PanelApp (staging)

Activity

Filter

Cancel
Date Panel Item Activity
969 actions
Mendeliome v1.2226 CC2D1A Zornitza Stark Phenotypes for gene: CC2D1A were changed from Autosomal recessive mental retardation, (MIM#608443) to Intellectual developmental disorder, autosomal recessive 3, MIM# 608443
Mendeliome v1.2225 CC2D1A Zornitza Stark edited their review of gene: CC2D1A: Changed phenotypes: Intellectual developmental disorder, autosomal recessive 3, MIM# 608443
Mendeliome v1.2197 RUNX1T1 Chirag Patel gene: RUNX1T1 was added
gene: RUNX1T1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RUNX1T1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RUNX1T1 were set to PMID: 39568205, 19172993, 22644616, 31223340
Phenotypes for gene: RUNX1T1 were set to Neurodevelopmental disorder MONDO:0700092
Review for gene: RUNX1T1 was set to GREEN
Added comment: RUNX1T1 encodes a transcription regulator for hematopoietic genes and is well-known for its involvement in hematologic malignancies. Germline RUNX1T1 variants may also play a role in human congenital neurodevelopmental disorders.

PMID: 39568205
3 unrelated individuals with developmental delay, learning disability, ASD, ADHD, and dysmorphism (1 x heart defects). Trio WES identified de novo variants in RUNX1T1 gene (1 x nonsense variant in 5' region [p.Gln36Ter], 2 x missense variants in C-terminus [p.Gly412Arg and p.His521Tyr]).

PMID: 19172993
1 individual with mild-moderate ID and congenital heart disease, and chromosome t(5;8)(q32;q21.3) translocation. Molecular characterization revealed that one of the break points was within the RUNX1T1 gene. Analysis of RUNX1T1 expression in human embryonic and fetal tissues suggests a role of RUNX1T1 in brain and heart development.

PMID: 22644616
1 individual with mild ID and dysmorphism, and de novo deletion exons 3-7 in RUNX1T1.

PMID: 31223340
1 individual with ID, anaemia, atrial septal defect, dysmorphism, and seizures. Found to have a 2.1 Mb deletion at 8q21.3q22.1 involving entire RUNX1T1 gene (and 2 adjacent genes - SLC26A7 and TRIQK), and a benign familial 4.3 Mb duplication at 1p22.1p21.3 (present in unaffected healthy brother).
Sources: Literature
Mendeliome v1.2184 HMGCS1 Zornitza Stark gene: HMGCS1 was added
gene: HMGCS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HMGCS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HMGCS1 were set to 39531736
Phenotypes for gene: HMGCS1 were set to Rigid spine syndrome, MONDO:0019951, HMGCS1-related
Review for gene: HMGCS1 was set to GREEN
Added comment: Five individuals from four families reported. All individuals presented with spinal rigidity primarily affecting the cervical and dorsolumbar regions, scoliosis, and respiratory insufficiency. Creatine kinase levels were variably elevated. The clinical course worsened with intercurrent disease or certain drugs in some; one individual died from respiratory failure following infection. Muscle biopsies revealed irregularities in oxidative enzyme staining with occasional internal nuclei and rimmed vacuoles.
HMGCS1 encodes a critical enzyme of the mevalonate pathway. Notably, biallelic hypomorphic variants in downstream enzymes including HMGCR and GGPS1 are associated with muscular dystrophy. Hmgcs1 mutant zebrafish displayed severe early defects, including immobility at 2 days and death by day 3 post-fertilisation and were rescued by HMGCS1 mRNA. Four variants tested (S447P, Q29L M70T, and C268S) have reduced function compared to wildtype HMGCS1 in zebrafish rescue assays
Sources: Literature
Mendeliome v1.2147 NFATC2 Bryony Thompson Classified gene: NFATC2 as Amber List (moderate evidence)
Mendeliome v1.2147 NFATC2 Bryony Thompson Gene: nfatc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2146 NFATC2 Bryony Thompson reviewed gene: NFATC2: Rating: AMBER; Mode of pathogenicity: None; Publications: 35789258, 38427060; Phenotypes: Lymphoproliferative syndrome, MONDO:0016537, NFATC2-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2090 NT5C2 Sangavi Sivagnanasundram reviewed gene: NT5C2: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008372; Phenotypes: complex hereditary spastic paraplegia MONDO:0015150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2090 SLC24A1 Sangavi Sivagnanasundram reviewed gene: SLC24A1: Rating: GREEN; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:008419; Phenotypes: inherited retinal dystrophy MONDO:0019118; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2067 WFDC2 Zornitza Stark Phenotypes for gene: WFDC2 were changed from bronchiectasis, MONDO:0004822, WFDC2-related to Bronchiectasis and nasal polyposis, MIM# 620984
Mendeliome v1.2066 WFDC2 Zornitza Stark edited their review of gene: WFDC2: Changed phenotypes: Bronchiectasis and nasal polyposis, MIM# 620984
Mendeliome v1.2063 WFDC2 Zornitza Stark Marked gene: WFDC2 as ready
Mendeliome v1.2063 WFDC2 Zornitza Stark Gene: wfdc2 has been classified as Green List (High Evidence).
Mendeliome v1.2063 WFDC2 Zornitza Stark Classified gene: WFDC2 as Green List (high evidence)
Mendeliome v1.2063 WFDC2 Zornitza Stark Gene: wfdc2 has been classified as Green List (High Evidence).
Mendeliome v1.2062 WFDC2 Zornitza Stark gene: WFDC2 was added
gene: WFDC2 was added to Mendeliome. Sources: Literature
founder tags were added to gene: WFDC2.
Mode of inheritance for gene: WFDC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WFDC2 were set to 38626355
Phenotypes for gene: WFDC2 were set to bronchiectasis, MONDO:0004822, WFDC2-related
Review for gene: WFDC2 was set to GREEN
Added comment: 11 individuals from 10 families reported with bi-allelic variants in this gene and bronchiectasis and nasal polyps. p.Cys49Arg is recurrent and may be a founder variant.
Sources: Literature
Mendeliome v1.1992 RFC4 Chirag Patel gene: RFC4 was added
gene: RFC4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RFC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RFC4 were set to PMID: 39106866
Phenotypes for gene: RFC4 were set to RFC4-related multisystem disorder
Review for gene: RFC4 was set to GREEN
gene: RFC4 was marked as current diagnostic
Added comment: 9 affected individuals (aged birth to 47yrs) from 8 unrelated families with a multisystem disorder. Clinical features included: muscle weakness/myopathy (9/9), motor incoordination/gait disturbance (8/8), delayed gross motor development (6/9), dysarthria (5/5), peripheral neuropathy (3/3 adults), bilateral sensorineural hearing impairment (6/9), decreased body weight (8/9), short stature (5/9), microcephaly (4/9), respiratory issues/insufficiency (6/9), cerebellar atrophy (4/9), pituitary hypoplasia (3/9).

WES or WGS identified biallelic loss-of-function variants in RFC4 (3 frameshift, 2 splice site, 1 single AA duplication, 2 single AA deletions, 2 missense), and almost all are likely to disrupt the C-terminal domain indispensable for Replication factor C (RFC) complex formation. All variants segregated with the disease.

The RFC complex (with 5 subunits) is central to process of regulation of DNA replication, and it loads proliferating cell nuclear antigen onto DNA to facilitate the recruitment of replication and repair proteins and enhance DNA polymerase processivity. RFC1 is associated with CANVAS but the contributions of RFC2-5 subunits on human Mendelian disorders is unknown.

Analysis of a previously determined cryo-EM structure of RFC bound to proliferating cell nuclear antigen suggested that the variants disrupt interactions within RFC4 and/or destabilize the RFC complex. Cellular studies using RFC4-deficient HeLa cells and primary fibroblasts demonstrated decreased RFC4 protein, compromised stability of the other RFC complex subunits, and perturbed RFC complex formation. Additionally, functional studies of the RFC4 variants affirmed diminished RFC complex formation, and cell cycle studies suggested perturbation of DNA replication and cell cycle progression.
Sources: Literature
Mendeliome v1.1921 NFATC2 Zornitza Stark Phenotypes for gene: NFATC2 were changed from Skeletal system disorder MONDO:0005172 to Skeletal system disorder MONDO:0005172; Lymphoproliferative syndrome, MONDO:0016537, NFATC2-related
Mendeliome v1.1920 NFATC2 Zornitza Stark Publications for gene: NFATC2 were set to 35789258
Mendeliome v1.1919 NFATC2 Zornitza Stark reviewed gene: NFATC2: Rating: RED; Mode of pathogenicity: None; Publications: 38427060; Phenotypes: Lymphoproliferative syndrome, MONDO:0016537, NFATC2-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1806 LRRC23 Zornitza Stark Phenotypes for gene: LRRC23 were changed from Non-syndromic male infertility due to sperm motility disorder, (MONDO:0017173), LRRC23-related to Spermatogenic failure 92, MIM# 620848
Mendeliome v1.1805 LRRC23 Zornitza Stark Publications for gene: LRRC23 were set to 37804054
Mendeliome v1.1804 LRRC23 Zornitza Stark Classified gene: LRRC23 as Amber List (moderate evidence)
Mendeliome v1.1804 LRRC23 Zornitza Stark Gene: lrrc23 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1803 LRRC23 Zornitza Stark reviewed gene: LRRC23: Rating: AMBER; Mode of pathogenicity: None; Publications: 38091523; Phenotypes: Spermatogenic failure 92, MIM# 620848; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1782 CLIC2 Zornitza Stark edited their review of gene: CLIC2: Added comment: DISPUTED by ClinGen.; Changed phenotypes: Intellectual disability, X-linked, syndromic 32, 300886
Mendeliome v1.1774 TTC25 Zornitza Stark Tag new gene name tag was added to gene: TTC25.
Mendeliome v1.1773 C2orf71 Zornitza Stark Tag new gene name tag was added to gene: C2orf71.
Mendeliome v1.1770 C2orf71 Sangavi Sivagnanasundram reviewed gene: C2orf71: Rating: ; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005738; Phenotypes: PCARE-related retinopathy MONDO:0800404; Mode of inheritance: None
Mendeliome v1.1770 TTC25 Sangavi Sivagnanasundram reviewed gene: TTC25: Rating: ; Mode of pathogenicity: None; Publications: https://search.clinicalgenome.org/CCID:005700; Phenotypes: primary ciliary dyskinesia 35 MONDO:0014910; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1742 PQLC2 Zornitza Stark Marked gene: PQLC2 as ready
Mendeliome v1.1742 PQLC2 Zornitza Stark Gene: pqlc2 has been classified as Green List (High Evidence).
Mendeliome v1.1742 PQLC2 Zornitza Stark Phenotypes for gene: PQLC2 were changed from Retinitis pigmentosa, MONDO:0019200 to Retinitis pigmentosa, MONDO:0019200, PQLC2-related
Mendeliome v1.1741 PQLC2 Zornitza Stark Publications for gene: PQLC2 were set to PMID: 35486108; and online publication GiM Feb 2024
Mendeliome v1.1740 PQLC2 Zornitza Stark Tag new gene name tag was added to gene: PQLC2.
Mendeliome v1.1735 PQLC2 Chirag Patel Classified gene: PQLC2 as Green List (high evidence)
Mendeliome v1.1735 PQLC2 Chirag Patel Gene: pqlc2 has been classified as Green List (High Evidence).
Mendeliome v1.1734 PQLC2 Chirag Patel gene: PQLC2 was added
gene: PQLC2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PQLC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PQLC2 were set to PMID: 35486108; and online publication GiM Feb 2024
Phenotypes for gene: PQLC2 were set to Retinitis pigmentosa, MONDO:0019200
Review for gene: PQLC2 was set to GREEN
gene: PQLC2 was marked as current diagnostic
Added comment: HGNC Gene Symbol: SLC66A1
Total 8 individuals from 6 families.

Millo et al. (2022)(PMID: 35486108) -
WES (with targeted analysis of SLC genes) in 913 cases from 785 families with inherited retinal dystrophy. They identified 2 different homozygous variants in SLC66A1 in 3 individuals from 2 families with adult-onset retinal dystrophy. No functional data.


Olinger et al. (2024)(https://www.sciencedirect.com/science/article/pii/S2949774424009804) -
CNV analysis of trio and non-trio WGS data from Genomics England 100K genomes project. They identified homozygous 21kb deletion spanning nearly entire SLC66A1 gene in 2 siblings with adult-onset rod-cone dystrophy (parents HTZ carriers). Review of cohort data then identified homozygous LOF variants (1 nonsense, 2 frameshift) in another 3 individuals with rod-cone dystrophy.
Sources: Literature
Mendeliome v1.1697 IQSEC2 Ain Roesley Phenotypes for gene: IQSEC2 were changed from Mental retardation, X-linked 1/78, MIM# 309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347 to Intellectual developmental disorder, X-linked 1 MIM#309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347
Mendeliome v1.1550 TMTC2 Zornitza Stark Phenotypes for gene: TMTC2 were changed from Deafness to Deafness, autosomal recessive 122, MIM# 620714
Mendeliome v1.1549 TMTC2 Zornitza Stark Publications for gene: TMTC2 were set to 29671961; 27311106
Mendeliome v1.1548 TMTC2 Zornitza Stark Mode of inheritance for gene: TMTC2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1547 TMTC2 Zornitza Stark edited their review of gene: TMTC2: Added comment: Single family reported with bi-allelic variants.

Mouse model.; Changed publications: 29671961, 27311106, 37943620, 30188326; Changed phenotypes: Deafness, autosomal recessive 122, MIM# 620714; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1513 SP9 Suliman Khan commented on gene: SP9: PMID: 38288683: reported 5 unrelated patients with de novo heterozygous variants (missense and PTV) in SP9 gene. In silico and in vitro studies suggested a novel form of interneuronopathy with variable severity depending on the presence of loss or gain of function variants. Patients with loss-of-function variants had ID, ASD, and epilepsy, whereas missense variants in the second C2H2 binding domain result in hypomorphic and neomorphic DNA binding functions that cause severe epileptic encephalopathy. The author suggested a novel form of interneuronopathy with variable severity depending on the presence of loss or gain of function variants.
Mendeliome v1.1338 LRRC23 Elena Savva Phenotypes for gene: LRRC23 were changed from Non-syndromic male infertility due to sperm motility disorder, (MONDO:0017173), LRRC23-related to Non-syndromic male infertility due to sperm motility disorder, (MONDO:0017173), LRRC23-related
Mendeliome v1.1337 LRRC23 Elena Savva Marked gene: LRRC23 as ready
Mendeliome v1.1337 LRRC23 Elena Savva Gene: lrrc23 has been classified as Red List (Low Evidence).
Mendeliome v1.1337 LRRC23 Elena Savva Phenotypes for gene: LRRC23 were changed from Non-syndromic male infertility due to sperm motility disorder MONDO:0017173 to Non-syndromic male infertility due to sperm motility disorder, (MONDO:0017173), LRRC23-related
Mendeliome v1.1336 LRRC23 Elena Savva Classified gene: LRRC23 as Red List (low evidence)
Mendeliome v1.1336 LRRC23 Elena Savva Gene: lrrc23 has been classified as Red List (Low Evidence).
Mendeliome v1.1330 LRRC23 Belinda Chong gene: LRRC23 was added
gene: LRRC23 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LRRC23 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRRC23 were set to 37804054
Phenotypes for gene: LRRC23 were set to Non-syndromic male infertility due to sperm motility disorder MONDO:0017173
Review for gene: LRRC23 was set to RED
Added comment: PMID 37804054: A homozygous nonsense mutation in LRRC23 (c.376C>T: p. Arg126X) in an infertile AZS patient whose parents were consanguineous. We verified the adversity of this novel mutation because of its ability to disrupt LRRC23 synthesis and impair RSs integrity. Furthermore, we demonstrated an interaction between LRRC23 and RSPH3 in vitro, indicating that LCCR23 is associated with RS in humans. Meanwhile, the LRRC23-mutant patient had a good prognosis following intracytoplasmic sperm injection.
Sources: Literature
Mendeliome v1.1261 CDC23 Zornitza Stark Marked gene: CDC23 as ready
Mendeliome v1.1261 CDC23 Zornitza Stark Gene: cdc23 has been classified as Green List (High Evidence).
Mendeliome v1.1260 CDC23 Zornitza Stark Classified gene: CDC23 as Green List (high evidence)
Mendeliome v1.1260 CDC23 Zornitza Stark Gene: cdc23 has been classified as Green List (High Evidence).
Mendeliome v1.1251 CDC23 Michelle Torres gene: CDC23 was added
gene: CDC23 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CDC23 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDC23 were set to 37768355
Phenotypes for gene: CDC23 were set to inherited oocyte maturation defect MONDO#0014769, CDC23-related
Review for gene: CDC23 was set to GREEN
Added comment: Two missense variants, p.(Y329C) and p.(R330C), detected in three unrelated homozygous infertile females characterised by oocyte maturation defects.

In vitro studies using HeLa cells showed either decreased protein levels (Y329C) or impaired localisation (R330C). In vivo studies in mice homozygous for Y329C reproduced patient’s phenotype.
Sources: Literature
Mendeliome v1.1247 ZBTB47 Elena Savva gene: ZBTB47 was added
gene: ZBTB47 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZBTB47 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ZBTB47 were set to 37743782
Phenotypes for gene: ZBTB47 were set to Neurodevelopmental disorder (MONDO#0700092), ZBTB47-related
Review for gene: ZBTB47 was set to GREEN
Added comment: PMID 37743782:
- 5 patients with de novo missense, 4/5 have a recurring p.Gly477Lys. Probands have intellectual disability (5/5), seizures (5/5), hypotonia (5/5), gait abnormalities, and variable movement abnormalities (5/5).
- Missense variants are positioned close to His and Cys residues involved in forming C2H2 zinc fingers.
- No functional studies performed
- Minimal PTCs in gnomAD
Sources: Literature
Mendeliome v1.1156 APOO Zornitza Stark edited their review of gene: APOO: Added comment: PMID: 37649161
1 family, 2 individuals (male & female) with same NMD variant c.532G>T (p.E178*), maternally inherited (mother unaffected).

Both died before 18 months of age with partial agenesis of the corpus callosum, bilateral congenital cataract, hypothyroidism, and severe immune deficiencies.
Other phenotypes included partial syndactyly of the 2nd and 3rd toes, wrinkled palm, and sole skin.

Functional studies included site directed mutagenesis. This mutation resulted in a highly unstable and degradation
prone MIC26 protein, yet the remaining minute amounts of mutant MIC26 correctly localized to mitochondria and
interacted physically with other MICOS subunits. MIC26 KO cells expressing MIC26 harboring the respective APOO/MIC26 mutation showed mitochondria with perturbed cristae architecture and fragmented morphology resembling MIC26 KO cells.; Changed publications: 37649161; Changed phenotypes: Mitochondrial disease, MONDO:0044970, APOO-related, Developmental delay, Lactic acidosis, Muscle weakness, Hypotonia, Repetitive infections, Cognitive impairment, Autistic behaviour
Mendeliome v1.1071 MAMDC2 Elena Savva Marked gene: MAMDC2 as ready
Mendeliome v1.1071 MAMDC2 Elena Savva Gene: mamdc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1071 MAMDC2 Elena Savva Classified gene: MAMDC2 as Amber List (moderate evidence)
Mendeliome v1.1071 MAMDC2 Elena Savva Gene: mamdc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1068 MAMDC2 Belinda Chong gene: MAMDC2 was added
gene: MAMDC2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MAMDC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAMDC2 were set to 37503746
Phenotypes for gene: MAMDC2 were set to Muscular Dystrophy MONDO:0020121, MAMDC2-related
Review for gene: MAMDC2 was set to AMBER
Added comment: 17 individuals with an autosomal dominant muscular dystrophy belonging to two unrelated families in which different heterozygous truncating variants in the last exon of MAMDC2 co-segregate correctly with the disease.
Sources: Literature
Mendeliome v1.1032 SLC20A1 Zornitza Stark Phenotypes for gene: SLC20A1 were changed from Bladder-Exstrophy-Epispadias Complex (BEEC) to Bladder-Exstrophy-Epispadias Complex (BEEC), MONDO:0017919, SLC20A1-related
Mendeliome v1.1026 POPDC2 Zornitza Stark Marked gene: POPDC2 as ready
Mendeliome v1.1026 POPDC2 Zornitza Stark Gene: popdc2 has been classified as Green List (High Evidence).
Mendeliome v1.1026 POPDC2 Zornitza Stark Phenotypes for gene: POPDC2 were changed from Sinus node dysfunction to Sinoatrial node disorder, MONDO:0000469, POPDC2-related
Mendeliome v1.989 NAA60 Chirag Patel gene: NAA60 was added
gene: NAA60 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: NAA60 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NAA60 were set to Basal ganglia calcification
Review for gene: NAA60 was set to GREEN
gene: NAA60 was marked as current diagnostic
Added comment: ESHG 2023:
10 individuals from 7 families with biallelic variants in NAA60 (missense and framshift).
All with primary brain calcification - 4/10 childhood onset (DD, ID), 6/10 adult onset (cerebellar and pyramidal dysfunction, dystonia, parkinsonism, cognitive impairment, psychiatric manifestations).

NAA60 catalyses N-terminal acetylation of transmembrane proteins and localises to Golgi apparatus. In vitro assay of variants showed reduced capacity of Nt acetylation. Fibroblast studies showed significantly reduced levels of phosphate importer (SLC20A2). Loss of function variants in SLC20A2 (~50% of PFBC cases) lead to increased extracellular phosphate (which is thought to lead to calcium deposits in brain).
Sources: Other
Mendeliome v1.988 POPDC2 Chirag Patel Classified gene: POPDC2 as Green List (high evidence)
Mendeliome v1.988 POPDC2 Chirag Patel Gene: popdc2 has been classified as Green List (High Evidence).
Mendeliome v1.987 POPDC2 Chirag Patel gene: POPDC2 was added
gene: POPDC2 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: POPDC2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: POPDC2 were set to Sinus node dysfunction
Review for gene: POPDC2 was set to GREEN
gene: POPDC2 was marked as current diagnostic
Added comment: ESHG 2023:
3 families with 7 affected with sinus node dysfunction (bradycardia) and AV block (2/7 HCM).

3 x HMZ variants found in POPDC2 (2 x missense, 1 x indel). Variants predicted to diminish cAMP binding of POPDC2, and shown to disrupt regulation of TREK1 channels (lowering of outward K+ current).

POPDC2 is highly expressed in cardiac myocytes, sinoatrial node, and atrioventricular node. Knockdown in zebrafish leads to AV block, and knockout in mice leads to sinus node dysfunction. Sources: Other
Sources: Other
Mendeliome v1.895 SLC26A1 Ain Roesley reviewed gene: SLC26A1: Rating: RED; Mode of pathogenicity: None; Publications: 36719378; Phenotypes: perichondritis, hyposulphatemia, renal sulphate wasting; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.759 SLC25A36 Bryony Thompson Marked gene: SLC25A36 as ready
Mendeliome v1.759 SLC25A36 Bryony Thompson Gene: slc25a36 has been classified as Green List (High Evidence).
Mendeliome v1.759 SLC25A36 Bryony Thompson Classified gene: SLC25A36 as Green List (high evidence)
Mendeliome v1.759 SLC25A36 Bryony Thompson Gene: slc25a36 has been classified as Green List (High Evidence).
Mendeliome v1.752 SLC26A7 Zornitza Stark Marked gene: SLC26A7 as ready
Mendeliome v1.752 SLC26A7 Zornitza Stark Gene: slc26a7 has been classified as Green List (High Evidence).
Mendeliome v1.752 SLC26A7 Zornitza Stark Classified gene: SLC26A7 as Green List (high evidence)
Mendeliome v1.752 SLC26A7 Zornitza Stark Gene: slc26a7 has been classified as Green List (High Evidence).
Mendeliome v1.751 SLC26A7 Zornitza Stark gene: SLC26A7 was added
gene: SLC26A7 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SLC26A7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC26A7 were set to 34780050; 32486989; 31372509; 30333321
Phenotypes for gene: SLC26A7 were set to Congenital hypothyroidism, MONDO:0018612, SLC26A7-related
Review for gene: SLC26A7 was set to GREEN
Added comment: More than 10 unrelated families reported.
Sources: Expert list
Mendeliome v1.697 SLC25A36 Krithika Murali gene: SLC25A36 was added
gene: SLC25A36 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC25A36 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A36 were set to 34971397; 34576089; 31036718
Phenotypes for gene: SLC25A36 were set to Hyperinsulinemic hypoglycemia, familial, 8 - MIM#620211
Review for gene: SLC25A36 was set to GREEN
Added comment: Solute carrier family 25 members 33 (SLC25A33) and 36 (SLC25A36) are the only known mitochondrial pyrimidine nucleotide carriers in humans

PMID: 34971397 Sharoor et al 2022 report 2 siblings with hyperinsulinism, hypoglycemia and hyperammonemia from early infancy with homozygous SLC25A36 c.284 + 3 A > T variant identified through WES. Functional studies support LoF.

PMID: 34576089 report a 12-year-old patient with hypothyroidism, hyperinsulinism, hyperammonemia, chronical obstipation, short stature, along with language and general developmental delay. WES identified SLC25A36 gene homozygous c.803dupT, p.Ser269llefs*35 variant. Functional analysis of mutant SLC25A36 protein in proteoliposomes showed a virtually abolished transport activity. Immunoblotting results suggest that the mutant SLC25A36 protein in the patient undergoes fast degradation. Supplementation with uridine lead to some improvement in clinical course.

PMID: 31036718 deficiencies in SLC25A36 in mouse embryonic stem cells have been associated with mtDNA depletion as well as mitochondrial dysfunction
Sources: Literature
Mendeliome v1.606 SLC26A6 Zornitza Stark Marked gene: SLC26A6 as ready
Mendeliome v1.606 SLC26A6 Zornitza Stark Gene: slc26a6 has been classified as Red List (Low Evidence).
Mendeliome v1.606 SLC26A6 Zornitza Stark Phenotypes for gene: SLC26A6 were changed from Enteric hyperoxaluria and nephrolithiasis to Primary hyperoxaluria, MONDO:0002474, SLC26A6-related
Mendeliome v1.605 SLC26A6 Zornitza Stark Classified gene: SLC26A6 as Red List (low evidence)
Mendeliome v1.605 SLC26A6 Zornitza Stark Gene: slc26a6 has been classified as Red List (Low Evidence).
Mendeliome v1.604 SLC26A6 Zornitza Stark reviewed gene: SLC26A6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Primary hyperoxaluria, MONDO:0002474, SLC26A6-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.569 TNNC2 Zornitza Stark Phenotypes for gene: TNNC2 were changed from Congenital myopathy, MONDO:0019952, TNNC2-related to Myopathy, congenital, with neonatal respiratory insufficiency, MIM# 620161
Mendeliome v1.568 TNNC2 Zornitza Stark edited their review of gene: TNNC2: Changed phenotypes: Myopathy, congenital, with neonatal respiratory insufficiency, MIM# 620161
Mendeliome v1.563 SLC26A6 Arina Puzriakova gene: SLC26A6 was added
gene: SLC26A6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC26A6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SLC26A6 were set to 35115415; 21170874; 32660969
Phenotypes for gene: SLC26A6 were set to Enteric hyperoxaluria and nephrolithiasis
Added comment: Cornière et al. 2022 (PMID: 35115415) identified a single family with a heterozygous missense VUS (c.1519C>T/p.R507W) in the SLC26A6 gene. However, the variant was found in 5 out of 280 674 alleles reported in gnomAD (Europeans and South Asians). In vitro studies showed that the variant affects both SLC26A6 transport activity and membrane surface expression, in turn reducing Cl− dependant oxalate transport. Cotransfection studies indicated a dominant-negative effect on WT. Slc26a6 null mice similarly displayed hyperoxalemia and hyperoxaluria which were caused by defective intestinal back-secretion of dietary oxalate (PMID: 21170874; 32660969)

SLC26A6 is currently not associated with any human phenotype in OMIM or G2P.
Sources: Literature
Mendeliome v1.542 TNNC2 Zornitza Stark Marked gene: TNNC2 as ready
Mendeliome v1.542 TNNC2 Zornitza Stark Gene: tnnc2 has been classified as Green List (High Evidence).
Mendeliome v1.542 TNNC2 Zornitza Stark Classified gene: TNNC2 as Green List (high evidence)
Mendeliome v1.542 TNNC2 Zornitza Stark Gene: tnnc2 has been classified as Green List (High Evidence).
Mendeliome v1.541 TNNC2 Zornitza Stark gene: TNNC2 was added
gene: TNNC2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TNNC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TNNC2 were set to 33755597
Phenotypes for gene: TNNC2 were set to Congenital myopathy, MONDO:0019952, TNNC2-related
Review for gene: TNNC2 was set to GREEN
Added comment: Two families reported: Family 1: 4 individuals, three generations; missense variant p.(Asp34Tyr) Family 2: de novo variant, missense p.(Met79Ile)

Physiological studies in myofibers isolated from patients’ biopsies revealed a markedly reduced force response of the sarcomeres to [Ca2+]. This pathomechanism was further confirmed in experiments in which contractile dysfunction was evoked by replacing TnC in myofibers from healthy control subjects with recombinant, mutant TnC. Conversely, the contractile dysfunction of myofibers from patients was repaired by replacing endogenous, mutant TnC with recombinant, wild-type TnC.

Borderline Green: sufficient segregation in Fam 1 plus de novo status in Fam 2, plus functional data.
Sources: Literature
Mendeliome v1.531 MPC2 Zornitza Stark Marked gene: MPC2 as ready
Mendeliome v1.531 MPC2 Zornitza Stark Gene: mpc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.531 MPC2 Zornitza Stark Classified gene: MPC2 as Amber List (moderate evidence)
Mendeliome v1.531 MPC2 Zornitza Stark Gene: mpc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.530 MPC2 Zornitza Stark gene: MPC2 was added
gene: MPC2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MPC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MPC2 were set to 36417180
Phenotypes for gene: MPC2 were set to mitochondrial pyruvate carrier deficiency, MONDO:0013877, MPC2-related
Review for gene: MPC2 was set to AMBER
Added comment: Four patients from two unrelated consanguineous families reported with homozygous variants (missense and stop-loss). Siblings from family 1 were diagnosed prenatally with diffuse subcutaneous oedema, cardiomegaly, corpus callosum agenesis, ventriculomegaly and hypoplasia of the cerebellum. Siblings from family 2 had slightly different presentations, which included anoxo-ischemic encephalopathy, isolated dyspnea, neonatal respiratory distress, neonatal jaundice, hypotonia, visual impairment, microcephaly; both siblings had severe delayed psychomotor development. Immunoblot analysis of protein expression in lysates from patient-derived fibroblasts demonstrated reduced MPC1 and MPC2 protein levels.
Sources: Literature
Mendeliome v1.511 NPC1 Naomi Baker gene: NPC1 was added
gene: NPC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NPC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NPC1 were set to 36417180
Phenotypes for gene: NPC1 were set to mitochondrial pyruvate carrier deficiency, MONDO:0013877, MPC2-related
Review for gene: NPC1 was set to AMBER
Added comment: Four patients from two unrelated consanguineous families reported with homozygous variants (missense and stop-loss). Siblings from family 1 were diagnosed prenatally with diffuse subcutaneous oedema, cardiomegaly, corpus callosum agenesis, ventriculomegaly and hypoplasia of the cerebellum. Siblings from family 2 had slightly different presentations, which included anoxo-ischemic encephalopathy, isolated dyspnea, neonatal respiratory distress, neonatal jaundice, hypotonia, visual impairment, microcephaly; both siblings had severe delayed psychomotor development. Immunoblot analysis of protein expression in lysates from patient-derived fibroblasts demonstrated reduced MPC1 and MPC2 protein levels.
Sources: Literature
Mendeliome v1.343 SLC25A20 Zornitza Stark Tag treatable tag was added to gene: SLC25A20.
Mendeliome v1.343 SLC22A5 Zornitza Stark Tag treatable tag was added to gene: SLC22A5.
Mendeliome v1.343 MC2R Zornitza Stark Tag treatable tag was added to gene: MC2R.
Mendeliome v1.252 FOCAD Zornitza Stark gene: FOCAD was added
gene: FOCAD was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: FOCAD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FOCAD were set to 35864190
Phenotypes for gene: FOCAD were set to Liver disease, severe congenital, MIM# 619991
Review for gene: FOCAD was set to GREEN
Added comment: Moreno Traspas et al 2022 reported 14 children from ten unrelated families with syndromic form of pediatric liver cirrhosis. Genome/exome sequencing analysis reveled biallelic variants in the FOCAD gene. Most of the mutations were nonsense, frameshift, or splice site alterations, predicted to result in a loss of function, but there were also 3 missense variants at highly conserved residues. Western blot analysis of dermal fibroblasts derived from 2 patients showed near absent FOCAD expression in cellular extracts. There were also decreased levels of the SKIC2 protein, suggesting that FOCAD may contribute to the stability of RNA helicase (OMIM: 619991).
Sources: Expert Review
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
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).
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).
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).
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
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 v1.134 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 v1.114 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
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 v1.89 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
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 v0.14781 DNAJC21 Zornitza Stark Marked gene: DNAJC21 as ready
Mendeliome v0.14781 DNAJC21 Zornitza Stark Gene: dnajc21 has been classified as Green List (High Evidence).
Mendeliome v0.14781 DNAJC21 Zornitza Stark Phenotypes for gene: DNAJC21 were changed from to Bone marrow failure syndrome 3 - MIM#617052
Mendeliome v0.14780 DNAJC21 Zornitza Stark Publications for gene: DNAJC21 were set to
Mendeliome v0.14776 DNAJC21 Zornitza Stark Mode of inheritance for gene: DNAJC21 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14691 ATP2C2 Elena Savva Marked gene: ATP2C2 as ready
Mendeliome v0.14691 ATP2C2 Elena Savva Gene: atp2c2 has been classified as Red List (Low Evidence).
Mendeliome v0.14672 SLC26A1 Elena Savva Marked gene: SLC26A1 as ready
Mendeliome v0.14672 SLC26A1 Elena Savva Gene: slc26a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.14438 MCCC2 Zornitza Stark Marked gene: MCCC2 as ready
Mendeliome v0.14438 MCCC2 Zornitza Stark Gene: mccc2 has been classified as Green List (High Evidence).
Mendeliome v0.14438 MCCC2 Zornitza Stark Phenotypes for gene: MCCC2 were changed from to 3-Methylcrotonyl-CoA carboxylase 2 deficiency MIM#210210; Organic acidurias
Mendeliome v0.14437 MCCC2 Zornitza Stark Publications for gene: MCCC2 were set to
Mendeliome v0.14436 MCCC2 Zornitza Stark Mode of inheritance for gene: MCCC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14435 MCCC2 Zornitza Stark reviewed gene: MCCC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31730530; Phenotypes: 3-Methylcrotonyl-CoA carboxylase 2 deficiency MIM#210210, Organic acidurias; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14429 MC2R Zornitza Stark Marked gene: MC2R as ready
Mendeliome v0.14429 MC2R Zornitza Stark Gene: mc2r has been classified as Green List (High Evidence).
Mendeliome v0.14429 MC2R Zornitza Stark Phenotypes for gene: MC2R were changed from to Glucocorticoid deficiency, due to ACTH unresponsiveness, MIM# 202200
Mendeliome v0.14428 MC2R Zornitza Stark Publications for gene: MC2R were set to
Mendeliome v0.14427 MC2R Zornitza Stark Mode of inheritance for gene: MC2R was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14426 MC2R Zornitza Stark reviewed gene: MC2R: Rating: GREEN; Mode of pathogenicity: None; Publications: 8094489, 8227361; Phenotypes: Glucocorticoid deficiency, due to ACTH unresponsiveness, MIM# 202200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14337 UQCC2 Zornitza Stark Marked gene: UQCC2 as ready
Mendeliome v0.14337 UQCC2 Zornitza Stark Gene: uqcc2 has been classified as Green List (High Evidence).
Mendeliome v0.14337 UQCC2 Zornitza Stark Phenotypes for gene: UQCC2 were changed from to Mitochondrial complex III deficiency, nuclear type 7 - MIM#615824
Mendeliome v0.14336 UQCC2 Zornitza Stark Publications for gene: UQCC2 were set to
Mendeliome v0.14335 UQCC2 Zornitza Stark Mode of inheritance for gene: UQCC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14291 DNAJC21 Krithika Murali reviewed gene: DNAJC21: Rating: GREEN; Mode of pathogenicity: None; Publications: 29700810, 28062395, 27346687; Phenotypes: Bone marrow failure syndrome 3 - MIM#617052; Mode of inheritance: None
Mendeliome v0.14178 RFC2 Zornitza Stark Marked gene: RFC2 as ready
Mendeliome v0.14178 RFC2 Zornitza Stark Gene: rfc2 has been classified as Red List (Low Evidence).
Mendeliome v0.14178 RFC2 Zornitza Stark Classified gene: RFC2 as Red List (low evidence)
Mendeliome v0.14178 RFC2 Zornitza Stark Gene: rfc2 has been classified as Red List (Low Evidence).
Mendeliome v0.14177 RFC2 Zornitza Stark reviewed gene: RFC2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.14129 SLC22A5 Zornitza Stark Marked gene: SLC22A5 as ready
Mendeliome v0.14129 SLC22A5 Zornitza Stark Gene: slc22a5 has been classified as Green List (High Evidence).
Mendeliome v0.14129 SLC22A5 Zornitza Stark Phenotypes for gene: SLC22A5 were changed from to Carnitine deficiency, systemic primary, MIM# 212140, MONDO:0008919
Mendeliome v0.14128 SLC22A5 Zornitza Stark Publications for gene: SLC22A5 were set to
Mendeliome v0.14127 SLC22A5 Zornitza Stark Mode of inheritance for gene: SLC22A5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.14126 SLC22A12 Zornitza Stark Marked gene: SLC22A12 as ready
Mendeliome v0.14126 SLC22A12 Zornitza Stark Gene: slc22a12 has been classified as Green List (High Evidence).
Mendeliome v0.14126 SLC22A12 Zornitza Stark Phenotypes for gene: SLC22A12 were changed from to Hypouricemia, renal, MIM# 220150, MONDO:0020728
Mendeliome v0.14125 SLC22A12 Zornitza Stark Publications for gene: SLC22A12 were set to
Mendeliome v0.14124 SLC22A12 Zornitza Stark Mode of inheritance for gene: SLC22A12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13949 SLC22A12 Manny Jacobs reviewed gene: SLC22A12: Rating: GREEN; Mode of pathogenicity: None; Publications: 14655203, 34412930, 34756726, 34829836, 26821810; Phenotypes: Hypouricemia, renal, MIM# 220150, MONDO:0020728; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13930 SLC22A5 Manny Jacobs reviewed gene: SLC22A5: Rating: GREEN; Mode of pathogenicity: None; Publications: 9916797, 10072434, 10051646, 10425211, 10480371, 10679939, 9837751, 23379544, 31399326; Phenotypes: Carnitine deficiency, systemic primary, MIM# 212140, MONDO:0008919; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13873 APOC4-APOC2 Elena Savva Marked gene: APOC4-APOC2 as ready
Mendeliome v0.13873 APOC4-APOC2 Elena Savva Gene: apoc4-apoc2 has been classified as Red List (Low Evidence).
Mendeliome v0.13873 APOC4-APOC2 Elena Savva Publications for gene: APOC4-APOC2 were set to
Mendeliome v0.13873 APOC4-APOC2 Elena Savva Classified gene: APOC4-APOC2 as Red List (low evidence)
Mendeliome v0.13873 APOC4-APOC2 Elena Savva Gene: apoc4-apoc2 has been classified as Red List (Low Evidence).
Mendeliome v0.13872 APOC2 Elena Savva Phenotypes for gene: APOC2 were changed from Hyperlipoproteinemia, type Ib MIM#207750 to Hyperlipoproteinemia, type Ib MIM#207750
Mendeliome v0.13871 APOC4-APOC2 Elena Savva reviewed gene: APOC4-APOC2: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 31034468; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.13871 APOC2 Elena Savva Phenotypes for gene: APOC2 were changed from to Hyperlipoproteinemia, type Ib MIM#207750
Mendeliome v0.13870 APOC2 Elena Savva Marked gene: APOC2 as ready
Mendeliome v0.13870 APOC2 Elena Savva Gene: apoc2 has been classified as Green List (High Evidence).
Mendeliome v0.13869 APOC2 Elena Savva Publications for gene: APOC2 were set to
Mendeliome v0.13869 APOC2 Elena Savva Mode of inheritance for gene: APOC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13868 APOC2 Elena Savva reviewed gene: APOC2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32562799, 26044956, 32292609, 32280258; Phenotypes: Hyperlipoproteinemia, type Ib MIM#207750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13633 SLC24A1 Zornitza Stark Marked gene: SLC24A1 as ready
Mendeliome v0.13633 SLC24A1 Zornitza Stark Gene: slc24a1 has been classified as Green List (High Evidence).
Mendeliome v0.13633 SLC24A1 Zornitza Stark Phenotypes for gene: SLC24A1 were changed from to Night blindness, congenital stationary (complete), 1D, autosomal recessive, MIM#613830, MONDO:0013450
Mendeliome v0.13632 SLC24A1 Zornitza Stark Publications for gene: SLC24A1 were set to
Mendeliome v0.13631 SLC24A1 Zornitza Stark Mode of inheritance for gene: SLC24A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13630 SLC25A1 Zornitza Stark Marked gene: SLC25A1 as ready
Mendeliome v0.13630 SLC25A1 Zornitza Stark Gene: slc25a1 has been classified as Green List (High Evidence).
Mendeliome v0.13630 SLC25A1 Zornitza Stark Phenotypes for gene: SLC25A1 were changed from to Combined D-2- and L-2-hydroxyglutaric aciduria MIM#: 615182, MONDO:0014072; Myasthenic syndrome, congenital, 23, presynaptic, MIM#618197, MONDO:0032596
Mendeliome v0.13629 SLC25A1 Zornitza Stark Publications for gene: SLC25A1 were set to
Mendeliome v0.13628 SLC25A1 Zornitza Stark Mode of inheritance for gene: SLC25A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13616 SLC24A1 Manny Jacobs reviewed gene: SLC24A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35486108, 35446361, 20850105, 26822852; Phenotypes: Night blindness, congenital stationary (complete), 1D, autosomal recessive, MIM#613830, MONDO:0013450; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13613 SLC25A1 Manny Jacobs reviewed gene: SLC25A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26870663, 31527857, 31808147, 23561848, 23393310; Phenotypes: Combined D-2- and L-2-hydroxyglutaric aciduria MIM#: 615182, MONDO:0014072, Myasthenic syndrome, congenital, 23, presynaptic, MIM#618197, MONDO:0032596; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13154 CC2D2A Zornitza Stark Publications for gene: CC2D2A were set to 18387594; 18950740; 18513680; 18950740; 19574260; 21725307; 33486889
Mendeliome v0.13153 CC2D2A Zornitza Stark edited their review of gene: CC2D2A: Changed publications: 18387594, 18950740, 18513680, 18950740, 19574260, 21725307, 33486889, 30267408
Mendeliome v0.13153 CC2D2A Zornitza Stark edited their review of gene: CC2D2A: Changed phenotypes: COACH syndrome, MIM#216360, Joubert syndrome 9, MIM#612285, Meckel syndrome 6, MIM#612284, Retinitis pigmentosa 93, MIM# 619845
Mendeliome v0.12962 PSMC2 Zornitza Stark Marked gene: PSMC2 as ready
Mendeliome v0.12962 PSMC2 Zornitza Stark Gene: psmc2 has been classified as Red List (Low Evidence).
Mendeliome v0.12962 PSMC2 Zornitza Stark Classified gene: PSMC2 as Red List (low evidence)
Mendeliome v0.12962 PSMC2 Zornitza Stark Gene: psmc2 has been classified as Red List (Low Evidence).
Mendeliome v0.12961 PSMC2 Zornitza Stark reviewed gene: PSMC2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.12836 SLC25A12 Zornitza Stark Marked gene: SLC25A12 as ready
Mendeliome v0.12836 SLC25A12 Zornitza Stark Gene: slc25a12 has been classified as Green List (High Evidence).
Mendeliome v0.12836 SLC25A12 Zornitza Stark Phenotypes for gene: SLC25A12 were changed from to Developmental and epileptic encephalopathy 39, MIM# 612949
Mendeliome v0.12835 SLC25A12 Zornitza Stark Publications for gene: SLC25A12 were set to
Mendeliome v0.12834 SLC25A12 Zornitza Stark Mode of inheritance for gene: SLC25A12 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12833 SLC25A12 Zornitza Stark reviewed gene: SLC25A12: Rating: GREEN; Mode of pathogenicity: None; Publications: 19641205, 24515575, 35008954, 32700846, 31766059, 31514314; Phenotypes: Developmental and epileptic encephalopathy 39, MIM# 612949; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12833 SLC25A13 Zornitza Stark Marked gene: SLC25A13 as ready
Mendeliome v0.12833 SLC25A13 Zornitza Stark Gene: slc25a13 has been classified as Green List (High Evidence).
Mendeliome v0.12833 SLC25A13 Zornitza Stark Phenotypes for gene: SLC25A13 were changed from to Citrullinemia, type II, neonatal-onset, MIM# 605814; Citrullinemia, adult-onset type II, MIM# 603471
Mendeliome v0.12832 SLC25A13 Zornitza Stark Publications for gene: SLC25A13 were set to
Mendeliome v0.12831 SLC25A13 Zornitza Stark Mode of inheritance for gene: SLC25A13 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12830 SLC25A13 Zornitza Stark reviewed gene: SLC25A13: Rating: GREEN; Mode of pathogenicity: None; Publications: 21424115, 11343052; Phenotypes: Citrullinemia, type II, neonatal-onset, MIM# 605814, Citrullinemia, adult-onset type II, MIM# 603471; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12830 SLC25A15 Zornitza Stark Marked gene: SLC25A15 as ready
Mendeliome v0.12830 SLC25A15 Zornitza Stark Gene: slc25a15 has been classified as Green List (High Evidence).
Mendeliome v0.12830 SLC25A15 Zornitza Stark Phenotypes for gene: SLC25A15 were changed from to Hyperornithinaemia-hyperammonaemia-homocitrullinaemia syndrome , MIM#238970
Mendeliome v0.12829 SLC25A15 Zornitza Stark Publications for gene: SLC25A15 were set to
Mendeliome v0.12828 SLC25A15 Zornitza Stark Mode of inheritance for gene: SLC25A15 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12827 SLC25A15 Zornitza Stark reviewed gene: SLC25A15: Rating: GREEN; Mode of pathogenicity: None; Publications: 10369256, 19242930]; Phenotypes: Hyperornithinemia-hyperammonemia-homocitrullinemia syndrome , MIM#238970; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12827 SLC25A19 Zornitza Stark Marked gene: SLC25A19 as ready
Mendeliome v0.12827 SLC25A19 Zornitza Stark Gene: slc25a19 has been classified as Green List (High Evidence).
Mendeliome v0.12827 SLC25A19 Zornitza Stark Phenotypes for gene: SLC25A19 were changed from to Microcephaly, Amish type, MIM#607196; Thiamine metabolism dysfunction syndrome 4 (progressive polyneuropathy type), MIM#613710
Mendeliome v0.12826 SLC25A19 Zornitza Stark Publications for gene: SLC25A19 were set to
Mendeliome v0.12825 SLC25A19 Zornitza Stark Mode of inheritance for gene: SLC25A19 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12824 SLC25A19 Zornitza Stark reviewed gene: SLC25A19: Rating: GREEN; Mode of pathogenicity: None; Publications: 31506564, 31295743, 12185364, 19798730; Phenotypes: Microcephaly, Amish type, MIM#607196, Thiamine metabolism dysfunction syndrome 4 (progressive polyneuropathy type), MIM#613710; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12824 SLC25A22 Zornitza Stark Marked gene: SLC25A22 as ready
Mendeliome v0.12824 SLC25A22 Zornitza Stark Gene: slc25a22 has been classified as Green List (High Evidence).
Mendeliome v0.12824 SLC25A22 Zornitza Stark Phenotypes for gene: SLC25A22 were changed from to Developmental and epileptic encephalopathy 3, MIM# 609304
Mendeliome v0.12823 SLC25A22 Zornitza Stark Publications for gene: SLC25A22 were set to
Mendeliome v0.12822 SLC25A22 Zornitza Stark Mode of inheritance for gene: SLC25A22 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12821 SLC25A22 Zornitza Stark reviewed gene: SLC25A22: Rating: GREEN; Mode of pathogenicity: None; Publications: 15592994, 19780765, 24596948, 33821742, 33342683, 31285529; Phenotypes: Developmental and epileptic encephalopathy 3, MIM# 609304; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12815 TRAPPC2 Zornitza Stark Marked gene: TRAPPC2 as ready
Mendeliome v0.12815 TRAPPC2 Zornitza Stark Gene: trappc2 has been classified as Green List (High Evidence).
Mendeliome v0.12815 TRAPPC2 Zornitza Stark Phenotypes for gene: TRAPPC2 were changed from to Spondyloepiphyseal dysplasia tarda, MIM# 313400
Mendeliome v0.12814 TRAPPC2 Zornitza Stark Publications for gene: TRAPPC2 were set to
Mendeliome v0.12813 TRAPPC2 Zornitza Stark Mode of inheritance for gene: TRAPPC2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.12812 TRAPPC2 Zornitza Stark reviewed gene: TRAPPC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 10431248, 14755465, 33726005, 20301324, 32953644; Phenotypes: Spondyloepiphyseal dysplasia tarda, MIM# 313400; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.12731 TTC21B Dean Phelan edited their review of gene: TTC21B: Added comment: Correcting typographical error; Changed phenotypes: Glomerular disorder (MONDO:0019722), TTC21B-related
Mendeliome v0.12731 TTC21B Dean Phelan edited their review of gene: TTC21B: Added comment: Updated to include additional publications linking glomerular disorder.; Changed rating: GREEN; Changed publications: PMID: 35289079, 26940125, 28124483, 31208513, 34805047; Changed phenotypes: Glomerular disorder (MONOD:0019722), TTC21B-related
Mendeliome v0.12729 TTC21B Zornitza Stark Phenotypes for gene: TTC21B were changed from Nephronophthisis 12, MIM# 613820; Short-rib thoracic dysplasia 4 with or without polydactyly, MIM# 613819; Joubert syndrome to Nephronophthisis 12, MIM# 613820; Short-rib thoracic dysplasia 4 with or without polydactyly, MIM# 613819; Joubert syndrome; Glomerular disorder MONDO:0019722, TTC21B-related
Mendeliome v0.12720 TTC21B Dean Phelan reviewed gene: TTC21B: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 35289079; Phenotypes: early onset hypertension, proteinuria, progressive kidney disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12684 SLC25A26 Zornitza Stark Marked gene: SLC25A26 as ready
Mendeliome v0.12684 SLC25A26 Zornitza Stark Gene: slc25a26 has been classified as Green List (High Evidence).
Mendeliome v0.12682 SLC25A26 Zornitza Stark Phenotypes for gene: SLC25A26 were changed from to Combined oxidative phosphorylation deficiency 28, MIM# 616794
Mendeliome v0.12681 SLC25A26 Zornitza Stark Publications for gene: SLC25A26 were set to
Mendeliome v0.12680 SLC25A26 Zornitza Stark Mode of inheritance for gene: SLC25A26 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12679 SLC25A26 Zornitza Stark reviewed gene: SLC25A26: Rating: GREEN; Mode of pathogenicity: None; Publications: 26522469; Phenotypes: Combined oxidative phosphorylation deficiency 28, MIM# 616794; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12679 SLC25A3 Zornitza Stark Marked gene: SLC25A3 as ready
Mendeliome v0.12679 SLC25A3 Zornitza Stark Gene: slc25a3 has been classified as Green List (High Evidence).
Mendeliome v0.12679 SLC25A3 Zornitza Stark Publications for gene: SLC25A3 were set to
Mendeliome v0.12678 SLC25A3 Zornitza Stark Phenotypes for gene: SLC25A3 were changed from to Mitochondrial phosphate carrier deficiency, MIM# 610773
Mendeliome v0.12677 SLC25A3 Zornitza Stark Mode of inheritance for gene: SLC25A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12676 SLC25A3 Zornitza Stark reviewed gene: SLC25A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 17273968, 21763135, 25681081; Phenotypes: Mitochondrial phosphate carrier deficiency, MIM# 610773; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12676 SLC25A4 Zornitza Stark Marked gene: SLC25A4 as ready
Mendeliome v0.12676 SLC25A4 Zornitza Stark Gene: slc25a4 has been classified as Green List (High Evidence).
Mendeliome v0.12676 SLC25A4 Zornitza Stark Phenotypes for gene: SLC25A4 were changed from to Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) AD, MIM#617184; Mitochondrial DNA depletion syndrome 12B (cardiomyopathic type) AR, MIM#615418; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 2, MIM#609283
Mendeliome v0.12675 SLC25A4 Zornitza Stark Publications for gene: SLC25A4 were set to
Mendeliome v0.12674 SLC25A4 Zornitza Stark Mode of inheritance for gene: SLC25A4 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12673 SLC25A4 Zornitza Stark reviewed gene: SLC25A4: Rating: GREEN; Mode of pathogenicity: None; Publications: 30046662, 30013777, 29654543, 28823815; Phenotypes: Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) AD, MIM#617184, Mitochondrial DNA depletion syndrome 12B (cardiomyopathic type) AR, MIM#615418, Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 2, MIM#609283; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12673 SLC25A42 Zornitza Stark Marked gene: SLC25A42 as ready
Mendeliome v0.12673 SLC25A42 Zornitza Stark Gene: slc25a42 has been classified as Green List (High Evidence).
Mendeliome v0.12673 SLC25A42 Zornitza Stark Phenotypes for gene: SLC25A42 were changed from to Metabolic crises, recurrent, with variable encephalomyopathic features and neurologic regression , MIM#618416
Mendeliome v0.12672 SLC25A42 Zornitza Stark Publications for gene: SLC25A42 were set to
Mendeliome v0.12671 SLC25A42 Zornitza Stark Mode of inheritance for gene: SLC25A42 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12670 SLC25A42 Zornitza Stark Tag founder tag was added to gene: SLC25A42.
Mendeliome v0.12670 SLC25A42 Zornitza Stark reviewed gene: SLC25A42: Rating: GREEN; Mode of pathogenicity: None; Publications: 26541337, 29327420, 29923093, 34258143; Phenotypes: Metabolic crises, recurrent, with variable encephalomyopathic features and neurologic regression , MIM#618416; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12670 SLC2A10 Zornitza Stark Marked gene: SLC2A10 as ready
Mendeliome v0.12670 SLC2A10 Zornitza Stark Gene: slc2a10 has been classified as Green List (High Evidence).
Mendeliome v0.12670 SLC2A10 Zornitza Stark Phenotypes for gene: SLC2A10 were changed from to Arterial tortuosity syndrome, MIM# 208050
Mendeliome v0.12669 SLC2A10 Zornitza Stark Publications for gene: SLC2A10 were set to
Mendeliome v0.12668 SLC2A10 Zornitza Stark Mode of inheritance for gene: SLC2A10 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12667 SLC2A10 Zornitza Stark reviewed gene: SLC2A10: Rating: GREEN; Mode of pathogenicity: None; Publications: 30071989, 16550171, 17935213; Phenotypes: Arterial tortuosity syndrome, MIM# 208050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12667 SLC2A2 Zornitza Stark changed review comment from: Fanconi-Bickel syndrome is a rare but well-defined clinical entity, inherited in an autosomal recessive mode and characterized by hepatorenal glycogen accumulation, proximal renal tubular dysfunction, and impaired utilization of glucose and galactose.

> 5 patients previously reported with the associated condition, which is a glycogen storage disease. SLC2A2 encodes for the glucose transporter, GLUT2.; to: Fanconi-Bickel syndrome is characterized by hepatorenal glycogen accumulation, proximal renal tubular dysfunction, and impaired utilization of glucose and galactose.

> 5 patients previously reported with the associated condition, which is a glycogen storage disease. SLC2A2 encodes for the glucose transporter, GLUT2.
Mendeliome v0.12667 SLC2A2 Zornitza Stark Marked gene: SLC2A2 as ready
Mendeliome v0.12667 SLC2A2 Zornitza Stark Gene: slc2a2 has been classified as Green List (High Evidence).
Mendeliome v0.12667 SLC2A2 Zornitza Stark Phenotypes for gene: SLC2A2 were changed from to Fanconi-Bickel syndrome, MIM# 227810
Mendeliome v0.12666 SLC2A2 Zornitza Stark Publications for gene: SLC2A2 were set to
Mendeliome v0.12665 SLC2A2 Zornitza Stark Mode of inheritance for gene: SLC2A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12664 SLC2A2 Zornitza Stark reviewed gene: SLC2A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30950137, 22145468; Phenotypes: Fanconi-Bickel syndrome, MIM# 227810; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12664 SLC2A3 Zornitza Stark Marked gene: SLC2A3 as ready
Mendeliome v0.12664 SLC2A3 Zornitza Stark Gene: slc2a3 has been classified as Red List (Low Evidence).
Mendeliome v0.12664 SLC2A3 Zornitza Stark Classified gene: SLC2A3 as Red List (low evidence)
Mendeliome v0.12664 SLC2A3 Zornitza Stark Gene: slc2a3 has been classified as Red List (Low Evidence).
Mendeliome v0.12663 SLC2A3 Zornitza Stark reviewed gene: SLC2A3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.12663 SLC2A4 Zornitza Stark Marked gene: SLC2A4 as ready
Mendeliome v0.12663 SLC2A4 Zornitza Stark Gene: slc2a4 has been classified as Red List (Low Evidence).
Mendeliome v0.12663 SLC2A4 Zornitza Stark Classified gene: SLC2A4 as Red List (low evidence)
Mendeliome v0.12663 SLC2A4 Zornitza Stark Gene: slc2a4 has been classified as Red List (Low Evidence).
Mendeliome v0.12662 SLC2A4 Zornitza Stark reviewed gene: SLC2A4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.12457 SLC2A9 Zornitza Stark Marked gene: SLC2A9 as ready
Mendeliome v0.12457 SLC2A9 Zornitza Stark Gene: slc2a9 has been classified as Green List (High Evidence).
Mendeliome v0.12457 SLC2A9 Zornitza Stark Phenotypes for gene: SLC2A9 were changed from to Hypouricaemia, renal, 2, MIM# 612076
Mendeliome v0.12456 SLC2A9 Zornitza Stark Publications for gene: SLC2A9 were set to
Mendeliome v0.12455 SLC2A9 Zornitza Stark Mode of inheritance for gene: SLC2A9 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.12454 SLC2A9 Zornitza Stark reviewed gene: SLC2A9: Rating: GREEN; Mode of pathogenicity: None; Publications: 19026395, 19926891, 21810765, 25966807, 21256783; Phenotypes: Hypouricaemia, renal, 2, MIM# 612076; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.12370 BNIP1 Bryony Thompson gene: BNIP1 was added
gene: BNIP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BNIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BNIP1 were set to 35266227; 31344970
Phenotypes for gene: BNIP1 were set to spondyloepiphyseal dysplasia MONDO:0016761
Review for gene: BNIP1 was set to AMBER
Added comment: Two apparently unrelated cases with spondyloepiphyseal dysplasia from India were identified with the same variant (c.84+3A>T). The kindred coefficient comparison of the 2 cases exome data suggested they were unrelated, however there was a stretch of shared homozygosity suggesting remote consanguinity. ~80% aberrantly spliced BNIP1 pre-mRNAs, reduced BNIP1 mRNA level to ~80%, and BNIP1 protein level reduction by ~50% were detected in one of the cases fibroblasts. A block at the terminal stage of autolysosome formation and/or clearance in patient fibroblasts was suggested based on the data. A drosophila model of the BNIP1 orthologue Sec20 also demonstrated defective autolysosome formation.
Sources: Literature
Mendeliome v0.11771 C2CD6 Zornitza Stark Marked gene: C2CD6 as ready
Mendeliome v0.11771 C2CD6 Zornitza Stark Gene: c2cd6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11771 C2CD6 Zornitza Stark Classified gene: C2CD6 as Amber List (moderate evidence)
Mendeliome v0.11771 C2CD6 Zornitza Stark Gene: c2cd6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11770 C2CD6 Zornitza Stark gene: C2CD6 was added
gene: C2CD6 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: C2CD6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C2CD6 were set to 34919125; 34998468; 31985809
Phenotypes for gene: C2CD6 were set to Spermatogenic failure 68 , MIM# 619805
Review for gene: C2CD6 was set to AMBER
Added comment: Single individual and two mouse models.
Sources: Expert list
Mendeliome v0.11665 UQCC2 Belinda Chong reviewed gene: UQCC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24385928, 28804536; Phenotypes: Mitochondrial complex III deficiency, nuclear type 7 - MIM#615824; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.11394 C2 Ain Roesley Phenotypes for gene: C2 were changed from C2 deficiency MIM#217000 to C2 deficiency MIM#217000
Mendeliome v0.11394 C2 Ain Roesley Publications for gene: C2 were set to 16026838; 8621452; 35272074; 32385807
Mendeliome v0.11392 C2 Ain Roesley Phenotypes for gene: C2 were changed from to C2 deficiency MIM#217000
Mendeliome v0.11391 C2 Ain Roesley Publications for gene: C2 were set to
Mendeliome v0.11391 C2 Ain Roesley Marked gene: C2 as ready
Mendeliome v0.11391 C2 Ain Roesley Gene: c2 has been classified as Green List (High Evidence).
Mendeliome v0.11391 C2 Ain Roesley Mode of inheritance for gene: C2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11390 C2 Ain Roesley edited their review of gene: C2: Changed rating: GREEN
Mendeliome v0.11388 C2 Ain Roesley reviewed gene: C2: Rating: ; Mode of pathogenicity: None; Publications: 16026838, 8621452, 35272074, 32385807; Phenotypes: C2 deficiency MIM#217000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.11063 SLC22A4 Zornitza Stark Marked gene: SLC22A4 as ready
Mendeliome v0.11063 SLC22A4 Zornitza Stark Gene: slc22a4 has been classified as Red List (Low Evidence).
Mendeliome v0.11063 SLC22A4 Zornitza Stark Phenotypes for gene: SLC22A4 were changed from to susceptibility to rheumatoid arthritis MIM#180300
Mendeliome v0.11062 SLC22A4 Zornitza Stark Publications for gene: SLC22A4 were set to
Mendeliome v0.11061 SLC22A4 Zornitza Stark Classified gene: SLC22A4 as Red List (low evidence)
Mendeliome v0.11061 SLC22A4 Zornitza Stark Gene: slc22a4 has been classified as Red List (Low Evidence).
Mendeliome v0.11058 SLC22A4 Ain Roesley reviewed gene: SLC22A4: Rating: RED; Mode of pathogenicity: None; Publications: 15184985, 24972750; Phenotypes: susceptibility to rheumatoid arthritis MIM#180300; Mode of inheritance: None; Current diagnostic: yes
Mendeliome v0.10906 SLC26A8 Bryony Thompson Marked gene: SLC26A8 as ready
Mendeliome v0.10906 SLC26A8 Bryony Thompson Gene: slc26a8 has been classified as Green List (High Evidence).
Mendeliome v0.10906 SLC26A8 Bryony Thompson Phenotypes for gene: SLC26A8 were changed from to non-syndromic male infertility due to sperm motility disorder MONDO:0017173
Mendeliome v0.10905 SLC26A8 Bryony Thompson Publications for gene: SLC26A8 were set to
Mendeliome v0.10904 SLC26A8 Bryony Thompson Mode of inheritance for gene: SLC26A8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10903 SLC26A8 Bryony Thompson reviewed gene: SLC26A8: Rating: GREEN; Mode of pathogenicity: None; Publications: 34923715, 23582645, 22121115; Phenotypes: non-syndromic male infertility due to sperm motility disorder MONDO:0017173; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10743 UQCRC2 Zornitza Stark Publications for gene: UQCRC2 were set to 28275242; 23281071
Mendeliome v0.10742 UQCRC2 Zornitza Stark Classified gene: UQCRC2 as Green List (high evidence)
Mendeliome v0.10742 UQCRC2 Zornitza Stark Gene: uqcrc2 has been classified as Green List (High Evidence).
Mendeliome v0.10741 UQCRC2 Zornitza Stark edited their review of gene: UQCRC2: Added comment: Third family with different variant reported, together with functional data.; Changed rating: GREEN; Changed publications: 28275242, 23281071, 33865955
Mendeliome v0.10545 SLC27A4 Zornitza Stark Marked gene: SLC27A4 as ready
Mendeliome v0.10545 SLC27A4 Zornitza Stark Gene: slc27a4 has been classified as Green List (High Evidence).
Mendeliome v0.10545 SLC27A4 Zornitza Stark Phenotypes for gene: SLC27A4 were changed from to Ichthyosis prematurity syndrome, MIM#608649
Mendeliome v0.10544 SLC27A4 Zornitza Stark Publications for gene: SLC27A4 were set to
Mendeliome v0.10543 SLC27A4 Zornitza Stark Mode of inheritance for gene: SLC27A4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10542 SLC25A24 Zornitza Stark reviewed gene: SLC25A24: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fontaine progeroid syndrome, MIM# 612289; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10542 SLC27A4 Seb Lunke reviewed gene: SLC27A4: Rating: GREEN; Mode of pathogenicity: None; Publications: 21856041, 19631310, 31168818; Phenotypes: Ichthyosis prematurity syndrome, MIM#608649; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10539 SLC26A2 Seb Lunke Marked gene: SLC26A2 as ready
Mendeliome v0.10539 SLC26A2 Seb Lunke Gene: slc26a2 has been classified as Green List (High Evidence).
Mendeliome v0.10539 SLC26A2 Seb Lunke Phenotypes for gene: SLC26A2 were changed from to Achondrogenesis 1B, MIM#600972; Atelosteogenesis, type II, MIM#256050; Diastrophic dysplasia, MIM#222600; Epiphyseal dysplasia, multiple, 4, MIM#226900
Mendeliome v0.10538 SLC26A2 Seb Lunke Publications for gene: SLC26A2 were set to
Mendeliome v0.10537 SLC26A2 Seb Lunke Mode of inheritance for gene: SLC26A2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10536 SLC26A2 Seb Lunke reviewed gene: SLC26A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301483, 20301689; Phenotypes: Achondrogenesis 1B, MIM#600972, Atelosteogenesis, type II, MIM#256050, Diastrophic dysplasia, MIM#222600, Epiphyseal dysplasia, multiple, 4, MIM#226900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10530 SLC25A24 Seb Lunke Marked gene: SLC25A24 as ready
Mendeliome v0.10530 SLC25A24 Seb Lunke Gene: slc25a24 has been classified as Green List (High Evidence).
Mendeliome v0.10530 SLC25A24 Seb Lunke Phenotypes for gene: SLC25A24 were changed from to Fontaine progeroid syndrome, MIM#612289
Mendeliome v0.10529 SLC25A24 Seb Lunke Publications for gene: SLC25A24 were set to
Mendeliome v0.10528 SLC25A24 Seb Lunke Mode of inheritance for gene: SLC25A24 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10527 SLC25A24 Seb Lunke reviewed gene: SLC25A24: Rating: ; Mode of pathogenicity: None; Publications: 29100093, 29100094, 29100094, 31775791, 32732226, 32860237; Phenotypes: Fontaine progeroid syndrome, MIM#612289; Mode of inheritance: None; Current diagnostic: yes
Mendeliome v0.10452 FOXC2 Zornitza Stark Marked gene: FOXC2 as ready
Mendeliome v0.10452 FOXC2 Zornitza Stark Gene: foxc2 has been classified as Green List (High Evidence).
Mendeliome v0.10452 FOXC2 Zornitza Stark Phenotypes for gene: FOXC2 were changed from to Lymphoedema-distichiasis syndrome, MIM# 153400
Mendeliome v0.10451 FOXC2 Zornitza Stark Publications for gene: FOXC2 were set to
Mendeliome v0.10450 FOXC2 Zornitza Stark Mode of inheritance for gene: FOXC2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10449 FOXC2 Zornitza Stark reviewed gene: FOXC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 11078474, 11694548, 11371511; Phenotypes: Lymphoedema-distichiasis syndrome, MIM# 153400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10423 C2orf71 Zornitza Stark Marked gene: C2orf71 as ready
Mendeliome v0.10423 C2orf71 Zornitza Stark Gene: c2orf71 has been classified as Green List (High Evidence).
Mendeliome v0.10423 C2orf71 Zornitza Stark Phenotypes for gene: C2orf71 were changed from to Retinitis pigmentosa 54, MIM# 613428
Mendeliome v0.10422 C2orf71 Zornitza Stark Publications for gene: C2orf71 were set to
Mendeliome v0.10421 C2orf71 Zornitza Stark Mode of inheritance for gene: C2orf71 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10420 C2orf71 Zornitza Stark reviewed gene: C2orf71: Rating: GREEN; Mode of pathogenicity: None; Publications: 20398886, 20398884, 24780881, 31819343, 29946172, 28763557; Phenotypes: Retinitis pigmentosa 54, MIM# 613428; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10250 SLC26A5 Zornitza Stark Publications for gene: SLC26A5 were set to 24164807
Mendeliome v0.10249 SLC26A5 Zornitza Stark Classified gene: SLC26A5 as Amber List (moderate evidence)
Mendeliome v0.10249 SLC26A5 Zornitza Stark Gene: slc26a5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10248 SLC26A5 Zornitza Stark commented on gene: SLC26A5: Another publication identified, plus another individual with bi-allelic variants reported by a diagnostic laboratory. This gene-disease association is supported by mouse models, biochemical function studies and expression studies (12239568, 10821263, 11423665, 12719379, 18466744, 27091614, 17998209). Classified as LIMITED by ClinGen in 2017.
Mendeliome v0.10248 SLC26A5 Zornitza Stark edited their review of gene: SLC26A5: Changed rating: AMBER; Changed publications: 24164807, 12239568, 10821263, 11423665, 12719379, 18466744, 27091614, 17998209
Mendeliome v0.10191 CCDC22 Zornitza Stark Marked gene: CCDC22 as ready
Mendeliome v0.10191 CCDC22 Zornitza Stark Gene: ccdc22 has been classified as Green List (High Evidence).
Mendeliome v0.10191 CCDC22 Zornitza Stark Phenotypes for gene: CCDC22 were changed from to Ritscher-Schinzel syndrome 2, MIM# 300963
Mendeliome v0.10190 CCDC22 Zornitza Stark Publications for gene: CCDC22 were set to
Mendeliome v0.10189 CCDC22 Zornitza Stark Mode of inheritance for gene: CCDC22 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.10188 CCDC22 Zornitza Stark reviewed gene: CCDC22: Rating: GREEN; Mode of pathogenicity: None; Publications: 21826058, 24916641, 34020006, 33059814, 31971710; Phenotypes: Ritscher-Schinzel syndrome 2, MIM# 300963; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.10136 GJC2 Zornitza Stark reviewed gene: GJC2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.10136 GJC2 Zornitza Stark Marked gene: GJC2 as ready
Mendeliome v0.10136 GJC2 Zornitza Stark Gene: gjc2 has been classified as Green List (High Evidence).
Mendeliome v0.10136 GJC2 Zornitza Stark Phenotypes for gene: GJC2 were changed from to Spastic paraplegia 44, autosomal recessive MIM#613206; Leukodystrophy, hypomyelinating, 2 MIM#608804; Lymphatic malformation 3 MIM#613480
Mendeliome v0.10135 GJC2 Zornitza Stark Publications for gene: GJC2 were set to
Mendeliome v0.10134 GJC2 Zornitza Stark Mode of inheritance for gene: GJC2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.10089 GJC2 Ain Roesley reviewed gene: GJC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 19056803, 31431325, 25059390, 20537300, 21266381; Phenotypes: Spastic paraplegia 44, autosomal recessive MIM#613206, Leukodystrophy, hypomyelinating, 2 MIM#608804, Lymphatic malformation 3 MIM#613480; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10079 SLC29A3 Zornitza Stark Marked gene: SLC29A3 as ready
Mendeliome v0.10079 SLC29A3 Zornitza Stark Gene: slc29a3 has been classified as Green List (High Evidence).
Mendeliome v0.10079 SLC29A3 Zornitza Stark Phenotypes for gene: SLC29A3 were changed from to Histiocytosis-lymphadenopathy plus syndrome, MIM# 602782
Mendeliome v0.10078 SLC29A3 Zornitza Stark Publications for gene: SLC29A3 were set to
Mendeliome v0.10077 SLC29A3 Zornitza Stark Mode of inheritance for gene: SLC29A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10076 SLC29A3 Zornitza Stark reviewed gene: SLC29A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 18940313, 19336477, 22238637; Phenotypes: Histiocytosis-lymphadenopathy plus syndrome, MIM# 602782; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9906 CWC27 Zornitza Stark Marked gene: CWC27 as ready
Mendeliome v0.9906 CWC27 Zornitza Stark Gene: cwc27 has been classified as Green List (High Evidence).
Mendeliome v0.9906 CWC27 Zornitza Stark Phenotypes for gene: CWC27 were changed from to Retinitis pigmentosa with or without skeletal anomalies, MIM# 250410
Mendeliome v0.9905 CWC27 Zornitza Stark Publications for gene: CWC27 were set to
Mendeliome v0.9904 CWC27 Zornitza Stark Mode of inheritance for gene: CWC27 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9903 CWC27 Zornitza Stark reviewed gene: CWC27: Rating: GREEN; Mode of pathogenicity: None; Publications: 28285769, 31481716; Phenotypes: Retinitis pigmentosa with or without skeletal anomalies, MIM# 250410; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9896 ELAC2 Zornitza Stark Marked gene: ELAC2 as ready
Mendeliome v0.9896 ELAC2 Zornitza Stark Gene: elac2 has been classified as Green List (High Evidence).
Mendeliome v0.9896 ELAC2 Zornitza Stark Phenotypes for gene: ELAC2 were changed from to Combined oxidative phosphorylation deficiency 17, MIM#615440
Mendeliome v0.9895 ELAC2 Zornitza Stark Publications for gene: ELAC2 were set to
Mendeliome v0.9894 ELAC2 Zornitza Stark Mode of inheritance for gene: ELAC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9893 ELAC2 Zornitza Stark reviewed gene: ELAC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23849775, 31045291; Phenotypes: Combined oxidative phosphorylation deficiency 17, MIM#615440; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9600 AKR1C2 Zornitza Stark Marked gene: AKR1C2 as ready
Mendeliome v0.9600 AKR1C2 Zornitza Stark Gene: akr1c2 has been classified as Red List (Low Evidence).
Mendeliome v0.9600 AKR1C2 Zornitza Stark Phenotypes for gene: AKR1C2 were changed from to 46XY sex reversal 8, MIM# 614279; Obesity
Mendeliome v0.9599 AKR1C2 Zornitza Stark Publications for gene: AKR1C2 were set to
Mendeliome v0.9598 AKR1C2 Zornitza Stark Mode of inheritance for gene: AKR1C2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9597 AKR1C2 Zornitza Stark Classified gene: AKR1C2 as Red List (low evidence)
Mendeliome v0.9597 AKR1C2 Zornitza Stark Gene: akr1c2 has been classified as Red List (Low Evidence).
Mendeliome v0.9596 AKR1C2 Zornitza Stark reviewed gene: AKR1C2: Rating: RED; Mode of pathogenicity: None; Publications: 21802064, 25322899, 33675863; Phenotypes: 46XY sex reversal 8, MIM# 614279, Obesity; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9398 KCNC2 Zornitza Stark Marked gene: KCNC2 as ready
Mendeliome v0.9398 KCNC2 Zornitza Stark Gene: kcnc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9398 KCNC2 Zornitza Stark Publications for gene: KCNC2 were set to PMID:32392612; 31972370
Mendeliome v0.9397 KCNC2 Zornitza Stark Classified gene: KCNC2 as Amber List (moderate evidence)
Mendeliome v0.9397 KCNC2 Zornitza Stark Gene: kcnc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9392 KCNC2 Daniel Flanagan gene: KCNC2 was added
gene: KCNC2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: KCNC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNC2 were set to PMID:32392612; 31972370
Phenotypes for gene: KCNC2 were set to epileptic encephalopathy; spastic tetraplegia; opisthotonos attacks; intellectual disability; West syndrome
Review for gene: KCNC2 was set to AMBER
Added comment: PMID: 31972370. De novo missense variant (p.Val471Leu) identified in a child with early severe developmental and epileptic encephalopathy, spastic tetraplegia, opisthotonos attacks.

PMID: 32392612. De novo missense variant (p.Asp167Tyr) identified in a neurofibromatosis type 1 related West syndrome patient. Functional analysis showed a significant reduction of the mean potassium current and a shift in the voltage dependence of steady-state activation. Maternally inherited NF1 variant (p.T1951Nfs*5) also identified, the mother was "clinically unremarkable".
Sources: Expert list
Mendeliome v0.9383 KCNQ1OT1 Zornitza Stark gene: KCNQ1OT1 was added
gene: KCNQ1OT1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: KCNQ1OT1 was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Publications for gene: KCNQ1OT1 were set to 22205991; 15372379; 23511928; 30794780; 29377879; 10220444; 32447323; 33177595; 29047350
Phenotypes for gene: KCNQ1OT1 were set to Beckwith-Wiedemann syndrome OMIM:130650; Russell-Silver Syndrome
Review for gene: KCNQ1OT1 was set to AMBER
Added comment: Limited evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype.

KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. IC2 is located within KCNQ1 intron 10. KCNQ1OT1 is maternally imprinted and paternally expressed. On the paternal chromosome, KCNQ1OT1 is transcribed and represses in cis the flanking imprinted genes, including the growth inhibitor CDKN1C, which is normally transcribed from the maternal allele. In 50% of the BWS patients, loss of methylation (LOM) of IC2 leads to biallelic expression of KCNQ1OT1 and biallelic silencing of CDKN1C (PMID 30635621). Expression is increased in BWS due to IC2 epimutations or paternal UPD.

Single nucleotide variants within KCNQ1OT1 have not been definitively associated with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350).

Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation.

Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LoF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172).
Sources: Expert Review
Mendeliome v0.9344 TTC26 Zornitza Stark Phenotypes for gene: TTC26 were changed from Ciliopathy Syndrome with Biliary, Renal, Neurological, and Skeletal Manifestations to Biliary, renal, neurologic, and skeletal syndrome, MIM# 619534; Ciliopathy Syndrome with Biliary, Renal, Neurological, and Skeletal Manifestations
Mendeliome v0.9343 TTC26 Zornitza Stark edited their review of gene: TTC26: Changed phenotypes: Biliary, renal, neurologic, and skeletal syndrome, MIM# 619534, Ciliopathy Syndrome with Biliary, Renal, Neurological, and Skeletal Manifestations
Mendeliome v0.9125 SLC26A1 Zornitza Stark Phenotypes for gene: SLC26A1 were changed from to Nephrolithiasis, calcium oxalate, MIM#167030
Mendeliome v0.9124 SLC26A1 Zornitza Stark Publications for gene: SLC26A1 were set to
Mendeliome v0.9123 SLC26A1 Zornitza Stark Mode of inheritance for gene: SLC26A1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.9122 SLC26A1 Zornitza Stark Classified gene: SLC26A1 as Amber List (moderate evidence)
Mendeliome v0.9122 SLC26A1 Zornitza Stark Gene: slc26a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9121 SLC26A1 Zornitza Stark reviewed gene: SLC26A1: Rating: AMBER; Mode of pathogenicity: None; Publications: 27210743, 20160351, 30383413, 27125215; Phenotypes: Nephrolithiasis, calcium oxalate, MIM#167030; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8939 RAC2 Zornitza Stark Marked gene: RAC2 as ready
Mendeliome v0.8939 RAC2 Zornitza Stark Gene: rac2 has been classified as Green List (High Evidence).
Mendeliome v0.8939 RAC2 Zornitza Stark Phenotypes for gene: RAC2 were changed from to Immunodeficiency 73A with defective neutrophil chemotaxix and leukocytosis MIM# 608203; Immunodeficiency 73C with defective neutrophil chemotaxis and hypogammaglobulinaemia MIM# 618987; Immunodeficiency 73B with defective neutrophil chemotaxis and lymphopaenia MIM# 618986
Mendeliome v0.8938 RAC2 Zornitza Stark Publications for gene: RAC2 were set to
Mendeliome v0.8937 RAC2 Zornitza Stark Mode of pathogenicity for gene: RAC2 was changed from to Other
Mendeliome v0.8936 RAC2 Zornitza Stark Mode of inheritance for gene: RAC2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8935 RAC2 Danielle Ariti reviewed gene: RAC2: Rating: GREEN; Mode of pathogenicity: Other; Publications: 21167572, 10758162, 10072071, 25512081, 32542921, 31919089; Phenotypes: Immunodeficiency 73A with defective neutrophil chemotaxix and leukocytosis MIM# 608203, Immunodeficiency 73C with defective neutrophil chemotaxis and hypogammaglobulinaemia MIM# 618987, Immunodeficiency 73B with defective neutrophil chemotaxis and lymphopaenia MIM# 618986; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8799 SLC24A4 Zornitza Stark Marked gene: SLC24A4 as ready
Mendeliome v0.8799 SLC24A4 Zornitza Stark Gene: slc24a4 has been classified as Green List (High Evidence).
Mendeliome v0.8799 SLC24A4 Zornitza Stark Phenotypes for gene: SLC24A4 were changed from to Amelogenesis imperfecta, type IIA5, MIM# 615887
Mendeliome v0.8798 SLC24A4 Zornitza Stark Publications for gene: SLC24A4 were set to
Mendeliome v0.8797 SLC24A4 Zornitza Stark Mode of inheritance for gene: SLC24A4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8796 SLC24A4 Zornitza Stark reviewed gene: SLC24A4: Rating: GREEN; Mode of pathogenicity: None; Publications: 23375655, 24621671, 25442250, 24532815, 26502894, 27129268; Phenotypes: Amelogenesis imperfecta, type IIA5, MIM# 615887; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8713 ABCC2 Zornitza Stark Marked gene: ABCC2 as ready
Mendeliome v0.8713 ABCC2 Zornitza Stark Gene: abcc2 has been classified as Green List (High Evidence).
Mendeliome v0.8713 ABCC2 Zornitza Stark Phenotypes for gene: ABCC2 were changed from to Dubin-Johnson syndrome, MIM# 237500
Mendeliome v0.8712 ABCC2 Zornitza Stark Mode of inheritance for gene: ABCC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8711 ABCC2 Zornitza Stark reviewed gene: ABCC2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dubin-Johnson syndrome, MIM# 237500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8376 EVC2 Zornitza Stark Marked gene: EVC2 as ready
Mendeliome v0.8376 EVC2 Zornitza Stark Gene: evc2 has been classified as Green List (High Evidence).
Mendeliome v0.8376 EVC2 Zornitza Stark Phenotypes for gene: EVC2 were changed from to Ellis-van Creveld syndrome (MIM#225500)
Mendeliome v0.8375 EVC2 Zornitza Stark Publications for gene: EVC2 were set to
Mendeliome v0.8374 EVC2 Zornitza Stark Mode of inheritance for gene: EVC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8370 DCDC2 Zornitza Stark Marked gene: DCDC2 as ready
Mendeliome v0.8370 DCDC2 Zornitza Stark Gene: dcdc2 has been classified as Green List (High Evidence).
Mendeliome v0.8370 DCDC2 Zornitza Stark Phenotypes for gene: DCDC2 were changed from to Nephronophthisis 19, MIM# 616217; Sclerosing cholangitis, neonatal, MIM# 617394
Mendeliome v0.8369 DCDC2 Zornitza Stark Publications for gene: DCDC2 were set to
Mendeliome v0.8368 DCDC2 Zornitza Stark Mode of inheritance for gene: DCDC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8367 DCDC2 Zornitza Stark edited their review of gene: DCDC2: Changed rating: GREEN; Changed publications: 25557784, 27319779, 27469900; Changed phenotypes: Nephronophthisis 19, MIM# 616217, Sclerosing cholangitis, neonatal, MIM# 617394; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8352 C2CD3 Zornitza Stark Marked gene: C2CD3 as ready
Mendeliome v0.8352 C2CD3 Zornitza Stark Gene: c2cd3 has been classified as Green List (High Evidence).
Mendeliome v0.8352 C2CD3 Zornitza Stark Phenotypes for gene: C2CD3 were changed from to Orofaciodigital syndrome XIV, MIM# 615948; MONDO:0014413
Mendeliome v0.8351 C2CD3 Zornitza Stark Publications for gene: C2CD3 were set to
Mendeliome v0.8350 C2CD3 Zornitza Stark Mode of inheritance for gene: C2CD3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8335 DYNC2H1 Zornitza Stark Publications for gene: DYNC2H1 were set to 19442771; 19361615; 22499340; 23456818; 27925158
Mendeliome v0.8334 DYNC2H1 Zornitza Stark edited their review of gene: DYNC2H1: Changed publications: 19442771, 19361615, 22499340, 23456818, 27925158, 32753734; Changed phenotypes: Short-rib thoracic dysplasia 3 with or without polydactyly, MIM# 613091, MONDO:0013127, Non-syndromic retinitis pigmentosa
Mendeliome v0.8313 C2orf69 Zornitza Stark Marked gene: C2orf69 as ready
Mendeliome v0.8313 C2orf69 Zornitza Stark Gene: c2orf69 has been classified as Green List (High Evidence).
Mendeliome v0.8313 C2orf69 Zornitza Stark Classified gene: C2orf69 as Green List (high evidence)
Mendeliome v0.8313 C2orf69 Zornitza Stark Gene: c2orf69 has been classified as Green List (High Evidence).
Mendeliome v0.8312 C2orf69 Zornitza Stark gene: C2orf69 was added
gene: C2orf69 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: C2orf69 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C2orf69 were set to 34038740; 33945503
Phenotypes for gene: C2orf69 were set to Combined oxidative phosphorylation deficiency-53 (COXPD53), MIM#619423
Review for gene: C2orf69 was set to GREEN
Added comment: PMID 34038740: 20 affected children from 8 unrelated families reported, presenting with fatal syndrome consisting of severe autoinflammation and progredient leukoencephalopathy with recurrent seizures; 12 of these subjects, whose DNA was available, segregated homozygous loss-of-function C2orf69 variants. Endogenous C2ORF69 was found to be (1) loosely bound to mitochondria, (2) affects mitochondrial membrane potential and oxidative respiration in cultured neurons, and (3) controls the levels of the glycogen branching enzyme 1 (GBE1) consistent with a glycogen-storage-associated mitochondriopathy. Zebrafish model.

PMID 33945503: 8 individuals from 5 families reported with muscle hypotonia, developmental delay, progressive microcephaly, and brain MRI abnormalities. Age at onset ranged from birth to 6 months of age. Six patients had vision impairment, liver abnormalities, inflammation/inflammatory arthritis, and 5 patients had seizures.
Sources: Literature
Mendeliome v0.8242 TTC21B Zornitza Stark Marked gene: TTC21B as ready
Mendeliome v0.8242 TTC21B Zornitza Stark Gene: ttc21b has been classified as Green List (High Evidence).
Mendeliome v0.8242 TTC21B Zornitza Stark Phenotypes for gene: TTC21B were changed from to Nephronophthisis 12, MIM# 613820; Short-rib thoracic dysplasia 4 with or without polydactyly, MIM# 613819; Joubert syndrome
Mendeliome v0.8241 TTC21B Zornitza Stark Publications for gene: TTC21B were set to
Mendeliome v0.8240 TTC21B Zornitza Stark Mode of inheritance for gene: TTC21B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8239 TTC21B Zornitza Stark reviewed gene: TTC21B: Rating: GREEN; Mode of pathogenicity: None; Publications: 21258341, 25492405, 18327258, 33875766; Phenotypes: Nephronophthisis 12, MIM# 613820, Short-rib thoracic dysplasia 4 with or without polydactyly, MIM# 613819, Joubert syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8235 ATP2C2 Zornitza Stark Classified gene: ATP2C2 as Red List (low evidence)
Mendeliome v0.8235 ATP2C2 Zornitza Stark Gene: atp2c2 has been classified as Red List (Low Evidence).
Mendeliome v0.8229 ATP2C2 Eleanor Williams gene: ATP2C2 was added
gene: ATP2C2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATP2C2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ATP2C2 were set to 33864365; 28440294
Phenotypes for gene: ATP2C2 were set to language impairment, HP:0002463
Review for gene: ATP2C2 was set to RED
Added comment: PMID: 33864365 - Martinelli et al 2021 - report a family with a missense variant NM_001286527.2:c.304G>A, p.(Val102Met) in ATP2C2 in a father and two siblings with specific language impairment. However two other affected siblings did not have this variant. This variant was also reported by Chen et al. They found that the variant had a higher frequency in language cases (1.8%, N = 360) compared with cohorts selected for dyslexia (0.8%, N = 520) and ADHD (0.7%, N = 150), which presented frequencies comparable to reference databases (0.9%, N = 24 046 gnomAD controls). They postulate that variant is not sufficient on its own to cause a disorder but is a susceptibility factor which increases the risk for language impairment.

PMID: 28440294 - Chen et al 2017 - report 2 probands with severe learning impairment, and missense variants in ATP2C2 (NM_001286527: c.G304A:p.V102M and NM_001291454:exon21: c.C1936T:p.R646W).
Sources: Literature
Mendeliome v0.8186 TTC26 Zornitza Stark Marked gene: TTC26 as ready
Mendeliome v0.8186 TTC26 Zornitza Stark Gene: ttc26 has been classified as Green List (High Evidence).
Mendeliome v0.8186 TTC26 Zornitza Stark Classified gene: TTC26 as Green List (high evidence)
Mendeliome v0.8186 TTC26 Zornitza Stark Gene: ttc26 has been classified as Green List (High Evidence).
Mendeliome v0.8185 TTC26 Zornitza Stark gene: TTC26 was added
gene: TTC26 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TTC26 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTC26 were set to 34177428; 32617964; 31595528; 24596149; 22718903
Phenotypes for gene: TTC26 were set to Ciliopathy Syndrome with Biliary, Renal, Neurological, and Skeletal Manifestations
Review for gene: TTC26 was set to GREEN
Added comment: Three unrelated families and functional data including zebrafish model.
Sources: Literature
Mendeliome v0.8175 DYNC2H1 Zornitza Stark Marked gene: DYNC2H1 as ready
Mendeliome v0.8175 DYNC2H1 Zornitza Stark Gene: dync2h1 has been classified as Green List (High Evidence).
Mendeliome v0.8175 DYNC2H1 Zornitza Stark Phenotypes for gene: DYNC2H1 were changed from to Short-rib thoracic dysplasia 3 with or without polydactyly, MIM# 613091; MONDO:0013127
Mendeliome v0.8174 DYNC2H1 Zornitza Stark Publications for gene: DYNC2H1 were set to
Mendeliome v0.8173 DYNC2H1 Zornitza Stark Mode of inheritance for gene: DYNC2H1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8172 DYNC2H1 Zornitza Stark reviewed gene: DYNC2H1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19442771, 19361615, 22499340, 23456818, 27925158; Phenotypes: Short-rib thoracic dysplasia 3 with or without polydactyly, MIM# 613091, MONDO:0013127; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8130 C21orf2 Zornitza Stark Tag new gene name tag was added to gene: C21orf2.
Mendeliome v0.8130 C21orf2 Zornitza Stark Marked gene: C21orf2 as ready
Mendeliome v0.8130 C21orf2 Zornitza Stark Gene: c21orf2 has been classified as Green List (High Evidence).
Mendeliome v0.8130 C21orf2 Zornitza Stark Phenotypes for gene: C21orf2 were changed from to Spondylometaphyseal dysplasia, axial, MIM# 602271; Retinal dystrophy with macular staphyloma, MIM# 617547
Mendeliome v0.8129 C21orf2 Zornitza Stark Publications for gene: C21orf2 were set to
Mendeliome v0.8128 C21orf2 Zornitza Stark Mode of inheritance for gene: C21orf2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8127 C21orf2 Zornitza Stark reviewed gene: C21orf2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26974433, 27548899, 28422394, 26294103, 23105016, 27548899; Phenotypes: Spondylometaphyseal dysplasia, axial, MIM# 602271, Retinal dystrophy with macular staphyloma, MIM# 617547; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7945 MYBPC2 Zornitza Stark Marked gene: MYBPC2 as ready
Mendeliome v0.7945 MYBPC2 Zornitza Stark Gene: mybpc2 has been classified as Red List (Low Evidence).
Mendeliome v0.7945 MYBPC2 Zornitza Stark gene: MYBPC2 was added
gene: MYBPC2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MYBPC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYBPC2 were set to 32732226
Phenotypes for gene: MYBPC2 were set to Fetal akinesia; Hydrops; Hygroma; Multiple pterygium
Review for gene: MYBPC2 was set to RED
Added comment: Novel candidate gene identified in a fetus with fetal akinesia detected by ultrasound. Autopsy showed multiple congenital abnormalities including hydrops, hygroma, multiple pterygium. A homozygous variant (c.3394G>A/ p.Glu1132Lys) in MYBPC2 was found by exome sequencing with concordant segregation among one affected sib and two unaffected sibs.
Sources: Literature
Mendeliome v0.7867 IQSEC2 Zornitza Stark Phenotypes for gene: IQSEC2 were changed from Mental retardation, X-linked 1/78, MIM#309530 to Mental retardation, X-linked 1/78, MIM# 309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347
Mendeliome v0.7866 IQSEC2 Zornitza Stark Publications for gene: IQSEC2 were set to 31415821; 20473311; 30842726
Mendeliome v0.7865 IQSEC2 Zornitza Stark reviewed gene: IQSEC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33368194, 20473311, 23674175; Phenotypes: Mental retardation, X-linked 1/78, MIM# 309530, MONDO:0010656, Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.7841 SLC24A5 Zornitza Stark Marked gene: SLC24A5 as ready
Mendeliome v0.7841 SLC24A5 Zornitza Stark Gene: slc24a5 has been classified as Green List (High Evidence).
Mendeliome v0.7841 SLC24A5 Zornitza Stark Phenotypes for gene: SLC24A5 were changed from to Albinism, oculocutaneous, type VI, MIM# 113750
Mendeliome v0.7840 SLC24A5 Zornitza Stark Publications for gene: SLC24A5 were set to
Mendeliome v0.7839 SLC24A5 Zornitza Stark Mode of inheritance for gene: SLC24A5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7838 SLC24A5 Zornitza Stark reviewed gene: SLC24A5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23364476, 23985994, 26491832; Phenotypes: Albinism, oculocutaneous, type VI, MIM# 113750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7643 THOC2 Zornitza Stark Marked gene: THOC2 as ready
Mendeliome v0.7643 THOC2 Zornitza Stark Gene: thoc2 has been classified as Green List (High Evidence).
Mendeliome v0.7643 THOC2 Zornitza Stark Phenotypes for gene: THOC2 were changed from to Mental retardation, X-linked 12/35 MIM#300957
Mendeliome v0.7642 THOC2 Zornitza Stark Publications for gene: THOC2 were set to
Mendeliome v0.7641 THOC2 Zornitza Stark Mode of inheritance for gene: THOC2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.7637 THOC2 Paul De Fazio edited their review of gene: THOC2: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.7637 THOC2 Paul De Fazio reviewed gene: THOC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26166480, 32116545, 29851191, 32960281; Phenotypes: Mental retardation, X-linked 12/35 MIM#300957; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.7627 SLC2A4RG Zornitza Stark Marked gene: SLC2A4RG as ready
Mendeliome v0.7627 SLC2A4RG Zornitza Stark Gene: slc2a4rg has been classified as Red List (Low Evidence).
Mendeliome v0.7627 SLC2A4RG Zornitza Stark Classified gene: SLC2A4RG as Red List (low evidence)
Mendeliome v0.7627 SLC2A4RG Zornitza Stark Gene: slc2a4rg has been classified as Red List (Low Evidence).
Mendeliome v0.7623 SLC2A4RG Melanie Marty reviewed gene: SLC2A4RG: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: Unknown
Mendeliome v0.7611 NR3C2 Zornitza Stark Marked gene: NR3C2 as ready
Mendeliome v0.7611 NR3C2 Zornitza Stark Gene: nr3c2 has been classified as Green List (High Evidence).
Mendeliome v0.7611 NR3C2 Zornitza Stark Phenotypes for gene: NR3C2 were changed from to Pseudohypoaldosteronism type I, autosomal dominant, MIM# 177735; MONDO:0008329
Mendeliome v0.7610 NR3C2 Zornitza Stark Publications for gene: NR3C2 were set to
Mendeliome v0.7609 NR3C2 Zornitza Stark Mode of inheritance for gene: NR3C2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7608 NR3C2 Zornitza Stark reviewed gene: NR3C2: Rating: GREEN; Mode of pathogenicity: None; Publications: 9662404, 11134129, 11344206, 12788847, 16972228; Phenotypes: Pseudohypoaldosteronism type I, autosomal dominant, MIM# 177735, MONDO:0008329; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7602 SPTLC2 Zornitza Stark Marked gene: SPTLC2 as ready
Mendeliome v0.7602 SPTLC2 Zornitza Stark Gene: sptlc2 has been classified as Green List (High Evidence).
Mendeliome v0.7602 SPTLC2 Zornitza Stark Phenotypes for gene: SPTLC2 were changed from to Neuropathy, hereditary sensory and autonomic, type IC, 613640; MONDO:0013337; Serine palmitoyl transferase deficiency (Disorders of complex lipid synthesis)
Mendeliome v0.7601 SPTLC2 Zornitza Stark Publications for gene: SPTLC2 were set to
Mendeliome v0.7600 SPTLC2 Zornitza Stark Mode of inheritance for gene: SPTLC2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7562 SLC25A46 Zornitza Stark Phenotypes for gene: SLC25A46 were changed from Neuropathy, hereditary motor and sensory, type VIB, MIM# 616505 to Neuropathy, hereditary motor and sensory, type VIB, MIM# 616505; Pontocerebellar hypoplasia, type 1E, MIM# 619303
Mendeliome v0.7561 SLC25A46 Zornitza Stark edited their review of gene: SLC25A46: Changed phenotypes: Neuropathy, hereditary motor and sensory, type VIB, MIM# 616505, Pontocerebellar hypoplasia, type 1E, MIM# 619303
Mendeliome v0.7559 EXOC2 Zornitza Stark Phenotypes for gene: EXOC2 were changed from Global developmental delay; Intellectual disability; Abnormality of the face; Abnormality of brain morphology to Neurodevelopmental disorder with dysmorphic facies and cerebellar hypoplasia, MIM# 619306; Global developmental delay; Intellectual disability; Abnormality of the face; Abnormality of brain morphology
Mendeliome v0.7558 EXOC2 Zornitza Stark edited their review of gene: EXOC2: Changed phenotypes: Neurodevelopmental disorder with dysmorphic facies and cerebellar hypoplasia, MIM# 619306, Global developmental delay, Intellectual disability, Abnormality of the face, Abnormality of brain morphology
Mendeliome v0.7338 ZIC2 Zornitza Stark Marked gene: ZIC2 as ready
Mendeliome v0.7338 ZIC2 Zornitza Stark Gene: zic2 has been classified as Green List (High Evidence).
Mendeliome v0.7338 ZIC2 Zornitza Stark Phenotypes for gene: ZIC2 were changed from to Holoprosencephaly 5, MIM# 609637; MONDO:0012322
Mendeliome v0.7337 ZIC2 Zornitza Stark Publications for gene: ZIC2 were set to
Mendeliome v0.7336 ZIC2 Zornitza Stark Mode of inheritance for gene: ZIC2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7335 ZIC2 Zornitza Stark reviewed gene: ZIC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 9771712, 11285244; Phenotypes: Holoprosencephaly 5, MIM# 609637, MONDO:0012322; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7216 ERCC2 Zornitza Stark Marked gene: ERCC2 as ready
Mendeliome v0.7216 ERCC2 Zornitza Stark Gene: ercc2 has been classified as Green List (High Evidence).
Mendeliome v0.7216 ERCC2 Zornitza Stark Phenotypes for gene: ERCC2 were changed from to Cerebrooculofacioskeletal syndrome 2, MIM# 610756; MONDO:0012553; Trichothiodystrophy 1, photosensitive, MIM# 601675; MONDO:0011125; Xeroderma pigmentosum, group D, MIM# 278730; MONDO:0010212
Mendeliome v0.7215 ERCC2 Zornitza Stark Publications for gene: ERCC2 were set to
Mendeliome v0.7214 ERCC2 Zornitza Stark Mode of inheritance for gene: ERCC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7213 ERCC2 Zornitza Stark reviewed gene: ERCC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 7849702, 9758621, 11443545, 33733458; Phenotypes: Cerebrooculofacioskeletal syndrome 2, MIM# 610756, MONDO:0012553, Trichothiodystrophy 1, photosensitive, MIM# 601675, MONDO:0011125, Xeroderma pigmentosum, group D, MIM# 278730, MONDO:0010212; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6762 CC2D2A Zornitza Stark Marked gene: CC2D2A as ready
Mendeliome v0.6762 CC2D2A Zornitza Stark Gene: cc2d2a has been classified as Green List (High Evidence).
Mendeliome v0.6762 CC2D2A Zornitza Stark Phenotypes for gene: CC2D2A were changed from to Joubert syndrome 9, MIM# 612285; Meckel syndrome 6, MIM# 612284; COACH syndrome 2, MIM# 619111
Mendeliome v0.6761 CC2D2A Zornitza Stark Publications for gene: CC2D2A were set to
Mendeliome v0.6760 CC2D2A Zornitza Stark Mode of inheritance for gene: CC2D2A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6759 CC2D2A Zornitza Stark reviewed gene: CC2D2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 18387594, 18950740, 18513680, 18950740, 19574260, 21725307, 33486889; Phenotypes: Joubert syndrome 9, MIM# 612285, Meckel syndrome 6, MIM# 612284, COACH syndrome 2, MIM# 619111; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6712 NT5C2 Zornitza Stark Marked gene: NT5C2 as ready
Mendeliome v0.6712 NT5C2 Zornitza Stark Gene: nt5c2 has been classified as Green List (High Evidence).
Mendeliome v0.6712 NT5C2 Zornitza Stark Phenotypes for gene: NT5C2 were changed from to Spastic paraplegia 45, autosomal recessive, MIM# 613162; MONDO:0013165
Mendeliome v0.6711 NT5C2 Zornitza Stark Publications for gene: NT5C2 were set to
Mendeliome v0.6710 NT5C2 Zornitza Stark Mode of inheritance for gene: NT5C2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6709 NT5C2 Zornitza Stark reviewed gene: NT5C2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24482476, 32153630, 29123918, 28884889, 28327087; Phenotypes: Spastic paraplegia 45, autosomal recessive, MIM# 613162, MONDO:0013165; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6667 CC2D1A Zornitza Stark Marked gene: CC2D1A as ready
Mendeliome v0.6667 CC2D1A Zornitza Stark Gene: cc2d1a has been classified as Green List (High Evidence).
Mendeliome v0.6667 CC2D1A Zornitza Stark Phenotypes for gene: CC2D1A were changed from to Autosomal recessive mental retardation, (MIM#608443)
Mendeliome v0.6666 CC2D1A Zornitza Stark Publications for gene: CC2D1A were set to
Mendeliome v0.6665 CC2D1A Zornitza Stark Mode of inheritance for gene: CC2D1A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6664 CC2D1A Zornitza Stark reviewed gene: CC2D1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 25066123; Phenotypes: Autosomal recessive mental retardation, (MIM#608443); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6347 LAMC2 Zornitza Stark Marked gene: LAMC2 as ready
Mendeliome v0.6347 LAMC2 Zornitza Stark Gene: lamc2 has been classified as Green List (High Evidence).
Mendeliome v0.6347 LAMC2 Zornitza Stark Phenotypes for gene: LAMC2 were changed from to Epidermolysis bullosa, junctional, Herlitz type, MIM# 226700; Epidermolysis bullosa, junctional, non-Herlitz type, MIM# 226650
Mendeliome v0.6346 LAMC2 Zornitza Stark Publications for gene: LAMC2 were set to
Mendeliome v0.6345 LAMC2 Zornitza Stark Mode of inheritance for gene: LAMC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6344 LAMC2 Zornitza Stark reviewed gene: LAMC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 11810295, 25888738, 24533970; Phenotypes: Epidermolysis bullosa, junctional, Herlitz type, MIM# 226700, Epidermolysis bullosa, junctional, non-Herlitz type, MIM# 226650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6142 NDUFC2 Zornitza Stark Marked gene: NDUFC2 as ready
Mendeliome v0.6142 NDUFC2 Zornitza Stark Gene: ndufc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6142 NDUFC2 Zornitza Stark Classified gene: NDUFC2 as Amber List (moderate evidence)
Mendeliome v0.6142 NDUFC2 Zornitza Stark Gene: ndufc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6141 NDUFC2 Zornitza Stark gene: NDUFC2 was added
gene: NDUFC2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: NDUFC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFC2 were set to 32969598
Phenotypes for gene: NDUFC2 were set to Mitochondrial complex I deficiency, nuclear type 36, MIM# 619170
Review for gene: NDUFC2 was set to AMBER
Added comment: Mitochondrial complex I deficiency nuclear type 36 (MC1DN36) is an autosomal recessive metabolic disorder characterized by global developmental delay, hypotonia, and failure to thrive apparent from infancy or early childhood. Affected individuals usually do not acquire ambulation, show progressive spasticity, and have impaired intellectual development with absent speech. More variable features may include pale optic discs, poor eye contact, seizures, and congenital heart defects. Laboratory studies show increased serum lactate; metabolic acidosis may occur during stress or infection. Brain imaging shows T2-weighted abnormalities in the basal ganglia and brainstem, consistent with a clinical diagnosis of Leigh syndrome. Two unrelated families reported, some functional data.
Sources: Expert list
Mendeliome v0.6027 MORC2 Zornitza Stark Phenotypes for gene: MORC2 were changed from Charcot-Marie-Tooth disease, axonal, type 2Z, MIM# 616688; Intellectual disability to Charcot-Marie-Tooth disease, axonal, type 2Z, MIM# 616688; Developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy, MIM# 619090
Mendeliome v0.6026 MORC2 Zornitza Stark edited their review of gene: MORC2: Changed phenotypes: Charcot-Marie-Tooth disease, axonal, type 2Z, MIM# 616688, Developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy, MIM# 619090
Mendeliome v0.5950 SLC26A3 Zornitza Stark Marked gene: SLC26A3 as ready
Mendeliome v0.5950 SLC26A3 Zornitza Stark Gene: slc26a3 has been classified as Green List (High Evidence).
Mendeliome v0.5950 SLC26A3 Zornitza Stark Phenotypes for gene: SLC26A3 were changed from to Diarrhoea 1, secretory chloride, congenital, MIM# 214700
Mendeliome v0.5949 SLC26A3 Zornitza Stark Publications for gene: SLC26A3 were set to
Mendeliome v0.5948 SLC26A3 Zornitza Stark Mode of inheritance for gene: SLC26A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5947 SLC26A3 Zornitza Stark reviewed gene: SLC26A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 31325522, 19861545, 11524734; Phenotypes: Diarrhoea 1, secretory chloride, congenital, MIM# 214700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5882 SLC25A20 Zornitza Stark Marked gene: SLC25A20 as ready
Mendeliome v0.5882 SLC25A20 Zornitza Stark Gene: slc25a20 has been classified as Green List (High Evidence).
Mendeliome v0.5882 SLC25A20 Zornitza Stark Phenotypes for gene: SLC25A20 were changed from to Carnitine-acylcarnitine translocase deficiency, MIM# 212138
Mendeliome v0.5881 SLC25A20 Zornitza Stark Publications for gene: SLC25A20 were set to
Mendeliome v0.5880 SLC25A20 Zornitza Stark Mode of inheritance for gene: SLC25A20 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5879 SLC25A20 Zornitza Stark reviewed gene: SLC25A20: Rating: GREEN; Mode of pathogenicity: None; Publications: 15363639, 15365988, 24088670; Phenotypes: Carnitine-acylcarnitine translocase deficiency, MIM# 212138; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5758 SEC23B Zornitza Stark Phenotypes for gene: SEC23B were changed from Dyserythropoietic anemia, congenital, type II , MIM#224100 to Dyserythropoietic anemia, congenital, type II , MIM#224100; Cowden syndrome 7, MIM# 616858
Mendeliome v0.5757 SEC23B Zornitza Stark Publications for gene: SEC23B were set to 19561605; 19621418
Mendeliome v0.5756 SEC23B Zornitza Stark edited their review of gene: SEC23B: Changed phenotypes: Dyserythropoietic anemia, congenital, type II , MIM#224100, Cowden syndrome 7, MIM# 616858
Mendeliome v0.5756 SEC23B Zornitza Stark edited their review of gene: SEC23B: Changed publications: 19561605, 19621418, 26522472
Mendeliome v0.5681 SLC2A1 Zornitza Stark Marked gene: SLC2A1 as ready
Mendeliome v0.5681 SLC2A1 Zornitza Stark Gene: slc2a1 has been classified as Green List (High Evidence).
Mendeliome v0.5681 SLC2A1 Zornitza Stark Phenotypes for gene: SLC2A1 were changed from to GLUT1 deficiency syndrome 1, infantile onset, severe, MIM#606777; Dystonia 9, MIM#601042; Stomatin-deficient cryohydrocytosis with neurologic defects, MIM#608885; GLUT1 deficiency syndrome 2, childhood onset, MIM#612126; {Epilepsy, idiopathic generalized, susceptibility to, 12}, MIM#614847
Mendeliome v0.5680 SLC2A1 Zornitza Stark Publications for gene: SLC2A1 were set to
Mendeliome v0.5679 SLC2A1 Zornitza Stark Mode of inheritance for gene: SLC2A1 was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.5677 SLC2A1 Elena Savva reviewed gene: SLC2A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:18451999, 20129935, 10980529, 20221955, 31196579; Phenotypes: GLUT1 deficiency syndrome 1, infantile onset, severe, MIM#606777, Dystonia 9, MIM#601042, Stomatin-deficient cryohydrocytosis with neurologic defects, MIM#608885, GLUT1 deficiency syndrome 2, childhood onset, MIM#612126, {Epilepsy, idiopathic generalized, susceptibility to, 12}, MIM#614847; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.5254 NHLRC2 Zornitza Stark Marked gene: NHLRC2 as ready
Mendeliome v0.5254 NHLRC2 Zornitza Stark Gene: nhlrc2 has been classified as Green List (High Evidence).
Mendeliome v0.5254 NHLRC2 Zornitza Stark Phenotypes for gene: NHLRC2 were changed from to Fibrosis, neurodegeneration, and cerebral angiomatosis (FINCA) syndrome MIM#618278
Mendeliome v0.5253 NHLRC2 Zornitza Stark Publications for gene: NHLRC2 were set to
Mendeliome v0.5252 NHLRC2 Zornitza Stark Mode of inheritance for gene: NHLRC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5246 NHLRC2 Paul De Fazio reviewed gene: NHLRC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29423877, 32435055; Phenotypes: Fibrosis, neurodegeneration, and cerebral angiomatosis (FINCA) syndrome MIM#618278; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.5102 PRKACB Konstantinos Varvagiannis gene: PRKACB was added
gene: PRKACB was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRKACB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRKACB were set to 33058759
Phenotypes for gene: PRKACB were set to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability
Penetrance for gene: PRKACB were set to unknown
Mode of pathogenicity for gene: PRKACB 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: PRKACB was set to GREEN
Added comment: Palencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 3 individuals heterozygous for PRKACA and 4 individuals heterozygous for PRKACB pathogenic variants.

The most characteristic features in all individuals with PRKACA/PRKACB mutation, included postaxial polydactyly of hands (6/7 bilateral, 1/7 unilateral) and feet (4/7 bilateral, 1/7 unilateral), brachydactyly and congenital heart defects (CHD 5/7) namely a common atrium or AVSD. Two individuals with PRKACA variant who did not have CHD had offspring with the same variant and an AVSD.

Other variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. One individual with PRKACB variant presented tumors.

Intellectual disability was reported in 2/4 individuals with PRKACB variant (1/4: mild, 1/4: severe). The 3 individuals with PRKACA variant did not present ID.

As the phenotype was overall suggestive of Ellis-van Creveld syndrome (or the allelic Weyers acrofacial dysostosis), although these diagnoses were ruled out following analysis of EVC and EVC2 genes.

WES was carried out in all.

PRKACA : A single heterozygous missense variant was identified in 3 individuals from 3 families (NM_002730.4:c.409G>A / p.Gly137Arg) with 1 of the probands harboring the variant in mosaic state (28% of reads) and having 2 similarly affected offspring. The variant was de novo in one individual and inherited in a third one having a similarly affected fetus (narrow thorax, postaxial polyd, AVSD).

PRKACB : 4 different variants were identified (NM_002731.3: p.His88Arg/Asn, p.Gly235Arg, c.161C>T - p.Ser54Leu). One of the individuals was mosaic for the latter variant, while in all other cases the variant had occurred de novo.

Protein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes.

The authors provide evidence that the variants confer increased sensitivity of PKA holoenzymes to activation by cAMP (compared to wt).

By performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACA p.Gly137Arg / PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors demonstrate that inhibition of hedgehog signaling likely underlyies the developmental defects observed in affected individuals.

As for PRKACA, the authors cite another study where a 31-month old female with EvC syndrome diagnosis was found to harbor the aforementioned variant (NM_001304349.1:c.637G>A:p.Gly213Arg corresponding to NM_002730.4:c.409G>A / p.Gly137Arg) as a de novo event. Without additional evidence at the time, the variant was considered to be a candidate for this subject's phenotype (Monies et al 2019 – PMID: 31130284).
Sources: Literature
Mendeliome v0.5102 PRKACA Konstantinos Varvagiannis gene: PRKACA was added
gene: PRKACA was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRKACA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRKACA were set to 33058759; 31130284
Phenotypes for gene: PRKACA were set to Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability
Penetrance for gene: PRKACA were set to unknown
Mode of pathogenicity for gene: PRKACA 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: PRKACA was set to GREEN
Added comment: Palencia-Campos et al (2020 - PMID: 33058759) report on the phenotype of 3 individuals heterozygous for PRKACA and 4 individuals heterozygous for PRKACB pathogenic variants.

The most characteristic features in all individuals with PRKACA/PRKACB mutation, included postaxial polydactyly of hands (6/7 bilateral, 1/7 unilateral) and feet (4/7 bilateral, 1/7 unilateral), brachydactyly and congenital heart defects (CHD 5/7) namely a common atrium or AVSD. Two individuals with PRKACA variant who did not have CHD had offspring with the same variant and an AVSD.

Other variably occurring features included short stature, limbs, narrow chest, abnormal teeth, oral frenula, nail dysplasia. One individual with PRKACB variant presented tumors.

Intellectual disability was reported in 2/4 individuals with PRKACB variant (1/4: mild, 1/4: severe). The 3 individuals with PRKACA variant did not present ID.

As the phenotype was overall suggestive of Ellis-van Creveld syndrome (or the allelic Weyers acrofacial dysostosis), although these diagnoses were ruled out following analysis of EVC and EVC2 genes.

WES was carried out in all.

PRKACA : A single heterozygous missense variant was identified in 3 individuals from 3 families (NM_002730.4:c.409G>A / p.Gly137Arg) with 1 of the probands harboring the variant in mosaic state (28% of reads) and having 2 similarly affected offspring. The variant was de novo in one individual and inherited in a third one having a similarly affected fetus (narrow thorax, postaxial polyd, AVSD).

PRKACB : 4 different variants were identified (NM_002731.3: p.His88Arg/Asn, p.Gly235Arg, c.161C>T - p.Ser54Leu). One of the individuals was mosaic for the latter variant, while in all other cases the variant had occurred de novo.

Protein kinase A (PKA) is a tetrameric holoenzyme formed by the association of 2 catalytic (C) subunits with a regulatory (R) subunit dimer. Activation of PKA is achieved through binding of 2 cAMP molecules to each R-subunit, and unleashing(/dissociation) of C-subunits to engage substrates. PRKACA/B genes encode the Cα- and Cβ-subunits while the 4 functionally non-redundant regulatory subunits are encoded by PRKAR1A/1B/2A/2B genes.

The authors provide evidence that the variants confer increased sensitivity of PKA holoenzymes to activation by cAMP (compared to wt).

By performing ectopic expression of wt or mt PRKACA/B (variants studied : PRKACA p.Gly137Arg / PRKACB p.Gly235Arg) in NIH 3T3 fibroblasts, the authors demonstrate that inhibition of hedgehog signaling likely underlyies the developmental defects observed in affected individuals.

As for PRKACA, the authors cite another study where a 31-month old female with EvC syndrome diagnosis was found to harbor the aforementioned variant (NM_001304349.1:c.637G>A:p.Gly213Arg corresponding to NM_002730.4:c.409G>A / p.Gly137Arg) as a de novo event. Without additional evidence at the time, the variant was considered to be a candidate for this subject's phenotype (Monies et al 2019 – PMID: 31130284).
Sources: Literature
Mendeliome v0.4923 DYNC2LI1 Zornitza Stark Marked gene: DYNC2LI1 as ready
Mendeliome v0.4923 DYNC2LI1 Zornitza Stark Gene: dync2li1 has been classified as Green List (High Evidence).
Mendeliome v0.4923 DYNC2LI1 Zornitza Stark Phenotypes for gene: DYNC2LI1 were changed from to Short-rib thoracic dysplasia 15 with polydactyly (MIM#617088)
Mendeliome v0.4922 DYNC2LI1 Zornitza Stark Publications for gene: DYNC2LI1 were set to
Mendeliome v0.4921 DYNC2LI1 Zornitza Stark Mode of inheritance for gene: DYNC2LI1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4920 SLC20A2 Zornitza Stark Phenotypes for gene: SLC20A2 were changed from Basal ganglia calcification, idiopathic, 1, MIM# 213600 to Basal ganglia calcification, idiopathic, 1, MIM# 213600; ?hereditary multiple exostoses
Mendeliome v0.4919 SLC20A2 Zornitza Stark Publications for gene: SLC20A2 were set to 22327515; 23334463
Mendeliome v0.4917 DYNC2LI1 Ain Roesley reviewed gene: DYNC2LI1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33030252; Phenotypes: Short-rib thoracic dysplasia 15 with polydactyly (MIM#617088); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4917 SLC20A2 Elena Savva reviewed gene: SLC20A2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID 24209445, 23437308, 32705272, 27943094; Phenotypes: Basal ganglia calcification, idiopathic, 1213600, ?hereditary multiple exostoses; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.4856 SH3TC2 Zornitza Stark Marked gene: SH3TC2 as ready
Mendeliome v0.4856 SH3TC2 Zornitza Stark Gene: sh3tc2 has been classified as Green List (High Evidence).
Mendeliome v0.4856 SH3TC2 Zornitza Stark Phenotypes for gene: SH3TC2 were changed from to Charcot-Marie-Tooth disease, type 4C MIM#601596, Mononeuropathy of the median nerve, mild MIM#613353
Mendeliome v0.4855 SH3TC2 Zornitza Stark Publications for gene: SH3TC2 were set to
Mendeliome v0.4854 SH3TC2 Zornitza Stark Mode of inheritance for gene: SH3TC2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4853 SH3TC2 Zornitza Stark reviewed gene: SH3TC2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4843 SH3TC2 Elena Savva reviewed gene: SH3TC2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19744956, 20220177, 19744956, 20028792; Phenotypes: Charcot-Marie-Tooth disease, type 4C MIM#601596, Mononeuropathy of the median nerve, mild MIM#613353; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.4513 SMOC2 Zornitza Stark Marked gene: SMOC2 as ready
Mendeliome v0.4513 SMOC2 Zornitza Stark Gene: smoc2 has been classified as Green List (High Evidence).
Mendeliome v0.4513 SMOC2 Zornitza Stark Phenotypes for gene: SMOC2 were changed from to Dentin dysplasia, type I, with microdontia and misshapen teeth, MIM# 125400
Mendeliome v0.4512 SMOC2 Zornitza Stark Publications for gene: SMOC2 were set to
Mendeliome v0.4511 SMOC2 Zornitza Stark Mode of inheritance for gene: SMOC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4510 SMOC2 Zornitza Stark reviewed gene: SMOC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22152679, 23317772, 32908163; Phenotypes: Dentin dysplasia, type I, with microdontia and misshapen teeth, MIM# 125400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4449 XRCC2 Zornitza Stark Marked gene: XRCC2 as ready
Mendeliome v0.4449 XRCC2 Zornitza Stark Gene: xrcc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4449 XRCC2 Zornitza Stark Phenotypes for gene: XRCC2 were changed from to Fanconi anemia, complementation group U, MIM# 617247
Mendeliome v0.4448 XRCC2 Zornitza Stark Publications for gene: XRCC2 were set to
Mendeliome v0.4447 XRCC2 Zornitza Stark Mode of inheritance for gene: XRCC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4446 XRCC2 Zornitza Stark Classified gene: XRCC2 as Amber List (moderate evidence)
Mendeliome v0.4446 XRCC2 Zornitza Stark Gene: xrcc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4445 XRCC2 Zornitza Stark reviewed gene: XRCC2: Rating: AMBER; Mode of pathogenicity: None; Publications: 27208205, 22232082, 11118202; Phenotypes: Fanconi anemia, complementation group U, MIM# 617247; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4437 SLC25A38 Zornitza Stark Marked gene: SLC25A38 as ready
Mendeliome v0.4437 SLC25A38 Zornitza Stark Gene: slc25a38 has been classified as Green List (High Evidence).
Mendeliome v0.4437 SLC25A38 Zornitza Stark Phenotypes for gene: SLC25A38 were changed from to Anemia, sideroblastic, 2, pyridoxine-refractory, MIM# 205950
Mendeliome v0.4436 SLC25A38 Zornitza Stark Publications for gene: SLC25A38 were set to
Mendeliome v0.4435 SLC25A38 Zornitza Stark Mode of inheritance for gene: SLC25A38 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4434 SLC25A38 Zornitza Stark reviewed gene: SLC25A38: Rating: GREEN; Mode of pathogenicity: None; Publications: 19412178; Phenotypes: Anemia, sideroblastic, 2, pyridoxine-refractory, MIM# 205950; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4431 SEC23B Zornitza Stark Marked gene: SEC23B as ready
Mendeliome v0.4431 SEC23B Zornitza Stark Gene: sec23b has been classified as Green List (High Evidence).
Mendeliome v0.4431 SEC23B Zornitza Stark Phenotypes for gene: SEC23B were changed from to Dyserythropoietic anemia, congenital, type II , MIM#224100
Mendeliome v0.4430 SEC23B Zornitza Stark Publications for gene: SEC23B were set to
Mendeliome v0.4429 SEC23B Zornitza Stark Mode of inheritance for gene: SEC23B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4428 SEC23B Zornitza Stark commented on gene: SEC23B: Over 20 families reported.
Mendeliome v0.4428 SEC23B Zornitza Stark reviewed gene: SEC23B: Rating: GREEN; Mode of pathogenicity: None; Publications: 19561605, 19621418; Phenotypes: Dyserythropoietic anemia, congenital, type II , MIM#224100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4395 SLC25A46 Zornitza Stark Marked gene: SLC25A46 as ready
Mendeliome v0.4395 SLC25A46 Zornitza Stark Gene: slc25a46 has been classified as Green List (High Evidence).
Mendeliome v0.4395 SLC25A46 Zornitza Stark Phenotypes for gene: SLC25A46 were changed from to Neuropathy, hereditary motor and sensory, type VIB, MIM# 616505
Mendeliome v0.4394 SLC25A46 Zornitza Stark Publications for gene: SLC25A46 were set to
Mendeliome v0.4393 SLC25A46 Zornitza Stark Mode of inheritance for gene: SLC25A46 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.4392 SLC25A46 Zornitza Stark edited their review of gene: SLC25A46: Changed publications: 30178502, 26168012, 27543974, 27430653, 27390132, 28934388, 28558379
Mendeliome v0.4355 SHOC2 Zornitza Stark Marked gene: SHOC2 as ready
Mendeliome v0.4355 SHOC2 Zornitza Stark Gene: shoc2 has been classified as Green List (High Evidence).
Mendeliome v0.4355 SHOC2 Zornitza Stark Phenotypes for gene: SHOC2 were changed from to Noonan syndrome-like with loose anagen hair 1, MIM# 607721
Mendeliome v0.4354 SHOC2 Zornitza Stark Publications for gene: SHOC2 were set to
Mendeliome v0.4353 SHOC2 Zornitza Stark Mode of pathogenicity for gene: SHOC2 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mendeliome v0.4352 SHOC2 Zornitza Stark Mode of inheritance for gene: SHOC2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4351 SHOC2 Zornitza Stark reviewed gene: SHOC2: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 19684605, 23918763, 20882035; Phenotypes: Noonan syndrome-like with loose anagen hair 1, MIM# 607721; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4298 SLC20A2 Zornitza Stark Marked gene: SLC20A2 as ready
Mendeliome v0.4298 SLC20A2 Zornitza Stark Gene: slc20a2 has been classified as Green List (High Evidence).
Mendeliome v0.4298 SLC20A2 Zornitza Stark Phenotypes for gene: SLC20A2 were changed from to Basal ganglia calcification, idiopathic, 1, MIM# 213600
Mendeliome v0.4297 SLC20A2 Zornitza Stark Publications for gene: SLC20A2 were set to
Mendeliome v0.4296 SLC20A2 Zornitza Stark Mode of inheritance for gene: SLC20A2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4295 SLC20A2 Zornitza Stark reviewed gene: SLC20A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22327515, 23334463; Phenotypes: Basal ganglia calcification, idiopathic, 1, MIM# 213600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4275 SLC20A1 Zornitza Stark Marked gene: SLC20A1 as ready
Mendeliome v0.4275 SLC20A1 Zornitza Stark Gene: slc20a1 has been classified as Green List (High Evidence).
Mendeliome v0.4275 SLC20A1 Zornitza Stark Phenotypes for gene: SLC20A1 were changed from to Bladder-Exstrophy-Epispadias Complex (BEEC)
Mendeliome v0.4274 SLC20A1 Zornitza Stark Publications for gene: SLC20A1 were set to
Mendeliome v0.4273 SLC20A1 Zornitza Stark Mode of inheritance for gene: SLC20A1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4272 SLC20A1 Zornitza Stark reviewed gene: SLC20A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32850778, 27013921; Phenotypes: Bladder-Exstrophy-Epispadias Complex (BEEC); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.4143 TRAPPC2L Zornitza Stark Tag founder tag was added to gene: TRAPPC2L.
Mendeliome v0.4143 TRAPPC2L Zornitza Stark Marked gene: TRAPPC2L as ready
Mendeliome v0.4143 TRAPPC2L Zornitza Stark Gene: trappc2l has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4143 TRAPPC2L Zornitza Stark Classified gene: TRAPPC2L as Amber List (moderate evidence)
Mendeliome v0.4143 TRAPPC2L Zornitza Stark Gene: trappc2l has been classified as Amber List (Moderate Evidence).
Mendeliome v0.4134 TRAPPC2L Arina Puzriakova changed review comment from: Gene is associated with Encephalopathy, progressive, early-onset, with episodic rhabdomyolysis in OMIM, but not in G2P.

PMID: 30120216 (2018) - Two unrelated probands with an identical homozygous missense (c.109G>T, p.Asp37Tyr) variant in TRAPPC2L. Both individuals presented neurodevelopmental delay, febrile illness-induced encephalopathy, and episodic rhabdomyolysis, followed by developmental arrest, seizures and tetraplegia. The variant segregated with the phenotype in each family, and haplotype analysis suggested a founder effect.

The mutant protein was expressed in patient fibroblasts, but displayed membrane trafficking delays. Studies in yeast showed that the variant impaired interaction with TRAPPC10, and increased levels of the active RAB11.


PMID: 32843486 (2020) - In an Ashkenazi Jewish family with three affected sibs with GDD/ID, WGS revealed a segregating homozygous missense variant (c.5G>C, p.Ala2Gly) in the TRAPPC2L gene. No seizures, brain MRI abnormalities, or illness provoked regression were documented in this family.

Comparable to the previous study, the variant resulted in delayed ER-to-Golgi trafficking and elevated levels of active RAB11. Studies using yeast and in vitro binding, showed that the variant disrupted interaction with another core TRAPP protein, TRAPPC6a.
Sources: Literature; to: Total of three families, but two share a founder variant, and there are some disparities between the clinical presentations reported in the two publications. Rating Amber as additional cases required to delineate the genotype-phenotype relationship.

PMID: 30120216 (2018) - Two unrelated probands with an identical homozygous missense (c.109G>T, p.Asp37Tyr) variant in TRAPPC2L. Both individuals presented neurodevelopmental delay, febrile illness-induced encephalopathy, and episodic rhabdomyolysis, followed by developmental arrest, seizures and tetraplegia. The variant segregated with the phenotype in each family, and haplotype analysis suggested a founder effect.

The mutant protein was expressed in patient fibroblasts, but displayed membrane trafficking delays. Studies in yeast showed that the variant impaired interaction with TRAPPC10, and increased levels of the active RAB11.


PMID: 32843486 (2020) - In an Ashkenazi Jewish family with three affected sibs with GDD/ID, WGS revealed a segregating homozygous missense variant (c.5G>C, p.Ala2Gly) in the TRAPPC2L gene. No seizures, brain MRI abnormalities, or illness provoked regression were documented in this family.

Comparable to the previous study, the variant resulted in delayed ER-to-Golgi trafficking and elevated levels of active RAB11. Studies using yeast and in vitro binding, showed that the variant disrupted interaction with another core TRAPP protein, TRAPPC6a.

Sources: Literature
Mendeliome v0.4134 TRAPPC2L Arina Puzriakova gene: TRAPPC2L was added
gene: TRAPPC2L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TRAPPC2L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRAPPC2L were set to 30120216; 32843486
Phenotypes for gene: TRAPPC2L were set to Encephalopathy, progressive, early-onset, with episodic rhabdomyolysis, 618331
Review for gene: TRAPPC2L was set to AMBER
Added comment: Gene is associated with Encephalopathy, progressive, early-onset, with episodic rhabdomyolysis in OMIM, but not in G2P.

PMID: 30120216 (2018) - Two unrelated probands with an identical homozygous missense (c.109G>T, p.Asp37Tyr) variant in TRAPPC2L. Both individuals presented neurodevelopmental delay, febrile illness-induced encephalopathy, and episodic rhabdomyolysis, followed by developmental arrest, seizures and tetraplegia. The variant segregated with the phenotype in each family, and haplotype analysis suggested a founder effect.

The mutant protein was expressed in patient fibroblasts, but displayed membrane trafficking delays. Studies in yeast showed that the variant impaired interaction with TRAPPC10, and increased levels of the active RAB11.


PMID: 32843486 (2020) - In an Ashkenazi Jewish family with three affected sibs with GDD/ID, WGS revealed a segregating homozygous missense variant (c.5G>C, p.Ala2Gly) in the TRAPPC2L gene. No seizures, brain MRI abnormalities, or illness provoked regression were documented in this family.

Comparable to the previous study, the variant resulted in delayed ER-to-Golgi trafficking and elevated levels of active RAB11. Studies using yeast and in vitro binding, showed that the variant disrupted interaction with another core TRAPP protein, TRAPPC6a.
Sources: Literature
Mendeliome v0.4091 ZFYVE19 Arina Puzriakova gene: ZFYVE19 was added
gene: ZFYVE19 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZFYVE19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZFYVE19 were set to 32737136
Phenotypes for gene: ZFYVE19 were set to Cholestasis
Review for gene: ZFYVE19 was set to GREEN
Added comment: PMID: 32737136 (2020) - Nine Han Chinese children from seven families with biallelic, predicted complete LoF variants in ZFYVE19. All patients had high-GGT intrahepatic cholestasis, portal hypertension, and histopathological features of the ductal plate malformation/congenital hepatic fibrosis.

ZFYVE19 depletion in cultured cells from one patient yielded centriolar and axonemal abnormalities, and immunostaining for two ciliary proteins DCDC2 and ACALT showed abnormal localisation in patient cholangiocytes, indicating this as a novel ciliopathy disorder.
Sources: Literature
Mendeliome v0.3732 FAM50A Zornitza Stark gene: FAM50A was added
gene: FAM50A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FAM50A 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: FAM50A were set to 32703943
Phenotypes for gene: FAM50A were set to Mental retardation syndrome, X-linked, Armfield type (MIM #300261)
Review for gene: FAM50A was set to GREEN
Added comment: Lee et al (2020 - PMID: 32703943) provide evidence that Armfield X-Linked intellectual disability syndrome is caused by monoallelic FAM50A pathogenic variants. The current review is based only on this reference. The authors provide clinical details on 6 affected individuals from 5 families. Features included postnatal growth delay, DD and ID (6/6 - also evident for those without formal IQ assesment), seizures (3/6 from 2 families), prominent forehead with presence of other facial features and variable head circumference (5th to >97th %le), ocular anomalies (5/6 - strabismus/nystagmus/Axenfeld-Rieger), cardiac (3/6 - ASD/Fallot) and genitourinary anomalies (3/6). In the first of these families (Armfield et al 1999 - PMID: 10398235), linkage analysis followed by additional studies (Sanger, NGS of 718 genes on chrX, X-exome NGS - several refs provided) allowed the identification of a FAM50A variant. Variants in other families were identified by singleton (1 fam) or trio-ES (3 fam). In affected individuals from 3 families, the variant had occurred de novo. Carrier females in the other families were unaffected (based on pedigrees and/or the original publication). XCI was rather biased in most obligate carrier females from the 1st family (although this ranged from 95:5 to 60:40). Missense variants were reported in all affected subjects incl. Trp206Gly, Asp255Gly, Asp255Asn (dn), Glu254Gly (dn), Arg273Trp (dn) (NM_004699.3). Previous studies have demonstrated that FAM50A has ubiquitous expression in human fetal and adult tissues (incl. brain in fetal ones). Immunostaining suggests a nuclear localization for the protein (NIH/3T3 cells). Comparison of protein levels in LCLs from affected males and controls did not demonstrate significant differences. Protein localization for 3 variants (transfection of COS-7 cells) was shown to be similar to wt. Complementation studies in zebrafish provided evidence that the identified variants confer partial loss of function (rescue of the morpholino phenotype with co-injection of wt but not mt mRNA). The zebrafish ko model seemed to recapitulate the abnormal development of cephalic structures and was indicative of diminished/defective neurogenesis. Transcriptional dysregulation was demonstrated in zebrafish (altered levels and mis-splicing). Upregulation of spliceosome effectors was demonstrated in ko zebrafish. Similarly, mRNA expression and splicing defects were demonstrated in LCLs from affected individuals. FAM50A pulldown followed by mass spectrometry in transfected HEK293T cells demonstrated enrichment of binding proteins involved in RNA processing and co-immunoprecipitation assays (transfected U-87 cells) suggested that FAM50A interacts with spliceosome U5 and C-complex proteins. Overall aberrant spliceosome C-complex function is suggested as the underlying pathogenetic mechanism. Several other neurodevelopmental syndromes are caused by variants in genes encoding C-complex affiliated proteins (incl. EFTUD2, EIF4A3, THOC2, etc.).
Sources: Literature
Mendeliome v0.3727 SEC24D Zornitza Stark Marked gene: SEC24D as ready
Mendeliome v0.3727 SEC24D Zornitza Stark Gene: sec24d has been classified as Green List (High Evidence).
Mendeliome v0.3727 SEC24D Zornitza Stark Phenotypes for gene: SEC24D were changed from to Cole-Carpenter syndrome 2, MIM# 616294
Mendeliome v0.3726 SEC24D Zornitza Stark Publications for gene: SEC24D were set to
Mendeliome v0.3725 SEC24D Zornitza Stark Mode of inheritance for gene: SEC24D was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3724 SEC24D Zornitza Stark reviewed gene: SEC24D: Rating: GREEN; Mode of pathogenicity: None; Publications: 30462379, 27942778, 26467156, 25683121; Phenotypes: Cole-Carpenter syndrome 2, MIM# 616294; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3693 SLC25A10 Zornitza Stark Phenotypes for gene: SLC25A10 were changed from Intractable epileptic encephalopathy to Intractable epileptic encephalopathy; Mitochondrial DNA depletion syndrome 19, MIM# 618972
Mendeliome v0.3692 SLC25A10 Zornitza Stark edited their review of gene: SLC25A10: Changed phenotypes: Intractable epileptic encephalopathy, Mitochondrial DNA depletion syndrome 19, MIM# 618972
Mendeliome v0.3663 MORC2 Zornitza Stark Phenotypes for gene: MORC2 were changed from Charcot-Marie-Tooth disease, axonal, type 2Z, MIM# 616688; Intellectual disability to Charcot-Marie-Tooth disease, axonal, type 2Z, MIM# 616688; Intellectual disability
Mendeliome v0.3657 MORC2 Dean Phelan reviewed gene: MORC2: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 32693025; Phenotypes: Spinal muscular atrophy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3513 MORC2 Zornitza Stark Marked gene: MORC2 as ready
Mendeliome v0.3513 MORC2 Zornitza Stark Gene: morc2 has been classified as Green List (High Evidence).
Mendeliome v0.3513 MORC2 Zornitza Stark Phenotypes for gene: MORC2 were changed from to Charcot-Marie-Tooth disease, axonal, type 2Z, MIM# 616688; Intellectual disability
Mendeliome v0.3512 MORC2 Zornitza Stark Publications for gene: MORC2 were set to
Mendeliome v0.3511 MORC2 Zornitza Stark Mode of inheritance for gene: MORC2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3510 MORC2 Zornitza Stark reviewed gene: MORC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32693025, 26497905, 26659848; Phenotypes: Charcot-Marie-Tooth disease, axonal, type 2Z, MIM# 616688, Intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.3464 SEC23A Zornitza Stark Marked gene: SEC23A as ready
Mendeliome v0.3464 SEC23A Zornitza Stark Gene: sec23a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3464 SEC23A Zornitza Stark Phenotypes for gene: SEC23A were changed from to Craniolenticulosutural dysplasia (MIM# 607812)
Mendeliome v0.3463 SEC23A Zornitza Stark Publications for gene: SEC23A were set to
Mendeliome v0.3462 SEC23A Zornitza Stark Mode of inheritance for gene: SEC23A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3461 SEC23A Zornitza Stark Classified gene: SEC23A as Amber List (moderate evidence)
Mendeliome v0.3461 SEC23A Zornitza Stark Gene: sec23a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3444 SEC23A Paul De Fazio reviewed gene: SEC23A: Rating: AMBER; Mode of pathogenicity: None; Publications: 16980979, 21039434, 16980978, 27148587; Phenotypes: Craniolenticulosutural dysplasia (MIM# 607812); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.3325 TBC1D2B Zornitza Stark gene: TBC1D2B was added
gene: TBC1D2B was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: TBC1D2B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBC1D2B were set to 32623794
Phenotypes for gene: TBC1D2B were set to Global developmental delay; Intellectual disability; Seizures; Gingival overgrowth; Behavioral abnormality; Abnormality of the mandible; Abnormality of brain morphology; Abnormality of the eye; Hearing abnormality
Review for gene: TBC1D2B was set to GREEN
Added comment: Harms et al (2020 - PMID: 32623794) report on 3 unrelated individuals with biallelic pLoF TBC1D2B variants. Features included cognitive impairment (mild ID in one case, regression at the age of 12y in another, hypotonia and delayed milestones in a third aged 8m), seizures (3/3 - variable age of onset) and/or gingival overgrowth (2/3 - prior to initiation of AEDs). Other findings included behavioral abnormalities, mandibular anomalies, abnormal brain imaging and ophthalmologic or (rarely) audiometric evaluations. All were born to non-consanguineous couples and additional investigations were performed in some. Variants were identified by WES or trio WGS, with Sanger confirmation/compatible segregation analyses. In line with the pLoF variants, mRNA studies in fibroblasts from 2 unrelated affected individuals demonstrated significantly reduced (~80-90%) TBC1C2D mRNA levels compared to controls, restored following cycloheximide treatment. Protein was absent in patient fibroblasts. TBC-domain containing GTPase activating proteins are known as key regulators of RAB GTPase activity. TBC1D2B was shown to colocalize with RAB5-positive endocytic vesicles. CRISPR/Cas9-mediated ko of TBC1D2B in HeLa cells suggested a role in EGF receptor endocytosis and decreased cell viability of TBC1D2B-deficient HeLa cells upon serum deprivation. Genes encoding other TBC domain-containg GTPase-activating proteins, e.g. TBC1D7 and TBC1D20, TBC1D24 are associated with recessive neurodevelopmental disorders (with ID and/or seizures) and the pathophysiological defect in TBC1D2B-related disorder (deficit in vesicle trafficking and/or cell survival) is proposed to be similar to that of TBC1D24.
Sources: Expert Review
Mendeliome v0.3324 EXOC2 Zornitza Stark Marked gene: EXOC2 as ready
Mendeliome v0.3324 EXOC2 Zornitza Stark Gene: exoc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3324 EXOC2 Zornitza Stark Classified gene: EXOC2 as Amber List (moderate evidence)
Mendeliome v0.3324 EXOC2 Zornitza Stark Gene: exoc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.3323 EXOC2 Zornitza Stark gene: EXOC2 was added
gene: EXOC2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: EXOC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOC2 were set to 32639540
Phenotypes for gene: EXOC2 were set to Global developmental delay; Intellectual disability; Abnormality of the face; Abnormality of brain morphology
Review for gene: EXOC2 was set to AMBER
Added comment: Van Bergen et al (2020 - PMID: 32639540) report on 3 individuals from 2 families, harboring biallelic EXOC2 mutations. Clinical presentation included DD, ID (severe in 2 subjects from fam1, borderline intellectual functioning in fam2), dysmorphic features and brain abnormalities. Cerebellar anomalies were common to all with a molar tooth sign observed in one (1/3). Other findings limited to subjects from one family included acquired microcephaly, congenital contractures, spastic quadriplegia (each observed 2/3). Previous investigations were in all cases non-diagnostic. WES identified biallelic EXOC2 mutations in all affected individuals. EXOC2 encodes an exocyst subunit. The latter is an octameric complex, component of the membrane transport machinery, required for tethering and fusion of vesicles at the plasma membrane. As discussed ,vesicle transport is important for the development of brain and the function of neurons and glia. Exocyst function is also important for delivery of Arl13b to the primary cilium (biallelic ARL13B mutations cause Joubert syndrome 8) and ciliogenesis. Affected subjects from a broader consanguineous family (fam1) were homozygous for a truncating variant. Fibroblast studies revealed mRNA levels compatible with NMD (further restored in presence of CHX) as well as reduced protein levels. The female belonging to the second non-consanguineous family was found to harbor 2 missense variants in trans configuration. An exocytosis defect was demonstrated in fibroblasts from individuals belonging to both families. Ciliogenesis appeared to be normal, however Arl13b localization/recruitment to the cilia was reduced compared with control cells with the defect rescued upon exogenous expression of wt EXOC2. Mutations in other genes encoding components of the exocyst complex have been previously reported in individuals with relevant phenotypes (e.g. EXOC8 in a boy with features of Joubert s. or EXOC4 in nephrotic syndrome). The authors discuss on the essential role of EXOC2 based on model organism studies (e.g. impaired neuronal membrane traffic, failure of neuronal polarization and neuromuscular junction expansion seen in Drosophila Sec5 (EXOC2) null mutants).
Sources: Expert Review
Mendeliome v0.3317 HERC2 Zornitza Stark Marked gene: HERC2 as ready
Mendeliome v0.3317 HERC2 Zornitza Stark Gene: herc2 has been classified as Green List (High Evidence).
Mendeliome v0.3317 HERC2 Zornitza Stark Phenotypes for gene: HERC2 were changed from to Mental retardation, autosomal recessive 38 (MIM 615516)
Mendeliome v0.3316 HERC2 Zornitza Stark Publications for gene: HERC2 were set to
Mendeliome v0.3315 HERC2 Zornitza Stark Mode of inheritance for gene: HERC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3314 HERC2 Zornitza Stark reviewed gene: HERC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23065719, 23243086, 30902390, 32571899, 27848944, 26077850, 27759030; Phenotypes: Mental retardation, autosomal recessive 38 (MIM 615516); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3143 TANC2 Zornitza Stark Phenotypes for gene: TANC2 were changed from Intellectual disability; autism; epilepsy; dysmorphism to Intellectual disability; autism; epilepsy; dysmorphism; Intellectual developmental disorder with autistic features and language delay, with or without seizures, MIM# 618906
Mendeliome v0.3142 TANC2 Zornitza Stark edited their review of gene: TANC2: Changed phenotypes: Intellectual disability, autism, epilepsy, dysmorphism, Intellectual developmental disorder with autistic features and language delay, with or without seizures, MIM# 618906
Mendeliome v0.2747 TTC25 Zornitza Stark Marked gene: TTC25 as ready
Mendeliome v0.2747 TTC25 Zornitza Stark Gene: ttc25 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2747 TTC25 Zornitza Stark Phenotypes for gene: TTC25 were changed from to Ciliary dyskinesia, primary, 35 (MIM#617092)
Mendeliome v0.2746 TTC25 Zornitza Stark Publications for gene: TTC25 were set to
Mendeliome v0.2745 TTC25 Zornitza Stark Mode of inheritance for gene: TTC25 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2744 TTC25 Zornitza Stark Classified gene: TTC25 as Amber List (moderate evidence)
Mendeliome v0.2744 TTC25 Zornitza Stark Gene: ttc25 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2743 TTC25 Zornitza Stark reviewed gene: TTC25: Rating: AMBER; Mode of pathogenicity: None; Publications: 27486780; Phenotypes: Ciliary dyskinesia, primary, 35 (MIM#617092); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2730 CCDC28B Zornitza Stark Classified gene: CCDC28B as Amber List (moderate evidence)
Mendeliome v0.2730 CCDC28B Zornitza Stark Gene: ccdc28b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2729 CCDC28B Zornitza Stark edited their review of gene: CCDC28B: Added comment: PMID: 32139166 - Single family with Joubert syndrome. Patient was homozygous for a missense, with polydactyly, severe ID, and the molar tooth sign observed in MRI. Sibling fetus MRI showed vermis hypoplasia, and was also homozygous for the variant. Parents confirmed unaffected carriers. Knockdown of CCDC28B in human TERT retinal pigment epithelial cells reduced both the number and length of cilia 430C-T variant is postulated to be a modifier of BBS.; Changed rating: AMBER; Changed publications: 32139166; Changed phenotypes: {Bardet-Biedl syndrome 1, modifier of}, MIM#209900, Joubert syndrome
Mendeliome v0.2729 C21orf59 Zornitza Stark Marked gene: C21orf59 as ready
Mendeliome v0.2729 C21orf59 Zornitza Stark Gene: c21orf59 has been classified as Green List (High Evidence).
Mendeliome v0.2729 C21orf59 Zornitza Stark Tag founder tag was added to gene: C21orf59.
Mendeliome v0.2706 C21orf59 Zornitza Stark Marked gene: C21orf59 as ready
Mendeliome v0.2706 C21orf59 Zornitza Stark Gene: c21orf59 has been classified as Green List (High Evidence).
Mendeliome v0.2706 C21orf59 Zornitza Stark Phenotypes for gene: C21orf59 were changed from to Ciliary dyskinesia, primary, 26, MIM# 615500
Mendeliome v0.2705 C21orf59 Zornitza Stark Publications for gene: C21orf59 were set to
Mendeliome v0.2704 C21orf59 Zornitza Stark Mode of inheritance for gene: C21orf59 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2703 C21orf59 Zornitza Stark Tag new gene name tag was added to gene: C21orf59.
Mendeliome v0.2703 C21orf59 Zornitza Stark reviewed gene: C21orf59: Rating: GREEN; Mode of pathogenicity: None; Publications: 24094744; Phenotypes: Ciliary dyskinesia, primary, 26, MIM# 615500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2607 FOXF2 Hazel Phillimore changed review comment from: Homozygous missense, NM_001452.1: c.325A>T (p.I109F), in a 10 year old girl (consanguineous, parents were first cousins) with profound sensorineural hearing loss (SNHL) associated with incomplete partition type I anomaly of the cochlea. This variant is absent in the gnomAD v2.1.1. In vitro studies indicated instability, shorter half-life of the protein compared to wildtype. Embryonic knockout mouse showed shortened and malformed cochleae, in addition to altered shape of hair cells with innervation and planar cell polarity defects. Homozygous knockout mice do not survive. (Bademci, G. et al. (2019); PMID: 30561639).
This gene has also been reported in association with other anomalies including cleft lip, cleft palate, brain anomalies, intestine anomalies, and eye anomalies. Eye anomalies include anterior segment dysgenesis, as shown in mice with variant, W174R, affecting the Fox domain. Homozygote mice do not survive. (McKeone, R. et al. (2011); PMID: 22022403).
Sources: Literature; to: Homozygous missense, NM_001452.1: c.325A>T (p.I109F), in a 10 year old girl (consanguineous, parents were first cousins) with profound sensorineural hearing loss (SNHL) associated with incomplete partition type I anomaly of the cochlea. This variant is absent in the gnomAD v2.1.1. In vitro studies indicated instability, shorter half-life of the protein compared to wildtype. Embryonic knockout mouse showed shortened and malformed cochleae, in addition to altered shape of hair cells with innervation and planar cell polarity defects. Homozygous knockout mice do not survive. (Bademci, G. et al. (2019); PMID: 30561639).
This gene has also been reported in association with other anomalies including cleft lip, cleft palate, brain anomalies, intestine anomalies, and eye anomalies. Eye anomalies include anterior segment dysgenesis, as shown in mice with variant, W174R, affecting the Fox domain. Homozygote mice do not survive. (McKeone, R. et al. (2011); PMID: 22022403).
Previous names for FOXF2 include FKHL6 and FREAC2.
Sources: Literature
Mendeliome v0.2589 KLC2 Zornitza Stark Marked gene: KLC2 as ready
Mendeliome v0.2589 KLC2 Zornitza Stark Gene: klc2 has been classified as Green List (High Evidence).
Mendeliome v0.2589 KLC2 Zornitza Stark Tag SV/CNV tag was added to gene: KLC2.
Mendeliome v0.2589 KLC2 Zornitza Stark Classified gene: KLC2 as Green List (high evidence)
Mendeliome v0.2589 KLC2 Zornitza Stark Gene: klc2 has been classified as Green List (High Evidence).
Mendeliome v0.2588 KLC2 Zornitza Stark gene: KLC2 was added
gene: KLC2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: KLC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KLC2 were set to 26385635
Phenotypes for gene: KLC2 were set to Spastic paraplegia, optic atrophy, and neuropathy MIM#609541
Review for gene: KLC2 was set to GREEN
Added comment: In 73 Brazilian patients and 2 sibs of Egyptian descent with SPOAN, a homozygous 216-bp deletion in the noncoding upstream region of the KLC2 gene was identified. Only reported cause of condition is the upstream large deletion, which is not detected by whole-exome sequencing.
Sources: Expert Review
Mendeliome v0.2222 SLC26A4 Zornitza Stark Marked gene: SLC26A4 as ready
Mendeliome v0.2222 SLC26A4 Zornitza Stark Gene: slc26a4 has been classified as Green List (High Evidence).
Mendeliome v0.2222 SLC26A4 Zornitza Stark Phenotypes for gene: SLC26A4 were changed from to Deafness, autosomal recessive 4, with enlarged vestibular aqueduct 600791; Pendred syndrome 274600
Mendeliome v0.2221 SLC26A4 Zornitza Stark Publications for gene: SLC26A4 were set to
Mendeliome v0.2220 SLC26A4 Zornitza Stark Mode of inheritance for gene: SLC26A4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.2200 TMTC2 Zornitza Stark Marked gene: TMTC2 as ready
Mendeliome v0.2200 TMTC2 Zornitza Stark Gene: tmtc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.2200 TMTC2 Zornitza Stark Phenotypes for gene: TMTC2 were changed from to Deafness
Mendeliome v0.2199 TMTC2 Zornitza Stark Publications for gene: TMTC2 were set to
Mendeliome v0.2195 TMTC2 Zornitza Stark Mode of inheritance for gene: TMTC2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.2194 TMTC2 Zornitza Stark Classified gene: TMTC2 as Amber List (moderate evidence)
Mendeliome v0.2194 TMTC2 Zornitza Stark Gene: tmtc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1824 SLC25A21 Zornitza Stark Marked gene: SLC25A21 as ready
Mendeliome v0.1824 SLC25A21 Zornitza Stark Gene: slc25a21 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1824 SLC25A21 Zornitza Stark Classified gene: SLC25A21 as Amber List (moderate evidence)
Mendeliome v0.1824 SLC25A21 Zornitza Stark Gene: slc25a21 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1823 SLC25A21 Zornitza Stark gene: SLC25A21 was added
gene: SLC25A21 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: SLC25A21 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A21 were set to 29517768
Phenotypes for gene: SLC25A21 were set to Mitochondrial DNA depletion syndrome-18, MIM#618811
Review for gene: SLC25A21 was set to AMBER
Added comment: One case with a homozygous variant and functional assays showing mitochondrial dysfunction.
Sources: NHS GMS
Mendeliome v0.1822 SLC25A10 Zornitza Stark Marked gene: SLC25A10 as ready
Mendeliome v0.1822 SLC25A10 Zornitza Stark Gene: slc25a10 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1822 SLC25A10 Zornitza Stark Classified gene: SLC25A10 as Amber List (moderate evidence)
Mendeliome v0.1822 SLC25A10 Zornitza Stark Gene: slc25a10 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1821 SLC25A10 Zornitza Stark gene: SLC25A10 was added
gene: SLC25A10 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: SLC25A10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A10 were set to 29211846
Phenotypes for gene: SLC25A10 were set to Intractable epileptic encephalopathy
Review for gene: SLC25A10 was set to AMBER
Added comment: One case with intractable epileptic encephalopathy with complex I deficiency, with biallelic variants. Yeast SLC25A10 ortholog lack-of-function causes impairment in mitochondrial respiration, reduced mtDNA copy number and oxidative stress vulnerability.
Sources: NHS GMS
Mendeliome v0.1761 UQCRC2 Zornitza Stark Marked gene: UQCRC2 as ready
Mendeliome v0.1761 UQCRC2 Zornitza Stark Gene: uqcrc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1761 UQCRC2 Zornitza Stark Phenotypes for gene: UQCRC2 were changed from to Mitochondrial complex III deficiency, nuclear type 5, MIM# 615160
Mendeliome v0.1760 UQCRC2 Zornitza Stark Publications for gene: UQCRC2 were set to
Mendeliome v0.1759 UQCRC2 Zornitza Stark Mode of inheritance for gene: UQCRC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1758 UQCRC2 Zornitza Stark Classified gene: UQCRC2 as Amber List (moderate evidence)
Mendeliome v0.1758 UQCRC2 Zornitza Stark Gene: uqcrc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.1757 UQCRC2 Zornitza Stark reviewed gene: UQCRC2: Rating: AMBER; Mode of pathogenicity: None; Publications: 28275242, 23281071; Phenotypes: Mitochondrial complex III deficiency, nuclear type 5, MIM# 615160; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1745 SLC25A32 Zornitza Stark Marked gene: SLC25A32 as ready
Mendeliome v0.1745 SLC25A32 Zornitza Stark Gene: slc25a32 has been classified as Green List (High Evidence).
Mendeliome v0.1745 SLC25A32 Zornitza Stark Classified gene: SLC25A32 as Green List (high evidence)
Mendeliome v0.1745 SLC25A32 Zornitza Stark Gene: slc25a32 has been classified as Green List (High Evidence).
Mendeliome v0.1744 SLC25A32 Zornitza Stark gene: SLC25A32 was added
gene: SLC25A32 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SLC25A32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A32 were set to 26933868; 28443623
Phenotypes for gene: SLC25A32 were set to Exercise intolerance, riboflavin-responsive, MIM# 616839
Review for gene: SLC25A32 was set to GREEN
Added comment: Two unrelated families reported with functional data. Muscle biopsy showed ragged-red fibers and lipid storage mainly in type I oxidative fibers, small type II fibers, and poor immunostaining for succinate dehydrogenase (FAD-dependent mitochondrial respiratory chain complex II). Oral supplementation with riboflavin led to dramatic improvement in the clinical and biologic abnormalities.
Sources: Expert list
Mendeliome v0.1635 SLC26A4 Elena Savva reviewed gene: SLC26A4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 24599119; Phenotypes: Deafness, autosomal recessive 4, with enlarged vestibular aqueduct 600791, Pendred syndrome 274600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1278 IQSEC2 Zornitza Stark Marked gene: IQSEC2 as ready
Mendeliome v0.1278 IQSEC2 Zornitza Stark Gene: iqsec2 has been classified as Green List (High Evidence).
Mendeliome v0.1278 IQSEC2 Zornitza Stark Publications for gene: IQSEC2 were set to
Mendeliome v0.1277 IQSEC2 Zornitza Stark Phenotypes for gene: IQSEC2 were changed from to Mental retardation, X-linked 1/78, MIM#309530
Mendeliome v0.1276 IQSEC2 Zornitza Stark Mode of pathogenicity for gene: IQSEC2 was changed from to Other
Mendeliome v0.1275 IQSEC2 Zornitza Stark Mode of inheritance for gene: IQSEC2 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.1274 IQSEC2 Elena Savva reviewed gene: IQSEC2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 31415821, 20473311, 30842726; Phenotypes: Mental retardation, X-linked 1/78; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes
Mendeliome v0.1001 ATP6V1C2 Zornitza Stark Marked gene: ATP6V1C2 as ready
Mendeliome v0.1001 ATP6V1C2 Zornitza Stark Gene: atp6v1c2 has been classified as Red List (Low Evidence).
Mendeliome v0.1001 ATP6V1C2 Zornitza Stark gene: ATP6V1C2 was added
gene: ATP6V1C2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATP6V1C2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP6V1C2 were set to 31959358
Phenotypes for gene: ATP6V1C2 were set to Distal renal tubular acidosis
Review for gene: ATP6V1C2 was set to RED
Added comment: Single family reported, limited functional data.
Sources: Literature
Mendeliome v0.980 CLIC2 Zornitza Stark Marked gene: CLIC2 as ready
Mendeliome v0.980 CLIC2 Zornitza Stark Gene: clic2 has been classified as Red List (Low Evidence).
Mendeliome v0.980 CLIC2 Zornitza Stark Mode of inheritance for gene: CLIC2 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.979 CLIC2 Zornitza Stark Phenotypes for gene: CLIC2 were changed from to Mental retardation, X-linked, syndromic 32, 300886
Mendeliome v0.978 CLIC2 Zornitza Stark Publications for gene: CLIC2 were set to
Mendeliome v0.977 CLIC2 Zornitza Stark Classified gene: CLIC2 as Red List (low evidence)
Mendeliome v0.977 CLIC2 Zornitza Stark Gene: clic2 has been classified as Red List (Low Evidence).
Mendeliome v0.976 CLIC2 Zornitza Stark reviewed gene: CLIC2: Rating: RED; Mode of pathogenicity: None; Publications: 22814392, 25927380; Phenotypes: Mental retardation, X-linked, syndromic 32, 300886; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.903 PIK3C2A Zornitza Stark Marked gene: PIK3C2A as ready
Mendeliome v0.903 PIK3C2A Zornitza Stark Gene: pik3c2a has been classified as Green List (High Evidence).
Mendeliome v0.903 PIK3C2A Zornitza Stark Mode of inheritance for gene: PIK3C2A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.902 PIK3C2A Zornitza Stark Classified gene: PIK3C2A as Green List (high evidence)
Mendeliome v0.902 PIK3C2A Zornitza Stark Gene: pik3c2a has been classified as Green List (High Evidence).
Mendeliome v0.901 PIK3C2A Zornitza Stark gene: PIK3C2A was added
gene: PIK3C2A was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: PIK3C2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PIK3C2A were set to 31034465
Phenotypes for gene: PIK3C2A were set to Oculoskeletodental syndrome, MIM# 618440
Review for gene: PIK3C2A was set to GREEN
gene: PIK3C2A was marked as current diagnostic
Added comment: Three unrelated consanguineous families reported.
Sources: Expert list
Mendeliome v0.848 Sebastian Lunke removed gene:DSC2 from the panel
Mendeliome v0.808 BNC2 Zornitza Stark Marked gene: BNC2 as ready
Mendeliome v0.808 BNC2 Zornitza Stark Gene: bnc2 has been classified as Green List (High Evidence).
Mendeliome v0.808 BNC2 Zornitza Stark Classified gene: BNC2 as Green List (high evidence)
Mendeliome v0.808 BNC2 Zornitza Stark Gene: bnc2 has been classified as Green List (High Evidence).
Mendeliome v0.807 BNC2 Zornitza Stark gene: BNC2 was added
gene: BNC2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: BNC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BNC2 were set to 31656805; 31051115
Phenotypes for gene: BNC2 were set to Lower urinary tract obstruction, congenital; OMIM #618612
Review for gene: BNC2 was set to GREEN
gene: BNC2 was marked as current diagnostic
Added comment: At least four unrelated families reported.
Sources: Expert list
Mendeliome v0.678 SLC2A8 Zornitza Stark Marked gene: SLC2A8 as ready
Mendeliome v0.678 SLC2A8 Zornitza Stark Gene: slc2a8 has been classified as Red List (Low Evidence).
Mendeliome v0.678 SLC2A8 Zornitza Stark Classified gene: SLC2A8 as Red List (low evidence)
Mendeliome v0.678 SLC2A8 Zornitza Stark Gene: slc2a8 has been classified as Red List (Low Evidence).
Mendeliome v0.643 RUSC2 Zornitza Stark Marked gene: RUSC2 as ready
Mendeliome v0.643 RUSC2 Zornitza Stark Gene: rusc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.643 RUSC2 Zornitza Stark Phenotypes for gene: RUSC2 were changed from to Mental retardation, autosomal recessive 61, MIM# 617773
Mendeliome v0.642 RUSC2 Zornitza Stark Publications for gene: RUSC2 were set to
Mendeliome v0.641 RUSC2 Zornitza Stark Mode of inheritance for gene: RUSC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.640 RUSC2 Zornitza Stark Classified gene: RUSC2 as Amber List (moderate evidence)
Mendeliome v0.640 RUSC2 Zornitza Stark Gene: rusc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.639 RUSC2 Zornitza Stark reviewed gene: RUSC2: Rating: AMBER; Mode of pathogenicity: None; Publications: 27612186; Phenotypes: Mental retardation, autosomal recessive 61, MIM# 617773; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.524 SLC26A5 Zornitza Stark Marked gene: SLC26A5 as ready
Mendeliome v0.524 SLC26A5 Zornitza Stark Gene: slc26a5 has been classified as Red List (Low Evidence).
Mendeliome v0.524 SLC26A5 Zornitza Stark Phenotypes for gene: SLC26A5 were changed from to Deafness, autosomal recessive 61, MIM# 613865
Mendeliome v0.523 SLC26A5 Zornitza Stark Publications for gene: SLC26A5 were set to
Mendeliome v0.522 SLC26A5 Zornitza Stark Mode of inheritance for gene: SLC26A5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.521 SLC26A5 Zornitza Stark Classified gene: SLC26A5 as Red List (low evidence)
Mendeliome v0.521 SLC26A5 Zornitza Stark Gene: slc26a5 has been classified as Red List (Low Evidence).
Mendeliome v0.520 SLC26A5 Zornitza Stark reviewed gene: SLC26A5: Rating: RED; Mode of pathogenicity: None; Publications: 24164807; Phenotypes: Deafness, autosomal recessive 61, MIM# 613865; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.444 CCDC28B Zornitza Stark Marked gene: CCDC28B as ready
Mendeliome v0.444 CCDC28B Zornitza Stark Gene: ccdc28b has been classified as Red List (Low Evidence).
Mendeliome v0.444 CCDC28B Zornitza Stark Mode of inheritance for gene: CCDC28B was changed from Unknown to Other
Mendeliome v0.443 CCDC28B Zornitza Stark Phenotypes for gene: CCDC28B were changed from to {Bardet-Biedl syndrome 1, modifier of}, MIM#209900
Mendeliome v0.442 CCDC28B Zornitza Stark Classified gene: CCDC28B as Red List (low evidence)
Mendeliome v0.442 CCDC28B Zornitza Stark Gene: ccdc28b has been classified as Red List (Low Evidence).
Mendeliome v0.441 CCDC28B Zornitza Stark reviewed gene: CCDC28B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Bardet-Biedl syndrome 1, modifier of}, MIM#209900; Mode of inheritance: Other
Mendeliome v0.325 TANC2 Zornitza Stark Marked gene: TANC2 as ready
Mendeliome v0.325 TANC2 Zornitza Stark Gene: tanc2 has been classified as Green List (High Evidence).
Mendeliome v0.325 TANC2 Zornitza Stark Classified gene: TANC2 as Green List (high evidence)
Mendeliome v0.325 TANC2 Zornitza Stark Gene: tanc2 has been classified as Green List (High Evidence).
Mendeliome v0.324 TANC2 Zornitza Stark gene: TANC2 was added
gene: TANC2 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: TANC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TANC2 were set to 31616000
Phenotypes for gene: TANC2 were set to Intellectual disability; autism; epilepsy; dysmorphism
Review for gene: TANC2 was set to GREEN
Added comment: 19 families with potentially disruptive heterozygous TANC2 variants, including 16 likely gene-disrupting mutations and three intragenic microdeletions. Patients presented with autism, intellectual disability, delayed language and motor development, epilepsy, facial dysmorphism, with complex psychiatric dysfunction or behavioral problems in adult probands or carrier parents. No functional evidence of specific variants, but they show TANC2 is expressed broadly in the human developing brain, especially in excitatory neurons and glial cells, and shows a more restricted pattern in Drosophila glial cells where its disruption affects behavioral outcomes.
Sources: Literature
Mendeliome v0.238 SMARCC2 Zornitza Stark Marked gene: SMARCC2 as ready
Mendeliome v0.238 SMARCC2 Zornitza Stark Gene: smarcc2 has been classified as Green List (High Evidence).
Mendeliome v0.238 SMARCC2 Zornitza Stark Classified gene: SMARCC2 as Green List (high evidence)
Mendeliome v0.238 SMARCC2 Zornitza Stark Gene: smarcc2 has been classified as Green List (High Evidence).
Mendeliome v0.237 SMARCC2 Zornitza Stark gene: SMARCC2 was added
gene: SMARCC2 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: SMARCC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMARCC2 were set to 30580808
Phenotypes for gene: SMARCC2 were set to Coffin-Siris syndrome 8; OMIM #618362
Review for gene: SMARCC2 was set to GREEN
Added comment: 15 individuals with variable degrees of neurodevelopmental delay, growth retardation, prominent speech impairment, hypotonia, feeding difficulties, behavioral abnormalities, and dysmorphic features.
Sources: Literature
Mendeliome v0.225 APC2 Zornitza Stark Marked gene: APC2 as ready
Mendeliome v0.225 APC2 Zornitza Stark Gene: apc2 has been classified as Green List (High Evidence).
Mendeliome v0.225 APC2 Zornitza Stark Classified gene: APC2 as Green List (high evidence)
Mendeliome v0.225 APC2 Zornitza Stark Gene: apc2 has been classified as Green List (High Evidence).
Mendeliome v0.224 APC2 Zornitza Stark gene: APC2 was added
gene: APC2 was added to Mendeliome_VCGS. Sources: Literature
Mode of inheritance for gene: APC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: APC2 were set to 31585108
Phenotypes for gene: APC2 were set to Cortical dysplasia, complex, with other brain malformations 10, MIM#618677
Review for gene: APC2 was set to GREEN
Added comment: 12 individuals from 8 unrelated families; intellectual disability, seizures, cortical dysplasia including posterior to anterior predominant pattern of lissencephaly, heterotopias, paucity of white matter, thin corpus callosum.
Sources: Literature
Mendeliome v0.145 EXOSC2 Zornitza Stark Marked gene: EXOSC2 as ready
Mendeliome v0.145 EXOSC2 Zornitza Stark Gene: exosc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.145 EXOSC2 Zornitza Stark Phenotypes for gene: EXOSC2 were changed from to Short stature, hearing loss, retinitis pigmentosa, and distinctive facies, MIM# 617763
Mendeliome v0.144 EXOSC2 Zornitza Stark Publications for gene: EXOSC2 were set to
Mendeliome v0.143 EXOSC2 Zornitza Stark Mode of inheritance for gene: EXOSC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.142 EXOSC2 Zornitza Stark Classified gene: EXOSC2 as Amber List (moderate evidence)
Mendeliome v0.142 EXOSC2 Zornitza Stark Gene: exosc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.51 SLC27A5 Zornitza Stark Marked gene: SLC27A5 as ready
Mendeliome v0.51 SLC27A5 Zornitza Stark Gene: slc27a5 has been classified as Red List (Low Evidence).
Mendeliome v0.51 SLC27A5 Zornitza Stark Classified gene: SLC27A5 as Red List (low evidence)
Mendeliome v0.51 SLC27A5 Zornitza Stark Gene: slc27a5 has been classified as Red List (Low Evidence).
Mendeliome v0.37 G6PC2 Zornitza Stark Marked gene: G6PC2 as ready
Mendeliome v0.37 G6PC2 Zornitza Stark Gene: g6pc2 has been classified as Red List (Low Evidence).
Mendeliome v0.37 G6PC2 Zornitza Stark Classified gene: G6PC2 as Red List (low evidence)
Mendeliome v0.37 G6PC2 Zornitza Stark Gene: g6pc2 has been classified as Red List (Low Evidence).
Mendeliome v0.36 G6PC2 Zornitza Stark reviewed gene: G6PC2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mendeliome v0.0 ZIC2 Zornitza Stark gene: ZIC2 was added
gene: ZIC2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ZIC2 was set to Unknown
Mendeliome v0.0 XRCC2 Zornitza Stark gene: XRCC2 was added
gene: XRCC2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: XRCC2 was set to Unknown
Mendeliome v0.0 UQCRC2 Zornitza Stark gene: UQCRC2 was added
gene: UQCRC2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: UQCRC2 was set to Unknown
Mendeliome v0.0 UQCC2 Zornitza Stark gene: UQCC2 was added
gene: UQCC2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: UQCC2 was set to Unknown
Mendeliome v0.0 TTC25 Zornitza Stark gene: TTC25 was added
gene: TTC25 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TTC25 was set to Unknown
Mendeliome v0.0 TTC21B Zornitza Stark gene: TTC21B was added
gene: TTC21B was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TTC21B was set to Unknown
Mendeliome v0.0 TRAPPC2 Zornitza Stark gene: TRAPPC2 was added
gene: TRAPPC2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TRAPPC2 was set to Unknown
Mendeliome v0.0 TMTC2 Zornitza Stark gene: TMTC2 was added
gene: TMTC2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: TMTC2 was set to Unknown
Mendeliome v0.0 THOC2 Zornitza Stark gene: THOC2 was added
gene: THOC2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: THOC2 was set to Unknown
Mendeliome v0.0 SPTLC2 Zornitza Stark gene: SPTLC2 was added
gene: SPTLC2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SPTLC2 was set to Unknown
Mendeliome v0.0 SMOC2 Zornitza Stark gene: SMOC2 was added
gene: SMOC2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SMOC2 was set to Unknown
Mendeliome v0.0 SLC2A9 Zornitza Stark gene: SLC2A9 was added
gene: SLC2A9 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC2A9 was set to Unknown
Mendeliome v0.0 SLC2A8 Zornitza Stark gene: SLC2A8 was added
gene: SLC2A8 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC2A8 was set to Unknown
Mendeliome v0.0 SLC2A4RG Zornitza Stark gene: SLC2A4RG was added
gene: SLC2A4RG was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC2A4RG was set to Unknown
Mendeliome v0.0 SLC2A4 Zornitza Stark gene: SLC2A4 was added
gene: SLC2A4 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC2A4 was set to Unknown
Mendeliome v0.0 SLC2A3 Zornitza Stark gene: SLC2A3 was added
gene: SLC2A3 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC2A3 was set to Unknown
Mendeliome v0.0 SLC2A2 Zornitza Stark gene: SLC2A2 was added
gene: SLC2A2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC2A2 was set to Unknown
Mendeliome v0.0 SLC2A10 Zornitza Stark gene: SLC2A10 was added
gene: SLC2A10 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC2A10 was set to Unknown
Mendeliome v0.0 SLC2A1 Zornitza Stark gene: SLC2A1 was added
gene: SLC2A1 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC2A1 was set to Unknown
Mendeliome v0.0 SLC29A3 Zornitza Stark gene: SLC29A3 was added
gene: SLC29A3 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC29A3 was set to Unknown
Mendeliome v0.0 SLC27A5 Zornitza Stark gene: SLC27A5 was added
gene: SLC27A5 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC27A5 was set to Unknown
Mendeliome v0.0 SLC27A4 Zornitza Stark gene: SLC27A4 was added
gene: SLC27A4 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC27A4 was set to Unknown
Mendeliome v0.0 SLC26A8 Zornitza Stark gene: SLC26A8 was added
gene: SLC26A8 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC26A8 was set to Unknown
Mendeliome v0.0 SLC26A5 Zornitza Stark gene: SLC26A5 was added
gene: SLC26A5 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC26A5 was set to Unknown
Mendeliome v0.0 SLC26A4 Zornitza Stark gene: SLC26A4 was added
gene: SLC26A4 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC26A4 was set to Unknown
Mendeliome v0.0 SLC26A3 Zornitza Stark gene: SLC26A3 was added
gene: SLC26A3 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC26A3 was set to Unknown
Mendeliome v0.0 SLC26A2 Zornitza Stark gene: SLC26A2 was added
gene: SLC26A2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC26A2 was set to Unknown
Mendeliome v0.0 SLC26A1 Zornitza Stark gene: SLC26A1 was added
gene: SLC26A1 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC26A1 was set to Unknown
Mendeliome v0.0 SLC25A46 Zornitza Stark gene: SLC25A46 was added
gene: SLC25A46 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC25A46 was set to Unknown
Mendeliome v0.0 SLC25A42 Zornitza Stark gene: SLC25A42 was added
gene: SLC25A42 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC25A42 was set to Unknown
Mendeliome v0.0 SLC25A4 Zornitza Stark gene: SLC25A4 was added
gene: SLC25A4 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC25A4 was set to Unknown
Mendeliome v0.0 SLC25A38 Zornitza Stark gene: SLC25A38 was added
gene: SLC25A38 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC25A38 was set to Unknown
Mendeliome v0.0 SLC25A3 Zornitza Stark gene: SLC25A3 was added
gene: SLC25A3 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC25A3 was set to Unknown
Mendeliome v0.0 SLC25A26 Zornitza Stark gene: SLC25A26 was added
gene: SLC25A26 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC25A26 was set to Unknown
Mendeliome v0.0 SLC25A24 Zornitza Stark gene: SLC25A24 was added
gene: SLC25A24 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC25A24 was set to Unknown
Mendeliome v0.0 SLC25A22 Zornitza Stark gene: SLC25A22 was added
gene: SLC25A22 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC25A22 was set to Unknown
Mendeliome v0.0 SLC25A20 Zornitza Stark gene: SLC25A20 was added
gene: SLC25A20 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC25A20 was set to Unknown
Mendeliome v0.0 SLC25A19 Zornitza Stark gene: SLC25A19 was added
gene: SLC25A19 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC25A19 was set to Unknown
Mendeliome v0.0 SLC25A15 Zornitza Stark gene: SLC25A15 was added
gene: SLC25A15 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC25A15 was set to Unknown
Mendeliome v0.0 SLC25A13 Zornitza Stark gene: SLC25A13 was added
gene: SLC25A13 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC25A13 was set to Unknown
Mendeliome v0.0 SLC25A12 Zornitza Stark gene: SLC25A12 was added
gene: SLC25A12 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC25A12 was set to Unknown
Mendeliome v0.0 SLC25A1 Zornitza Stark gene: SLC25A1 was added
gene: SLC25A1 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC25A1 was set to Unknown
Mendeliome v0.0 SLC24A5 Zornitza Stark gene: SLC24A5 was added
gene: SLC24A5 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC24A5 was set to Unknown
Mendeliome v0.0 SLC24A4 Zornitza Stark gene: SLC24A4 was added
gene: SLC24A4 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC24A4 was set to Unknown
Mendeliome v0.0 SLC24A1 Zornitza Stark gene: SLC24A1 was added
gene: SLC24A1 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC24A1 was set to Unknown
Mendeliome v0.0 SLC22A5 Zornitza Stark gene: SLC22A5 was added
gene: SLC22A5 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC22A5 was set to Unknown
Mendeliome v0.0 SLC22A4 Zornitza Stark gene: SLC22A4 was added
gene: SLC22A4 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC22A4 was set to Unknown
Mendeliome v0.0 SLC22A12 Zornitza Stark gene: SLC22A12 was added
gene: SLC22A12 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC22A12 was set to Unknown
Mendeliome v0.0 SLC20A2 Zornitza Stark gene: SLC20A2 was added
gene: SLC20A2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC20A2 was set to Unknown
Mendeliome v0.0 SLC20A1 Zornitza Stark gene: SLC20A1 was added
gene: SLC20A1 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SLC20A1 was set to Unknown
Mendeliome v0.0 SHOC2 Zornitza Stark gene: SHOC2 was added
gene: SHOC2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SHOC2 was set to Unknown
Mendeliome v0.0 SH3TC2 Zornitza Stark gene: SH3TC2 was added
gene: SH3TC2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SH3TC2 was set to Unknown
Mendeliome v0.0 SEC24D Zornitza Stark gene: SEC24D was added
gene: SEC24D was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SEC24D was set to Unknown
Mendeliome v0.0 SEC23B Zornitza Stark gene: SEC23B was added
gene: SEC23B was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SEC23B was set to Unknown
Mendeliome v0.0 SEC23A Zornitza Stark gene: SEC23A was added
gene: SEC23A was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: SEC23A was set to Unknown
Mendeliome v0.0 RUSC2 Zornitza Stark gene: RUSC2 was added
gene: RUSC2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: RUSC2 was set to Unknown
Mendeliome v0.0 RFC2 Zornitza Stark gene: RFC2 was added
gene: RFC2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: RFC2 was set to Unknown
Mendeliome v0.0 RAC2 Zornitza Stark gene: RAC2 was added
gene: RAC2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: RAC2 was set to Unknown
Mendeliome v0.0 PSMC2 Zornitza Stark gene: PSMC2 was added
gene: PSMC2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PSMC2 was set to Unknown
Mendeliome v0.0 C2orf71 Zornitza Stark gene: C2orf71 was added
gene: C2orf71 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: C2orf71 was set to Unknown
Mendeliome v0.0 NT5C2 Zornitza Stark gene: NT5C2 was added
gene: NT5C2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: NT5C2 was set to Unknown
Mendeliome v0.0 NR3C2 Zornitza Stark gene: NR3C2 was added
gene: NR3C2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: NR3C2 was set to Unknown
Mendeliome v0.0 NHLRC2 Zornitza Stark gene: NHLRC2 was added
gene: NHLRC2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: NHLRC2 was set to Unknown
Mendeliome v0.0 MORC2 Zornitza Stark gene: MORC2 was added
gene: MORC2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MORC2 was set to Unknown
Mendeliome v0.0 MCCC2 Zornitza Stark gene: MCCC2 was added
gene: MCCC2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MCCC2 was set to Unknown
Mendeliome v0.0 MC2R Zornitza Stark gene: MC2R was added
gene: MC2R was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: MC2R was set to Unknown
Mendeliome v0.0 LAMC2 Zornitza Stark gene: LAMC2 was added
gene: LAMC2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: LAMC2 was set to Unknown
Mendeliome v0.0 IQSEC2 Zornitza Stark gene: IQSEC2 was added
gene: IQSEC2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: IQSEC2 was set to Unknown
Mendeliome v0.0 HERC2 Zornitza Stark gene: HERC2 was added
gene: HERC2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: HERC2 was set to Unknown
Mendeliome v0.0 GJC2 Zornitza Stark gene: GJC2 was added
gene: GJC2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: GJC2 was set to Unknown
Mendeliome v0.0 G6PC2 Zornitza Stark gene: G6PC2 was added
gene: G6PC2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: G6PC2 was set to Unknown
Mendeliome v0.0 FOXC2 Zornitza Stark gene: FOXC2 was added
gene: FOXC2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: FOXC2 was set to Unknown
Mendeliome v0.0 EXOSC2 Zornitza Stark gene: EXOSC2 was added
gene: EXOSC2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: EXOSC2 was set to Unknown
Mendeliome v0.0 EVC2 Zornitza Stark gene: EVC2 was added
gene: EVC2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: EVC2 was set to Unknown
Mendeliome v0.0 ERCC2 Zornitza Stark gene: ERCC2 was added
gene: ERCC2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ERCC2 was set to Unknown
Mendeliome v0.0 ELAC2 Zornitza Stark gene: ELAC2 was added
gene: ELAC2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ELAC2 was set to Unknown
Mendeliome v0.0 DYNC2LI1 Zornitza Stark gene: DYNC2LI1 was added
gene: DYNC2LI1 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: DYNC2LI1 was set to Unknown
Mendeliome v0.0 DYNC2H1 Zornitza Stark gene: DYNC2H1 was added
gene: DYNC2H1 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: DYNC2H1 was set to Unknown
Mendeliome v0.0 DSC2 Zornitza Stark gene: DSC2 was added
gene: DSC2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: DSC2 was set to Unknown
Mendeliome v0.0 DNAJC21 Zornitza Stark gene: DNAJC21 was added
gene: DNAJC21 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: DNAJC21 was set to Unknown
Mendeliome v0.0 DCDC2 Zornitza Stark gene: DCDC2 was added
gene: DCDC2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: DCDC2 was set to Unknown
Mendeliome v0.0 CWC27 Zornitza Stark gene: CWC27 was added
gene: CWC27 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CWC27 was set to Unknown
Mendeliome v0.0 CLIC2 Zornitza Stark gene: CLIC2 was added
gene: CLIC2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CLIC2 was set to Unknown
Mendeliome v0.0 C21orf2 Zornitza Stark gene: C21orf2 was added
gene: C21orf2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: C21orf2 was set to Unknown
Mendeliome v0.0 C21orf59 Zornitza Stark gene: C21orf59 was added
gene: C21orf59 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: C21orf59 was set to Unknown
Mendeliome v0.0 CCDC28B Zornitza Stark gene: CCDC28B was added
gene: CCDC28B was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CCDC28B was set to Unknown
Mendeliome v0.0 CCDC22 Zornitza Stark gene: CCDC22 was added
gene: CCDC22 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CCDC22 was set to Unknown
Mendeliome v0.0 CC2D2A Zornitza Stark gene: CC2D2A was added
gene: CC2D2A was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CC2D2A was set to Unknown
Mendeliome v0.0 CC2D1A Zornitza Stark gene: CC2D1A was added
gene: CC2D1A was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: CC2D1A was set to Unknown
Mendeliome v0.0 C2CD3 Zornitza Stark gene: C2CD3 was added
gene: C2CD3 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: C2CD3 was set to Unknown
Mendeliome v0.0 C2 Zornitza Stark gene: C2 was added
gene: C2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: C2 was set to Unknown
Mendeliome v0.0 APOC4-APOC2 Zornitza Stark gene: APOC4-APOC2 was added
gene: APOC4-APOC2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: APOC4-APOC2 was set to Unknown
Mendeliome v0.0 APOC2 Zornitza Stark gene: APOC2 was added
gene: APOC2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: APOC2 was set to Unknown
Mendeliome v0.0 AKR1C2 Zornitza Stark gene: AKR1C2 was added
gene: AKR1C2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: AKR1C2 was set to Unknown
Mendeliome v0.0 ABCC2 Zornitza Stark gene: ABCC2 was added
gene: ABCC2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: ABCC2 was set to Unknown