Zornitza Stark gene: SPG11 was added
gene: SPG11 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SPG11 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SPG11 were set to Spastic paraplegia 11, autosomal recessive, 604360 (3)
Prepair 1000+ v0.0 SPEG Zornitza Stark gene: SPEG was added
gene: SPEG was added to Reproductive Carrier Screen_VCGS. Sources: Expert Review,Expert Review Green
Mode of inheritance for gene: SPEG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPEG were set to 29614691; 30157964; 25087613; 29474540; 31625632; 28624463; 26578207; 30412272
Phenotypes for gene: SPEG were set to Centronuclear myopathy 5, MIM# 615959
Prepair 1000+ v0.0 SPATA7 Zornitza Stark gene: SPATA7 was added
gene: SPATA7 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SPATA7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SPATA7 were set to Leber congenital amaurosis 3, 604232 (3)
Prepair 1000+ v0.0 SPATA5 Zornitza Stark gene: SPATA5 was added
gene: SPATA5 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SPATA5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SPATA5 were set to Epilepsy, hearing loss, and mental retardation syndrome, 616577 (3), Autosomal recessive
Prepair 1000+ v0.0 SPART Zornitza Stark gene: SPART was added
gene: SPART was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SPART was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SPART were set to Troyer syndrome, 275900 (3)
Prepair 1000+ v0.0 SPAG1 Zornitza Stark gene: SPAG1 was added
gene: SPAG1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SPAG1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SPAG1 were set to Ciliary dyskinesia, primary, 28, 615505 (3)
Prepair 1000+ v0.0 SP110 Zornitza Stark gene: SP110 was added
gene: SP110 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SP110 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SP110 were set to Hepatic venoocclusive disease with immunodeficiency, 235550 (3)
Prepair 1000+ v0.0 SOST Zornitza Stark gene: SOST was added
gene: SOST was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SOST was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SOST were set to Sclerosteosis 1, 269500 (3)
Prepair 1000+ v0.0 SNX14 Zornitza Stark gene: SNX14 was added
gene: SNX14 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SNX14 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SNX14 were set to Spinocerebellar ataxia, autosomal recessive 20, 616354 (3)
Prepair 1000+ v0.0 SNORD118 Zornitza Stark gene: SNORD118 was added
gene: SNORD118 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SNORD118 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SNORD118 were set to Leukoencephalopathy, brain calcifications, and cysts, 614561 (3), Autosomal recessive
Prepair 1000+ v0.0 SNAP29 Zornitza Stark gene: SNAP29 was added
gene: SNAP29 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SNAP29 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SNAP29 were set to Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome, 609528 (3)
Prepair 1000+ v0.0 SMS Zornitza Stark gene: SMS was added
gene: SMS was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SMS was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: SMS were set to Mental retardation, X-linked, Snyder-Robinson type, 309583 (3)
Prepair 1000+ v0.0 SMPD1 Zornitza Stark gene: SMPD1 was added
gene: SMPD1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SMPD1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SMPD1 were set to Niemann-Pick disease, type A, 257200 (3)
Prepair 1000+ v0.0 SMN1 Zornitza Stark gene: SMN1 was added
gene: SMN1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SMN1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SMN1 were set to Spinal muscular atrophy-1, 253300 (3)
Prepair 1000+ v0.0 SMARCAL1 Zornitza Stark gene: SMARCAL1 was added
gene: SMARCAL1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SMARCAL1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SMARCAL1 were set to Schimke immunoosseous dysplasia, 242900 (3)
Prepair 1000+ v0.0 SLC9A6 Zornitza Stark gene: SLC9A6 was added
gene: SLC9A6 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green
Mode of inheritance for gene: SLC9A6 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: SLC9A6 were set to Mental retardation, X-linked syndromic, Christianson type