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Mendeliome v0.10959 ZFYVE26 Zornitza Stark Phenotypes for gene: ZFYVE26 were changed from to Spastic paraplegia 15, autosomal recessive MIM#270700
Mendeliome v0.10958 ZFYVE26 Zornitza Stark Publications for gene: ZFYVE26 were set to
Mendeliome v0.10957 ZFYVE26 Zornitza Stark Mode of inheritance for gene: ZFYVE26 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3424 SURF1 Zornitza Stark Marked gene: SURF1 as ready
Fetal anomalies v0.3424 SURF1 Zornitza Stark Gene: surf1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3424 SURF1 Zornitza Stark Phenotypes for gene: SURF1 were changed from LEIGH SYNDROME; COMPLEX IV DEFICIENCY to Mitochondrial complex IV deficiency, nuclear type 1 (MIM#220110)
Fetal anomalies v0.3423 SURF1 Zornitza Stark Publications for gene: SURF1 were set to
Fetal anomalies v0.3422 ZDHHC9 Zornitza Stark Marked gene: ZDHHC9 as ready
Fetal anomalies v0.3422 ZDHHC9 Zornitza Stark Gene: zdhhc9 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3422 ZDHHC9 Zornitza Stark Phenotypes for gene: ZDHHC9 were changed from MENTAL RETARDATION SYNDROMIC X-LINKED ZDHHC9-RELATED to Mental retardation, X-linked syndromic, Raymond type, MIM# 300799
Fetal anomalies v0.3421 ZDHHC9 Zornitza Stark Classified gene: ZDHHC9 as Amber List (moderate evidence)
Fetal anomalies v0.3421 ZDHHC9 Zornitza Stark Gene: zdhhc9 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3420 ZDHHC9 Zornitza Stark reviewed gene: ZDHHC9: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, X-linked syndromic, Raymond type, MIM# 300799; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.10956 ZDHHC9 Zornitza Stark Marked gene: ZDHHC9 as ready
Mendeliome v0.10956 ZDHHC9 Zornitza Stark Gene: zdhhc9 has been classified as Green List (High Evidence).
Mendeliome v0.10956 ZDHHC9 Zornitza Stark Phenotypes for gene: ZDHHC9 were changed from to Mental retardation, X-linked syndromic, Raymond type MIM# 300799
Mendeliome v0.10955 ZDHHC9 Zornitza Stark Publications for gene: ZDHHC9 were set to
Mendeliome v0.10954 ZDHHC9 Zornitza Stark Mode of inheritance for gene: ZDHHC9 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v0.3420 STXBP1 Zornitza Stark Marked gene: STXBP1 as ready
Fetal anomalies v0.3420 STXBP1 Zornitza Stark Gene: stxbp1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3420 STXBP1 Zornitza Stark Phenotypes for gene: STXBP1 were changed from ANGELMAN/PITT HOPKINS SYNDROME-LIKE DISORDER; EPILEPTIC ENCEPHALOPATHY EARLY INFANTILE TYPE 4 to Developmental and epileptic encephalopathy 4 (MIM#612164)
Fetal anomalies v0.3419 STXBP1 Zornitza Stark Publications for gene: STXBP1 were set to
Fetal anomalies v0.3418 STXBP1 Zornitza Stark Mode of inheritance for gene: STXBP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.3417 STXBP1 Zornitza Stark reviewed gene: STXBP1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 4 (MIM#612164); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.3417 XPC Zornitza Stark Marked gene: XPC as ready
Fetal anomalies v0.3417 XPC Zornitza Stark Gene: xpc has been classified as Red List (Low Evidence).
Fetal anomalies v0.3417 XPC Zornitza Stark Phenotypes for gene: XPC were changed from XERODERMA PIGMENTOSUM, GROUP C to Xeroderma pigmentosum, group C, MIM# 278720; MONDO:0010211
Fetal anomalies v0.3416 XPC Zornitza Stark Publications for gene: XPC were set to
Fetal anomalies v0.3415 WDR45 Zornitza Stark Marked gene: WDR45 as ready
Fetal anomalies v0.3415 WDR45 Zornitza Stark Gene: wdr45 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3415 WDR45 Zornitza Stark Phenotypes for gene: WDR45 were changed from NEURODEGENERATION WITH BRAIN IRON ACCUMULATION to Neurodegeneration with brain iron accumulation 5, MIM# 300894; Rett syndrome; Rett-like phenotypes
Fetal anomalies v0.3414 WDR45 Zornitza Stark Publications for gene: WDR45 were set to
Fetal anomalies v0.3413 COQ7 Krithika Murali gene: COQ7 was added
gene: COQ7 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: COQ7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COQ7 were set to 33215859; 28125198; 31240163; 28409910; 26084283
Phenotypes for gene: COQ7 were set to Coenzyme Q10 deficiency, primary, 8 - MIM#616733
Review for gene: COQ7 was set to GREEN
Added comment: Biallelic variants associated with primary coenzyme Q10 (CoQ10) deficiency, a heterogeneous multi-system disorder including early-postnatal features such as neonatal encephalopathy, contractures. Antenatal features reported include IUGR, oligohydramnios, feetal lung hypoplasia, dysplastic kidneys.

Specifically for COQ7-related CoQ10 deficiency:

PMID 33215859 Hashemi et al 2020 - report two affected individuals from a consanguineous Iranian family with homozygous COQ7 variants progressive spastic paraparesis diagnosed at age 1.5-2 with normal antenatal history.

PMID 31240163 Kwong et al 2019 - report a patient with compound hetereozygous COQ7 variants, encephalo‐myo‐nephro‐cardiopathy, persistent lactic acidosis, and basal ganglia lesions resulting in early infantile death. Skin fibroblast studies showed decreased combined complex II + III activity and reduction in CoQ10 level. The proband was a DCDA twin, noted to have IUGR, oligohydramnios, cardiomegaly and tricuspid regurgitation antenatally.

PMID 28409910 Wang et al 2017 - no antenatal features reported in their proband

PMID 26084283 Freyer et al 2015 - report x1 patient with homozygous COQ7 variant. The pregnancy was complicated by oligohydramniosis, fetal lung hypoplasia and growth retardation.
Sources: Literature
Pulmonary Fibrosis_Interstitial Lung Disease v0.41 TMEM173 Zornitza Stark Publications for gene: TMEM173 were set to 27613991; 32398023
Fetal anomalies v0.3413 SPTBN5 Zornitza Stark Marked gene: SPTBN5 as ready
Fetal anomalies v0.3413 SPTBN5 Zornitza Stark Gene: sptbn5 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3413 SPTBN5 Zornitza Stark Mode of inheritance for gene: SPTBN5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3412 SPTBN2 Zornitza Stark Marked gene: SPTBN2 as ready
Fetal anomalies v0.3412 SPTBN2 Zornitza Stark Gene: sptbn2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3412 SPTBN2 Zornitza Stark Phenotypes for gene: SPTBN2 were changed from Infantile ataxia with oculomotor and pyramidal signs; SCA14; Spinocerebellar ataxia, autosomal recessive 14, 615386 to Spinocerebellar ataxia 5 (MIM#600224); Spinocerebellar ataxia, autosomal recessive 14 (MIM#615386)
Fetal anomalies v0.3411 SPTBN2 Zornitza Stark Publications for gene: SPTBN2 were set to 28636205; 29196973
Fetal anomalies v0.3410 SPTBN2 Zornitza Stark Mode of inheritance for gene: SPTBN2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.3409 SMARCAL1 Zornitza Stark Marked gene: SMARCAL1 as ready
Fetal anomalies v0.3409 SMARCAL1 Zornitza Stark Gene: smarcal1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3409 SMARCAL1 Zornitza Stark Phenotypes for gene: SMARCAL1 were changed from SCHIMKE IMMUNOOSSEOUS DYSPLASIA to Schimke immunoosseous dysplasia (MIM#242900)
Fetal anomalies v0.3408 SMARCAL1 Zornitza Stark Publications for gene: SMARCAL1 were set to
Fetal anomalies v0.3407 SMARCAL1 Zornitza Stark Classified gene: SMARCAL1 as Green List (high evidence)
Fetal anomalies v0.3407 SMARCAL1 Zornitza Stark Gene: smarcal1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3406 SP110 Zornitza Stark Marked gene: SP110 as ready
Fetal anomalies v0.3406 SP110 Zornitza Stark Gene: sp110 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3406 SP110 Zornitza Stark Publications for gene: SP110 were set to
Fetal anomalies v0.3405 SLC6A8 Zornitza Stark Marked gene: SLC6A8 as ready
Fetal anomalies v0.3405 SLC6A8 Zornitza Stark Gene: slc6a8 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3405 SLC6A8 Zornitza Stark Phenotypes for gene: SLC6A8 were changed from X-LINKED CREATINE DEFICIENCY SYNDROME to Cerebral creatine deficiency syndrome 1 (MIM#300352)
Fetal anomalies v0.3404 SLC6A8 Zornitza Stark Publications for gene: SLC6A8 were set to
Fetal anomalies v0.3403 SLC6A8 Zornitza Stark Classified gene: SLC6A8 as Amber List (moderate evidence)
Fetal anomalies v0.3403 SLC6A8 Zornitza Stark Gene: slc6a8 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3402 SLC52A3 Zornitza Stark Marked gene: SLC52A3 as ready
Fetal anomalies v0.3402 SLC52A3 Zornitza Stark Gene: slc52a3 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3402 SLC52A3 Zornitza Stark Phenotypes for gene: SLC52A3 were changed from BROWN-VIALETTO-VAN LAERE SYNDROME to Brown-Vialetto-Van Laere syndrome 1 (MIM#211530)
Fetal anomalies v0.3401 SLC52A3 Zornitza Stark Publications for gene: SLC52A3 were set to
Fetal anomalies v0.3400 CDX2 Krithika Murali gene: CDX2 was added
gene: CDX2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CDX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDX2 were set to 29177441
Phenotypes for gene: CDX2 were set to Persistent cloaca
Review for gene: CDX2 was set to AMBER
Added comment: De novo heterozygous variants detected in 2 patients with persistent cloaca. This condition. can rarely be detected antenatally.
Sources: Literature
Fetal anomalies v0.3400 TLK2 Krithika Murali gene: TLK2 was added
gene: TLK2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: TLK2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: TLK2 were set to 29861108; 31558842; 34821460
Phenotypes for gene: TLK2 were set to Intellectual developmental disorder, autosomal dominant 57 - MIM#618050
Review for gene: TLK2 was set to GREEN
Added comment: Associated with syndromic ID. Potential to detect reported phenotypic features of microcephaly, IUGR, craniosynostosis (rare) antenatally.
Sources: Literature
Fetal anomalies v0.3400 STAT3 Krithika Murali gene: STAT3 was added
gene: STAT3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: STAT3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: STAT3 were set to 30617622; 31771449; 34366294
Phenotypes for gene: STAT3 were set to Hyper-IgE recurrent infection syndrome - MIM#147060; Autoimmune disease, multisystem, infantile-onset, 1 - MIM#615952
Added comment: Well known association with Hyper IgE syndrome and multisystem autoimmune disease. Early post-natal diagnosis reported. Prenatally detectable features include craniosynostosis and IUGR.

31771449 Terry et al 2020 report a baby with a de novo heterozygous likely pathogenic STAT3 variant. Severe IUGR and oligohydramnios was noted on USS at 21 weeks gestation.
Sources: Literature
Fetal anomalies v0.3400 RNU12 Krithika Murali gene: RNU12 was added
gene: RNU12 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: RNU12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNU12 were set to 34085356
Phenotypes for gene: RNU12 were set to CDAGS syndrome MIM#603116; Craniosynostosis, Delayed closure of the fontanelles, cranial defects, clavicular hypoplasia, Anal and Genitourinary malformations, and Skin manifestations
Review for gene: RNU12 was set to GREEN
Added comment: No new publications since last PanelApp review July 2021

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5 CDAGS syndrome families with biallelic variants all including NC_000022.10:g.43011402C>T and another variant on the second allele. Whole transcriptome sequencing analysis of patient lymphoblastoid cells identified differentially expressed genes, and differential alternative splicing analysis indicated there was an enrichment of alternative splicing events.
Sources: Literature
Fetal anomalies v0.3400 PJA1 Krithika Murali gene: PJA1 was added
gene: PJA1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PJA1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PJA1 were set to 32530565
Phenotypes for gene: PJA1 were set to Trigonocephaly, intellectual disability
Review for gene: PJA1 was set to AMBER
Added comment: No new publications since last PanelApp review August 2020

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Recurrent variant, p.Arg376Cys, reported in 7 Japanese individuals, supportive mouse model. Individuals shared a common haplotype, suggestive of founder effect.
Sources: Literature
Fetal anomalies v0.3400 PHEX Krithika Murali gene: PHEX was added
gene: PHEX was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PHEX 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: PHEX were set to 29791829; 16055933; 19219621; 9106524
Phenotypes for gene: PHEX were set to Hypophosphatemic rickets, X-linked dominant - MIM#307800
Review for gene: PHEX was set to GREEN
Added comment: Well-known association with hypophosphataemic rickets with some phenotypic features potentially detectable antenatally (skeletal, craniosynostosis). Early therapeutic interventions available.
Sources: Literature
Fetal anomalies v0.3400 LTBP1 Krithika Murali gene: LTBP1 was added
gene: LTBP1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: LTBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LTBP1 were set to 33991472
Phenotypes for gene: LTBP1 were set to Cutis laxa, autosomal recessive, type IIE - MIM#619451
Review for gene: LTBP1 was set to GREEN
Added comment: Homozygous premature truncating LTBP1 variants in eight affected individuals from four unrelated consanguineous families reported associated with autosomal recessive cutis laxa type IIE. Phenotypic features relevant in the prenatal setting include:
- Congenital diaphragmatic hernia (1 individual)
- Cleft palate (2 individuals)
- Congenital heart defects
- Renal anomalies (1 individual)
- Microretrognathia (1 individual)
- Hydrocephalus (1 individual)
- Skeletal anomalies (craniosynostosis, short stature, brachydactyly, and syndactyly).

Supportive patient-derived fibroblast and zebrafish studies.
Sources: Literature
Fetal anomalies v0.3400 EFNA4 Krithika Murali gene: EFNA4 was added
gene: EFNA4 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: EFNA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EFNA4 were set to 29215649; 29168297; 16540516
Phenotypes for gene: EFNA4 were set to Craniosynostosis
Review for gene: EFNA4 was set to AMBER
Added comment: PMID 29215649 Lee et al 2018 - Cohort of 309 individuals with craniosynostosis tested with a 20-gene panel. Report 1 individual with unicoronal CS with a likely pathogenic EFNA4 variant.

PMID 29168297 Clarke et al 2018 - Study enrolled 397 probands with single suture CS. Report one maternally inherited EFNA4 VUS NM_005227.2:c.550C>T; p.(Leu184Phe) with metopic CS, x1 het in gnomad (v2), variant predicted to escape NMD, not reported in ClinVar/Decipher.

PMID 16540516 Merrill et al 2006 - Tested 81 patients with non-syndromic coronal CS. 3 heterozygous EFNA4 variants detected - x2 missense variants:
- c.178C>T p.H60Y -- 361 hets gnomad
- c.349 C>A p.P117T - 337 hets
- novel frameshift delin 471_472delCCinsA.

All 3 variants inherited from unaffected parent. Functional studies on fibroblast cells from the proband with the frameshift delin variant demonstrated an alternatively spliced minor isoform of EFNA4.
Sources: Literature
Fetal anomalies v0.3400 DHH Belinda Chong edited their review of gene: DHH: Changed rating: RED
Fetal anomalies v0.3400 DHH Belinda Chong reviewed gene: DHH: Rating: ; Mode of pathogenicity: None; Publications: 31018998, 29471294, 11017805; Phenotypes: 46XY gonadal dysgenesis with minifascicular neuropathy MIM#607080; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3400 DEPDC5 Belinda Chong reviewed gene: DEPDC5: Rating: RED; Mode of pathogenicity: None; Publications: 23542697, 23542701, 24814846, 24585383, 26505888, 27173016, 31444548; Phenotypes: Epilepsy, familial focal, with variable foci 1 MIM#604364; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Fetal anomalies v0.3400 DDHD2 Belinda Chong reviewed gene: DDHD2: Rating: RED; Mode of pathogenicity: None; Publications: 23486545, 24482476, 23176823, 31302745; Phenotypes: Spastic paraplegia 54, autosomal recessive, MIM# 615033, MONDO:0014018; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3400 DDHD1 Belinda Chong reviewed gene: DDHD1: Rating: RED; Mode of pathogenicity: None; Publications: 23176821; Phenotypes: Spastic paraplegia 28, autosomal recessive, 609340, MONDO:0012256; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3400 DDC Belinda Chong reviewed gene: DDC: Rating: RED; Mode of pathogenicity: None; Publications: 20505134, 33528536, 30799092, 33996177; Phenotypes: Aromatic L-amino acid decarboxylase deficiency MIM#608643; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3400 DDB2 Belinda Chong reviewed gene: DDB2: Rating: RED; Mode of pathogenicity: None; Publications: 33544716, 32457468, 32239545, 32228487; Phenotypes: Xeroderma pigmentosum, group E, DDB-negative subtype MIM#278740; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3400 FUZ Ain Roesley reviewed gene: FUZ: Rating: RED; Mode of pathogenicity: None; Publications: 21840926; Phenotypes: {Neural tube defects, susceptibility to} MIM#182940; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.10953 FUZ Ain Roesley gene: FUZ was added
gene: FUZ was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FUZ was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FUZ were set to 21840926
Phenotypes for gene: FUZ were set to {Neural tube defects, susceptibility to} MIM#182940
Penetrance for gene: FUZ were set to unknown
Review for gene: FUZ was set to RED
gene: FUZ was marked as current diagnostic
Added comment: Spina bifida cohort. Negative for VANGL1 and VANGL2, only FUZ was sequenced.
Variants identified in 5 individuals.
Arg404Gln (39 hets in gnomAD) and Asp354Tyr (6 hets in gnomAD). These variants are listed as risk factor in ClinVar
Pro39Ser (absent in gnomAD) was de novo by parental sanger and showed reduced cell mobility on scratch assays.

2 other variants Gly140Glu and Ser142Thr were deemed non-causative due to poor in silicos and conservation

Finally, hom KO mouse models were done to prove neural tube defects
Sources: Literature
Fetal anomalies v0.3400 DBT Belinda Chong reviewed gene: DBT: Rating: RED; Mode of pathogenicity: None; Publications: 9239422, 10915611, 20570198; Phenotypes: Maple syrup urine disease, type II (MIM#248600); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3400 DARS2 Belinda Chong edited their review of gene: DARS2: Set current diagnostic: yes
Fetal anomalies v0.3400 DARS2 Belinda Chong reviewed gene: DARS2: Rating: RED; Mode of pathogenicity: None; Publications: 17384640, 15002045, 16788019, 30352563; Phenotypes: Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, MIM# 611105; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3400 TTC19 Daniel Flanagan reviewed gene: TTC19: Rating: RED; Mode of pathogenicity: None; Publications: 23532514, 24368687; Phenotypes: Mitochondrial complex III deficiency, nuclear type 2 (MIM#615157); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3400 CYP19A1 Belinda Chong reviewed gene: CYP19A1: Rating: RED; Mode of pathogenicity: None; Publications: 17164303, 25264451; Phenotypes: Aromatase deficiency (MIM#613546), AR, Aromatase excess syndrome (MIM#139300), AD; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3400 TNXB Daniel Flanagan reviewed gene: TNXB: Rating: RED; Mode of pathogenicity: None; Publications: 19921645, 28306229, 28306225, 23620400; Phenotypes: Vesicoureteral reflux 8 (MIM#615963), Ehlers-Danlos syndrome, classic-like, 1 (MIM#606408); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.3400 FTSJ1 Ain Roesley reviewed gene: FTSJ1: Rating: RED; Mode of pathogenicity: None; Publications: 15342698, 18081026, 15162322, 26310293; Phenotypes: 15342698, 18081026, 15162322, 26310293; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Mendeliome v0.10953 FTSJ1 Ain Roesley reviewed gene: FTSJ1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15342698, 18081026, 15162322, 26310293; Phenotypes: Intellectual developmental disorder, X-linked 9 MIM#309549; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Fetal anomalies v0.3400 MYOCD Zornitza Stark Marked gene: MYOCD as ready
Fetal anomalies v0.3400 MYOCD Zornitza Stark Gene: myocd has been classified as Green List (High Evidence).
Fetal anomalies v0.3400 MYOCD Zornitza Stark Classified gene: MYOCD as Green List (high evidence)
Fetal anomalies v0.3400 MYOCD Zornitza Stark Gene: myocd has been classified as Green List (High Evidence).
Fetal anomalies v0.3399 MYO9A Zornitza Stark Marked gene: MYO9A as ready
Fetal anomalies v0.3399 MYO9A Zornitza Stark Gene: myo9a has been classified as Green List (High Evidence).
Fetal anomalies v0.3399 MYO9A Zornitza Stark Classified gene: MYO9A as Green List (high evidence)
Fetal anomalies v0.3399 MYO9A Zornitza Stark Gene: myo9a has been classified as Green List (High Evidence).
Fetal anomalies v0.3398 MYO9A Zornitza Stark reviewed gene: MYO9A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Myasthenic syndrome, congenital, 24, presynaptic, MIM# 618198; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3398 MYMK Zornitza Stark Marked gene: MYMK as ready
Fetal anomalies v0.3398 MYMK Zornitza Stark Gene: mymk has been classified as Red List (Low Evidence).
Fetal anomalies v0.3398 MYMK Zornitza Stark Classified gene: MYMK as Red List (low evidence)
Fetal anomalies v0.3398 MYMK Zornitza Stark Gene: mymk has been classified as Red List (Low Evidence).
Fetal anomalies v0.3397 FLRT3 Ain Roesley reviewed gene: FLRT3: Rating: RED; Mode of pathogenicity: None; Publications: 23643382, 31200363; Phenotypes: Hypogonadotropic hypogonadism 21 with anosmia (MIM# 615271); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Fetal anomalies v0.3397 MYL1 Zornitza Stark Marked gene: MYL1 as ready
Fetal anomalies v0.3397 MYL1 Zornitza Stark Gene: myl1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3397 MYL1 Zornitza Stark Classified gene: MYL1 as Red List (low evidence)
Fetal anomalies v0.3397 MYL1 Zornitza Stark Gene: myl1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3396 TMEM126B Daniel Flanagan reviewed gene: TMEM126B: Rating: AMBER; Mode of pathogenicity: None; Publications: 27374774, 27374773; Phenotypes: Mitochondrial complex I deficiency, nuclear type 29 (MIM#618250); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10953 FLAD1 Ain Roesley reviewed gene: FLAD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34454814, 34718578, 31392824, 30982706, 30311138, 30427553, 28433476, 27259049, 25058219; Phenotypes: Lipid storage myopathy due to flavin adenine dinucleotide synthetase deficiency MIM#255100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3396 FLAD1 Ain Roesley reviewed gene: FLAD1: Rating: RED; Mode of pathogenicity: None; Publications: Lipid storage myopathy due to flavin adenine dinucleotide synthetase deficiency MIM#255100; Phenotypes: Lipid storage myopathy due to flavin adenine dinucleotide synthetase deficiency MIM#255100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3396 TK2 Daniel Flanagan reviewed gene: TK2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial DNA depletion syndrome 2 (myopathic type) (MIM#609560); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3396 FGF20 Ain Roesley commented on gene: FGF20: Multiple affected fetuses in a consanguineous family; functional data.
Fetal anomalies v0.3396 FGF20 Ain Roesley reviewed gene: FGF20: Rating: AMBER; Mode of pathogenicity: None; Publications: 22698282; Phenotypes: Renal hypodysplasia/aplasia 2, MIM#615721; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3396 FGF17 Ain Roesley reviewed gene: FGF17: Rating: RED; Mode of pathogenicity: None; Publications: 31200363, 31748124, 23643382; Phenotypes: Hypogonadotropic hypogonadism 20 with or without anosmia MIM#615270; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Fetal anomalies v0.3396 TEK Daniel Flanagan reviewed gene: TEK: Rating: RED; Mode of pathogenicity: None; Publications: 19888299; Phenotypes: Glaucoma 3, primary congenital, E (MIM#617272), Venous malformations, multiple cutaneous and mucosal (MIM#600195); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10953 FGF17 Ain Roesley changed review comment from: 31200363;
1x individual

31748124
3x unrelated individuals. 1 has p.48_52del and another variant in OTUD4 (no current mendelian disease association), 1x with Pro120Leu (5 hets in gnomAD) and 1x with Lys191Arg (55 hets in gnomad)

23643382
3x unrelated individuals, including 1 large consanguineous 10-generation French Canadian family.
In this large family, 3 other variants in FGFR1, HS6ST1, and FLRT3 were identified. None of the other affecteds carried the FGF17 variant

Summary: 3x individuals with convincing evidence; to: PMID:31200363;
1x individual

PMID:31748124
3x unrelated individuals. 1 has p.48_52del and another variant in OTUD4 (no current mendelian disease association), 1x with Pro120Leu (5 hets in gnomAD) and 1x with Lys191Arg (55 hets in gnomad)

PMID:23643382
3x unrelated individuals, including 1 large consanguineous 10-generation French Canadian family.
In this large family, 3 other variants in FGFR1, HS6ST1, and FLRT3 were identified. None of the other affecteds carried the FGF17 variant

Summary: 3x individuals with convincing evidence
Mendeliome v0.10953 FGF17 Ain Roesley reviewed gene: FGF17: Rating: GREEN; Mode of pathogenicity: None; Publications: 31200363, 31748124, 23643382; Phenotypes: Hypogonadotropic hypogonadism 20 with or without anosmia MIM#615270; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Fetal anomalies v0.3396 TBXAS1 Daniel Flanagan reviewed gene: TBXAS1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ghosal hematodiaphyseal syndrome (MIM#231095); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3396 TANGO2 Daniel Flanagan reviewed gene: TANGO2: Rating: RED; Mode of pathogenicity: None; Publications: 26805781, 26805782, 30245509; Phenotypes: Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration (MIM#616878); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3396 ZFYVE26 Ain Roesley reviewed gene: ZFYVE26: Rating: RED; Mode of pathogenicity: None; Publications: 34057829; Phenotypes: Spastic paraplegia 15, autosomal recessive MIM#270700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3396 SYP Daniel Flanagan reviewed gene: SYP: Rating: RED; Mode of pathogenicity: None; Publications: 19377476; Phenotypes: Intellectual developmental disorder, X-linked 96 (MIM#300802); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v0.3396 CYC1 Belinda Chong reviewed gene: CYC1: Rating: RED; Mode of pathogenicity: None; Publications: 23910460; Phenotypes: Mitochondrial complex III deficiency, nuclear type 6, MIM# 615453; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10953 ZFYVE26 Ain Roesley changed review comment from: Genereviews:
>70 individuals reported; to: Genereviews:
>70 individuals reported.

While onset of spasticity is typically in mid- to late childhood or adolescence (i.e., between ages 5 and 18 years), other manifestations, such as developmental delay or learning disability, may be present earlier, often preceding motor involvement. Individuals with adult onset have also been reported.
Mendeliome v0.10953 ZFYVE26 Ain Roesley reviewed gene: ZFYVE26: Rating: GREEN; Mode of pathogenicity: None; Publications: 34057829; Phenotypes: Spastic paraplegia 15, autosomal recessive MIM#270700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3396 SURF1 Daniel Flanagan reviewed gene: SURF1: Rating: RED; Mode of pathogenicity: None; Publications: 23829769; Phenotypes: Charcot-Marie-Tooth disease, type 4K (MIM#616684), Mitochondrial complex IV deficiency, nuclear type 1 (MIM#220110); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3396 ZDHHC9 Ain Roesley reviewed gene: ZDHHC9: Rating: RED; Mode of pathogenicity: None; Publications: Mental retardation, X-linked syndromic, Raymond typeMIM# 300799; Phenotypes: Mental retardation, X-linked syndromic, Raymond typeMIM# 300799; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Fetal anomalies v0.3396 MYH7 Zornitza Stark Marked gene: MYH7 as ready
Fetal anomalies v0.3396 MYH7 Zornitza Stark Gene: myh7 has been classified as Green List (High Evidence).
Fetal anomalies v0.3396 MYH7 Zornitza Stark Phenotypes for gene: MYH7 were changed from Cardiomyopathy, hypertrophic, 1, OMIM:192600; Laing early-onset distal myopathy, MONDO:0008050; Left ventricular noncompaction 5, OMIM:613426; Cardiomyopathy, dilated, 1S, OMIM:613426; Hypertrophic cardiomyopathy 1, MONDO:0008647; Laing distal myopathy, OMIM:160500; Dilated cardiomyopathy 1S, MONDO:0013262 to Ebstein anomaly; Laing distal myopathy, MIM# 160500
Fetal anomalies v0.3395 MYH7 Zornitza Stark Publications for gene: MYH7 were set to 22859017; 26337809; 25547560
Fetal anomalies v0.3394 MYH7 Zornitza Stark Mode of pathogenicity for gene: MYH7 was changed from to Other
Fetal anomalies v0.3393 MYH7 Zornitza Stark Classified gene: MYH7 as Green List (high evidence)
Fetal anomalies v0.3393 MYH7 Zornitza Stark Gene: myh7 has been classified as Green List (High Evidence).
Fetal anomalies v0.3392 MYH2 Zornitza Stark Marked gene: MYH2 as ready
Fetal anomalies v0.3392 MYH2 Zornitza Stark Gene: myh2 has been classified as Green List (High Evidence).
Fetal anomalies v0.3392 MYH2 Zornitza Stark Publications for gene: MYH2 were set to 15548556; 11114175; 24193343; 23388406; 20418530; 23489661
Fetal anomalies v0.3391 MYH2 Zornitza Stark Classified gene: MYH2 as Green List (high evidence)
Fetal anomalies v0.3391 MYH2 Zornitza Stark Gene: myh2 has been classified as Green List (High Evidence).
Fetal anomalies v0.3390 MSMO1 Zornitza Stark Marked gene: MSMO1 as ready
Fetal anomalies v0.3390 MSMO1 Zornitza Stark Gene: msmo1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3390 MSMO1 Zornitza Stark Publications for gene: MSMO1 were set to 21285510; 24144731
Fetal anomalies v0.3389 MSMO1 Zornitza Stark Classified gene: MSMO1 as Green List (high evidence)
Fetal anomalies v0.3389 MSMO1 Zornitza Stark Gene: msmo1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3388 MRPS34 Zornitza Stark Marked gene: MRPS34 as ready
Fetal anomalies v0.3388 MRPS34 Zornitza Stark Gene: mrps34 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3388 MRPS34 Zornitza Stark Phenotypes for gene: MRPS34 were changed from Leigh Syndrome with Instability of the Small Mitoribosomal Subunit to Combined oxidative phosphorylation deficiency 32, MIM# 617664
Fetal anomalies v0.3387 MRPS34 Zornitza Stark Publications for gene: MRPS34 were set to
Fetal anomalies v0.3386 MRPS34 Zornitza Stark changed review comment from: Six individuals from 4 unrelated families; clinical presentation is with developmental delay/regression. More variable features include movement disorders, microcephaly, strabismus, nystagmus, optic atrophy.
Sources: Expert list; to: Six individuals from 4 unrelated families; clinical presentation is with developmental delay/regression. More variable features include movement disorders, microcephaly, strabismus, nystagmus, optic atrophy.

Onset of microcephaly uncertain, other clinical features present post-natally.

Sources: Expert list
Mendeliome v0.10953 ZDHHC9 Ain Roesley changed review comment from: >10 families reported; to: >10 families reported.

Intra-genic CNV in 2 families
Fetal anomalies v0.3386 MRPS34 Zornitza Stark edited their review of gene: MRPS34: Changed rating: AMBER; Changed phenotypes: Combined oxidative phosphorylation deficiency 32, MIM# 617664
Fetal anomalies v0.3386 MRAS Zornitza Stark Marked gene: MRAS as ready
Fetal anomalies v0.3386 MRAS Zornitza Stark Gene: mras has been classified as Green List (High Evidence).
Fetal anomalies v0.3386 MRAS Zornitza Stark Mode of inheritance for gene: MRAS was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3385 MRAS Zornitza Stark Classified gene: MRAS as Green List (high evidence)
Fetal anomalies v0.3385 MRAS Zornitza Stark Gene: mras has been classified as Green List (High Evidence).
Mendeliome v0.10953 ZDHHC9 Ain Roesley reviewed gene: ZDHHC9: Rating: GREEN; Mode of pathogenicity: None; Publications: 26000327, 29681091; Phenotypes: Mental retardation, X-linked syndromic, Raymond typeMIM# 300799; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Fetal anomalies v0.3384 MOGS Zornitza Stark Marked gene: MOGS as ready
Fetal anomalies v0.3384 MOGS Zornitza Stark Gene: mogs has been classified as Green List (High Evidence).
Fetal anomalies v0.3384 MOGS Zornitza Stark Publications for gene: MOGS were set to
Fetal anomalies v0.3383 MOGS Zornitza Stark Classified gene: MOGS as Green List (high evidence)
Fetal anomalies v0.3383 MOGS Zornitza Stark Gene: mogs has been classified as Green List (High Evidence).
Fetal anomalies v0.3382 STXBP1 Daniel Flanagan reviewed gene: STXBP1: Rating: RED; Mode of pathogenicity: None; Publications: 31855252, 18469812; Phenotypes: Developmental and epileptic encephalopathy 4 (MIM#612164); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.3382 MN1 Zornitza Stark Marked gene: MN1 as ready
Fetal anomalies v0.3382 MN1 Zornitza Stark Gene: mn1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3382 MN1 Zornitza Stark Mode of inheritance for gene: MN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3381 MN1 Zornitza Stark Classified gene: MN1 as Green List (high evidence)
Fetal anomalies v0.3381 MN1 Zornitza Stark Gene: mn1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3380 MN1 Zornitza Stark changed review comment from: Over 20 individuals described with de novo truncating variants in this gene; these cluster in the C-terminal and the authors postulate that that syndrome is not due to MN1 haploinsufficiency but rather is the result of dominantly acting C-terminally truncated MN1 protein.
Sources: Literature; to: Over 20 individuals described with de novo truncating variants in this gene; these cluster in the C-terminal and the authors postulate that that syndrome is not due to MN1 haploinsufficiency but rather is the result of dominantly acting C-terminally truncated MN1 protein.

Diaphragmatic hernia, craniosynostosis and brain abnormalities reported.

Sources: Literature
Fetal anomalies v0.3380 MITF Zornitza Stark Marked gene: MITF as ready
Fetal anomalies v0.3380 MITF Zornitza Stark Gene: mitf has been classified as Green List (High Evidence).
Fetal anomalies v0.3380 XPC Ain Roesley reviewed gene: XPC: Rating: RED; Mode of pathogenicity: None; Publications: 10447254; Phenotypes: Xeroderma pigmentosum, group C, MIM# 278720, MONDO:0010211; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3380 MITF Zornitza Stark Phenotypes for gene: MITF were changed from Tietz albinism-deafness syndrome, 103500; Waardenburg syndrome/ocular albinism, digenic, 103470; TIETZ SYNDROME; Waardenburg syndrome, type 2A, 193510; Coloboma, Osteopetrosis, Microphthalmia, Macrocephaly, Albinism, and Deafness; WAARDENBURG SYNDROME TYPE 2A; COMMAD syndrome, 617306; WAARDENBURG SYNDROME TYPE 2 WITH OCULAR ALBINISM to COMMAD syndrome, MIM# 617306
Fetal anomalies v0.3379 MITF Zornitza Stark Publications for gene: MITF were set to 27889061
Fetal anomalies v0.3378 MITF Zornitza Stark Classified gene: MITF as Green List (high evidence)
Fetal anomalies v0.3378 MITF Zornitza Stark Gene: mitf has been classified as Green List (High Evidence).
Fetal anomalies v0.3377 WDR45 Ain Roesley edited their review of gene: WDR45: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Fetal anomalies v0.3377 WDR45 Ain Roesley reviewed gene: WDR45: Rating: RED; Mode of pathogenicity: None; Publications: 30842224, 23176820; Phenotypes: Neurodegeneration with brain iron accumulation 5, MIM# 300894, Rett syndrome, Rett-like phenotypes; Mode of inheritance: None; Current diagnostic: yes
Fetal anomalies v0.3377 MIR17HG Zornitza Stark Marked gene: MIR17HG as ready
Fetal anomalies v0.3377 MIR17HG Zornitza Stark Gene: mir17hg has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3377 MIR17HG Zornitza Stark Phenotypes for gene: MIR17HG were changed from FEINGOLD SYNDROME to Feingold syndrome 2, MIM #614326
Fetal anomalies v0.3376 MIR17HG Zornitza Stark Publications for gene: MIR17HG were set to
Fetal anomalies v0.3375 MIR17HG Zornitza Stark Mode of inheritance for gene: MIR17HG was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3374 MIR17HG Zornitza Stark Tag SV/CNV tag was added to gene: MIR17HG.
Fetal anomalies v0.3374 MANBA Zornitza Stark Marked gene: MANBA as ready
Fetal anomalies v0.3374 MANBA Zornitza Stark Gene: manba has been classified as Red List (Low Evidence).
Fetal anomalies v0.3374 MANBA Zornitza Stark Phenotypes for gene: MANBA were changed from LYSOSOMAL BETA-MANNOSIDOSIS to Mannosidosis, beta, MIM# 248510; MONDO:0009562
Fetal anomalies v0.3373 MANBA Zornitza Stark Classified gene: MANBA as Red List (low evidence)
Fetal anomalies v0.3373 MANBA Zornitza Stark Gene: manba has been classified as Red List (Low Evidence).
Fetal anomalies v0.3372 MANBA Zornitza Stark changed review comment from: Variable severity. Well established gene-disease association.; to: Well established gene-disease association but clinical presentation is typically post-natal.
Fetal anomalies v0.3372 MANBA Zornitza Stark edited their review of gene: MANBA: Changed rating: RED
Pulmonary Fibrosis_Interstitial Lung Disease v0.40 TMEM173 Lucy Spencer reviewed gene: TMEM173: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32673614; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3372 SPTBN5 Daniel Flanagan reviewed gene: SPTBN5: Rating: RED; Mode of pathogenicity: None; Publications: 32732226, 28007035; Phenotypes: Sacral agenesis, congenital anomalies; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3372 SMARCAL1 Daniel Flanagan changed review comment from: Well-established gene-disease association; over 40 patients with biallelic mutations in SMARCAL1; Zebrafish and mouse models that recapitulates phenotype have been reported.

This disorder combines abnormality of the immune and skeletal systems. Primary features include growth retardation (IUGR in 50%), renal failure, cerebral infarcts, skin pigmentation and CID (lymphocytopaenia, recurrent infections and/or T-cell immunodeficiency) beginning in childhood.

GeneReviews: Short stature (99% of individuals) that typically manifests as a short neck and trunk with lumbar lordosis and a protruding abdomen.; to: Well-established gene-disease association; over 40 patients with biallelic mutations in SMARCAL1; Zebrafish and mouse models that recapitulates phenotype have been reported.

This disorder combines abnormality of the immune and skeletal systems. Primary features include growth retardation (IUGR in 50%), renal failure, cerebral infarcts, skin pigmentation and CID (lymphocytopaenia, recurrent infections and/or T-cell immunodeficiency) beginning in childhood.

GeneReviews: Short stature (99% of individuals) that typically manifests as a short neck and trunk with lumbar lordosis and a protruding abdomen. Most affected children have prenatal and postnatal disproportionate growth failure. A few have normal intrauterine growth followed by postnatal growth failure.
Fetal anomalies v0.3372 SPTBN2 Daniel Flanagan reviewed gene: SPTBN2: Rating: RED; Mode of pathogenicity: None; Publications: 23236289, 23838597, 22781464, 31617442, 31066025; Phenotypes: Spinocerebellar ataxia 5 (MIM#600224), Spinocerebellar ataxia, autosomal recessive 14 (MIM#615386); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.3372 SMARCAL1 Daniel Flanagan reviewed gene: SMARCAL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15523612, 20301550, 20301550, 17089404, 20036229; Phenotypes: Schimke immunoosseous dysplasia (MIM#242900); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3372 SP110 Daniel Flanagan reviewed gene: SP110: Rating: RED; Mode of pathogenicity: None; Publications: 20301448, 31721003; Phenotypes: Hepatic venoocclusive disease with immunodeficiency (MIM#235550); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3372 SLC6A8 Daniel Flanagan reviewed gene: SLC6A8: Rating: AMBER; Mode of pathogenicity: None; Publications: 11898126, 16738945, 16086185; Phenotypes: Cerebral creatine deficiency syndrome 1 (MIM#300352); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v0.3372 SLC52A3 Daniel Flanagan reviewed gene: SLC52A3: Rating: RED; Mode of pathogenicity: None; Publications: 29053833, 29193829; Phenotypes: Brown-Vialetto-Van Laere syndrome 1 (MIM#211530); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3372 MAN1B1 Zornitza Stark Marked gene: MAN1B1 as ready
Fetal anomalies v0.3372 MAN1B1 Zornitza Stark Gene: man1b1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3372 MAN1B1 Zornitza Stark Phenotypes for gene: MAN1B1 were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION to Rafiq syndrome, MIM# 614202
Fetal anomalies v0.3371 MAN1B1 Zornitza Stark Classified gene: MAN1B1 as Red List (low evidence)
Fetal anomalies v0.3371 MAN1B1 Zornitza Stark Gene: man1b1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3370 MAN1B1 Zornitza Stark commented on gene: MAN1B1: Clinical presentation is typically post-natal.
Fetal anomalies v0.3370 MAN1B1 Zornitza Stark edited their review of gene: MAN1B1: Changed rating: RED; Changed phenotypes: Rafiq syndrome, MIM# 614202
Fetal anomalies v0.3370 MACF1 Zornitza Stark Marked gene: MACF1 as ready
Fetal anomalies v0.3370 MACF1 Zornitza Stark Gene: macf1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3370 MACF1 Zornitza Stark Mode of pathogenicity for gene: MACF1 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
Fetal anomalies v0.3369 MACF1 Zornitza Stark Mode of inheritance for gene: MACF1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3368 MACF1 Zornitza Stark Classified gene: MACF1 as Green List (high evidence)
Fetal anomalies v0.3368 MACF1 Zornitza Stark Gene: macf1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3367 LRRC56 Zornitza Stark Marked gene: LRRC56 as ready
Fetal anomalies v0.3367 LRRC56 Zornitza Stark Gene: lrrc56 has been classified as Green List (High Evidence).
Fetal anomalies v0.3367 LRRC56 Zornitza Stark Classified gene: LRRC56 as Green List (high evidence)
Fetal anomalies v0.3367 LRRC56 Zornitza Stark Gene: lrrc56 has been classified as Green List (High Evidence).
Fetal anomalies v0.3366 LRBA Zornitza Stark Marked gene: LRBA as ready
Fetal anomalies v0.3366 LRBA Zornitza Stark Gene: lrba has been classified as Red List (Low Evidence).
Fetal anomalies v0.3366 LRBA Zornitza Stark Phenotypes for gene: LRBA were changed from CHILDHOOD-ONSET HYPOGAMMAGLOBULINEMIA to Immunodeficiency, common variable, 8, with autoimmunity MIM#614700
Fetal anomalies v0.3365 LRBA Zornitza Stark Classified gene: LRBA as Red List (low evidence)
Fetal anomalies v0.3365 LRBA Zornitza Stark Gene: lrba has been classified as Red List (Low Evidence).
Fetal anomalies v0.3364 LRBA Zornitza Stark reviewed gene: LRBA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency, common variable, 8, with autoimmunity MIM#614700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3364 LONP1 Zornitza Stark Marked gene: LONP1 as ready
Fetal anomalies v0.3364 LONP1 Zornitza Stark Gene: lonp1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3364 LONP1 Zornitza Stark Publications for gene: LONP1 were set to
Fetal anomalies v0.3363 LONP1 Zornitza Stark Classified gene: LONP1 as Green List (high evidence)
Fetal anomalies v0.3363 LONP1 Zornitza Stark Gene: lonp1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3362 LONP1 Zornitza Stark changed review comment from: At least three unrelated cases described in the literature, ID is part of the phenotype.; to: At least three unrelated cases described in the literature, multiple congenital anomalies are part of the phenotype.
Fetal anomalies v0.3362 LIPT2 Zornitza Stark Marked gene: LIPT2 as ready
Fetal anomalies v0.3362 LIPT2 Zornitza Stark Gene: lipt2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3362 LIPT2 Zornitza Stark Phenotypes for gene: LIPT2 were changed from Mitochondrial Lipoylation Defect Associated with Severe Neonatal Encephalopathy to Encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities, MIM#617668
Fetal anomalies v0.3361 LIPT2 Zornitza Stark Publications for gene: LIPT2 were set to
Fetal anomalies v0.3360 LIPT2 Zornitza Stark Classified gene: LIPT2 as Red List (low evidence)
Fetal anomalies v0.3360 LIPT2 Zornitza Stark Gene: lipt2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3359 LIPT2 Zornitza Stark changed review comment from: Three individuals from two unrelated families; profound ID.
Sources: Expert list; to: Three individuals from two unrelated families; onset is typically post-natal, though brain abnormalities reported in some.
Sources: Expert list
Fetal anomalies v0.3359 LIPT2 Zornitza Stark edited their review of gene: LIPT2: Changed rating: RED
Fetal anomalies v0.3359 LIPT1 Zornitza Stark Marked gene: LIPT1 as ready
Fetal anomalies v0.3359 LIPT1 Zornitza Stark Gene: lipt1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3359 LIPT1 Zornitza Stark Phenotypes for gene: LIPT1 were changed from Leigh syndrome with secondary deficiency for pyruvate and alpha-ketoglutarate dehydrogenase. to Lipoyltransferase 1 deficiency, MIM#616299
Fetal anomalies v0.3358 LIPT1 Zornitza Stark Publications for gene: LIPT1 were set to
Fetal anomalies v0.3357 LIPT1 Zornitza Stark Classified gene: LIPT1 as Red List (low evidence)
Fetal anomalies v0.3357 LIPT1 Zornitza Stark Gene: lipt1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3356 LIPT1 Zornitza Stark changed review comment from: Cognitive development is affected in this metabolic condition.; to: Clinical presentation is typically post-natal.
Fetal anomalies v0.3356 LIPT1 Zornitza Stark edited their review of gene: LIPT1: Changed rating: RED
Fetal anomalies v0.3356 LIAS Zornitza Stark Marked gene: LIAS as ready
Fetal anomalies v0.3356 LIAS Zornitza Stark Gene: lias has been classified as Red List (Low Evidence).
Fetal anomalies v0.3356 LIAS Zornitza Stark Phenotypes for gene: LIAS were changed from Neonatal-onset epilepsy, defective mitochondrial energy metabolism, and glycine elevation to Hyperglycinemia, lactic acidosis, and seizures, MIM#614462
Fetal anomalies v0.3355 LIAS Zornitza Stark Publications for gene: LIAS were set to
Fetal anomalies v0.3354 LIAS Zornitza Stark Classified gene: LIAS as Red List (low evidence)
Fetal anomalies v0.3354 LIAS Zornitza Stark Gene: lias has been classified as Red List (Low Evidence).
Fetal anomalies v0.3353 LIAS Zornitza Stark changed review comment from: At least three families reported, severe ID is part of the phenotype.; to: At least three families reported, clinical presentation is typically post-natal.
Fetal anomalies v0.3353 LIAS Zornitza Stark edited their review of gene: LIAS: Changed rating: RED
Fetal anomalies v0.3353 LARS2 Zornitza Stark Marked gene: LARS2 as ready
Fetal anomalies v0.3353 LARS2 Zornitza Stark Gene: lars2 has been classified as Green List (High Evidence).
Fetal anomalies v0.3353 LARS2 Zornitza Stark Classified gene: LARS2 as Green List (high evidence)
Fetal anomalies v0.3353 LARS2 Zornitza Stark Gene: lars2 has been classified as Green List (High Evidence).
Fetal anomalies v0.3352 LAMB1 Zornitza Stark Marked gene: LAMB1 as ready
Fetal anomalies v0.3352 LAMB1 Zornitza Stark Gene: lamb1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3352 LAMB1 Zornitza Stark Classified gene: LAMB1 as Green List (high evidence)
Fetal anomalies v0.3352 LAMB1 Zornitza Stark Gene: lamb1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3351 KPTN Zornitza Stark Marked gene: KPTN as ready
Fetal anomalies v0.3351 KPTN Zornitza Stark Gene: kptn has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3351 KPTN Zornitza Stark Phenotypes for gene: KPTN were changed from MACROCEPHALY, NEURODEVELOPMENTAL DELAY, AND SEIZURES to Mental retardation, autosomal recessive 41 (MIM#615637)
Fetal anomalies v0.3350 KPTN Zornitza Stark Publications for gene: KPTN were set to
Fetal anomalies v0.3349 KPTN Zornitza Stark changed review comment from: 15 patients (9 from Amish families) reported with macrocephaly and intellectual disability with hom or chet variants in KPTN (PMID: 32808430).; to: 15 patients (9 from Amish families) reported with macrocephaly and intellectual disability with hom or chet variants in KPTN (PMID: 32808430). Age of onset of macrocephaly uncertain.
Fetal anomalies v0.3349 KPTN Zornitza Stark edited their review of gene: KPTN: Changed rating: AMBER
Fetal anomalies v0.3349 KNL1 Zornitza Stark Marked gene: KNL1 as ready
Fetal anomalies v0.3349 KNL1 Zornitza Stark Gene: knl1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3349 KNL1 Zornitza Stark Publications for gene: KNL1 were set to 26626498; 26621532; 22983954
Fetal anomalies v0.3348 KNL1 Zornitza Stark Classified gene: KNL1 as Green List (high evidence)
Fetal anomalies v0.3348 KNL1 Zornitza Stark Gene: knl1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3347 KMT2B Zornitza Stark Marked gene: KMT2B as ready
Fetal anomalies v0.3347 KMT2B Zornitza Stark Gene: kmt2b has been classified as Red List (Low Evidence).
Fetal anomalies v0.3347 KMT2B Zornitza Stark Phenotypes for gene: KMT2B were changed from Complex early-onset dystonia to Dystonia 28, childhood-onset, MIM#617284
Fetal anomalies v0.3346 KMT2B Zornitza Stark Mode of inheritance for gene: KMT2B was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3345 KMT2B Zornitza Stark Classified gene: KMT2B as Red List (low evidence)
Fetal anomalies v0.3345 KMT2B Zornitza Stark Gene: kmt2b has been classified as Red List (Low Evidence).
Fetal anomalies v0.3344 KMT2B Zornitza Stark changed review comment from: ID described as part of the phenotype in some patients.; to: Clinical presentation is typically post-natal.
Fetal anomalies v0.3344 KMT2B Zornitza Stark edited their review of gene: KMT2B: Changed rating: RED
Fetal anomalies v0.3344 KLHL7 Zornitza Stark Marked gene: KLHL7 as ready
Fetal anomalies v0.3344 KLHL7 Zornitza Stark Gene: klhl7 has been classified as Green List (High Evidence).
Fetal anomalies v0.3344 KLHL7 Zornitza Stark Publications for gene: KLHL7 were set to
Fetal anomalies v0.3343 KLHL7 Zornitza Stark Classified gene: KLHL7 as Green List (high evidence)
Fetal anomalies v0.3343 KLHL7 Zornitza Stark Gene: klhl7 has been classified as Green List (High Evidence).
Fetal anomalies v0.3342 KLHL7 Zornitza Stark changed review comment from: IUGR and contractures.; to: IUGR and contractures. More than 10 families reported.
Fetal anomalies v0.3342 KLHL7 Zornitza Stark changed review comment from: Overall IUGR rather than microcephaly, head sizes when reported appear to be in the -1-2SD range.; to: IUGR and contractures.
Fetal anomalies v0.3342 KLHL7 Zornitza Stark edited their review of gene: KLHL7: Changed rating: GREEN
Fetal anomalies v0.3342 KIF5C Zornitza Stark Marked gene: KIF5C as ready
Fetal anomalies v0.3342 KIF5C Zornitza Stark Gene: kif5c has been classified as Green List (High Evidence).
Fetal anomalies v0.3342 KIF5C Zornitza Stark Publications for gene: KIF5C were set to
Fetal anomalies v0.3341 KIF5C Zornitza Stark Mode of inheritance for gene: KIF5C was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3340 KIF5C Zornitza Stark Classified gene: KIF5C as Green List (high evidence)
Fetal anomalies v0.3340 KIF5C Zornitza Stark Gene: kif5c has been classified as Green List (High Evidence).
Fetal anomalies v0.3339 KIF2A Zornitza Stark Marked gene: KIF2A as ready
Fetal anomalies v0.3339 KIF2A Zornitza Stark Gene: kif2a has been classified as Green List (High Evidence).
Fetal anomalies v0.3339 KIF2A Zornitza Stark Publications for gene: KIF2A were set to
Fetal anomalies v0.3338 KIF2A Zornitza Stark Mode of inheritance for gene: KIF2A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3337 KIF2A Zornitza Stark Classified gene: KIF2A as Green List (high evidence)
Fetal anomalies v0.3337 KIF2A Zornitza Stark Gene: kif2a has been classified as Green List (High Evidence).
Fetal anomalies v0.3336 KIF14 Zornitza Stark Marked gene: KIF14 as ready
Fetal anomalies v0.3336 KIF14 Zornitza Stark Gene: kif14 has been classified as Green List (High Evidence).
Fetal anomalies v0.3336 KIF14 Zornitza Stark Publications for gene: KIF14 were set to 29343805; 24128419; 30388224; 28892560
Fetal anomalies v0.3335 KIF14 Zornitza Stark Classified gene: KIF14 as Green List (high evidence)
Fetal anomalies v0.3335 KIF14 Zornitza Stark Gene: kif14 has been classified as Green List (High Evidence).
Fetal anomalies v0.3334 SPRED2 Zornitza Stark Phenotypes for gene: SPRED2 were changed from cardiac defects; skeletal anomalies to Noonan syndrome 14, MIM# 619745
Fetal anomalies v0.3333 SPRED2 Zornitza Stark reviewed gene: SPRED2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Noonan syndrome 14, MIM# 619745; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Growth failure v1.37 SPRED2 Zornitza Stark Phenotypes for gene: SPRED2 were changed from Rasopathy; developmental delay; intellectual disability; cardiac defects; short stature; skeletal anomalies; a typical facial gestalt to Noonan syndrome 14, MIM# 619745
Growth failure v1.36 SPRED2 Zornitza Stark reviewed gene: SPRED2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Noonan syndrome 14, MIM# 619745; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4500 SPRED2 Zornitza Stark Phenotypes for gene: SPRED2 were changed from Rasopathy; developmental delay; intellectual disability; cardiac defects; short stature; skeletal anomalies; a typical facial gestalt to Noonan syndrome 14, MIM# 619745
Intellectual disability syndromic and non-syndromic v0.4499 SPRED2 Zornitza Stark reviewed gene: SPRED2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Noonan syndrome 14, MIM# 619745; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rasopathy v0.95 SPRED2 Zornitza Stark Phenotypes for gene: SPRED2 were changed from Noonan syndrome 14, MIM# 619745 to Noonan syndrome 14, MIM# 619745
Rasopathy v0.95 SPRED2 Zornitza Stark Phenotypes for gene: SPRED2 were changed from Rasopathy; developmental delay; intellectual disability; cardiac defects; short stature; skeletal anomalies; a typical facial gestalt to Noonan syndrome 14, MIM# 619745
Rasopathy v0.94 SPRED2 Zornitza Stark reviewed gene: SPRED2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Noonan syndrome 14, MIM# 619745; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10953 SPRED2 Zornitza Stark Phenotypes for gene: SPRED2 were changed from Rasopathy; developmental delay; intellectual disability; cardiac defects; short stature; skeletal anomalies; a typical facial gestalt to Noonan syndrome 14, MIM# 619745
Mendeliome v0.10952 SPRED2 Zornitza Stark reviewed gene: SPRED2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Noonan syndrome 14, MIM# 619745; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Heart Defect v0.189 SPRED2 Zornitza Stark Phenotypes for gene: SPRED2 were changed from Rasopathy; developmental delay; intellectual disability; cardiac defects; short stature; skeletal anomalies; a typical facial gestalt to Noonan syndrome 14, MIM# 619745
Congenital Heart Defect v0.188 SPRED2 Zornitza Stark reviewed gene: SPRED2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Noonan syndrome 14, MIM# 619745; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4499 POLRMT Zornitza Stark Phenotypes for gene: POLRMT were changed from Mitochondrial disorder; intellectual disability; hypotonia to Combined oxidative phosphorylation deficiency 55, MIM# 619743; intellectual disability; hypotonia
Intellectual disability syndromic and non-syndromic v0.4498 POLRMT Zornitza Stark edited their review of gene: POLRMT: Changed phenotypes: Combined oxidative phosphorylation deficiency 55, MIM# 619743, intellectual disability, hypotonia
Mitochondrial disease v0.693 POLRMT Zornitza Stark Phenotypes for gene: POLRMT were changed from Mitochondrial disorder; intellectual disability; hypotonia to Combined oxidative phosphorylation deficiency 55, MIM# 619743; intellectual disability; hypotonia
Mitochondrial disease v0.692 POLRMT Zornitza Stark edited their review of gene: POLRMT: Changed phenotypes: Combined oxidative phosphorylation deficiency 55, MIM# 619743, intellectual disability, hypotonia
Mendeliome v0.10952 POLRMT Zornitza Stark Phenotypes for gene: POLRMT were changed from Mitochondrial disorder; intellectual disability; hypotonia to Combined oxidative phosphorylation deficiency 55, MIM# 619743; intellectual disability; hypotonia
Mendeliome v0.10951 POLRMT Zornitza Stark edited their review of gene: POLRMT: Changed phenotypes: Combined oxidative phosphorylation deficiency 55, MIM# 619743, intellectual disability, hypotonia
Mendeliome v0.10951 BAG5 Zornitza Stark Marked gene: BAG5 as ready
Mendeliome v0.10951 BAG5 Zornitza Stark Gene: bag5 has been classified as Green List (High Evidence).
Mendeliome v0.10951 BAG5 Zornitza Stark Classified gene: BAG5 as Green List (high evidence)
Mendeliome v0.10951 BAG5 Zornitza Stark Gene: bag5 has been classified as Green List (High Evidence).
Mendeliome v0.10950 BAG5 Zornitza Stark gene: BAG5 was added
gene: BAG5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BAG5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BAG5 were set to 35044787
Phenotypes for gene: BAG5 were set to Cardiomyopathy, dilated, 2F, MIM# 619747
Review for gene: BAG5 was set to GREEN
Added comment: 5 individuals from four unrelated families reported. All had early-onset disease, with the diagnosis being made in the second decade of life in 4 patients (families 1, 3, and 4) and at age 34 in 1 (family 2). Refractory ventricular arrhythmias (tachycardia or fibrillation), severely reduced left ventricular ejection fractions, elevated left ventricular diastolic dimensions, and elevated brain natriuretic peptide (BNP) levels reported. All developed severe heart failure requiring placement of a left ventricular assist device for circulatory support, and at least 1 underwent cardiac transplantation.
Sources: Literature
Dilated Cardiomyopathy v1.7 BAG5 Zornitza Stark Marked gene: BAG5 as ready
Dilated Cardiomyopathy v1.7 BAG5 Zornitza Stark Gene: bag5 has been classified as Green List (High Evidence).
Dilated Cardiomyopathy v1.7 BAG5 Zornitza Stark Classified gene: BAG5 as Green List (high evidence)
Dilated Cardiomyopathy v1.7 BAG5 Zornitza Stark Gene: bag5 has been classified as Green List (High Evidence).
Dilated Cardiomyopathy v1.6 BAG5 Zornitza Stark gene: BAG5 was added
gene: BAG5 was added to Dilated Cardiomyopathy. Sources: Literature
Mode of inheritance for gene: BAG5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BAG5 were set to 35044787
Phenotypes for gene: BAG5 were set to Cardiomyopathy, dilated, 2F, MIM# 619747
Review for gene: BAG5 was set to GREEN
Added comment: 5 individuals from four unrelated families reported. All had early-onset disease, with the diagnosis being made in the second decade of life in 4 patients (families 1, 3, and 4) and at age 34 in 1 (family 2). Refractory ventricular arrhythmias (tachycardia or fibrillation), severely reduced left ventricular ejection fractions, elevated left ventricular diastolic dimensions, and elevated brain natriuretic peptide (BNP) levels reported. All developed severe heart failure requiring placement of a left ventricular assist device for circulatory support, and at least 1 underwent cardiac transplantation.
Sources: Literature
Fetal anomalies v0.3333 NEXMIF Zornitza Stark Marked gene: NEXMIF as ready
Fetal anomalies v0.3333 NEXMIF Zornitza Stark Gene: nexmif has been classified as Red List (Low Evidence).
Fetal anomalies v0.3333 NEXMIF Zornitza Stark Phenotypes for gene: NEXMIF were changed from Intellectual disability and epilepsy; KIAA2022 to Mental retardation, X-linked 98 300912
Fetal anomalies v0.3332 NEXMIF Zornitza Stark Publications for gene: NEXMIF were set to
Fetal anomalies v0.3331 NEXMIF Zornitza Stark Classified gene: NEXMIF as Red List (low evidence)
Fetal anomalies v0.3331 NEXMIF Zornitza Stark Gene: nexmif has been classified as Red List (Low Evidence).
Fetal anomalies v0.3330 NEXMIF Zornitza Stark changed review comment from: Females have been described as both asymptomatic carriers or affected. Given only PTCs have been reported, there is no genotype-phenotype correlation. OMIM describes that a phenotype manifests depending on X-inactivation skewing No reported pathogenic missense to date except for the one LP hemizygous in DDD that is maternally inherited (Decipher) Compared with its hemizygous male counterpart, the heterozygous female disease has less severe intellectual disability, but is more often associated with a severe and intractable myoclonic epilepsy.; to: Females have been described as both asymptomatic carriers or affected. Given only PTCs have been reported, there is no genotype-phenotype correlation. OMIM describes that a phenotype manifests depending on X-inactivation skewing No reported pathogenic missense to date except for the one LP hemizygous in DDD that is maternally inherited (Decipher) Compared with its hemizygous male counterpart, the heterozygous female disease has less severe intellectual disability, but is more often associated with a severe and intractable myoclonic epilepsy.

Typically presents post-natally.
Fetal anomalies v0.3330 NEXMIF Zornitza Stark edited their review of gene: NEXMIF: Changed rating: RED
Fetal anomalies v0.3330 NHP2 Zornitza Stark Marked gene: NHP2 as ready
Fetal anomalies v0.3330 NHP2 Zornitza Stark Gene: nhp2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3330 NHP2 Zornitza Stark Phenotypes for gene: NHP2 were changed from DYSKERATOSIS CONGENITA, AUTOSOMAL RECESSIVE 2 to Dyskeratosis congenita, autosomal recessive 2, MIM# 613987; Høyeraal-Hreidarsson syndrome
Fetal anomalies v0.3329 NHP2 Zornitza Stark Publications for gene: NHP2 were set to
Fetal anomalies v0.3328 NHP2 Zornitza Stark Classified gene: NHP2 as Red List (low evidence)
Fetal anomalies v0.3328 NHP2 Zornitza Stark Gene: nhp2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3327 NHP2 Zornitza Stark changed review comment from: Three individuals reported altogether, of those two had DD/ID.; to: Three individuals reported altogether, one of whom had the more severe HH phenotype.
Fetal anomalies v0.3327 NHP2 Zornitza Stark edited their review of gene: NHP2: Changed rating: RED
Fetal anomalies v0.3327 NONO Zornitza Stark Marked gene: NONO as ready
Fetal anomalies v0.3327 NONO Zornitza Stark Gene: nono has been classified as Green List (High Evidence).
Fetal anomalies v0.3327 NONO Zornitza Stark Phenotypes for gene: NONO were changed from Atresia; Ventricular septal defect (VSD); Pulmonary stenosis; Ebstein s anomaly; Left ventricular non-compaction cardiomyopathy (LVNC) to Mental retardation, X-linked, syndromic 34, MIM# 300967; Ventricular septal defect (VSD); Pulmonary stenosis; Ebstein s anomaly; Left ventricular non-compaction cardiomyopathy (LVNC)
Fetal anomalies v0.3326 NONO Zornitza Stark Publications for gene: NONO were set to 32397791; 26571461; 27329731; 27550220
Fetal anomalies v0.3326 NONO Zornitza Stark Publications for gene: NONO were set to 32397791
Fetal anomalies v0.3325 NONO Zornitza Stark Classified gene: NONO as Green List (high evidence)
Fetal anomalies v0.3325 NONO Zornitza Stark Gene: nono has been classified as Green List (High Evidence).
Fetal anomalies v0.3324 KIAA0753 Zornitza Stark Marked gene: KIAA0753 as ready
Fetal anomalies v0.3324 KIAA0753 Zornitza Stark Gene: kiaa0753 has been classified as Green List (High Evidence).
Fetal anomalies v0.3324 KIAA0753 Zornitza Stark Phenotypes for gene: KIAA0753 were changed from Orofaciodigital syndrome XV, MONDO:0014932; ?Orofaciodigital syndrome XV, OMIM:617127 to Orofaciodigital syndrome XV, MONDO:0014932; Orofaciodigital syndrome XV, OMIM:617127; Joubert syndrome
Fetal anomalies v0.3323 KIAA0753 Zornitza Stark Publications for gene: KIAA0753 were set to 28220259; 29138412; 26643951
Fetal anomalies v0.3322 KIAA0753 Zornitza Stark Classified gene: KIAA0753 as Green List (high evidence)
Fetal anomalies v0.3322 KIAA0753 Zornitza Stark Gene: kiaa0753 has been classified as Green List (High Evidence).
Fetal anomalies v0.3321 KIAA0753 Zornitza Stark edited their review of gene: KIAA0753: Changed rating: GREEN
Fetal anomalies v0.3321 KDM1A Zornitza Stark Marked gene: KDM1A as ready
Fetal anomalies v0.3321 KDM1A Zornitza Stark Gene: kdm1a has been classified as Green List (High Evidence).
Fetal anomalies v0.3321 KDM1A Zornitza Stark Phenotypes for gene: KDM1A were changed from Developmental delay and distinctive facial features to Cleft palate, psychomotor retardation, and distinctive facial features 616728
Fetal anomalies v0.3320 KDM1A Zornitza Stark Publications for gene: KDM1A were set to
Fetal anomalies v0.3319 KDM1A Zornitza Stark Mode of inheritance for gene: KDM1A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3318 KDM1A Zornitza Stark Classified gene: KDM1A as Green List (high evidence)
Fetal anomalies v0.3318 KDM1A Zornitza Stark Gene: kdm1a has been classified as Green List (High Evidence).
Fetal anomalies v0.3317 KDM1A Zornitza Stark changed review comment from: Three unrelated individuals with de novo missense variants in this gene and a neurodevelopmental phenotype. Note one of the individuals also had a de novo indel in ANKRD11. Some data published subsequently demonstrating functional impact of all three variants.; to: Three unrelated individuals with de novo missense variants in this gene and a neurodevelopmental phenotype. Note one of the individuals also had a de novo indel in ANKRD11. Some data published subsequently demonstrating functional impact of all three variants.

LGA, cleft palate, brain abnormalities reported.
Fetal anomalies v0.3317 KCNQ5 Zornitza Stark Marked gene: KCNQ5 as ready
Fetal anomalies v0.3317 KCNQ5 Zornitza Stark Gene: kcnq5 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3317 KCNQ5 Zornitza Stark Phenotypes for gene: KCNQ5 were changed from Intellectual Disability with or without Epileptic Encephalopathy to Mental retardation, autosomal dominant 46, MIM# 617601
Fetal anomalies v0.3316 KCNQ5 Zornitza Stark Publications for gene: KCNQ5 were set to
Fetal anomalies v0.3315 KCNQ5 Zornitza Stark Mode of inheritance for gene: KCNQ5 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3314 KCNQ5 Zornitza Stark Classified gene: KCNQ5 as Red List (low evidence)
Fetal anomalies v0.3314 KCNQ5 Zornitza Stark Gene: kcnq5 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3313 KCNQ5 Zornitza Stark changed review comment from: Four unrelated individuals reported with de novo missense variants in this gene and a neurodevelopmental disorder, including epileptic encephalopathy in some. Three of the variants demonstrated to be LoF and one GoF. Further individual reported in PMID 30359776 with mild ID and absence epilepsy and an intragenic duplication causing likely LoF.; to: Four unrelated individuals reported with de novo missense variants in this gene and a neurodevelopmental disorder, including epileptic encephalopathy in some. Three of the variants demonstrated to be LoF and one GoF. Further individual reported in PMID 30359776 with mild ID and absence epilepsy and an intragenic duplication causing likely LoF.

Clinical presentation is typically post-natal.
Fetal anomalies v0.3313 KCNQ5 Zornitza Stark edited their review of gene: KCNQ5: Changed rating: RED
Fetal anomalies v0.3313 KCNJ6 Zornitza Stark Marked gene: KCNJ6 as ready
Fetal anomalies v0.3313 KCNJ6 Zornitza Stark Gene: kcnj6 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3313 KCNJ6 Zornitza Stark Phenotypes for gene: KCNJ6 were changed from KEPPEN-LUBINSKY SYNDROME to Keppen-Lubinsky syndrome, MIM# 614098; MONDO:0013572
Fetal anomalies v0.3312 KCNJ6 Zornitza Stark Publications for gene: KCNJ6 were set to
Fetal anomalies v0.3311 KCNJ6 Zornitza Stark Mode of inheritance for gene: KCNJ6 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3310 KCNJ6 Zornitza Stark Classified gene: KCNJ6 as Red List (low evidence)
Fetal anomalies v0.3310 KCNJ6 Zornitza Stark Gene: kcnj6 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3309 KCNJ6 Zornitza Stark changed review comment from: Keppen-Lubinsky syndrome characterised by severely delayed psychomotor development, hypertonia, hyperreflexia, generalized lipodystrophy giving an aged appearance, and distinctive dysmorphic features, including microcephaly, prominent eyes, narrow nasal bridge, and open mouth.

Four unrelated individuals reported with de novo variants in this gene (one recurred in 2), mouse model. One of the individuals did not have lipodystrophy but had a prominent hyperkinetic movement disorder.; to: Keppen-Lubinsky syndrome characterised by severely delayed psychomotor development, hypertonia, hyperreflexia, generalized lipodystrophy giving an aged appearance, and distinctive dysmorphic features, including microcephaly, prominent eyes, narrow nasal bridge, and open mouth.

Four unrelated individuals reported with de novo variants in this gene (one recurred in 2), mouse model. One of the individuals did not have lipodystrophy but had a prominent hyperkinetic movement disorder.

Clinical presentation is typically post-natal, with normal growth parameters at birth.
Fetal anomalies v0.3309 KCNJ6 Zornitza Stark edited their review of gene: KCNJ6: Changed rating: RED
Fetal anomalies v0.3309 KCNH1 Zornitza Stark Marked gene: KCNH1 as ready
Fetal anomalies v0.3309 KCNH1 Zornitza Stark Gene: kcnh1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3309 KCNH1 Zornitza Stark Phenotypes for gene: KCNH1 were changed from TEMPLE BARRAISTER SYNDROME to Zimmermann-Laband syndrome 1, OMIM:135500
Fetal anomalies v0.3308 KCNH1 Zornitza Stark Publications for gene: KCNH1 were set to
Fetal anomalies v0.3307 KCNH1 Zornitza Stark Mode of inheritance for gene: KCNH1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3306 KCNH1 Zornitza Stark Classified gene: KCNH1 as Green List (high evidence)
Fetal anomalies v0.3306 KCNH1 Zornitza Stark Gene: kcnh1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3305 KCNH1 Zornitza Stark reviewed gene: KCNH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Zimmermann-Laband syndrome 1, OMIM:135500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3305 KCNC3 Zornitza Stark Marked gene: KCNC3 as ready
Fetal anomalies v0.3305 KCNC3 Zornitza Stark Gene: kcnc3 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3305 KCNC3 Zornitza Stark Phenotypes for gene: KCNC3 were changed from SPINOCEREBELLAR ATAXIA TYPE 13 to Spinocerebellar ataxia 13, MIM#605259
Fetal anomalies v0.3304 KCNC3 Zornitza Stark Mode of inheritance for gene: KCNC3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3303 KCNC3 Zornitza Stark Classified gene: KCNC3 as Red List (low evidence)
Fetal anomalies v0.3303 KCNC3 Zornitza Stark Gene: kcnc3 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3302 KCNC3 Zornitza Stark changed review comment from: Mild ID reported only in some individuals with this progressive neurological disorder.; to: Progressive neurological disorder, childhood onset.
Fetal anomalies v0.3302 KATNB1 Zornitza Stark Marked gene: KATNB1 as ready
Fetal anomalies v0.3302 KATNB1 Zornitza Stark Gene: katnb1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3302 KATNB1 Zornitza Stark Classified gene: KATNB1 as Green List (high evidence)
Fetal anomalies v0.3302 KATNB1 Zornitza Stark Gene: katnb1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3301 JAM3 Zornitza Stark Marked gene: JAM3 as ready
Fetal anomalies v0.3301 JAM3 Zornitza Stark Gene: jam3 has been classified as Green List (High Evidence).
Fetal anomalies v0.3301 JAM3 Zornitza Stark Phenotypes for gene: JAM3 were changed from HEMORRHAGIC DESTRUCTION OF THE BRAIN, SUBEPENDYMAL CALCIFICATION, AND CATARACTS to Haemorrhagic destruction of the brain, subependymal calcification, and cataracts, MIM# 613730
Fetal anomalies v0.3300 JAM3 Zornitza Stark Publications for gene: JAM3 were set to
Fetal anomalies v0.3299 JAM3 Zornitza Stark Classified gene: JAM3 as Green List (high evidence)
Fetal anomalies v0.3299 JAM3 Zornitza Stark Gene: jam3 has been classified as Green List (High Evidence).
Fetal anomalies v0.3298 JAM3 Zornitza Stark changed review comment from: Autosomal recessive disorder with a distinctive phenotype comprising haemorrhagic destruction of the brain, subependymal calcification, and congenital cataracts. Affected individuals have a catastrophic neurologic clinical course resulting in death in infancy. Four unrelated families reported.; to: Autosomal recessive disorder with a distinctive phenotype comprising haemorrhagic destruction of the brain, subependymal calcification, and congenital cataracts. Affected individuals have a catastrophic neurologic clinical course resulting in death in infancy. Four unrelated families reported.

Perinatal presentation.
Fetal anomalies v0.3298 ITCH Zornitza Stark Marked gene: ITCH as ready
Fetal anomalies v0.3298 ITCH Zornitza Stark Gene: itch has been classified as Red List (Low Evidence).
Fetal anomalies v0.3298 ITCH Zornitza Stark Phenotypes for gene: ITCH were changed from AUTOIMMUNE DISEASE, SYNDROMIC MULTISYSTEM to Autoimmune disease, multisystem, with facial dysmorphism, MIM#613385
Fetal anomalies v0.3297 ITCH Zornitza Stark Publications for gene: ITCH were set to
Fetal anomalies v0.3296 ITCH Zornitza Stark Classified gene: ITCH as Red List (low evidence)
Fetal anomalies v0.3296 ITCH Zornitza Stark Gene: itch has been classified as Red List (Low Evidence).
Fetal anomalies v0.3295 ITCH Zornitza Stark changed review comment from: Multiple affected individuals reported from Amish community, however, single variant, founder effect.; to: Multiple affected individuals reported from Amish community, however, single variant, founder effect. Short stature but age of onset uncertain.
Fetal anomalies v0.3295 ITCH Zornitza Stark edited their review of gene: ITCH: Changed rating: RED
Fetal anomalies v0.3295 IRX5 Zornitza Stark Marked gene: IRX5 as ready
Fetal anomalies v0.3295 IRX5 Zornitza Stark Gene: irx5 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3295 IRX5 Zornitza Stark Phenotypes for gene: IRX5 were changed from HYPERTELORISM, SEVERE, WITH MIDFACE PROMINENCE, MYOPIA, MENTAL RETARDATION, AND BONE FRAGILITY to Hamamy syndrome, MIM# 611174
Fetal anomalies v0.3294 IRX5 Zornitza Stark Publications for gene: IRX5 were set to
Fetal anomalies v0.3293 IRX5 Zornitza Stark changed review comment from: Two families reported with Hamamy syndrome, some functional data. ID was borderline.; to: Two families reported with Hamamy syndrome, some functional data. Multiple congenital anomalies reported: CHD, craniosynostosis, syndactyly.
Fetal anomalies v0.3293 IRX5 Zornitza Stark edited their review of gene: IRX5: Changed rating: AMBER
Fetal anomalies v0.3293 IFT81 Zornitza Stark Marked gene: IFT81 as ready
Fetal anomalies v0.3293 IFT81 Zornitza Stark Gene: ift81 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3293 IFT52 Zornitza Stark Marked gene: IFT52 as ready
Fetal anomalies v0.3293 IFT52 Zornitza Stark Gene: ift52 has been classified as Green List (High Evidence).
Fetal anomalies v0.3293 IFT52 Zornitza Stark Classified gene: IFT52 as Green List (high evidence)
Fetal anomalies v0.3293 IFT52 Zornitza Stark Gene: ift52 has been classified as Green List (High Evidence).
Fetal anomalies v0.3292 ICK Zornitza Stark Marked gene: ICK as ready
Fetal anomalies v0.3292 ICK Zornitza Stark Gene: ick has been classified as Green List (High Evidence).
Fetal anomalies v0.3292 ICK Zornitza Stark Publications for gene: ICK were set to 24853502; 19185282; 27466187; 27069622
Fetal anomalies v0.3291 ICK Zornitza Stark Classified gene: ICK as Green List (high evidence)
Fetal anomalies v0.3291 ICK Zornitza Stark Gene: ick has been classified as Green List (High Evidence).
Fetal anomalies v0.3290 ICK Zornitza Stark changed review comment from: 6 affected individuals from 2 Amish families reported originally (founder effect); another Turkish family reported since. However, renal cysts only reported in the Amish families, emerging ciliopathy gene, renal phenotype remains to be elucidated.
Sources: Expert list; to: Ciliopathy phenotype.

Sources: Expert list
Fetal anomalies v0.3290 ICK Zornitza Stark edited their review of gene: ICK: Changed rating: GREEN; Changed phenotypes: Endocrine-cerebroosteodysplasia, MIM# 612651
Mendeliome v0.10949 BCO1 Zornitza Stark Marked gene: BCO1 as ready
Mendeliome v0.10949 BCO1 Zornitza Stark Gene: bco1 has been classified as Red List (Low Evidence).
Mendeliome v0.10949 BCO1 Zornitza Stark Classified gene: BCO1 as Red List (low evidence)
Mendeliome v0.10949 BCO1 Zornitza Stark Gene: bco1 has been classified as Red List (Low Evidence).
Mendeliome v0.10948 PRKCH Zornitza Stark Marked gene: PRKCH as ready
Mendeliome v0.10948 PRKCH Zornitza Stark Gene: prkch has been classified as Red List (Low Evidence).
Mendeliome v0.10948 PRKCH Zornitza Stark Classified gene: PRKCH as Red List (low evidence)
Mendeliome v0.10948 PRKCH Zornitza Stark Gene: prkch has been classified as Red List (Low Evidence).
Mendeliome v0.10947 ALDH2 Zornitza Stark Marked gene: ALDH2 as ready
Mendeliome v0.10947 ALDH2 Zornitza Stark Gene: aldh2 has been classified as Red List (Low Evidence).
Mendeliome v0.10947 ALDH2 Zornitza Stark Publications for gene: ALDH2 were set to
Mendeliome v0.10946 ALDH2 Zornitza Stark Classified gene: ALDH2 as Red List (low evidence)
Mendeliome v0.10946 ALDH2 Zornitza Stark Gene: aldh2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3290 CTNS Zornitza Stark Marked gene: CTNS as ready
Fetal anomalies v0.3290 CTNS Zornitza Stark Gene: ctns has been classified as Red List (Low Evidence).
Fetal anomalies v0.3290 CTNS Zornitza Stark Phenotypes for gene: CTNS were changed from CYSTINOSIS NEPHROPATHIC TYPE; CYSTINOSIS LATE-ONSET JUVENILE OR ADOLESCENT NEPHROPATHIC TYPE; CYSTINOSIS ADULT NON-NEPHROPATHIC TYPE to Cystinosis, late-onset juvenile or adolescent nephropathic MIM#219900; Cystinosis, nephropathic MIM#219800; Cystinosis, ocular nonnephropathic MIM#219750
Fetal anomalies v0.3289 CTNS Zornitza Stark Publications for gene: CTNS were set to
Fetal anomalies v0.3288 CTNS Zornitza Stark reviewed gene: CTNS: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Cystinosis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3288 SLC52A2 Zornitza Stark Marked gene: SLC52A2 as ready
Fetal anomalies v0.3288 SLC52A2 Zornitza Stark Gene: slc52a2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3288 SLC52A2 Zornitza Stark Phenotypes for gene: SLC52A2 were changed from Brown-Vialetto-Van Laere syndrome 2 to Brown-Vialetto-Van Laere syndrome 2 (MIM#614707)
Fetal anomalies v0.3287 SLC52A2 Zornitza Stark Publications for gene: SLC52A2 were set to 22740598; 24253200
Fetal anomalies v0.3286 SLC4A4 Zornitza Stark Marked gene: SLC4A4 as ready
Fetal anomalies v0.3286 SLC4A4 Zornitza Stark Gene: slc4a4 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3286 SLC4A4 Zornitza Stark Phenotypes for gene: SLC4A4 were changed from PROXIMAL RENAL TUBULAR ACIDOSIS WITH OCULAR ABNORMALITIES to Renal tubular acidosis, proximal, with ocular abnormalities (MIM#604278)
Fetal anomalies v0.3285 SLC39A13 Zornitza Stark Marked gene: SLC39A13 as ready
Fetal anomalies v0.3285 SLC39A13 Zornitza Stark Gene: slc39a13 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3285 SLC39A13 Zornitza Stark Phenotypes for gene: SLC39A13 were changed from SPONDYLOEPIMETAPHYSEAL DYSPLASIA WITH ABNORMAL DENTITION; EHLERS-DANLOS SYNDROME-LIKE SPONDYLOCHEIRODYSPLASIA to Ehlers-Danlos syndrome, spondylodysplastic type, 3 (MIM#612350)
Fetal anomalies v0.3284 SLC39A13 Zornitza Stark Publications for gene: SLC39A13 were set to
Clefting disorders v0.175 ZBTB24 Zornitza Stark Marked gene: ZBTB24 as ready
Clefting disorders v0.175 ZBTB24 Zornitza Stark Gene: zbtb24 has been classified as Red List (Low Evidence).
Clefting disorders v0.175 ZBTB24 Zornitza Stark Phenotypes for gene: ZBTB24 were changed from IMMUNODEFICIENCY-CENTROMERIC INSTABILITY-FACIAL ANOMALIES SYNDROME 2; ICF2 to Immunodeficiency-centromeric instability-facial anomalies syndrome 2 - MIM#614069
Clefting disorders v0.174 ZBTB24 Zornitza Stark Publications for gene: ZBTB24 were set to 23486536
Clefting disorders v0.173 ZBTB24 Zornitza Stark Classified gene: ZBTB24 as Red List (low evidence)
Clefting disorders v0.173 ZBTB24 Zornitza Stark Gene: zbtb24 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3283 ZBTB24 Zornitza Stark Marked gene: ZBTB24 as ready
Fetal anomalies v0.3283 ZBTB24 Zornitza Stark Gene: zbtb24 has been classified as Green List (High Evidence).
Fetal anomalies v0.3283 ZBTB24 Zornitza Stark Classified gene: ZBTB24 as Green List (high evidence)
Fetal anomalies v0.3283 ZBTB24 Zornitza Stark Gene: zbtb24 has been classified as Green List (High Evidence).
Fetal anomalies v0.3282 SLC25A26 Zornitza Stark Marked gene: SLC25A26 as ready
Fetal anomalies v0.3282 SLC25A26 Zornitza Stark Gene: slc25a26 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3282 SLC25A26 Zornitza Stark Phenotypes for gene: SLC25A26 were changed from INTRA-MITOCHONDRIAL METHYLATION DEFICIENCY to Combined oxidative phosphorylation deficiency 28 (MIM#616794)
Fetal anomalies v0.3281 SLC25A26 Zornitza Stark Publications for gene: SLC25A26 were set to
Fetal anomalies v0.3280 SLC25A26 Zornitza Stark Classified gene: SLC25A26 as Amber List (moderate evidence)
Fetal anomalies v0.3280 SLC25A26 Zornitza Stark Gene: slc25a26 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10945 BCO1 Ain Roesley reviewed gene: BCO1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None; Current diagnostic: yes
Mendeliome v0.10945 PRKCH Ain Roesley reviewed gene: PRKCH: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None; Current diagnostic: yes
Mendeliome v0.10945 ALDH2 Ain Roesley reviewed gene: ALDH2: Rating: RED; Mode of pathogenicity: None; Publications: 31368097; Phenotypes: ; Mode of inheritance: None; Current diagnostic: yes
Fetal anomalies v0.3279 CTNS Belinda Chong reviewed gene: CTNS: Rating: RED; Mode of pathogenicity: None; Publications: 32564281, 20301574, 9537412, 31068690; Phenotypes: Cystinosis, late-onset juvenile or adolescent nephropathic MIM#219900, Cystinosis, nephropathic MIM#219800, Cystinosis, ocular nonnephropathic MIM#219750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Hereditary Spastic Paraplegia - paediatric v1.25 ABHD16A Zornitza Stark Phenotypes for gene: ABHD16A were changed from Spastic paraplegia; intellectual disability; callosome to Spastic paraplegia 86, autosomal recessive, MIM# 619735; Intellectual Disability; Corpus callosum abnormalities
Hereditary Spastic Paraplegia - paediatric v1.24 ABHD16A Zornitza Stark reviewed gene: ABHD16A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 86, autosomal recessive, MIM# 619735, Intellectual Disability, Corpus callosum abnormalities; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy - paediatric v0.244 ABHD16A Zornitza Stark Phenotypes for gene: ABHD16A were changed from Spastic paraplegia; intellectual disability; callosome to Spastic paraplegia 86, autosomal recessive, MIM# 619735; Intellectual Disability; Corpus callosum abnormalities
Leukodystrophy - paediatric v0.243 ABHD16A Zornitza Stark reviewed gene: ABHD16A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 86, autosomal recessive, MIM# 619735, Intellectual Disability, Corpus callosum abnormalities; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4498 ABHD16A Zornitza Stark Phenotypes for gene: ABHD16A were changed from Spastic paraplegia; Intellectual Disability; Callosome to Spastic paraplegia 86, autosomal recessive, MIM# 619735; Intellectual Disability; Corpus callosum abnormalities
Intellectual disability syndromic and non-syndromic v0.4497 ABHD16A Zornitza Stark edited their review of gene: ABHD16A: Changed phenotypes: Spastic paraplegia 86, autosomal recessive, MIM# 619735, Intellectual Disability, Corpus callosum abnormalities; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Callosome v0.357 ABHD16A Zornitza Stark Phenotypes for gene: ABHD16A were changed from Spastic paraplegia; Intellectual Disability; Callosome to Spastic paraplegia 86, autosomal recessive, MIM# 619735; Intellectual Disability; Corpus callosum abnormalities
Callosome v0.356 ABHD16A Zornitza Stark reviewed gene: ABHD16A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 86, autosomal recessive, MIM# 619735, Intellectual Disability, Corpus callosum abnormalities; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10945 ABHD16A Zornitza Stark Marked gene: ABHD16A as ready
Mendeliome v0.10945 ABHD16A Zornitza Stark Gene: abhd16a has been classified as Green List (High Evidence).
Mendeliome v0.10945 ABHD16A Zornitza Stark Phenotypes for gene: ABHD16A were changed from Spastic paraplegia; Intellectual Disability; Callosome to Spastic paraplegia 86, autosomal recessive, MIM# 619735; Intellectual Disability; Corpus callosum abnormalities
Mendeliome v0.10944 ABHD16A Zornitza Stark reviewed gene: ABHD16A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 86, autosomal recessive, MIM# 619735; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3279 SLC52A2 Daniel Flanagan reviewed gene: SLC52A2: Rating: RED; Mode of pathogenicity: None; Publications: 10797435, 22740598, 22864630; Phenotypes: Brown-Vialetto-Van Laere syndrome 2 (MIM#614707); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3279 SLC4A4 Daniel Flanagan reviewed gene: SLC4A4: Rating: RED; Mode of pathogenicity: None; Publications: 10545938, 11274232; Phenotypes: Renal tubular acidosis, proximal, with ocular abnormalities (MIM#604278); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3279 SLC39A13 Daniel Flanagan reviewed gene: SLC39A13: Rating: RED; Mode of pathogenicity: None; Publications: 18985159, 18513683, 28306229, 28306225; Phenotypes: Ehlers-Danlos syndrome, spondylodysplastic type, 3 (MIM#612350); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Clefting disorders v0.172 ZBTB24 Krithika Murali reviewed gene: ZBTB24: Rating: RED; Mode of pathogenicity: None; Publications: 32865561, 21596365, 29023266, 32061411, 21906047, 28128455, 23739126, 22786748; Phenotypes: Immunodeficiency-centromeric instability-facial anomalies syndrome 2 - MIM#614069; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3279 ZBTB24 Krithika Murali gene: ZBTB24 was added
gene: ZBTB24 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ZBTB24 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZBTB24 were set to 32865561; 21596365; 29023266; 32061411; 21906047; 28128455; 23739126; 22786748
Phenotypes for gene: ZBTB24 were set to Immunodeficiency-centromeric instability-facial anomalies syndrome 2 - MIM#614069
Review for gene: ZBTB24 was set to GREEN
Added comment: Well reported association with ICF2 (immunodeficiency-centromeric instability facial anomalies syndrome 2). Patients have immunodeficiency (mainly hypo/agammaglobulinemia in the presence of B cells), recurrent infections (namely respiratory and gastrointestinal) and dysmorphic facies.

Although antenatal features not thoroughly described for published cases, low birth weight has been a reported feature as well as hypertelorism and micrognathia/retrognathia - these have the potential to be detected prenatally.

PMID 32865561 Helfricht et al 2020 - "loss of ZBTB24 in B cells from mice and ICF2 patients affects nonhomologous end-joining (NHEJ) during immunoglobulin class-switch recombination and consequently impairs immunoglobulin production and isotype balance".

PMID 32061411 Banday. et al 2020 - report a patient with this condition and granulomatous hepatitis. Review phenotype of previously reported patients, low birth weight and facial dysmorphism including micrognathia noted in other cases.

PMID 29023266 Conrad et al 2017 - describe a 17 month old boy with recurrent infections, growth failure, facial anomalies (including hyperterlorism/low set ears), and inflammatory bowel disease. No antenatal information.

PMID 28128455 van den Boogaard 2017 - 5 new patients described

PMID 23739126 Nitta et al 2013 - report 3 unrelated patients, x1 patient - lower birth weight and head circumference. At age 5 had macrocephaly, hyperterlorism. Noted to have bilateral hydronephrosis. x1 patient BW 2660g, micrognathia, hyperterlorism.

PMID 21906047 Chouery et al 2012 - 3 siblings from a Lebanese family with novel homozygous LoF variant. Apparently normal pregnancies, at time of diagnostic assessment HC between the 5th and 15th centiles, height below the 5th percentile. Dysmorphic features including high arched palate, small chin, retrognathism and everted lower lips.

PMID 22786748 Cerbone et al 2012 - report an 8 year old M of consanguineous Moroccan ancestry with ID, dysmorphic features, cafe au last macules and a large arachnoid cyst in the right temporal region, causing compression of the temporal lobe and lateral ventricle

PMID 21596365 de Greef et al 2011 - report 4 new unrelated patients, no antenatal information
Sources: Literature
Fetal anomalies v0.3279 SLC25A26 Daniel Flanagan reviewed gene: SLC25A26: Rating: AMBER; Mode of pathogenicity: None; Publications: 26522469; Phenotypes: Combined oxidative phosphorylation deficiency 28 (MIM#616794); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.105 EHMT1 Zornitza Stark Marked gene: EHMT1 as ready
Microcephaly v1.105 EHMT1 Zornitza Stark Gene: ehmt1 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.105 EHMT1 Zornitza Stark Classified gene: EHMT1 as Amber List (moderate evidence)
Microcephaly v1.105 EHMT1 Zornitza Stark Gene: ehmt1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3279 SLC19A3 Zornitza Stark Marked gene: SLC19A3 as ready
Fetal anomalies v0.3279 SLC19A3 Zornitza Stark Gene: slc19a3 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3279 SLC19A3 Zornitza Stark Phenotypes for gene: SLC19A3 were changed from THIAMINE METABOLISM DYSFUNCTION SYNDROME 2 to Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2) (MIM#607483)
Fetal anomalies v0.3278 SLC19A3 Zornitza Stark Publications for gene: SLC19A3 were set to
Fetal anomalies v0.3277 SIX1 Zornitza Stark Marked gene: SIX1 as ready
Fetal anomalies v0.3277 SIX1 Zornitza Stark Gene: six1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3277 SIX1 Zornitza Stark Phenotypes for gene: SIX1 were changed from BRANCHIOOTIC SYNDROME TYPE 3; DEAFNESS AUTOSOMAL DOMINANT TYPE 23 to Deafness, autosomal dominant 23 (MIM# 605192); Branchiootic syndrome 3 (MIM# 608389)
Fetal anomalies v0.3276 SIX1 Zornitza Stark Mode of inheritance for gene: SIX1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3275 SIX1 Zornitza Stark reviewed gene: SIX1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Branchiootic syndrome 3, MIM# 608389; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v1.104 EHMT1 Elena Savva gene: EHMT1 was added
gene: EHMT1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: EHMT1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: EHMT1 were set to PMID: 29228531; 28361100; 21910222; 19264732
Phenotypes for gene: EHMT1 were set to Kleefstra syndrome 1 MIM#610253
Review for gene: EHMT1 was set to AMBER
Added comment: OMIM/PMID: 29228531/PMID: 21910222 - microcephaly describes as a feature of kleefstra syndrome

PMID: 28361100 - 18-year-old woman with intellectual disability, severely limited speech, hypotonia, microcephaly, and facial dysmorphisms, de novo single-base frameshift deletion

PMID: 19264732 - Microcephaly was noted in 6/15 patients with a deletion and 2/6 cases with a "mutation and was already present at birth" unclear what mutations these are

Common cause of disease is a microdeletion of 9q34.3, in which microcephaly is commonly reported.

Amber due to inconsistent reports in SNV cases.
Sources: Literature
Fetal anomalies v0.3275 SIM1 Zornitza Stark Marked gene: SIM1 as ready
Fetal anomalies v0.3275 SIM1 Zornitza Stark Gene: sim1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3275 SIM1 Zornitza Stark Mode of inheritance for gene: SIM1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3274 SIK1 Zornitza Stark Marked gene: SIK1 as ready
Fetal anomalies v0.3274 SIK1 Zornitza Stark Gene: sik1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3274 SIK1 Zornitza Stark Phenotypes for gene: SIK1 were changed from NEONATAL EPILEPSY SPECTRUM to Developmental and epileptic encephalopathy 30 (MIM#616341)
Fetal anomalies v0.3273 SIK1 Zornitza Stark Publications for gene: SIK1 were set to
Fetal anomalies v0.3272 SIK1 Zornitza Stark Mode of inheritance for gene: SIK1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3271 SDHA Zornitza Stark Marked gene: SDHA as ready
Fetal anomalies v0.3271 SDHA Zornitza Stark Gene: sdha has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3271 SDHA Zornitza Stark Phenotypes for gene: SDHA were changed from LEIGH SYNDROME to Cardiomyopathy, dilated, 1GG (MIM#613642); Mitochondrial complex II deficiency, nuclear type 1 (MIM#252011)
Fetal anomalies v0.3270 SDHA Zornitza Stark Publications for gene: SDHA were set to
Fetal anomalies v0.3269 SDHA Zornitza Stark Classified gene: SDHA as Amber List (moderate evidence)
Fetal anomalies v0.3269 SDHA Zornitza Stark Gene: sdha has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3268 HMX1 Zornitza Stark Marked gene: HMX1 as ready
Fetal anomalies v0.3268 HMX1 Zornitza Stark Gene: hmx1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3268 HMX1 Zornitza Stark Phenotypes for gene: HMX1 were changed from OCULOAURICULAR SYNDROME to Oculoauricular syndrome, MIM#612109
Fetal anomalies v0.3267 HMX1 Zornitza Stark Classified gene: HMX1 as Green List (high evidence)
Fetal anomalies v0.3267 HMX1 Zornitza Stark Gene: hmx1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3266 HIST1H4C Zornitza Stark Marked gene: HIST1H4C as ready
Fetal anomalies v0.3266 HIST1H4C Zornitza Stark Gene: hist1h4c has been classified as Green List (High Evidence).
Fetal anomalies v0.3266 HIST1H4C Zornitza Stark Phenotypes for gene: HIST1H4C were changed from HIST1H4C to Growth delay, microcephaly and intellectual disability
Fetal anomalies v0.3265 HIST1H4C Zornitza Stark Publications for gene: HIST1H4C were set to
Fetal anomalies v0.3264 HIST1H4C Zornitza Stark Mode of inheritance for gene: HIST1H4C was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3263 HIST1H4C Zornitza Stark Classified gene: HIST1H4C as Green List (high evidence)
Fetal anomalies v0.3263 HIST1H4C Zornitza Stark Gene: hist1h4c has been classified as Green List (High Evidence).
Fetal anomalies v0.3262 SLC19A3 Daniel Flanagan reviewed gene: SLC19A3: Rating: RED; Mode of pathogenicity: None; Publications: 23423671, 24878502, 19387023, 20065143; Phenotypes: Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2) (MIM#607483); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3262 HIST1H1E Zornitza Stark Marked gene: HIST1H1E as ready
Fetal anomalies v0.3262 HIST1H1E Zornitza Stark Gene: hist1h1e has been classified as Green List (High Evidence).
Fetal anomalies v0.3262 HIST1H1E Zornitza Stark Publications for gene: HIST1H1E were set to
Fetal anomalies v0.3261 HIST1H1E Zornitza Stark Mode of inheritance for gene: HIST1H1E was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3260 HIST1H1E Zornitza Stark Classified gene: HIST1H1E as Green List (high evidence)
Fetal anomalies v0.3260 HIST1H1E Zornitza Stark Gene: hist1h1e has been classified as Green List (High Evidence).
Fetal anomalies v0.3259 HGSNAT Zornitza Stark Marked gene: HGSNAT as ready
Fetal anomalies v0.3259 HGSNAT Zornitza Stark Gene: hgsnat has been classified as Red List (Low Evidence).
Fetal anomalies v0.3259 HGSNAT Zornitza Stark Phenotypes for gene: HGSNAT were changed from MUCOPOLYSACCHARIDOSIS TYPE 3C to Mucopolysaccharidosis type IIIC (Sanfilippo C), MIM# 252930; MONDO:0009657
Fetal anomalies v0.3258 HGSNAT Zornitza Stark Publications for gene: HGSNAT were set to
Fetal anomalies v0.3257 HGSNAT Zornitza Stark Classified gene: HGSNAT as Red List (low evidence)
Fetal anomalies v0.3257 HGSNAT Zornitza Stark Gene: hgsnat has been classified as Red List (Low Evidence).
Fetal anomalies v0.3256 HGSNAT Zornitza Stark edited their review of gene: HGSNAT: Changed rating: RED
Fetal anomalies v0.3256 HESX1 Zornitza Stark Marked gene: HESX1 as ready
Fetal anomalies v0.3256 HESX1 Zornitza Stark Gene: hesx1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3256 HESX1 Zornitza Stark Publications for gene: HESX1 were set to
Fetal anomalies v0.3255 HESX1 Zornitza Stark Classified gene: HESX1 as Green List (high evidence)
Fetal anomalies v0.3255 HESX1 Zornitza Stark Gene: hesx1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3254 HESX1 Zornitza Stark changed review comment from: Variants in this gene are associated with a spectrum of abnormalities: isolated pituitary deficiency through to septo-optic dysplasia. Optic nerve hypoplasia reported as part of this rather than AMC.; to: Variants in this gene are associated with a spectrum of abnormalities including corpus callosum abnormalities and hand abnormalities.
Fetal anomalies v0.3254 HESX1 Zornitza Stark edited their review of gene: HESX1: Changed rating: GREEN; Changed phenotypes: Septooptic dysplasia, MIM# 182230, Pituitary hormone deficiency, combined, 5, MIM# 182230
Fetal anomalies v0.3254 SIX1 Daniel Flanagan reviewed gene: SIX1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Deafness, autosomal dominant 23 (MIM# 605192), Branchiootic syndrome 3 (MIM# 608389); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3254 SIM1 Daniel Flanagan reviewed gene: SIM1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3254 HADHB Zornitza Stark Marked gene: HADHB as ready
Fetal anomalies v0.3254 HADHB Zornitza Stark Gene: hadhb has been classified as Green List (High Evidence).
Fetal anomalies v0.3254 HADHB Zornitza Stark Classified gene: HADHB as Green List (high evidence)
Fetal anomalies v0.3254 HADHB Zornitza Stark Gene: hadhb has been classified as Green List (High Evidence).
Fetal anomalies v0.3253 HADHB Zornitza Stark changed review comment from: ID is part of the phenotype.; to: SGA and cardiomyopathy reported.
Fetal anomalies v0.3253 GTF2E2 Zornitza Stark Marked gene: GTF2E2 as ready
Fetal anomalies v0.3253 GTF2E2 Zornitza Stark Gene: gtf2e2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3253 GTF2E2 Zornitza Stark Phenotypes for gene: GTF2E2 were changed from DNA Repair-Proficient Trichothiodystrophy to Trichothiodystrophy 6, nonphotosensitive, MIM #616943
Fetal anomalies v0.3252 GTF2E2 Zornitza Stark Publications for gene: GTF2E2 were set to
Fetal anomalies v0.3251 GTF2E2 Zornitza Stark Classified gene: GTF2E2 as Red List (low evidence)
Fetal anomalies v0.3251 GTF2E2 Zornitza Stark Gene: gtf2e2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3250 GTF2E2 Zornitza Stark commented on gene: GTF2E2: Microcephaly reported but onset uncertain. Craniosynostosis in one individual.
Fetal anomalies v0.3250 GTF2E2 Zornitza Stark edited their review of gene: GTF2E2: Changed rating: RED
Fetal anomalies v0.3250 SIK1 Daniel Flanagan reviewed gene: SIK1: Rating: RED; Mode of pathogenicity: None; Publications: 25839329; Phenotypes: Developmental and epileptic encephalopathy 30 (MIM#616341); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10944 GSPT2 Zornitza Stark Marked gene: GSPT2 as ready
Mendeliome v0.10944 GSPT2 Zornitza Stark Gene: gspt2 has been classified as Red List (Low Evidence).
Mendeliome v0.10944 GSPT2 Zornitza Stark gene: GSPT2 was added
gene: GSPT2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: GSPT2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: GSPT2 were set to 28414775
Phenotypes for gene: GSPT2 were set to Intellectual disability
Review for gene: GSPT2 was set to RED
Added comment: Gene is contained in multi-gene deletions linked to ID.
Sources: Expert Review
Fetal anomalies v0.3250 GSPT2 Zornitza Stark Marked gene: GSPT2 as ready
Fetal anomalies v0.3250 GSPT2 Zornitza Stark Gene: gspt2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3250 GSPT2 Zornitza Stark Phenotypes for gene: GSPT2 were changed from XL INTELLECTUAL DISABILITY to XL intellectual disability
Fetal anomalies v0.3249 GSPT2 Zornitza Stark Publications for gene: GSPT2 were set to
Fetal anomalies v0.3248 GSPT2 Zornitza Stark Classified gene: GSPT2 as Red List (low evidence)
Fetal anomalies v0.3248 GSPT2 Zornitza Stark Gene: gspt2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3247 SDHA Daniel Flanagan reviewed gene: SDHA: Rating: AMBER; Mode of pathogenicity: None; Publications: 20551992, 22972948, 12794685; Phenotypes: Cardiomyopathy, dilated, 1GG (MIM#613642), Mitochondrial complex II deficiency, nuclear type 1 (MIM#252011); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3247 GRIN2D Zornitza Stark Marked gene: GRIN2D as ready
Fetal anomalies v0.3247 GRIN2D Zornitza Stark Gene: grin2d has been classified as Red List (Low Evidence).
Fetal anomalies v0.3247 GRIN2D Zornitza Stark Phenotypes for gene: GRIN2D were changed from Severe Epileptic Encephalopathy Treatable with NMDA Receptor Channel Blockers to Epileptic encephalopathy, early infantile, 46, MIM# 617162; intellectual disability
Fetal anomalies v0.3246 GRIN2D Zornitza Stark Publications for gene: GRIN2D were set to
Fetal anomalies v0.3245 GRIN2D Zornitza Stark Mode of pathogenicity for gene: GRIN2D was changed from to Other
Fetal anomalies v0.3244 GRIN2D Zornitza Stark Classified gene: GRIN2D as Red List (low evidence)
Fetal anomalies v0.3244 GRIN2D Zornitza Stark Gene: grin2d has been classified as Red List (Low Evidence).
Fetal anomalies v0.3243 GRIN2D Zornitza Stark changed review comment from: Five unrelated individuals reported, two with recurrent variant (NM_000836.2:c.1999G>A or p.Val667Ile). GoF postulated as mechanism.
Sources: Expert list; to: Five unrelated individuals reported, two with recurrent variant (NM_000836.2:c.1999G>A or p.Val667Ile). GoF postulated as mechanism.

Clinical presentation is typically post-natal.

Sources: Expert list
Fetal anomalies v0.3243 GRIN2D Zornitza Stark edited their review of gene: GRIN2D: Changed rating: RED
Fetal anomalies v0.3243 GRHL2 Zornitza Stark Marked gene: GRHL2 as ready
Fetal anomalies v0.3243 GRHL2 Zornitza Stark Gene: grhl2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3243 GRHL2 Zornitza Stark Phenotypes for gene: GRHL2 were changed from ECTODERMAL DYSPLASIA/SHORT STATURE SYNDROME to Ectodermal dysplasia/short stature syndrome MIM#616029
Fetal anomalies v0.3242 GRHL2 Zornitza Stark Publications for gene: GRHL2 were set to
Fetal anomalies v0.3241 GRHL2 Zornitza Stark reviewed gene: GRHL2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Ectodermal dysplasia/short stature syndrome MIM#616029; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3241 GPAA1 Zornitza Stark Marked gene: GPAA1 as ready
Fetal anomalies v0.3241 GPAA1 Zornitza Stark Gene: gpaa1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3241 GPAA1 Zornitza Stark Phenotypes for gene: GPAA1 were changed from Developmental Delay, Epilepsy, Cerebellar Atrophy, and Osteopenia to Glycosylphosphatidylinositol biosynthesis defect 15, MIM# 617810
Fetal anomalies v0.3240 GPAA1 Zornitza Stark Publications for gene: GPAA1 were set to
Fetal anomalies v0.3239 GPAA1 Zornitza Stark Classified gene: GPAA1 as Red List (low evidence)
Fetal anomalies v0.3239 GPAA1 Zornitza Stark Gene: gpaa1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3238 GPAA1 Zornitza Stark changed review comment from: At least 5 unrelated families reported with bi-allelic variants in this gene and delayed psychomotor development, variable intellectual disability, hypotonia, early-onset seizures in most, and cerebellar atrophy, resulting in cerebellar signs including gait ataxia and dysarthria. The disorder is caused by a defect in glycosylphosphatidylinositol (GPI) biosynthesis.; to: At least 5 unrelated families reported with bi-allelic variants in this gene and delayed psychomotor development, variable intellectual disability, hypotonia, early-onset seizures in most, and cerebellar atrophy, resulting in cerebellar signs including gait ataxia and dysarthria. The disorder is caused by a defect in glycosylphosphatidylinositol (GPI) biosynthesis.

Clinical presentation is typically post-natal.
Fetal anomalies v0.3238 GPAA1 Zornitza Stark edited their review of gene: GPAA1: Changed rating: RED
IBMDx study v0.16 Zornitza Stark Panel types changed to Victorian Clinical Genetics Services; Research
Fetal anomalies v0.3238 UQCC2 Zornitza Stark Marked gene: UQCC2 as ready
Fetal anomalies v0.3238 UQCC2 Zornitza Stark Gene: uqcc2 has been classified as Green List (High Evidence).
Fetal anomalies v0.3238 UQCC2 Zornitza Stark Classified gene: UQCC2 as Green List (high evidence)
Fetal anomalies v0.3238 UQCC2 Zornitza Stark Gene: uqcc2 has been classified as Green List (High Evidence).
IBMDx study v0.15 RPL27 Zornitza Stark Marked gene: RPL27 as ready
IBMDx study v0.15 RPL27 Zornitza Stark Gene: rpl27 has been classified as Amber List (Moderate Evidence).
IBMDx study v0.15 RPL27 Zornitza Stark Publications for gene: RPL27 were set to
IBMDx study v0.14 RPL27 Zornitza Stark Mode of inheritance for gene: RPL27 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
IBMDx study v0.13 RPL27 Zornitza Stark Classified gene: RPL27 as Amber List (moderate evidence)
IBMDx study v0.13 RPL27 Zornitza Stark Gene: rpl27 has been classified as Amber List (Moderate Evidence).
IBMDx study v0.12 RPL26 Zornitza Stark Marked gene: RPL26 as ready
IBMDx study v0.12 RPL26 Zornitza Stark Gene: rpl26 has been classified as Amber List (Moderate Evidence).
IBMDx study v0.12 RPL26 Zornitza Stark Publications for gene: RPL26 were set to
IBMDx study v0.11 RPL26 Zornitza Stark Mode of pathogenicity for gene: RPL26 was changed from to None
IBMDx study v0.10 RPL26 Zornitza Stark Mode of inheritance for gene: RPL26 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
IBMDx study v0.9 RPL26 Zornitza Stark Classified gene: RPL26 as Amber List (moderate evidence)
IBMDx study v0.9 RPL26 Zornitza Stark Gene: rpl26 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3237 CPS1 Zornitza Stark Marked gene: CPS1 as ready
Fetal anomalies v0.3237 CPS1 Zornitza Stark Gene: cps1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3237 CPS1 Zornitza Stark Phenotypes for gene: CPS1 were changed from CARBAMOYL PHOSPHATE SYNTHETASE 1 DEFICIENCY to Carbamoylphosphate synthetase I deficiency MIM#237300
Fetal anomalies v0.3236 CPS1 Zornitza Stark Publications for gene: CPS1 were set to
Fetal anomalies v0.3235 CPS1 Zornitza Stark reviewed gene: CPS1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Carbamoylphosphate synthetase I deficiency MIM#237300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
IBMDx study v0.8 FANCM Zornitza Stark Marked gene: FANCM as ready
IBMDx study v0.8 FANCM Zornitza Stark Gene: fancm has been classified as Amber List (Moderate Evidence).
IBMDx study v0.8 FANCM Zornitza Stark Phenotypes for gene: FANCM were changed from Fanconi anaemia to FA-like syndromes, chemotherapy toxicity
IBMDx study v0.7 FANCM Zornitza Stark Publications for gene: FANCM were set to
IBMDx study v0.6 FANCM Zornitza Stark Mode of inheritance for gene: FANCM was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
IBMDx study v0.5 FANCM Zornitza Stark Classified gene: FANCM as Amber List (moderate evidence)
IBMDx study v0.5 FANCM Zornitza Stark Gene: fancm has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10943 SUMO1 Zornitza Stark Marked gene: SUMO1 as ready
Mendeliome v0.10943 SUMO1 Zornitza Stark Gene: sumo1 has been classified as Red List (Low Evidence).
Mendeliome v0.10943 SUMO1 Zornitza Stark Phenotypes for gene: SUMO1 were changed from to Cleft lip and palate
Mendeliome v0.10942 SUMO1 Zornitza Stark Publications for gene: SUMO1 were set to
Mendeliome v0.10941 SUMO1 Zornitza Stark Classified gene: SUMO1 as Red List (low evidence)
Mendeliome v0.10941 SUMO1 Zornitza Stark Gene: sumo1 has been classified as Red List (Low Evidence).
IBMDx study v0.4 CXCR4 Zornitza Stark Marked gene: CXCR4 as ready
IBMDx study v0.4 CXCR4 Zornitza Stark Gene: cxcr4 has been classified as Green List (High Evidence).
IBMDx study v0.4 CXCR4 Zornitza Stark Publications for gene: CXCR4 were set to
IBMDx study v0.3 CXCR4 Zornitza Stark Mode of inheritance for gene: CXCR4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3235 UQCC2 Krithika Murali gene: UQCC2 was added
gene: UQCC2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: UQCC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UQCC2 were set to 24385928; 28804536
Phenotypes for gene: UQCC2 were set to Mitochondrial complex III deficiency, nuclear type 7 - MIM#615824
Review for gene: UQCC2 was set to GREEN
Added comment: Biallelic variants associated with mitochondrial complex III deficiency. 2 unrelated families and variant-specific functional evidence/segregation information provided.

PMID 24385928 Tucker et al 2013 - report a patient with homozygous splice site UQCC2 variants. Presented with severe intrauterine growth retardation, neonatal lactic acidosis and renal tubular dysfunction of consanguineous Lebanese ancestry. Supportive functional studies including using patient fibroblasts.

PMID: 28804536 Feichtinger et al 2017 - report a second unrelated patient of consanguineous Turkish ancestry with UQCC2 deficiency, a female infant born at 32 weeks gestation after a a pregnancy complicated by IUGR and oligohydramnios. Followed by a fulminant postnatal course including respiratory distress syndrome, developed epileptic seizures progressing to status epilepticus, profound lactic acidosis with elevated urinary pyruvate and death at day 33 of life. Homozygous missense UQCC2 variants identified leading to a severe reduction of UQCC2 protein in patient's muscle and fibroblast cells.
Sources: Literature
IBMDx study v0.2 RPS27 vahid pazhakh reviewed gene: RPS27: Rating: AMBER; Mode of pathogenicity: None; Publications: Publications (PMID: 25424902); Phenotypes: Diamond-Blackfan anemia 17, MIM# 617409; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
IBMDx study v0.2 RPL27 vahid pazhakh reviewed gene: RPL27: Rating: AMBER; Mode of pathogenicity: None; Publications: Publications (PMID: 25424902); Phenotypes: Diamond-Blackfan anemia 16, MIM# 617408; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
IBMDx study v0.2 RPL26 vahid pazhakh reviewed gene: RPL26: Rating: AMBER; 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: Publications (PMID: 22431104); Phenotypes: Diamond-Blackfan anemia 11, MIM# 614900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10940 CPS1 Belinda Chong reviewed gene: CPS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 8486760, 17310273, 21120950; Phenotypes: Carbamoylphosphate synthetase I deficiency MIM#237300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3235 CPS1 Belinda Chong reviewed gene: CPS1: Rating: RED; Mode of pathogenicity: None; Publications: 8486760, 17310273, 21120950; Phenotypes: Carbamoylphosphate synthetase I deficiency MIM#237300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
IBMDx study v0.2 FANCM vahid pazhakh reviewed gene: FANCM: Rating: AMBER; Mode of pathogenicity: None; Publications: Publications (PMID: 28837162, 28837157, 34793962, 31942822, 19423727, 19561169, 25010009); Phenotypes: FA-like syndromes, mainly characterized by increased risk for breast and other types of cancer, and chemotherapy toxicity; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10940 SUMO1 Krithika Murali reviewed gene: SUMO1: Rating: RED; Mode of pathogenicity: None; Publications: 25111678, 18983974, 22522387; Phenotypes: cleft lip and palate; Mode of inheritance: None
IBMDx study v0.2 CXCR4 vahid pazhakh reviewed gene: CXCR4: Rating: GREEN; Mode of pathogenicity: None; Publications: Publications (PMID: 12692554, 15536153, 23009155, 18274673, 28928741, 16946301, 17715292); Phenotypes: WHIM syndrome, MIM# 193670; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3235 GNB5 Zornitza Stark Marked gene: GNB5 as ready
Fetal anomalies v0.3235 GNB5 Zornitza Stark Gene: gnb5 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3235 GNB5 Zornitza Stark Phenotypes for gene: GNB5 were changed from Sinus Bradycardia and Cognitive Disability to Intellectual developmental disorder with cardiac arrhythmia, 617173; Language delay and ADHD/cognitive impairment with or without cardiac arrhythmia, 617182; Early infantile epileptic encephalopathy (EIEE)
Fetal anomalies v0.3234 GNB5 Zornitza Stark Publications for gene: GNB5 were set to
Fetal anomalies v0.3233 GNB5 Zornitza Stark Classified gene: GNB5 as Red List (low evidence)
Fetal anomalies v0.3233 GNB5 Zornitza Stark Gene: gnb5 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3232 GNB5 Zornitza Stark changed review comment from: Multiple affected individuals reported.
Sources: Expert list; to: Presentation is typically post-natal.

Sources: Expert list
Fetal anomalies v0.3232 GNB5 Zornitza Stark edited their review of gene: GNB5: Changed rating: RED
Fetal anomalies v0.3232 GNAQ Zornitza Stark Marked gene: GNAQ as ready
Fetal anomalies v0.3232 GNAQ Zornitza Stark Gene: gnaq has been classified as Red List (Low Evidence).
Fetal anomalies v0.3232 GNAQ Zornitza Stark Phenotypes for gene: GNAQ were changed from Congenital Hemangioma to Sturge-Weber syndrome, somatic, mosaic, MIM#185300
Fetal anomalies v0.3231 GNAQ Zornitza Stark Mode of inheritance for gene: GNAQ was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Fetal anomalies v0.3230 GNAQ Zornitza Stark Classified gene: GNAQ as Red List (low evidence)
Fetal anomalies v0.3230 GNAQ Zornitza Stark Gene: gnaq has been classified as Red List (Low Evidence).
Fetal anomalies v0.3229 GNAQ Zornitza Stark changed review comment from: ID can be part of the phenotype; however this condition is due to somatic mosaic gain of function variants so there may be issues with detection depending on tissue used and sequencing depth.; to: This condition is due to somatic mosaic gain of function variants so there may be issues with detection depending on tissue used and sequencing depth.
Fetal anomalies v0.3229 GNAQ Zornitza Stark edited their review of gene: GNAQ: Changed rating: RED
Fetal anomalies v0.3229 GNAI1 Zornitza Stark Marked gene: GNAI1 as ready
Fetal anomalies v0.3229 GNAI1 Zornitza Stark Gene: gnai1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3229 GNAI1 Zornitza Stark Phenotypes for gene: GNAI1 were changed from GNAI1 syndrome to GNAI1 syndrome; Developmental delay, seizures, and hypotonia
Fetal anomalies v0.3228 GNAI1 Zornitza Stark Publications for gene: GNAI1 were set to
Fetal anomalies v0.3227 GNAI1 Zornitza Stark Mode of inheritance for gene: GNAI1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3226 GNAI1 Zornitza Stark Classified gene: GNAI1 as Red List (low evidence)
Fetal anomalies v0.3226 GNAI1 Zornitza Stark Gene: gnai1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3225 GNAI1 Zornitza Stark changed review comment from: 7 de novo missense and 1 PTV variants reported in the DDD paper Table 1.; to: 7 de novo missense and 1 PTV variants reported in the DDD paper Table 1. Typically presents post-natally.
Fetal anomalies v0.3225 GNAI1 Zornitza Stark edited their review of gene: GNAI1: Changed rating: RED
Fetal anomalies v0.3225 GNA14 Zornitza Stark Marked gene: GNA14 as ready
Fetal anomalies v0.3225 GNA14 Zornitza Stark Gene: gna14 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3225 GNA14 Zornitza Stark Classified gene: GNA14 as Red List (low evidence)
Fetal anomalies v0.3225 GNA14 Zornitza Stark Gene: gna14 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3224 GMNN Zornitza Stark Marked gene: GMNN as ready
Fetal anomalies v0.3224 GMNN Zornitza Stark Gene: gmnn has been classified as Green List (High Evidence).
Fetal anomalies v0.3224 GMNN Zornitza Stark Publications for gene: GMNN were set to
Fetal anomalies v0.3223 GMNN Zornitza Stark Mode of inheritance for gene: GMNN was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3222 GMNN Zornitza Stark Classified gene: GMNN as Green List (high evidence)
Fetal anomalies v0.3222 GMNN Zornitza Stark Gene: gmnn has been classified as Green List (High Evidence).
Fetal anomalies v0.3221 GMNN Zornitza Stark changed review comment from: Two of the three reported individuals had ID.
Sources: Expert list; to: IUGR is a key feature.

Sources: Expert list
Fetal anomalies v0.3221 GMNN Zornitza Stark edited their review of gene: GMNN: Changed rating: GREEN; Changed phenotypes: Meier-Gorlin syndrome 6, MIM# 616835
Fetal anomalies v0.3221 GLIS2 Zornitza Stark Marked gene: GLIS2 as ready
Fetal anomalies v0.3221 GLIS2 Zornitza Stark Gene: glis2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3221 GLIS2 Zornitza Stark Phenotypes for gene: GLIS2 were changed from NEPHRONOPHTHISIS 7 to Nephronophthisis 7, OMIM#611498; MONDO:0012680
Fetal anomalies v0.3220 GLIS2 Zornitza Stark Publications for gene: GLIS2 were set to
Fetal anomalies v0.3219 GFPT1 Zornitza Stark Marked gene: GFPT1 as ready
Fetal anomalies v0.3219 GFPT1 Zornitza Stark Gene: gfpt1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3219 GFPT1 Zornitza Stark Publications for gene: GFPT1 were set to
Fetal anomalies v0.3218 GFPT1 Zornitza Stark Classified gene: GFPT1 as Red List (low evidence)
Fetal anomalies v0.3218 GFPT1 Zornitza Stark Gene: gfpt1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3217 GFPT1 Zornitza Stark changed review comment from: 15 unrelated families reported with bi-allelic variants and a congenital myasthenic syndrome. Two families with leukoencephalopathy as well as CMS.

The GFPT1 gene encodes an isoform of glutamine:fructose-6-phosphate amidotransferase (GFAT), which catalyzes the transfer of an amino group from glutamine onto fructose-6-phosphate, yielding glucosamine 6-phosphate and glutamate. It is the first and rate-limiting enzyme of the hexosamine biosynthetic pathway. Hexosamine is the obligatory source of essential amino sugars for the synthesis of glycoproteins, glycolipids, and proteoglycans. Muscle samples from several patients showed decreased protein glycosylation, suggesting this is a disorder of glycosylation. However, there is also some data put forward in PMID 30635494 that this may be a mitochondrial condition.; to: 15 unrelated families reported with bi-allelic variants and a congenital myasthenic syndrome. Two families with leukoencephalopathy as well as CMS.

Presentation typically in childhood/adolescence.
Fetal anomalies v0.3217 GFPT1 Zornitza Stark edited their review of gene: GFPT1: Changed rating: RED
Fetal anomalies v0.3217 GALNT2 Zornitza Stark Marked gene: GALNT2 as ready
Fetal anomalies v0.3217 GALNT2 Zornitza Stark Gene: galnt2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3217 GALNT2 Zornitza Stark changed review comment from: Seven individuals from four families reported with bi-allelic LOF variants and global developmental delay, intellectual disability with language deficit, autistic features, behavioural abnormalities, epilepsy, chronic insomnia, white matter changes on brain MRI, dysmorphic features, decreased stature, and decreased high density lipoprotein cholesterol levels. Rodent (mouse and rat) models of GALNT2-CDG recapitulated much of the human phenotype, including poor growth and neurodevelopmental abnormalities.
Sources: Literature; to: Seven individuals from four families reported with bi-allelic LOF variants and global developmental delay, intellectual disability with language deficit, autistic features, behavioural abnormalities, epilepsy, chronic insomnia, white matter changes on brain MRI, dysmorphic features, decreased stature, and decreased high density lipoprotein cholesterol levels. Rodent (mouse and rat) models of GALNT2-CDG recapitulated much of the human phenotype, including poor growth and neurodevelopmental abnormalities.

Microcephaly and poor growth but age of onset of these features is uncertain.

Sources: Literature
Fetal anomalies v0.3217 GALNT2 Zornitza Stark edited their review of gene: GALNT2: Changed phenotypes: Congenital disorder of glycosylation, type IIt, MIM# 618885
Fetal anomalies v0.3217 GALNT2 Zornitza Stark edited their review of gene: GALNT2: Changed rating: AMBER
Fetal anomalies v0.3217 GABRG2 Zornitza Stark Marked gene: GABRG2 as ready
Fetal anomalies v0.3217 GABRG2 Zornitza Stark Gene: gabrg2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3217 GABRG2 Zornitza Stark Phenotypes for gene: GABRG2 were changed from EPILEPSY, GENERALIZED, WITH FEBRILE SEIZURES PLUS, TYPE 3; GENERALIZED EPILEPSY WITH FEBRILE SEIZURES PLUS, TYPE 3 to Epileptic encephalopathy, early infantile, 74 618396; Epilepsy, generalized, with febrile seizures plus, type 3, 607681
Fetal anomalies v0.3216 GABRG2 Zornitza Stark Publications for gene: GABRG2 were set to
Fetal anomalies v0.3215 GABRG2 Zornitza Stark Mode of inheritance for gene: GABRG2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3214 GABRG2 Zornitza Stark Classified gene: GABRG2 as Red List (low evidence)
Fetal anomalies v0.3214 GABRG2 Zornitza Stark Gene: gabrg2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3213 GABRG2 Zornitza Stark changed review comment from: Multiple unrelated families reported, variable severity of both seizures and ID.; to: Multiple unrelated families reported, variable severity of both seizures and ID. Typically presents post-natally.
Fetal anomalies v0.3213 GABRG2 Zornitza Stark edited their review of gene: GABRG2: Changed rating: RED
Fetal anomalies v0.3213 GABRA1 Zornitza Stark Marked gene: GABRA1 as ready
Fetal anomalies v0.3213 GABRA1 Zornitza Stark Gene: gabra1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3213 GABRA1 Zornitza Stark Phenotypes for gene: GABRA1 were changed from JUVENILE MYOCLONIC EPILEPSY; EPILEPTIC ENCEPHALOPATHY to Epileptic encephalopathy, early infantile, 19 615744; Rett syndrome; Rett-like phenotypes; idiopathic generalized Epilepsy; Dravet syndrome
Fetal anomalies v0.3212 GABRA1 Zornitza Stark Publications for gene: GABRA1 were set to
Fetal anomalies v0.3211 GABRA1 Zornitza Stark Mode of inheritance for gene: GABRA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3210 GABRA1 Zornitza Stark Classified gene: GABRA1 as Red List (low evidence)
Fetal anomalies v0.3210 GABRA1 Zornitza Stark Gene: gabra1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3209 GABRA1 Zornitza Stark changed review comment from: PMID: 11992121; 1 large family with Juvenile Myoclonic Epilepsy PMID: 21714819; 2 probands with idiopathic generalized epilepsy PMID: 24623842; 4 patients with Dravet syndrome PMID: 30842224; non-MECP2 probands with Rett-like syndromes categorised into 1) typical RTT, 2) atypical RTT, 3) RTT-like phenotype. Total of 1 family with SNV in GABRA1 in Rett-like cohort.; to: PMID: 11992121; 1 large family with Juvenile Myoclonic Epilepsy PMID: 21714819; 2 probands with idiopathic generalized epilepsy PMID: 24623842; 4 patients with Dravet syndrome PMID: 30842224; non-MECP2 probands with Rett-like syndromes categorised into 1) typical RTT, 2) atypical RTT, 3) RTT-like phenotype. Total of 1 family with SNV in GABRA1 in Rett-like cohort.

Typically presents post-natally.
Fetal anomalies v0.3209 GABRA1 Zornitza Stark edited their review of gene: GABRA1: Changed rating: RED
Fetal anomalies v0.3209 FZD5 Zornitza Stark Marked gene: FZD5 as ready
Fetal anomalies v0.3209 FZD5 Zornitza Stark Gene: fzd5 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3209 FZD5 Zornitza Stark Publications for gene: FZD5 were set to
Fetal anomalies v0.3208 FZD5 Zornitza Stark Classified gene: FZD5 as Red List (low evidence)
Fetal anomalies v0.3208 FZD5 Zornitza Stark Gene: fzd5 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3207 FZD5 Zornitza Stark edited their review of gene: FZD5: Changed rating: RED
Fetal anomalies v0.3207 FZD5 Zornitza Stark changed review comment from: Four unrelated families reported.
Sources: Literature; to: Four unrelated families reported. Coloboma tends to be isolated, which would be difficult to detect antenatally.
Sources: Literature
Fetal anomalies v0.3207 FUT8 Zornitza Stark Marked gene: FUT8 as ready
Fetal anomalies v0.3207 FUT8 Zornitza Stark Gene: fut8 has been classified as Green List (High Evidence).
Fetal anomalies v0.3207 FUT8 Zornitza Stark Publications for gene: FUT8 were set to
Fetal anomalies v0.3206 FUT8 Zornitza Stark Classified gene: FUT8 as Green List (high evidence)
Fetal anomalies v0.3206 FUT8 Zornitza Stark Gene: fut8 has been classified as Green List (High Evidence).
Fetal anomalies v0.3205 FUT8 Zornitza Stark changed review comment from: Three unrelated individuals reported with bi-allelic variants in this gene.
Sources: Expert list; to: Three unrelated individuals reported with bi-allelic variants in this gene. IUGR and congenital anomalies reported.
Sources: Expert list
Fetal anomalies v0.3205 FUCA1 Zornitza Stark Marked gene: FUCA1 as ready
Fetal anomalies v0.3205 FUCA1 Zornitza Stark Gene: fuca1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3205 FUCA1 Zornitza Stark Phenotypes for gene: FUCA1 were changed from FUCOSIDOSIS to Fucosidosis, MIM# 230000
Fetal anomalies v0.3204 FUCA1 Zornitza Stark Classified gene: FUCA1 as Red List (low evidence)
Fetal anomalies v0.3204 FUCA1 Zornitza Stark Gene: fuca1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3203 FRRS1L Zornitza Stark Marked gene: FRRS1L as ready
Fetal anomalies v0.3203 FRRS1L Zornitza Stark Gene: frrs1l has been classified as Red List (Low Evidence).
Fetal anomalies v0.3203 FRRS1L Zornitza Stark Phenotypes for gene: FRRS1L were changed from Epileptic encephalopathy with continuous spike-and-wave during sleep to Epileptic encephalopathy, early infantile, 37, MIM#616981
Fetal anomalies v0.3202 FRRS1L Zornitza Stark Publications for gene: FRRS1L were set to
Fetal anomalies v0.3201 FRRS1L Zornitza Stark Classified gene: FRRS1L as Red List (low evidence)
Fetal anomalies v0.3201 FRRS1L Zornitza Stark Gene: frrs1l has been classified as Red List (Low Evidence).
Fetal anomalies v0.3200 FRRS1L Zornitza Stark changed review comment from: Five unrelated individuals reported.
Sources: Expert list; to: Five unrelated individuals reported. Presentation is typically post-natal.
Sources: Expert list
Fetal anomalies v0.3200 FRRS1L Zornitza Stark edited their review of gene: FRRS1L: Changed rating: RED
Fetal anomalies v0.3200 FRMPD4 Zornitza Stark Marked gene: FRMPD4 as ready
Fetal anomalies v0.3200 FRMPD4 Zornitza Stark Gene: frmpd4 has been classified as Green List (High Evidence).
Fetal anomalies v0.3200 FRMPD4 Zornitza Stark Phenotypes for gene: FRMPD4 were changed from Intellectual Disability to Intellectual Disability, X-linked 104, MIM#300983
Fetal anomalies v0.3199 FRMPD4 Zornitza Stark Publications for gene: FRMPD4 were set to
Fetal anomalies v0.3198 FRMPD4 Zornitza Stark Classified gene: FRMPD4 as Green List (high evidence)
Fetal anomalies v0.3198 FRMPD4 Zornitza Stark Gene: frmpd4 has been classified as Green List (High Evidence).
Fetal anomalies v0.3197 FRMPD4 Zornitza Stark changed review comment from: Multiple affected individuals from unrelated families.; to: Multiple affected individuals from unrelated families. Corpus callosum abnormalities, retrognathia reported.
Fetal anomalies v0.3197 FOXP4 Zornitza Stark Marked gene: FOXP4 as ready
Fetal anomalies v0.3197 FOXP4 Zornitza Stark Gene: foxp4 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3197 FOXP4 Zornitza Stark Mode of inheritance for gene: FOXP4 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3196 FOXP2 Zornitza Stark Marked gene: FOXP2 as ready
Fetal anomalies v0.3196 FOXP2 Zornitza Stark Gene: foxp2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3196 FOXP2 Zornitza Stark Phenotypes for gene: FOXP2 were changed from SPEECH-LANGUAGE DISORDER 1 to Speech-language disorder-1, MIM# 602081
Fetal anomalies v0.3195 FOXP2 Zornitza Stark Publications for gene: FOXP2 were set to
Fetal anomalies v0.3194 FOXP2 Zornitza Stark Mode of inheritance for gene: FOXP2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3193 FOXP2 Zornitza Stark Classified gene: FOXP2 as Red List (low evidence)
Fetal anomalies v0.3193 FOXP2 Zornitza Stark Gene: foxp2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3192 FOXP2 Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association but typically presents post-natally.
Fetal anomalies v0.3192 FOXP2 Zornitza Stark edited their review of gene: FOXP2: Changed rating: RED
Fetal anomalies v0.3192 FIG4 Zornitza Stark Marked gene: FIG4 as ready
Fetal anomalies v0.3192 FIG4 Zornitza Stark Gene: fig4 has been classified as Green List (High Evidence).
Fetal anomalies v0.3192 FIG4 Zornitza Stark Phenotypes for gene: FIG4 were changed from Charcot-Marie-Tooth disease, type 4J, OMIM:611228; Charcot-Marie-Tooth disease type 4J, MONDO:0012640; Yunis-Varon syndrome, OMIM:216340; Yunis-Varon syndrome, MONDO:0008995; ?Polymicrogyria, bilateral temporooccipital, OMIM:612691; Bilateral parasagittal parieto-occipital polymicrogyria, MONDO:0012986 to Yunis-Varon syndrome, OMIM:216340; Yunis-Varon syndrome, MONDO:0008995; ?Polymicrogyria, bilateral temporooccipital, OMIM:612691; Bilateral parasagittal parieto-occipital polymicrogyria, MONDO:0012986
Fetal anomalies v0.3191 FIG4 Zornitza Stark Publications for gene: FIG4 were set to
Fetal anomalies v0.3190 FIG4 Zornitza Stark Classified gene: FIG4 as Green List (high evidence)
Fetal anomalies v0.3190 FIG4 Zornitza Stark Gene: fig4 has been classified as Green List (High Evidence).
Fetal anomalies v0.3189 FANCM Zornitza Stark Marked gene: FANCM as ready
Fetal anomalies v0.3189 FANCM Zornitza Stark Gene: fancm has been classified as Red List (Low Evidence).
Fetal anomalies v0.3189 FANCM Zornitza Stark Phenotypes for gene: FANCM were changed from FANCONI ANEMIA; FANCM-RELATED FANCONI ANEMIA to Fanconi anaemia
Fetal anomalies v0.3188 FANCM Zornitza Stark Classified gene: FANCM as Red List (low evidence)
Fetal anomalies v0.3188 FANCM Zornitza Stark Gene: fancm has been classified as Red List (Low Evidence).
Fetal anomalies v0.3187 FANCL Zornitza Stark Marked gene: FANCL as ready
Fetal anomalies v0.3187 FANCL Zornitza Stark Gene: fancl has been classified as Green List (High Evidence).
Fetal anomalies v0.3187 FANCL Zornitza Stark Publications for gene: FANCL were set to
Fetal anomalies v0.3186 FANCL Zornitza Stark Classified gene: FANCL as Green List (high evidence)
Fetal anomalies v0.3186 FANCL Zornitza Stark Gene: fancl has been classified as Green List (High Evidence).
Growth failure v1.36 THUMPD1 Zornitza Stark Marked gene: THUMPD1 as ready
Growth failure v1.36 THUMPD1 Zornitza Stark Gene: thumpd1 has been classified as Green List (High Evidence).
Growth failure v1.36 THUMPD1 Zornitza Stark Phenotypes for gene: THUMPD1 were changed from Syndromic form of intellectual disability associated with developmental delay, behavioral abnormalities, hearing loss and facial dysmorphism, AR to Syndromic disease, MONDO:0002254, THUMPD1-related
Growth failure v1.35 THUMPD1 Zornitza Stark Classified gene: THUMPD1 as Green List (high evidence)
Growth failure v1.35 THUMPD1 Zornitza Stark Gene: thumpd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4497 THUMPD1 Zornitza Stark reviewed gene: THUMPD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.4497 THUMPD1 Zornitza Stark Marked gene: THUMPD1 as ready
Intellectual disability syndromic and non-syndromic v0.4497 THUMPD1 Zornitza Stark Gene: thumpd1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4497 THUMPD1 Zornitza Stark Phenotypes for gene: THUMPD1 were changed from Syndromic form of intellectual disability associated with developmental delay, behavioral abnormalities, hearing loss and facial dysmorphism, AR to Syndromic disease, MONDO:0002254, THUMPD1-related
Intellectual disability syndromic and non-syndromic v0.4496 THUMPD1 Zornitza Stark Classified gene: THUMPD1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4496 THUMPD1 Zornitza Stark Gene: thumpd1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.116 THUMPD1 Zornitza Stark Marked gene: THUMPD1 as ready
Deafness_IsolatedAndComplex v1.116 THUMPD1 Zornitza Stark Gene: thumpd1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.116 THUMPD1 Zornitza Stark Phenotypes for gene: THUMPD1 were changed from Syndromic form of intellectual disability associated with developmental delay, behavioral abnormalities, hearing loss and facial dysmorphism, AR to Syndromic disease, MONDO:0002254, THUMPD1-related
Deafness_IsolatedAndComplex v1.115 THUMPD1 Zornitza Stark Classified gene: THUMPD1 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.115 THUMPD1 Zornitza Stark Gene: thumpd1 has been classified as Green List (High Evidence).
Microcephaly v1.104 THUMPD1 Zornitza Stark Marked gene: THUMPD1 as ready
Microcephaly v1.104 THUMPD1 Zornitza Stark Gene: thumpd1 has been classified as Green List (High Evidence).
Microcephaly v1.104 THUMPD1 Zornitza Stark Phenotypes for gene: THUMPD1 were changed from Syndromic form of intellectual disability associated with developmental delay, behavioral abnormalities, hearing loss and facial dysmorphism, AR to Syndromic disease, MONDO:0002254, THUMPD1-related
Microcephaly v1.103 THUMPD1 Zornitza Stark Classified gene: THUMPD1 as Green List (high evidence)
Microcephaly v1.103 THUMPD1 Zornitza Stark Gene: thumpd1 has been classified as Green List (High Evidence).
Mendeliome v0.10940 THUMPD1 Zornitza Stark Marked gene: THUMPD1 as ready
Mendeliome v0.10940 THUMPD1 Zornitza Stark Gene: thumpd1 has been classified as Green List (High Evidence).
Mendeliome v0.10940 THUMPD1 Zornitza Stark Phenotypes for gene: THUMPD1 were changed from Syndromic form of intellectual disability associated with developmental delay, behavioral abnormalities, hearing loss and facial dysmorphism, AR to Syndromic disease, MONDO:0002254, THUMPD1-related
Mendeliome v0.10939 THUMPD1 Zornitza Stark Classified gene: THUMPD1 as Green List (high evidence)
Mendeliome v0.10939 THUMPD1 Zornitza Stark Gene: thumpd1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3185 SF3B2 Zornitza Stark Marked gene: SF3B2 as ready
Fetal anomalies v0.3185 SF3B2 Zornitza Stark Gene: sf3b2 has been classified as Green List (High Evidence).
Fetal anomalies v0.3185 SF3B2 Zornitza Stark Classified gene: SF3B2 as Green List (high evidence)
Fetal anomalies v0.3185 SF3B2 Zornitza Stark Gene: sf3b2 has been classified as Green List (High Evidence).
Inflammatory bowel disease v0.67 PTEN Zornitza Stark Marked gene: PTEN as ready
Inflammatory bowel disease v0.67 PTEN Zornitza Stark Gene: pten has been classified as Red List (Low Evidence).
Inflammatory bowel disease v0.67 PTEN Zornitza Stark Phenotypes for gene: PTEN were changed from to Colitis
Inflammatory bowel disease v0.66 PTEN Zornitza Stark Publications for gene: PTEN were set to
Inflammatory bowel disease v0.65 PTEN Zornitza Stark Mode of inheritance for gene: PTEN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Inflammatory bowel disease v0.64 PTEN Zornitza Stark Classified gene: PTEN as Red List (low evidence)
Inflammatory bowel disease v0.64 PTEN Zornitza Stark Gene: pten has been classified as Red List (Low Evidence).
Fetal anomalies v0.3184 SEPT9 Zornitza Stark Marked gene: SEPT9 as ready
Fetal anomalies v0.3184 SEPT9 Zornitza Stark Gene: sept9 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3184 SEPT9 Zornitza Stark Classified gene: SEPT9 as Red List (low evidence)
Fetal anomalies v0.3184 SEPT9 Zornitza Stark Gene: sept9 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3183 SEPT9 Zornitza Stark reviewed gene: SEPT9: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v0.3183 PLCH1 Zornitza Stark Marked gene: PLCH1 as ready
Fetal anomalies v0.3183 PLCH1 Zornitza Stark Gene: plch1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3183 PLCH1 Zornitza Stark Classified gene: PLCH1 as Amber List (moderate evidence)
Fetal anomalies v0.3183 PLCH1 Zornitza Stark Gene: plch1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3182 PLEKHA5 Zornitza Stark Marked gene: PLEKHA5 as ready
Fetal anomalies v0.3182 PLEKHA5 Zornitza Stark Gene: plekha5 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3182 PLEKHA5 Zornitza Stark Classified gene: PLEKHA5 as Amber List (moderate evidence)
Fetal anomalies v0.3182 PLEKHA5 Zornitza Stark Gene: plekha5 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3181 PLEKHA7 Zornitza Stark Marked gene: PLEKHA7 as ready
Fetal anomalies v0.3181 PLEKHA7 Zornitza Stark Gene: plekha7 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3181 PLEKHA7 Zornitza Stark Classified gene: PLEKHA7 as Amber List (moderate evidence)
Fetal anomalies v0.3181 PLEKHA7 Zornitza Stark Gene: plekha7 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3180 PPP1R13L Zornitza Stark Marked gene: PPP1R13L as ready
Fetal anomalies v0.3180 PPP1R13L Zornitza Stark Gene: ppp1r13l has been classified as Green List (High Evidence).
Fetal anomalies v0.3180 PPP1R13L Zornitza Stark Classified gene: PPP1R13L as Green List (high evidence)
Fetal anomalies v0.3180 PPP1R13L Zornitza Stark Gene: ppp1r13l has been classified as Green List (High Evidence).
Fetal anomalies v0.3179 METTL23 Zornitza Stark Marked gene: METTL23 as ready
Fetal anomalies v0.3179 METTL23 Zornitza Stark Gene: mettl23 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3179 METTL23 Zornitza Stark Classified gene: METTL23 as Red List (low evidence)
Fetal anomalies v0.3179 METTL23 Zornitza Stark Gene: mettl23 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3178 LRRC32 Zornitza Stark Marked gene: LRRC32 as ready
Fetal anomalies v0.3178 LRRC32 Zornitza Stark Gene: lrrc32 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3178 LRRC32 Zornitza Stark Classified gene: LRRC32 as Amber List (moderate evidence)
Fetal anomalies v0.3178 LRRC32 Zornitza Stark Gene: lrrc32 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3177 SCN8A Zornitza Stark Marked gene: SCN8A as ready
Fetal anomalies v0.3177 SCN8A Zornitza Stark Gene: scn8a has been classified as Red List (Low Evidence).
Fetal anomalies v0.3177 SCN8A Zornitza Stark Phenotypes for gene: SCN8A were changed from EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 13; COGNITIVE IMPAIRMENT WITH OR WITHOUT CEREBELLAR ATAXIA to Developmental and epileptic encephalopathy 13, MIM#614558, dominant and recessive; Myoclonus, familial, 2, MIM# 618364; paroxysmal kinesigenic dyskinesias; Cognitive impairment with or without cerebellar ataxia, MIM# 614306
Fetal anomalies v0.3176 RFWD3 Zornitza Stark Marked gene: RFWD3 as ready
Fetal anomalies v0.3176 RFWD3 Zornitza Stark Gene: rfwd3 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3176 RFWD3 Zornitza Stark Phenotypes for gene: RFWD3 were changed from ?Fanconi anemia, complementation group W, OMIM:617784 to Fanconi anaemia, complementation group W, OMIM:617784
Mendeliome v0.10938 THUMPD1 Chern Lim changed review comment from: Broly, M. et al. (2022), AJHG:
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other; to: Broly, M. et al. (2022), AJHG:
- 13 individuals from 8 families, biallelic loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other
Intellectual disability syndromic and non-syndromic v0.4495 THUMPD1 Chern Lim changed review comment from: Broly, M. et al. (2022), AJHG:
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other; to: Broly, M. et al. (2022), AJHG:
- 13 individuals from 8 families, biallelic loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other
Deafness_IsolatedAndComplex v1.114 THUMPD1 Chern Lim changed review comment from: Broly, M. et al. (2022), AJHG:
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other; to: Broly, M. et al. (2022), AJHG:
- 13 individuals from 8 families, biallelic loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other
Microcephaly v1.102 THUMPD1 Chern Lim changed review comment from: Broly, M. et al. (2022), AJHG:
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other; to: Broly, M. et al. (2022), AJHG:
- 13 individuals from 8 families, biallelic loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other
Growth failure v1.34 THUMPD1 Chern Lim changed review comment from: Broly, M. et al. (2022), AJHG:
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other; to: Broly, M. et al. (2022), AJHG:
- 13 individuals from 8 families, biallelic loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other
Growth failure v1.34 THUMPD1 Chern Lim changed review comment from: Broly, M. et al. (2022) manuscript accepted in AJHG:
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other; to: Broly, M. et al. (2022), AJHG:
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other
Microcephaly v1.102 THUMPD1 Chern Lim changed review comment from: Broly, M. et al. (2022) manuscript accepted in AJHG:
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other; to: Broly, M. et al. (2022), AJHG:
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other
Deafness_IsolatedAndComplex v1.114 THUMPD1 Chern Lim changed review comment from: Broly, M. et al. (2022) manuscript accepted in AJHG:
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other; to: Broly, M. et al. (2022), AJHG:
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other
Mendeliome v0.10938 THUMPD1 Chern Lim changed review comment from: Broly, M. et al. (2022):
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other; to: Broly, M. et al. (2022), AJHG:
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other
Intellectual disability syndromic and non-syndromic v0.4495 THUMPD1 Chern Lim changed review comment from: Broly, M. et al. (2022) manuscript accepted in AJHG:
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other; to: Broly, M. et al. (2022), AJHG:
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other
Mendeliome v0.10938 THUMPD1 Chern Lim changed review comment from: Broly, M. et al. (2022) manuscript accepted in AJHG:
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other; to: Broly, M. et al. (2022):
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other
Microcephaly v1.102 THUMPD1 Chern Lim gene: THUMPD1 was added
gene: THUMPD1 was added to Microcephaly. Sources: Other
Mode of inheritance for gene: THUMPD1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: THUMPD1 were set to Syndromic form of intellectual disability associated with developmental delay, behavioral abnormalities, hearing loss and facial dysmorphism, AR
Review for gene: THUMPD1 was set to GREEN
gene: THUMPD1 was marked as current diagnostic
Added comment: Broly, M. et al. (2022) manuscript accepted in AJHG:
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other
Growth failure v1.34 THUMPD1 Chern Lim gene: THUMPD1 was added
gene: THUMPD1 was added to Growth failure. Sources: Other
Mode of inheritance for gene: THUMPD1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: THUMPD1 were set to Syndromic form of intellectual disability associated with developmental delay, behavioral abnormalities, hearing loss and facial dysmorphism, AR
Review for gene: THUMPD1 was set to GREEN
gene: THUMPD1 was marked as current diagnostic
Added comment: Broly, M. et al. (2022) manuscript accepted in AJHG:
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other
Deafness_IsolatedAndComplex v1.114 THUMPD1 Chern Lim gene: THUMPD1 was added
gene: THUMPD1 was added to Deafness_IsolatedAndComplex. Sources: Other
Mode of inheritance for gene: THUMPD1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: THUMPD1 were set to Syndromic form of intellectual disability associated with developmental delay, behavioral abnormalities, hearing loss and facial dysmorphism, AR
Review for gene: THUMPD1 was set to GREEN
gene: THUMPD1 was marked as current diagnostic
Added comment: Broly, M. et al. (2022) manuscript accepted in AJHG:
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other
Intellectual disability syndromic and non-syndromic v0.4495 THUMPD1 Chern Lim gene: THUMPD1 was added
gene: THUMPD1 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: THUMPD1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: THUMPD1 were set to Syndromic form of intellectual disability associated with developmental delay, behavioral abnormalities, hearing loss and facial dysmorphism, AR
gene: THUMPD1 was marked as current diagnostic
Added comment: Broly, M. et al. (2022) manuscript accepted in AJHG:
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other
Mendeliome v0.10938 THUMPD1 Chern Lim gene: THUMPD1 was added
gene: THUMPD1 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: THUMPD1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: THUMPD1 were set to Syndromic form of intellectual disability associated with developmental delay, behavioral abnormalities, hearing loss and facial dysmorphism, AR
Review for gene: THUMPD1 was set to GREEN
gene: THUMPD1 was marked as current diagnostic
Added comment: Broly, M. et al. (2022) manuscript accepted in AJHG:
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other
Fetal anomalies v0.3175 RAB39B Zornitza Stark Marked gene: RAB39B as ready
Fetal anomalies v0.3175 RAB39B Zornitza Stark Gene: rab39b has been classified as Red List (Low Evidence).
Fetal anomalies v0.3175 RAB39B Zornitza Stark Phenotypes for gene: RAB39B were changed from MENTAL RETARDATION X-LINKED TYPE 72 (MRX72) +/- PARKINSONS to Intellectual developmental disorder, X-linked 72 MIM#300271; Waisman syndrome MIM#311510
Fetal anomalies v0.3174 RAB39B Zornitza Stark Publications for gene: RAB39B were set to 29152164; 20159109
Mendeliome v0.10938 RAB39B Zornitza Stark Marked gene: RAB39B as ready
Mendeliome v0.10938 RAB39B Zornitza Stark Gene: rab39b has been classified as Green List (High Evidence).
Mendeliome v0.10938 RAB39B Zornitza Stark Phenotypes for gene: RAB39B were changed from to Intellectual developmental disorder, X-linked 72 MIM#300271; Waisman syndrome MIM#311510
Mendeliome v0.10937 RAB39B Zornitza Stark Publications for gene: RAB39B were set to
Mendeliome v0.10936 RAB39B Zornitza Stark Mode of inheritance for gene: RAB39B was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Complement Deficiencies v0.44 MASP2 Bryony Thompson Publications for gene: MASP2 were set to
Fetal anomalies v0.3173 LRP6 Zornitza Stark Marked gene: LRP6 as ready
Fetal anomalies v0.3173 LRP6 Zornitza Stark Gene: lrp6 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3173 LRP6 Zornitza Stark Classified gene: LRP6 as Amber List (moderate evidence)
Fetal anomalies v0.3173 LRP6 Zornitza Stark Gene: lrp6 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3172 PTCHD1 Zornitza Stark Marked gene: PTCHD1 as ready
Fetal anomalies v0.3172 PTCHD1 Zornitza Stark Gene: ptchd1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3172 PTCHD1 Zornitza Stark Phenotypes for gene: PTCHD1 were changed from AUTISM/ID to intellectual disability MIM#300830
Fetal anomalies v0.3171 PTCHD1 Zornitza Stark Publications for gene: PTCHD1 were set to
Mendeliome v0.10935 PTCHD1 Zornitza Stark Marked gene: PTCHD1 as ready
Mendeliome v0.10935 PTCHD1 Zornitza Stark Gene: ptchd1 has been classified as Green List (High Evidence).
Mendeliome v0.10935 PTCHD1 Zornitza Stark Phenotypes for gene: PTCHD1 were changed from to intellectual disability MIM#300830
Mendeliome v0.10934 PTCHD1 Zornitza Stark Publications for gene: PTCHD1 were set to
Mendeliome v0.10933 PTCHD1 Zornitza Stark Mode of inheritance for gene: PTCHD1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v0.3170 PSMB8 Zornitza Stark Marked gene: PSMB8 as ready
Fetal anomalies v0.3170 PSMB8 Zornitza Stark Gene: psmb8 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3170 PSMB8 Zornitza Stark Phenotypes for gene: PSMB8 were changed from NAKAJO SYNDROME to Proteasome-associated autoinflammatory syndrome 1, MIM# 256040; MONDO:0054698
Fetal anomalies v0.3169 PSMB8 Zornitza Stark Publications for gene: PSMB8 were set to
Fetal anomalies v0.3168 PRSS12 Zornitza Stark Marked gene: PRSS12 as ready
Fetal anomalies v0.3168 PRSS12 Zornitza Stark Gene: prss12 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3168 PRSS12 Zornitza Stark Phenotypes for gene: PRSS12 were changed from MENTAL RETARDATION AUTOSOMAL RECESSIVE TYPE 1 to Intellectual disability, PRSS12 related MIM#249500
Fetal anomalies v0.3167 PRSS12 Zornitza Stark Publications for gene: PRSS12 were set to
Fetal anomalies v0.3166 PRPS1 Zornitza Stark Marked gene: PRPS1 as ready
Fetal anomalies v0.3166 PRPS1 Zornitza Stark Gene: prps1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3166 PRPS1 Zornitza Stark Phenotypes for gene: PRPS1 were changed from DEAFNESS X-LINKED TYPE 1; PHOSPHORIBOSYLPYROPHOSPHATE SYNTHETASE SUPERACTIVITY; CHARCOT-MARIE-TOOTH DISEASE X-LINKED RECESSIVE TYPE 5; ARTS SYNDROME to Arts syndrome MIM#301835
Fetal anomalies v0.3165 PRPS1 Zornitza Stark Publications for gene: PRPS1 were set to
Fetal anomalies v0.3164 PRPS1 Zornitza Stark Classified gene: PRPS1 as Amber List (moderate evidence)
Fetal anomalies v0.3164 PRPS1 Zornitza Stark Gene: prps1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3163 PPP3CA Zornitza Stark changed review comment from: The mono-allelic condition is relevant antenatally. However, only 2 individuals reported.

DEE tends to present post-natally.; to: Condition causing multiple congenital anomalies is postulated to be due to GoF variants. However, only 2 individuals reported.

DEE postulated to be due to LoF variants, and presents post-natally.
Mendeliome v0.10932 PPP3CA Zornitza Stark Marked gene: PPP3CA as ready
Mendeliome v0.10932 PPP3CA Zornitza Stark Gene: ppp3ca has been classified as Green List (High Evidence).
Mendeliome v0.10932 PPP3CA Zornitza Stark Phenotypes for gene: PPP3CA were changed from to Developmental and epileptic encephalopathy 91, MIM#617711; Arthrogryposis, cleft palate, craniosynostosis and impaired intellectual development, MIM#618265
Mendeliome v0.10931 PPP3CA Zornitza Stark Publications for gene: PPP3CA were set to
Mendeliome v0.10930 PPP3CA Zornitza Stark Mode of inheritance for gene: PPP3CA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3163 PPT1 Zornitza Stark Marked gene: PPT1 as ready
Fetal anomalies v0.3163 PPT1 Zornitza Stark Gene: ppt1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3163 PPT1 Zornitza Stark Phenotypes for gene: PPT1 were changed from NEURONAL CEROID LIPOFUSCINOSIS TYPE 1 to Ceroid lipofuscinosis, neuronal, 1, MIM# 256730; MONDO:0009744
Fetal anomalies v0.3162 PPT1 Zornitza Stark Publications for gene: PPT1 were set to
Fetal anomalies v0.3161 PPA2 Zornitza Stark Marked gene: PPA2 as ready
Fetal anomalies v0.3161 PPA2 Zornitza Stark Gene: ppa2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3161 PPA2 Zornitza Stark Phenotypes for gene: PPA2 were changed from Sudden arrhythmic cardiac death after infectious or alcohol trigger to Sudden cardiac failure, alcohol-induced, 617223; Sudden cardiac failure, infantile, 617222
Fetal anomalies v0.3160 PPA2 Zornitza Stark Publications for gene: PPA2 were set to
Fetal anomalies v0.3159 PLP1 Zornitza Stark Marked gene: PLP1 as ready
Fetal anomalies v0.3159 PLP1 Zornitza Stark Gene: plp1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3159 PLP1 Zornitza Stark Phenotypes for gene: PLP1 were changed from LEUKODYSTROPHY HYPOMYELINATING TYPE 1; SPASTIC PARAPLEGIA X-LINKED TYPE 2 to Pelizaeus-Merzbacher disease MIM#312080; Spastic paraplegia 2, X-linked MIM#312920
Fetal anomalies v0.3158 PLP1 Zornitza Stark Publications for gene: PLP1 were set to
Mendeliome v0.10929 PLP1 Zornitza Stark Marked gene: PLP1 as ready
Mendeliome v0.10929 PLP1 Zornitza Stark Gene: plp1 has been classified as Green List (High Evidence).
Mendeliome v0.10929 PLP1 Zornitza Stark Phenotypes for gene: PLP1 were changed from to Pelizaeus-Merzbacher disease MIM#312080; Spastic paraplegia 2, X-linked MIM#312920
Mendeliome v0.10928 PLP1 Zornitza Stark Publications for gene: PLP1 were set to
Mendeliome v0.10927 PLP1 Zornitza Stark Mode of inheritance for gene: PLP1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.10926 LDB3 Zornitza Stark Marked gene: LDB3 as ready
Mendeliome v0.10926 LDB3 Zornitza Stark Gene: ldb3 has been classified as Green List (High Evidence).
Mendeliome v0.10926 LDB3 Zornitza Stark Phenotypes for gene: LDB3 were changed from to Cardiomyopathy, dilated, 1C, with or without LVNC MIM#601493; Cardiomyopathy, hypertrophic, 24 MIM#601493; Left ventricular noncompaction 3 MIM#601493; Myopathy, myofibrillar, 4 MIM#609452
Mendeliome v0.10925 LDB3 Zornitza Stark Publications for gene: LDB3 were set to
Mendeliome v0.10924 LDB3 Zornitza Stark Mode of inheritance for gene: LDB3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3157 LDB3 Zornitza Stark Marked gene: LDB3 as ready
Fetal anomalies v0.3157 LDB3 Zornitza Stark Gene: ldb3 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3157 LDB3 Zornitza Stark Phenotypes for gene: LDB3 were changed from MYOPATHY MYOFIBRILLAR TYPE 4; LEFT VENTRICULAR NON-COMPACTION TYPE 3; CARDIOMYOPATHY DILATED TYPE 1C to Cardiomyopathy, dilated, 1C, with or without LVNC MIM#601493; Cardiomyopathy, hypertrophic, 24 MIM#601493; Left ventricular noncompaction 3 MIM#601493; Myopathy, myofibrillar, 4 MIM#609452
Fetal anomalies v0.3156 LDB3 Zornitza Stark Publications for gene: LDB3 were set to 17394203
Fetal anomalies v0.3155 LDB3 Zornitza Stark Mode of inheritance for gene: LDB3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3154 Zornitza Stark removed gene:IL17RD from the panel
Fetal anomalies v0.3153 IGSF1 Zornitza Stark edited their review of gene: IGSF1: Changed rating: RED
Fetal anomalies v0.3153 IGSF1 Zornitza Stark Marked gene: IGSF1 as ready
Fetal anomalies v0.3153 IGSF1 Zornitza Stark Added comment: Comment when marking as ready: Not LGA, unlikely to present antenatally
Fetal anomalies v0.3153 IGSF1 Zornitza Stark Gene: igsf1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3153 IGSF1 Zornitza Stark Phenotypes for gene: IGSF1 were changed from CENTRAL HYPOTHYROIDISM AND TESTICULAR ENLARGEMENT to Hypothyroidism, central, and testicular enlargement MIM#300888
Fetal anomalies v0.3152 IGSF1 Zornitza Stark Publications for gene: IGSF1 were set to
Pulmonary Arterial Hypertension v1.10 NOTCH3 Zornitza Stark Phenotypes for gene: NOTCH3 were changed from Pulmonary arterial hypertension to Pulmonary arterial hypertension, MONDO:0015924
Pulmonary Arterial Hypertension v1.9 NOTCH3 Zornitza Stark Publications for gene: NOTCH3 were set to 19855400; 31868216; 24936512
Pulmonary Arterial Hypertension v1.8 NOTCH3 Zornitza Stark Classified gene: NOTCH3 as Red List (low evidence)
Pulmonary Arterial Hypertension v1.8 NOTCH3 Zornitza Stark Gene: notch3 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3151 SF3B2 Krithika Murali gene: SF3B2 was added
gene: SF3B2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SF3B2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SF3B2 were set to 34344887
Phenotypes for gene: SF3B2 were set to Craniofacial microsomia
Review for gene: SF3B2 was set to GREEN
Added comment: No new relevant published evidence since PanelApp review Aug 2021

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Twenty individuals from seven families reported with de novo or transmitted haploinsufficient variants in SF3B2. Affected individuals had mandibular hypoplasia, microtia, facial and preauricular tags, epibulbar dermoids, lateral oral clefts in addition to skeletal and cardiac abnormalities.

Targeted morpholino knockdown of SF3B2 in Xenopus resulted in disruption of cranial neural crest precursor formation and subsequent craniofacial cartilage defects, supporting a link between spliceosome mutations and impaired neural crest development in congenital craniofacial disease.

The families were ascertained from a cohort and the authors suggest that haploinsufficient variants in SF3B2 are the most prevalent genetic cause of CFM, explaining ~3% of sporadic and ~25% of familial cases.
Sources: Literature
Inflammatory bowel disease v0.63 PTEN Nicola Poplawski reviewed gene: PTEN: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v0.3151 SEPT9 Krithika Murali gene: SEPT9 was added
gene: SEPT9 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SEPT9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SEPT9 were set to 16186812; 19451530; 19939853; 19139049; 18492087
Phenotypes for gene: SEPT9 were set to Amyotrophy, hereditary neuralgic, MIM# 162100
Review for gene: SEPT9 was set to AMBER
Added comment: No new relevant published evidence since last PanelApp review May 2021

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Only one report identified from 2008 of dysmorphic features including cleft palate co-occurring with HNA.

New gene name is SEPTIN9, also note founder variants as well as 5'UTR variants and intragenic duplications reported.
Sources: Literature
Fetal anomalies v0.3151 PLCH1 Krithika Murali gene: PLCH1 was added
gene: PLCH1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PLCH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLCH1 were set to 33820834
Phenotypes for gene: PLCH1 were set to Holoprosencephaly spectrum; Severe developmental delay; Brain malformations
Review for gene: PLCH1 was set to AMBER
Added comment: No new published evidence since last PanelApp review April 2021

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PMID: 33820834 (2021) - Two sibling pairs from two unrelated families with a holoprosencephaly spectrum phenotype and different homozygous PLCH1 variants (c.2065C>T, p.Arg689* and c.4235delA, p.Cys1079ValfsTer16, respectively). One family presented with congenital hydrocephalus, epilepsy, significant developmental delay and a monoventricle or fused thalami; while sibs from the second family had alobar holoprosencephaly and cyclopia. 3/4 individuals also displayed a cleft palate and congenital heart disease. Human embryo immunohistochemistry showed PLCH1 to be expressed in the notorcord, developing spinal cord (in a ventral to dorsal gradient), dorsal root ganglia, cerebellum and dermatomyosome.
Sources: Literature
Fetal anomalies v0.3151 PLEKHA5 Krithika Murali gene: PLEKHA5 was added
gene: PLEKHA5 was added to Fetal anomalies. Sources: Literature,Expert list
Mode of inheritance for gene: PLEKHA5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLEKHA5 were set to 29805042
Phenotypes for gene: PLEKHA5 were set to cleft lip; cleft palate
Review for gene: PLEKHA5 was set to AMBER
Added comment: No new published evidence since last PanelApp review April 2020

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One de novo variant reported, another 5 '3C' rare variants reported in 6 families in this cohort; unclear if monogenic or polygenic contribution to CL/P.
Sources: Literature, Expert list
Fetal anomalies v0.3151 PLEKHA7 Krithika Murali gene: PLEKHA7 was added
gene: PLEKHA7 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PLEKHA7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLEKHA7 were set to 29805042
Phenotypes for gene: PLEKHA7 were set to Cleft palate
Review for gene: PLEKHA7 was set to AMBER
Added comment: No new evidence since last PanelApp review in Jan 2021

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Six rare variants identified in 4 individuals in a CL/P cohort, however, only one of these classified as likely pathogenic. One individual had bi-allelic variants. Some supportive functional data
Sources: Literature
Fetal anomalies v0.3151 PPP1R13L Krithika Murali gene: PPP1R13L was added
gene: PPP1R13L was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PPP1R13L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPP1R13L were set to 32666529; 28864777
Phenotypes for gene: PPP1R13L were set to Dilated cardiomyopathy, onset in infancy; Cleft lip and palate
Review for gene: PPP1R13L was set to GREEN
Added comment: No new information since last PanelApp review June 2021

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At least 6 unrelated families. NMD-predicted, missense and stop-loss (extension) variants have been reported in individuals with autosomal recessive PPP1R13L-related syndrome. Patients described with biallelic pathogenic variants in PPP1R13L all had severe infantile-onset dilated cardiomyopathy, with additional features including cleft lip and palate, wedge-shaped teeth, and sparse, dry, woolly hair described in several individuals. Death due to HF progression before 5yo reported in cases that didn't receive a heart transplant. Cognitive delay also reported in two unrelated individuals (PMID: 28069640, PMID: 32666529).
Sources: Literature
Fetal anomalies v0.3151 METTL23 Krithika Murali gene: METTL23 was added
gene: METTL23 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: METTL23 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: METTL23 were set to 32878022; 32439618; 32067349; 24626631; 24501276
Phenotypes for gene: METTL23 were set to Mental retardation, autosomal recessive 44 - #615942
Review for gene: METTL23 was set to RED
Added comment: Biallelic variants associated with syndromic ID. Published studies provide no or limited antenatal information with no consistent prenatal phenotype described.

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PMID: 32878022 – Khan et al 2020 - homozygous missense variants identified in consanguineous Pakistani family with 3 affected siblings having ID, epilepsy, behavioural issues, hypotonia and dysmorphic features (prominent large-size eyes, eyebrows, ears, short upturned nose with flat nasal bridge, and thin upper lip). Authors report that prenatal, perinatal and neonatal medical records of all patients were normal.

PMID 32439618 – Smaili et al 2020 report two Moroccan siblings presenting with mild intellectual disability and dysmorphic features. WES identified homozygous METTL23 gene variants. Describe uneventful pregnancies and postnatal course. Macrocephaly reported in both siblings (HC 52cm in a 7 year old M and 50cm in 6 yo F) - no information regarding HC of parents provided, macrocephaly not a consistently reported feature of this condition.

PMID: 32067349 – Almannai et al 2020 - 6 individuals from 4 families - 2 families unrelated, 2 families come from same Saudi tribe and are therefore likely to be distantly related with same homozygous METTL23 variant identified in both. No prenatal features or immediate postnatal issues described related to this condtion. One subject reported to have an MRI-B showing mild ventriculomegaly at a later age which may reflect mild white matter volume loss. This subject also had a 618 Kilobases duplication at 7p11.2 (57,261,112-57,878,853) identified on CGH array.

PMID: 24626631 – Bernkopf 2014 - describe 2 unrelated families. Provide no antenatal information or report no issues antenatally/at birth apart from one baby being large and cyanosed postnatally

PMID: 24501276 – Reiff et al 2014 - report 7 affected members of a large, consanguineous Arab family with ID and mild dysmorphic features. X1 patient had cleft uvula and submucosal cleft palate.
Sources: Literature
Fetal anomalies v0.3151 LRRC32 Krithika Murali gene: LRRC32 was added
gene: LRRC32 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: LRRC32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRRC32 were set to 30976112
Phenotypes for gene: LRRC32 were set to Cleft palate, proliferative retinopathy, and developmental delay - MIM#619074
Review for gene: LRRC32 was set to AMBER
Added comment: Gene previously reviewed for PanelApp Feb 2021 - no new relevant publications since

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Three individuals from two consanguineous families with cleft palate, proliferative retinopathy, and developmental delay had the same homozygous biallelic variant, c.1630C>T; p.(Arg544Ter), segregated and shared haplotype indicative of founder effect. Mouse model has cleft palate and neonatal death.
Sources: Literature
Fetal anomalies v0.3151 SCN8A Ain Roesley reviewed gene: SCN8A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 13, MIM#614558, dominant and recessive, Myoclonus, familial, 2, MIM# 618364, paroxysmal kinesigenic dyskinesias, Cognitive impairment with or without cerebellar ataxia, MIM# 614306; Mode of inheritance: None; Current diagnostic: yes
Fetal anomalies v0.3151 RFWD3 Ain Roesley reviewed gene: RFWD3: Rating: RED; Mode of pathogenicity: None; Publications: 28691929; Phenotypes: Fanconi anemia, complementation group W, MIM# 617784; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3151 RAB39B Ain Roesley reviewed gene: RAB39B: Rating: RED; Mode of pathogenicity: None; Publications: 34761259, 20159109, 25434005, 27066548, 26399558, 27943471, 28851564, 28851564, 29152164, 33880059, 27448726, 32670181; Phenotypes: Intellectual developmental disorder, X-linked 72 MIM#300271, Waisman syndrome MIM#311510; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Mendeliome v0.10923 RAB39B Ain Roesley reviewed gene: RAB39B: Rating: GREEN; Mode of pathogenicity: None; Publications: 34761259, 20159109, 25434005, 27066548, 26399558, 27943471, 28851564, 28851564, 29152164, 33880059, 27448726, 32670181; Phenotypes: Intellectual developmental disorder, X-linked 72 MIM#300271, Waisman syndrome MIM#311510; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Fetal anomalies v0.3151 LRP6 Krithika Murali gene: LRP6 was added
gene: LRP6 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: LRP6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LRP6 were set to 16126904; 30950205; 26387593; 26963285; 28813618; 29500247; 33164649; 34306029
Phenotypes for gene: LRP6 were set to Tooth agenesis, selective, 7 - MIM#616724; cleft lip/palate
Review for gene: LRP6 was set to AMBER
Added comment: LoF variants known to be associated with tooth agenesis. In addition, x2 unrelated families from 2 different studies with heterozygous LRP6 variant had tooth agenesis and cleft lip/palate (PMID 29500247; 26963285). Growth failure reported in some individuals but unclear if prenatal in onset (PMID 26963285). Minor finger/ear anomalies reported in x2 patients (PMID 26387593; 30950205)- unlikely to be detected antenatally and one of the reported patients (30950205) had x2 chromosome deletions, one of which involved LRP6 and multiple other genes.

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PMID: 34306029 Huang et al 2021 - Heterozygous LRP6: c.2570G > A (p.R857H), harbored by six members of a Chinese family, including 4 with tooth agenesis. Sparse hair another phenotypic feature.

PMID: 33164649 Yu et al 2021 - identified 4 novel LRP6 heterozygous mutations in 4 of 77 oligodontia patients. One patient with a nonsense paternally inherited variant had a hypohidrotic ectodermal dysplasia phenotype - no antenatal features, father had oligodontia. Supportive functional evidence

PMID: 29500247 Basha et al 2018 - Nonsense LRP6 variant identified in a family with cleft lip/palate. Proband had bilateral cleft lip and palate with missing upper lateral incisors, mother had bilateral cleft lip. x1 unaffected brother but family members not reassessed for oligodontia after variant identified.

PMID: 28813618 Dinckan et al 2018 - heterozygous splice site LRP6 variant identified in 1 family with isolated tooth agenesis. Affected family members also had mild periocular hyperpigmentation and hypoplastic alae nasi - thought to be unrelated to phenotype

PMID: 26963285 Ockeloen et al 2016 - frameshift variant identified in patient with tooth agenesis and orofacial clefting - boy born with bilateral cleft lip, L) sided cleft of the alveolus and complete cleft of the hard and soft palate. Also noted to have growth retardation, hypermetropia and small median alveolar manibular cleft. Maternal relatives with variant had severe tooth agenesis but no clefting. Canonical splice site variant identified in a patient with isolated severe tooth agenesis. Targeted resequencing showed statistically significant enrichment of unique LRP6 variants in tooth agenesis patients (7/67 versus 13/706 controls), not orofacial clefting cohort. 4/7 of these patients required growth hormone therapy and 3/7 had clinodactyly in addition to dental anomalies.

PMID: 26387593 – Massink et al 2015 - x4 LoF heterozygous LRP6 variants identified in 4 unrelated families with isolated severe tooth agenesis. All affected members of one family showed minor anatomical variation of the ear and underdevelopment of the thumb

PMID: 30950205 Ross et al 2019 - Proband with oligodontia and thrombocytopenia, also had mild finger and ear anomalies. Array revealed an interstitial loss of 150 kb in 8p23.1 encompassing MCPH1 and ANGPT2 and an interstitial loss of 290 kb in 12p13.2 encompassing ETV6, BCL2L14 and LRP6.
Sources: Literature
Fetal anomalies v0.3151 PTCHD1 Ain Roesley reviewed gene: PTCHD1: Rating: RED; Mode of pathogenicity: None; Publications: 33856728, 25131214; Phenotypes: intellectual disability MIM#300830; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Mendeliome v0.10923 PTCHD1 Ain Roesley reviewed gene: PTCHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33856728, 25131214; Phenotypes: intellectual disability MIM#300830; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Fetal anomalies v0.3151 PSMB8 Ain Roesley reviewed gene: PSMB8: Rating: RED; Mode of pathogenicity: None; Publications: 21129723, 21881205, 21852578, 21953331; Phenotypes: Proteasome-associated autoinflammatory syndrome 1, MIM# 256040, MONDO:0054698; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.4495 PRSS12 Ain Roesley reviewed gene: PRSS12: Rating: RED; Mode of pathogenicity: None; Publications: 12459588, 22090715, 23344636; Phenotypes: Intellectual disability, PRSS12 related MIM#249500; Mode of inheritance: None; Current diagnostic: yes
Mendeliome v0.10923 PRSS12 Ain Roesley reviewed gene: PRSS12: Rating: RED; Mode of pathogenicity: None; Publications: 12459588, 22090715, 23344636; Phenotypes: Intellectual disability, PRSS12 related MIM#249500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3151 PRSS12 Ain Roesley reviewed gene: PRSS12: Rating: RED; Mode of pathogenicity: None; Publications: 12459588, 22090715, 23344636; Phenotypes: Intellectual disability, PRSS12 related MIM#249500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3151 PRPS1 Ain Roesley reviewed gene: PRPS1: Rating: AMBER; Mode of pathogenicity: None; Publications: 32781272, 24961627; Phenotypes: Arts syndrome MIM#301835; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Mendeliome v0.10923 PPP3CA Chern Lim changed review comment from: PMID: 29432562:
- Overexpression studies using yeast showed missense variants in the autoinhibitory domain resulted in gain of function, missense variants in the catalytic domain resulted in loss of function (however dom-neg has not been ruled out).
- Loss-of-function and gain-of-function mutations of PPP3CA lead to early onset epileptic encephalopathy and multiple congenital abnormalities, respectively.

PMID: 32593294:
- Reported a patient with PTV in the C-term predicted to escape NMD, clinical features consistent with MIM#617711.
- Summarised that missense variants in catalytic domain and those upstream of autoinhibitory domain, PTVs in C-term predicted to escape NMD: LoF, MIM#617711. Missense in autoinhibitory domain: GoF, MIM#618265.; to: PMID: 29432562:
- Overexpression studies using yeast showed missense variants in the autoinhibitory domain resulted in gain of function, missense variants in the catalytic domain resulted in loss of function (however dom-neg has not been ruled out).
- Loss-of-function and gain-of-function mutations of PPP3CA lead to early onset epileptic encephalopathy and multiple congenital abnormalities, respectively.

PMID: 32593294:
- Reported a patient with PTV in the C-term predicted to escape NMD, clinical features consistent with MIM#617711.
- 15 variants have been reported. Summarised that missense variants in catalytic domain and those upstream of autoinhibitory domain, PTVs in C-term predicted to escape NMD: LoF, MIM#617711; missense in autoinhibitory domain: GoF, MIM#618265.
Mendeliome v0.10923 PPP3CA Chern Lim reviewed gene: PPP3CA: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 29432562, 32593294; Phenotypes: Developmental and epileptic encephalopathy 91, MIM#617711, Arthrogryposis, cleft palate, craniosynostosis and impaired intellectual development, MIM#618265; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Fetal anomalies v0.3151 PPT1 Ain Roesley reviewed gene: PPT1: Rating: RED; Mode of pathogenicity: None; Publications: 7637805, 9425237, 9664077; Phenotypes: Ceroid lipofuscinosis, neuronal, 1, MIM# 256730, MONDO:0009744; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3151 PPA2 Ain Roesley reviewed gene: PPA2: Rating: RED; Mode of pathogenicity: None; Publications: 27523598, 34400813; Phenotypes: Sudden cardiac failure, alcohol-induced, 617223, Sudden cardiac failure, infantile, 617222; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3151 PLP1 Ain Roesley reviewed gene: PLP1: Rating: RED; Mode of pathogenicity: None; Publications: 20301361; Phenotypes: Pelizaeus-Merzbacher disease MIM#312080, Spastic paraplegia 2, X-linked MIM#312920; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Mendeliome v0.10923 PLP1 Ain Roesley reviewed gene: PLP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301361; Phenotypes: Pelizaeus-Merzbacher disease MIM#312080, Spastic paraplegia 2, X-linked MIM#312920; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Mendeliome v0.10923 LDB3 Ain Roesley reviewed gene: LDB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 26419279, 16427346, 14660611, 14662268, 27546599, 25911362; Phenotypes: Cardiomyopathy, dilated, 1C, with or without LVNC MIM#601493, Cardiomyopathy, hypertrophic, 24 MIM#601493, Left ventricular noncompaction 3 MIM#601493, Myopathy, myofibrillar, 4 MIM#609452; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Fetal anomalies v0.3151 LDB3 Ain Roesley reviewed gene: LDB3: Rating: RED; Mode of pathogenicity: None; Publications: 26419279, 16427346, 14660611, 14662268, 27546599, 25911362; Phenotypes: Cardiomyopathy, dilated, 1C, with or without LVNC MIM#601493, Cardiomyopathy, hypertrophic, 24 MIM#601493, Left ventricular noncompaction 3 MIM#601493, Myopathy, myofibrillar, 4 MIM#609452; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Fetal anomalies v0.3151 IL17RD Ain Roesley reviewed gene: IL17RD: Rating: RED; Mode of pathogenicity: None; Publications: 23643382, 32389901; Phenotypes: Hypogonadotropic hypogonadism 18 with or without anosmia, MIM# 615267; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3151 IGSF1 Ain Roesley reviewed gene: IGSF1: Rating: AMBER; Mode of pathogenicity: None; Publications: 26840047; Phenotypes: Hypothyroidism, central, and testicular enlargement MIM#300888; 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
Pulmonary Arterial Hypertension v1.7 NOTCH3 Nicola Poplawski reviewed gene: NOTCH3: Rating: RED; Mode of pathogenicity: None; Publications: PMID:33712516, 24936512; Phenotypes: 125310; Mode of inheritance: None
Fetal anomalies v0.3151 KAT5 Zornitza Stark Marked gene: KAT5 as ready
Fetal anomalies v0.3151 KAT5 Zornitza Stark Gene: kat5 has been classified as Green List (High Evidence).
Fetal anomalies v0.3151 KAT5 Zornitza Stark Classified gene: KAT5 as Green List (high evidence)
Fetal anomalies v0.3151 KAT5 Zornitza Stark Gene: kat5 has been classified as Green List (High Evidence).
Fetal anomalies v0.3150 INTS1 Zornitza Stark Marked gene: INTS1 as ready
Fetal anomalies v0.3150 INTS1 Zornitza Stark Gene: ints1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3150 INTS1 Zornitza Stark Classified gene: INTS1 as Green List (high evidence)
Fetal anomalies v0.3150 INTS1 Zornitza Stark Gene: ints1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3149 COL25A1 Zornitza Stark Marked gene: COL25A1 as ready
Fetal anomalies v0.3149 COL25A1 Zornitza Stark Gene: col25a1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3149 COL25A1 Zornitza Stark Classified gene: COL25A1 as Green List (high evidence)
Fetal anomalies v0.3149 COL25A1 Zornitza Stark Gene: col25a1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3148 COL25A1 Zornitza Stark gene: COL25A1 was added
gene: COL25A1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: COL25A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COL25A1 were set to 35077597; 26437029
Phenotypes for gene: COL25A1 were set to Arthrogryposis multiplex congenita MONDO:0015168
Review for gene: COL25A1 was set to GREEN
Added comment: 6 cases from 4 unrelated families with AMC as a feature of the phenotype PMID: 35077597 - 5 patients from 3 unrelated families with biallelic missense and splice site COL25A1 variants presenting with arthrogryposis multiplex congenita with or without an ocular congenital cranial dysinnervation disorder phenotype PMID: 26437029 - Patient: 273182 in DECIPHER with compound het missense variants. Phenotype includes Congenital finger flexion contractures, Contracture of the distal interphalangeal joint of the 2nd finger, Duane anomaly
Sources: Literature
Cerebral Palsy v1.22 SCN2A Zornitza Stark Marked gene: SCN2A as ready
Cerebral Palsy v1.22 SCN2A Zornitza Stark Gene: scn2a has been classified as Green List (High Evidence).
Cerebral Palsy v1.22 SCN2A Zornitza Stark Classified gene: SCN2A as Green List (high evidence)
Cerebral Palsy v1.22 SCN2A Zornitza Stark Gene: scn2a has been classified as Green List (High Evidence).
Congenital Heart Defect v0.188 HYAL2 Zornitza Stark Marked gene: HYAL2 as ready
Congenital Heart Defect v0.188 HYAL2 Zornitza Stark Gene: hyal2 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.188 HYAL2 Zornitza Stark Classified gene: HYAL2 as Green List (high evidence)
Congenital Heart Defect v0.188 HYAL2 Zornitza Stark Gene: hyal2 has been classified as Green List (High Evidence).
Mendeliome v0.10923 HYAL2 Zornitza Stark Publications for gene: HYAL2 were set to 28081210; 23172227; 26515055
Mendeliome v0.10922 HYAL2 Zornitza Stark Classified gene: HYAL2 as Green List (high evidence)
Mendeliome v0.10922 HYAL2 Zornitza Stark Gene: hyal2 has been classified as Green List (High Evidence).
Fetal anomalies v0.3147 HYAL2 Zornitza Stark Marked gene: HYAL2 as ready
Fetal anomalies v0.3147 HYAL2 Zornitza Stark Gene: hyal2 has been classified as Green List (High Evidence).
Fetal anomalies v0.3147 HYAL2 Zornitza Stark Classified gene: HYAL2 as Green List (high evidence)
Fetal anomalies v0.3147 HYAL2 Zornitza Stark Gene: hyal2 has been classified as Green List (High Evidence).
Clefting disorders v0.172 HYAL2 Zornitza Stark Publications for gene: HYAL2 were set to 28081210; 23172227; 26515055
Clefting disorders v0.171 HYAL2 Zornitza Stark Classified gene: HYAL2 as Green List (high evidence)
Clefting disorders v0.171 HYAL2 Zornitza Stark Gene: hyal2 has been classified as Green List (High Evidence).
Fetal anomalies v0.3146 HOXA2 Zornitza Stark Marked gene: HOXA2 as ready
Fetal anomalies v0.3146 HOXA2 Zornitza Stark Gene: hoxa2 has been classified as Green List (High Evidence).
Fetal anomalies v0.3146 HOXA2 Zornitza Stark Classified gene: HOXA2 as Green List (high evidence)
Fetal anomalies v0.3146 HOXA2 Zornitza Stark Gene: hoxa2 has been classified as Green List (High Evidence).
Mendeliome v0.10921 PAX5 Zornitza Stark Marked gene: PAX5 as ready
Mendeliome v0.10921 PAX5 Zornitza Stark Gene: pax5 has been classified as Green List (High Evidence).
Mendeliome v0.10921 PAX5 Zornitza Stark Phenotypes for gene: PAX5 were changed from to Neurodevelopmental disorder MONDO:0700092, PAX5-related
Genetic Epilepsy v0.1449 EEF1B2 Zornitza Stark Marked gene: EEF1B2 as ready
Genetic Epilepsy v0.1449 EEF1B2 Zornitza Stark Gene: eef1b2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1449 EEF1B2 Zornitza Stark Classified gene: EEF1B2 as Green List (high evidence)
Genetic Epilepsy v0.1449 EEF1B2 Zornitza Stark Gene: eef1b2 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1448 EEF1B2 Zornitza Stark gene: EEF1B2 was added
gene: EEF1B2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: EEF1B2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EEF1B2 were set to 31845318; 21937992; 35015920
Phenotypes for gene: EEF1B2 were set to Neurodevelopmental disorder MONDO:0700092; non-syndromic ID and seizures
Review for gene: EEF1B2 was set to GREEN
Added comment: Now 7 individuals in 3 unrelated families with a phenotype of non-syndromic ID and fever-sensitive seizures. Knockout zebrafish model demonstrated abnormal development and a photosensitive seizure-like behavioural phenotype.
Sources: Literature
Fetal anomalies v0.3145 ESRP2 Zornitza Stark Marked gene: ESRP2 as ready
Fetal anomalies v0.3145 ESRP2 Zornitza Stark Gene: esrp2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3145 ESRP2 Zornitza Stark Classified gene: ESRP2 as Amber List (moderate evidence)
Fetal anomalies v0.3145 ESRP2 Zornitza Stark Gene: esrp2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3144 EIF3F Zornitza Stark Marked gene: EIF3F as ready
Fetal anomalies v0.3144 EIF3F Zornitza Stark Gene: eif3f has been classified as Green List (High Evidence).
Fetal anomalies v0.3144 EIF3F Zornitza Stark Phenotypes for gene: EIF3F were changed from ntellectual developmental disorder, autosomal recessive 67- MIM#618295 to Intellectual developmental disorder, autosomal recessive 67- MIM#618295
Fetal anomalies v0.3143 EIF3F Zornitza Stark Classified gene: EIF3F as Green List (high evidence)
Fetal anomalies v0.3143 EIF3F Zornitza Stark Gene: eif3f has been classified as Green List (High Evidence).
Fetal anomalies v0.3142 COL9A3 Zornitza Stark Marked gene: COL9A3 as ready
Fetal anomalies v0.3142 COL9A3 Zornitza Stark Gene: col9a3 has been classified as Green List (High Evidence).
Fetal anomalies v0.3142 COL9A3 Zornitza Stark Classified gene: COL9A3 as Green List (high evidence)
Fetal anomalies v0.3142 COL9A3 Zornitza Stark Gene: col9a3 has been classified as Green List (High Evidence).
Fetal anomalies v0.3141 FTO Zornitza Stark Marked gene: FTO as ready
Fetal anomalies v0.3141 FTO Zornitza Stark Gene: fto has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3141 FTO Zornitza Stark Marked gene: FTO as ready
Fetal anomalies v0.3141 FTO Zornitza Stark Gene: fto has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3141 FTO Zornitza Stark Classified gene: FTO as Amber List (moderate evidence)
Fetal anomalies v0.3141 FTO Zornitza Stark Gene: fto has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3140 KAT5 Krithika Murali gene: KAT5 was added
gene: KAT5 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: KAT5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KAT5 were set to 32822602
Phenotypes for gene: KAT5 were set to Neurodevelopmental disorder wtih dysmorphic facies, sleep disturbance, and brain abnormalities- MIM#619103
Review for gene: KAT5 was set to GREEN
Added comment: PMID: 32822602 Humbert et al 2020 - single study reporting 3 individuals with syndromic ID and de novo heterozygous missense variants in KAT5, supportive functional data

Individual 1 – diagnosed as an adult, syndromic ID, brachydactyly, partial agenesis of the corpus callosum

Indidual 2 – 13 yo M with ID and multiple malformations – born at 38 weeks with a unilateral CL/P, horshoe kidney, progressive cerebellar atrophy, dysgenesis of the corpus callosum

Individual 3 – presented with congenital microcephay, short stature, VSD, dysplastic pulmonary valve with supravalvular and valvular stenosis, submucous cleft, hypospadias, MRI B PMG R) sylvian fissure, cystic dilation of 4th ventricle and inferior cerebellar vermis atrophy
Sources: Literature
Fetal anomalies v0.3140 INTS1 Krithika Murali gene: INTS1 was added
gene: INTS1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: INTS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INTS1 were set to 28542170; 30622326; 31428919
Phenotypes for gene: INTS1 were set to Neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies - MIM#618571
Review for gene: INTS1 was set to GREEN
Added comment: PMID: 28542170 Oegema et al 2017 - 3 unrelated individuals with syndromic ID of Dutch ancestry showed the same homozygous truncating INTS1 mutation - 1/3 Cleft palate/lip, 1/3 renal malformation

PMID: 30622326 – Krall et al 2019 - 5 patients from 4 families with biallelic sequence variants in INTS1. The patients manifested absent or severely limited speech, an abnormal gait, hypotonia and cataracts. Other phenotypic features included:
o Micropthalmia – 2/5
o Frontal bossing 2/5
o Hypertelorism – 5/5
o Microretrognathia – 4/5
o Renal malformation 2/5


PMID: 31428919 – Zhang et al 2020 - 2 Chinese siblings with ID found to have INTST1 compound het variants, both had cataracts, facial dysmorphism, short stature, severe ID and anomalous genitalia
Sources: Literature
Mendeliome v0.10920 COL25A1 Bryony Thompson Phenotypes for gene: COL25A1 were changed from Fibrosis of extraocular muscles, congenital, 5, MIM# 616219 to Fibrosis of extraocular muscles, congenital, 5, MIM# 616219; arthrogryposis multiplex congenita MONDO:0015168
Mendeliome v0.10919 COL25A1 Bryony Thompson Publications for gene: COL25A1 were set to 25500261; 26486031; 31875546; 26437029
Mendeliome v0.10918 COL25A1 Bryony Thompson reviewed gene: COL25A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35077597, 26437029; Phenotypes: arthrogryposis multiplex congenita MONDO:0015168; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v0.322 COL25A1 Bryony Thompson Marked gene: COL25A1 as ready
Arthrogryposis v0.322 COL25A1 Bryony Thompson Gene: col25a1 has been classified as Green List (High Evidence).
Arthrogryposis v0.322 COL25A1 Bryony Thompson Classified gene: COL25A1 as Green List (high evidence)
Arthrogryposis v0.322 COL25A1 Bryony Thompson Gene: col25a1 has been classified as Green List (High Evidence).
Arthrogryposis v0.321 COL25A1 Bryony Thompson gene: COL25A1 was added
gene: COL25A1 was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: COL25A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COL25A1 were set to 35077597; 26437029
Phenotypes for gene: COL25A1 were set to arthrogryposis multiplex congenita MONDO:0015168
Review for gene: COL25A1 was set to GREEN
Added comment: 6 cases from 4 unrelated families with AMC as a feature of the phenotype
PMID: 35077597 - 5 patients from 3 unrelated families with biallelic missense and splice site COL25A1 variants presenting with arthrogryposis multiplex congenita with or without an ocular congenital cranial dysinnervation disorder phenotype
PMID: 26437029 - Patient: 273182 in DECIPHER with compound het missense variants. Phenotype includes Congenital finger flexion contractures, Contracture of the distal interphalangeal joint of the 2nd finger, Duane anomaly
Sources: Literature
Cerebral Palsy v1.21 SCN2A Clare van Eyk gene: SCN2A was added
gene: SCN2A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SCN2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SCN2A were set to 33528536; 29761117; 34114234
Phenotypes for gene: SCN2A were set to Developmental and epileptic encephalopathy 11 (DEE11), MIM# 613721
Review for gene: SCN2A was set to GREEN
Added comment: Four single cases with de novo pathogenic/likely pathogenic missense variants in individuals with a clinical diagnosis of cerebral palsy. Mutations in SCN2A cause a spectrum of early-onset epileptic encephalopathies, with some cases reported to have movement disorders clinically overlapping with cerebral palsy.
Sources: Literature
Congenital Heart Defect v0.187 HYAL2 Krithika Murali gene: HYAL2 was added
gene: HYAL2 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: HYAL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HYAL2 were set to 34906488; 28081210; 23172227; 26515055
Phenotypes for gene: HYAL2 were set to Cleft lip and palate; cor triatriatum; congenital cardiac malformations
Review for gene: HYAL2 was set to GREEN
Added comment: Combined reported phenotypic features of 17 individuals from both studies
• Hyperterlorism 13/16
• External ear anomalies – 11/14
• Cleft lip/palate – 10/17
• Micrognathia – 9/14
• Cardiac anomalies 12/17
• Frontal bossing 5/14
• Ptosis 5/13
• Pectus excavatum 7/16
• Myopia 11/11
• Cataract 2/8
• Hearing loss 7/16
Sources: Literature
Mendeliome v0.10918 RPL8 Bryony Thompson Marked gene: RPL8 as ready
Mendeliome v0.10918 RPL8 Bryony Thompson Gene: rpl8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10918 RPL8 Bryony Thompson Classified gene: RPL8 as Amber List (moderate evidence)
Mendeliome v0.10918 RPL8 Bryony Thompson Gene: rpl8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10917 HYAL2 Krithika Murali reviewed gene: HYAL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34906488, 28081210, 23172227, 26515055; Phenotypes: Cleft lip and palate, cor triatriatum, congenital cardiac malformations; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3140 HYAL2 Krithika Murali gene: HYAL2 was added
gene: HYAL2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: HYAL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HYAL2 were set to 34906488; 28081210; 23172227; 26515055
Phenotypes for gene: HYAL2 were set to Cleft lip and palate; cor triatriatum; congenital cardiac malformations
Review for gene: HYAL2 was set to GREEN
Added comment: PMID 28081210 Muggenthaler et al 2017 - 2 unrelated consanguineous extended families (Amish and Arab) with an orofacial clefting phenotype with cardiac anomalies

PMID 34906488 Fasham et al 2021 - report 10 additional individuals from 6 unrelated families (Amish x2 - same founder variant as in previous study, Romanian, Italian, Northern European ancestry)

Combined reported phenotypic features of 17 individuals from both studies most relevant in the prenatal setting include:
• Hyperterlorism 13/16
• External ear anomalies – 11/14
• Cleft lip/palate – 10/17
• Micrognathia – 9/14
• Cardiac anomalies 12/17
Sources: Literature
Clefting disorders v0.170 HYAL2 Krithika Murali reviewed gene: HYAL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34906488, 28081210, 23172227, 26515055; Phenotypes: Cleft lip and palate, cor triatriatum, congenital cardiac malformations; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cholestasis v0.222 ABCB4 Zornitza Stark Phenotypes for gene: ABCB4 were changed from Cholestasis, progressive familial intrahepatic 3 MIM#602347; disorder of bile acid metabolism to Cholestasis, progressive familial intrahepatic 3 MIM#602347; disorder of bile acid metabolism; Cholestasis, intrahepatic, of pregnancy, 3 (MIM#614972); Gallbladder disease 1 (MIM#600803)
Cholestasis v0.221 ABCB4 Zornitza Stark Publications for gene: ABCB4 were set to 8666348; 17726488
Cholestasis v0.220 ABCB4 Zornitza Stark Mode of inheritance for gene: ABCB4 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.10917 ABCB4 Zornitza Stark Phenotypes for gene: ABCB4 were changed from Cholestasis, progressive familial intrahepatic 3 MIM#602347; disorder of bile acid metabolism to Cholestasis, progressive familial intrahepatic 3 MIM#602347; disorder of bile acid metabolism; Gallbladder disease 1 (MIM#600803)
Mendeliome v0.10916 ABCB4 Zornitza Stark Publications for gene: ABCB4 were set to 8666348; 17726488
Mendeliome v0.10915 ABCB4 Zornitza Stark Mode of inheritance for gene: ABCB4 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.10914 RPL8 Bryony Thompson gene: RPL8 was added
gene: RPL8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RPL8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPL8 were set to 25424902; 34961992
Phenotypes for gene: RPL8 were set to Diamond-Blackfan anemia MONDO:0015253
Review for gene: RPL8 was set to AMBER
Added comment: 2 unrelated DBA cases with de novo missense variants, and functional studies in lymphoblastoid cells and yeast models demonstrate the 2 missense variants are functionally deficient proteins that affect ribosome production.
Sources: Literature
Diamond Blackfan anaemia v1.2 RPL8 Bryony Thompson Marked gene: RPL8 as ready
Diamond Blackfan anaemia v1.2 RPL8 Bryony Thompson Gene: rpl8 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4495 PAX5 Bryony Thompson Marked gene: PAX5 as ready
Intellectual disability syndromic and non-syndromic v0.4495 PAX5 Bryony Thompson Gene: pax5 has been classified as Green List (High Evidence).
Diamond Blackfan anaemia v1.2 RPL8 Bryony Thompson Classified gene: RPL8 as Amber List (moderate evidence)
Diamond Blackfan anaemia v1.2 RPL8 Bryony Thompson Gene: rpl8 has been classified as Amber List (Moderate Evidence).
Diamond Blackfan anaemia v1.1 RPL8 Bryony Thompson gene: RPL8 was added
gene: RPL8 was added to Diamond Blackfan anaemia. Sources: Literature
Mode of inheritance for gene: RPL8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPL8 were set to 25424902; 34961992
Phenotypes for gene: RPL8 were set to Diamond-Blackfan anemia MONDO:0015253
Review for gene: RPL8 was set to AMBER
Added comment: 2 unrelated DBA cases with de novo missense variants, and functional studies in lymphoblastoid cells and yeast models demonstrate the 2 missense variants are functionally deficient proteins that affect ribosome production.
Sources: Literature
Cholestasis v0.219 ABCB4 Lucy Spencer reviewed gene: ABCB4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 18482588, 28924228, 32376413; Phenotypes: Cholestasis, intrahepatic, of pregnancy, 3 (MIM#614972), Gallbladder disease 1 (MIM#600803); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.10913 ABCB4 Lucy Spencer reviewed gene: ABCB4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 18482588, 28924228, 32376413; Phenotypes: Cholestasis, intrahepatic, of pregnancy, 3 (MIM#614972), Gallbladder disease 1 (MIM#600803); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Fetal anomalies v0.3140 HOXA2 Krithika Murali gene: HOXA2 was added
gene: HOXA2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: HOXA2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: HOXA2 were set to 18394579; 23775976; 27503514; 28109504; 31567444; 32649979
Phenotypes for gene: HOXA2 were set to Microtia with or without hearing impairment (AD) - MIM#612290
Review for gene: HOXA2 was set to GREEN
Added comment: Heterozygous variants associated with non-syndromic microtia and hearing loss reported in over 5 families

Homozygous variant associated with severe microtia, hearing loss and partial cleft palate reported in 3 affected individuals in 1 family.

Supportive mouse models

---

PMID: 18394579 Alasti et al 2008 - first identified 3 affected individuals from one consanguineous Persian family also had partial cleft palate with homozygous HOXA2 variant. Only family with AR inheritance reported so far.

PMID: 23775976 Brown et al 2013 – multiple affected individuals from one family with non-syndromic bilateral microtia and hearing loss segregating as an autosomal dominant trait. Exome sequencing identified heterozygous protein truncating HOXA2 nonsense change (c.703C>T, p.Q235*).

PMID: 27503514 Piceci et al 2017 – reported one family with isolated bilateral microtia segregating as an autosomal dominant trait. Heterozygous protein truncating nonsense variant identified [c.670G>T, p.(Glu224*)] segregating in all affected individuals

PMID: 28109504 Hao et al 2017 - 2 novel variants in the 5’ UTR of HOXA2 identified in a screen of patients with microtia, limited phenotypic information

PMID: 31567444 Meddaugh et al 2020 - reported heterozygous variant in 4-year-old Caucasian male with bilateral dysplastic ears and conductive hearing loss.

PMID: 32649979 Si et al 2020 – reported two Chinese families with non-syndromic bilateral microtia identifying two separate heterozygous nonsense HOXA2 variants
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4495 PAX5 Bryony Thompson Classified gene: PAX5 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4495 PAX5 Bryony Thompson Gene: pax5 has been classified as Green List (High Evidence).
Mendeliome v0.10913 PAX5 Bryony Thompson Publications for gene: PAX5 were set to
Intellectual disability syndromic and non-syndromic v0.4494 PAX5 Bryony Thompson gene: PAX5 was added
gene: PAX5 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: PAX5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PAX5 were set to 35094443; 31452935; 28263302; 25418537; 8001127; 27626380
Phenotypes for gene: PAX5 were set to neurodevelopmental disorder MONDO:0700092
Review for gene: PAX5 was set to GREEN
Added comment: 5 individuals from 4 families with large deletions involving PAX5 and 11 individuals from 9 families with frameshift/stopgain/missense variants and neurodevelopmental phenotypes that included delayed developmental milestones (DD), intellectual disability (ID), and/or ASD. 6 of the variants are de novo. Null mouse have retarded growth and altered patterning of the posterior midbrain. Pax5+/− mice of both sexes are hyperactive and have abnormal auditory brainstem responses.
Sources: Literature
Mendeliome v0.10912 PAX5 Bryony Thompson Mode of inheritance for gene: PAX5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10911 PAX5 Bryony Thompson reviewed gene: PAX5: Rating: GREEN; Mode of pathogenicity: None; Publications: 35094443, 31452935, 28263302, 25418537, 8001127, 27626380; Phenotypes: neurodevelopmental disorder MONDO:0700092; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4493 EEF1B2 Bryony Thompson Phenotypes for gene: EEF1B2 were changed from Intellectual disability to neurodevelopmental disorder MONDO:0700092; non-syndromic ID and seizures; Intellectual disability
Intellectual disability syndromic and non-syndromic v0.4492 EEF1B2 Bryony Thompson Publications for gene: EEF1B2 were set to 31845318; 21937992
Intellectual disability syndromic and non-syndromic v0.4491 EEF1B2 Bryony Thompson Classified gene: EEF1B2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4491 EEF1B2 Bryony Thompson Gene: eef1b2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4490 EEF1B2 Bryony Thompson reviewed gene: EEF1B2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31845318, 21937992, 35015920; Phenotypes: neurodevelopmental disorder MONDO:0700092, non-syndromic ID and seizures; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10911 EEF1B2 Bryony Thompson Phenotypes for gene: EEF1B2 were changed from Intellectual disability to neurodevelopmental disorder MONDO:0700092; non-syndromic ID and seizures; Intellectual disability
Mendeliome v0.10910 EEF1B2 Bryony Thompson Publications for gene: EEF1B2 were set to 31845318; 21937992
Mendeliome v0.10909 EEF1B2 Bryony Thompson Classified gene: EEF1B2 as Green List (high evidence)
Mendeliome v0.10909 EEF1B2 Bryony Thompson Gene: eef1b2 has been classified as Green List (High Evidence).
Mendeliome v0.10908 EEF1B2 Bryony Thompson reviewed gene: EEF1B2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31845318, 21937992, 35015920; Phenotypes: neurodevelopmental disorder MONDO:0700092, non-syndromic ID and seizures; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10908 ARR3 Bryony Thompson Marked gene: ARR3 as ready
Mendeliome v0.10908 ARR3 Bryony Thompson Gene: arr3 has been classified as Green List (High Evidence).
Mendeliome v0.10908 ARR3 Bryony Thompson Classified gene: ARR3 as Green List (high evidence)
Mendeliome v0.10908 ARR3 Bryony Thompson Gene: arr3 has been classified as Green List (High Evidence).
Mendeliome v0.10907 ARR3 Bryony Thompson gene: ARR3 was added
gene: ARR3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARR3 was set to Other
Publications for gene: ARR3 were set to 27829781; 35001458
Phenotypes for gene: ARR3 were set to Myopia 26, X-linked, female-limited MIM#301010
Review for gene: ARR3 was set to GREEN
Added comment: At least 6 multi-generational families with female-limited early-onset high myopia. Only female carriers are affected and hemizygous males are unaffected. Authors hypothesise the mode of inheritance might be explained by metabolic interference due to X-inactivation.
Sources: Literature
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
Mitochondrial disease v0.692 PYROXD2 Zornitza Stark Classified gene: PYROXD2 as Amber List (moderate evidence)
Mitochondrial disease v0.692 PYROXD2 Zornitza Stark Gene: pyroxd2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3140 FTO Krithika Murali gene: FTO was added
gene: FTO was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: FTO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FTO were set to 19559399; 26378117
Phenotypes for gene: FTO were set to Growth retardation, developmental delay, facial dysmorphism - MIM#612938; multiple congenital malformations
Review for gene: FTO was set to AMBER
Added comment: Biallelic variants associated with syndromic ID reported in 2 unrelated families.

PMID: 26378117 Daoud et al 2016 - homozygous missense variant identified in a female proband. 3rd child to consanguineous Tunisian parents. Proband also carried a paternally inherited balanced translocation. Antenatal USS identified IUGR. Postnatal Echo showed PDA and hypertrabeculation of LV apex.

PMID 19559399 Boissel et al 2009 - homozygous missense variant identified in 9 affected individuals from a consanguineous Palestinian Arab family. Phenotypic features identified most pertinent to the prenatal setting include: 3/7 IUGR, 7/7 retrognathia, congenital heart disease 6/8, lissencephaly 3/8, hypertrophic cardiomyopathy 4/8, hydrocephalus 4/8, cleft palate/bifid uvula 3/6.
Sources: Literature
Mendeliome v0.10903 PYROXD2 Zornitza Stark Marked gene: PYROXD2 as ready
Mendeliome v0.10903 PYROXD2 Zornitza Stark Gene: pyroxd2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3140 ESRP2 Krithika Murali gene: ESRP2 was added
gene: ESRP2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ESRP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ESRP2 were set to 29805042
Phenotypes for gene: ESRP2 were set to Cleft lip
Review for gene: ESRP2 was set to AMBER
Added comment: No new publications since last PanelApp review Feb 2021

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PMID: 29805042 Cox et al. Identified ESRP2 as a potential gene in a cohort of 72 multi generational families with cleft lip with or without cleft palate. 1 likely pathogenic variant (chr16:g.68266284C>T;p.Arg315) was identified in one family. Further analysis of 497 individuals identified a further likely pathogenic variant (chr16:g.68265234G>A;p.Arg520*) in another family.
Sources: Literature
Fetal anomalies v0.3140 EIF3F Krithika Murali gene: EIF3F was added
gene: EIF3F was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: EIF3F was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EIF3F were set to 33736665
Phenotypes for gene: EIF3F were set to ntellectual developmental disorder, autosomal recessive 67- MIM#618295
Review for gene: EIF3F was set to GREEN
Added comment: No new publications since PanelApp review Oct 2021

Hüffmeier et al (2021) reported 21 patients who were homozygous/compound heterozygous for Phe232Val variant in EIF3F. All affected individuals had developmental delay and speech delay. About half had behavioural problems, altered muscular tone, hearing loss, and short stature (3/7 from birth). The study suggests that microcephaly (4/10 from birth), reduced sensitivity to pain, cleft lip/palate (1/21), congenital heart defect (1/21), gastrointestinal symptoms and ophthalmological symptoms are part of the phenotypic spectrum.
Sources: Literature
Fetal anomalies v0.3140 COL9A3 Krithika Murali gene: COL9A3 was added
gene: COL9A3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: COL9A3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: COL9A3 were set to 33570243; 31090205; 30450842; 25381065; 24273071; 15551337
Phenotypes for gene: COL9A3 were set to Epiphyseal dysplasia, multiple, 3, with or without myopathy - MIM#600969; Stickler syndrome
Review for gene: COL9A3 was set to GREEN
Added comment: 6 patients from 4 families reported with biallelic variants associated with a Stickler syndrome like phenotype. All of these cases characterised by the absence of cleft palate, which is noted more commonly in other autosomal dominant forms of Stickler syndrome.

Potential antenatally detectable features described with biallelic COL9A3 variants include fetal growth restriction (1/6), midface hypoplasia (6/6), tibial and femoral bowing (1/6)

PMID 33570243 Markova et al 2021 - report a patient with novel Class 4 compound heterozygous COL9A3 variants confirmed to be in trans. Antenatal USS identified fetal growth restriction in the third trimester. Examination findings by clinical geneticist aged 2 provided, including dysmorphic facial features noted - slightly flattened nasal bridge, small nose, mild mid-facial hypoplasia, high palate.

PMID 31090205 – Nixon et al 2019 - homozygous COL9A3 variant identified in proband, consanguineous family. Antenatal phenotype not provided, mid-facial hypoplasia noted.

PMID: 30450842 – Hanson-Kahn et al 2018 - proband homozygous for LoF COL9A3 variants.
Phenotypic features included moderate to severe sensorineural hearing loss, high myopia, mid-face hypoplasia and both tibial and femoral bowing at birth.

PMID 24273071 Faletra et al 2014 - first reported family with AR COL9A3 associated Stickler syndrome due to homozygous LoF variants. 3 siblings with hearing loss, midface hypoplasia, high myopia, variable severity ID from consanguineous Moroccan family.

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Variants in COL9A3 have previously been associated with autosomal dominant multiple epiphyseal dysplasia, susceptibility to an intervertebral disc disease, and hearing loss. Generally milder phenotype than individuals with biallelic variants. However, PMID 33633367 Nash et al 2021 - report 2 families with heterozygous COL9A3 variants with a more severe Stickler-like phenotype including severe peripheral lattice vitreoretinal abnormalities and mild/moderate sensorineural hearing loss in some cases. No antenatal information provided
Sources: Literature
Mendeliome v0.10903 PYROXD2 Zornitza Stark Classified gene: PYROXD2 as Amber List (moderate evidence)
Mendeliome v0.10903 PYROXD2 Zornitza Stark Gene: pyroxd2 has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v0.691 PYROXD2 Zornitza Stark Classified gene: PYROXD2 as Amber List (moderate evidence)
Mitochondrial disease v0.691 PYROXD2 Zornitza Stark Gene: pyroxd2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10902 PYROXD2 Zornitza Stark gene: PYROXD2 was added
gene: PYROXD2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PYROXD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PYROXD2 were set to 35055180
Phenotypes for gene: PYROXD2 were set to Mitochondrial disease, MONDO:0044970
Review for gene: PYROXD2 was set to AMBER
Added comment: Single individual reported, functional data.
Sources: Literature
Mitochondrial disease v0.690 PYROXD2 Zornitza Stark Classified gene: PYROXD2 as Amber List (moderate evidence)
Mitochondrial disease v0.690 PYROXD2 Zornitza Stark Gene: pyroxd2 has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v0.689 PYROXD2 Zornitza Stark Marked gene: PYROXD2 as ready
Mitochondrial disease v0.689 PYROXD2 Zornitza Stark Gene: pyroxd2 has been classified as Red List (Low Evidence).
Mitochondrial disease v0.689 PYROXD2 Zornitza Stark gene: PYROXD2 was added
gene: PYROXD2 was added to Mitochondrial disease. Sources: Literature
Mode of inheritance for gene: PYROXD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PYROXD2 were set to 35055180
Phenotypes for gene: PYROXD2 were set to Mitochondrial disease, MONDO:0044970
Review for gene: PYROXD2 was set to AMBER
Added comment: Single individual reported, functional data.
Sources: Literature
Hereditary Spastic Paraplegia - paediatric v1.24 SOD1 Zornitza Stark Marked gene: SOD1 as ready
Hereditary Spastic Paraplegia - paediatric v1.24 SOD1 Zornitza Stark Gene: sod1 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v1.24 SOD1 Zornitza Stark Classified gene: SOD1 as Green List (high evidence)
Hereditary Spastic Paraplegia - paediatric v1.24 SOD1 Zornitza Stark Gene: sod1 has been classified as Green List (High Evidence).
Mendeliome v0.10901 Zornitza Stark removed gene:BAP1 from the panel
Growth failure v1.34 BAP1 Zornitza Stark Marked gene: BAP1 as ready
Growth failure v1.34 BAP1 Zornitza Stark Gene: bap1 has been classified as Green List (High Evidence).
Growth failure v1.34 BAP1 Zornitza Stark Classified gene: BAP1 as Green List (high evidence)
Growth failure v1.34 BAP1 Zornitza Stark Gene: bap1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4490 BAP1 Zornitza Stark Marked gene: BAP1 as ready
Intellectual disability syndromic and non-syndromic v0.4490 BAP1 Zornitza Stark Gene: bap1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4490 BAP1 Zornitza Stark Classified gene: BAP1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4490 BAP1 Zornitza Stark Gene: bap1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1447 BAP1 Zornitza Stark Marked gene: BAP1 as ready
Genetic Epilepsy v0.1447 BAP1 Zornitza Stark Gene: bap1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1447 BAP1 Zornitza Stark Classified gene: BAP1 as Green List (high evidence)
Genetic Epilepsy v0.1447 BAP1 Zornitza Stark Gene: bap1 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.153 TMEM53 Zornitza Stark Marked gene: TMEM53 as ready
Skeletal dysplasia v0.153 TMEM53 Zornitza Stark Gene: tmem53 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.153 TMEM53 Zornitza Stark Classified gene: TMEM53 as Green List (high evidence)
Skeletal dysplasia v0.153 TMEM53 Zornitza Stark Gene: tmem53 has been classified as Green List (High Evidence).
Osteopetrosis v0.9 TMEM53 Zornitza Stark Marked gene: TMEM53 as ready
Osteopetrosis v0.9 TMEM53 Zornitza Stark Gene: tmem53 has been classified as Green List (High Evidence).
Osteopetrosis v0.9 TMEM53 Zornitza Stark Classified gene: TMEM53 as Green List (high evidence)
Osteopetrosis v0.9 TMEM53 Zornitza Stark Gene: tmem53 has been classified as Green List (High Evidence).
Mendeliome v0.10900 OBSCN Zornitza Stark Phenotypes for gene: OBSCN were changed from Hypertrophic cardiomyopathy to Rhabdomyolysis MONDO:0005290, OBSCN-related
Mendeliome v0.10899 OBSCN Zornitza Stark Publications for gene: OBSCN were set to 30681346; 26573135; 17716621; 25173926; 28630914; 33438037
Mendeliome v0.10898 OBSCN Zornitza Stark Mode of inheritance for gene: OBSCN was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10897 OBSCN Zornitza Stark Classified gene: OBSCN as Green List (high evidence)
Mendeliome v0.10897 OBSCN Zornitza Stark Gene: obscn has been classified as Green List (High Evidence).
Fetal anomalies v0.3140 ANKRD17 Krithika Murali gene: ANKRD17 was added
gene: ANKRD17 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ANKRD17 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANKRD17 were set to 33909992
Phenotypes for gene: ANKRD17 were set to Chopra-Amiel-Gordon syndrome - MIM#619504; multiple congenital malformations
Review for gene: ANKRD17 was set to GREEN
Added comment: 33909992 - Chopra et al 2021 reported 34 individuals from 33 families with a syndromic ID

Multiple cases with antenatal anomalies or features detectable antenatally reported
- 3/34 with cleft lip and/or palate (including 2 with Pierre Robin sequence)
- 1/34 retrognathia
- 5/34 renal anomalies including 3 with unilateral renal agenesis and 1 with antenatal diagnosis of horseshoe kidney
- 2/34 microcephaly
- 4/34 macrocephaly (1 noted on 37/40 antenatal USS to have macrocephaly and enlarged cisterna magna, 1 also had NSD1 variant)
- 5/34 IUGR/fetal growth concerns
-1/34 with VSD
Sources: Literature
Clefting disorders v0.170 ANKRD17 Krithika Murali reviewed gene: ANKRD17: Rating: AMBER; Mode of pathogenicity: None; Publications: 33909992; Phenotypes: Chopra-Amiel-Gordon syndrome - MIM#619504; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3140 ACBD5 Krithika Murali gene: ACBD5 was added
gene: ACBD5 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ACBD5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACBD5 were set to 27799409; 23105016; 33427402; 34668366
Phenotypes for gene: ACBD5 were set to Retinal dystrophy with leukodystrophy - MIM#618863
Review for gene: ACBD5 was set to RED
Added comment: Biallelic ACBD5 variants cause impairment of very long-chain fatty acid metabolism. Patients have retinal dystrophy and leukodystrophy. Other features include ataxia, spastic paraparesis, developmental delay and facial dysmorphism. One patient with cleft palate reported but this may be an incidental finding and not related to this condition. No other antenatal features reported.

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PMID 27799409 Ferdinandusse et al 2017 - patient born full-term with cleft palate, progressive leukodystrophy, ataxia, retinal dystrophy and facial dysmorphism

PMID 23105016 Abu-Safieh et al 2013 - limited phenotypic information, reported 3 siblings with homozygous splice site ACBD5 variants with spastic paraparesis and leukodystrophy.

PMID: 33427402 Bartlett et al 2020 - 36 year old F proband born at term after an uncomplicated pregnancy, normal growth parameters.

PMID: 34668366 Gorukmez et al 2021 - x2 siblings with homozygous variant – no antenatal features reported
Sources: Literature
Fetal anomalies v0.3140 ROBO3 Belinda Chong reviewed gene: ROBO3: Rating: GREEN; Mode of pathogenicity: None; Publications: 16525029, 15105459; Phenotypes: Gaze palsy, familial horizontal, with progressive scoliosis, 1 MIM#607313; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3140 CFAP74 Zornitza Stark Marked gene: CFAP74 as ready
Fetal anomalies v0.3140 CFAP74 Zornitza Stark Gene: cfap74 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3140 CFAP74 Zornitza Stark Classified gene: CFAP74 as Red List (low evidence)
Fetal anomalies v0.3140 CFAP74 Zornitza Stark Gene: cfap74 has been classified as Red List (Low Evidence).
Mendeliome v0.10896 HAND2 Zornitza Stark Marked gene: HAND2 as ready
Mendeliome v0.10896 HAND2 Zornitza Stark Gene: hand2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10896 HAND2 Zornitza Stark Phenotypes for gene: HAND2 were changed from to Congenital heart disease
Mendeliome v0.10895 HAND2 Zornitza Stark Publications for gene: HAND2 were set to
Mendeliome v0.10894 HAND2 Zornitza Stark Mode of inheritance for gene: HAND2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10893 HAND2 Zornitza Stark Classified gene: HAND2 as Amber List (moderate evidence)
Mendeliome v0.10893 HAND2 Zornitza Stark Gene: hand2 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.187 HAND2 Zornitza Stark Marked gene: HAND2 as ready
Congenital Heart Defect v0.187 HAND2 Zornitza Stark Gene: hand2 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.187 HAND2 Zornitza Stark Phenotypes for gene: HAND2 were changed from to Congenital heart disease
Congenital Heart Defect v0.186 HAND2 Zornitza Stark Publications for gene: HAND2 were set to
Congenital Heart Defect v0.185 HAND2 Zornitza Stark Mode of inheritance for gene: HAND2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital Heart Defect v0.184 HAND2 Zornitza Stark Classified gene: HAND2 as Amber List (moderate evidence)
Congenital Heart Defect v0.184 HAND2 Zornitza Stark Gene: hand2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3139 HAND2 Zornitza Stark Marked gene: HAND2 as ready
Fetal anomalies v0.3139 HAND2 Zornitza Stark Gene: hand2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3139 HAND2 Zornitza Stark Classified gene: HAND2 as Amber List (moderate evidence)
Fetal anomalies v0.3139 HAND2 Zornitza Stark Gene: hand2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3138 RMND1 Belinda Chong reviewed gene: RMND1: Rating: RED; Mode of pathogenicity: None; Publications: 23022099, 25604853, 27843092; Phenotypes: Combined oxidative phosphorylation deficiency 11 MIM#614922; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3138 QRICH1 Zornitza Stark Marked gene: QRICH1 as ready
Fetal anomalies v0.3138 QRICH1 Zornitza Stark Gene: qrich1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3138 QRICH1 Zornitza Stark Phenotypes for gene: QRICH1 were changed from QRICH1 syndrome to Ververi-Brady syndrome, MIM#617982
Fetal anomalies v0.3137 QRICH1 Zornitza Stark Publications for gene: QRICH1 were set to
Fetal anomalies v0.3136 QARS Zornitza Stark Marked gene: QARS as ready
Fetal anomalies v0.3136 QARS Zornitza Stark Gene: qars has been classified as Green List (High Evidence).
Fetal anomalies v0.3136 QARS Zornitza Stark Phenotypes for gene: QARS were changed from MICROCEPHALY, PROGRESSIVE, SEIZURES, AND CEREBRAL AND CEREBELLAR ATROPHY to Microcephaly, progressive, seizures, and cerebral and cerebellar atrophy, MIM# 615760
Fetal anomalies v0.3135 QARS Zornitza Stark Publications for gene: QARS were set to
Fetal anomalies v0.3134 QARS Zornitza Stark Classified gene: QARS as Green List (high evidence)
Fetal anomalies v0.3134 QARS Zornitza Stark Gene: qars has been classified as Green List (High Evidence).
Fetal anomalies v0.3133 PXDN Zornitza Stark Marked gene: PXDN as ready
Fetal anomalies v0.3133 PXDN Zornitza Stark Gene: pxdn has been classified as Green List (High Evidence).
Fetal anomalies v0.3133 PXDN Zornitza Stark Phenotypes for gene: PXDN were changed from CONGENITAL CATARACT, CORNEAL OPACITY, AND DEVELOPMENTAL GLAUCOMA to Anterior segment dysgenesis 7, with sclerocornea, MIM# 269400
Fetal anomalies v0.3132 PXDN Zornitza Stark Publications for gene: PXDN were set to
Fetal anomalies v0.3131 PXDN Zornitza Stark Classified gene: PXDN as Green List (high evidence)
Fetal anomalies v0.3131 PXDN Zornitza Stark Gene: pxdn has been classified as Green List (High Evidence).
Fetal anomalies v0.3130 PSAT1 Zornitza Stark Marked gene: PSAT1 as ready
Fetal anomalies v0.3130 PSAT1 Zornitza Stark Gene: psat1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3130 PSAT1 Zornitza Stark Publications for gene: PSAT1 were set to 25152457; 31903955
Fetal anomalies v0.3129 PSAT1 Zornitza Stark Classified gene: PSAT1 as Green List (high evidence)
Fetal anomalies v0.3129 PSAT1 Zornitza Stark Gene: psat1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3128 PSAT1 Zornitza Stark edited their review of gene: PSAT1: Changed phenotypes: Neu-Laxova syndrome 2, MIM# 616038
Fetal anomalies v0.3128 PSAT1 Zornitza Stark changed review comment from: Neu-Laxova syndrome: severe perinatal presentation with high mortality, not relevant to this panel. PSAT1 deficiency: single family described, ID is part of the phenotype. There is probably a spectrum of disorders related to this gene, downgrade to Amber on this panel for now.; to: Neu-Laxova syndrome: severe perinatal presentation with high mortality.
Fetal anomalies v0.3128 PSAT1 Zornitza Stark edited their review of gene: PSAT1: Changed rating: GREEN
Fetal anomalies v0.3128 PRUNE1 Zornitza Stark Marked gene: PRUNE1 as ready
Fetal anomalies v0.3128 PRUNE1 Zornitza Stark Gene: prune1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3128 PRUNE1 Zornitza Stark Classified gene: PRUNE1 as Green List (high evidence)
Fetal anomalies v0.3128 PRUNE1 Zornitza Stark Gene: prune1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3127 PREPL Zornitza Stark Marked gene: PREPL as ready
Fetal anomalies v0.3127 PREPL Zornitza Stark Gene: prepl has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3127 PREPL Zornitza Stark Phenotypes for gene: PREPL were changed from HYPOTONIA-CYSTINURIA SYNDROME to Myasthenic syndrome, congenital, 22, MIM#616224; Hypotonia-cystinuria syndrome
Fetal anomalies v0.3126 PREPL Zornitza Stark Publications for gene: PREPL were set to
Fetal anomalies v0.3125 PREPL Zornitza Stark edited their review of gene: PREPL: Added comment: At least six unrelated individuals and bi-allelic variants of this gene; however, several are said to have normal EMG/nerve conduction studies, therefore uncertain if this is truly a myasthenic syndrome.

In addition, different recessive contiguous gene deletion syndromes involving PREPL and a variable combination of SLC3A1 (hypotonia-cystinuria syndrome), CAMKMT (atypical hypotonia-cystinuria syndrome), and PPM1B (2p21 deletion syndrome) have been described. Presentation for these is post-natal.; Changed rating: AMBER; Changed publications: 29483676, 28726805, 24610330, 27472506
Mendeliome v0.10892 POP1 Zornitza Stark Marked gene: POP1 as ready
Mendeliome v0.10892 POP1 Zornitza Stark Gene: pop1 has been classified as Green List (High Evidence).
Mendeliome v0.10892 POP1 Zornitza Stark Phenotypes for gene: POP1 were changed from to Anauxetic dysplasia 2, OMIM:617396; Anauxetic dysplasia 2, MONDO:0054561
Mendeliome v0.10891 POP1 Zornitza Stark Publications for gene: POP1 were set to
Mendeliome v0.10890 POP1 Zornitza Stark Mode of inheritance for gene: POP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10889 POP1 Zornitza Stark reviewed gene: POP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21455487, 27380734, 28067412; Phenotypes: Anauxetic dysplasia 2, OMIM:617396, Anauxetic dysplasia 2, MONDO:0054561; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3125 POP1 Zornitza Stark Marked gene: POP1 as ready
Fetal anomalies v0.3125 POP1 Zornitza Stark Gene: pop1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3125 POP1 Zornitza Stark Publications for gene: POP1 were set to
Fetal anomalies v0.3124 POP1 Zornitza Stark Classified gene: POP1 as Green List (high evidence)
Fetal anomalies v0.3124 POP1 Zornitza Stark Gene: pop1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3123 POP1 Zornitza Stark changed review comment from: Anauxetic dysplasia is a spondyloepimetaphyseal dysplasia characterized by severe short stature of prenatal onset, very short adult height (less than 1 meter), hypodontia, midface hypoplasia, and mild intellectual disability.; to: Anauxetic dysplasia is a spondyloepimetaphyseal dysplasia characterized by severe short stature of prenatal onset, very short adult height (less than 1 meter), hypodontia, midface hypoplasia, and mild intellectual disability.

At least 4 unrelated families reported.
Fetal anomalies v0.3123 POP1 Zornitza Stark edited their review of gene: POP1: Changed publications: 21455487, 27380734, 28067412
Fetal anomalies v0.3123 POP1 Zornitza Stark changed review comment from: Primarily a skeletal dysplasia, mild LD described in some but overall I don't think this is the right panel.; to: Anauxetic dysplasia is a spondyloepimetaphyseal dysplasia characterized by severe short stature of prenatal onset, very short adult height (less than 1 meter), hypodontia, midface hypoplasia, and mild intellectual disability.
Fetal anomalies v0.3123 POP1 Zornitza Stark edited their review of gene: POP1: Changed rating: GREEN
Fetal anomalies v0.3123 POLE Zornitza Stark Marked gene: POLE as ready
Fetal anomalies v0.3123 POLE Zornitza Stark Gene: pole has been classified as Green List (High Evidence).
Fetal anomalies v0.3123 POLE Zornitza Stark Phenotypes for gene: POLE were changed from severe growth failure of prenatal onset; IUGR; FILS syndrome, 615139; facial dysmorphism, immunodeficiency, livedo, and short stature (FILS) to IMAGE-I syndrome 618336
Fetal anomalies v0.3122 POLE Zornitza Stark Publications for gene: POLE were set to 23230001; 25948378
Fetal anomalies v0.3121 POLE Zornitza Stark Classified gene: POLE as Green List (high evidence)
Fetal anomalies v0.3121 POLE Zornitza Stark Gene: pole has been classified as Green List (High Evidence).
Fetal anomalies v0.3120 PLPBP Zornitza Stark Marked gene: PLPBP as ready
Fetal anomalies v0.3120 PLPBP Zornitza Stark Gene: plpbp has been classified as Green List (High Evidence).
Fetal anomalies v0.3120 PLPBP Zornitza Stark Phenotypes for gene: PLPBP were changed from Vitamin-B6-Dependent Epilepsy to Epilepsy, early-onset, vitamin B6-dependent, MIM# 617290
Fetal anomalies v0.3119 PLPBP Zornitza Stark Publications for gene: PLPBP were set to
Fetal anomalies v0.3118 PLPBP Zornitza Stark Classified gene: PLPBP as Green List (high evidence)
Fetal anomalies v0.3118 PLPBP Zornitza Stark Gene: plpbp has been classified as Green List (High Evidence).
Fetal anomalies v0.3117 PLPBP Zornitza Stark changed review comment from: Over 20 individuals reported. The most severe phenotypes were associated with variants leading to loss of function of PLPBP or significantly affecting protein stability/PLP-binding.; to: Over 20 individuals reported. The most severe phenotypes were associated with variants leading to loss of function of PLPBP or significantly affecting protein stability/PLP-binding.

Abnormal fetal movements reported.
Fetal anomalies v0.3117 PLG Zornitza Stark Marked gene: PLG as ready
Fetal anomalies v0.3117 PLG Zornitza Stark Gene: plg has been classified as Green List (High Evidence).
Fetal anomalies v0.3117 PLG Zornitza Stark Phenotypes for gene: PLG were changed from Plasminogen deficiency, type I, OMIM:217090; Dysplasminogenemia, OMIM:217090 to Plasminogen deficiency, type I, MIM# 217090; Hydrocephalus
Fetal anomalies v0.3116 PLG Zornitza Stark Publications for gene: PLG were set to
Fetal anomalies v0.3115 PLG Zornitza Stark Classified gene: PLG as Green List (high evidence)
Fetal anomalies v0.3115 PLG Zornitza Stark Gene: plg has been classified as Green List (High Evidence).
Fetal anomalies v0.3114 PLD1 Zornitza Stark Marked gene: PLD1 as ready
Fetal anomalies v0.3114 PLD1 Zornitza Stark Gene: pld1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3114 PLD1 Zornitza Stark Classified gene: PLD1 as Green List (high evidence)
Fetal anomalies v0.3114 PLD1 Zornitza Stark Gene: pld1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3113 TOPORS Zornitza Stark Marked gene: TOPORS as ready
Fetal anomalies v0.3113 TOPORS Zornitza Stark Gene: topors has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3113 TOPORS Zornitza Stark Classified gene: TOPORS as Amber List (moderate evidence)
Fetal anomalies v0.3113 TOPORS Zornitza Stark Gene: topors has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3112 SPINT2 Zornitza Stark Phenotypes for gene: SPINT2 were changed from Diarrhea 3, secretory sodium, congenital, syndromic - MIM#270420; congenital secretory sodium diarrhea 3 - MONDO0010036 to Diarrhoea 3, secretory sodium, congenital, syndromic - MIM#270420; congenital secretory sodium diarrhea 3 - MONDO#0010036
Fetal anomalies v0.3111 SPINT2 Zornitza Stark reviewed gene: SPINT2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diarrhoea 3, secretory sodium, congenital, syndromic - MIM#270420, congenital secretory sodium diarrhea 3 - MONDO#0010036; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3111 SPINT2 Zornitza Stark Marked gene: SPINT2 as ready
Fetal anomalies v0.3111 SPINT2 Zornitza Stark Gene: spint2 has been classified as Green List (High Evidence).
Fetal anomalies v0.3111 SPINT2 Zornitza Stark Classified gene: SPINT2 as Green List (high evidence)
Fetal anomalies v0.3111 SPINT2 Zornitza Stark Gene: spint2 has been classified as Green List (High Evidence).
Fetal anomalies v0.3110 RPS29 Zornitza Stark Marked gene: RPS29 as ready
Fetal anomalies v0.3110 RPS29 Zornitza Stark Gene: rps29 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3110 RPS29 Zornitza Stark Classified gene: RPS29 as Amber List (moderate evidence)
Fetal anomalies v0.3110 RPS29 Zornitza Stark Gene: rps29 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3109 RPS28 Zornitza Stark Marked gene: RPS28 as ready
Fetal anomalies v0.3109 RPS28 Zornitza Stark Gene: rps28 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3109 RPS28 Zornitza Stark Classified gene: RPS28 as Amber List (moderate evidence)
Fetal anomalies v0.3109 RPS28 Zornitza Stark Gene: rps28 has been classified as Amber List (Moderate Evidence).
Hydrops fetalis v0.219 RPL15 Zornitza Stark Marked gene: RPL15 as ready
Hydrops fetalis v0.219 RPL15 Zornitza Stark Gene: rpl15 has been classified as Green List (High Evidence).
Hydrops fetalis v0.219 RPL15 Zornitza Stark Classified gene: RPL15 as Green List (high evidence)
Hydrops fetalis v0.219 RPL15 Zornitza Stark Gene: rpl15 has been classified as Green List (High Evidence).
Fetal anomalies v0.3108 RPL15 Zornitza Stark Marked gene: RPL15 as ready
Fetal anomalies v0.3108 RPL15 Zornitza Stark Gene: rpl15 has been classified as Green List (High Evidence).
Fetal anomalies v0.3108 RPL15 Zornitza Stark Classified gene: RPL15 as Green List (high evidence)
Fetal anomalies v0.3108 RPL15 Zornitza Stark Gene: rpl15 has been classified as Green List (High Evidence).
Polydactyly v0.253 PNPLA6 Zornitza Stark Marked gene: PNPLA6 as ready
Polydactyly v0.253 PNPLA6 Zornitza Stark Gene: pnpla6 has been classified as Red List (Low Evidence).
Polydactyly v0.253 PNPLA6 Zornitza Stark Phenotypes for gene: PNPLA6 were changed from to Laurence-Moon syndrome - MIM#245800; Boucher-Neuhauser syndrome - MIM#215470; Oliver-McFarlane syndrome - #275400; Spastic paraplegia 39, autosomal recessive - #612020
Polydactyly v0.252 PNPLA6 Zornitza Stark Publications for gene: PNPLA6 were set to
Polydactyly v0.251 PNPLA6 Zornitza Stark Classified gene: PNPLA6 as Red List (low evidence)
Polydactyly v0.251 PNPLA6 Zornitza Stark Gene: pnpla6 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.4489 CENPJ Zornitza Stark Publications for gene: CENPJ were set to 20522431; 23166506; 15793586; 20978018; 22775483; 32677750; 32549991
Intellectual disability syndromic and non-syndromic v0.4488 CENPJ Zornitza Stark commented on gene: CENPJ: PMID 34068194: two further families reported with Seckel syndrome, same homozygous missense, founder?
Microcephaly v1.102 CENPJ Zornitza Stark Publications for gene: CENPJ were set to 15793586; 16900296; 2097801822775483; 20522431; 32677750; 32549991; 30626697
Microcephaly v1.101 CENPJ Zornitza Stark edited their review of gene: CENPJ: Added comment: PMID 34068194: two further families reported with Seckel syndrome, same homozygous missense, founder?; Changed publications: 15793586, 16900296, 2097801822775483, 20522431, 32677750, 32549991, 30626697, 34068194
Mendeliome v0.10889 CENPJ Zornitza Stark Publications for gene: CENPJ were set to 20522431; 23166506; 15793586; 20978018; 22775483; 32677750; 32549991
Mendeliome v0.10888 CENPJ Zornitza Stark edited their review of gene: CENPJ: Added comment: PMID 34068194: two further families reported with Seckel syndrome, same homozygous missense, founder?; Changed publications: 20522431, 23166506, 15793586, 20978018, 22775483, 32677750, 32549991, 34068194
Growth failure v1.33 CENPJ Zornitza Stark Classified gene: CENPJ as Amber List (moderate evidence)
Growth failure v1.33 CENPJ Zornitza Stark Gene: cenpj has been classified as Amber List (Moderate Evidence).
Growth failure v1.32 CENPJ Zornitza Stark edited their review of gene: CENPJ: Added comment: PMID 34068194: two further families reported, same homozygous missense, founder?; Changed rating: AMBER; Changed publications: 20522431, 23166506, 34068194
Fetal anomalies v0.3107 PNPLA6 Zornitza Stark Marked gene: PNPLA6 as ready
Fetal anomalies v0.3107 PNPLA6 Zornitza Stark Gene: pnpla6 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3107 PNPLA6 Zornitza Stark Classified gene: PNPLA6 as Amber List (moderate evidence)
Fetal anomalies v0.3107 PNPLA6 Zornitza Stark Gene: pnpla6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10888 MVD Zornitza Stark Phenotypes for gene: MVD were changed from Porokeratosis 7, multiple types, MIM# 614714 to Porokeratosis 7, multiple types, MIM# 614714; Nonsyndromic genetic hearing loss MONDO:0019497, MVD-related, AR
Mendeliome v0.10887 MVD Zornitza Stark Publications for gene: MVD were set to 30942823; 33491095
Deafness_Isolated v1.23 MVD Zornitza Stark Marked gene: MVD as ready
Deafness_Isolated v1.23 MVD Zornitza Stark Gene: mvd has been classified as Red List (Low Evidence).
Deafness_Isolated v1.23 MVD Zornitza Stark Classified gene: MVD as Red List (low evidence)
Deafness_Isolated v1.23 MVD Zornitza Stark Gene: mvd has been classified as Red List (Low Evidence).
Fetal anomalies v0.3106 TOPORS Krithika Murali gene: TOPORS was added
gene: TOPORS was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: TOPORS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOPORS were set to 34132027
Phenotypes for gene: TOPORS were set to MONDO:0005308; ciliopathy; postaxial polydactyly; multiple lingual hamartomas; dysmorphic features
Review for gene: TOPORS was set to AMBER
Added comment: Gene recently reviewed, no new publications since

--

PMID:34132027 - Two unrelated probands with postaxial polydactyly, multiple lingual hamartomas, and dysmorphic features both found to be homozygous for the same missense variant (p.Pro10Gln). Suggested possible founder allele. Further search did not identify any additional publications.

Note mono-allelic variants associated with RP.
Sources: Literature
Fetal anomalies v0.3106 SPINT2 Krithika Murali reviewed gene: SPINT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33029133, 29575628, 28716867, 24142340, 30445423, 19185281, 20009592, 24142340; Phenotypes: Diarrhea 3, secretory sodium, congenital, syndromic - MIM#270420, congenital secretory sodium diarrhea 3 - MONDO#0010036; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3106 SPINT2 Krithika Murali gene: SPINT2 was added
gene: SPINT2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SPINT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPINT2 were set to 19185281; 20009592; 24142340; 30445423; 33547739; 33374714; 33029133
Phenotypes for gene: SPINT2 were set to Diarrhea 3, secretory sodium, congenital, syndromic - MIM#270420; congenital secretory sodium diarrhea 3 - MONDO0010036
Fetal anomalies v0.3106 RPS29 Krithika Murali gene: RPS29 was added
gene: RPS29 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: RPS29 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPS29 were set to 24829207
Phenotypes for gene: RPS29 were set to Diamond-Blackfan anemia 13 - MIM#615909
Review for gene: RPS29 was set to AMBER
Added comment: 2 unrelated families reported with Diamond Blackfan anaemia. DBA known to be associated with congenital malformations. 1 affected individual reported in this publication to have congenital aortic stenosis and Sprengel deformity.
Sources: Literature
Fetal anomalies v0.3106 RPS28 Krithika Murali gene: RPS28 was added
gene: RPS28 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: RPS28 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPS28 were set to 24942156
Phenotypes for gene: RPS28 were set to Diamond Blackfan anemia 15 with mandibulofacial dysostosis - MIM#606164
Review for gene: RPS28 was set to AMBER
Added comment: 2 unrelated families reported in 2014. Antenatally detectable phenotypic features included cleft palate, micrognathia, cardiac, auricular and renal anomalies
Sources: Literature
Mendeliome v0.10886 PLCD1 Zornitza Stark Marked gene: PLCD1 as ready
Mendeliome v0.10886 PLCD1 Zornitza Stark Gene: plcd1 has been classified as Green List (High Evidence).
Mendeliome v0.10886 PLCD1 Zornitza Stark Phenotypes for gene: PLCD1 were changed from to Nail disorder, nonsyndromic congenital, 3, (leukonychia) MIM#151600; nonsyndromic congenital nail disorder 3 MONDO:0007900
Mendeliome v0.10885 PLCD1 Zornitza Stark Publications for gene: PLCD1 were set to
Mendeliome v0.10884 PLCD1 Zornitza Stark Mode of inheritance for gene: PLCD1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.10883 AKAP10 Zornitza Stark Marked gene: AKAP10 as ready
Mendeliome v0.10883 AKAP10 Zornitza Stark Gene: akap10 has been classified as Red List (Low Evidence).
Mendeliome v0.10883 AKAP10 Zornitza Stark Phenotypes for gene: AKAP10 were changed from to {Cardiac conduction defect, susceptibility to} MIM#115080; sudden cardiac arrest MONDO:0007264
Mendeliome v0.10882 AKAP10 Zornitza Stark Publications for gene: AKAP10 were set to
Mendeliome v0.10881 AKAP10 Zornitza Stark Classified gene: AKAP10 as Red List (low evidence)
Mendeliome v0.10881 AKAP10 Zornitza Stark Gene: akap10 has been classified as Red List (Low Evidence).
Mendeliome v0.10880 HMCN1 Zornitza Stark Marked gene: HMCN1 as ready
Mendeliome v0.10880 HMCN1 Zornitza Stark Gene: hmcn1 has been classified as Red List (Low Evidence).
Mendeliome v0.10880 HMCN1 Zornitza Stark Phenotypes for gene: HMCN1 were changed from to {Macular degeneration, age-related, 1} MIM#603075; age related macular degeneration 1 MONDO:0011285
Mendeliome v0.10879 HMCN1 Zornitza Stark Publications for gene: HMCN1 were set to
Mendeliome v0.10878 HMCN1 Zornitza Stark Mode of inheritance for gene: HMCN1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10877 HMCN1 Zornitza Stark Classified gene: HMCN1 as Red List (low evidence)
Mendeliome v0.10877 HMCN1 Zornitza Stark Gene: hmcn1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3106 PYROXD1 Zornitza Stark Marked gene: PYROXD1 as ready
Fetal anomalies v0.3106 PYROXD1 Zornitza Stark Gene: pyroxd1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3106 PYROXD1 Zornitza Stark Phenotypes for gene: PYROXD1 were changed from Early-Onset Myopathy with Internalized Nuclei and Myofibrillar Disorganization to Myopathy, myofibrillar, 8 (MIM#617258)
Fetal anomalies v0.3105 PYROXD1 Zornitza Stark Publications for gene: PYROXD1 were set to
Fetal anomalies v0.3104 PYROXD1 Zornitza Stark Classified gene: PYROXD1 as Red List (low evidence)
Fetal anomalies v0.3104 PYROXD1 Zornitza Stark Gene: pyroxd1 has been classified as Red List (Low Evidence).
Mendeliome v0.10876 CCND1 Zornitza Stark Marked gene: CCND1 as ready
Mendeliome v0.10876 CCND1 Zornitza Stark Gene: ccnd1 has been classified as Red List (Low Evidence).
Mendeliome v0.10876 CCND1 Zornitza Stark Publications for gene: CCND1 were set to
Mendeliome v0.10875 CCND1 Zornitza Stark Phenotypes for gene: CCND1 were changed from to {Colorectal cancer, susceptibility to} MIM#114500; {Multiple myeloma, susceptibility to} MIM#254500; {von Hippel-Lindau syndrome, modifier of} MIM#193300
Mendeliome v0.10874 CCND1 Zornitza Stark Classified gene: CCND1 as Red List (low evidence)
Mendeliome v0.10874 CCND1 Zornitza Stark Gene: ccnd1 has been classified as Red List (Low Evidence).
Hydrops fetalis v0.218 RPL15 Krithika Murali gene: RPL15 was added
gene: RPL15 was added to Hydrops fetalis. Sources: Literature
Mode of inheritance for gene: RPL15 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPL15 were set to 20301769; 29599205; 23812780
Phenotypes for gene: RPL15 were set to Diamond-Blackfan anemia 12 - MIM#615550; hydrops
Review for gene: RPL15 was set to GREEN
Added comment: Known association with Diamond Blackfan anaemia (~1% of cases) which in turn is known to be associated with congenital malformations (craniofacial, upper limb, heart and genitourinary malformations). 3 of 4 unrelated patients with truncating RPL15 variants had severe non-immune hydrops fetalis and required intrauterine transfusions.
Sources: Literature
Fetal anomalies v0.3103 RPL15 Krithika Murali gene: RPL15 was added
gene: RPL15 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: RPL15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RPL15 were set to 20301769; 29599205; 23812780
Phenotypes for gene: RPL15 were set to Diamond-Blackfan anemia 12 - MIM#615550; multiple congenital malformations; hydrops
Review for gene: RPL15 was set to GREEN
Added comment: Known association with Diamond Blackfan anaemia (~1% of cases) which in turn is known to be associated with congenital malformations (craniofacial, upper limb, heart and genitourinary malformations). 3 of 4 patients with truncating RPL15 variants had severe non-immune hydrops fetalis and required intrauterine transfusions.
Sources: Literature
Fetal anomalies v0.3103 PYGM Zornitza Stark Marked gene: PYGM as ready
Fetal anomalies v0.3103 PYGM Zornitza Stark Gene: pygm has been classified as Red List (Low Evidence).
Fetal anomalies v0.3103 PYGM Zornitza Stark Publications for gene: PYGM were set to
Fetal anomalies v0.3102 PYGM Zornitza Stark Classified gene: PYGM as Red List (low evidence)
Fetal anomalies v0.3102 PYGM Zornitza Stark Gene: pygm has been classified as Red List (Low Evidence).
Fetal anomalies v0.3101 PTPN14 Zornitza Stark Marked gene: PTPN14 as ready
Fetal anomalies v0.3101 PTPN14 Zornitza Stark Gene: ptpn14 has been classified as Green List (High Evidence).
Fetal anomalies v0.3101 PTPN14 Zornitza Stark Publications for gene: PTPN14 were set to
Fetal anomalies v0.3100 PTPN14 Zornitza Stark Classified gene: PTPN14 as Green List (high evidence)
Fetal anomalies v0.3100 PTPN14 Zornitza Stark Gene: ptpn14 has been classified as Green List (High Evidence).
Fetal anomalies v0.3099 PRKAG2 Zornitza Stark Marked gene: PRKAG2 as ready
Fetal anomalies v0.3099 PRKAG2 Zornitza Stark Gene: prkag2 has been classified as Green List (High Evidence).
Fetal anomalies v0.3099 PRKAG2 Zornitza Stark Phenotypes for gene: PRKAG2 were changed from Glycogen storage disease of heart, lethal congenital, OMIM:261740; Cardiomyopathy, hypertrophic 6, OMIM:600858; Lethal congenital glycogen storage disease of heart, MONDO:0009867; Hypertrophic cardiomyopathy 6, MONDO:0010946 to Glycogen storage disease of heart, lethal congenital, OMIM:261740; Lethal congenital glycogen storage disease of heart, MONDO:0009867
Fetal anomalies v0.3098 PRKAG2 Zornitza Stark Publications for gene: PRKAG2 were set to
Fetal anomalies v0.3097 PRKAG2 Zornitza Stark Classified gene: PRKAG2 as Green List (high evidence)
Fetal anomalies v0.3097 PRKAG2 Zornitza Stark Gene: prkag2 has been classified as Green List (High Evidence).
Mendeliome v0.10873 PADI4 Zornitza Stark Marked gene: PADI4 as ready
Mendeliome v0.10873 PADI4 Zornitza Stark Gene: padi4 has been classified as Red List (Low Evidence).
Mendeliome v0.10873 PADI4 Zornitza Stark Phenotypes for gene: PADI4 were changed from to Susceptibility to rheumatoid arthritis
Mendeliome v0.10872 PADI4 Zornitza Stark Publications for gene: PADI4 were set to
Mendeliome v0.10871 PADI4 Zornitza Stark Classified gene: PADI4 as Red List (low evidence)
Mendeliome v0.10871 PADI4 Zornitza Stark Gene: padi4 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3096 PPP3CA Zornitza Stark Marked gene: PPP3CA as ready
Fetal anomalies v0.3096 PPP3CA Zornitza Stark Gene: ppp3ca has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3096 PPP3CA Zornitza Stark Phenotypes for gene: PPP3CA were changed from Severe Neurodevelopmental Disease with Seizures to Arthrogryposis, cleft palate, craniosynostosis, and impaired intellectual development MIM#618265
Fetal anomalies v0.3095 PPP3CA Zornitza Stark Publications for gene: PPP3CA were set to
Fetal anomalies v0.3094 PPP3CA Zornitza Stark reviewed gene: PPP3CA: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Arthrogryposis, cleft palate, craniosynostosis, and impaired intellectual development MIM#618265; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3094 POLR1A Zornitza Stark Marked gene: POLR1A as ready
Fetal anomalies v0.3094 POLR1A Zornitza Stark Gene: polr1a has been classified as Green List (High Evidence).
Fetal anomalies v0.3094 POLR1A Zornitza Stark Publications for gene: POLR1A were set to
Fetal anomalies v0.3093 POLR1A Zornitza Stark Mode of inheritance for gene: POLR1A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3092 POLR1A Zornitza Stark Classified gene: POLR1A as Green List (high evidence)
Fetal anomalies v0.3092 POLR1A Zornitza Stark Gene: polr1a has been classified as Green List (High Evidence).
Fetal anomalies v0.3091 POLG2 Zornitza Stark Marked gene: POLG2 as ready
Fetal anomalies v0.3091 POLG2 Zornitza Stark Gene: polg2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3091 POLG2 Zornitza Stark Publications for gene: POLG2 were set to
Fetal anomalies v0.3090 POLG2 Zornitza Stark Classified gene: POLG2 as Red List (low evidence)
Fetal anomalies v0.3090 POLG2 Zornitza Stark Gene: polg2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3089 POLG2 Zornitza Stark reviewed gene: POLG2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4, MIM# 610131, Mitochondrial DNA depletion syndrome 16 , MIM# 618528; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.3089 PLCB4 Zornitza Stark Marked gene: PLCB4 as ready
Fetal anomalies v0.3089 PLCB4 Zornitza Stark Gene: plcb4 has been classified as Green List (High Evidence).
Fetal anomalies v0.3089 PLCB4 Zornitza Stark Phenotypes for gene: PLCB4 were changed from AURICULOCONDYLAR SYNDROME to Auriculocondylar syndrome 2, MIM# 614669
Fetal anomalies v0.3088 PLCB4 Zornitza Stark Publications for gene: PLCB4 were set to
Fetal anomalies v0.3087 PLCB4 Zornitza Stark Mode of inheritance for gene: PLCB4 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.3086 PLCB4 Zornitza Stark Classified gene: PLCB4 as Green List (high evidence)
Fetal anomalies v0.3086 PLCB4 Zornitza Stark Gene: plcb4 has been classified as Green List (High Evidence).
Fetal anomalies v0.3085 WDR26 Zornitza Stark reviewed gene: WDR26: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v0.3085 WDR62 Zornitza Stark Publications for gene: WDR62 were set to
Polydactyly v0.250 PNPLA6 Krithika Murali reviewed gene: PNPLA6: Rating: RED; Mode of pathogenicity: None; Publications: 35069422, 33818269, 25299038, 34157508, 33210227, 33141049, 32758583, 32586184, 31135245, 30097146, 25574898; Phenotypes: Laurence-Moon syndrome - MIM#245800, Boucher-Neuhauser syndrome - MIM#215470, Oliver-McFarlane syndrome - #275400, Spastic paraplegia 39, autosomal recessive - #612020; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3084 PNPLA6 Krithika Murali gene: PNPLA6 was added
gene: PNPLA6 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PNPLA6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNPLA6 were set to 35069422; 33818269; 25299038; 33210227; 33141049; 32758583; 32586184
Phenotypes for gene: PNPLA6 were set to Oliver-McFarlane syndrome - MIM#275400
Review for gene: PNPLA6 was set to AMBER
Added comment: Heterogenous group of neurodegenerative conditions associated with biallelic PNPLA6 gene variants with childhood or adult onset symptoms. Oliver-McFarlane syndrome (OMFS) though is a rare congenital disorder characterised by trichomegaly, severe chorioretinal atrophy and multiple pituitary hormone deficiencies. Congenital hypogonadism is present in half of patients. Low birth weight, preterm delivery and being small for gestational age has been reported as a feature of OMFS. One case of microcephaly has been reported. Overall, limited prenatal phenotypic information for all reported cases of OMFS but associated growth restriction has the potential to be detected antenatally.

--

33818269 - report two unrelated patients with Oliver McFarlane syndrome with biallelic PNPLA6 variants who were born pre-term and small for gestational age.

32758583 Liu et al 2020 - report one boy with Oliver McFarlane syndrome diagnosed with microcephaly and small for gestational age after delivery at 35 weeks.
Sources: Literature
Fetal anomalies v0.3084 PDE6D Zornitza Stark Marked gene: PDE6D as ready
Fetal anomalies v0.3084 PDE6D Zornitza Stark Gene: pde6d has been classified as Green List (High Evidence).
Fetal anomalies v0.3084 PDE6D Zornitza Stark Classified gene: PDE6D as Green List (high evidence)
Fetal anomalies v0.3084 PDE6D Zornitza Stark Gene: pde6d has been classified as Green List (High Evidence).
Fetal anomalies v0.3083 NPM1 Zornitza Stark Marked gene: NPM1 as ready
Fetal anomalies v0.3083 NPM1 Zornitza Stark Gene: npm1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3083 NPM1 Zornitza Stark Phenotypes for gene: NPM1 were changed from Dyskeratosis congenita to Dyskeratosis congenita, MONDO:0015780, NPM1-related
Fetal anomalies v0.3082 NPM1 Zornitza Stark Classified gene: NPM1 as Amber List (moderate evidence)
Fetal anomalies v0.3082 NPM1 Zornitza Stark Gene: npm1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3081 KIAA0825 Zornitza Stark Marked gene: KIAA0825 as ready
Fetal anomalies v0.3081 KIAA0825 Zornitza Stark Gene: kiaa0825 has been classified as Green List (High Evidence).
Fetal anomalies v0.3081 KIAA0825 Zornitza Stark Classified gene: KIAA0825 as Green List (high evidence)
Fetal anomalies v0.3081 KIAA0825 Zornitza Stark Gene: kiaa0825 has been classified as Green List (High Evidence).
Fetal anomalies v0.3080 IQCE Zornitza Stark Marked gene: IQCE as ready
Fetal anomalies v0.3080 IQCE Zornitza Stark Gene: iqce has been classified as Green List (High Evidence).
Fetal anomalies v0.3080 IQCE Zornitza Stark Classified gene: IQCE as Green List (high evidence)
Fetal anomalies v0.3080 IQCE Zornitza Stark Gene: iqce has been classified as Green List (High Evidence).
Fetal anomalies v0.3079 IFT27 Zornitza Stark Marked gene: IFT27 as ready
Fetal anomalies v0.3079 IFT27 Zornitza Stark Gene: ift27 has been classified as Green List (High Evidence).
Fetal anomalies v0.3079 IFT27 Zornitza Stark Classified gene: IFT27 as Green List (high evidence)
Fetal anomalies v0.3079 IFT27 Zornitza Stark Gene: ift27 has been classified as Green List (High Evidence).
Mendeliome v0.10870 HMGB1 Zornitza Stark Phenotypes for gene: HMGB1 were changed from Mirror image foot polydactyly; Developmental delay and microcephaly, no OMIM # to Mirror image foot polydactyly; Neurodevelopmental disorder MONDO:0700092, HMGB1-related
Fetal anomalies v0.3078 HMGB1 Zornitza Stark Marked gene: HMGB1 as ready
Fetal anomalies v0.3078 HMGB1 Zornitza Stark Gene: hmgb1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3078 HMGB1 Zornitza Stark Phenotypes for gene: HMGB1 were changed from microcephaly; intellectual disability to Neurodevelopmental disorder MONDO:0700092, HMGB1-related; microcephaly; intellectual disability
Fetal anomalies v0.3077 HMGB1 Zornitza Stark Classified gene: HMGB1 as Green List (high evidence)
Fetal anomalies v0.3077 HMGB1 Zornitza Stark Gene: hmgb1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3076 FAM92A Zornitza Stark Marked gene: FAM92A as ready
Fetal anomalies v0.3076 FAM92A Zornitza Stark Gene: fam92a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3076 FAM92A Zornitza Stark Classified gene: FAM92A as Amber List (moderate evidence)
Fetal anomalies v0.3076 FAM92A Zornitza Stark Gene: fam92a has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3075 PDSS2 Zornitza Stark Marked gene: PDSS2 as ready
Fetal anomalies v0.3075 PDSS2 Zornitza Stark Gene: pdss2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3075 PDSS2 Zornitza Stark Phenotypes for gene: PDSS2 were changed from COENZYME Q10 DEFICIENCY, PRIMARY, 3 to Coenzyme Q10 deficiency, primary, 3 MIM#614652
Fetal anomalies v0.3074 PDSS2 Zornitza Stark Publications for gene: PDSS2 were set to
Mendeliome v0.10869 PDSS2 Zornitza Stark Marked gene: PDSS2 as ready
Mendeliome v0.10869 PDSS2 Zornitza Stark Gene: pdss2 has been classified as Green List (High Evidence).
Mendeliome v0.10869 PDSS2 Zornitza Stark Phenotypes for gene: PDSS2 were changed from to Coenzyme Q10 deficiency, primary, 3 MIM#614652
Mendeliome v0.10868 PDSS2 Zornitza Stark Publications for gene: PDSS2 were set to
Mendeliome v0.10867 PDSS2 Zornitza Stark Mode of inheritance for gene: PDSS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3073 PDHX Zornitza Stark Marked gene: PDHX as ready
Fetal anomalies v0.3073 PDHX Zornitza Stark Gene: pdhx has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3073 PDHX Zornitza Stark Phenotypes for gene: PDHX were changed from LACTICACIDEMIA DUE TO PDX1 DEFICIENCY to Lactic acidaemia due to PDX1 deficiency MIM#245349
Fetal anomalies v0.3072 PDHX Zornitza Stark Publications for gene: PDHX were set to
Fetal anomalies v0.3071 PDHX Zornitza Stark Classified gene: PDHX as Amber List (moderate evidence)
Fetal anomalies v0.3071 PDHX Zornitza Stark Gene: pdhx has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10866 PDHX Zornitza Stark Marked gene: PDHX as ready
Mendeliome v0.10866 PDHX Zornitza Stark Gene: pdhx has been classified as Green List (High Evidence).
Mendeliome v0.10866 PDHX Zornitza Stark Phenotypes for gene: PDHX were changed from to Lactic acidaemia due to PDX1 deficiency MIM#245349
Mendeliome v0.10865 PDHX Zornitza Stark Publications for gene: PDHX were set to
Mendeliome v0.10864 PDHX Zornitza Stark Mode of inheritance for gene: PDHX was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10863 PDHX Zornitza Stark Tag founder tag was added to gene: PDHX.
Fetal anomalies v0.3070 TRRAP Zornitza Stark Marked gene: TRRAP as ready
Fetal anomalies v0.3070 TRRAP Zornitza Stark Gene: trrap has been classified as Green List (High Evidence).
Fetal anomalies v0.3070 TRRAP Zornitza Stark Classified gene: TRRAP as Green List (high evidence)
Fetal anomalies v0.3070 TRRAP Zornitza Stark Gene: trrap has been classified as Green List (High Evidence).
Fetal anomalies v0.3069 G6PD Zornitza Stark Marked gene: G6PD as ready
Fetal anomalies v0.3069 G6PD Zornitza Stark Gene: g6pd has been classified as Red List (Low Evidence).
Fetal anomalies v0.3069 G6PD Zornitza Stark Classified gene: G6PD as Red List (low evidence)
Fetal anomalies v0.3069 G6PD Zornitza Stark Gene: g6pd has been classified as Red List (Low Evidence).
Fetal anomalies v0.3068 NT5C3A Zornitza Stark Marked gene: NT5C3A as ready
Fetal anomalies v0.3068 NT5C3A Zornitza Stark Gene: nt5c3a has been classified as Red List (Low Evidence).
Fetal anomalies v0.3068 NT5C3A Zornitza Stark Phenotypes for gene: NT5C3A were changed from HEMOLYTIC ANEMIA DUE TO UMPH1 DEFICIENCY to Anaemia, haemolytic, due to UMPH1 deficiency, MIM# 266120
Fetal anomalies v0.3067 NT5C3A Zornitza Stark Publications for gene: NT5C3A were set to
Mendeliome v0.10863 MVD Paul De Fazio reviewed gene: MVD: Rating: RED; Mode of pathogenicity: None; Publications: 34135477; Phenotypes: Nonsyndromic genetic hearing loss MONDO:0019497, MVD-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3066 NDUFV1 Zornitza Stark Marked gene: NDUFV1 as ready
Fetal anomalies v0.3066 NDUFV1 Zornitza Stark Gene: ndufv1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3066 NDUFV1 Zornitza Stark Phenotypes for gene: NDUFV1 were changed from MITOCHONDRIAL COMPLEX I DEFICIENCY to Mitochondrial complex I deficiency, nuclear type 4 MIM#618225
Fetal anomalies v0.3065 NDUFV1 Zornitza Stark Publications for gene: NDUFV1 were set to
Mendeliome v0.10863 NDUFS8 Zornitza Stark Marked gene: NDUFS8 as ready
Mendeliome v0.10863 NDUFS8 Zornitza Stark Gene: ndufs8 has been classified as Green List (High Evidence).
Mendeliome v0.10863 NDUFS8 Zornitza Stark Phenotypes for gene: NDUFS8 were changed from to Mitochondrial complex I deficiency, nuclear type 2 MIM#618222
Mendeliome v0.10862 NDUFS8 Zornitza Stark Publications for gene: NDUFS8 were set to
Mendeliome v0.10861 NDUFS8 Zornitza Stark Mode of inheritance for gene: NDUFS8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10860 NDUFV1 Zornitza Stark Marked gene: NDUFV1 as ready
Mendeliome v0.10860 NDUFV1 Zornitza Stark Gene: ndufv1 has been classified as Green List (High Evidence).
Mendeliome v0.10860 NDUFV1 Zornitza Stark Phenotypes for gene: NDUFV1 were changed from to Mitochondrial complex I deficiency, nuclear type 4 MIM#618225
Mendeliome v0.10859 NDUFV1 Zornitza Stark Publications for gene: NDUFV1 were set to
Mendeliome v0.10858 NDUFV1 Zornitza Stark Mode of inheritance for gene: NDUFV1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Deafness_IsolatedAndComplex v1.114 COL4A6 Zornitza Stark Publications for gene: COL4A6 were set to 23714752
Deafness_IsolatedAndComplex v1.113 COL4A6 Zornitza Stark Classified gene: COL4A6 as Green List (high evidence)
Deafness_IsolatedAndComplex v1.113 COL4A6 Zornitza Stark Gene: col4a6 has been classified as Green List (High Evidence).
Deafness_Isolated v1.22 MVD Paul De Fazio edited their review of gene: MVD: Changed phenotypes: Nonsyndromic genetic hearing loss MONDO:0019497, MVD-related
Mendeliome v0.10857 FZR1 Alison Yeung Marked gene: FZR1 as ready
Mendeliome v0.10857 FZR1 Alison Yeung Gene: fzr1 has been classified as Green List (High Evidence).
Mendeliome v0.10857 FZR1 Alison Yeung Classified gene: FZR1 as Green List (high evidence)
Mendeliome v0.10857 FZR1 Alison Yeung Gene: fzr1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1446 FZR1 Alison Yeung Marked gene: FZR1 as ready
Genetic Epilepsy v0.1446 FZR1 Alison Yeung Gene: fzr1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1446 FZR1 Alison Yeung Classified gene: FZR1 as Green List (high evidence)
Genetic Epilepsy v0.1446 FZR1 Alison Yeung Gene: fzr1 has been classified as Green List (High Evidence).
Deafness_IsolatedAndComplex v1.112 COL4A6 Lucy Spencer reviewed gene: COL4A6: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33840813; Phenotypes: ?Deafness, X-linked 6, MIM#300914; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Deafness_Isolated v1.22 MVD Paul De Fazio gene: MVD was added
gene: MVD was added to Deafness_Isolated. Sources: Literature
Mode of inheritance for gene: MVD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MVD were set to 34135477
Phenotypes for gene: MVD were set to Nonsyndromic genetic hearing loss MONDO:0019497, MPDZ-related
Review for gene: MVD was set to RED
gene: MVD was marked as current diagnostic
Added comment: Homozygous missense variant p.(Pro379His) identified in 2 affected siblings from a single consanguineous Pakistani family by WES. A third unaffected sibling was heterozygous for the variant. Variant is in gnomad (1 het, 0 hom).

RNA expression studies show the gene is expressed in the mouse inner ear, but no functional studies were performed on the variant (in silico analysis only).
Sources: Literature
Mendeliome v0.10856 COL4A6 Zornitza Stark Classified gene: COL4A6 as Green List (high evidence)
Mendeliome v0.10856 COL4A6 Zornitza Stark Gene: col4a6 has been classified as Green List (High Evidence).
Deafness_Isolated v1.22 MPDZ Alison Yeung Marked gene: MPDZ as ready
Deafness_Isolated v1.22 MPDZ Alison Yeung Gene: mpdz has been classified as Red List (Low Evidence).
Deafness_Isolated v1.22 MPDZ Alison Yeung Classified gene: MPDZ as Red List (low evidence)
Deafness_Isolated v1.22 MPDZ Alison Yeung Added comment: Comment on list classification: Single affected family, no functional studies on variant
Deafness_Isolated v1.22 MPDZ Alison Yeung Gene: mpdz has been classified as Red List (Low Evidence).
Deafness_Isolated v1.21 SEZ6 Alison Yeung Marked gene: SEZ6 as ready
Deafness_Isolated v1.21 SEZ6 Alison Yeung Gene: sez6 has been classified as Red List (Low Evidence).
Deafness_Isolated v1.21 SEZ6 Alison Yeung Classified gene: SEZ6 as Red List (low evidence)
Deafness_Isolated v1.21 SEZ6 Alison Yeung Gene: sez6 has been classified as Red List (Low Evidence).
Mendeliome v0.10855 SEZ6 Alison Yeung Marked gene: SEZ6 as ready
Mendeliome v0.10855 SEZ6 Alison Yeung Gene: sez6 has been classified as Red List (Low Evidence).
Mendeliome v0.10855 SEZ6 Alison Yeung Classified gene: SEZ6 as Red List (low evidence)
Mendeliome v0.10855 SEZ6 Alison Yeung Gene: sez6 has been classified as Red List (Low Evidence).
Mendeliome v0.10854 ADAMTS1 Zornitza Stark Marked gene: ADAMTS1 as ready
Mendeliome v0.10854 ADAMTS1 Zornitza Stark Gene: adamts1 has been classified as Red List (Low Evidence).
Mendeliome v0.10854 ADAMTS1 Zornitza Stark Classified gene: ADAMTS1 as Red List (low evidence)
Mendeliome v0.10854 ADAMTS1 Zornitza Stark Gene: adamts1 has been classified as Red List (Low Evidence).
Deafness_Isolated v1.20 ADAMTS1 Zornitza Stark Marked gene: ADAMTS1 as ready
Deafness_Isolated v1.20 ADAMTS1 Zornitza Stark Gene: adamts1 has been classified as Red List (Low Evidence).
Deafness_Isolated v1.20 ADAMTS1 Zornitza Stark Classified gene: ADAMTS1 as Red List (low evidence)
Deafness_Isolated v1.20 ADAMTS1 Zornitza Stark Gene: adamts1 has been classified as Red List (Low Evidence).
Deafness_Isolated v1.19 MPDZ Paul De Fazio gene: MPDZ was added
gene: MPDZ was added to Deafness_Isolated. Sources: Literature
Mode of inheritance for gene: MPDZ was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MPDZ were set to 34135477; 29026089
Phenotypes for gene: MPDZ were set to Nonsyndromic genetic hearing loss MONDO:0019497, MPDZ-related
Review for gene: MPDZ was set to AMBER
gene: MPDZ was marked as current diagnostic
Added comment: Homozygous missense variant p.(Pro775Leu) identified in 2 affected siblings from a single consanguineous Pakistani family by WES. A third unaffected sibling was homozygous wild type. Variant is in gnomad (8 hets, 0 hom).

RNA expression studies show the gene is expressed in the mouse inner ear, but no functional studies were performed on the variant (in silico analysis only). A mouse model has increased threshold for auditory brainstem response.
Sources: Literature
Mendeliome v0.10853 MPDZ Paul De Fazio reviewed gene: MPDZ: Rating: AMBER; Mode of pathogenicity: None; Publications: 34135477, 29026089; Phenotypes: Nonsyndromic genetic hearing loss MONDO:0019497, MPDZ-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic Epilepsy v0.1445 RBL2 Zornitza Stark Marked gene: RBL2 as ready
Genetic Epilepsy v0.1445 RBL2 Zornitza Stark Gene: rbl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10853 DHDDS Zornitza Stark Publications for gene: DHDDS were set to 27343064; 29100083; 21295283
Genetic Epilepsy v0.1445 RBL2 Zornitza Stark Phenotypes for gene: RBL2 were changed from PMID: 33980986; 32105419; 9806916 to Brunet-Wagner neurodevelopmental syndrome, MIM# 619690
Mendeliome v0.10852 ITSN1 Zornitza Stark Phenotypes for gene: ITSN1 were changed from Nephrotic syndrome to Nephrotic syndrome; Neurodevelopmental disorder MONDO:0700092, ITSN1-related
Mendeliome v0.10851 ITSN1 Zornitza Stark Mode of inheritance for gene: ITSN1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Genetic Epilepsy v0.1444 RBL2 Zornitza Stark Classified gene: RBL2 as Amber List (moderate evidence)
Genetic Epilepsy v0.1444 RBL2 Zornitza Stark Gene: rbl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10850 ATP5O Alison Yeung Marked gene: ATP5O as ready
Mendeliome v0.10850 ATP5O Alison Yeung Gene: atp5o has been classified as Red List (Low Evidence).
Mendeliome v0.10850 DHDDS Chern Lim reviewed gene: DHDDS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34382076; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Genetic Epilepsy v0.1443 RBL2 Zornitza Stark Classified gene: RBL2 as Amber List (moderate evidence)
Genetic Epilepsy v0.1443 RBL2 Zornitza Stark Gene: rbl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10850 ATP5O Alison Yeung Classified gene: ATP5O as Red List (low evidence)
Mendeliome v0.10850 ATP5O Alison Yeung Gene: atp5o has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.4488 SOD1 Zornitza Stark Marked gene: SOD1 as ready
Intellectual disability syndromic and non-syndromic v0.4488 SOD1 Zornitza Stark Gene: sod1 has been classified as Green List (High Evidence).
Mendeliome v0.10849 ITSN1 Ee Ming Wong reviewed gene: ITSN1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34707297; Phenotypes: neurodevelopmental disorder MONDO:0700092, ITSN1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Genetic Epilepsy v0.1442 RBL2 Elena Savva gene: RBL2 was added
gene: RBL2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: RBL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RBL2 were set to PMID: 33980986; 32105419; 9806916
Phenotypes for gene: RBL2 were set to PMID: 33980986; 32105419; 9806916
Review for gene: RBL2 was set to AMBER
Added comment: PMID: 33980986: 2 unrelated patients (3 total) with infantile hypotonia, severe developmental delay and microcephaly. Functional studies on patient fibroblasts supports loss of protein and mRNA expression. Patients were homozygous for a PTC, and a CNV (exon 4-5 del)

PMID: 32105419: affecting siblings with severe intellectual disability, stereotypies and dysmorphic features. Chet PTC/CNV (exon 13-17 del).

3 unrelated families - 2/3 corpus callosum hypoplasia/cerebral atrophy, 2/3 epilepsy, 2/3 microcephaly

PMID: 9806916: mouse model in support
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4488 SOD1 Zornitza Stark Classified gene: SOD1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4488 SOD1 Zornitza Stark Gene: sod1 has been classified as Green List (High Evidence).
Hereditary Spastic Paraplegia - paediatric v1.23 SOD1 Naomi Baker gene: SOD1 was added
gene: SOD1 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Literature
Mode of inheritance for gene: SOD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SOD1 were set to PMID: 31314961; 31332433; 34788402
Phenotypes for gene: SOD1 were set to Spastic tetraplegia and axial hypotonia, progressive, MIM#618598
Review for gene: SOD1 was set to GREEN
Added comment: Three individuals reported with biallelic LoF variants, with two apparently unrelated individuals having the same variant (c.335dupG).

Phenotypes include one individual with axial hypotonia and loss of gross and fine motor function beginning at 6 months of age, after which severe, progressive spastic tetraparesis developed and Babinski’s sign was present in both feet. MRI of brain detected mild frontoparietal atrophy.

The second individual had severe and marked by progressive loss of motor abilities from 9 months of age, tetraspasticity with predominance in the lower extremities, mild cerebellar atrophy, and hyperekplexia-like symptoms. Dysmorphic features such as low set, posteriorly rotated ears, and overlapping toes.

The third individual is an infant with severe global developmental delay, axial hypotonia and limb spasticity. No dysmorphic facial features were noted, but she had a high arched palate, bilateral 5th finger clinodactyly, partial toe syndactyly of the second and third toes, and a single hyperpigmented macule tongue fasciculations, axial hypotonia with limb spasticity (more pronounced in the lower limbs), ankle clonus, and brisk patellar deep tendon reflexes.
Sources: Literature
Deafness_Isolated v1.19 SEZ6 Paul De Fazio gene: SEZ6 was added
gene: SEZ6 was added to Deafness_Isolated. Sources: Literature
Mode of inheritance for gene: SEZ6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SEZ6 were set to 34135477
Phenotypes for gene: SEZ6 were set to Nonsyndromic genetic hearing loss MONDO:0019497, SEZ6-related
Review for gene: SEZ6 was set to RED
gene: SEZ6 was marked as current diagnostic
Added comment: Homozygous missense variant p.(Val698Ile) identified in 4 affected individuals from a single consanguineous Pakistani family by WES. 5 other genotyped unaffected individuals were heterozygous or homozygous wild-type. Variant is in gnomad (36 hets, 0 hom).

RNA expression studies show the gene is expressed in the mouse inner ear, but no functional studies were performed on the variant (in silico analysis only).
Sources: Literature
Mendeliome v0.10849 SEZ6 Paul De Fazio gene: SEZ6 was added
gene: SEZ6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SEZ6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SEZ6 were set to 34135477
Phenotypes for gene: SEZ6 were set to Nonsyndromic genetic hearing loss MONDO:0019497, SEZ6-related
Review for gene: SEZ6 was set to RED
gene: SEZ6 was marked as current diagnostic
Added comment: Homozygous missense variant p.(Val698Ile) identified in 4 affected individuals from a single consanguineous Pakistani family by WES. 5 other genotyped unaffected individuals were heterozygous or homozygous wild-type. Variant is in gnomad (36 hets, 0 hom).

RNA expression studies show the gene is expressed in the mouse inner ear, but no functional studies were performed on the variant (in silico analysis only).
Sources: Literature
Regression v0.398 SOD1 Zornitza Stark Marked gene: SOD1 as ready
Regression v0.398 SOD1 Zornitza Stark Gene: sod1 has been classified as Green List (High Evidence).
Regression v0.398 SOD1 Zornitza Stark Classified gene: SOD1 as Green List (high evidence)
Regression v0.398 SOD1 Zornitza Stark Gene: sod1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4487 ITSN1 Zornitza Stark Marked gene: ITSN1 as ready
Intellectual disability syndromic and non-syndromic v0.4487 ITSN1 Zornitza Stark Gene: itsn1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4487 ITSN1 Zornitza Stark Classified gene: ITSN1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4487 ITSN1 Zornitza Stark Gene: itsn1 has been classified as Green List (High Evidence).
Mendeliome v0.10849 COL4A6 Lucy Spencer reviewed gene: COL4A6: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33840813; Phenotypes: Hearing loss; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Microcephaly v1.101 RBL2 Alison Yeung Marked gene: RBL2 as ready
Microcephaly v1.101 RBL2 Alison Yeung Gene: rbl2 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.101 RBL2 Alison Yeung Classified gene: RBL2 as Amber List (moderate evidence)
Microcephaly v1.101 RBL2 Alison Yeung Gene: rbl2 has been classified as Amber List (Moderate Evidence).
Growth failure v1.32 BAP1 Anna Ritchie gene: BAP1 was added
gene: BAP1 was added to Growth failure. Sources: Literature
Mode of inheritance for gene: BAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BAP1 were set to PMID: 35051358
Phenotypes for gene: BAP1 were set to syndromic intellectual disability MONDO:0000508
Penetrance for gene: BAP1 were set to unknown
Review for gene: BAP1 was set to GREEN
Added comment: 11 de novo germline heterozygous missense BAP1 variants associated with a rare syndromic neurodevelopmental disorder. Functional analysis showed that most of the variants cannot rescue the consequences of BAP1 inactivation, suggesting a loss-of-function mechanism. All affected individuals harboring a de novo BAP1 variant had DD or ID (11/11) characterized notably by speech (11/ 11) and motor delay (6/11). Most of them had hypotonia (7/11), seizures (6/11), and abnormal behavior (8/10), including autism spectrum disorder, attention deficit hyperactivity disorder, and hypersensitivity. Almost all individuals showed dysmorphic facial features (10/11), and more than half (6/11) had skeletal malformations (involving the hands [4/11], feet [3/11], or spine [2/11]). Most of the individuals had growth failure (9/11), including four individuals with a very short stature.
Sources: Literature
Cerebellar and Pontocerebellar Hypoplasia v1.45 RBL2 Alison Yeung Marked gene: RBL2 as ready
Cerebellar and Pontocerebellar Hypoplasia v1.45 RBL2 Alison Yeung Gene: rbl2 has been classified as Red List (Low Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.45 RBL2 Alison Yeung Classified gene: RBL2 as Red List (low evidence)
Cerebellar and Pontocerebellar Hypoplasia v1.45 RBL2 Alison Yeung Added comment: Comment on list classification: pontocerebellar hypoplasia not a consistent feature
Cerebellar and Pontocerebellar Hypoplasia v1.45 RBL2 Alison Yeung Gene: rbl2 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.4486 ATP5E Ain Roesley gene: ATP5E was added
gene: ATP5E was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ATP5E was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP5E were set to 34954817; 20566710; 27626380; 20026007
Phenotypes for gene: ATP5E were set to Mitochondrial complex V (ATP synthase) deficiency, nuclear type 3 MIM#614053
Penetrance for gene: ATP5E were set to Complete
Review for gene: ATP5E was set to AMBER
gene: ATP5E was marked as current diagnostic
Added comment: 3 unrelated with the same Tyr12Cys avriant

3/3 with dev delay. 2/3 with ID (the other NA)
Sources: Literature
Genetic Epilepsy v0.1442 BAP1 Anna Ritchie gene: BAP1 was added
gene: BAP1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: BAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BAP1 were set to PMID: 35051358
Phenotypes for gene: BAP1 were set to syndromic intellectual disability MONDO:0000508
Penetrance for gene: BAP1 were set to unknown
Review for gene: BAP1 was set to GREEN
Added comment: 11 de novo germline heterozygous missense BAP1 variants associated with a rare syndromic neurodevelopmental disorder. Functional analysis showed that most of the variants cannot rescue the consequences of BAP1 inactivation, suggesting a loss-of-function mechanism. All affected individuals harboring a de novo BAP1 variant had DD or ID (11/11) characterized notably by speech (11/ 11) and motor delay (6/11). Most of them had hypotonia (7/11), seizures (6/11), and abnormal behavior (8/10), including autism spectrum disorder, attention deficit hyperactivity disorder, and hypersensitivity. Almost all individuals showed dysmorphic facial features (10/11), and more than half (6/11) had skeletal malformations (involving the hands [4/11], feet [3/11], or spine [2/11]). Most of the individuals had growth failure (9/11), including four individuals with a very short stature.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4486 SLC38A3 Zornitza Stark Marked gene: SLC38A3 as ready
Intellectual disability syndromic and non-syndromic v0.4486 SLC38A3 Zornitza Stark Gene: slc38a3 has been classified as Green List (High Evidence).
Mitochondrial disease v0.688 ATP5E Ain Roesley reviewed gene: ATP5E: Rating: GREEN; Mode of pathogenicity: None; Publications: 34954817; Phenotypes: Mitochondrial complex V (ATP synthase) deficiency, nuclear type 3 MIM#614053; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.4486 RBL2 Alison Yeung Phenotypes for gene: RBL2 were changed from Intellectual disability; Brunet-Wagner neurodevelopmental syndrome MIM#619690 to Intellectual disability; Brunet-Wagner neurodevelopmental syndrome MIM#619690
Mendeliome v0.10849 ATP5E Zornitza Stark Publications for gene: ATP5E were set to 20566710; 27626380; 20026007
Intellectual disability syndromic and non-syndromic v0.4486 RBL2 Alison Yeung Phenotypes for gene: RBL2 were changed from Intellectual disability to Intellectual disability; Brunet-Wagner neurodevelopmental syndrome MIM#619690
Intellectual disability syndromic and non-syndromic v0.4485 BAP1 Anna Ritchie gene: BAP1 was added
gene: BAP1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: BAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BAP1 were set to PMID: 35051358
Phenotypes for gene: BAP1 were set to syndromic intellectual disability MONDO:0000508
Penetrance for gene: BAP1 were set to unknown
Review for gene: BAP1 was set to GREEN
Added comment: 11 de novo germline heterozygous missense BAP1 variants associated with a rare syndromic neurodevelopmental disorder. Functional analysis showed that most of the variants cannot rescue the consequences of BAP1 inactivation, suggesting a loss-of-function mechanism. All affected individuals harboring a de novo BAP1 variant had DD or ID (11/11) characterized notably by speech (11/ 11) and motor delay (6/11). Most of them had hypotonia (7/11), seizures (6/11), and abnormal behavior (8/10), including autism spectrum disorder, attention deficit hyperactivity disorder, and hypersensitivity. Almost all individuals showed dysmorphic facial features (10/11), and more than half (6/11) had skeletal malformations (involving the hands [4/11], feet [3/11], or spine [2/11]). Most of the individuals had growth failure (9/11), including four individuals with a very short stature.
Sources: Literature
Mendeliome v0.10848 ATP5E Zornitza Stark Classified gene: ATP5E as Green List (high evidence)
Mendeliome v0.10848 ATP5E Zornitza Stark Gene: atp5e has been classified as Green List (High Evidence).
Mendeliome v0.10847 OBSCN Ee Ming Wong reviewed gene: OBSCN: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34957489; Phenotypes: Rhabdomyolysis MONDO:0005290, OBSCN-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.4485 RBL2 Alison Yeung Classified gene: RBL2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4485 RBL2 Alison Yeung Gene: rbl2 has been classified as Green List (High Evidence).
Osteopetrosis v0.8 TMEM53 Lucy Spencer gene: TMEM53 was added
gene: TMEM53 was added to Osteopetrosis. Sources: Literature
Mode of inheritance for gene: TMEM53 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM53 were set to PMID: 33824347
Phenotypes for gene: TMEM53 were set to Primary Bone Dysplasia MONDO: 0018230
Review for gene: TMEM53 was set to GREEN
Added comment: PMID: 33824347- 4 families with sclerosing bone disorder
Sources: Literature
Skeletal dysplasia v0.152 TMEM53 Lucy Spencer gene: TMEM53 was added
gene: TMEM53 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: TMEM53 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM53 were set to PMID: 33824347
Phenotypes for gene: TMEM53 were set to Primary Bone Dysplasia MONDO: 0018230
Review for gene: TMEM53 was set to GREEN
Added comment: PMID: 33824347- 4 families with sclerosing bone disorder.
Sources: Literature
Mendeliome v0.10847 RBL2 Alison Yeung Phenotypes for gene: RBL2 were changed from Severe motor and cognitive impairment; Intellectual disability; Brunet-Wagner neurodevelopmental syndrome, MIM# 619690 to Intellectual disability; Brunet-Wagner neurodevelopmental syndrome, MIM# 619690
Deafness_Isolated v1.19 ADAMTS1 Paul De Fazio gene: ADAMTS1 was added
gene: ADAMTS1 was added to Deafness_Isolated. Sources: Literature
Mode of inheritance for gene: ADAMTS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTS1 were set to 34135477
Phenotypes for gene: ADAMTS1 were set to Nonsyndromic genetic hearing loss MONDO:0019497, ADAMTS1-related
Review for gene: ADAMTS1 was set to RED
gene: ADAMTS1 was marked as current diagnostic
Added comment: Homozygous missense variant p.(Ser135Ala) identified in 3 affected siblings from a single consanguineous Pakistani family by WES. A fourth unaffected sibling was homozygous wild type. Variant is in gnomad (26 hets, 1 hom).

RNA expression studies show the gene is expressed in the mouse inner ear, but no functional studies were performed on the variant (in silico analysis only).
Sources: Literature
Mendeliome v0.10846 ADAMTS1 Paul De Fazio gene: ADAMTS1 was added
gene: ADAMTS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ADAMTS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTS1 were set to 34135477
Phenotypes for gene: ADAMTS1 were set to Nonsyndromic genetic hearing loss MONDO:0019497, ADAMTS1-related
Review for gene: ADAMTS1 was set to RED
gene: ADAMTS1 was marked as current diagnostic
Added comment: Homozygous missense variant p.(Ser135Ala) identified in 3 affected siblings from a single consanguineous Pakistani family by WES. A fourth unaffected sibling was homozygous wild type. Variant is in gnomad (26 hets, 1 hom).

RNA expression studies show the gene is expressed in the mouse inner ear, but no functional studies were performed on the variant (in silico analysis only).
Sources: Literature
Mendeliome v0.10846 RBL2 Alison Yeung Classified gene: RBL2 as Green List (high evidence)
Mendeliome v0.10846 RBL2 Alison Yeung Gene: rbl2 has been classified as Green List (High Evidence).
Mendeliome v0.10845 RBL2 Alison Yeung Phenotypes for gene: RBL2 were changed from Intellectual disability to Severe motor and cognitive impairment; Intellectual disability; Brunet-Wagner neurodevelopmental syndrome, MIM# 619690
Intellectual disability syndromic and non-syndromic v0.4484 SOD1 Naomi Baker gene: SOD1 was added
gene: SOD1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SOD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SOD1 were set to PMID: 31314961; 31332433; 34788402
Phenotypes for gene: SOD1 were set to Spastic tetraplegia and axial hypotonia, progressive, MIM#618598
Review for gene: SOD1 was set to GREEN
Added comment: Phenotypes include one individual with axial hypotonia and loss of gross and fine motor function beginning at 6 months of age, after which severe, progressive spastic tetraparesis developed and Babinski’s sign was present in both feet. MRI of brain detected mild frontoparietal atrophy.

The second individual had severe and marked by progressive loss of motor abilities from 9 months of age, tetraspasticity with predominance in the lower extremities, mild cerebellar atrophy, and hyperekplexia-like symptoms. Dysmorphic features such as low set, posteriorly rotated ears, and overlapping toes

The third individual is an infant with severe global developmental delay, axial hypotonia and limb spasticity. No dysmorphic facial features were noted, but she had a high arched palate, bilateral 5th finger clinodactyly, partial toe syndactyly of the second and third toes, and a single hyperpigmented macule tongue fasciculations, axial hypotonia with limb spasticity (more pronounced in the lower limbs), ankle clonus, and brisk patellar deep tendon reflexes.
Sources: Literature
Rhabdomyolysis and Metabolic Myopathy v0.87 OBSCN Zornitza Stark Phenotypes for gene: OBSCN were changed from Rhabdomyolysis, MONDO:0005290 to Rhabdomyolysis, MONDO:0005290, OBSCN-related
Mendeliome v0.10844 ATP5O Ain Roesley gene: ATP5O was added
gene: ATP5O was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATP5O was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP5O were set to 34954817
Phenotypes for gene: ATP5O were set to mitochondrial disease, ATP5F1E-related MONDO:0044970
Penetrance for gene: ATP5O were set to Complete
Review for gene: ATP5O was set to RED
gene: ATP5O was marked as current diagnostic
Added comment: Now known as ATP5PO (HGNC)

1 compound het individual with dev delay, muscular hypotonia, ID, dystonia, seizures and neurologic regression
Sources: Literature
Mendeliome v0.10844 BAP1 Anna Ritchie changed review comment from: 11 de novo germline heterozygous missense BAP1 variants associated with a rare syndromic neurodevelopmental disorder. Functional analysis showed that most of the variants cannot rescue the consequences of BAP1 inactivation, suggesting a loss-of-function mechanism. All affected individuals harboring a de novo BAP1 variant had DD or ID (11/11) characterized notably by speech (11/ 11) and motor delay (6/11). Most of them had hypotonia (7/11), seizures (6/11), and abnormal behavior (8/10), including autism spectrum disorder, attention deficit hyperactivity disorder, and hypersensitivity. Almost all individuals showed dysmorphic facial features (10/11), and more than half (6/11) had skeletal mal- formations (involving the hands [4/11], feet [3/11], or spine [2/11],). Most of the individuals had growth failure (9/11), including four individuals with a very short stature.
Sources: Literature; to: 11 de novo germline heterozygous missense BAP1 variants associated with a rare syndromic neurodevelopmental disorder. Functional analysis showed that most of the variants cannot rescue the consequences of BAP1 inactivation, suggesting a loss-of-function mechanism. All affected individuals harboring a de novo BAP1 variant had DD or ID (11/11) characterized notably by speech (11/ 11) and motor delay (6/11). Most of them had hypotonia (7/11), seizures (6/11), and abnormal behavior (8/10), including autism spectrum disorder, attention deficit hyperactivity disorder, and hypersensitivity. Almost all individuals showed dysmorphic facial features (10/11), and more than half (6/11) had skeletal malformations (involving the hands [4/11], feet [3/11], or spine [2/11]). Most of the individuals had growth failure (9/11), including four individuals with a very short stature.
Sources: Literature
Rhabdomyolysis and Metabolic Myopathy v0.86 OBSCN Zornitza Stark Marked gene: OBSCN as ready
Rhabdomyolysis and Metabolic Myopathy v0.86 OBSCN Zornitza Stark Gene: obscn has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.86 OBSCN Zornitza Stark Classified gene: OBSCN as Green List (high evidence)
Rhabdomyolysis and Metabolic Myopathy v0.86 OBSCN Zornitza Stark Gene: obscn has been classified as Green List (High Evidence).
Regression v0.397 SOD1 Naomi Baker gene: SOD1 was added
gene: SOD1 was added to Regression. Sources: Literature
Mode of inheritance for gene: SOD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SOD1 were set to PMID: 31314961; 31332433; 34788402
Phenotypes for gene: SOD1 were set to Spastic tetraplegia and axial hypotonia, progressive, MIM#618598
Review for gene: SOD1 was set to GREEN
Added comment: Three individuals reported with biallelic LoF variants, with two apparently unrelated individuals having the same variant (c.335dupG).

Phenotypes include one individual with axial hypotonia and loss of gross and fine motor function beginning at 6 months of age, after which severe, progressive spastic tetraparesis developed and Babinski’s sign was present in both feet. MRI of brain detected mild frontoparietal atrophy.

The second individual had severe and marked by progressive loss of motor abilities from 9 months of age, tetraspasticity with predominance in the lower extremities, mild cerebellar atrophy, and hyperekplexia-like symptoms. Dysmorphic features such as low set, posteriorly rotated ears, and overlapping toes

The third individual is an infant with severe global developmental delay, axial hypotonia and limb spasticity. No dysmorphic facial features were noted, but she had a high arched palate, bilateral 5th finger clinodactyly, partial toe syndactyly of the second and third toes, and a single hyperpigmented macule tongue fasciculations, axial hypotonia with limb spasticity (more pronounced in the lower limbs), ankle clonus, and brisk patellar deep tendon reflexes.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4484 ITSN1 Ee Ming Wong changed review comment from: -10 individuals from eight unrelated with neurodevelopmental disorder spectrum including ASD, ID, major behavioral difficulties and/or verbal impairment.
-variants included heterozygous premature truncating and missense variants
-Majority of variants were de novo; in two patients the reported variant was inherited from paucisymptomatic father
Sources: Literature; to: -10 individuals from eight unrelated families with neurodevelopmental disorder spectrum including ASD, ID, major behavioral difficulties and/or verbal impairment.
-variants included heterozygous premature truncating and missense variants
-Majority of variants were de novo; in two patients the reported variant was inherited from paucisymptomatic father
Sources: Literature
Cerebellar and Pontocerebellar Hypoplasia v1.44 MAN2C1 Alison Yeung Classified gene: MAN2C1 as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v1.44 MAN2C1 Alison Yeung Gene: man2c1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4484 ITSN1 Ee Ming Wong gene: ITSN1 was added
gene: ITSN1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ITSN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ITSN1 were set to PMID: 34707297
Phenotypes for gene: ITSN1 were set to neurodevelopmental disorder MONDO:0700092 ITSN1-related
Penetrance for gene: ITSN1 were set to unknown
gene: ITSN1 was marked as current diagnostic
Added comment: -10 individuals from eight unrelated with neurodevelopmental disorder spectrum including ASD, ID, major behavioral difficulties and/or verbal impairment.
-variants included heterozygous premature truncating and missense variants
-Majority of variants were de novo; in two patients the reported variant was inherited from paucisymptomatic father
Sources: Literature
Cerebellar and Pontocerebellar Hypoplasia v1.44 MAN2C1 Alison Yeung Classified gene: MAN2C1 as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v1.44 MAN2C1 Alison Yeung Gene: man2c1 has been classified as Green List (High Evidence).
Mendeliome v0.10844 ATP5E Ain Roesley reviewed gene: ATP5E: Rating: GREEN; Mode of pathogenicity: None; Publications: 34954817; Phenotypes: Mitochondrial complex V (ATP synthase) deficiency, nuclear type 3 MIM#614053; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Cerebellar and Pontocerebellar Hypoplasia v1.44 MAN2C1 Alison Yeung Marked gene: MAN2C1 as ready
Cerebellar and Pontocerebellar Hypoplasia v1.44 MAN2C1 Alison Yeung Gene: man2c1 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.44 MAN2C1 Alison Yeung Classified gene: MAN2C1 as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v1.44 MAN2C1 Alison Yeung Gene: man2c1 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.171 MAN2C1 Alison Yeung Classified gene: MAN2C1 as Green List (high evidence)
Polymicrogyria and Schizencephaly v0.171 MAN2C1 Alison Yeung Gene: man2c1 has been classified as Green List (High Evidence).
Mendeliome v0.10844 BAP1 Anna Ritchie changed review comment from: 11 de novo germline heterozygous missense BAP1 variants associated with a rare syndromic neurodevelopmental disorder. Functional analysis showed that most of the variants cannot rescue the consequences of BAP1 inactivation, suggesting a loss-of-function mechanism. Patients phenotypes also included developmental delay, speech and motor delay, seizures, hypotonia, abnormal behaviour, autism, attention deficit hyperactivity disorder, and hypersensitivity.
Sources: Literature; to: 11 de novo germline heterozygous missense BAP1 variants associated with a rare syndromic neurodevelopmental disorder. Functional analysis showed that most of the variants cannot rescue the consequences of BAP1 inactivation, suggesting a loss-of-function mechanism. All affected individuals harboring a de novo BAP1 variant had DD or ID (11/11) characterized notably by speech (11/ 11) and motor delay (6/11). Most of them had hypotonia (7/11), seizures (6/11), and abnormal behavior (8/10), including autism spectrum disorder, attention deficit hyperactivity disorder, and hypersensitivity. Almost all individuals showed dysmorphic facial features (10/11), and more than half (6/11) had skeletal mal- formations (involving the hands [4/11], feet [3/11], or spine [2/11],). Most of the individuals had growth failure (9/11), including four individuals with a very short stature.
Sources: Literature
Mendeliome v0.10844 TMEM53 Zornitza Stark Marked gene: TMEM53 as ready
Mendeliome v0.10844 TMEM53 Zornitza Stark Gene: tmem53 has been classified as Green List (High Evidence).
Mendeliome v0.10844 TMEM53 Zornitza Stark Classified gene: TMEM53 as Green List (high evidence)
Mendeliome v0.10844 TMEM53 Zornitza Stark Gene: tmem53 has been classified as Green List (High Evidence).
Mendeliome v0.10843 TMEM53 Zornitza Stark Phenotypes for gene: TMEM53 were changed from Sclerosing bone disorder, macrocephaly, impaired vision, short stature to Primary bone dysplasia MONDO:0018230, TMEM53-related; Sclerosing bone disorder, macrocephaly, impaired vision, short stature
Polymicrogyria and Schizencephaly v0.171 MAN2C1 Alison Yeung Classified gene: MAN2C1 as Green List (high evidence)
Polymicrogyria and Schizencephaly v0.171 MAN2C1 Alison Yeung Gene: man2c1 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.172 MAN2C1 Alison Yeung Phenotypes for gene: MAN2C1 were changed from neurodevelopmental disorder, MAN2C1-related, MONDO:0700092 to neurodevelopmental disorder, MAN2C1-related, MONDO:0700092
Polymicrogyria and Schizencephaly v0.171 MAN2C1 Alison Yeung Marked gene: MAN2C1 as ready
Polymicrogyria and Schizencephaly v0.171 MAN2C1 Alison Yeung Gene: man2c1 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.171 MAN2C1 Alison Yeung Classified gene: MAN2C1 as Green List (high evidence)
Polymicrogyria and Schizencephaly v0.171 MAN2C1 Alison Yeung Gene: man2c1 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.171 MAN2C1 Alison Yeung Phenotypes for gene: MAN2C1 were changed from neurodevelopmental disorder MONDO:0700092 MAN2C1-related to neurodevelopmental disorder, MAN2C1-related, MONDO:0700092
Intellectual disability syndromic and non-syndromic v0.4484 SLC38A3 Zornitza Stark Classified gene: SLC38A3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4484 SLC38A3 Zornitza Stark Gene: slc38a3 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.171 MAN2C1 Alison Yeung Classified gene: MAN2C1 as Green List (high evidence)
Polymicrogyria and Schizencephaly v0.171 MAN2C1 Alison Yeung Gene: man2c1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1442 SLC38A3 Zornitza Stark Phenotypes for gene: SLC38A3 were changed from developmental epileptic encephalopathy, SLC38A3-related MONDO:0100062 to Developmental epileptic encephalopathy MONDO:0100062, SLC38A3-related
Cerebellar and Pontocerebellar Hypoplasia v1.43 MAN2C1 Michelle Torres gene: MAN2C1 was added
gene: MAN2C1 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Literature
Mode of inheritance for gene: MAN2C1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAN2C1 were set to 35045343
Phenotypes for gene: MAN2C1 were set to neurodevelopmental disorder MONDO:0700092 MAN2C1-related
Review for gene: MAN2C1 was set to GREEN
Added comment: Six individuals from four different families, including two fetuses, exhibiting dysmorphic facial features, congenital anomalies such as tongue hamartoma, variable degrees of intellectual disability, and brain anomalies including polymicrogyria, interhemispheric cysts, hypothalamic hamartoma, callosal anomalies, and hypoplasia of brainstem and cerebellar vermis. Variants include PTC and missense.
*3 individuals (2 families) presented hypoplasia of brainstem and/or cerebellar
Sources: Literature
Genetic Epilepsy v0.1441 SLC38A3 Zornitza Stark Marked gene: SLC38A3 as ready
Genetic Epilepsy v0.1441 SLC38A3 Zornitza Stark Gene: slc38a3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4483 SLC38A3 Zornitza Stark Classified gene: SLC38A3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4483 SLC38A3 Zornitza Stark Gene: slc38a3 has been classified as Green List (High Evidence).
Polymicrogyria and Schizencephaly v0.170 MAN2C1 Michelle Torres gene: MAN2C1 was added
gene: MAN2C1 was added to Polymicrogyria and Schizencephaly. Sources: Literature,Research
Mode of inheritance for gene: MAN2C1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAN2C1 were set to 35045343
Phenotypes for gene: MAN2C1 were set to neurodevelopmental disorder MONDO:0700092 MAN2C1-related
Review for gene: MAN2C1 was set to GREEN
Added comment: Six individuals from four different families, including two fetuses, exhibiting dysmorphic facial features, congenital anomalies such as tongue hamartoma, variable degrees of intellectual disability, and brain anomalies including polymicrogyria, interhemispheric cysts, hypothalamic hamartoma, callosal anomalies, and hypoplasia of brainstem and cerebellar vermis. Variants include PTC and missense.
*3 unrelated individuals presented polymicrogyria
Sources: Literature, Research
Genetic Epilepsy v0.1441 SLC38A3 Zornitza Stark Classified gene: SLC38A3 as Green List (high evidence)
Genetic Epilepsy v0.1441 SLC38A3 Zornitza Stark Gene: slc38a3 has been classified as Green List (High Evidence).
Mendeliome v0.10842 MAN2C1 Alison Yeung Marked gene: MAN2C1 as ready
Mendeliome v0.10842 MAN2C1 Alison Yeung Gene: man2c1 has been classified as Green List (High Evidence).
Lysosomal Storage Disorder v1.4 ARSK Zornitza Stark Marked gene: ARSK as ready
Lysosomal Storage Disorder v1.4 ARSK Zornitza Stark Gene: arsk has been classified as Green List (High Evidence).
Mendeliome v0.10842 MAN2C1 Alison Yeung Phenotypes for gene: MAN2C1 were changed from neurodevelopmental disorder MONDO:0700092 MAN2C1-related to neurodevelopmental disorder, MAN2C1-related, MONDO:0700092
Microcephaly v1.100 SLC38A3 Zornitza Stark Marked gene: SLC38A3 as ready
Microcephaly v1.100 SLC38A3 Zornitza Stark Gene: slc38a3 has been classified as Green List (High Evidence).
Mendeliome v0.10841 MAN2C1 Alison Yeung Classified gene: MAN2C1 as Green List (high evidence)
Mendeliome v0.10841 MAN2C1 Alison Yeung Gene: man2c1 has been classified as Green List (High Evidence).
Microcephaly v1.100 SLC38A3 Zornitza Stark Phenotypes for gene: SLC38A3 were changed from developmental epileptic encephalopathy, SLC38A3-related MONDO:0100062 to Developmental epileptic encephalopathy MONDO:0100062, SLC38A3-related
Microcephaly v1.99 SLC38A3 Zornitza Stark Classified gene: SLC38A3 as Green List (high evidence)
Microcephaly v1.99 SLC38A3 Zornitza Stark Gene: slc38a3 has been classified as Green List (High Evidence).
Mendeliome v0.10840 SLC38A3 Zornitza Stark Marked gene: SLC38A3 as ready
Mendeliome v0.10840 SLC38A3 Zornitza Stark Gene: slc38a3 has been classified as Green List (High Evidence).
Microcephaly v1.98 SLC38A3 Ain Roesley gene: SLC38A3 was added
gene: SLC38A3 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: SLC38A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC38A3 were set to 34605855
Phenotypes for gene: SLC38A3 were set to developmental epileptic encephalopathy, SLC38A3-related MONDO:0100062
Penetrance for gene: SLC38A3 were set to Complete
Review for gene: SLC38A3 was set to GREEN
gene: SLC38A3 was marked as current diagnostic
Added comment: 7 families 6 of whom are consanguineous but unique variants in all of them

Acquired microcephaly noted (8/10 with >-2 SD, 5/10 >-3 SD)
Sources: Literature
Mendeliome v0.10840 SLC38A3 Zornitza Stark Phenotypes for gene: SLC38A3 were changed from developmental epileptic encephalopathy, SLC38A3-related MONDO:0100062 to Developmental epileptic encephalopathy MONDO:0100062, SLC38A3-related
Mendeliome v0.10839 SLC38A3 Zornitza Stark Classified gene: SLC38A3 as Green List (high evidence)
Mendeliome v0.10839 SLC38A3 Zornitza Stark Gene: slc38a3 has been classified as Green List (High Evidence).
Skeletal dysplasia v0.152 ARSK Paul De Fazio gene: ARSK was added
gene: ARSK was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: ARSK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARSK were set to 34916232; 32856704
Phenotypes for gene: ARSK were set to Mucopolysaccharidosis MONDO:0019249, ARSK-related
Review for gene: ARSK was set to GREEN
gene: ARSK was marked as current diagnostic
Added comment: 4 individuals from 2 unrelated consanguineous families reported with a homozygous missense and an NMD-predicted nonsense variant, who had features of mucopolysaccharidosis such as short stature, coarse facial features and dysostosis multiplex. Urinary GAG excretion was normal by conventional methods, but LC-MS/MS in 2 individuals revealed an increase in specific dermatan sulfate-derived disaccharides. Functional studies showed reduced protein levels and reduced enzyme activity for the nonsense and missense variant respectively.

A mouse model also shows a mucopolysaccharidosis phenotype, albeit milder.

Rated green (2 families, functional evidence, mouse model).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4482 MAN2C1 Michelle Torres gene: MAN2C1 was added
gene: MAN2C1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: MAN2C1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAN2C1 were set to 35045343
Phenotypes for gene: MAN2C1 were set to neurodevelopmental disorder MONDO:0700092 MAN2C1-related
Review for gene: MAN2C1 was set to GREEN
Added comment: Six individuals from four different families, including two fetuses, exhibiting dysmorphic facial features, congenital anomalies such as tongue hamartoma, variable degrees of intellectual disability, and brain anomalies including polymicrogyria, interhemispheric cysts, hypothalamic hamartoma, callosal anomalies, and hypoplasia of brainstem and cerebellar vermis. Variants include PTC and missense.
Sources: Literature
Lysosomal Storage Disorder v1.4 ARSK Zornitza Stark Phenotypes for gene: ARSK were changed from Mucopolysaccharidosis MONDO:0019249, ARSK-related to Mucopolysaccharidosis MONDO:0019249, ARSK-related
Mendeliome v0.10838 BAP1 Anna Ritchie gene: BAP1 was added
gene: BAP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BAP1 were set to PMID: 35051358
Phenotypes for gene: BAP1 were set to syndromic intellectual disability MONDO:0000508
Penetrance for gene: BAP1 were set to unknown
Review for gene: BAP1 was set to GREEN
Added comment: 11 de novo germline heterozygous missense BAP1 variants associated with a rare syndromic neurodevelopmental disorder. Functional analysis showed that most of the variants cannot rescue the consequences of BAP1 inactivation, suggesting a loss-of-function mechanism. Patients phenotypes also included developmental delay, speech and motor delay, seizures, hypotonia, abnormal behaviour, autism, attention deficit hyperactivity disorder, and hypersensitivity.
Sources: Literature
Lysosomal Storage Disorder v1.4 ARSK Zornitza Stark Phenotypes for gene: ARSK were changed from Mucopolysaccharidosis to Mucopolysaccharidosis MONDO:0019249, ARSK-related
Dystonia - isolated/combined v1.18 KCNN2 Alison Yeung Marked gene: KCNN2 as ready
Dystonia - isolated/combined v1.18 KCNN2 Alison Yeung Gene: kcnn2 has been classified as Green List (High Evidence).
Lysosomal Storage Disorder v1.3 ARSK Zornitza Stark Classified gene: ARSK as Green List (high evidence)
Lysosomal Storage Disorder v1.3 ARSK Zornitza Stark Gene: arsk has been classified as Green List (High Evidence).
Rhabdomyolysis and Metabolic Myopathy v0.85 OBSCN Ee Ming Wong gene: OBSCN was added
gene: OBSCN was added to Rhabdomyolysis. Sources: Literature
Mode of inheritance for gene: OBSCN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OBSCN were set to PMID: 34957489
Phenotypes for gene: OBSCN were set to Rhabdomyolysis, MONDO:0005290
Penetrance for gene: OBSCN were set to unknown
Review for gene: OBSCN was set to GREEN
gene: OBSCN was marked as current diagnostic
Added comment: -Six unrelated individuals with severe, recurrent rhabdomyolysis carrying bi-allelic loss of function variants
-Three of six probands experienced acute renal failure
-None presented with cardiac involvement/symptoms of cardiac disease
-Patient muscles demonstrated reduced OBSCN expression and loss of obscurin protein
Sources: Literature
Dystonia - isolated/combined v1.18 KCNN2 Alison Yeung Publications for gene: KCNN2 were set to PMID: 32212350; 33242881
Mendeliome v0.10838 ARSK Zornitza Stark Marked gene: ARSK as ready
Mendeliome v0.10838 ARSK Zornitza Stark Gene: arsk has been classified as Green List (High Evidence).
Mendeliome v0.10838 ARSK Zornitza Stark Phenotypes for gene: ARSK were changed from Mucopolysaccharidosis to Mucopolysaccharidosis MONDO:0019249, ARSK-related
Dystonia - isolated/combined v1.17 KCNN2 Alison Yeung Classified gene: KCNN2 as Green List (high evidence)
Dystonia - isolated/combined v1.17 KCNN2 Alison Yeung Gene: kcnn2 has been classified as Green List (High Evidence).
Mendeliome v0.10837 ARSK Zornitza Stark Classified gene: ARSK as Green List (high evidence)
Mendeliome v0.10837 ARSK Zornitza Stark Gene: arsk has been classified as Green List (High Evidence).
Mendeliome v0.10836 RBL2 Elena Savva reviewed gene: RBL2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33980986, 32105419, 9806916; Phenotypes: Severe motor and cognitive impairment, Intellectual disability, Brunet-Wagner neurodevelopmental syndrome MIM#619690; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4482 RBL2 Elena Savva reviewed gene: RBL2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33980986, 32105419, 9806916; Phenotypes: Severe motor and cognitive impairment, Intellectual disability, Brunet-Wagner neurodevelopmental syndrome MIM#619690; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Microcephaly v1.98 RBL2 Elena Savva gene: RBL2 was added
gene: RBL2 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: RBL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RBL2 were set to PMID: 33980986; 32105419; 9806916
Phenotypes for gene: RBL2 were set to Severe motor and cognitive impairment; Intellectual disability; Brunet-Wagner neurodevelopmental syndrome MIM#619690
Review for gene: RBL2 was set to AMBER
Added comment: PMID: 33980986: 2 unrelated patients (3 total) with infantile hypotonia, severe developmental delay and microcephaly. Functional studies on patient fibroblasts supports loss of protein and mRNA expression. Patients were homozygous for a PTC, and a CNV (exon 4-5 del)

PMID: 32105419: affecting siblings with severe intellectual disability, stereotypies and dysmorphic features. Chet PTC/CNV (exon 13-17 del).

3 unrelated families - 2/3 corpus callosum hypoplasia/cerebral atrophy, 2/3 epilepsy, 2/3 microcephaly

PMID: 9806916: mouse model in support
Sources: Literature
Cerebellar and Pontocerebellar Hypoplasia v1.43 RBL2 Elena Savva gene: RBL2 was added
gene: RBL2 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Literature
Mode of inheritance for gene: RBL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RBL2 were set to PMID: 33980986; 32105419; 9806916
Phenotypes for gene: RBL2 were set to Severe motor and cognitive impairment; Intellectual disability; Brunet-Wagner neurodevelopmental syndrome MIM#619690
Review for gene: RBL2 was set to AMBER
Added comment: PMID: 33980986: 2 unrelated patients (3 total) with infantile hypotonia, severe developmental delay and microcephaly. Functional studies on patient fibroblasts supports loss of protein and mRNA expression. Patients were homozygous for a PTC, and a CNV (exon 4-5 del)

PMID: 32105419: affecting siblings with severe intellectual disability, stereotypies and dysmorphic features. Chet PTC/CNV (exon 13-17 del).

3 unrelated families - 2/3 corpus callosum hypoplasia/cerebral atrophy, 2/3 epilepsy, 2/3 microcephaly

PMID: 9806916: mouse model in support
Sources: Literature
Microcephaly v1.98 FRA10AC1 Zornitza Stark Marked gene: FRA10AC1 as ready
Microcephaly v1.98 FRA10AC1 Zornitza Stark Gene: fra10ac1 has been classified as Green List (High Evidence).
Microcephaly v1.98 FRA10AC1 Zornitza Stark Classified gene: FRA10AC1 as Green List (high evidence)
Microcephaly v1.98 FRA10AC1 Zornitza Stark Gene: fra10ac1 has been classified as Green List (High Evidence).
Mendeliome v0.10836 SLC38A3 Ain Roesley changed review comment from: 7 families 6 of whom are consanguineous but unique variants in all of them

Acquired microcephaly noted (8/10 with <-2 SD, 5/10 <-3 SD)

10/10 with axial hopotonia, absent speech, GDD/ID
9/10 with visual impairment
8/10 with seizures
8/10 with peripheral hypertonia
Sources: Literature; to: 7 families 6 of whom are consanguineous but unique variants in all of them

Acquired microcephaly noted (8/10 with >-2 SD, 5/10 >-3 SD)

10/10 with axial hopotonia, absent speech, GDD/ID
9/10 with visual impairment
8/10 with seizures
8/10 with peripheral hypertonia
Sources: Literature
Microcephaly v1.97 FRA10AC1 Zornitza Stark gene: FRA10AC1 was added
gene: FRA10AC1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: FRA10AC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FRA10AC1 were set to 34694367
Phenotypes for gene: FRA10AC1 were set to Neurodevelopmental disorder, MONDO:0700092, FRA10AC1-related
Review for gene: FRA10AC1 was set to GREEN
Added comment: PMID 34694367: 5 individuals from 3 unrelated families reported. Variable ID, possibly related to variant type with LoF variants associated with more severe ID. All individuals had microcephaly, hypoplasia or agenesis of the corpus callosum, growth retardation, and craniofacial dysmorphism.
Sources: Literature
Genetic Epilepsy v0.1440 FZR1 Alison Yeung gene: FZR1 was added
gene: FZR1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: FZR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FZR1 were set to 34788397
Phenotypes for gene: FZR1 were set to Developmental and epileptic encephalopathy, FZR1-related, MONDO:0100062
Review for gene: FZR1 was set to GREEN
Added comment: >3 unrelated individuals reported with de novo missense variants. Functional studies in Drosophila demonstrate missense variants cause LOF.
Sources: Literature
Callosome v0.356 FRA10AC1 Zornitza Stark Marked gene: FRA10AC1 as ready
Callosome v0.356 FRA10AC1 Zornitza Stark Gene: fra10ac1 has been classified as Green List (High Evidence).
Callosome v0.356 FRA10AC1 Zornitza Stark Classified gene: FRA10AC1 as Green List (high evidence)
Callosome v0.356 FRA10AC1 Zornitza Stark Gene: fra10ac1 has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1439 SLC38A3 Ain Roesley gene: SLC38A3 was added
gene: SLC38A3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SLC38A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC38A3 were set to 34605855
Phenotypes for gene: SLC38A3 were set to developmental epileptic encephalopathy, SLC38A3-related MONDO:0100062
Penetrance for gene: SLC38A3 were set to Complete
Review for gene: SLC38A3 was set to GREEN
gene: SLC38A3 was marked as current diagnostic
Added comment: 7 families 6 of whom are consanguineous but unique variants in all of them

8/10 with seizures
Sources: Literature
Callosome v0.355 FRA10AC1 Zornitza Stark gene: FRA10AC1 was added
gene: FRA10AC1 was added to Callosome. Sources: Literature
Mode of inheritance for gene: FRA10AC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FRA10AC1 were set to 34694367
Phenotypes for gene: FRA10AC1 were set to Neurodevelopmental disorder, MONDO:0700092, FRA10AC1-related
Review for gene: FRA10AC1 was set to GREEN
Added comment: PMID 34694367: 5 individuals from 3 unrelated families reported. Variable ID, possibly related to variant type with LoF variants associated with more severe ID. All individuals had microcephaly, hypoplasia or agenesis of the corpus callosum, growth retardation, and craniofacial dysmorphism.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4482 SLC38A3 Ain Roesley gene: SLC38A3 was added
gene: SLC38A3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: SLC38A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC38A3 were set to 34605855
Phenotypes for gene: SLC38A3 were set to developmental epileptic encephalopathy, SLC38A3-related MONDO:0100062
Penetrance for gene: SLC38A3 were set to Complete
Review for gene: SLC38A3 was set to GREEN
gene: SLC38A3 was marked as current diagnostic
Added comment: 7 families 6 of whom are consanguineous but unique variants in all of them

10/10 with GDD/ID
Sources: Literature
Mendeliome v0.10836 TMEM53 Lucy Spencer gene: TMEM53 was added
gene: TMEM53 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TMEM53 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM53 were set to PMID: 33824347
Phenotypes for gene: TMEM53 were set to Sclerosing bone disorder, macrocephaly, impaired vision, short stature
Review for gene: TMEM53 was set to GREEN
Added comment: PMID: 33824347- Previously unknown type of sclerosing bone disorder in 4 independent families, bi-allelic LOF variants in TMEM53. 5 individuals from 4 families, all have proportional or short limbed stature, not identifiable at birth. Head deformities (macrocephaly, dolichocephaly, prominent forehead), epicanthic folds, thick vermilion of upper and lower lips. Vision diminished after early childhood due to optic nerve compression.

3 of 4 families confirmed consanguineous, and all affected members from all 4 families have homozygous variants inherited from heterozygous parents. 3 families have the same splicing variant proven to cause exon 2 skipping and an NMD frameshift by RT-PCR. The other family has a an NMD frameshift variant. So 4 families but only 2 variants.
Sources: Literature
Mendeliome v0.10836 SLC38A3 Ain Roesley gene: SLC38A3 was added
gene: SLC38A3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC38A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC38A3 were set to 34605855
Phenotypes for gene: SLC38A3 were set to developmental epileptic encephalopathy, SLC38A3-related MONDO:0100062
Review for gene: SLC38A3 was set to GREEN
gene: SLC38A3 was marked as current diagnostic
Added comment: 7 families 6 of whom are consanguineous but unique variants in all of them

Acquired microcephaly noted (8/10 with <-2 SD, 5/10 <-3 SD)

10/10 with axial hopotonia, absent speech, GDD/ID
9/10 with visual impairment
8/10 with seizures
8/10 with peripheral hypertonia
Sources: Literature
Growth failure v1.32 FRA10AC1 Zornitza Stark Marked gene: FRA10AC1 as ready
Growth failure v1.32 FRA10AC1 Zornitza Stark Gene: fra10ac1 has been classified as Green List (High Evidence).
Growth failure v1.32 FRA10AC1 Zornitza Stark Classified gene: FRA10AC1 as Green List (high evidence)
Growth failure v1.32 FRA10AC1 Zornitza Stark Gene: fra10ac1 has been classified as Green List (High Evidence).
Growth failure v1.31 FRA10AC1 Zornitza Stark gene: FRA10AC1 was added
gene: FRA10AC1 was added to Growth failure. Sources: Literature
Mode of inheritance for gene: FRA10AC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FRA10AC1 were set to 34694367
Phenotypes for gene: FRA10AC1 were set to Neurodevelopmental disorder, MONDO:0700092, FRA10AC1-related
Review for gene: FRA10AC1 was set to GREEN
Added comment: PMID 34694367: 5 individuals from 3 unrelated families reported. Variable ID, possibly related to variant type with LoF variants associated with more severe ID. All individuals had microcephaly, hypoplasia or agenesis of the corpus callosum, growth retardation, and craniofacial dysmorphism.
Sources: Literature
Mendeliome v0.10836 FZR1 Alison Yeung gene: FZR1 was added
gene: FZR1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FZR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FZR1 were set to 34788397
Phenotypes for gene: FZR1 were set to Developmental and epileptic encephalopathy, FZR1-related, MONDO:0100062
Review for gene: FZR1 was set to GREEN
Added comment: >3 unrelated individuals reported with de novo missense variants. Functional studies in Drosophila demonstrate missense variants cause LOF.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4482 FRA10AC1 Zornitza Stark Marked gene: FRA10AC1 as ready
Intellectual disability syndromic and non-syndromic v0.4482 FRA10AC1 Zornitza Stark Gene: fra10ac1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4482 FRA10AC1 Zornitza Stark Classified gene: FRA10AC1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.4482 FRA10AC1 Zornitza Stark Gene: fra10ac1 has been classified as Green List (High Evidence).
Lysosomal Storage Disorder v1.2 ARSK Paul De Fazio gene: ARSK was added
gene: ARSK was added to Lysosomal Storage Disorder. Sources: Literature
Mode of inheritance for gene: ARSK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARSK were set to 34916232; 32856704
Phenotypes for gene: ARSK were set to Mucopolysaccharidosis
Review for gene: ARSK was set to GREEN
gene: ARSK was marked as current diagnostic
Added comment: 4 individuals from 2 unrelated consanguineous families reported with a homozygous missense and an NMD-predicted nonsense variant, who had features of mucopolysaccharidosis such as short stature, coarse facial features and dysostosis multiplex. Urinary GAG excretion was normal by conventional methods, but LC-MS/MS in 2 individuals revealed an increase in specific dermatan sulfate-derived disaccharides. Functional studies showed reduced protein levels and reduced enzyme activity for the nonsense and missense variant respectively.

A mouse model also shows a mucopolysaccharidosis phenotype, albeit milder.

Rated green (2 families, functional evidence, mouse model).
Sources: Literature
Mendeliome v0.10835 MAN2C1 Michelle Torres gene: MAN2C1 was added
gene: MAN2C1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MAN2C1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAN2C1 were set to 35045343
Phenotypes for gene: MAN2C1 were set to neurodevelopmental disorder MONDO:0700092 MAN2C1-related
Review for gene: MAN2C1 was set to GREEN
Added comment: Six individuals from four different families, including two fetuses, exhibiting dysmorphic facial features, congenital anomalies such as tongue hamartoma, variable degrees of intellectual disability, and brain anomalies including polymicrogyria, interhemispheric cysts, hypothalamic hamartoma, callosal anomalies, and hypoplasia of brainstem and cerebellar vermis. Variants include PTC and missense.
Sources: Literature
Dystonia - isolated/combined v1.16 KCNN2 Chern Lim gene: KCNN2 was added
gene: KCNN2 was added to Dystonia - isolated/combined. Sources: Literature
Mode of inheritance for gene: KCNN2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNN2 were set to PMID: 32212350; 33242881
Phenotypes for gene: KCNN2 were set to Dystonia 34, myoclonic, MIM#619724; Neurodevelopmental disorder with or without variable movement or behavioural abnormalities, MIM#619725
Review for gene: KCNN2 was set to GREEN
gene: KCNN2 was marked as current diagnostic
Added comment: PMID: 32212350: one family with multiple affected individuals, autosomal-dominant tremulous
myoclonus-dystonia.

PMID: 33242881: one of the patients had myoclonus-dystonia, one with dystonia and dyskinesia (limbs and trunk).
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4481 FRA10AC1 Zornitza Stark gene: FRA10AC1 was added
gene: FRA10AC1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: FRA10AC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FRA10AC1 were set to 34694367
Phenotypes for gene: FRA10AC1 were set to Neurodevelopmental disorder, MONDO:0700092, FRA10AC1-related
Review for gene: FRA10AC1 was set to GREEN
Added comment: PMID 34694367: 5 individuals from 3 unrelated families reported.

Variable ID, possibly related to variant type with LoF variants associated with more severe ID. All individuals had microcephaly, hypoplasia or agenesis of the corpus callosum, growth retardation, and craniofacial dysmorphism.
Sources: Literature
Mendeliome v0.10835 ARSK Paul De Fazio gene: ARSK was added
gene: ARSK was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARSK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARSK were set to 34916232; 32856704
Phenotypes for gene: ARSK were set to Mucopolysaccharidosis
Review for gene: ARSK was set to GREEN
gene: ARSK was marked as current diagnostic
Added comment: 4 individuals from 2 unrelated consanguineous families (Turkish and Indian) reported with a homozygous missense and an NMD-predicted nonsense variant. Affected individuals had features of mucopolysaccharidosis such as short stature, coarse facial features and dysostosis multiplex. Urinary GAG excretion was normal by conventional methods, but LC-MS/MS in 2 individuals revealed an increase in specific dermatan sulfate-derived disaccharides. Functional studies showed reduced protein levels and reduced enzyme activity for the nonsense and missense variant respectively.

A mouse model also shows a mucopolysaccharidosis phenotype, albeit milder.

Rated green (2 families, functional evidence, mouse model).
Sources: Literature
Mendeliome v0.10835 FRA10AC1 Zornitza Stark changed review comment from: Conclusion of this study was that FRA10A is likely a benign folate-sensitive fragile site.; to: PMID 15203205: Conclusion of this study was that FRA10A is likely a benign folate-sensitive fragile site.
Mendeliome v0.10835 FRA10AC1 Zornitza Stark edited their review of gene: FRA10AC1: Added comment: PMID 34694367: 5 individuals from 3 unrelated families reported.

Variable ID, possibly related to variant type with LoF variants associated with more severe ID. All individuals had microcephaly, hypoplasia or agenesis of the corpus callosum, growth retardation, and craniofacial dysmorphism.; Changed rating: GREEN; Changed publications: 15203205, 34694367; Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, FRA10AC1-related; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3064 MYBPC1 Zornitza Stark Publications for gene: MYBPC1 were set to
Fetal anomalies v0.3063 NDUFS8 Zornitza Stark Marked gene: NDUFS8 as ready
Fetal anomalies v0.3063 NDUFS8 Zornitza Stark Gene: ndufs8 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3063 NDUFS8 Zornitza Stark Phenotypes for gene: NDUFS8 were changed from MITOCHONDRIAL RESPIRATORY CHAIN COMPLEX I DEFICIENCY to Mitochondrial complex I deficiency, nuclear type 2 MIM#618222
Fetal anomalies v0.3062 NDUFS8 Zornitza Stark Publications for gene: NDUFS8 were set to
Fetal anomalies v0.3061 MUSK Zornitza Stark Publications for gene: MUSK were set to
Fetal anomalies v0.3060 MTOR Zornitza Stark Publications for gene: MTOR were set to
Fetal anomalies v0.3059 MTOR Zornitza Stark Mode of pathogenicity for gene: MTOR was changed from to Other
Fetal anomalies v0.3058 MTOR Zornitza Stark Mode of inheritance for gene: MTOR was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10835 NDUFS7 Zornitza Stark Marked gene: NDUFS7 as ready
Mendeliome v0.10835 NDUFS7 Zornitza Stark Gene: ndufs7 has been classified as Green List (High Evidence).
Mendeliome v0.10835 NDUFS7 Zornitza Stark Phenotypes for gene: NDUFS7 were changed from to Mitochondrial complex I deficiency, nuclear type 3 MIM#618224
Mendeliome v0.10834 NDUFS7 Zornitza Stark Publications for gene: NDUFS7 were set to
Mendeliome v0.10833 NDUFS7 Zornitza Stark Mode of inheritance for gene: NDUFS7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3057 NDUFA1 Zornitza Stark Marked gene: NDUFA1 as ready
Fetal anomalies v0.3057 NDUFA1 Zornitza Stark Gene: ndufa1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3057 NDUFA1 Zornitza Stark Phenotypes for gene: NDUFA1 were changed from MITOCHONDRIAL RESPIRATORY CHAIN COMPLEX I DEFICIENCY to Mitochondrial complex I deficiency, nuclear type 12 MIM#301020
Fetal anomalies v0.3056 NDUFA1 Zornitza Stark Publications for gene: NDUFA1 were set to
Mendeliome v0.10832 NDUFA1 Zornitza Stark Marked gene: NDUFA1 as ready
Mendeliome v0.10832 NDUFA1 Zornitza Stark Gene: ndufa1 has been classified as Green List (High Evidence).
Mendeliome v0.10832 NDUFA1 Zornitza Stark Phenotypes for gene: NDUFA1 were changed from to Mitochondrial complex I deficiency, nuclear type 12 MIM#301020
Mendeliome v0.10831 NDUFA1 Zornitza Stark Publications for gene: NDUFA1 were set to
Mendeliome v0.10830 NDUFA1 Zornitza Stark Mode of inheritance for gene: NDUFA1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v0.3055 MYO5A Zornitza Stark Marked gene: MYO5A as ready
Fetal anomalies v0.3055 MYO5A Zornitza Stark Gene: myo5a has been classified as Red List (Low Evidence).
Fetal anomalies v0.3055 MYO5A Zornitza Stark Phenotypes for gene: MYO5A were changed from GRISCELLI SYNDROME TYPE 3; ELEJALDE SYNDROME to Griscelli syndrome, type 1 MIM#214450
Fetal anomalies v0.3054 MYO5A Zornitza Stark Publications for gene: MYO5A were set to
Mendeliome v0.10829 MYO5A Zornitza Stark Marked gene: MYO5A as ready
Mendeliome v0.10829 MYO5A Zornitza Stark Gene: myo5a has been classified as Green List (High Evidence).
Mendeliome v0.10829 MYO5A Zornitza Stark Phenotypes for gene: MYO5A were changed from to Griscelli syndrome, type 1 MIM#214450
Mendeliome v0.10828 MYO5A Zornitza Stark Mode of inheritance for gene: MYO5A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10827 MYO5A Zornitza Stark Publications for gene: MYO5A were set to
Fetal anomalies v0.3053 LTBP2 Zornitza Stark Marked gene: LTBP2 as ready
Fetal anomalies v0.3053 LTBP2 Zornitza Stark Gene: ltbp2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3053 LTBP2 Zornitza Stark Phenotypes for gene: LTBP2 were changed from MICROSPHEROPHAKIA; PRIMARY CONGENITAL GLAUCOMA TYPE 3D to Glaucoma 3, primary congenital, D 613086; Microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma, MIM# 251750
Fetal anomalies v0.3052 LTBP2 Zornitza Stark Publications for gene: LTBP2 were set to
Fetal anomalies v0.3051 MTO1 Zornitza Stark Publications for gene: MTO1 were set to
Fetal anomalies v0.3050 LRPPRC Zornitza Stark Marked gene: LRPPRC as ready
Fetal anomalies v0.3050 LRPPRC Zornitza Stark Gene: lrpprc has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3050 LRPPRC Zornitza Stark Phenotypes for gene: LRPPRC were changed from LEIGH SYNDROME, FRENCH-CANADIAN TYPE to Mitochondrial complex IV deficiency, nuclear type 5, (French-Canadian) MIM#220111
Fetal anomalies v0.3049 LRPPRC Zornitza Stark Publications for gene: LRPPRC were set to
Fetal anomalies v0.3048 LRPPRC Zornitza Stark Classified gene: LRPPRC as Amber List (moderate evidence)
Fetal anomalies v0.3048 LRPPRC Zornitza Stark Gene: lrpprc has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10826 LRPPRC Zornitza Stark Marked gene: LRPPRC as ready
Mendeliome v0.10826 LRPPRC Zornitza Stark Gene: lrpprc has been classified as Green List (High Evidence).
Mendeliome v0.10826 LRPPRC Zornitza Stark Phenotypes for gene: LRPPRC were changed from to Mitochondrial complex IV deficiency, nuclear type 5, (French-Canadian) MIM#220111
Mendeliome v0.10825 LRPPRC Zornitza Stark Publications for gene: LRPPRC were set to
Mendeliome v0.10824 LRPPRC Zornitza Stark Mode of inheritance for gene: LRPPRC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10823 LRPPRC Zornitza Stark reviewed gene: LRPPRC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 5, (French-Canadian) MIM#220111; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3047 MPLKIP Zornitza Stark Publications for gene: MPLKIP were set to
Fetal anomalies v0.3046 MPDU1 Zornitza Stark Publications for gene: MPDU1 were set to
Fetal anomalies v0.3045 MOCS1 Zornitza Stark Publications for gene: MOCS1 were set to
Fetal anomalies v0.3044 MNX1 Zornitza Stark Mode of inheritance for gene: MNX1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3043 MMP21 Zornitza Stark Publications for gene: MMP21 were set to
Fetal anomalies v0.3042 MLYCD Zornitza Stark Publications for gene: MLYCD were set to
Fetal anomalies v0.3041 LMOD1 Zornitza Stark Marked gene: LMOD1 as ready
Fetal anomalies v0.3041 LMOD1 Zornitza Stark Gene: lmod1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3041 LMOD1 Zornitza Stark Phenotypes for gene: LMOD1 were changed from Megacystis Microcolon Intestinal Hypoperistalsis Syndrome (MMIH) to Megacystis-microcolon-intestinal hypoperistalsis syndrome 3, MIM# 619362
Fetal anomalies v0.3040 LMOD1 Zornitza Stark Publications for gene: LMOD1 were set to
Fetal anomalies v0.3039 LMOD1 Zornitza Stark Classified gene: LMOD1 as Amber List (moderate evidence)
Fetal anomalies v0.3039 LMOD1 Zornitza Stark Gene: lmod1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3038 LEMD3 Zornitza Stark Marked gene: LEMD3 as ready
Fetal anomalies v0.3038 LEMD3 Zornitza Stark Gene: lemd3 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3038 LEMD3 Zornitza Stark Phenotypes for gene: LEMD3 were changed from BUSCHKE-OLLENDORFF SYNDROME; MELORHEOSTOSIS to Buschke-Ollendorff syndrome MIM#166700; Osteopoikilosis with or without melorheostosis MIM#166700
Fetal anomalies v0.3037 LEMD3 Zornitza Stark Mode of inheritance for gene: LEMD3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3036 ITPR1 Zornitza Stark Marked gene: ITPR1 as ready
Fetal anomalies v0.3036 ITPR1 Zornitza Stark Gene: itpr1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3036 ITPR1 Zornitza Stark Phenotypes for gene: ITPR1 were changed from SPINOCEREBELLAR ATAXIA 29, CONGENITAL NONPROGRESSIVE; Gillespie Syndrome; SPINOCEREBELLAR ATAXIA TYPE15 to Spinocerebellar ataxia 15 MIM#606658; Spinocerebellar ataxia 29, congenital nonprogressive MIM#117360; Gillespie syndrome, MIM# 206700
Fetal anomalies v0.3035 ITPR1 Zornitza Stark Publications for gene: ITPR1 were set to
Fetal anomalies v0.3034 UROS Zornitza Stark Marked gene: UROS as ready
Fetal anomalies v0.3034 UROS Zornitza Stark Gene: uros has been classified as Green List (High Evidence).
Fetal anomalies v0.3034 UROS Zornitza Stark Classified gene: UROS as Green List (high evidence)
Fetal anomalies v0.3034 UROS Zornitza Stark Gene: uros has been classified as Green List (High Evidence).
Fetal anomalies v0.3033 MVK Zornitza Stark Marked gene: MVK as ready
Fetal anomalies v0.3033 MVK Zornitza Stark Gene: mvk has been classified as Green List (High Evidence).
Fetal anomalies v0.3033 MVK Zornitza Stark Classified gene: MVK as Green List (high evidence)
Fetal anomalies v0.3033 MVK Zornitza Stark Gene: mvk has been classified as Green List (High Evidence).
Oligodontia v0.12 SMOC2 Zornitza Stark Marked gene: SMOC2 as ready
Oligodontia v0.12 SMOC2 Zornitza Stark Gene: smoc2 has been classified as Green List (High Evidence).
Oligodontia v0.12 SMOC2 Zornitza Stark Publications for gene: SMOC2 were set to PMID: 22152679, 23317772, 32908163
Fetal anomalies v0.3032 LAMB2 Zornitza Stark Marked gene: LAMB2 as ready
Fetal anomalies v0.3032 LAMB2 Zornitza Stark Gene: lamb2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3032 LAMB2 Zornitza Stark Classified gene: LAMB2 as Amber List (moderate evidence)
Fetal anomalies v0.3032 LAMB2 Zornitza Stark Gene: lamb2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10823 PLCD1 Paul De Fazio reviewed gene: PLCD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21665001, 22458588, 21665001, 30003652, 33786625, 31082376, 32265483, 31049339; Phenotypes: Nail disorder, nonsyndromic congenital, 3, (leukonychia) MIM#151600, nonsyndromic congenital nail disorder 3 MONDO:0007900; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10823 AKAP10 Paul De Fazio reviewed gene: AKAP10: Rating: RED; Mode of pathogenicity: None; Publications: 12646697, 17485678; Phenotypes: {Cardiac conduction defect, susceptibility to} MIM#115080, sudden cardiac arrest MONDO:0007264; Mode of inheritance: Unknown; Current diagnostic: yes
Mendeliome v0.10823 HMCN1 Paul De Fazio reviewed gene: HMCN1: Rating: RED; Mode of pathogenicity: None; Publications: 25986072, 16020313, 14570714, 27007659; Phenotypes: {Macular degeneration, age-related, 1} MIM#603075, age related macular degeneration 1 MONDO:0011285; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Fetal anomalies v0.3031 PYROXD1 Belinda Chong reviewed gene: PYROXD1: Rating: RED; Mode of pathogenicity: None; Publications: 30345904, 30515627, 27745833; Phenotypes: Myopathy, myofibrillar, 8 (MIM#617258); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10823 CCND1 Paul De Fazio reviewed gene: CCND1: Rating: RED; Mode of pathogenicity: None; Publications: 12097293, 23502783, 21131975, 14657069, 23540573, 20633772; Phenotypes: {Colorectal cancer, susceptibility to} MIM#114500, {Multiple myeloma, susceptibility to} MIM#254500, {von Hippel-Lindau syndrome, modifier of} MIM#193300; Mode of inheritance: Unknown; Current diagnostic: yes
Fetal anomalies v0.3031 PYGM Belinda Chong reviewed gene: PYGM: Rating: RED; Mode of pathogenicity: None; Publications: 1701414, 8316268, 17915571, 17994553, 21880526; Phenotypes: McArdle disease, MIM# 232600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3031 PTPN14 Belinda Chong reviewed gene: PTPN14: Rating: GREEN; Mode of pathogenicity: None; Publications: 20826270, https://doi.org/10.1016/j.mgene.2017.07.006; Phenotypes: Choanal atresia and lymphedema MIM#613611; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3031 PRKAG2 Belinda Chong reviewed gene: PRKAG2: Rating: GREEN; Mode of pathogenicity: None; Publications: 15877279, 17667862, 32646569; Phenotypes: Glycogen storage disease of heart, lethal congenital MIM#261740; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.10823 PADI4 Paul De Fazio reviewed gene: PADI4: Rating: RED; Mode of pathogenicity: None; Publications: 16449362, 19470526, 26474773; Phenotypes: Susceptibility to rheumatoid arthritis; Mode of inheritance: Unknown; Current diagnostic: yes
Fetal anomalies v0.3031 PPP3CA Belinda Chong reviewed gene: PPP3CA: Rating: AMBER; Mode of pathogenicity: None; Publications: 29432562, 28942967, 28942967; Phenotypes: Arthrogryposis, cleft palate, craniosynostosis, and impaired intellectual development MIM#618265, Developmental and epileptic encephalopathy 91 617711; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Fetal anomalies v0.3031 POLR1A Belinda Chong reviewed gene: POLR1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 25913037, 28051070; Phenotypes: Acrofacial dysostosis, Cincinnati type, (MIM#616462); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Fetal anomalies v0.3031 POLG2 Belinda Chong reviewed gene: POLG2: Rating: AMBER; Mode of pathogenicity: None; Publications: 16685652, 21555342, 27592148, 31778857; Phenotypes: Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4, MIM# 610131, Mitochondrial DNA depletion syndrome 16 , MIM# 618528; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.3031 PLCB4 Belinda Chong reviewed gene: PLCB4: Rating: GREEN; Mode of pathogenicity: None; Publications: 22560091, 23315542, 33131036, 32201334, 28328130, 27007857, 23913798; Phenotypes: Auriculocondylar syndrome 2, MIM# 614669; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10823 PLCB1 Zornitza Stark Marked gene: PLCB1 as ready
Mendeliome v0.10823 PLCB1 Zornitza Stark Gene: plcb1 has been classified as Green List (High Evidence).
Mendeliome v0.10823 PLCB1 Zornitza Stark Phenotypes for gene: PLCB1 were changed from to Epileptic encephalopathy, early infantile, 12 (MIM#613722)
Mendeliome v0.10822 PLCB1 Zornitza Stark Publications for gene: PLCB1 were set to
Mendeliome v0.10821 PLCB1 Zornitza Stark Mode of inheritance for gene: PLCB1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10820 PLCB1 Zornitza Stark Tag SV/CNV tag was added to gene: PLCB1.
Mendeliome v0.10820 PLCB1 Zornitza Stark reviewed gene: PLCB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24684524, 20833646, 22690784, 26818157; Phenotypes: Epileptic encephalopathy, early infantile, 12 (MIM#613722); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3031 PLCB1 Zornitza Stark Marked gene: PLCB1 as ready
Fetal anomalies v0.3031 PLCB1 Zornitza Stark Gene: plcb1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3031 PLCB1 Zornitza Stark Phenotypes for gene: PLCB1 were changed from EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 12 to Epileptic encephalopathy, early infantile, 12 (MIM#613722)
Fetal anomalies v0.3030 PLCB1 Zornitza Stark Publications for gene: PLCB1 were set to
Fetal anomalies v0.3029 PLCB1 Zornitza Stark Classified gene: PLCB1 as Red List (low evidence)
Fetal anomalies v0.3029 PLCB1 Zornitza Stark Gene: plcb1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3028 PLCB1 Zornitza Stark reviewed gene: PLCB1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Epileptic encephalopathy, early infantile, 12 (MIM#613722); Mode of inheritance: None
Fetal anomalies v0.3028 PLAG1 Zornitza Stark Marked gene: PLAG1 as ready
Fetal anomalies v0.3028 PLAG1 Zornitza Stark Gene: plag1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3028 PLAG1 Zornitza Stark Publications for gene: PLAG1 were set to
Fetal anomalies v0.3027 PLAG1 Zornitza Stark Mode of inheritance for gene: PLAG1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3026 PLAG1 Zornitza Stark Classified gene: PLAG1 as Green List (high evidence)
Fetal anomalies v0.3026 PLAG1 Zornitza Stark Gene: plag1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3025 PLAG1 Zornitza Stark reviewed gene: PLAG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28796236, 29913240, 33291420, 32546215; Phenotypes: Silver-Russell syndrome, MIM#618907; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1439 PLAA Zornitza Stark Marked gene: PLAA as ready
Genetic Epilepsy v0.1439 PLAA Zornitza Stark Gene: plaa has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1439 PLAA Zornitza Stark Phenotypes for gene: PLAA were changed from to Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, MIM# 617527
Genetic Epilepsy v0.1438 PLAA Zornitza Stark Publications for gene: PLAA were set to
Genetic Epilepsy v0.1437 PLAA Zornitza Stark Mode of inheritance for gene: PLAA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1436 PLAA Zornitza Stark reviewed gene: PLAA: Rating: GREEN; Mode of pathogenicity: None; Publications: 28007986, 28413018, 31322726; Phenotypes: Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, MIM# 617527; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4480 PLAA Zornitza Stark Marked gene: PLAA as ready
Intellectual disability syndromic and non-syndromic v0.4480 PLAA Zornitza Stark Gene: plaa has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4480 PLAA Zornitza Stark Phenotypes for gene: PLAA were changed from to Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, MIM# 617527
Intellectual disability syndromic and non-syndromic v0.4479 PLAA Zornitza Stark Publications for gene: PLAA were set to
Intellectual disability syndromic and non-syndromic v0.4478 PLAA Zornitza Stark Mode of inheritance for gene: PLAA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4477 PLAA Zornitza Stark reviewed gene: PLAA: Rating: GREEN; Mode of pathogenicity: None; Publications: 28007986, 28413018, 31322726; Phenotypes: Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, MIM# 617527; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10820 PLAA Zornitza Stark Marked gene: PLAA as ready
Mendeliome v0.10820 PLAA Zornitza Stark Gene: plaa has been classified as Green List (High Evidence).
Mendeliome v0.10820 PLAA Zornitza Stark Phenotypes for gene: PLAA were changed from to Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, MIM# 617527
Mendeliome v0.10819 PLAA Zornitza Stark Publications for gene: PLAA were set to
Mendeliome v0.10818 PLAA Zornitza Stark Mode of inheritance for gene: PLAA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10817 PLAA Zornitza Stark reviewed gene: PLAA: Rating: GREEN; Mode of pathogenicity: None; Publications: 28007986, 28413018, 31322726; Phenotypes: Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, MIM# 617527; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3025 PLAA Zornitza Stark Marked gene: PLAA as ready
Fetal anomalies v0.3025 PLAA Zornitza Stark Gene: plaa has been classified as Green List (High Evidence).
Fetal anomalies v0.3025 PLAA Zornitza Stark Phenotypes for gene: PLAA were changed from Lethal Infantile Epileptic Encephalopathy to Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, MIM# 617527
Fetal anomalies v0.3024 PLAA Zornitza Stark Publications for gene: PLAA were set to
Fetal anomalies v0.3023 PLAA Zornitza Stark Classified gene: PLAA as Green List (high evidence)
Fetal anomalies v0.3023 PLAA Zornitza Stark Gene: plaa has been classified as Green List (High Evidence).
Fetal anomalies v0.3022 PLAA Zornitza Stark changed review comment from: NDMSBA is an autosomal recessive neurodevelopmental disorder characterized by infantile onset of progressive microcephaly and spasticity and severe global developmental delay resulting in profound mental retardation and severely impaired or absent motor function. More variable features include seizures and optic atrophy. Brain imaging may show myelinating abnormalities and white matter lesions consistent with a leukoencephalopathy, as well as structural anomalies, including thin corpus callosum, gyral abnormalities, and cerebral or cerebellar atrophy.

At least 5 families reported.; to: NDMSBA is an autosomal recessive neurodevelopmental disorder characterized by infantile onset of progressive microcephaly and spasticity and severe global developmental delay resulting in profound mental retardation and severely impaired or absent motor function. More variable features include seizures and optic atrophy. Brain imaging may show myelinating abnormalities and white matter lesions consistent with a leukoencephalopathy, as well as structural anomalies, including thin corpus callosum, gyral abnormalities, and cerebral or cerebellar atrophy.

At least 5 families reported. Mouse model.
Fetal anomalies v0.3022 PLAA Zornitza Stark edited their review of gene: PLAA: Changed rating: GREEN
Fetal anomalies v0.3022 PLAA Zornitza Stark reviewed gene: PLAA: Rating: ; Mode of pathogenicity: None; Publications: 28007986, 28413018, 31322726; Phenotypes: Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, MIM# 617527; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3022 PIK3C2A Zornitza Stark Marked gene: PIK3C2A as ready
Fetal anomalies v0.3022 PIK3C2A Zornitza Stark Gene: pik3c2a has been classified as Green List (High Evidence).
Fetal anomalies v0.3022 PIK3C2A Zornitza Stark Publications for gene: PIK3C2A were set to
Fetal anomalies v0.3021 PIK3C2A Zornitza Stark Classified gene: PIK3C2A as Green List (high evidence)
Fetal anomalies v0.3021 PIK3C2A Zornitza Stark Gene: pik3c2a has been classified as Green List (High Evidence).
Fetal anomalies v0.3020 PIK3C2A Zornitza Stark changed review comment from: Three unrelated families, ID is part of the phenotype.
Sources: Expert list; to: Three unrelated families, cataracts and skeletal abnormalities are part of the phenotype.
Sources: Expert list
Fetal anomalies v0.3020 PIH1D3 Zornitza Stark Marked gene: PIH1D3 as ready
Fetal anomalies v0.3020 PIH1D3 Zornitza Stark Gene: pih1d3 has been classified as Green List (High Evidence).
Fetal anomalies v0.3020 PIH1D3 Zornitza Stark Publications for gene: PIH1D3 were set to
Fetal anomalies v0.3019 PIH1D3 Zornitza Stark Classified gene: PIH1D3 as Green List (high evidence)
Fetal anomalies v0.3019 PIH1D3 Zornitza Stark Gene: pih1d3 has been classified as Green List (High Evidence).
Fetal anomalies v0.3018 PIGY Zornitza Stark Marked gene: PIGY as ready
Fetal anomalies v0.3018 PIGY Zornitza Stark Gene: pigy has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3018 PIGY Zornitza Stark Phenotypes for gene: PIGY were changed from Glycosylphosphatidylinositol deficiency to Hyperphosphatasia with mental retardation syndrome 6, MIM# 616809
Fetal anomalies v0.3017 PIGY Zornitza Stark Publications for gene: PIGY were set to
Fetal anomalies v0.3016 PIGY Zornitza Stark changed review comment from: Two unrelated families only; variable phenotype described. One family had a promoter region homozygous variant.; to: Two unrelated families only; variable phenotype described. One family had a promoter region homozygous variant.

Joint contractures, microcephaly, cataracts and other ultrasound-detectable abnormalities reported.
Fetal anomalies v0.3016 PIGN Zornitza Stark Marked gene: PIGN as ready
Fetal anomalies v0.3016 PIGN Zornitza Stark Gene: pign has been classified as Green List (High Evidence).
Fetal anomalies v0.3016 PIGN Zornitza Stark Publications for gene: PIGN were set to
Fetal anomalies v0.3015 PIGN Zornitza Stark Classified gene: PIGN as Green List (high evidence)
Fetal anomalies v0.3015 PIGN Zornitza Stark Gene: pign has been classified as Green List (High Evidence).
Fetal anomalies v0.3014 PIGG Zornitza Stark Marked gene: PIGG as ready
Fetal anomalies v0.3014 PIGG Zornitza Stark Gene: pigg has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3014 PIGG Zornitza Stark Phenotypes for gene: PIGG were changed from Intellectual Disability with Seizures and Hypotonia to Intellectual developmental disorder, autosomal recessive 53, MIM#616917
Fetal anomalies v0.3013 PIGG Zornitza Stark Publications for gene: PIGG were set to
Fetal anomalies v0.3012 PIGG Zornitza Stark changed review comment from: Five patients from 3 unrelated families described with bi-allelic variants in this gene.
Sources: Expert Review; to: Five patients from 3 unrelated families described with bi-allelic variants in this gene.

Some had brain abnormalities (cerebellar atrophy and thin CC): uncertain if this is a consistent/prominent feature of this disorder at present. Otherwise, clinical presentation is typically post-natal.

Sources: Expert Review
Fetal anomalies v0.3012 PIGG Zornitza Stark edited their review of gene: PIGG: Changed phenotypes: Intellectual developmental disorder, autosomal recessive 53, MIM#616917
Fetal anomalies v0.3012 PIGG Zornitza Stark edited their review of gene: PIGG: Changed rating: AMBER
Fetal anomalies v0.3012 PIBF1 Zornitza Stark Marked gene: PIBF1 as ready
Fetal anomalies v0.3012 PIBF1 Zornitza Stark Gene: pibf1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3012 PIBF1 Zornitza Stark Publications for gene: PIBF1 were set to
Fetal anomalies v0.3011 PIBF1 Zornitza Stark Classified gene: PIBF1 as Green List (high evidence)
Fetal anomalies v0.3011 PIBF1 Zornitza Stark Gene: pibf1 has been classified as Green List (High Evidence).
Fetal anomalies v0.3010 PHF21A Zornitza Stark Marked gene: PHF21A as ready
Fetal anomalies v0.3010 PHF21A Zornitza Stark Gene: phf21a has been classified as Green List (High Evidence).
Fetal anomalies v0.3010 PHF21A Zornitza Stark Phenotypes for gene: PHF21A were changed from POTOCKI-SHAFFER SYNDROME to Intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures, MIIM# 618725
Fetal anomalies v0.3009 PHF21A Zornitza Stark Publications for gene: PHF21A were set to
Fetal anomalies v0.3008 PHF21A Zornitza Stark Mode of inheritance for gene: PHF21A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3007 PHF21A Zornitza Stark Classified gene: PHF21A as Green List (high evidence)
Fetal anomalies v0.3007 PHF21A Zornitza Stark Gene: phf21a has been classified as Green List (High Evidence).
Fetal anomalies v0.3006 PHF21A Zornitza Stark changed review comment from: Macrocephaly at birth.; to: Macrosomia at birth.
Fetal anomalies v0.3006 PHF21A Zornitza Stark commented on gene: PHF21A: Macrocephaly at birth.
Fetal anomalies v0.3006 PGM3 Zornitza Stark edited their review of gene: PGM3: Changed publications: 30578875, 31231132, 33098103, 30157810, 28704707, 28543917, 24931394
Fetal anomalies v0.3006 PGM3 Zornitza Stark changed review comment from: Phosphoglucomutase 3 (PGM3) protein catalyzes the conversion of N-acetyl-d-glucosamine-6-phosphate (GlcNAc-6-P) to N-acetyl-d-glucosamine-1-phosphate (GlcNAc-1-P), which is required for the synthesis of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) an important precursor for protein glycosylation.

Bi-allelic variants in this gene are associated with a primary immunodeficiency syndrome characterised by onset of recurrent infections, usually respiratory or cutaneous, in early childhood. Immune workup usually shows neutropenia, lymphopenia, eosinophilia, and increased serum IgE or IgA. Neutrophil chemotactic defects have also been reported. Infectious agents include bacteria, viruses, and fungi. Many patients develop atopic dermatitis, eczema, and other signs of autoinflammation. Affected individuals may also show developmental delay or cognitive impairment of varying severity.

More than 10 unrelated families reported.

Typically presents post-natally.; to: Phosphoglucomutase 3 (PGM3) protein catalyzes the conversion of N-acetyl-d-glucosamine-6-phosphate (GlcNAc-6-P) to N-acetyl-d-glucosamine-1-phosphate (GlcNAc-1-P), which is required for the synthesis of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) an important precursor for protein glycosylation.

Bi-allelic variants in this gene are associated with a primary immunodeficiency syndrome characterised by onset of recurrent infections, usually respiratory or cutaneous, in early childhood. Immune workup usually shows neutropenia, lymphopenia, eosinophilia, and increased serum IgE or IgA. Neutrophil chemotactic defects have also been reported. Infectious agents include bacteria, viruses, and fungi. Many patients develop atopic dermatitis, eczema, and other signs of autoinflammation. Affected individuals may also show developmental delay or cognitive impairment of varying severity.

More than 10 unrelated families reported.

Typically presents post-natally. However, more severe presentations with skeletal abnormalities and congenital malformations reported in PMID 28543917 and 24931394.
Fetal anomalies v0.3006 PGM3 Zornitza Stark edited their review of gene: PGM3: Changed publications: 30578875, 31231132, 33098103, 30157810, 28704707, 28543917 24931394
Fetal anomalies v0.3006 PGM3 Zornitza Stark edited their review of gene: PGM3: Changed rating: AMBER
Fetal anomalies v0.3006 PGM3 Zornitza Stark Classified gene: PGM3 as Amber List (moderate evidence)
Fetal anomalies v0.3006 PGM3 Zornitza Stark Gene: pgm3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3005 PGM3 Zornitza Stark Marked gene: PGM3 as ready
Fetal anomalies v0.3005 PGM3 Zornitza Stark Gene: pgm3 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3005 PGM3 Zornitza Stark Publications for gene: PGM3 were set to 28543917; 24931394
Fetal anomalies v0.3004 PGM3 Zornitza Stark Classified gene: PGM3 as Red List (low evidence)
Fetal anomalies v0.3004 PGM3 Zornitza Stark Gene: pgm3 has been classified as Red List (Low Evidence).
Fetal anomalies v0.3003 PGM3 Zornitza Stark changed review comment from: Phosphoglucomutase 3 (PGM3) protein catalyzes the conversion of N-acetyl-d-glucosamine-6-phosphate (GlcNAc-6-P) to N-acetyl-d-glucosamine-1-phosphate (GlcNAc-1-P), which is required for the synthesis of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) an important precursor for protein glycosylation.

Bi-allelic variants in this gene are associated with a primary immunodeficiency syndrome characterised by onset of recurrent infections, usually respiratory or cutaneous, in early childhood. Immune workup usually shows neutropenia, lymphopenia, eosinophilia, and increased serum IgE or IgA. Neutrophil chemotactic defects have also been reported. Infectious agents include bacteria, viruses, and fungi. Many patients develop atopic dermatitis, eczema, and other signs of autoinflammation. Affected individuals may also show developmental delay or cognitive impairment of varying severity.

More than 10 unrelated families reported.; to: Phosphoglucomutase 3 (PGM3) protein catalyzes the conversion of N-acetyl-d-glucosamine-6-phosphate (GlcNAc-6-P) to N-acetyl-d-glucosamine-1-phosphate (GlcNAc-1-P), which is required for the synthesis of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) an important precursor for protein glycosylation.

Bi-allelic variants in this gene are associated with a primary immunodeficiency syndrome characterised by onset of recurrent infections, usually respiratory or cutaneous, in early childhood. Immune workup usually shows neutropenia, lymphopenia, eosinophilia, and increased serum IgE or IgA. Neutrophil chemotactic defects have also been reported. Infectious agents include bacteria, viruses, and fungi. Many patients develop atopic dermatitis, eczema, and other signs of autoinflammation. Affected individuals may also show developmental delay or cognitive impairment of varying severity.

More than 10 unrelated families reported.

Typically presents post-natally.
Fetal anomalies v0.3003 PGM3 Zornitza Stark edited their review of gene: PGM3: Changed rating: RED
Intellectual disability syndromic and non-syndromic v0.4477 PGAP1 Zornitza Stark Marked gene: PGAP1 as ready
Intellectual disability syndromic and non-syndromic v0.4477 PGAP1 Zornitza Stark Gene: pgap1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4477 PGAP1 Zornitza Stark Phenotypes for gene: PGAP1 were changed from to Neurodevelopmental disorder with dysmorphic features, spasticity, and brain abnormalities, MIM# 615802
Intellectual disability syndromic and non-syndromic v0.4476 PGAP1 Zornitza Stark Publications for gene: PGAP1 were set to
Intellectual disability syndromic and non-syndromic v0.4475 PGAP1 Zornitza Stark Mode of inheritance for gene: PGAP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4474 PGAP1 Zornitza Stark reviewed gene: PGAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24482476, 24784135, 25823418, 25804403, 26050939; Phenotypes: Neurodevelopmental disorder with dysmorphic features, spasticity, and brain abnormalities, MIM# 615802; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10817 PGAP1 Zornitza Stark Marked gene: PGAP1 as ready
Mendeliome v0.10817 PGAP1 Zornitza Stark Gene: pgap1 has been classified as Green List (High Evidence).
Mendeliome v0.10817 PGAP1 Zornitza Stark Phenotypes for gene: PGAP1 were changed from to Neurodevelopmental disorder with dysmorphic features, spasticity, and brain abnormalities, MIM# 615802
Mendeliome v0.10816 PGAP1 Zornitza Stark Publications for gene: PGAP1 were set to
Mendeliome v0.10815 PGAP1 Zornitza Stark Mode of inheritance for gene: PGAP1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10814 PGAP1 Zornitza Stark reviewed gene: PGAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24482476, 24784135, 25823418, 25804403, 26050939; Phenotypes: Neurodevelopmental disorder with dysmorphic features, spasticity, and brain abnormalities, MIM# 615802; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3003 WDR26 Seb Lunke Marked gene: WDR26 as ready
Fetal anomalies v0.3003 WDR26 Seb Lunke Gene: wdr26 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3003 WDR26 Seb Lunke Phenotypes for gene: WDR26 were changed from Intellectual Disability, Seizures, Abnormal Gait, and Distinctive Facial Features to Skraban-Deardorff syndrome, MIM#617616; Intellectual Disability, Seizures, Abnormal Gait, and Distinctive Facial Features
Fetal anomalies v0.3002 WDR26 Seb Lunke Publications for gene: WDR26 were set to
Fetal anomalies v0.3001 WDR26 Seb Lunke Classified gene: WDR26 as Amber List (moderate evidence)
Fetal anomalies v0.3001 WDR26 Seb Lunke Added comment: Comment on list classification: Craniofacial features to subtle for US, brain abnormalities are not always present and also subtle.
Fetal anomalies v0.3001 WDR26 Seb Lunke Gene: wdr26 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.3000 WDR34 Seb Lunke Marked gene: WDR34 as ready
Fetal anomalies v0.3000 WDR34 Seb Lunke Gene: wdr34 has been classified as Green List (High Evidence).
Fetal anomalies v0.3000 WDR34 Seb Lunke Phenotypes for gene: WDR34 were changed from SHORT-RIB POLYDACTYLY SYNDROME TYPE III; SEVERE ASPHYXIATING THORACIC DYSPLASIA to Short-rib thoracic dysplasia 11 with or without polydactyly, MIM# 615633
Fetal anomalies v0.2999 WDR34 Seb Lunke Publications for gene: WDR34 were set to
Fetal anomalies v0.2998 WDR35 Seb Lunke Marked gene: WDR35 as ready
Fetal anomalies v0.2998 WDR35 Seb Lunke Gene: wdr35 has been classified as Green List (High Evidence).
Fetal anomalies v0.2998 WDR35 Seb Lunke Publications for gene: WDR35 were set to
Fetal anomalies v0.2997 WDR35 Seb Lunke Phenotypes for gene: WDR35 were changed from CRANIOECTODERMAL DYSPLASIA 2; SHORT RIB-POLYDACTYLY SYNDROME, TYPE V to Short-rib thoracic dysplasia 7 with or without polydactyly, MIM#614091; MONDO:0013569
Fetal anomalies v0.2996 WDR60 Seb Lunke Marked gene: WDR60 as ready
Fetal anomalies v0.2996 WDR60 Seb Lunke Gene: wdr60 has been classified as Green List (High Evidence).
Fetal anomalies v0.2996 WDR60 Seb Lunke Publications for gene: WDR60 were set to
Fetal anomalies v0.2995 WDR60 Seb Lunke Phenotypes for gene: WDR60 were changed from SHORT-RIB POLYDACTYLY; JEUNE SYNDROMES to Short-rib thoracic dysplasia 8 with or without polydactyly, MIM# 615503
Fetal anomalies v0.2994 WDR62 Seb Lunke Marked gene: WDR62 as ready
Fetal anomalies v0.2994 WDR62 Seb Lunke Gene: wdr62 has been classified as Green List (High Evidence).
Fetal anomalies v0.2994 WDR62 Seb Lunke Phenotypes for gene: WDR62 were changed from MICROCEPHALY CORTICAL MALFORMATIONS AND MENTAL RETARDATION to Microcephaly 2, primary, autosomal recessive, with or without cortical malformations, MIM# 604317; MONDO:0011435
Fetal anomalies v0.2993 PDE6D Krithika Murali gene: PDE6D was added
gene: PDE6D was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PDE6D was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDE6D were set to 30423442; 24166846
Phenotypes for gene: PDE6D were set to Joubert syndrome 22 - MIM#615665
Review for gene: PDE6D was set to GREEN
Added comment: Biallelic variants associated with Joubert syndrome identified in 2 families. Antenatal detection possible.

30423442 Megarbane et al 2018
Report homozygous truncating PDE6D variant in a male infant with post-axial polydactyly noted at birth on all extremities. Brain MRI at 6 months of age showed cerebellar vermis agenesis, hypoplastic corpus callosum, cortical atrophy of the temporal lobes and molar tooth sign.

PMID 24166846 Thomas et al 2014 report a consanguineous family with three affected and 2 healthy sibs. Features noted in both liveborn children:
- 1/2 IUGR
- 1/2 facial dysmorphism
- 2/2 postaxial polydactyly
- 1/2 syndactyly
- 1/2 renal hypoplasia
- 2/2 microphthalmia
- 1/2 supportive MRI-B features
- 1/2 coloboma

3rd sibling is a male fetus terminated at 14 weeks gestation following findings of brain anomalies and polydactyly.

Supportive animal models
Sources: Literature
Fetal anomalies v0.2993 NPM1 Krithika Murali gene: NPM1 was added
gene: NPM1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: NPM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NPM1 were set to 31570891
Phenotypes for gene: NPM1 were set to Dyskeratosis congenita
Review for gene: NPM1 was set to AMBER
Added comment: Heterozygous variants identified in 2 patients with dyskeratosis congenita (DKC).

x1 patient with NPM1 missense mutation presented with severe growth defects at birth, thumb abnormalities and thrombocytopenia.

x1 patient with in-frame NPM1 deletion presented with skin pigmentation abnormalities, nail dystrophy, microcephaly, developmental delay, short stature, skeletal abnormalities in the
radius and bone marrow failure by age 6.

Some of these features may be amenable to antenatal detection.
Sources: Literature
Fetal anomalies v0.2993 PGAP1 Zornitza Stark Marked gene: PGAP1 as ready
Fetal anomalies v0.2993 PGAP1 Zornitza Stark Gene: pgap1 has been classified as Green List (High Evidence).
Fetal anomalies v0.2993 PGAP1 Zornitza Stark Phenotypes for gene: PGAP1 were changed from Intellectual disability, encephalopathy, impaired GPI-anchor maturation to Neurodevelopmental disorder with dysmorphic features, spasticity, and brain abnormalities, MIM# 615802
Fetal anomalies v0.2992 PGAP1 Zornitza Stark Publications for gene: PGAP1 were set to
Fetal anomalies v0.2991 PGAP1 Zornitza Stark Classified gene: PGAP1 as Green List (high evidence)
Fetal anomalies v0.2991 PGAP1 Zornitza Stark Gene: pgap1 has been classified as Green List (High Evidence).
Fetal anomalies v0.2990 PGAP1 Zornitza Stark reviewed gene: PGAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24482476, 24784135, 25823418, 25804403, 26050939; Phenotypes: Neurodevelopmental disorder with dysmorphic features, spasticity, and brain abnormalities, MIM# 615802; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.2990 PET100 Zornitza Stark Marked gene: PET100 as ready
Fetal anomalies v0.2990 PET100 Zornitza Stark Gene: pet100 has been classified as Green List (High Evidence).
Fetal anomalies v0.2990 PET100 Zornitza Stark Phenotypes for gene: PET100 were changed from MITOCHONDRIAL COMPLEX IV DEFICIENCY to Mitochondrial complex IV deficiency, nuclear type 12, MIM# 619055
Fetal anomalies v0.2989 PET100 Zornitza Stark Publications for gene: PET100 were set to
Fetal anomalies v0.2988 PET100 Zornitza Stark Classified gene: PET100 as Green List (high evidence)
Fetal anomalies v0.2988 PET100 Zornitza Stark Gene: pet100 has been classified as Green List (High Evidence).
Fetal anomalies v0.2987 PET100 Zornitza Stark changed review comment from: Founder effect in 6 Australian families of Lebanese origin (M1?) reported originally; functional data. Second family with different variants also reported; and another 2 Lebanese families with same founder variant.; to: Founder effect in 6 Australian families of Lebanese origin (M1?) reported originally; functional data. Second family with different variants also reported; and another 2 Lebanese families with same founder variant.

IUGR is a feature.
Fetal anomalies v0.2987 PDSS1 Zornitza Stark Marked gene: PDSS1 as ready
Fetal anomalies v0.2987 PDSS1 Zornitza Stark Gene: pdss1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.2987 PDSS1 Zornitza Stark Phenotypes for gene: PDSS1 were changed from COENZYME Q10 DEFICIENCY, PRIMARY, 2 to Coenzyme Q10 deficiency, primary, 2 MIM#614651
Fetal anomalies v0.2986 PDSS1 Zornitza Stark Publications for gene: PDSS1 were set to
Fetal anomalies v0.2985 PDSS1 Zornitza Stark Classified gene: PDSS1 as Red List (low evidence)
Fetal anomalies v0.2985 PDSS1 Zornitza Stark Gene: pdss1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.2984 PDSS1 Zornitza Stark reviewed gene: PDSS1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Coenzyme Q10 deficiency, primary, 2 MIM#614651; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.2984 PDE10A Zornitza Stark Marked gene: PDE10A as ready
Fetal anomalies v0.2984 PDE10A Zornitza Stark Gene: pde10a has been classified as Red List (Low Evidence).
Fetal anomalies v0.2984 PDE10A Zornitza Stark Phenotypes for gene: PDE10A were changed from Childhood-Onset Chorea with Bilateral Striatal Lesions to Dyskinesia, limb and orofacial, infantile-onset, MIM#616921; Striatal degeneration, autosomal dominant, MIM#616922
Fetal anomalies v0.2983 PDE10A Zornitza Stark Publications for gene: PDE10A were set to
Fetal anomalies v0.2982 PDE10A Zornitza Stark Mode of inheritance for gene: PDE10A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.2981 PDE10A Zornitza Stark Classified gene: PDE10A as Red List (low evidence)
Fetal anomalies v0.2981 PDE10A Zornitza Stark Gene: pde10a has been classified as Red List (Low Evidence).
Fetal anomalies v0.2980 PDE10A Zornitza Stark Deleted their comment
Fetal anomalies v0.2980 PDE10A Zornitza Stark Deleted their comment
Fetal anomalies v0.2980 PDE10A Zornitza Stark edited their review of gene: PDE10A: Added comment: Both disorders typically present post-natally.; Changed rating: RED; Changed phenotypes: Dyskinesia, limb and orofacial, infantile-onset, MIM#616921, Striatal degeneration, autosomal dominant, MIM#616922; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.2980 Zornitza Stark removed gene:PDE6H from the panel
Fetal anomalies v0.2979 PAICS Zornitza Stark Marked gene: PAICS as ready
Fetal anomalies v0.2979 PAICS Zornitza Stark Gene: paics has been classified as Red List (Low Evidence).
Fetal anomalies v0.2979 PAICS Zornitza Stark Classified gene: PAICS as Red List (low evidence)
Fetal anomalies v0.2979 PAICS Zornitza Stark Gene: paics has been classified as Red List (Low Evidence).
Fetal anomalies v0.2978 PAICS Zornitza Stark reviewed gene: PAICS: Rating: RED; Mode of pathogenicity: None; Publications: 31600779; Phenotypes: Polyhydramnios, multiple congenital abnormalities; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.2978 PACS1 Zornitza Stark Marked gene: PACS1 as ready
Fetal anomalies v0.2978 PACS1 Zornitza Stark Gene: pacs1 has been classified as Green List (High Evidence).
Fetal anomalies v0.2978 PACS1 Zornitza Stark Phenotypes for gene: PACS1 were changed from INTELLECTUAL DISABILITY to Schuurs-Hoeijmakers syndrome (MIM# 615009)
Fetal anomalies v0.2977 PACS1 Zornitza Stark Publications for gene: PACS1 were set to 30712880
Fetal anomalies v0.2976 PACS1 Zornitza Stark Mode of inheritance for gene: PACS1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.2975 KIAA0825 Krithika Murali gene: KIAA0825 was added
gene: KIAA0825 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: KIAA0825 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA0825 were set to 33776623; 32147526; 30982135
Phenotypes for gene: KIAA0825 were set to Polydactyly, postaxial, type A10 - MIM#618498
Review for gene: KIAA0825 was set to GREEN
Added comment: 4 families of Pakistani/Sindhi origin reported with post-axial polydactyly
Sources: Literature
Fetal anomalies v0.2975 PACS1 Zornitza Stark Classified gene: PACS1 as Green List (high evidence)
Fetal anomalies v0.2975 PACS1 Zornitza Stark Gene: pacs1 has been classified as Green List (High Evidence).
Fetal anomalies v0.2974 PACS1 Zornitza Stark changed review comment from: Multiple individuals reported with recurrent p.Arg203Trp variant; in vitro assays is suggestive of dominant-negative disease mechanism; to: Multiple individuals reported with recurrent p.Arg203Trp variant; in vitro assays is suggestive of dominant-negative disease mechanism

Brain, cardiac and renal abnormalities reported.
Fetal anomalies v0.2974 P4HB Zornitza Stark Marked gene: P4HB as ready
Fetal anomalies v0.2974 P4HB Zornitza Stark Gene: p4hb has been classified as Green List (High Evidence).
Fetal anomalies v0.2974 P4HB Zornitza Stark Publications for gene: P4HB were set to
Fetal anomalies v0.2973 P4HB Zornitza Stark Mode of inheritance for gene: P4HB was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.2972 P4HB Zornitza Stark Classified gene: P4HB as Green List (high evidence)
Fetal anomalies v0.2972 P4HB Zornitza Stark Gene: p4hb has been classified as Green List (High Evidence).
Fetal anomalies v0.2971 OTUD5 Zornitza Stark Marked gene: OTUD5 as ready
Fetal anomalies v0.2971 OTUD5 Zornitza Stark Gene: otud5 has been classified as Green List (High Evidence).
Fetal anomalies v0.2971 OTUD5 Zornitza Stark Classified gene: OTUD5 as Green List (high evidence)
Fetal anomalies v0.2971 OTUD5 Zornitza Stark Gene: otud5 has been classified as Green List (High Evidence).
Fetal anomalies v0.2970 IQCE Krithika Murali gene: IQCE was added
gene: IQCE was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: IQCE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IQCE were set to 31549751; 28488682
Phenotypes for gene: IQCE were set to Polydactyly, postaxial, type A7 - MIM#617642
Review for gene: IQCE was set to GREEN
Added comment: Known association with polydactyly, syndactyly and brachydactyly.
Sources: Literature
Fetal anomalies v0.2970 IFT27 Krithika Murali gene: IFT27 was added
gene: IFT27 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: IFT27 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFT27 were set to 24488770; 30761183; 26763875; 25443296
Phenotypes for gene: IFT27 were set to Bardet-Biedl syndrome 19-MIM#615996
Review for gene: IFT27 was set to GREEN
Added comment: Biallelic variants associated with Bardet-Biedl syndrome. Phenotypic features detectable antenatally include polydactyly, cardiac and brain anomalies also reported.
Sources: Literature
Fetal anomalies v0.2970 HMGB1 Krithika Murali gene: HMGB1 was added
gene: HMGB1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: HMGB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HMGB1 were set to 34164801
Phenotypes for gene: HMGB1 were set to microcephaly; intellectual disability
Review for gene: HMGB1 was set to GREEN
Added comment: 34164801 Uguen et al 2021 report 6 unrelated individuals with LoF HMGB1 variants associated with syndromic ID. 4 individuals reported to have microcephaly - majority noted to have microcephaly at birth +/- growth restriction.
Sources: Literature
Fetal anomalies v0.2970 FAM92A Krithika Murali gene: FAM92A was added
gene: FAM92A was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: FAM92A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM92A were set to 30395363
Phenotypes for gene: FAM92A were set to Polydactyly, postaxial, type A9 - MIM#618219
Review for gene: FAM92A was set to AMBER
Added comment: 30395363 - homozygous nonsense variants in FAM92A segregated with postaxial polydactyly in x1 consanguineous Parkistani family. Supportive mouse model reported.
Sources: Literature
Fetal anomalies v0.2970 OSGEP Zornitza Stark Marked gene: OSGEP as ready
Fetal anomalies v0.2970 OSGEP Zornitza Stark Gene: osgep has been classified as Green List (High Evidence).
Fetal anomalies v0.2970 OSGEP Zornitza Stark Publications for gene: OSGEP were set to
Fetal anomalies v0.2969 OSGEP Zornitza Stark Classified gene: OSGEP as Green List (high evidence)
Fetal anomalies v0.2969 OSGEP Zornitza Stark Gene: osgep has been classified as Green List (High Evidence).
Fetal anomalies v0.2968 OSGEP Zornitza Stark changed review comment from: 25 families reported.
Sources: Expert list; to: 25 families reported. IUGR and oligohydramnios are a feature.
Sources: Expert list
Fetal anomalies v0.2968 NUS1 Zornitza Stark Marked gene: NUS1 as ready
Fetal anomalies v0.2968 NUS1 Zornitza Stark Gene: nus1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.2968 NUS1 Zornitza Stark Publications for gene: NUS1 were set to 31656175; 29100083; 610463; 25066056
Fetal anomalies v0.2967 NUS1 Zornitza Stark Phenotypes for gene: NUS1 were changed from Epilepsy and intellectual disability to Congenital disorder of glycosylation, type 1aa, MIM#617082
Fetal anomalies v0.2966 NUS1 Zornitza Stark Publications for gene: NUS1 were set to
Fetal anomalies v0.2965 NUS1 Zornitza Stark Mode of inheritance for gene: NUS1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.2964 NUS1 Zornitza Stark edited their review of gene: NUS1: Added comment: The CDG disorder caused by bi-allelic variants in this gene has iUGR as a feature. Note limited reports (one published, one ClinVar).

The DEE disorder associated with mono-allelic variants typically presents post-natally.; Changed rating: AMBER; Changed phenotypes: Congenital disorder of glycosylation, type 1aa; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.2964 NUP88 Zornitza Stark Marked gene: NUP88 as ready
Fetal anomalies v0.2964 NUP88 Zornitza Stark Gene: nup88 has been classified as Green List (High Evidence).
Fetal anomalies v0.2964 NUP88 Zornitza Stark Classified gene: NUP88 as Green List (high evidence)
Fetal anomalies v0.2964 NUP88 Zornitza Stark Gene: nup88 has been classified as Green List (High Evidence).
Fetal anomalies v0.2963 NUP62 Zornitza Stark Marked gene: NUP62 as ready
Fetal anomalies v0.2963 NUP62 Zornitza Stark Gene: nup62 has been classified as Red List (Low Evidence).
Fetal anomalies v0.2963 NUP62 Zornitza Stark Phenotypes for gene: NUP62 were changed from INFANTILE STRIATONIGRAL DEGENERATION to Striatonigral degeneration, infantile, MIM#271930
Fetal anomalies v0.2962 NUP62 Zornitza Stark Classified gene: NUP62 as Red List (low evidence)
Fetal anomalies v0.2962 NUP62 Zornitza Stark Gene: nup62 has been classified as Red List (Low Evidence).
Fetal anomalies v0.2961 NUP62 Zornitza Stark changed review comment from: A neurodegenerative disorder rather than ID.; to: A neurodegenerative disorder with post-natal onset.
Fetal anomalies v0.2961 NTRK2 Zornitza Stark Marked gene: NTRK2 as ready
Fetal anomalies v0.2961 NTRK2 Zornitza Stark Gene: ntrk2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.2961 NTRK2 Zornitza Stark Phenotypes for gene: NTRK2 were changed from Epilepsy and intellectual disability to Obesity, hyperphagia, and developmental delay, MIM# 613886; Developmental and epileptic encephalopathy 58, MIM# 617830
Fetal anomalies v0.2960 NTRK2 Zornitza Stark Publications for gene: NTRK2 were set to
Fetal anomalies v0.2959 NTRK2 Zornitza Stark Mode of inheritance for gene: NTRK2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.2958 NTRK2 Zornitza Stark Classified gene: NTRK2 as Red List (low evidence)
Fetal anomalies v0.2958 NTRK2 Zornitza Stark Gene: ntrk2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.2957 NTRK2 Zornitza Stark changed review comment from: Three unrelated individuals reported with this phenotype.
Note recurrent missense in this gene also causes EE.
Sources: Expert list; to: Clinical presentation for both disorders is typically post-natal.

Sources: Expert list
Fetal anomalies v0.2957 NTRK2 Zornitza Stark edited their review of gene: NTRK2: Changed rating: RED; Changed phenotypes: Obesity, hyperphagia, and developmental delay, MIM# 613886, Developmental and epileptic encephalopathy 58, MIM# 617830
Fetal anomalies v0.2957 NSUN2 Zornitza Stark Marked gene: NSUN2 as ready
Fetal anomalies v0.2957 NSUN2 Zornitza Stark Gene: nsun2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.2957 NSUN2 Zornitza Stark Phenotypes for gene: NSUN2 were changed from AUTOSOMAL- RECESSIVE INTELLECTUAL DISABILITY MRT5 to Mental retardation, autosomal recessive 5, MIM# 611091
Fetal anomalies v0.2956 NSUN2 Zornitza Stark Publications for gene: NSUN2 were set to
Fetal anomalies v0.2955 NSUN2 Zornitza Stark edited their review of gene: NSUN2: Added comment: Low birth weight reported. Microcephaly also reported, age of onset unclear.; Changed rating: AMBER; Changed publications: 22541559, 22541562, 22577224
Fetal anomalies v0.2955 NRXN2 Zornitza Stark Marked gene: NRXN2 as ready
Fetal anomalies v0.2955 NRXN2 Zornitza Stark Gene: nrxn2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.2955 NRXN2 Zornitza Stark Phenotypes for gene: NRXN2 were changed from AUTISM to Autism
Fetal anomalies v0.2954 NRXN2 Zornitza Stark Publications for gene: NRXN2 were set to
Fetal anomalies v0.2953 NRXN2 Zornitza Stark Mode of inheritance for gene: NRXN2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.2952 NRXN2 Zornitza Stark Classified gene: NRXN2 as Red List (low evidence)
Fetal anomalies v0.2952 NRXN2 Zornitza Stark Gene: nrxn2 has been classified as Red List (Low Evidence).
Ataxia - paediatric v0.323 KCNN2 Zornitza Stark Phenotypes for gene: KCNN2 were changed from Neurodevelopmental disorder; Ataxia to Neurodevelopmental disorder with or without variable movement or behavioural abnormalities, MIM#619725
Ataxia - paediatric v0.322 KCNN2 Zornitza Stark reviewed gene: KCNN2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with or without variable movement or behavioural abnormalities, MIM#619725; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4474 KCNN2 Zornitza Stark Phenotypes for gene: KCNN2 were changed from Neurodevelopmental movement disorders; Developmental Delay; Seizures to Neurodevelopmental disorder with or without variable movement or behavioural abnormalities, MIM#619725
Intellectual disability syndromic and non-syndromic v0.4473 KCNN2 Zornitza Stark Mode of inheritance for gene: KCNN2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4472 KCNN2 Zornitza Stark reviewed gene: KCNN2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with or without variable movement or behavioural abnormalities, MIM#619725; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1436 KCNN2 Zornitza Stark Phenotypes for gene: KCNN2 were changed from Neurological Disorder; Developmental Delay; Seizures to Neurodevelopmental disorder with or without variable movement or behavioural abnormalities, MIM#619725
Genetic Epilepsy v0.1435 KCNN2 Zornitza Stark Mode of inheritance for gene: KCNN2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1434 KCNN2 Zornitza Stark reviewed gene: KCNN2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with or without variable movement or behavioural abnormalities, MIM#619725; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10814 KCNN2 Zornitza Stark Phenotypes for gene: KCNN2 were changed from Neurodevelopmental movement disorders; Developmental Delay; Seizures to Neurodevelopmental disorder with or without variable movement or behavioural abnormalities, MIM#619725
Mendeliome v0.10813 KCNN2 Zornitza Stark edited their review of gene: KCNN2: Changed phenotypes: Neurodevelopmental disorder with or without variable movement or behavioural abnormalities, MIM#619725
Mendeliome v0.10813 KCNN2 Zornitza Stark reviewed gene: KCNN2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with or without variable movement or behavioral abnormalities, MIM#619725; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4472 NAA20 Zornitza Stark Phenotypes for gene: NAA20 were changed from Autosomal recessive developmental delay, intellectual disability, and microcephaly to Intellectual developmental disorder, autosomal recessive 73, MIM# 619717
Intellectual disability syndromic and non-syndromic v0.4471 NAA20 Zornitza Stark edited their review of gene: NAA20: Changed phenotypes: Intellectual developmental disorder, autosomal recessive 73, MIM# 619717
Microcephaly v1.96 NAA20 Zornitza Stark Marked gene: NAA20 as ready
Microcephaly v1.96 NAA20 Zornitza Stark Gene: naa20 has been classified as Green List (High Evidence).
Microcephaly v1.96 NAA20 Zornitza Stark Phenotypes for gene: NAA20 were changed from Autosomal recessive developmental delay, intellectual disability, and microcephaly to Intellectual developmental disorder, autosomal recessive 73, MIM# 619717
Microcephaly v1.95 NAA20 Zornitza Stark reviewed gene: NAA20: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal recessive 73, MIM# 619717; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.2951 PDSS2 Ain Roesley reviewed gene: PDSS2: Rating: RED; Mode of pathogenicity: None; Publications: 29032433, 25349199, 17186472, 21723727, 10972372; Phenotypes: Coenzyme Q10 deficiency, primary, 3 MIM#614652; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10813 PDSS2 Ain Roesley reviewed gene: PDSS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29032433, 25349199, 17186472, 21723727, 10972372; Phenotypes: Coenzyme Q10 deficiency, primary, 3 MIM#614652; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10813 NAA20 Zornitza Stark Phenotypes for gene: NAA20 were changed from Intellectual disability; Microcephaly; Neurodevelopmental disorder MONDO:0700092 to Intellectual developmental disorder, autosomal recessive 73, MIM# 619717
Mendeliome v0.10812 NAA20 Zornitza Stark edited their review of gene: NAA20: Changed phenotypes: Intellectual developmental disorder, autosomal recessive 73, MIM# 619717
Mendeliome v0.10812 PDHX Ain Roesley edited their review of gene: PDHX: Changed rating: GREEN
Fetal anomalies v0.2951 NDUFV1 Ain Roesley edited their review of gene: NDUFV1: Changed rating: RED
Fetal anomalies v0.2951 PDHX Ain Roesley reviewed gene: PDHX: Rating: AMBER; Mode of pathogenicity: None; Publications: 20002125 34873726 33092611 30981218 25087164 22766002; Phenotypes: Lacticacidemia due to PDX1 deficiency MIM#245349; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10812 PDHX Ain Roesley changed review comment from: >10 unrelated probands reported

PDHX c.1336C>T (p.Arg446Ter) is a Roma founder variant; c.1182+2T>C (p.Ile386SerfsTer13) is a Moroccan founder variant.; to: established gene-disease association

PDHX c.1336C>T (p.Arg446Ter) is a Roma founder variant; c.1182+2T>C (p.Ile386SerfsTer13) is a Moroccan founder variant.
Mendeliome v0.10812 PDHX Ain Roesley reviewed gene: PDHX: Rating: ; Mode of pathogenicity: None; Publications: 20002125, 34873726, 33092611, 30981218, 25087164, 22766002; Phenotypes: Lacticacidemia due to PDX1 deficiency MIM#245349; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.2951 TRRAP Krithika Murali gene: TRRAP was added
gene: TRRAP was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: TRRAP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRRAP were set to 30827496
Phenotypes for gene: TRRAP were set to Developmental delay with or without dysmorphic facies and autism- #618454; multiple congenital anomalies
Review for gene: TRRAP was set to GREEN
Added comment: 13 unrelated individuals reported with a complex syndromic neurodevelopmental disorder associated with malformations that can be detected antenatally. This includes, brain, heart, kidney, urogenital anomalies, abdominal wall hernias, cleft lip/palate
Sources: Literature
Fetal anomalies v0.2951 G6PD Krithika Murali reviewed gene: G6PD: Rating: RED; Mode of pathogenicity: None; Publications: 1316704, 26279483, 18177777, 17825683, 1127504, 7472841; Phenotypes: Haemolytic anaemia, G6PD deficient (300908); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v0.2951 G6PD Krithika Murali Deleted their review
Fetal anomalies v0.2951 G6PD Krithika Murali gene: G6PD was added
gene: G6PD was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: G6PD was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: G6PD were set to 1316704; 26279483; 18177777; 17825683; 1127504; 7472841
Phenotypes for gene: G6PD were set to Haemolytic anaemia, G6PD deficient (300908)
Review for gene: G6PD was set to AMBER
Added comment: Well-known association with G6PD deficiency. Borderline red-amber gene for fetal anomalies. However, as features of anaemia can sometimes be detected in fetus antenatally and therapeutic/maternal trigger avoidance options available, I have favoured amber rating.

PMID: 26279483 Keller et al 2015 - report a mother who is a carrier for a G6PD variant (Guadalajara variant) with a family history of a brother and paternal uncle who died as neonates from severe hydrops. She was counselled to avoid substances that could precipitate oxidative stress from 22 weeks gestation onwards. During her first pregnancy, a male fetus was found to have mild cardiomegaly at 31 weeks with elevated MCAPSV - suggestive of anaemia. Intrauterine transfusion instituted. Presence of maternally inherited G6PD variant confirmed in the fetus.

There are other case reports of hydrops fetalis presumed secondary to G6PD deficiency but evidence is limited..

4999390; 1127504 - older studies, no genomic confirmation available.

4999390 Perkins et al 1971 - Mother presumed to be a carrier for G6PD deficiency and all 3 babies presumed to have the same
- 1st child neonatal jaundice with abnormal G6PD test result and death at 59 days of life from undetermined cause
- 2nd pregnancy - mother given sulfizoxazole for UTI during pregnancy, delivered stillborn infant at 36 weeks with hydrops fetalis and severe anaemia
- 3rd child - well, neonatal jaundice and abnormal G6PD test.

Mother O neg blood group, all three babies +ve blood group, DAT -ve and RhoGam given each pregnancy.

1127504 - Mentzer and Collier et al 1975
Male infant died at 2 hours of life with evidence of haemolysis and autopsy findings of hydrops. G6PD screening test in baby abnormal. Mother had low-normal G6PD activity, abnormal ascorbate cyanide test, abnormal MTT cytochemical however no abnormal migrating band of G6PD activity was present on electrophoresis. URTI episode during pregnancy, ascorbic acid consumption and fava bean consumption noted. G6PD deficiency presumed in mother and infant but not genomically confirmed.

23719252; 24999569 - Two case reports identified. However, a second diagnosis was present in both and the G6PD deficiency may have contributed to severity rather than being the primary factor.
Sources: Literature
Fetal anomalies v0.2951 NT5C3A Ain Roesley reviewed gene: NT5C3A: Rating: RED; Mode of pathogenicity: None; Publications: 11369620, 12714505, 30951028, 25153905; Phenotypes: Anaemia, haemolytic, due to UMPH1 deficiency, MIM# 266120; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.2951 NDUFV1 Ain Roesley reviewed gene: NDUFV1: Rating: ; Mode of pathogenicity: None; Publications: 34807224; Phenotypes: Mitochondrial complex I deficiency, nuclear type 4 MIM#618225; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.2951 MYBPC1 Alison Yeung Marked gene: MYBPC1 as ready
Fetal anomalies v0.2951 MYBPC1 Alison Yeung Gene: mybpc1 has been classified as Green List (High Evidence).
Fetal anomalies v0.2951 MYBPC1 Alison Yeung Phenotypes for gene: MYBPC1 were changed from Arthrogryposis, distal, type 1B 614335; Lethal congenital contracture syndrome 4 614915 to Arthrogryposis, distal, type 1B 614335; Lethal congenital contracture syndrome 4, MIM# 614915
Mendeliome v0.10812 NDUFV1 Ain Roesley reviewed gene: NDUFV1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34807224; Phenotypes: Mitochondrial complex I deficiency, nuclear type 4 MIM#618225; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.2950 MYBPC1 Alison Yeung reviewed gene: MYBPC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Arthrogryposis, distal, type 1B, MIM# 614335, Lethal congenital contracture syndrome 4, MIM# 614915; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.2950 NDUFS8 Ain Roesley reviewed gene: NDUFS8: Rating: RED; Mode of pathogenicity: None; Publications: 23430795, 9837812, 15159508, 22499348, 20818383, 20819849; Phenotypes: Mitochondrial complex I deficiency, nuclear type 2 MIM#618222; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.2950 MUSK Alison Yeung Marked gene: MUSK as ready
Fetal anomalies v0.2950 MUSK Alison Yeung Gene: musk has been classified as Green List (High Evidence).
Fetal anomalies v0.2950 MUSK Alison Yeung Phenotypes for gene: MUSK were changed from Myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency; Fetal akinesia deformation sequence to Fetal akinesia deformation sequence 1, MIM# 208150; MONDO:0100101
Fetal anomalies v0.2949 MUSK Alison Yeung reviewed gene: MUSK: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fetal akinesia deformation sequence 1, MIM# 208150; Mode of inheritance: None
Fetal anomalies v0.2949 MTOR Alison Yeung Marked gene: MTOR as ready
Fetal anomalies v0.2949 MTOR Alison Yeung Gene: mtor has been classified as Green List (High Evidence).
Fetal anomalies v0.2949 MTOR Alison Yeung Phenotypes for gene: MTOR were changed from Smith-Kingsmore syndrome to Smith-Kingsmore syndrome, MIM# 616638
Fetal anomalies v0.2948 MTOR Alison Yeung reviewed gene: MTOR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Smith-Kingsmore syndrome, MIM#616638; Mode of inheritance: None
Mendeliome v0.10812 NDUFS8 Ain Roesley reviewed gene: NDUFS8: Rating: GREEN; Mode of pathogenicity: None; Publications: 23430795, 9837812, 15159508, 22499348, 20818383, 20819849; Phenotypes: Mitochondrial complex I deficiency, nuclear type 2 MIM#618222; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10812 NDUFS7 Ain Roesley reviewed gene: NDUFS7: Rating: GREEN; Mode of pathogenicity: None; Publications: 17604671, 17275378, 10360771; Phenotypes: Mitochondrial complex I deficiency, nuclear type 3 MIM#618224; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.2948 NDUFS7 Ain Roesley reviewed gene: NDUFS7: Rating: RED; Mode of pathogenicity: None; Publications: 17604671, 17275378, 10360771; Phenotypes: Mitochondrial complex I deficiency, nuclear type 3 MIM#618224; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.2948 NDUFS7 Ain Roesley Deleted their review
Mendeliome v0.10812 NDUFAF5 Ain Roesley reviewed gene: NDUFAF5: Rating: GREEN; Mode of pathogenicity: None; Publications: 34797029; Phenotypes: Mitochondrial complex I deficiency, nuclear type 3 MIM#618224; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10812 NDUFS7 Ain Roesley Deleted their review
Mendeliome v0.10812 NDUFS7 Ain Roesley Deleted their comment
Mendeliome v0.10812 NDUFS7 Ain Roesley reviewed gene: NDUFS7: Rating: GREEN; Mode of pathogenicity: None; Publications: 34797029; Phenotypes: Mitochondrial complex I deficiency, nuclear type 3 MIM#618224; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.2948 NDUFS7 Ain Roesley reviewed gene: NDUFS7: Rating: RED; Mode of pathogenicity: None; Publications: 34797029; Phenotypes: Mitochondrial complex I deficiency, nuclear type 3 MIM#618224; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.2948 NDUFA1 Ain Roesley reviewed gene: NDUFA1: Rating: RED; Mode of pathogenicity: None; Publications: 29506883, 19185523, 17262856, 21596602; Phenotypes: Mitochondrial complex I deficiency, nuclear type 12 MIM#301020; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Mendeliome v0.10812 NDUFA1 Ain Roesley reviewed gene: NDUFA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29506883, 19185523, 17262856, 21596602; Phenotypes: Mitochondrial complex I deficiency, nuclear type 12 MIM#301020; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Fetal anomalies v0.2948 MYO5A Ain Roesley reviewed gene: MYO5A: Rating: RED; Mode of pathogenicity: None; Publications: 32275080, 22711375, 25283056; Phenotypes: Griscelli syndrome, type 1 MIM#214450; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10812 MYO5A Ain Roesley reviewed gene: MYO5A: Rating: GREEN; Mode of pathogenicity: None; Publications: 32275080, 22711375, 25283056; Phenotypes: Griscelli syndrome, type 1 MIM#214450; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.2948 LTBP2 Ain Roesley reviewed gene: LTBP2: Rating: RED; Mode of pathogenicity: None; Publications: 19656777, 19361779, 20617341, 32165823, 30380740, 30565850; Phenotypes: Glaucoma 3, primary congenital, D 613086, Microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma, MIM# 251750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.2948 MTO1 Alison Yeung Marked gene: MTO1 as ready
Fetal anomalies v0.2948 MTO1 Alison Yeung Gene: mto1 has been classified as Green List (High Evidence).
Fetal anomalies v0.2948 MTO1 Alison Yeung Phenotypes for gene: MTO1 were changed from INFANTILE HYPERTROPHIC CARDIOMYOPATHY AND LACTIC ACIDOSIS to Combined oxidative phosphorylation deficiency 10, MIM# 61702
Fetal anomalies v0.2947 MTO1 Alison Yeung reviewed gene: MTO1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined oxidative phosphorylation deficiency 10, MIM# 61702; Mode of inheritance: None
Fetal anomalies v0.2947 MSL3 Alison Yeung Marked gene: MSL3 as ready
Fetal anomalies v0.2947 MSL3 Alison Yeung Gene: msl3 has been classified as Green List (High Evidence).
Fetal anomalies v0.2947 MSL3 Alison Yeung Phenotypes for gene: MSL3 were changed from Basilicata-Akhtar syndrome, 301032; MSL3 syndrome to Basilicata-Akhtar syndrome, MIM# 301032
Fetal anomalies v0.2946 MSL3 Alison Yeung reviewed gene: MSL3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Basilicata-Akhtar syndrome, MIM# 301032; Mode of inheritance: None
Fetal anomalies v0.2946 LRPPRC Ain Roesley reviewed gene: LRPPRC: Rating: AMBER; Mode of pathogenicity: None; Publications: 32972427, 26510951, 21266382; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 5, (French-Canadian) MIM#220111; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10812 LRPPRC Ain Roesley changed review comment from: Established gene-disease association; to: Established gene-disease association

Onset in infancy and death usually occurs by age 2 years
Fetal anomalies v0.2946 MOCS1 Alison Yeung Marked gene: MOCS1 as ready
Fetal anomalies v0.2946 MOCS1 Alison Yeung Gene: mocs1 has been classified as Green List (High Evidence).
Mendeliome v0.10812 LRPPRC Ain Roesley reviewed gene: LRPPRC: Rating: GREEN; Mode of pathogenicity: None; Publications: 32972427, 26510951, 21266382; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 5, (French-Canadian) MIM#220111; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.2946 MPLKIP Alison Yeung Marked gene: MPLKIP as ready
Fetal anomalies v0.2946 MPLKIP Alison Yeung Gene: mplkip has been classified as Green List (High Evidence).
Fetal anomalies v0.2946 MPLKIP Alison Yeung Phenotypes for gene: MPLKIP were changed from TRICHOTHIODYSTROPHY NON-PHOTOSENSITIVE TYPE 1 to Trichothiodystrophy 4, nonphotosensitive, MIM# 234050; MONDO:0021013
Fetal anomalies v0.2945 MPLKIP Alison Yeung reviewed gene: MPLKIP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Trichothiodystrophy 4, nonphotosensitive, MIM# 234050; Mode of inheritance: None
Fetal anomalies v0.2945 MPDU1 Alison Yeung Marked gene: MPDU1 as ready
Fetal anomalies v0.2945 MPDU1 Alison Yeung Gene: mpdu1 has been classified as Green List (High Evidence).
Fetal anomalies v0.2945 MPDU1 Alison Yeung Phenotypes for gene: MPDU1 were changed from Congenital disorder of glycosylation, type If, MIM# 609180; MPDU1-CDG, MONDO:0012211 to Congenital disorder of glycosylation, type If, MIM# 609180; MPDU1-CDG, MONDO:0012211
Fetal anomalies v0.2945 MPDU1 Alison Yeung Phenotypes for gene: MPDU1 were changed from CONGENITAL DISORDERS OF GLYCOSYLATION to Congenital disorder of glycosylation, type If, MIM# 609180; MPDU1-CDG, MONDO:0012211
Fetal anomalies v0.2944 MPDU1 Alison Yeung Added comment: Comment on phenotypes: Congenital disorder of glycosylation, type If, MIM# 609180; MPDU1-CDG, MONDO:0012211
Fetal anomalies v0.2944 MPDU1 Alison Yeung Phenotypes for gene: MPDU1 were changed from CONGENITAL DISORDERS OF GLYCOSYLATION to CONGENITAL DISORDERS OF GLYCOSYLATION
Fetal anomalies v0.2943 MPDU1 Alison Yeung commented on gene: MPDU1: Fetal presentation includes microcephaly and severe growth restriction
Fetal anomalies v0.2943 MPDU1 Alison Yeung reviewed gene: MPDU1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital disorder of glycosylation, type If, MIM# 609180; Mode of inheritance: None
Fetal anomalies v0.2943 MOCS1 Alison Yeung Phenotypes for gene: MOCS1 were changed from MOLYBDENUM COFACTOR DEFICIENCY to Molybdenum cofactor deficiency A, MIM# 252150
Fetal anomalies v0.2942 MOCS1 Alison Yeung reviewed gene: MOCS1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Molybdenum cofactor deficiency A, MIM# 252150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.2942 MNX1 Alison Yeung Marked gene: MNX1 as ready
Fetal anomalies v0.2942 MNX1 Alison Yeung Gene: mnx1 has been classified as Green List (High Evidence).
Fetal anomalies v0.2942 MNX1 Alison Yeung Phenotypes for gene: MNX1 were changed from CURRARINO SYNDROME to Currarino syndrome, MIM# 176450
Fetal anomalies v0.2941 MNX1 Alison Yeung reviewed gene: MNX1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Currarino syndrome, MIM# 176450; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.2941 MMP21 Alison Yeung Marked gene: MMP21 as ready
Fetal anomalies v0.2941 MMP21 Alison Yeung Gene: mmp21 has been classified as Green List (High Evidence).
Fetal anomalies v0.2941 MMP21 Alison Yeung Phenotypes for gene: MMP21 were changed from MMP21-associated heterotaxy to Heterotaxy, visceral, 7, autosomal, MIM# 616749
Fetal anomalies v0.2940 MMP21 Alison Yeung reviewed gene: MMP21: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v0.2940 MLYCD Alison Yeung Marked gene: MLYCD as ready
Fetal anomalies v0.2940 MLYCD Alison Yeung Gene: mlycd has been classified as Green List (High Evidence).
Fetal anomalies v0.2940 MLYCD Alison Yeung Phenotypes for gene: MLYCD were changed from MALONYL-COA DECARBOXYLASE DEFICIENCY to Malonyl-CoA decarboxylase deficiency, MIM# 248360
Fetal anomalies v0.2939 MLYCD Alison Yeung reviewed gene: MLYCD: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v0.2939 LMOD1 Ain Roesley reviewed gene: LMOD1: Rating: AMBER; Mode of pathogenicity: None; Publications: 28292896; Phenotypes: Megacystis-microcolon-intestinal hypoperistalsis syndrome 3, MIM# 619362; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10812 LEMD3 Ain Roesley reviewed gene: LEMD3: Rating: GREEN; Mode of pathogenicity: None; Publications: 34098227, 33598273, 32519343, 32151766, 32151766; Phenotypes: Buschke-Ollendorff syndrome MIM#166700, Osteopoikilosis with or without melorheostosis MIM#166700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Fetal anomalies v0.2939 LEMD3 Ain Roesley reviewed gene: LEMD3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Buschke-Ollendorff syndrome MIM#166700, Osteopoikilosis with or without melorheostosis MIM#166700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Fetal anomalies v0.2939 ITPR1 Ain Roesley reviewed gene: ITPR1: Rating: RED; Mode of pathogenicity: None; Publications: 27108797, 31340402, 30242502, 29169895; Phenotypes: Spinocerebellar ataxia 15 MIM#606658, Spinocerebellar ataxia 29, congenital nonprogressive MIM#117360, Gillespie syndrome, MIM# 206700; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.2939 STAT5B Zornitza Stark Marked gene: STAT5B as ready
Fetal anomalies v0.2939 STAT5B Zornitza Stark Gene: stat5b has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.2939 STAT5B Zornitza Stark Phenotypes for gene: STAT5B were changed from GROWTH HORMONE INSENSITIVITY WITH IMMUNODEFICIENCY to Growth hormone insensitivity with immune dysregulation 1, autosomal recessive, MIM# 245590
Fetal anomalies v0.2938 STAT5B Zornitza Stark reviewed gene: STAT5B: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Growth hormone insensitivity with immune dysregulation 1, autosomal recessive, MIM# 245590; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.2938 STAC3 Zornitza Stark Marked gene: STAC3 as ready
Fetal anomalies v0.2938 STAC3 Zornitza Stark Gene: stac3 has been classified as Green List (High Evidence).
Fetal anomalies v0.2938 STAC3 Zornitza Stark Publications for gene: STAC3 were set to 30168660
Fetal anomalies v0.2937 STAC3 Zornitza Stark Classified gene: STAC3 as Green List (high evidence)
Fetal anomalies v0.2937 STAC3 Zornitza Stark Gene: stac3 has been classified as Green List (High Evidence).
Fetal anomalies v0.2936 ST3GAL3 Zornitza Stark Marked gene: ST3GAL3 as ready
Fetal anomalies v0.2936 ST3GAL3 Zornitza Stark Gene: st3gal3 has been classified as Red List (Low Evidence).
Fetal anomalies v0.2936 ST3GAL3 Zornitza Stark Phenotypes for gene: ST3GAL3 were changed from MENTAL RETARDATION, AUTOSOMAL RECESSIVE 12 to Mental retardation, autosomal recessive 12 MIM# 611090; Developmental and epileptic encephalopathy 15, MIM# 615006
Fetal anomalies v0.2935 ST3GAL3 Zornitza Stark Publications for gene: ST3GAL3 were set to
Fetal anomalies v0.2934 ST3GAL3 Zornitza Stark Classified gene: ST3GAL3 as Red List (low evidence)
Fetal anomalies v0.2934 ST3GAL3 Zornitza Stark Gene: st3gal3 has been classified as Red List (Low Evidence).
Fetal anomalies v0.2933 ST3GAL3 Zornitza Stark changed review comment from: PMID: 31584066 reports on two di-chorionic infant twins p.Y220*, presenting with epileptic encephalopathy with impaired neuromotor development.; to: Clinical presentation is typically post-natal.
Fetal anomalies v0.2933 ST3GAL3 Zornitza Stark edited their review of gene: ST3GAL3: Changed rating: RED; Changed phenotypes: Mental retardation, autosomal recessive 12 MIM# 611090, Developmental and epileptic encephalopathy 15, MIM# 615006
Fetal anomalies v0.2933 SPECC1L Zornitza Stark Marked gene: SPECC1L as ready
Fetal anomalies v0.2933 SPECC1L Zornitza Stark Gene: specc1l has been classified as Green List (High Evidence).
Fetal anomalies v0.2933 SPECC1L Zornitza Stark Phenotypes for gene: SPECC1L were changed from ?Facial clefting, oblique, 1, OMIM:600251; Hypertelorism, Teebi type, MONDO:0007780; Opitz GBBB syndrome, type II, OMIM:145410; Autosomal dominant Opitz G/BBB syndrome, MONDO:0007779; Tessier number 4 facial cleft, MONDO:0010850; Hypertelorism, Teebi type, OMIM:145420 to Opitz GBBB syndrome, type II, MIM# 145410; Autosomal dominant Opitz G/BBB syndrome, MONDO:0007779
Fetal anomalies v0.2932 SPECC1L Zornitza Stark Publications for gene: SPECC1L were set to
Fetal anomalies v0.2931 SPECC1L Zornitza Stark Mode of inheritance for gene: SPECC1L was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.2930 SPECC1L Zornitza Stark Classified gene: SPECC1L as Green List (high evidence)
Fetal anomalies v0.2930 SPECC1L Zornitza Stark Gene: specc1l has been classified as Green List (High Evidence).
Fetal anomalies v0.2929 SP7 Zornitza Stark Marked gene: SP7 as ready
Fetal anomalies v0.2929 SP7 Zornitza Stark Gene: sp7 has been classified as Red List (Low Evidence).
Fetal anomalies v0.2929 SP7 Zornitza Stark Classified gene: SP7 as Red List (low evidence)
Fetal anomalies v0.2929 SP7 Zornitza Stark Gene: sp7 has been classified as Red List (Low Evidence).
Fetal anomalies v0.2928 SP7 Zornitza Stark reviewed gene: SP7: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Osteogenesis imperfecta, type XII, MIM# 613849; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.2928 SOX6 Zornitza Stark Marked gene: SOX6 as ready
Fetal anomalies v0.2928 SOX6 Zornitza Stark Gene: sox6 has been classified as Green List (High Evidence).
Fetal anomalies v0.2928 SOX6 Zornitza Stark Publications for gene: SOX6 were set to
Fetal anomalies v0.2927 SOX6 Zornitza Stark Mode of inheritance for gene: SOX6 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.2926 SOX6 Zornitza Stark Classified gene: SOX6 as Green List (high evidence)
Fetal anomalies v0.2926 SOX6 Zornitza Stark Gene: sox6 has been classified as Green List (High Evidence).
Fetal anomalies v0.2925 SOX6 Zornitza Stark changed review comment from: Comment when marking as ready: Most individuals had ID, ranging from mild to severe.; to: Comment when marking as ready: Congenital anomalies, in particular craniosynostosis.
Fetal anomalies v0.2925 SOX5 Zornitza Stark Marked gene: SOX5 as ready
Fetal anomalies v0.2925 SOX5 Zornitza Stark Gene: sox5 has been classified as Red List (Low Evidence).
Fetal anomalies v0.2925 SOX5 Zornitza Stark Phenotypes for gene: SOX5 were changed from 12P12.5 INTRAGENIC DELETIONS ASSOCIATED WITH INTELLECTUAL DISABILITY to Lamb-Shaffer syndrome, MIM#616803
Fetal anomalies v0.2924 SOX5 Zornitza Stark Publications for gene: SOX5 were set to
Fetal anomalies v0.2923 SOX5 Zornitza Stark Mode of inheritance for gene: SOX5 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.2922 SOX5 Zornitza Stark Classified gene: SOX5 as Red List (low evidence)
Fetal anomalies v0.2922 SOX5 Zornitza Stark Gene: sox5 has been classified as Red List (Low Evidence).
Fetal anomalies v0.2921 SOX5 Zornitza Stark changed review comment from: Comment when marking as ready: Note many cases reported of intragenic deletion.; to: Comment when marking as ready: Note many cases reported of intragenic deletion.

Presentation is typically post-natal.
Fetal anomalies v0.2921 SOX5 Zornitza Stark edited their review of gene: SOX5: Changed rating: RED
Fetal anomalies v0.2921 SOX18 Zornitza Stark Marked gene: SOX18 as ready
Fetal anomalies v0.2921 SOX18 Zornitza Stark Gene: sox18 has been classified as Green List (High Evidence).
Fetal anomalies v0.2921 SOX18 Zornitza Stark Phenotypes for gene: SOX18 were changed from Hypotrichosis-lymphedema-telangiectasia syndrome, MONDO:0011914; Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome, OMIM:137940; Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome, MONDO:0019073; Hypotrichosis-lymphedema-telangiectasia syndrome, OMIM:607823 to Hypotrichosis-lymphedema-telangiectasia syndrome, MIM# 607823; Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome, MIM# 137940
Fetal anomalies v0.2920 SOX18 Zornitza Stark Publications for gene: SOX18 were set to
Fetal anomalies v0.2919 SOX18 Zornitza Stark Classified gene: SOX18 as Green List (high evidence)
Fetal anomalies v0.2919 SOX18 Zornitza Stark Gene: sox18 has been classified as Green List (High Evidence).
Fetal anomalies v0.2918 SNRPE Zornitza Stark Marked gene: SNRPE as ready
Fetal anomalies v0.2918 SNRPE Zornitza Stark Gene: snrpe has been classified as Red List (Low Evidence).
Fetal anomalies v0.2918 SNRPE Zornitza Stark Phenotypes for gene: SNRPE were changed from AUTOSOMAL-DOMINANT HYPOTRICHOSIS SIMPLEX to Hypotrichosis 11, MIM #615059
Fetal anomalies v0.2917 SNRPE Zornitza Stark Mode of inheritance for gene: SNRPE was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.2916 SNRPE Zornitza Stark Classified gene: SNRPE as Red List (low evidence)
Fetal anomalies v0.2916 SNRPE Zornitza Stark Gene: snrpe has been classified as Red List (Low Evidence).
Fetal anomalies v0.2915 SNAP29 Zornitza Stark Marked gene: SNAP29 as ready
Fetal anomalies v0.2915 SNAP29 Zornitza Stark Gene: snap29 has been classified as Green List (High Evidence).
Fetal anomalies v0.2915 SNAP29 Zornitza Stark Publications for gene: SNAP29 were set to 28388629; 21073448; 15968592
Fetal anomalies v0.2914 SNAP29 Zornitza Stark Classified gene: SNAP29 as Green List (high evidence)
Fetal anomalies v0.2914 SNAP29 Zornitza Stark Gene: snap29 has been classified as Green List (High Evidence).
Fetal anomalies v0.2913 SNAP25 Zornitza Stark Marked gene: SNAP25 as ready
Fetal anomalies v0.2913 SNAP25 Zornitza Stark Gene: snap25 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.2913 SNAP25 Zornitza Stark Phenotypes for gene: SNAP25 were changed from Epilepsy and intellectual disability to Myasthenic syndrome, congenital, 18, MIM# 616330; Developmental and epileptic encephalopathy
Fetal anomalies v0.2912 SNAP25 Zornitza Stark Publications for gene: SNAP25 were set to
Fetal anomalies v0.2911 SNAP25 Zornitza Stark Mode of inheritance for gene: SNAP25 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.2910 SNAP25 Zornitza Stark reviewed gene: SNAP25: Rating: AMBER; Mode of pathogenicity: None; Publications: 25381298; Phenotypes: Myasthenic syndrome, congenital, 18, MIM# 616330; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.2910 SMPD4 Zornitza Stark Marked gene: SMPD4 as ready
Fetal anomalies v0.2910 SMPD4 Zornitza Stark Gene: smpd4 has been classified as Green List (High Evidence).
Fetal anomalies v0.2910 SMPD4 Zornitza Stark Classified gene: SMPD4 as Green List (high evidence)
Fetal anomalies v0.2910 SMPD4 Zornitza Stark Gene: smpd4 has been classified as Green List (High Evidence).
Fetal anomalies v0.2909 SMG9 Zornitza Stark Marked gene: SMG9 as ready
Fetal anomalies v0.2909 SMG9 Zornitza Stark Gene: smg9 has been classified as Green List (High Evidence).
Fetal anomalies v0.2909 SMG9 Zornitza Stark Phenotypes for gene: SMG9 were changed from Heart and brain malformation syndrome, 616920; SMG9 Multiple Congenital Anomaly Syndrome to Heart and brain malformation syndrome, MIM# 616920
Fetal anomalies v0.2908 SMG9 Zornitza Stark Classified gene: SMG9 as Green List (high evidence)
Fetal anomalies v0.2908 SMG9 Zornitza Stark Gene: smg9 has been classified as Green List (High Evidence).
Fetal anomalies v0.2907 SMG9 Zornitza Stark changed review comment from: Three unrelated families reported, severe congenital malformation syndrome, ID is part of the phenotype in survivors.
Sources: Expert list; to: Three unrelated families reported, severe congenital malformation syndrome.
Sources: Expert list
Fetal anomalies v0.2907 SMARCC1 Zornitza Stark Marked gene: SMARCC1 as ready
Fetal anomalies v0.2907 SMARCC1 Zornitza Stark Gene: smarcc1 has been classified as Green List (High Evidence).
Fetal anomalies v0.2907 SMARCC1 Zornitza Stark Classified gene: SMARCC1 as Green List (high evidence)
Fetal anomalies v0.2907 SMARCC1 Zornitza Stark Gene: smarcc1 has been classified as Green List (High Evidence).
Fetal anomalies v0.2906 SLC5A7 Zornitza Stark Marked gene: SLC5A7 as ready
Fetal anomalies v0.2906 SLC5A7 Zornitza Stark Gene: slc5a7 has been classified as Green List (High Evidence).
Fetal anomalies v0.2906 SLC5A7 Zornitza Stark Publications for gene: SLC5A7 were set to 27569547; 31299140
Fetal anomalies v0.2905 SLC5A7 Zornitza Stark Classified gene: SLC5A7 as Green List (high evidence)
Fetal anomalies v0.2905 SLC5A7 Zornitza Stark Gene: slc5a7 has been classified as Green List (High Evidence).
Fetal anomalies v0.2904 SLC29A3 Zornitza Stark Marked gene: SLC29A3 as ready
Fetal anomalies v0.2904 SLC29A3 Zornitza Stark Gene: slc29a3 has been classified as Green List (High Evidence).
Fetal anomalies v0.2904 SLC29A3 Zornitza Stark Publications for gene: SLC29A3 were set to
Fetal anomalies v0.2903 SLC29A3 Zornitza Stark Classified gene: SLC29A3 as Green List (high evidence)
Fetal anomalies v0.2903 SLC29A3 Zornitza Stark Gene: slc29a3 has been classified as Green List (High Evidence).
Fetal anomalies v0.2902 SLC25A4 Zornitza Stark Marked gene: SLC25A4 as ready
Fetal anomalies v0.2902 SLC25A4 Zornitza Stark Gene: slc25a4 has been classified as Green List (High Evidence).
Fetal anomalies v0.2902 SLC25A4 Zornitza Stark Phenotypes for gene: SLC25A4 were changed from Severe Early-Onset Mitochondrial Disease and Loss of Mitochondrial DNA Copy Number to Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) AD, MIM#617184
Fetal anomalies v0.2901 SLC25A4 Zornitza Stark Publications for gene: SLC25A4 were set to
Fetal anomalies v0.2900 SLC25A4 Zornitza Stark Mode of inheritance for gene: SLC25A4 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.2899 SLC25A4 Zornitza Stark Classified gene: SLC25A4 as Green List (high evidence)
Fetal anomalies v0.2899 SLC25A4 Zornitza Stark Gene: slc25a4 has been classified as Green List (High Evidence).
Fetal anomalies v0.2898 SLC25A4 Zornitza Stark changed review comment from: Variants in this gene cause both dominant and recessive disease. MIM#617184 reported as causing profound hypotonia and frequent need for respiratory support; the other two conditions, one AR and the other AD, appear less severe. Not convinced ID is an intrinsic part of the phenotype.; to: Variants in this gene cause both dominant and recessive disease. MIM#617184 reported as causing profound hypotonia and frequent need for respiratory support; the other two conditions, one AR and the other AD, appear less severe.
Fetal anomalies v0.2898 SLC25A4 Zornitza Stark edited their review of gene: SLC25A4: Added comment: Hypertrophic cardiomyopathy is an early feature.; Changed rating: GREEN; Changed phenotypes: Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) AD, MIM#617184; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.2898 SLC1A2 Zornitza Stark Marked gene: SLC1A2 as ready
Fetal anomalies v0.2898 SLC1A2 Zornitza Stark Gene: slc1a2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.2898 SLC1A2 Zornitza Stark Phenotypes for gene: SLC1A2 were changed from Developmental and epileptic encephalopathy 41 617105 to Developmental and epileptic encephalopathy 41, MIM# 617105
Fetal anomalies v0.2897 SLC1A2 Zornitza Stark Phenotypes for gene: SLC1A2 were changed from EPILEPTIC ENCEPHALOPATHY to Developmental and epileptic encephalopathy 41 617105
Fetal anomalies v0.2896 SLC1A2 Zornitza Stark Publications for gene: SLC1A2 were set to
Fetal anomalies v0.2895 SLC1A2 Zornitza Stark Mode of inheritance for gene: SLC1A2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.2894 SLC1A2 Zornitza Stark Classified gene: SLC1A2 as Red List (low evidence)
Fetal anomalies v0.2894 SLC1A2 Zornitza Stark Gene: slc1a2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.2893 SLC1A2 Zornitza Stark edited their review of gene: SLC1A2: Changed rating: RED
Fetal anomalies v0.2893 SLC1A2 Zornitza Stark changed review comment from: Four unrelated individuals reported.
Sources: Expert list; to: Four unrelated individuals reported. Post-natal presentation.
Sources: Expert list
Fetal anomalies v0.2893 SLC18A3 Zornitza Stark Marked gene: SLC18A3 as ready
Fetal anomalies v0.2893 SLC18A3 Zornitza Stark Gene: slc18a3 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.2893 SLC18A3 Zornitza Stark Publications for gene: SLC18A3 were set to 31059209
Fetal anomalies v0.2892 UROS Krithika Murali gene: UROS was added
gene: UROS was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: UROS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UROS were set to 34187847; 34828434; 15065102
Phenotypes for gene: UROS were set to Porphyria, congenital erythropoietic - MIM#263700; hydrops fetalis; multiple congenital anomalies
Review for gene: UROS was set to GREEN
Added comment: Biallelic variants associated with congenital erytropoietic porphyria (CEP).

PMID 34187847 Khalouaoui A et al 2021 report one infant with CEP secondary to homozygous UROS variants. Prenatal ultrasound at 25 weeks of gestation revealed an increased nuchal translucency and myocardial hypertrophy.

PMID: 34828434 Arnaud et al 2021 - report one fetus miscarried in the 2nd trimester with 22 weeks ultrasound showing hyperechogenic small intestine with short femurs. Subsequent pregnancy MTOP after antenatal USS showed hygroma coli, ascites, short femurs, double outlet right ventricle. Genomic sequencing on stored fetal DNA samples confirmed homozygous UROS p.Cys73Arg variants in both fetuses.

PMID 15065102 Lazebnik et al 2004 reported the prenatal findings of two siblings with CEP secondary to homozygous pathogenic C73R variants. 1st child - USS at 17.5 weeks gestation showed increased nuchal thickness (9.7mm) with mild ascites, pericardial effusion, and skin oedema which persisted on subsequent scans. 2nd child - 16 week USS showed increased nuchal thickness (8.7mm) with scalp oedema, ascites, pericardial effusion, skin oedema and hepatomegaly.

Other cases with antenatal features, particularly non-immune hydrops, secondary to suspected CEP reported but not confirmed molecularly.
Sources: Literature
Fetal anomalies v0.2892 MVK Krithika Murali gene: MVK was added
gene: MVK was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: MVK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MVK were set to 27012807; 16722536
Phenotypes for gene: MVK were set to Mevalonic aciduria-#610377; Hyper-IgD syndrome - #260920
Review for gene: MVK was set to GREEN
Added comment: Biallelic MVK variants associated with mevalonate kinate deficiencies - an overlapping spectrum of phenotypes includes mevalonic aciduria (MVA) on the severe end and hyper-IgD syndrome (HIDS) generally having a less severe clinical course and later diagnosis.

Fetal manifestations of MVA reported include microcephaly and hydrops fetalis.
Sources: Literature
Oligodontia v0.11 SMOC2 Chirag Patel Classified gene: SMOC2 as Green List (high evidence)
Oligodontia v0.11 SMOC2 Chirag Patel Gene: smoc2 has been classified as Green List (High Evidence).
Oligodontia v0.11 SMOC2 Chirag Patel Classified gene: SMOC2 as Green List (high evidence)
Oligodontia v0.11 SMOC2 Chirag Patel Gene: smoc2 has been classified as Green List (High Evidence).
Oligodontia v0.10 SMOC2 Chirag Patel gene: SMOC2 was added
gene: SMOC2 was added to Oligodontia. Sources: Literature
Mode of inheritance for gene: SMOC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMOC2 were set to PMID: 22152679, 23317772, 32908163
Phenotypes for gene: SMOC2 were set to Dentin dysplasia, type I, with microdontia and misshapen teeth, MIM# 125400
Review for gene: SMOC2 was set to GREEN
Added comment: Three unrelated families reported with oligodontia, microdontia, tooth root deficiencies, alveolar bone hypoplasia, and a range of skeletal malformations. Mouse model: germline Smoc2 homozygous mutants are viable, but have tooth number anomalies, reduced tooth size, altered enamel prism patterning, and spontaneous age-induced periodontal bone and root loss.
Sources: Literature
Fetal anomalies v0.2892 LAMB2 Krithika Murali gene: LAMB2 was added
gene: LAMB2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: LAMB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LAMB2 were set to 16450351
Phenotypes for gene: LAMB2 were set to Pierson syndrome-MIM#609049; Nephrotic syndrome, type 5, with or without ocular abnormalities-MIM#614199
Review for gene: LAMB2 was set to AMBER
Added comment: Biallelic variants associated with Pierson syndrome. Phenotypic features include congenital nephrotic syndrome, ocular anomalies including microcoria. Most affected individuals die early from renal disease with survivors tending to have ID/visual loss.

Prenatal features reported in 1 consanguineous Turkish family with 4 pregnancies affected by Pierson syndrome. Antenatal ultrasound features noted include:
- 2/4 homogenous hyperechogenicity of the kidneys similar to bone tissue
- 2/4 enlargement of fetal kidneys
- 2/4 bilateral pyelectasis
- 1/4 oligohydramnios --> anhydramnios
- 1/4 hydrops
- 1/4 ancencephaly

All 4 fetuses had ultrasound anomalies. Anencephaly seen in the 4th pregnancy noted at 11 weeks resulting in MTOP. Homozygosity for LAMB2 variant confirmed. PM showed that kidneys were appropriate for gestational age. I could not find another case report of anencephaly with Pierson syndrome, this may be an incidental finding.
Sources: Literature
Fetal anomalies v0.2892 HS2ST1 Zornitza Stark Marked gene: HS2ST1 as ready
Fetal anomalies v0.2892 HS2ST1 Zornitza Stark Gene: hs2st1 has been classified as Green List (High Evidence).
Fetal anomalies v0.2892 HS2ST1 Zornitza Stark Classified gene: HS2ST1 as Green List (high evidence)
Fetal anomalies v0.2892 HS2ST1 Zornitza Stark Gene: hs2st1 has been classified as Green List (High Evidence).
Fetal anomalies v0.2891 FLNC Zornitza Stark Marked gene: FLNC as ready
Fetal anomalies v0.2891 FLNC Zornitza Stark Gene: flnc has been classified as Green List (High Evidence).
Fetal anomalies v0.2891 FLNC Zornitza Stark Phenotypes for gene: FLNC were changed from Arthrogryposis; congenital myopathy; Cardiomyopathy, familial restrictive 5 - MIM #617047; Cardiomyopathy, familial hypertrophic, 26 -MIM# 617047; Myopathy, distal, 4 - #614065; Myopathy, myofibrillar, 5 - MIM#609524 to Arthrogryposis; congenital myopathy; Myopathy, myofibrillar, 5 - MIM#609524
Fetal anomalies v0.2890 FLNC Zornitza Stark Classified gene: FLNC as Green List (high evidence)
Fetal anomalies v0.2890 FLNC Zornitza Stark Gene: flnc has been classified as Green List (High Evidence).
Fetal anomalies v0.2889 MKS1 Zornitza Stark Publications for gene: MKS1 were set to
Fetal anomalies v0.2888 MKKS Zornitza Stark Publications for gene: MKKS were set to
Mendeliome v0.10812 MGP Zornitza Stark Marked gene: MGP as ready
Mendeliome v0.10812 MGP Zornitza Stark Gene: mgp has been classified as Green List (High Evidence).
Mendeliome v0.10812 MGP Zornitza Stark Phenotypes for gene: MGP were changed from to Keutel syndrome, MIM #245150
Mendeliome v0.10811 MGP Zornitza Stark Publications for gene: MGP were set to
Mendeliome v0.10810 MGP Zornitza Stark Mode of inheritance for gene: MGP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10809 MGP Zornitza Stark reviewed gene: MGP: Rating: GREEN; Mode of pathogenicity: None; Publications: 9916809, 15810001, 33996798; Phenotypes: Keutel syndrome, MIM #245150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.2887 MFRP Zornitza Stark Phenotypes for gene: MFRP were changed from MICROPHTHALMIA ISOLATED TYPE 5; NANOPHTHALMOS 2 to Microphthalmia, isolated 5, MIM# 611040
Fetal anomalies v0.2886 MFRP Zornitza Stark Publications for gene: MFRP were set to
Fetal anomalies v0.2885 MFRP Zornitza Stark Deleted their review
Fetal anomalies v0.2885 IQCB1 Zornitza Stark Deleted their review
Fetal anomalies v0.2885 IARS Zornitza Stark Publications for gene: IARS were set to 27426735
Fetal anomalies v0.2884 SIX6 Zornitza Stark Marked gene: SIX6 as ready
Fetal anomalies v0.2884 SIX6 Zornitza Stark Gene: six6 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.2884 SIX6 Zornitza Stark Publications for gene: SIX6 were set to
Fetal anomalies v0.2883 SIX6 Zornitza Stark changed review comment from: Four unrelated families and a dog model.; to: Four unrelated families and a dog model. Microphthalmia in some individuals, otherwise features would not generally be detectable ante-natally.
Fetal anomalies v0.2883 SIX6 Zornitza Stark edited their review of gene: SIX6: Changed rating: AMBER
Fetal anomalies v0.2883 SHANK3 Zornitza Stark Marked gene: SHANK3 as ready
Fetal anomalies v0.2883 SHANK3 Zornitza Stark Gene: shank3 has been classified as Red List (Low Evidence).
Fetal anomalies v0.2883 SHANK3 Zornitza Stark Publications for gene: SHANK3 were set to
Fetal anomalies v0.2882 SHANK3 Zornitza Stark Mode of inheritance for gene: SHANK3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.2881 SHANK3 Zornitza Stark Classified gene: SHANK3 as Red List (low evidence)
Fetal anomalies v0.2881 SHANK3 Zornitza Stark Gene: shank3 has been classified as Red List (Low Evidence).
Fetal anomalies v0.2880 SHANK3 Zornitza Stark changed review comment from: Phelan-McDermid syndrome is a developmental disorder with variable features. Common features include neonatal hypotonia, global developmental delay, normal to accelerated growth, absent to severely delayed speech, autistic behaviour, and minor dysmorphic features. Well established gene-disease association, deletions are common.; to: Phelan-McDermid syndrome is a developmental disorder with variable features. Common features include neonatal hypotonia, global developmental delay, normal to accelerated growth, absent to severely delayed speech, autistic behaviour, and minor dysmorphic features. Well established gene-disease association, deletions are common.

Clinical presentation is typically post-natal.
Fetal anomalies v0.2880 SHANK3 Zornitza Stark edited their review of gene: SHANK3: Changed rating: RED
Intellectual disability syndromic and non-syndromic v0.4471 SHANK1 Zornitza Stark Phenotypes for gene: SHANK1 were changed from Neurodevelopmental disorder, no OMIM# to Neurodevelopmental disorder, MONDO:0700092, SHANK1-related
Intellectual disability syndromic and non-syndromic v0.4470 SHANK1 Zornitza Stark reviewed gene: SHANK1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, SHANK1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autism v0.169 SHANK1 Zornitza Stark Phenotypes for gene: SHANK1 were changed from Autism to Neurodevelopmental disorder, MONDO:0700092, SHANK1-related
Autism v0.168 SHANK1 Zornitza Stark reviewed gene: SHANK1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, SHANK1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10809 SHANK1 Zornitza Stark Phenotypes for gene: SHANK1 were changed from Neurodevelopmental disorder, no OMIM# to Neurodevelopmental disorder, MONDO:0700092, SHANK1-related
Mendeliome v0.10808 SHANK1 Zornitza Stark edited their review of gene: SHANK1: Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, SHANK1-related
Fetal anomalies v0.2880 SHANK1 Zornitza Stark Marked gene: SHANK1 as ready
Fetal anomalies v0.2880 SHANK1 Zornitza Stark Gene: shank1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.2880 SHANK1 Zornitza Stark Phenotypes for gene: SHANK1 were changed from AUTISM to Neurodevelopmental disorder, MONDO:0700092, SHANK1-related
Fetal anomalies v0.2879 SHANK1 Zornitza Stark Publications for gene: SHANK1 were set to
Fetal anomalies v0.2878 SHANK1 Zornitza Stark Mode of inheritance for gene: SHANK1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.2877 SHANK1 Zornitza Stark Classified gene: SHANK1 as Red List (low evidence)
Fetal anomalies v0.2877 SHANK1 Zornitza Stark Gene: shank1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.2876 SHANK1 Zornitza Stark reviewed gene: SHANK1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, SHANK1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.2876 SGSH Zornitza Stark Marked gene: SGSH as ready
Fetal anomalies v0.2876 SGSH Zornitza Stark Gene: sgsh has been classified as Red List (Low Evidence).
Fetal anomalies v0.2876 SGSH Zornitza Stark Phenotypes for gene: SGSH were changed from MUCOPOLYSACCHARIDOSIS TYPE 3A to Mucopolysaccharidosis type IIIA (Sanfilippo A), MIM# 252900; MONDO:0009655
Fetal anomalies v0.2875 SGSH Zornitza Stark Publications for gene: SGSH were set to
Fetal anomalies v0.2874 SGSH Zornitza Stark Classified gene: SGSH as Red List (low evidence)
Fetal anomalies v0.2874 SGSH Zornitza Stark Gene: sgsh has been classified as Red List (Low Evidence).
Fetal anomalies v0.2873 SGSH Zornitza Stark edited their review of gene: SGSH: Changed rating: RED
Fetal anomalies v0.2873 SETD2 Zornitza Stark Marked gene: SETD2 as ready
Fetal anomalies v0.2873 SETD2 Zornitza Stark Gene: setd2 has been classified as Green List (High Evidence).
Fetal anomalies v0.2873 SETD2 Zornitza Stark Phenotypes for gene: SETD2 were changed from SETD2-associated Overgrowth Syndrome to Luscan-Lumish syndrome, MIM#616831
Fetal anomalies v0.2872 SETD2 Zornitza Stark Publications for gene: SETD2 were set to
Fetal anomalies v0.2871 SETD2 Zornitza Stark Mode of inheritance for gene: SETD2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.2870 SETD2 Zornitza Stark Classified gene: SETD2 as Green List (high evidence)
Fetal anomalies v0.2870 SETD2 Zornitza Stark Gene: setd2 has been classified as Green List (High Evidence).
Fetal anomalies v0.2869 SETD2 Zornitza Stark changed review comment from: Multiple affected individuals with macrocephaly, intellectual disability, speech delay, low sociability, and behavioral problems. More variable features include postnatal overgrowth, obesity, advanced carpal ossification, developmental delay, and seizures; to: Multiple affected individuals with macrocephaly, intellectual disability, speech delay, low sociability, and behavioral problems. More variable features include postnatal overgrowth, obesity, advanced carpal ossification, developmental delay, and seizures.

Chiari malformation and ventriculomegaly reported.
Fetal anomalies v0.2869 SETD1A Zornitza Stark Marked gene: SETD1A as ready
Fetal anomalies v0.2869 SETD1A Zornitza Stark Gene: setd1a has been classified as Red List (Low Evidence).
Fetal anomalies v0.2869 SETD1A Zornitza Stark Phenotypes for gene: SETD1A were changed from INTELLECTUAL DISABILITY to Epilepsy, early-onset, with or without developmental delay, MIM# 618832; Neurodevelopmental disorder with speech impairment and dysmorphic facies, MIM# 619056
Fetal anomalies v0.2868 SETD1A Zornitza Stark Publications for gene: SETD1A were set to
Fetal anomalies v0.2867 SETD1A Zornitza Stark Mode of inheritance for gene: SETD1A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.2866 SETD1A Zornitza Stark Classified gene: SETD1A as Red List (low evidence)
Fetal anomalies v0.2866 SETD1A Zornitza Stark Gene: setd1a has been classified as Red List (Low Evidence).
Fetal anomalies v0.2865 SETD1A Zornitza Stark changed review comment from: OMIM has assigned a second phenotype in relation to the syndromic ID cohort reported in PMID 32346159. All variants were predicted to disrupt or delete the SET catalytic domain, and LOF is the established mechanism.

In addition, there are 4 families reported with a predominantly seizure phenotype without ID, PMID 31197650. All the variants are missense and mechanism of pathogenicity is not clearly established, hence it is difficult to know whether these are two distinct conditions or part of a spectrum of severity for SETD1A-related disorders.; to: OMIM has assigned a second phenotype in relation to the syndromic ID cohort reported in PMID 32346159. All variants were predicted to disrupt or delete the SET catalytic domain, and LOF is the established mechanism.

In addition, there are 4 families reported with a predominantly seizure phenotype without ID, PMID 31197650. All the variants are missense and mechanism of pathogenicity is not clearly established, hence it is difficult to know whether these are two distinct conditions or part of a spectrum of severity for SETD1A-related disorders.

Presentation of both disorders is typically post-natal.
Fetal anomalies v0.2865 SETD1A Zornitza Stark edited their review of gene: SETD1A: Changed rating: RED
Congenital hypothyroidism v0.33 SECISBP2 Zornitza Stark Marked gene: SECISBP2 as ready
Congenital hypothyroidism v0.33 SECISBP2 Zornitza Stark Gene: secisbp2 has been classified as Green List (High Evidence).
Congenital hypothyroidism v0.33 SECISBP2 Zornitza Stark Phenotypes for gene: SECISBP2 were changed from Short stature-delayed bone age due to thyroid hormone metabolism deficiency; Selenocysteine insertion sequence binding protein 2 (SBP2) defect; Abnormal thyroid hormone metabolism; Thyroid hormone metabolism, abnormal, 609698; THYROID HORMONE METABOLISM, ABNORMAL to Thyroid hormone metabolism, abnormal, MIM# 609698
Congenital hypothyroidism v0.32 SECISBP2 Zornitza Stark Publications for gene: SECISBP2 were set to 20501692; 16228000; Diversity Selenium Functions in Health and Disease, Edited by Regina Brigelius-Flohe and Helmut Sies, Chapter 16. Mutations in SECISBP2. Erik Schoenmakers, Carla Moran, Nadia Schoenmakers and Krishna Chatterjee. CRC Press 2015. Pages 343 376. Print ISBN: 978-1-4822-5126-5. eBook ISBN: 978-1-4822-5127-2. DOI: 10.1201/b18810-23; 22247018; 24629861; 22986150; 19602558; 21084748
Congenital hypothyroidism v0.31 SECISBP2 Zornitza Stark reviewed gene: SECISBP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thyroid hormone metabolism, abnormal, MIM# 609698; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.2865 SECISBP2 Zornitza Stark Marked gene: SECISBP2 as ready
Fetal anomalies v0.2865 SECISBP2 Zornitza Stark Gene: secisbp2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.2865 SECISBP2 Zornitza Stark Phenotypes for gene: SECISBP2 were changed from THYROID HORMONE METABOLISM, ABNORMAL to Thyroid hormone metabolism, abnormal, MIM# 609698
Fetal anomalies v0.2864 SECISBP2 Zornitza Stark Publications for gene: SECISBP2 were set to
Fetal anomalies v0.2863 SECISBP2 Zornitza Stark Classified gene: SECISBP2 as Red List (low evidence)
Fetal anomalies v0.2863 SECISBP2 Zornitza Stark Gene: secisbp2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.2862 SECISBP2 Zornitza Stark reviewed gene: SECISBP2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Thyroid hormone metabolism, abnormal, MIM# 609698; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.2862 SEC24D Zornitza Stark Marked gene: SEC24D as ready
Fetal anomalies v0.2862 SEC24D Zornitza Stark Gene: sec24d has been classified as Green List (High Evidence).
Fetal anomalies v0.2862 SEC24D Zornitza Stark Phenotypes for gene: SEC24D were changed from SYNDROMIC OSTEOGENESIS IMPERFECTA to Cole-Carpenter syndrome 2, MIM# 616294
Fetal anomalies v0.2861 SEC24D Zornitza Stark Publications for gene: SEC24D were set to
Fetal anomalies v0.2860 SEC24D Zornitza Stark Classified gene: SEC24D as Green List (high evidence)
Fetal anomalies v0.2860 SEC24D Zornitza Stark Gene: sec24d has been classified as Green List (High Evidence).
Fetal anomalies v0.2859 SCN3A Zornitza Stark Marked gene: SCN3A as ready
Fetal anomalies v0.2859 SCN3A Zornitza Stark Gene: scn3a has been classified as Green List (High Evidence).
Fetal anomalies v0.2859 SCN3A Zornitza Stark Phenotypes for gene: SCN3A were changed from Focal epilepsy to Epilepsy, familial focal, with variable foci 4, MIM# 617935; Epileptic encephalopathy, early infantile, 62, MIM# 617938; Intellectual disability; Malformations of cortical development
Fetal anomalies v0.2858 SCN3A Zornitza Stark Publications for gene: SCN3A were set to
Fetal anomalies v0.2857 SCN3A Zornitza Stark Mode of pathogenicity for gene: SCN3A was changed from to Other
Fetal anomalies v0.2856 SCN3A Zornitza Stark Mode of inheritance for gene: SCN3A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.2855 SCN3A Zornitza Stark Classified gene: SCN3A as Green List (high evidence)
Fetal anomalies v0.2855 SCN3A Zornitza Stark Gene: scn3a has been classified as Green List (High Evidence).
Fetal anomalies v0.2854 SCLT1 Zornitza Stark Marked gene: SCLT1 as ready
Fetal anomalies v0.2854 SCLT1 Zornitza Stark Gene: sclt1 has been classified as Green List (High Evidence).
Fetal anomalies v0.2854 SCLT1 Zornitza Stark Phenotypes for gene: SCLT1 were changed from Senior-L ken Syndrome; No OMIM phenotype; Oro-facio-digital syndrome type IX to Orofaciodigital syndrome type IX; Senior-Loken syndrome; Bardet-Biedl syndrome
Fetal anomalies v0.2853 SCLT1 Zornitza Stark Publications for gene: SCLT1 were set to 28486600; 30425282; 23348840; 24285566; 28005958
Fetal anomalies v0.2852 SCLT1 Zornitza Stark Classified gene: SCLT1 as Green List (high evidence)
Fetal anomalies v0.2852 SCLT1 Zornitza Stark Gene: sclt1 has been classified as Green List (High Evidence).
Fetal anomalies v0.2851 SCLT1 Zornitza Stark changed review comment from: Established ciliopathy gene but no clear association with ciliopathy/JS-type structural brain abnormalities.; to: Established ciliopathy gene.
Fetal anomalies v0.2851 SCLT1 Zornitza Stark edited their review of gene: SCLT1: Changed rating: GREEN
Fetal anomalies v0.2851 SASS6 Zornitza Stark Marked gene: SASS6 as ready
Fetal anomalies v0.2851 SASS6 Zornitza Stark Gene: sass6 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.2851 SASS6 Zornitza Stark Phenotypes for gene: SASS6 were changed from ?Microcephaly 14, primary, autosomal recessive 616402 to Microcephaly 14, primary, autosomal recessive, MIM# 616402
Fetal anomalies v0.2850 SASS6 Zornitza Stark Publications for gene: SASS6 were set to 24951542
Fetal anomalies v0.2849 HS2ST1 Krithika Murali gene: HS2ST1 was added
gene: HS2ST1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: HS2ST1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HS2ST1 were set to 33159882
Phenotypes for gene: HS2ST1 were set to Neurofacioskeletal syndrome with or without renal agenesis-MIM#619194; multiple congenital anomalies; arthrogryposis
Review for gene: HS2ST1 was set to GREEN
Added comment: PMID 33159882 - Scheenberger et al 2020

Biallelic HS2ST1 variants associated with disease reported in 4 affected individuals from 3 unrelated families, including one affected fetus with arthrogryposis, skeletal anomalies, bilateral renal agenesis. Other congenital anomalies reported include agenesis or hypoplasia of the corpus callosum.
Sources: Literature
Fetal anomalies v0.2849 SACS Zornitza Stark Marked gene: SACS as ready
Fetal anomalies v0.2849 SACS Zornitza Stark Gene: sacs has been classified as Red List (Low Evidence).
Fetal anomalies v0.2849 SACS Zornitza Stark Phenotypes for gene: SACS were changed from SPASTIC ATAXIA, CHARLEVOIX-SAGUENAY TYPE to Spastic ataxia, Charlevoix-Saguenay type, MIM# 270550
Fetal anomalies v0.2848 SACS Zornitza Stark Publications for gene: SACS were set to
Fetal anomalies v0.2847 SACS Zornitza Stark Classified gene: SACS as Red List (low evidence)
Fetal anomalies v0.2847 SACS Zornitza Stark Gene: sacs has been classified as Red List (Low Evidence).
Fetal anomalies v0.2846 SACS Zornitza Stark changed review comment from: ID has only been reported in a minority of individuals; predominantly a motor phenotype.; to: Progressive condition, onset in infancy/childhood.
Fetal anomalies v0.2846 SACS Zornitza Stark edited their review of gene: SACS: Changed rating: RED
Fetal anomalies v0.2846 FLNC Krithika Murali changed review comment from: ClinGen definitive gene-disease validation for myofibrillar myopathy type 5 and dilated cardiomyopathy. Predominantly adult onset phenotype, AD inheritance. 4 unrelated cases with likely de novo FLNC variants presenting with congenital myopathy and arthrogryposis have also been reported which are features amenable to antenatal detection.

PMID 29858533 Kiselev et al reported 4 unrelated patients with early onset myopathy and restrictive cardiomyopathy. 3/4 also presented with arthrogryposis.

x1 patient required delivery via CS due to breech presentation and at birth was noted to have arthrogryposis and hip dysplasia - de novo FLNC variant confirmed. RCM diagnosed age 2

x1 patient noted to have IUGR in a pregnancy complicated by pre-eclampsia. At birth was noted to have arthrogryposis, hip subluxation and abdominal wall weakness with herniation. RCM diagnosed age 6 months. Variant not present in unaffected mother, paternal DNA unavailable.

x1 patient required CS delivery due to insufficient rotation in birth canal. Noted to have arthrogryposis at birth. Variant confirmed to be de novo

x1 patient presented with muscle weakness first year of life, RCM age 3. Parents declined genetic testing.

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Other cases of interest

PMID 30260051 Schubert et al 2018 - report two restrictive cardiomyopathy families with childhood onset disease with age 1 being the earliest age of diagnosis in a DCDA monozygotic twin who was also diagnosed with a small VSD perinatally. Both twins were also noted to have extra-cardiac manifestations at the time of diagnosis including developmental delay, hypotonia, dysmorphic facial features, and clasped thumbs with onset of kidney dysfunction age 3 post-cardiac transplant.

PMID: 32516863 – Kolbel et al 2020 report one neonate with homozygous FLNC variant c.1325C>G (p.Pro442Arg). Absent from gnomad. Presented with weak suck first month of life with subsequent motor development delay, generalised muscular hypotonia, contractures. Variant confirmed in both unaffected parents. Authors postulate this is a novel case of homozygous FLNC variants associated with congenital presentation. This is a single case report, only heterozygous variants reported so far including in congenital presentations, both parents with het variants unaffected. Possibility of an alternative genetic explanation for this patient's presentation not excluded.
Sources: Literature; to: ClinGen definitive gene-disease validation for myofibrillar myopathy type 5 and dilated cardiomyopathy. Predominantly adult onset phenotype, AD inheritance. 4 unrelated cases with likely de novo FLNC variants presenting with congenital myopathy and arthrogryposis have also been reported. These features/complications of these features are amenable to antenatal detection.

PMID 29858533 Kiselev et al reported 4 unrelated patients with early onset myopathy and restrictive cardiomyopathy. 3/4 also presented with arthrogryposis.

x1 patient required delivery via CS due to breech presentation and at birth was noted to have arthrogryposis and hip dysplasia - de novo FLNC variant confirmed. RCM diagnosed age 2

x1 patient noted to have IUGR in a pregnancy complicated by pre-eclampsia. At birth was noted to have arthrogryposis, hip subluxation and abdominal wall weakness with herniation. RCM diagnosed age 6 months. Variant not present in unaffected mother, paternal DNA unavailable.

x1 patient required CS delivery due to insufficient rotation in birth canal. Noted to have arthrogryposis at birth. Variant confirmed to be de novo

x1 patient presented with muscle weakness first year of life, RCM age 3. Parents declined genetic testing.

---
Other cases of interest

PMID 30260051 Schubert et al 2018 - report two restrictive cardiomyopathy families with childhood onset disease with age 1 being the earliest age of diagnosis in a DCDA monozygotic twin who was also diagnosed with a small VSD perinatally. Both twins were also noted to have extra-cardiac manifestations at the time of diagnosis including developmental delay, hypotonia, dysmorphic facial features, and clasped thumbs with onset of kidney dysfunction age 3 post-cardiac transplant.

PMID: 32516863 – Kolbel et al 2020 report one neonate with homozygous FLNC variant c.1325C>G (p.Pro442Arg). Absent from gnomad. Presented with weak suck first month of life with subsequent motor development delay, generalised muscular hypotonia, contractures. Variant confirmed in both unaffected parents. Authors postulate this is a novel case of homozygous FLNC variants associated with congenital presentation. This is a single case report, only heterozygous variants reported so far including in congenital presentations, both parents with het variants unaffected. Possibility of an alternative genetic explanation for this patient's presentation not excluded.
Sources: Literature
Fetal anomalies v0.2846 FLNC Krithika Murali gene: FLNC was added
gene: FLNC was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: FLNC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FLNC were set to 29858533; 30260051; 32516863
Phenotypes for gene: FLNC were set to Arthrogryposis; congenital myopathy; Cardiomyopathy, familial restrictive 5 - MIM #617047; Cardiomyopathy, familial hypertrophic, 26 -MIM# 617047; Myopathy, distal, 4 - #614065; Myopathy, myofibrillar, 5 - MIM#609524
Review for gene: FLNC was set to GREEN
Added comment: ClinGen definitive gene-disease validation for myofibrillar myopathy type 5 and dilated cardiomyopathy. Predominantly adult onset phenotype, AD inheritance. 4 unrelated cases with likely de novo FLNC variants presenting with congenital myopathy and arthrogryposis have also been reported which are features amenable to antenatal detection.

PMID 29858533 Kiselev et al reported 4 unrelated patients with early onset myopathy and restrictive cardiomyopathy. 3/4 also presented with arthrogryposis.

x1 patient required delivery via CS due to breech presentation and at birth was noted to have arthrogryposis and hip dysplasia - de novo FLNC variant confirmed. RCM diagnosed age 2

x1 patient noted to have IUGR in a pregnancy complicated by pre-eclampsia. At birth was noted to have arthrogryposis, hip subluxation and abdominal wall weakness with herniation. RCM diagnosed age 6 months. Variant not present in unaffected mother, paternal DNA unavailable.

x1 patient required CS delivery due to insufficient rotation in birth canal. Noted to have arthrogryposis at birth. Variant confirmed to be de novo

x1 patient presented with muscle weakness first year of life, RCM age 3. Parents declined genetic testing.

---
Other cases of interest

PMID 30260051 Schubert et al 2018 - report two restrictive cardiomyopathy families with childhood onset disease with age 1 being the earliest age of diagnosis in a DCDA monozygotic twin who was also diagnosed with a small VSD perinatally. Both twins were also noted to have extra-cardiac manifestations at the time of diagnosis including developmental delay, hypotonia, dysmorphic facial features, and clasped thumbs with onset of kidney dysfunction age 3 post-cardiac transplant.

PMID: 32516863 – Kolbel et al 2020 report one neonate with homozygous FLNC variant c.1325C>G (p.Pro442Arg). Absent from gnomad. Presented with weak suck first month of life with subsequent motor development delay, generalised muscular hypotonia, contractures. Variant confirmed in both unaffected parents. Authors postulate this is a novel case of homozygous FLNC variants associated with congenital presentation. This is a single case report, only heterozygous variants reported so far including in congenital presentations, both parents with het variants unaffected. Possibility of an alternative genetic explanation for this patient's presentation not excluded.
Sources: Literature
Fetal anomalies v0.2846 MKS1 Alison Yeung Marked gene: MKS1 as ready
Fetal anomalies v0.2846 MKS1 Alison Yeung Gene: mks1 has been classified as Green List (High Evidence).
Fetal anomalies v0.2846 MKS1 Alison Yeung Phenotypes for gene: MKS1 were changed from MECKEL SYNDROME TYPE 1; BARDET-BIEDL SYNDROME TYPE 13 to Joubert syndrome 28, MIM# 617121; MONDO:0014928; Meckel syndrome 1, MIM# 249000; MONDO:0009571
Fetal anomalies v0.2845 MKKS Alison Yeung Marked gene: MKKS as ready
Fetal anomalies v0.2845 MKKS Alison Yeung Gene: mkks has been classified as Green List (High Evidence).
Fetal anomalies v0.2845 MKKS Alison Yeung Phenotypes for gene: MKKS were changed from BARDET-BIEDL SYNDROME TYPE 6; MCKUSICK-KAUFMAN SYNDROME to McKusick-Kaufman syndrome, MIM# 236700; Bardet-Biedl syndrome 6, MIM# 605231
Fetal anomalies v0.2844 MGP Alison Yeung Marked gene: MGP as ready
Fetal anomalies v0.2844 MGP Alison Yeung Gene: mgp has been classified as Green List (High Evidence).
Fetal anomalies v0.2844 MGP Alison Yeung Phenotypes for gene: MGP were changed from KEUTEL SYNDROME to Keutel syndrome, MIM #245150
Fetal anomalies v0.2843 MGP Alison Yeung reviewed gene: MGP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v0.2843 MTM1 Alison Yeung Marked gene: MTM1 as ready
Fetal anomalies v0.2843 MTM1 Alison Yeung Gene: mtm1 has been classified as Green List (High Evidence).
Fetal anomalies v0.2843 MTM1 Alison Yeung Phenotypes for gene: MTM1 were changed from MYOTUBULAR MYOPATHY, X-LINKED to Myotubular myopathy, X-linked, MIM# 310400
Fetal anomalies v0.2842 MTM1 Alison Yeung reviewed gene: MTM1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v0.2842 MFSD2A Alison Yeung Marked gene: MFSD2A as ready
Fetal anomalies v0.2842 MFSD2A Alison Yeung Gene: mfsd2a has been classified as Green List (High Evidence).
Fetal anomalies v0.2842 MFSD2A Alison Yeung Phenotypes for gene: MFSD2A were changed from Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain imaging abnormalities, 616486 to Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain imaging abnormalities, MIM# 616486
Leukodystrophy - paediatric v0.243 ABCC9 Zornitza Stark Marked gene: ABCC9 as ready
Leukodystrophy - paediatric v0.243 ABCC9 Zornitza Stark Gene: abcc9 has been classified as Amber List (Moderate Evidence).
Leukodystrophy - paediatric v0.243 ABCC9 Zornitza Stark Classified gene: ABCC9 as Amber List (moderate evidence)
Leukodystrophy - paediatric v0.243 ABCC9 Zornitza Stark Gene: abcc9 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.2841 MFRP Alison Yeung Marked gene: MFRP as ready
Fetal anomalies v0.2841 MFRP Alison Yeung Gene: mfrp has been classified as Red List (Low Evidence).
Fetal anomalies v0.2841 MFRP Alison Yeung Classified gene: MFRP as Red List (low evidence)
Fetal anomalies v0.2841 MFRP Alison Yeung Added comment: Comment on list classification: Ocular anomalies not detectable on US. No extra-ocular fetal anomalies reported. Marked as Red for fetal anomalies gene panel
Fetal anomalies v0.2841 MFRP Alison Yeung Gene: mfrp has been classified as Red List (Low Evidence).
Leukodystrophy - paediatric v0.242 ABCC9 Zornitza Stark gene: ABCC9 was added
gene: ABCC9 was added to Leukodystrophy - paediatric. Sources: Literature
Mode of inheritance for gene: ABCC9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCC9 were set to 31575858
Phenotypes for gene: ABCC9 were set to Intellectual disability and myopathy syndrome, MIM# 619719
Review for gene: ABCC9 was set to AMBER
Added comment: PMID 31575858: Report of 6 cases from 2 families, all with homozygous c.1320+1G>A. Phenotype of mild ID, similar facies, myopathy, cerebral white matter hyperintensities, and cardiac systolic dysfunction in the oldest cases.
'This mutation results in an in-frame deletion of exon 8, which results in non-functional KATP channels in recombinant assays. SUR2 loss-of-function causes fatigability and cardiac dysfunction in mice, and reduced activity, cardiac dysfunction and ventricular enlargement in zebrafish. We term this channelopathy resulting from loss-of-function of SUR2-containing KATP channels ABCC9-related Intellectual disability Myopathy Syndrome (AIMS). The phenotype differs from Cantú syndrome, which is caused by gain-of-function ABCC9 mutations, reflecting the opposing consequences of KATP loss- versus gain-of-function'.
Sources: Literature
Fetal anomalies v0.2840 MFRP Alison Yeung changed review comment from: Bi-allelic variants in this gene associated with posterior microphthalmia with retinitis pigmentosa, foveoschisis, and optic disc drusen. Ocular abnormalities not detectable on fetal US and no association with extra-ocular fetal anomalies.; to: Bi-allelic variants in this gene associated with posterior microphthalmia with retinitis pigmentosa, foveoschisis, and optic disc drusen. Ocular abnormalities not detectable on fetal US and no association with extra-ocular fetal anomalies.
Fetal anomalies v0.2840 MFRP Alison Yeung reviewed gene: MFRP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.4470 ABCC9 Zornitza Stark Marked gene: ABCC9 as ready
Intellectual disability syndromic and non-syndromic v0.4470 ABCC9 Zornitza Stark Gene: abcc9 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4470 ABCC9 Zornitza Stark Phenotypes for gene: ABCC9 were changed from to Intellectual disability and myopathy syndrome, MIM# 619719; Hypertrichotic osteochondrodysplasia, MIM# 239850 Cantu syndrome
Intellectual disability syndromic and non-syndromic v0.4469 ABCC9 Zornitza Stark Mode of inheritance for gene: ABCC9 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4468 ABCC9 Zornitza Stark reviewed gene: ABCC9: Rating: GREEN; Mode of pathogenicity: None; Publications: 31575858, 22610116, 22608503; Phenotypes: Intellectual disability and myopathy syndrome, MIM# 619719, Hypertrichotic osteochondrodysplasia, MIM# 239850 Cantu syndrome; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.10808 ABCC9 Zornitza Stark Phenotypes for gene: ABCC9 were changed from Hypertrichotic osteochondrodysplasia, MIM# 239850; Cantu syndrome; mild ID, similar facies, myopathy, cerebral white matter hyperintensities; cardiac systolic dysfunction to Hypertrichotic osteochondrodysplasia, MIM# 239850; Cantu syndrome; Intellectual disability and myopathy syndrome, MIM# 619719
Mendeliome v0.10807 ABCC9 Zornitza Stark Mode of inheritance for gene: ABCC9 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.10806 ABCC9 Zornitza Stark edited their review of gene: ABCC9: Changed phenotypes: Hypertrichotic osteochondrodysplasia, MIM# 239850, Cantu syndrome, Intellectual disability and myopathy syndrome, MIM# 619719
Fetal anomalies v0.2840 IQCB1 Alison Yeung Marked gene: IQCB1 as ready
Fetal anomalies v0.2840 IQCB1 Alison Yeung Added comment: Comment when marking as ready: Not associated with fetal anomalies. Marked as RED for fetal anomalies panel
Fetal anomalies v0.2840 IQCB1 Alison Yeung Gene: iqcb1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.2840 IQCB1 Alison Yeung Classified gene: IQCB1 as Red List (low evidence)
Fetal anomalies v0.2840 IQCB1 Alison Yeung Gene: iqcb1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.2839 IQCB1 Alison Yeung reviewed gene: IQCB1: Rating: RED; Mode of pathogenicity: None; Publications: 15723066, 21220633, 20881296, 21901789, 33512896, 33535056, 29219953; Phenotypes: Senior-Loken syndrome 5, MIM# 609254, MONDO:0012225; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.2839 IARS Alison Yeung Phenotypes for gene: IARS were changed from Growth retardation, impaired intellectual development, hypotonia, and hepatopathy, 617093 to Growth retardation, impaired intellectual development, hypotonia, and hepatopathy, OMIM# 617093
Fetal anomalies v0.2838 IARS Alison Yeung reviewed gene: IARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 27426735, 27891590; Phenotypes: Growth retardation, impaired intellectual development, hypotonia, and hepatopathy, MIM#617093; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.2838 IARS Alison Yeung Marked gene: IARS as ready
Fetal anomalies v0.2838 IARS Alison Yeung Gene: iars has been classified as Green List (High Evidence).
Fetal anomalies v0.2838 CTU2 Alison Yeung Marked gene: CTU2 as ready
Fetal anomalies v0.2838 CTU2 Alison Yeung Gene: ctu2 has been classified as Green List (High Evidence).
Fetal anomalies v0.2838 TNNI2 Zornitza Stark Marked gene: TNNI2 as ready
Fetal anomalies v0.2838 TNNI2 Zornitza Stark Gene: tnni2 has been classified as Green List (High Evidence).
Fetal anomalies v0.2838 TNNI2 Zornitza Stark Phenotypes for gene: TNNI2 were changed from Arthrogryposis multiplex congenita, distal, type 2B 601680 to Arthrogryposis multiplex congenita, distal, type 2B MIM#601680
Fetal anomalies v0.2837 TNNI2 Zornitza Stark Publications for gene: TNNI2 were set to
Fetal anomalies v0.2836 TNNI2 Zornitza Stark Mode of inheritance for gene: TNNI2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.2835 TNNI2 Zornitza Stark changed review comment from: Gain of function with increased ATPase activity in actin-activated myosin ATPase assays, reflecting increased calcium sensitivity and consistent with increased contractility demonstrated for at least two variants.; to: Gain of function with increased ATPase activity in actin-activated myosin ATPase assays, reflecting increased calcium sensitivity and consistent with increased contractility demonstrated for at least two variants.

Perinatal presentation.
Fetal anomalies v0.2835 TNNT1 Zornitza Stark Marked gene: TNNT1 as ready
Fetal anomalies v0.2835 TNNT1 Zornitza Stark Gene: tnnt1 has been classified as Green List (High Evidence).
Fetal anomalies v0.2835 TNNT1 Zornitza Stark Phenotypes for gene: TNNT1 were changed from Nemaline myopathy, Amish type 605355 to Nemaline myopathy 5, Amish type, MIM# 605355
Fetal anomalies v0.2834 TNNT1 Zornitza Stark Publications for gene: TNNT1 were set to
Fetal anomalies v0.2833 ACP5 Zornitza Stark Publications for gene: ACP5 were set to
Mendeliome v0.10806 ACP5 Zornitza Stark Phenotypes for gene: ACP5 were changed from to Spondyloenchondrodysplasia with immune dysregulation, OMIM# 607944
Mendeliome v0.10805 ACP5 Zornitza Stark Publications for gene: ACP5 were set to
Mendeliome v0.10804 ACP5 Zornitza Stark Mode of inheritance for gene: ACP5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10803 ACP2 Zornitza Stark Phenotypes for gene: ACP2 were changed from to Lysosomal acid phosphatase deficiency, MIM# 200950
Mendeliome v0.10802 ACP2 Zornitza Stark Publications for gene: ACP2 were set to
Mendeliome v0.10801 ACP2 Zornitza Stark Mode of inheritance for gene: ACP2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.2832 ACAN Zornitza Stark Phenotypes for gene: ACAN were changed from SPONDYLOEPIMETAPHYSEAL DYSPLASIA AGGRECAN TYPE; SPONDYLOEPIPHYSEAL DYSPLASIA TYPE KIMBERLEY to Spondyloepimetaphyseal dysplasia, aggrecan type, OMIM# 612813; Short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans, OMIM# 165800
Fetal anomalies v0.2831 ACAN Zornitza Stark Publications for gene: ACAN were set to
Cerebellar and Pontocerebellar Hypoplasia v1.43 TBCE Zornitza Stark Marked gene: TBCE as ready
Cerebellar and Pontocerebellar Hypoplasia v1.43 TBCE Zornitza Stark Gene: tbce has been classified as Green List (High Evidence).
Ataxia - paediatric v0.322 TBCE Zornitza Stark Marked gene: TBCE as ready
Ataxia - paediatric v0.322 TBCE Zornitza Stark Gene: tbce has been classified as Green List (High Evidence).
Regression v0.397 PIK3R5 Zornitza Stark Marked gene: PIK3R5 as ready
Regression v0.397 PIK3R5 Zornitza Stark Gene: pik3r5 has been classified as Red List (Low Evidence).
Regression v0.397 PIK3R5 Zornitza Stark Phenotypes for gene: PIK3R5 were changed from to Ataxia-oculomotor apraxia 3, OMIM #615217
Regression v0.396 PIK3R5 Zornitza Stark Publications for gene: PIK3R5 were set to
Regression v0.395 PIK3R5 Zornitza Stark Mode of inheritance for gene: PIK3R5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Regression v0.394 PIK3R5 Zornitza Stark Classified gene: PIK3R5 as Red List (low evidence)
Regression v0.394 PIK3R5 Zornitza Stark Gene: pik3r5 has been classified as Red List (Low Evidence).
Regression v0.393 PIK3R5 Zornitza Stark reviewed gene: PIK3R5: Rating: RED; Mode of pathogenicity: None; Publications: 22065524; Phenotypes: Ataxia-oculomotor apraxia 3, OMIM #615217; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10800 PIK3R5 Zornitza Stark Marked gene: PIK3R5 as ready
Mendeliome v0.10800 PIK3R5 Zornitza Stark Gene: pik3r5 has been classified as Red List (Low Evidence).
Mendeliome v0.10800 PIK3R5 Zornitza Stark Phenotypes for gene: PIK3R5 were changed from to Ataxia-oculomotor apraxia 3, OMIM #615217
Mendeliome v0.10799 PIK3R5 Zornitza Stark Publications for gene: PIK3R5 were set to
Mendeliome v0.10798 PIK3R5 Zornitza Stark Mode of inheritance for gene: PIK3R5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10797 PIK3R5 Zornitza Stark Classified gene: PIK3R5 as Red List (low evidence)
Mendeliome v0.10797 PIK3R5 Zornitza Stark Gene: pik3r5 has been classified as Red List (Low Evidence).
Mendeliome v0.10796 PIK3R5 Zornitza Stark reviewed gene: PIK3R5: Rating: RED; Mode of pathogenicity: None; Publications: 22065524; Phenotypes: Ataxia-oculomotor apraxia 3, OMIM #615217; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia - paediatric v0.322 PIK3R5 Zornitza Stark Marked gene: PIK3R5 as ready
Ataxia - paediatric v0.322 PIK3R5 Zornitza Stark Gene: pik3r5 has been classified as Red List (Low Evidence).
Ataxia - paediatric v0.322 PIGS Zornitza Stark Marked gene: PIGS as ready
Ataxia - paediatric v0.322 PIGS Zornitza Stark Gene: pigs has been classified as Green List (High Evidence).
Ataxia - paediatric v0.322 PIGS Zornitza Stark Publications for gene: PIGS were set to PubMed: 30269814, 33410539
Ataxia - paediatric v0.321 NUBPL Zornitza Stark Marked gene: NUBPL as ready
Ataxia - paediatric v0.321 NUBPL Zornitza Stark Gene: nubpl has been classified as Green List (High Evidence).
Ataxia - paediatric v0.321 NUBPL Zornitza Stark Publications for gene: NUBPL were set to PubMed: 23553477, 32518176,
Cerebellar and Pontocerebellar Hypoplasia v1.43 NOVA2 Zornitza Stark Marked gene: NOVA2 as ready
Cerebellar and Pontocerebellar Hypoplasia v1.43 NOVA2 Zornitza Stark Gene: nova2 has been classified as Green List (High Evidence).
Fetal anomalies v0.2830 NOVA2 Zornitza Stark Marked gene: NOVA2 as ready
Fetal anomalies v0.2830 NOVA2 Zornitza Stark Gene: nova2 has been classified as Green List (High Evidence).
Fetal anomalies v0.2830 NOVA2 Zornitza Stark Phenotypes for gene: NOVA2 were changed from Intellectual disability with ataxia/spasticity to Neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities, MIM# 618859
Fetal anomalies v0.2829 NOVA2 Zornitza Stark Publications for gene: NOVA2 were set to
Fetal anomalies v0.2828 NOVA2 Zornitza Stark Mode of pathogenicity for gene: NOVA2 was changed from to Other
Fetal anomalies v0.2827 NOVA2 Zornitza Stark Mode of inheritance for gene: NOVA2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.2826 NOVA2 Zornitza Stark Classified gene: NOVA2 as Green List (high evidence)
Fetal anomalies v0.2826 NOVA2 Zornitza Stark Gene: nova2 has been classified as Green List (High Evidence).
Fetal anomalies v0.2825 NOVA2 Zornitza Stark changed review comment from: Six individuals with de novo frameshift variants resulting in C-terminal extension suggesting partial LoF as mechanism.
Sources: Literature; to: Six individuals with de novo frameshift variants resulting in C-terminal extension suggesting partial LoF as mechanism.

Structural brain abnormalities reported.


Sources: Literature
Ataxia - paediatric v0.320 NOVA2 Zornitza Stark Marked gene: NOVA2 as ready
Ataxia - paediatric v0.320 NOVA2 Zornitza Stark Gene: nova2 has been classified as Green List (High Evidence).
Fetal anomalies v0.2825 KIF26B Zornitza Stark Marked gene: KIF26B as ready
Fetal anomalies v0.2825 KIF26B Zornitza Stark Gene: kif26b has been classified as Red List (Low Evidence).
Fetal anomalies v0.2825 KIF26B Zornitza Stark gene: KIF26B was added
gene: KIF26B was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: KIF26B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF26B were set to 30151950
Phenotypes for gene: KIF26B were set to Progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis
Review for gene: KIF26B was set to RED
Added comment: 1 report only of infant with progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis secondary to the involvement of anterior horn cells and ventral (motor) nerves. Whole exome sequencing on the trio identified a de novo KIF26B missense variant (p.Gly546Ser). Functional analysis of the variant protein in cultured cells revealed a reduction in the KIF26B protein's ability to promote cell adhesion, a defect that potentially contributes to its pathogenicity.
Sources: Expert Review
Microcephaly v1.95 KIF26B Zornitza Stark Marked gene: KIF26B as ready
Microcephaly v1.95 KIF26B Zornitza Stark Gene: kif26b has been classified as Red List (Low Evidence).
Microcephaly v1.95 KIF26B Zornitza Stark edited their review of gene: KIF26B: Changed rating: RED
Microcephaly v1.95 KIF26B Zornitza Stark gene: KIF26B was added
gene: KIF26B was added to Microcephaly. Sources: Expert Review
Mode of inheritance for gene: KIF26B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF26B were set to 30151950
Phenotypes for gene: KIF26B were set to Progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis
Added comment: 1 report only of infant with progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis secondary to the involvement of anterior horn cells and ventral (motor) nerves. Whole exome sequencing on the trio identified a de novo KIF26B missense variant (p.Gly546Ser). Functional analysis of the variant protein in cultured cells revealed a reduction in the KIF26B protein's ability to promote cell adhesion, a defect that potentially contributes to its pathogenicity.
Sources: Expert Review
Arthrogryposis v0.320 KIF26B Zornitza Stark Marked gene: KIF26B as ready
Arthrogryposis v0.320 KIF26B Zornitza Stark Gene: kif26b has been classified as Red List (Low Evidence).
Arthrogryposis v0.320 KIF26B Zornitza Stark gene: KIF26B was added
gene: KIF26B was added to Arthrogryposis. Sources: Expert Review
Mode of inheritance for gene: KIF26B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF26B were set to 30151950
Phenotypes for gene: KIF26B were set to Progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis
Review for gene: KIF26B was set to RED
Added comment: 1 report only of infant with progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis secondary to the involvement of anterior horn cells and ventral (motor) nerves. Whole exome sequencing on the trio identified a de novo KIF26B missense variant (p.Gly546Ser). Functional analysis of the variant protein in cultured cells revealed a reduction in the KIF26B protein's ability to promote cell adhesion, a defect that potentially contributes to its pathogenicity.
Sources: Expert Review
Cerebellar and Pontocerebellar Hypoplasia v1.43 Zornitza Stark removed gene:AL592103.1 from the panel
Cerebellar and Pontocerebellar Hypoplasia v1.42 KIF26B Zornitza Stark Marked gene: KIF26B as ready
Cerebellar and Pontocerebellar Hypoplasia v1.42 KIF26B Zornitza Stark Gene: kif26b has been classified as Red List (Low Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.42 KIF26B Zornitza Stark gene: KIF26B was added
gene: KIF26B was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Expert Review
Mode of inheritance for gene: KIF26B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF26B were set to 30151950
Phenotypes for gene: KIF26B were set to Progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis
Review for gene: KIF26B was set to RED
Added comment: 1 report only of infant with progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis secondary to the involvement of anterior horn cells and ventral (motor) nerves. Whole exome sequencing on the trio identified a de novo KIF26B missense variant (p.Gly546Ser). Functional analysis of the variant protein in cultured cells revealed a reduction in the KIF26B protein's ability to promote cell adhesion, a defect that potentially contributes to its pathogenicity.
Sources: Expert Review
Mendeliome v0.10796 KIF26B Zornitza Stark Marked gene: KIF26B as ready
Mendeliome v0.10796 KIF26B Zornitza Stark Gene: kif26b has been classified as Red List (Low Evidence).
Mendeliome v0.10796 KIF26B Zornitza Stark gene: KIF26B was added
gene: KIF26B was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: KIF26B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF26B were set to 30151950
Phenotypes for gene: KIF26B were set to Progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis
Review for gene: KIF26B was set to RED
Added comment: 1 report only of infant with progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis secondary to the involvement of anterior horn cells and ventral (motor) nerves. Whole exome sequencing on the trio identified a de novo KIF26B missense variant (p.Gly546Ser). Functional analysis of the variant protein in cultured cells revealed a reduction in the KIF26B protein's ability to promote cell adhesion, a defect that potentially contributes to its pathogenicity.
Sources: Expert Review
Fetal anomalies v0.2824 ACP5 Alison Yeung Marked gene: ACP5 as ready
Fetal anomalies v0.2824 ACP5 Alison Yeung Gene: acp5 has been classified as Green List (High Evidence).
Fetal anomalies v0.2824 ACP5 Alison Yeung Phenotypes for gene: ACP5 were changed from SPONDYLOENCHONDRODYSPLASIA WITH IMMUNE DYSREGULATION to Spondyloenchondrodysplasia with immune dysregulation, OMIM# 607944
Fetal anomalies v0.2823 ACP5 Alison Yeung reviewed gene: ACP5: Rating: GREEN; Mode of pathogenicity: None; Publications: 26854080, 26951490, 21217755, 26789720, 2363422, 21217752; Phenotypes: Spondyloenchondrodysplasia with immune dysregulation, OMIM# 607944; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10795 ACP5 Alison Yeung Marked gene: ACP5 as ready
Mendeliome v0.10795 ACP5 Alison Yeung Gene: acp5 has been classified as Green List (High Evidence).
Mendeliome v0.10795 ACP5 Alison Yeung reviewed gene: ACP5: Rating: GREEN; Mode of pathogenicity: None; Publications: 26854080, 26951490, 21217755, 26789720, 2363422, 21217752; Phenotypes: spondyloenchondrodysplasia with immune dysregulation, OMIM# 607944; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10795 ACP2 Alison Yeung Marked gene: ACP2 as ready
Mendeliome v0.10795 ACP2 Alison Yeung Gene: acp2 has been classified as Red List (Low Evidence).
Mendeliome v0.10795 ACP2 Alison Yeung Classified gene: ACP2 as Red List (low evidence)
Mendeliome v0.10795 ACP2 Alison Yeung Gene: acp2 has been classified as Red List (Low Evidence).
Mendeliome v0.10794 ACP2 Alison Yeung reviewed gene: ACP2: Rating: RED; Mode of pathogenicity: None; Publications: 5410815; Phenotypes: Lysosomal acid phosphatase deficiency, OMIM# 200950; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.2823 ACAN Alison Yeung Marked gene: ACAN as ready
Fetal anomalies v0.2823 ACAN Alison Yeung Gene: acan has been classified as Green List (High Evidence).
Fetal anomalies v0.2823 ACAN Alison Yeung reviewed gene: ACAN: Rating: GREEN; Mode of pathogenicity: None; Publications: 24762113, 27870580, 19110214, 30124491, 28331218, 20137779; Phenotypes: Spondyloepimetaphyseal dysplasia, aggrecan type, OMIM# 612813, Short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans, OMIM# 165800; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Cerebellar and Pontocerebellar Hypoplasia v1.41 TBCE Chirag Patel Classified gene: TBCE as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v1.41 TBCE Chirag Patel Gene: tbce has been classified as Green List (High Evidence).
Ataxia - paediatric v0.320 TBCE Chirag Patel Classified gene: TBCE as Green List (high evidence)
Ataxia - paediatric v0.320 TBCE Chirag Patel Gene: tbce has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.40 TBCE Chirag Patel gene: TBCE was added
gene: TBCE was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Literature
Mode of inheritance for gene: TBCE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBCE were set to PubMed: 27666369
Phenotypes for gene: TBCE were set to Encephalopathy, progressive, with amyotrophy and optic atrophy, OMIM #617207
Review for gene: TBCE was set to GREEN
Added comment: 5 patients from 3 unrelated Italian families with progressive encephalopathy with amyotrophy and optic atrophy (PEAMO), and biallelic variants in TCBE gene (WES or Sanger). PEAMO is a severe autosomal recessive neurodegenerative disorder characterized by delayed development with hypotonia apparent in infancy and subsequent motor regression. Most affected individuals are unable to or lose the ability to sit and show distal amyotrophy and weakness of all 4 limbs. The patients are cognitively impaired and unable to speak or have severe dysarthria. Additional features include optic atrophy, thin corpus callosum, and cerebellar atrophy.
Sources: Literature
Ataxia - paediatric v0.319 TBCE Chirag Patel gene: TBCE was added
gene: TBCE was added to Ataxia - paediatric. Sources: Literature
Mode of inheritance for gene: TBCE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBCE were set to PubMed: 27666369
Phenotypes for gene: TBCE were set to Encephalopathy, progressive, with amyotrophy and optic atrophy, OMIM #617207
Review for gene: TBCE was set to GREEN
Added comment: 5 patients from 3 unrelated Italian families with progressive encephalopathy with amyotrophy and optic atrophy (PEAMO), and biallelic variants in TCBE gene (WES or Sanger). PEAMO is a severe autosomal recessive neurodegenerative disorder characterized by delayed development with hypotonia apparent in infancy and subsequent motor regression. Most affected individuals are unable to or lose the ability to sit and show distal amyotrophy and weakness of all 4 limbs. The patients are cognitively impaired and unable to speak or have severe dysarthria. Additional features include optic atrophy, thin corpus callosum, and cerebellar atrophy.
Sources: Literature
Cerebellar and Pontocerebellar Hypoplasia v1.39 PIK3R5 Chirag Patel gene: PIK3R5 was added
gene: PIK3R5 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Literature
Mode of inheritance for gene: PIK3R5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIK3R5 were set to PubMed: 22065524
Phenotypes for gene: PIK3R5 were set to Ataxia-oculomotor apraxia 3, OMIM #615217
Review for gene: PIK3R5 was set to RED
Added comment: Al Tassan et al. (2012) reported 4 sibs, from consanguineous Saudi Arabian family, with ataxia-oculomotor apraxia. The proband developed progressive unsteady gait and had frequent falls at age 14 years with later onset of arm dysmetria and dysarthria. He became wheelchair-bound at age 23. Ocular movement was impaired, with slowed saccadic eye movements and head-eye lag resulting in head thrust, but smooth pursuit was normal. He had severe limb and axial dysmetria with mild distal atrophy and weakness affecting the lower limbs more than the upper limbs. He also had distal sensory impairment, more prominent in the lower limbs, areflexia, and axonal sensory polyneuropathy with absent sensory nerve action potentials in the lower limbs. Laboratory studies showed increased level of alpha-fetoprotein, and brain MRI showed atrophy of the cerebellar folia and vermis. His 3 sibs were similarly affected. A homozygous mutation in the PIK3R5 gene (P629S) was found by linkage analysis followed by sequencing of the genes within the region.
Sources: Literature
Ataxia - paediatric v0.318 PIK3R5 Chirag Patel gene: PIK3R5 was added
gene: PIK3R5 was added to Ataxia - paediatric. Sources: Literature
Mode of inheritance for gene: PIK3R5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIK3R5 were set to PubMed: 22065524
Phenotypes for gene: PIK3R5 were set to Ataxia-oculomotor apraxia 3, OMIM #615217
Review for gene: PIK3R5 was set to RED
Added comment: Al Tassan et al. (2012) reported 4 sibs, from consanguineous Saudi Arabian family, with ataxia-oculomotor apraxia. The proband developed progressive unsteady gait and had frequent falls at age 14 years with later onset of arm dysmetria and dysarthria. He became wheelchair-bound at age 23. Ocular movement was impaired, with slowed saccadic eye movements and head-eye lag resulting in head thrust, but smooth pursuit was normal. He had severe limb and axial dysmetria with mild distal atrophy and weakness affecting the lower limbs more than the upper limbs. He also had distal sensory impairment, more prominent in the lower limbs, areflexia, and axonal sensory polyneuropathy with absent sensory nerve action potentials in the lower limbs. Laboratory studies showed increased level of alpha-fetoprotein, and brain MRI showed atrophy of the cerebellar folia and vermis. His 3 sibs were similarly affected. A homozygous mutation in the PIK3R5 gene (P629S) was found by linkage analysis followed by sequencing of the genes within the region.
Sources: Literature
Ataxia - paediatric v0.317 PIGS Chirag Patel Classified gene: PIGS as Green List (high evidence)
Ataxia - paediatric v0.317 PIGS Chirag Patel Gene: pigs has been classified as Green List (High Evidence).
Ataxia - paediatric v0.316 PIGS Chirag Patel gene: PIGS was added
gene: PIGS was added to Ataxia - paediatric. Sources: Literature
Mode of inheritance for gene: PIGS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGS were set to PubMed: 30269814, 33410539
Phenotypes for gene: PIGS were set to Developmental and epileptic encephalopathy 95, OMIM # 618143
Review for gene: PIGS was set to GREEN
Added comment: DEE95 is a severe autosomal recessive developmental disorder characterized by severely impaired global development, hypotonia, weakness, ataxia, coarse facial features, and intractable seizures. Mutiple patients reported with biallelic variants. Some functional evidence with decreased levels of GPI-anchored proteins compared to controls.
Sources: Literature
Ataxia - paediatric v0.315 NUBPL Chirag Patel Classified gene: NUBPL as Green List (high evidence)
Ataxia - paediatric v0.315 NUBPL Chirag Patel Gene: nubpl has been classified as Green List (High Evidence).
Ataxia - paediatric v0.314 NUBPL Chirag Patel gene: NUBPL was added
gene: NUBPL was added to Ataxia - paediatric. Sources: Literature
Mode of inheritance for gene: NUBPL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUBPL were set to PubMed: 23553477, 32518176,
Phenotypes for gene: NUBPL were set to Mitochondrial complex I deficiency, nuclear type 21, OMIM # 618242
Review for gene: NUBPL was set to GREEN
Added comment: Many patients reported with biallelic variants in gene with mitochondrial complex I deficiency. Presents with various neurodevelopmental issues including ataxia.
Sources: Literature
Cerebellar and Pontocerebellar Hypoplasia v1.38 NOVA2 Chirag Patel Classified gene: NOVA2 as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v1.38 NOVA2 Chirag Patel Gene: nova2 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.38 NOVA2 Chirag Patel Classified gene: NOVA2 as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v1.38 NOVA2 Chirag Patel Gene: nova2 has been classified as Green List (High Evidence).
Ataxia - paediatric v0.313 NOVA2 Chirag Patel Classified gene: NOVA2 as Green List (high evidence)
Ataxia - paediatric v0.313 NOVA2 Chirag Patel Gene: nova2 has been classified as Green List (High Evidence).
Ataxia - paediatric v0.313 NOVA2 Chirag Patel Classified gene: NOVA2 as Green List (high evidence)
Ataxia - paediatric v0.313 NOVA2 Chirag Patel Gene: nova2 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.37 NOVA2 Chirag Patel gene: NOVA2 was added
gene: NOVA2 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Literature
Mode of inheritance for gene: NOVA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NOVA2 were set to PMID: 32197073
Phenotypes for gene: NOVA2 were set to Neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities, OMIM #618859
Review for gene: NOVA2 was set to GREEN
Added comment: Six individuals with de novo frameshift variants resulting in C-terminal extension suggesting partial LoF as mechanism. Early-onset neurologic disorder characterized by global developmental delay, poor or absent speech and language development, and behavioral abnormalities reminiscent of autism spectrum disorder. Additional features may include poor overall growth with small head circumference, axial hypotonia, spasticity, and seizures. Some patients have abnormal findings on brain imaging, including cerebral atrophy, cerebellar atrophy, and/or thin corpus callosum.
Sources: Literature
Ataxia - paediatric v0.312 NOVA2 Chirag Patel gene: NOVA2 was added
gene: NOVA2 was added to Ataxia - paediatric. Sources: Literature
Mode of inheritance for gene: NOVA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NOVA2 were set to PMID: 32197073
Phenotypes for gene: NOVA2 were set to Neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities, OMIM #618859
Review for gene: NOVA2 was set to GREEN
Added comment: Six individuals with de novo frameshift variants resulting in C-terminal extension suggesting partial LoF as mechanism. Early-onset neurologic disorder characterized by global developmental delay, poor or absent speech and language development, and behavioral abnormalities reminiscent of autism spectrum disorder. Additional features may include poor overall growth with small head circumference, axial hypotonia, spasticity, and seizures. Some patients have abnormal findings on brain imaging, including cerebral atrophy, cerebellar atrophy, and/or thin corpus callosum.
Sources: Literature
Cerebellar and Pontocerebellar Hypoplasia v1.36 AL592103.1 Chirag Patel gene: AL592103.1 was added
gene: AL592103.1 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Literature
Mode of inheritance for gene: AL592103.1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AL592103.1 were set to PMID: 30151950
Phenotypes for gene: AL592103.1 were set to Progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis
Review for gene: AL592103.1 was set to RED
Added comment: 1 report only of infant with progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis secondary to the involvement of anterior horn cells and ventral (motor) nerves. Whole exome sequencing on the trio identified a de novo KIF26B missense variant (p.Gly546Ser). Functional analysis of the variant protein in cultured cells revealed a reduction in the KIF26B protein's ability to promote cell adhesion, a defect that potentially contributes to its pathogenicity.
Sources: Literature
Genetic Epilepsy v0.1434 SLC45A1 Zornitza Stark Marked gene: SLC45A1 as ready
Genetic Epilepsy v0.1434 SLC45A1 Zornitza Stark Gene: slc45a1 has been classified as Amber List (Moderate Evidence).
Genetic Epilepsy v0.1434 SLC45A1 Zornitza Stark Phenotypes for gene: SLC45A1 were changed from to Intellectual developmental disorder with neuropsychiatric features, MIM# 617532
Genetic Epilepsy v0.1433 SLC45A1 Zornitza Stark Publications for gene: SLC45A1 were set to
Genetic Epilepsy v0.1432 SLC45A1 Zornitza Stark Mode of inheritance for gene: SLC45A1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Genetic Epilepsy v0.1431 SLC45A1 Zornitza Stark Classified gene: SLC45A1 as Amber List (moderate evidence)
Genetic Epilepsy v0.1431 SLC45A1 Zornitza Stark Gene: slc45a1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.2823 SLC45A1 Zornitza Stark Marked gene: SLC45A1 as ready
Fetal anomalies v0.2823 SLC45A1 Zornitza Stark Gene: slc45a1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.2823 SLC45A1 Zornitza Stark Phenotypes for gene: SLC45A1 were changed from Intellectual disability and epilepsy to Intellectual developmental disorder with neuropsychiatric features, MIM# 617532
Fetal anomalies v0.2822 SLC45A1 Zornitza Stark Publications for gene: SLC45A1 were set to
Fetal anomalies v0.2821 SLC45A1 Zornitza Stark Classified gene: SLC45A1 as Red List (low evidence)
Fetal anomalies v0.2821 SLC45A1 Zornitza Stark Gene: slc45a1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.2820 SLC45A1 Zornitza Stark changed review comment from: Intellectual developmental disorder with neuropsychiatric features is an autosomal recessive disorder characterized by moderate intellectual disability, relatively mild seizures, and neuropsychiatric abnormalities, such as anxiety, obsessive-compulsive behavior, and autistic features. Mild facial dysmorphic features may also be present.

Two families reported and some functional data.; to: Intellectual developmental disorder with neuropsychiatric features is an autosomal recessive disorder characterized by moderate intellectual disability, relatively mild seizures, and neuropsychiatric abnormalities, such as anxiety, obsessive-compulsive behavior, and autistic features. Mild facial dysmorphic features may also be present.

Two families reported and some functional data.

Clinical presentation is typically post-natal.
Fetal anomalies v0.2820 SLC45A1 Zornitza Stark edited their review of gene: SLC45A1: Changed rating: RED
Fetal anomalies v0.2820 SLC35A1 Zornitza Stark Marked gene: SLC35A1 as ready
Fetal anomalies v0.2820 SLC35A1 Zornitza Stark Gene: slc35a1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.2820 SLC35A1 Zornitza Stark Phenotypes for gene: SLC35A1 were changed from CONGENITAL DISORDERS OF GLYCOSYLATION to Congenital disorder of glycosylation, type IIf, MIM# 603585
Fetal anomalies v0.2819 SLC35A1 Zornitza Stark Publications for gene: SLC35A1 were set to
Fetal anomalies v0.2818 SLC35A1 Zornitza Stark changed review comment from: Three unrelated families reported.; to: Three unrelated families reported, variable severity, including onset. Microcephaly reported, but onset uncertain.
Fetal anomalies v0.2818 SLC35A1 Zornitza Stark edited their review of gene: SLC35A1: Changed rating: AMBER
Ataxia - paediatric v0.311 BRAT1 Zornitza Stark Marked gene: BRAT1 as ready
Ataxia - paediatric v0.311 BRAT1 Zornitza Stark Gene: brat1 has been classified as Green List (High Evidence).
Ataxia - paediatric v0.311 BRAT1 Zornitza Stark Publications for gene: BRAT1 were set to PMID: 26483087, 26494257, 27282546
Ataxia - paediatric v0.310 BRAT1 Zornitza Stark reviewed gene: BRAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with cerebellar atrophy and with or without seizures, MIM#618056; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebellar and Pontocerebellar Hypoplasia v1.35 BRAT1 Zornitza Stark Marked gene: BRAT1 as ready
Cerebellar and Pontocerebellar Hypoplasia v1.35 BRAT1 Zornitza Stark Gene: brat1 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.35 BRAT1 Zornitza Stark Publications for gene: BRAT1 were set to PMID: 26483087, 26494257, 27282546
Mendeliome v0.10794 CHP1 Zornitza Stark Marked gene: CHP1 as ready
Mendeliome v0.10794 CHP1 Zornitza Stark Gene: chp1 has been classified as Green List (High Evidence).
Mendeliome v0.10794 CHP1 Zornitza Stark Classified gene: CHP1 as Green List (high evidence)
Mendeliome v0.10794 CHP1 Zornitza Stark Gene: chp1 has been classified as Green List (High Evidence).
Mendeliome v0.10793 CHP1 Zornitza Stark gene: CHP1 was added
gene: CHP1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: CHP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHP1 were set to 29379881; 32787936
Phenotypes for gene: CHP1 were set to Spastic ataxia 9, autosomal recessive, MIM #618438
Review for gene: CHP1 was set to GREEN
Added comment: 2 different consanguineous families with 2 affected siblings with ataxia (1 paediatric onset, 1 adult onset). 3 of the patients had cerebellar atrophy. WES identified homozygous variants in CHP1 gene in both families (K19del and Arg91Cys), which segregated with the disorder in the family.

Decreased CHP1 protein on IHC of cerebellar tissue in family with Arg91Cys variant. In vitro functional expression studies in HEK293 cells showed that the K19del mutation resulted in decreased protein expression, with normal levels of transcript, suggesting defects in protein stability. The mutant protein formed massive protein aggregates in transfected neuronal cell bodies and neurite-like projections, whereas the wildtype protein showed a more uniform distribution. The mutant protein altered CHP1 association into functional complexes and impaired membrane localization of the Na+/H+ transporter NHE1. The findings indicated that the CHP1 mutation likely causes ataxia in an NHE1-dependent manner, resembling the mechanism observed in the Chp1 vacillator mutant mouse.
Sources: Expert Review
Ataxia - paediatric v0.310 CHP1 Zornitza Stark Marked gene: CHP1 as ready
Ataxia - paediatric v0.310 CHP1 Zornitza Stark Gene: chp1 has been classified as Amber List (Moderate Evidence).
Ataxia - paediatric v0.310 CHP1 Zornitza Stark Publications for gene: CHP1 were set to PMID: 29379881, 32787936
Ataxia - paediatric v0.309 CHP1 Zornitza Stark Classified gene: CHP1 as Amber List (moderate evidence)
Ataxia - paediatric v0.309 CHP1 Zornitza Stark Gene: chp1 has been classified as Amber List (Moderate Evidence).
Ataxia - paediatric v0.308 CHP1 Zornitza Stark reviewed gene: CHP1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic ataxia 9, autosomal recessive, OMIM #618438; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia - adult onset v0.150 CHP1 Zornitza Stark Marked gene: CHP1 as ready
Ataxia - adult onset v0.150 CHP1 Zornitza Stark Gene: chp1 has been classified as Amber List (Moderate Evidence).
Ataxia - adult onset v0.150 CHP1 Zornitza Stark Publications for gene: CHP1 were set to PMID: 29379881, 32787936
Ataxia - adult onset v0.149 CHP1 Zornitza Stark Classified gene: CHP1 as Amber List (moderate evidence)
Ataxia - adult onset v0.149 CHP1 Zornitza Stark Gene: chp1 has been classified as Amber List (Moderate Evidence).
Ataxia - adult onset v0.148 CHP1 Zornitza Stark reviewed gene: CHP1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Cerebellar and Pontocerebellar Hypoplasia v1.34 CHP1 Zornitza Stark Marked gene: CHP1 as ready
Cerebellar and Pontocerebellar Hypoplasia v1.34 CHP1 Zornitza Stark Gene: chp1 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.34 CHP1 Zornitza Stark Publications for gene: CHP1 were set to PMID: 29379881, 32787936
Combined Immunodeficiency v1.12 PI4KA Zornitza Stark Phenotypes for gene: PI4KA were changed from Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis MIM#616531; Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis MONDO:0014679 to Gastrointestinal defects and immunodeficiency syndrome 2, MIM# 619708
Combined Immunodeficiency v1.11 PI4KA Zornitza Stark edited their review of gene: PI4KA: Changed phenotypes: Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis MIM#616531, Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis MONDO:0014679, Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, MIM# 616531, Neurodevelopmental syndrome with hypomyelinating leukodystrophy, Spastic paraplegia 84, autosomal recessive, MIM# 619621, Gastrointestinal defects and immunodeficiency syndrome 2, MIM# 619708
Mendeliome v0.10792 PI4KA Zornitza Stark Phenotypes for gene: PI4KA were changed from Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, MIM# 616531; Neurodevelopmental syndrome with hypomyelinating leukodystrophy; Spastic paraplegia 84, autosomal recessive, MIM# 619621 to Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, MIM# 616531; Neurodevelopmental syndrome with hypomyelinating leukodystrophy; Spastic paraplegia 84, autosomal recessive, MIM# 619621; Gastrointestinal defects and immunodeficiency syndrome 2, MIM# 619708
Mendeliome v0.10791 PI4KA Zornitza Stark edited their review of gene: PI4KA: Changed phenotypes: Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, MIM# 616531, Neurodevelopmental syndrome with hypomyelinating leukodystrophy, Spastic paraplegia 84, autosomal recessive, MIM# 619621, Gastrointestinal defects and immunodeficiency syndrome 2, MIM# 619708
Cardiomyopathy_Paediatric v0.121 FNIP1 Zornitza Stark Phenotypes for gene: FNIP1 were changed from Hypertrophic Cardiomyopathy; Primary Immunodeficiency; Agammaglobulinemia; Neutropenia to Immunodeficiency 93 and hypertrophic cardiomyopathy, MIM# 619705
Cardiomyopathy_Paediatric v0.120 FNIP1 Zornitza Stark edited their review of gene: FNIP1: Changed phenotypes: Immunodeficiency 93 and hypertrophic cardiomyopathy, MIM# 619705
Combined Immunodeficiency v1.11 FNIP1 Zornitza Stark Phenotypes for gene: FNIP1 were changed from Hypertrophic Cardiomyopathy; Primary Immunodeficiency; Agammaglobulinemia; Neutropenia to Immunodeficiency 93 and hypertrophic cardiomyopathy, MIM# 619705
Combined Immunodeficiency v1.10 FNIP1 Zornitza Stark edited their review of gene: FNIP1: Changed phenotypes: Hypertrophic Cardiomyopathy, Primary Immunodeficiency, Agammaglobulinemia, Neutropenia, Immunodeficiency 93 and hypertrophic cardiomyopathy, MIM# 619705
Combined Immunodeficiency v1.10 FNIP1 Zornitza Stark edited their review of gene: FNIP1: Changed phenotypes: Hypertrophic Cardiomyopathy, Primary Immunodeficiency, Agammaglobulinemia, NeutropeniaImmunodeficiency 93 and hypertrophic cardiomyopathy, MIM# 619705
Mendeliome v0.10791 FNIP1 Zornitza Stark Phenotypes for gene: FNIP1 were changed from Hypertrophic Cardiomyopathy; Primary Immunodeficiency; Agammaglobulinemia; Neutropenia to Immunodeficiency 93 and hypertrophic cardiomyopathy, MIM# 619705
Mendeliome v0.10790 FNIP1 Zornitza Stark reviewed gene: FNIP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Immunodeficiency 93 and hypertrophic cardiomyopathy, MIM# 619705; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10790 TCF12 Zornitza Stark Phenotypes for gene: TCF12 were changed from Craniosynostosis 3, MIM# 615314; Kallman syndrome to Craniosynostosis 3, MIM# 615314; Hypogonadotropic hypogonadism 26 with or without anosmia, MIM# 619718; Kallman syndrome
Mendeliome v0.10789 TCF12 Zornitza Stark edited their review of gene: TCF12: Changed phenotypes: Craniosynostosis 3, MIM# 615314, Hypogonadotropic hypogonadism 26 with or without anosmia, MIM# 619718, Kallman syndrome
Differences of Sex Development v0.238 TCF12 Zornitza Stark Phenotypes for gene: TCF12 were changed from Kallmann syndrome to Hypogonadotropic hypogonadism 26 with or without anosmia, MIM# 619718; Kallmann syndrome
Differences of Sex Development v0.237 TCF12 Zornitza Stark edited their review of gene: TCF12: Changed phenotypes: Hypogonadotropic hypogonadism 26 with or without anosmia, MIM# 619718, Kallmann syndrome
Predominantly Antibody Deficiency v0.95 SPI1 Zornitza Stark Phenotypes for gene: SPI1 were changed from Agammaglobulinaemia to Agammaglobulinaemia 10, autosomal dominant, MIM# 619707
Predominantly Antibody Deficiency v0.94 SPI1 Zornitza Stark edited their review of gene: SPI1: Changed phenotypes: Agammaglobulinaemia 10, autosomal dominant, MIM# 619707
Mendeliome v0.10789 SPI1 Zornitza Stark Phenotypes for gene: SPI1 were changed from Agammaglobulinaemia to Agammaglobulinaemia 10, autosomal dominant, MIM# 619707
Mendeliome v0.10788 SPI1 Zornitza Stark edited their review of gene: SPI1: Changed phenotypes: Agammaglobulinaemia 10, autosomal dominant, MIM# 619707
Cerebellar and Pontocerebellar Hypoplasia v1.33 CHP1 Chirag Patel Classified gene: CHP1 as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v1.33 CHP1 Chirag Patel Gene: chp1 has been classified as Green List (High Evidence).
Ataxia - adult onset v0.148 CHP1 Chirag Patel Classified gene: CHP1 as Green List (high evidence)
Ataxia - adult onset v0.148 CHP1 Chirag Patel Gene: chp1 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.32 CHP1 Chirag Patel gene: CHP1 was added
gene: CHP1 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Literature
Mode of inheritance for gene: CHP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHP1 were set to PMID: 29379881, 32787936
Phenotypes for gene: CHP1 were set to Spastic ataxia 9, autosomal recessive, OMIM #618438
Review for gene: CHP1 was set to GREEN
Added comment: 2 different consanguineous families with 2 affected siblings with ataxia (1 paediatric onset, 1 adult onset). 3 of the patients had cerebellar atrophy. WES identified homozygous variants in CHP1 gene in both families (K19del and Arg91Cys), which segregated with the disorder in the family.

Decreased CHP1 protein on IHC of cerebellar tissue in family with Arg91Cys variant. In vitro functional expression studies in HEK293 cells showed that the K19del mutation resulted in decreased protein expression, with normal levels of transcript, suggesting defects in protein stability. The mutant protein formed massive protein aggregates in transfected neuronal cell bodies and neurite-like projections, whereas the wildtype protein showed a more uniform distribution. The mutant protein altered CHP1 association into functional complexes and impaired membrane localization of the Na+/H+ transporter NHE1. The findings indicated that the CHP1 mutation likely causes ataxia in an NHE1-dependent manner, resembling the mechanism observed in the Chp1 vacillator mutant mouse.
Sources: Literature
Ataxia - adult onset v0.147 CHP1 Chirag Patel gene: CHP1 was added
gene: CHP1 was added to Ataxia - adult onset. Sources: Literature
Mode of inheritance for gene: CHP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHP1 were set to PMID: 29379881, 32787936
Phenotypes for gene: CHP1 were set to Spastic ataxia 9, autosomal recessive, OMIM #618438
Review for gene: CHP1 was set to GREEN
Added comment: 2 different consanguineous families with 2 affected siblings with ataxia (1 paediatric onset, 1 adult onset). 3 of the patients had cerebellar atrophy. WES identified homozygous variants in CHP1 gene in both families (K19del and Arg91Cys), which segregated with the disorder in the family.

Decreased CHP1 protein on IHC of cerebellar tissue in family with Arg91Cys variant. In vitro functional expression studies in HEK293 cells showed that the K19del mutation resulted in decreased protein expression, with normal levels of transcript, suggesting defects in protein stability. The mutant protein formed massive protein aggregates in transfected neuronal cell bodies and neurite-like projections, whereas the wildtype protein showed a more uniform distribution. The mutant protein altered CHP1 association into functional complexes and impaired membrane localization of the Na+/H+ transporter NHE1. The findings indicated that the CHP1 mutation likely causes ataxia in an NHE1-dependent manner, resembling the mechanism observed in the Chp1 vacillator mutant mouse.
Sources: Literature
Mendeliome v0.10788 CYS1 Zornitza Stark Marked gene: CYS1 as ready
Mendeliome v0.10788 CYS1 Zornitza Stark Gene: cys1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10788 CYS1 Zornitza Stark Classified gene: CYS1 as Amber List (moderate evidence)
Mendeliome v0.10788 CYS1 Zornitza Stark Gene: cys1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10787 CYS1 Zornitza Stark gene: CYS1 was added
gene: CYS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CYS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYS1 were set to 34521872
Phenotypes for gene: CYS1 were set to Polycystic kidney disease, MONDO:0020642
Review for gene: CYS1 was set to AMBER
Added comment: Single family reported. However, extensive experimental data, including mouse model.
Sources: Literature
Ataxia - paediatric v0.308 CHP1 Chirag Patel Classified gene: CHP1 as Green List (high evidence)
Ataxia - paediatric v0.308 CHP1 Chirag Patel Gene: chp1 has been classified as Green List (High Evidence).
Ataxia - paediatric v0.307 CHP1 Chirag Patel gene: CHP1 was added
gene: CHP1 was added to Ataxia - paediatric. Sources: Literature
Mode of inheritance for gene: CHP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHP1 were set to PMID: 29379881, 32787936
Phenotypes for gene: CHP1 were set to Spastic ataxia 9, autosomal recessive, OMIM #618438
Review for gene: CHP1 was set to GREEN
Added comment: 2 different consanguineous families with 2 affected siblings with ataxia (1 paediatric onset, 1 adult onset). 3 of the patients had cerebellar atrophy. WES identified homozygous variants in CHP1 gene in both families (K19del and Arg91Cys), which segregated with the disorder in the family.

Decreased CHP1 protein on IHC of cerebellar tissue in family with Arg91Cys variant. In vitro functional expression studies in HEK293 cells showed that the K19del mutation resulted in decreased protein expression, with normal levels of transcript, suggesting defects in protein stability. The mutant protein formed massive protein aggregates in transfected neuronal cell bodies and neurite-like projections, whereas the wildtype protein showed a more uniform distribution. The mutant protein altered CHP1 association into functional complexes and impaired membrane localization of the Na+/H+ transporter NHE1. The findings indicated that the CHP1 mutation likely causes ataxia in an NHE1-dependent manner, resembling the mechanism observed in the Chp1 vacillator mutant mouse.
Sources: Literature
Renal Ciliopathies and Nephronophthisis v1.8 CYS1 Zornitza Stark Marked gene: CYS1 as ready
Renal Ciliopathies and Nephronophthisis v1.8 CYS1 Zornitza Stark Gene: cys1 has been classified as Amber List (Moderate Evidence).
Renal Ciliopathies and Nephronophthisis v1.8 CYS1 Zornitza Stark Classified gene: CYS1 as Amber List (moderate evidence)
Renal Ciliopathies and Nephronophthisis v1.8 CYS1 Zornitza Stark Gene: cys1 has been classified as Amber List (Moderate Evidence).
Renal Ciliopathies and Nephronophthisis v1.7 CYS1 Zornitza Stark gene: CYS1 was added
gene: CYS1 was added to Renal Ciliopathies and Nephronophthisis. Sources: Literature
Mode of inheritance for gene: CYS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYS1 were set to 34521872
Phenotypes for gene: CYS1 were set to Polycystic kidney disease, MONDO:0020642
Review for gene: CYS1 was set to AMBER
Added comment: Single family reported. However, extensive experimental data, including mouse model.
Sources: Literature
Ataxia - paediatric v0.306 BRAT1 Chirag Patel Classified gene: BRAT1 as Green List (high evidence)
Ataxia - paediatric v0.306 BRAT1 Chirag Patel Gene: brat1 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.31 BRAT1 Chirag Patel Classified gene: BRAT1 as Green List (high evidence)
Cerebellar and Pontocerebellar Hypoplasia v1.31 BRAT1 Chirag Patel Gene: brat1 has been classified as Green List (High Evidence).
Ataxia - paediatric v0.306 BRAT1 Chirag Patel Classified gene: BRAT1 as Green List (high evidence)
Ataxia - paediatric v0.306 BRAT1 Chirag Patel Gene: brat1 has been classified as Green List (High Evidence).
Cerebellar and Pontocerebellar Hypoplasia v1.30 BRAT1 Chirag Patel gene: BRAT1 was added
gene: BRAT1 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Literature
Mode of inheritance for gene: BRAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BRAT1 were set to PMID: 26483087, 26494257, 27282546
Phenotypes for gene: BRAT1 were set to Neurodevelopmental disorder with cerebellar atrophy and with or without seizures, MIM#618056
Review for gene: BRAT1 was set to GREEN
Added comment: At least 4 individuals reported from unrelated families and bi-allelic variants in this gene.
Sources: Literature
Ataxia - paediatric v0.305 BRAT1 Chirag Patel gene: BRAT1 was added
gene: BRAT1 was added to Ataxia - paediatric. Sources: Literature
Mode of inheritance for gene: BRAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BRAT1 were set to PMID: 26483087, 26494257, 27282546
Phenotypes for gene: BRAT1 were set to Neurodevelopmental disorder with cerebellar atrophy and with or without seizures, MIM#618056
Review for gene: BRAT1 was set to GREEN
Added comment: At least 4 individuals reported from unrelated families and bi-allelic variants in this gene.
Sources: Literature
Fetal anomalies v0.2818 PAX7 Zornitza Stark Marked gene: PAX7 as ready
Fetal anomalies v0.2818 PAX7 Zornitza Stark Gene: pax7 has been classified as Red List (Low Evidence).
Fetal anomalies v0.2818 PAX7 Zornitza Stark Classified gene: PAX7 as Red List (low evidence)
Fetal anomalies v0.2818 PAX7 Zornitza Stark Gene: pax7 has been classified as Red List (Low Evidence).
Fetal anomalies v0.2817 PAX7 Zornitza Stark changed review comment from: ID is not part of the phenotype.; to: Progressive disorder, onset in infancy.
Fetal anomalies v0.2817 DNAH2 Zornitza Stark Marked gene: DNAH2 as ready
Fetal anomalies v0.2817 DNAH2 Zornitza Stark Gene: dnah2 has been classified as Red List (Low Evidence).
Fetal anomalies v0.2817 DNAH2 Zornitza Stark Phenotypes for gene: DNAH2 were changed from Hydrops; Complex cardiopathy to Hydrops; complex congenital heart disease; heterotaxy
Fetal anomalies v0.2816 TSPAN7 Zornitza Stark Marked gene: TSPAN7 as ready
Fetal anomalies v0.2816 TSPAN7 Zornitza Stark Gene: tspan7 has been classified as Red List (Low Evidence).
Fetal anomalies v0.2816 TSPAN7 Zornitza Stark Phenotypes for gene: TSPAN7 were changed from MENTAL RETARDATION X-LINKED TYPE 58 to Intellectual developmental disorder, X-linked 58, MIM# 300210
Fetal anomalies v0.2815 TSPAN7 Zornitza Stark reviewed gene: TSPAN7: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, X-linked 58, MIM# 300210; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v0.2815 Zornitza Stark removed gene:TRAPPC2 from the panel
Fetal anomalies v0.2814 Zornitza Stark removed gene:TPP1 from the panel
Fetal anomalies v0.2813 TOGARAM1 Zornitza Stark Marked gene: TOGARAM1 as ready
Fetal anomalies v0.2813 TOGARAM1 Zornitza Stark Gene: togaram1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.2813 Zornitza Stark removed gene:TMPRSS6 from the panel
Fetal anomalies v0.2812 Zornitza Stark removed gene:TNFRSF11B from the panel
Fetal anomalies v0.2811 Zornitza Stark removed gene:TNFRSF13B from the panel
Fetal anomalies v0.2810 MEGF8 Zornitza Stark Marked gene: MEGF8 as ready
Fetal anomalies v0.2810 MEGF8 Zornitza Stark Gene: megf8 has been classified as Green List (High Evidence).
Fetal anomalies v0.2810 MEGF8 Zornitza Stark Phenotypes for gene: MEGF8 were changed from CARPENTER SYNDROME to Carpenter syndrome 2, MIM #614976
Fetal anomalies v0.2809 MEGF8 Zornitza Stark Publications for gene: MEGF8 were set to
Fetal anomalies v0.2808 MEGF8 Zornitza Stark changed review comment from: ID is described in this condition.
Sources: Expert list; to: Craniosynostosis and polysyndactyly.


Sources: Expert list
Fetal anomalies v0.2808 MEF2C Zornitza Stark Marked gene: MEF2C as ready
Fetal anomalies v0.2808 MEF2C Zornitza Stark Gene: mef2c has been classified as Green List (High Evidence).
Fetal anomalies v0.2808 MEF2C Zornitza Stark Phenotypes for gene: MEF2C were changed from MENTAL RETARDATION-STEREOTYPIC MOVEMENTS-EPILEPSY AND/OR CEREBRAL MALFORMATIONS to Mental retardation, stereotypic movements, epilepsy, and/or cerebral malformations, MIM# 613443; MONDO:0013266
Fetal anomalies v0.2807 MEF2C Zornitza Stark Publications for gene: MEF2C were set to
Fetal anomalies v0.2806 MEF2C Zornitza Stark Mode of inheritance for gene: MEF2C was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.2805 MEF2C Zornitza Stark Tag SV/CNV tag was added to gene: MEF2C.
Fetal anomalies v0.2805 MED12 Zornitza Stark Marked gene: MED12 as ready
Fetal anomalies v0.2805 MED12 Zornitza Stark Gene: med12 has been classified as Green List (High Evidence).
Fetal anomalies v0.2805 MED12 Zornitza Stark Phenotypes for gene: MED12 were changed from LUJAN-FRYNS SYNDROME; OPITZ-KAVEGGIA SYNDROME to Lujan-Fryns syndrome, MIM# 309520; Opitz-Kaveggia syndrome, MIM# 305450
Fetal anomalies v0.2804 MED12 Zornitza Stark Publications for gene: MED12 were set to
Fetal anomalies v0.2803 MCPH1 Zornitza Stark Marked gene: MCPH1 as ready
Fetal anomalies v0.2803 MCPH1 Zornitza Stark Gene: mcph1 has been classified as Green List (High Evidence).
Fetal anomalies v0.2803 MCPH1 Zornitza Stark Phenotypes for gene: MCPH1 were changed from MICROCEPHALY PRIMARY TYPE 1 to Microcephaly 1, primary, autosomal recessive, MIM# 251200
Fetal anomalies v0.2802 MCPH1 Zornitza Stark Publications for gene: MCPH1 were set to
Fetal anomalies v0.2801 MCPH1 Zornitza Stark changed review comment from: Well established primary micorcephaly gene.

Sources: Literature; to: Well established primary microcephaly gene.

Sources: Literature
Fetal anomalies v0.2801 MCPH1 Zornitza Stark changed review comment from: Single individual reported as part of a CDH cohort.
Sources: Literature; to: Well established primary micorcephaly gene.

Sources: Literature
Fetal anomalies v0.2801 MCPH1 Zornitza Stark edited their review of gene: MCPH1: Changed rating: GREEN; Changed phenotypes: Microcephaly 1, primary, autosomal recessive, MIM# 251200
Fetal anomalies v0.2801 MCOLN1 Zornitza Stark Marked gene: MCOLN1 as ready
Fetal anomalies v0.2801 MCOLN1 Zornitza Stark Gene: mcoln1 has been classified as Green List (High Evidence).
Fetal anomalies v0.2801 MCOLN1 Zornitza Stark Phenotypes for gene: MCOLN1 were changed from MUCOLIPIDOSIS IV to Mucolipidosis IV, MIM# 252650; MONDO:0009653
Fetal anomalies v0.2800 MCOLN1 Zornitza Stark Publications for gene: MCOLN1 were set to
Fetal anomalies v0.2799 MCOLN1 Zornitza Stark edited their review of gene: MCOLN1: Added comment: Prenatal presentations with brain abnormalities reported.; Changed rating: GREEN; Changed publications: 33963976
Fetal anomalies v0.2799 MCOLN1 Zornitza Stark edited their review of gene: MCOLN1: Changed rating: RED
Fetal anomalies v0.2799 MATN3 Zornitza Stark Marked gene: MATN3 as ready
Fetal anomalies v0.2799 MATN3 Zornitza Stark Gene: matn3 has been classified as Green List (High Evidence).
Fetal anomalies v0.2799 MATN3 Zornitza Stark Phenotypes for gene: MATN3 were changed from Spondyloepimetaphyseal dysplasia, Borochowitz-Cormier-Daire type (MIM#608728); Epiphyseal dysplasia, multiple, 5 (MIM#607078) to Spondyloepimetaphyseal dysplasia, Borochowitz-Cormier-Daire type, MIM# 608728
Fetal anomalies v0.2798 MATN3 Zornitza Stark Mode of inheritance for gene: MATN3 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.2797 MATN3 Zornitza Stark reviewed gene: MATN3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spondyloepimetaphyseal dysplasia, Borochowitz-Cormier-Daire type, MIM# 608728; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.2797 MASP1 Zornitza Stark Marked gene: MASP1 as ready
Fetal anomalies v0.2797 MASP1 Zornitza Stark Gene: masp1 has been classified as Green List (High Evidence).
Fetal anomalies v0.2797 MASP1 Zornitza Stark Phenotypes for gene: MASP1 were changed from 3MC SYNDROME 1 to 3MC syndrome 1, MIM# 257920; MONDO:0009770
Fetal anomalies v0.2796 MASP1 Zornitza Stark Publications for gene: MASP1 were set to
Fetal anomalies v0.2795 MAPRE2 Zornitza Stark Marked gene: MAPRE2 as ready
Fetal anomalies v0.2795 MAPRE2 Zornitza Stark Gene: mapre2 has been classified as Green List (High Evidence).
Fetal anomalies v0.2795 MAPRE2 Zornitza Stark Phenotypes for gene: MAPRE2 were changed from Symmetric circumferential skin creases, congenital, 2, 616734 to Symmetric circumferential skin creases, congenital, 2, MIM#616734
Fetal anomalies v0.2794 MAPRE2 Zornitza Stark Mode of inheritance for gene: MAPRE2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Fetal anomalies v0.2793 MAPRE2 Zornitza Stark changed review comment from: ID is part of the phenotype, more severe in those with bi-allelic variants.
Sources: Expert list; to: Cleft palate and microcephaly reported.

Sources: Expert list
Fetal anomalies v0.2793 MAP2K2 Zornitza Stark Marked gene: MAP2K2 as ready
Fetal anomalies v0.2793 MAP2K2 Zornitza Stark Gene: map2k2 has been classified as Green List (High Evidence).
Fetal anomalies v0.2793 MAP2K2 Zornitza Stark Phenotypes for gene: MAP2K2 were changed from CARDIOFACIOCUTANEOUS SYNDROME to Cardiofaciocutaneous syndrome 4, MIM# 615280
Fetal anomalies v0.2792 MAP2K2 Zornitza Stark Publications for gene: MAP2K2 were set to
Fetal anomalies v0.2791 MAP2K2 Zornitza Stark Mode of pathogenicity for gene: MAP2K2 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
Fetal anomalies v0.2790 MAP2K2 Zornitza Stark Mode of inheritance for gene: MAP2K2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.2789 MAP2K1 Zornitza Stark Marked gene: MAP2K1 as ready
Fetal anomalies v0.2789 MAP2K1 Zornitza Stark Gene: map2k1 has been classified as Green List (High Evidence).
Fetal anomalies v0.2789 MAP2K1 Zornitza Stark Phenotypes for gene: MAP2K1 were changed from CARDIOFACIOCUTANEOUS SYNDROME to Cardiofaciocutaneous syndrome 3, MIM# 615279
Fetal anomalies v0.2788 MAP2K1 Zornitza Stark Publications for gene: MAP2K1 were set to
Fetal anomalies v0.2787 MAP2K1 Zornitza Stark Mode of pathogenicity for gene: MAP2K1 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
Fetal anomalies v0.2786 MAP2K1 Zornitza Stark Mode of inheritance for gene: MAP2K1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.2785 MAGEL2 Zornitza Stark Marked gene: MAGEL2 as ready
Fetal anomalies v0.2785 MAGEL2 Zornitza Stark Gene: magel2 has been classified as Green List (High Evidence).
Fetal anomalies v0.2785 MAGEL2 Zornitza Stark Phenotypes for gene: MAGEL2 were changed from ARTHROGRYPOSIS MULTIPLEX CONGENITA; Schaaf-Yang syndrome, 615547; Schaaf-Yang syndrome to Schaaf-Yang syndrome, MIM# 615547
Fetal anomalies v0.2784 MAGEL2 Zornitza Stark Publications for gene: MAGEL2 were set to 26365340; 27195816
Fetal anomalies v0.2783 MAB21L2 Zornitza Stark Marked gene: MAB21L2 as ready
Fetal anomalies v0.2783 MAB21L2 Zornitza Stark Gene: mab21l2 has been classified as Green List (High Evidence).
Fetal anomalies v0.2783 MAB21L2 Zornitza Stark Phenotypes for gene: MAB21L2 were changed from MICROPHTHALMIA, SYNDROMIC 14 to Microphthalmia/coloboma and skeletal dysplasia syndrome, MIM# 615877
Fetal anomalies v0.2782 MAB21L2 Zornitza Stark Publications for gene: MAB21L2 were set to
Fetal anomalies v0.2781 LZTR1 Zornitza Stark Marked gene: LZTR1 as ready
Fetal anomalies v0.2781 LZTR1 Zornitza Stark Gene: lztr1 has been classified as Green List (High Evidence).
Fetal anomalies v0.2781 LZTR1 Zornitza Stark Phenotypes for gene: LZTR1 were changed from Noonan syndrome 10, 616564; Fetal hydrops to Noonan syndrome 10, MIM#616564; Noonan syndrome 2, MIM#605275; Fetal hydrops
Fetal anomalies v0.2780 LZTR1 Zornitza Stark Mode of pathogenicity for gene: LZTR1 was changed from to Other
Fetal anomalies v0.2779 LZTR1 Zornitza Stark Publications for gene: LZTR1 were set to
Fetal anomalies v0.2778 LZTFL1 Zornitza Stark Marked gene: LZTFL1 as ready
Fetal anomalies v0.2778 LZTFL1 Zornitza Stark Gene: lztfl1 has been classified as Green List (High Evidence).
Fetal anomalies v0.2778 LZTFL1 Zornitza Stark Phenotypes for gene: LZTFL1 were changed from Bardet-Biedl syndrome 17 615994 to Bardet-Biedl syndrome 17, MIM# 615994
Fetal anomalies v0.2777 LZTFL1 Zornitza Stark Publications for gene: LZTFL1 were set to
Fetal anomalies v0.2776 LZTFL1 Zornitza Stark Deleted their comment
Fetal anomalies v0.2776 LYST Zornitza Stark Marked gene: LYST as ready
Fetal anomalies v0.2776 LYST Zornitza Stark Gene: lyst has been classified as Red List (Low Evidence).
Fetal anomalies v0.2776 LYST Zornitza Stark Phenotypes for gene: LYST were changed from CHEDIAK-HIGASHI SYNDROME to Chediak-Higashi syndrome, MIM#214500
Fetal anomalies v0.2775 LYST Zornitza Stark Classified gene: LYST as Red List (low evidence)
Fetal anomalies v0.2775 LYST Zornitza Stark Gene: lyst has been classified as Red List (Low Evidence).
Fetal anomalies v0.2774 LYST Zornitza Stark commented on gene: LYST: Presentation is typically post-natal.
Fetal anomalies v0.2774 LYST Zornitza Stark edited their review of gene: LYST: Changed rating: RED
Fetal anomalies v0.2774 LYST Zornitza Stark Deleted their comment
Fetal anomalies v0.2774 LYST Zornitza Stark Deleted their comment
Fetal anomalies v0.2774 LRRC6 Zornitza Stark Marked gene: LRRC6 as ready
Fetal anomalies v0.2774 LRRC6 Zornitza Stark Gene: lrrc6 has been classified as Green List (High Evidence).
Fetal anomalies v0.2774 LRRC6 Zornitza Stark Phenotypes for gene: LRRC6 were changed from PRIMARY CILIARY DISKINESIA to Ciliary dyskinesia, primary, 19, MIM# 614935
Fetal anomalies v0.2773 LRRC6 Zornitza Stark Publications for gene: LRRC6 were set to
Fetal anomalies v0.2772 LRRC6 Zornitza Stark changed review comment from: More than 10 unrelated families reported.; to: More than 10 unrelated families reported. Situs inversus is a feature.
Fetal anomalies v0.2772 LRP5 Zornitza Stark Marked gene: LRP5 as ready
Fetal anomalies v0.2772 LRP5 Zornitza Stark Gene: lrp5 has been classified as Green List (High Evidence).
Fetal anomalies v0.2772 LRP5 Zornitza Stark Phenotypes for gene: LRP5 were changed from HIGH BONE MASS TRAIT; ENDOSTEAL HYPEROSTOSIS WORTH TYPE; VITREORETINOPATHY EXUDATIVE TYPE 4; OSTEOPETROSIS AUTOSOMAL DOMINANT TYPE 1; OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME to Osteoporosis-pseudoglioma syndrome, MIM# 259770; Polycystic liver disease 4 with or without kidney cysts, MIM# 617875
Fetal anomalies v0.2771 LRP5 Zornitza Stark Mode of inheritance for gene: LRP5 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.2770 LRP5 Zornitza Stark changed review comment from: ID generally normal in all of these conditions.; to: Variants in this gene are associated with multiple disorders. Some have congenital anomalies as a feature.
Fetal anomalies v0.2770 LRP5 Zornitza Stark edited their review of gene: LRP5: Changed rating: GREEN; Changed phenotypes: Osteoporosis-pseudoglioma syndrome, MIM# 259770, Polycystic liver disease 4 with or without kidney cysts, MIM# 617875
Fetal anomalies v0.2770 LRP2 Zornitza Stark Marked gene: LRP2 as ready
Fetal anomalies v0.2770 LRP2 Zornitza Stark Gene: lrp2 has been classified as Green List (High Evidence).
Fetal anomalies v0.2770 LRP2 Zornitza Stark Phenotypes for gene: LRP2 were changed from DONNAI-BARROW SYNDROME to Donnai-Barrow syndrome, MIM# 222448
Fetal anomalies v0.2769 LMX1B Zornitza Stark Marked gene: LMX1B as ready
Fetal anomalies v0.2769 LMX1B Zornitza Stark Gene: lmx1b has been classified as Green List (High Evidence).
Fetal anomalies v0.2769 LMX1B Zornitza Stark Phenotypes for gene: LMX1B were changed from NAIL-PATELLA SYNDROME to Nail-patella syndrome, MIM# 161200, MONDO:0008061
Fetal anomalies v0.2768 LMX1B Zornitza Stark Publications for gene: LMX1B were set to
Fetal anomalies v0.2767 LMX1B Zornitza Stark Mode of inheritance for gene: LMX1B was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.2766 LMX1B Zornitza Stark changed review comment from: Nail-patella syndrome (NPS) is an autosomal-dominant disease characterized by dysplastic nails, absent or hypoplastic patellae, elbow dysplasia, and iliac horns. Varying degrees of proteinuria or hematuria are present, and can occasionally progress to chronic renal failure. >300 families reported.; to: Nail-patella syndrome (NPS) is an autosomal-dominant disease characterized by dysplastic nails, absent or hypoplastic patellae, elbow dysplasia, and iliac horns. Varying degrees of proteinuria or hematuria are present, and can occasionally progress to chronic renal failure. >300 families reported.

Prenatal presentations with abnormal limb movement reported.
Fetal anomalies v0.2766 LMX1B Zornitza Stark Deleted their comment
Fetal anomalies v0.2766 LMX1B Zornitza Stark edited their review of gene: LMX1B: Changed publications: 29089684
Fetal anomalies v0.2766 LMOD3 Zornitza Stark Marked gene: LMOD3 as ready
Fetal anomalies v0.2766 LMOD3 Zornitza Stark Gene: lmod3 has been classified as Green List (High Evidence).
Fetal anomalies v0.2766 LMOD3 Zornitza Stark Phenotypes for gene: LMOD3 were changed from Nemaline myopathy 616165 to Nemaline myopathy 10, MIM# 616165
Fetal anomalies v0.2765 LMOD3 Zornitza Stark Publications for gene: LMOD3 were set to
Fetal anomalies v0.2764 LMNA Zornitza Stark Marked gene: LMNA as ready
Fetal anomalies v0.2764 LMNA Zornitza Stark Gene: lmna has been classified as Green List (High Evidence).
Fetal anomalies v0.2764 LMNA Zornitza Stark Phenotypes for gene: LMNA were changed from LETHAL TIGHT SKIN CONTRACTURE SYNDROME; CARDIOMYOPATHY DILATED WITH HYPERGONADOTROPIC HYPOGONADISM; FAMILIAL PARTIAL LIPODYSTROPHY TYPE 2; HUTCHINSON-GILFORD PROGERIA SYNDROME; EMERY-DREIFUSS MUSCULAR DYSTROPHY TYPE 2; MUSCULAR DYSTROPHY CONGENITAL LMNA-RELATED; CHARCOT-MARIE-TOOTH DISEASE TYPE 2B1; MANDIBULOACRAL DYSPLASIA WITH TYPE A LIPODYSTROPHY; HEART-HAND SYNDROME SLOVENIAN TYPE; CARDIOMYOPATHY DILATED TYPE 1A; LIMB-GIRDLE MUSCULAR DYSTROPHY TYPE 1B to Restrictive dermopathy, lethal, MIM# 275210; Mandibuloacral dysplasia, MIM# 248370
Fetal anomalies v0.2763 LMNA Zornitza Stark Deleted their comment
Fetal anomalies v0.2763 LMNA Zornitza Stark edited their review of gene: LMNA: Added comment: Variants in this gene are associated with multiple phenotypes. The more severe end of the spectrum may present antenatally.; Changed rating: GREEN; Changed phenotypes: Restrictive dermopathy, lethal, MIM# 275210, Mandibuloacral dysplasia, MIM# 248370; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.2763 LMBRD1 Zornitza Stark Marked gene: LMBRD1 as ready
Fetal anomalies v0.2763 LMBRD1 Zornitza Stark Gene: lmbrd1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.2763 LMBRD1 Zornitza Stark Phenotypes for gene: LMBRD1 were changed from METHYLMALONIC ACIDURIA AND HOMOCYSTINURIA TYPE CBLF to Methylmalonic aciduria and homocystinuria, cblF type, MIM# 277380
Fetal anomalies v0.2762 LMBRD1 Zornitza Stark Classified gene: LMBRD1 as Red List (low evidence)
Fetal anomalies v0.2762 LMBRD1 Zornitza Stark Gene: lmbrd1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.2761 LMBRD1 Zornitza Stark changed review comment from: DD/ID reported in many affected individuals.; to: Onset in infancy.
Fetal anomalies v0.2761 LMBRD1 Zornitza Stark edited their review of gene: LMBRD1: Changed rating: RED
Fetal anomalies v0.2761 LMBR1 Zornitza Stark Marked gene: LMBR1 as ready
Fetal anomalies v0.2761 LMBR1 Zornitza Stark Gene: lmbr1 has been classified as Green List (High Evidence).
Fetal anomalies v0.2761 LMBR1 Zornitza Stark Phenotypes for gene: LMBR1 were changed from Acheiropody 200500; Triphalangeal thumb, type I 174500; Laurin-Sandrow syndrome 135750; Triphalangeal thumb-polysyndactyly syndrome 174500; Hypoplastic or aplastic tibia with polydactyly 188740; Polydactyly, preaxial type II 174500; Syndactyly, type IV 186200 to Laurin-Sandrow syndrome, MIM# 135750; Polydactyly, preaxial type II 174500; Triphalangeal thumb, type I, MIM# 174500; Syndactyly, type IV, MIM# 186200; Acheiropody, MIM# 200500; Triphalangeal thumb-polysyndactyly syndrome, MIM# 174500; Hypoplastic or aplastic tibia with polydactyly, MIM# 188740
Fetal anomalies v0.2760 LMBR1 Zornitza Stark changed review comment from: Radial aplasia but with ulnar dimelia. Reported microduplications in LMBR1 associated with Laurin-Sandrow syndrome are in the SHH regulatory element (ZRS) that resides in intron 5 of the LMBR1 gene. Duplications are >10kb.
Sources: Expert list; to: Variants are associated with multiple types of limb anomalies.

Note that the reported microduplications in LMBR1 associated with Laurin-Sandrow syndrome are in the SHH regulatory element (ZRS) that resides in intron 5 of the LMBR1 gene. Duplications are >10kb.
Sources: Expert list
Fetal anomalies v0.2760 LMBR1 Zornitza Stark edited their review of gene: LMBR1: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.2760 LMBR1 Zornitza Stark edited their review of gene: LMBR1: Changed phenotypes: Laurin-Sandrow syndrome, MIM# 135750, Polydactyly, preaxial type II 174500, Triphalangeal thumb, type I, MIM# 174500, Syndactyly, type IV, MIM# 186200, Acheiropody, MIM# 200500, Triphalangeal thumb-polysyndactyly syndrome, MIM# 174500, Hypoplastic or aplastic tibia with polydactyly, MIM# 188740
Fetal anomalies v0.2760 ISPD Zornitza Stark Marked gene: ISPD as ready
Fetal anomalies v0.2760 ISPD Zornitza Stark Gene: ispd has been classified as Green List (High Evidence).
Fetal anomalies v0.2760 ISPD Zornitza Stark Phenotypes for gene: ISPD were changed from WALKER WARBURG SYNDROME to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7, MIM# 614643
Fetal anomalies v0.2759 ISPD Zornitza Stark Publications for gene: ISPD were set to
Fetal anomalies v0.2758 ERGIC1 Zornitza Stark Marked gene: ERGIC1 as ready
Fetal anomalies v0.2758 ERGIC1 Zornitza Stark Gene: ergic1 has been classified as Green List (High Evidence).
Fetal anomalies v0.2758 ERGIC1 Zornitza Stark Classified gene: ERGIC1 as Green List (high evidence)
Fetal anomalies v0.2758 ERGIC1 Zornitza Stark Gene: ergic1 has been classified as Green List (High Evidence).
Fetal anomalies v0.2757 ERBB3 Zornitza Stark Marked gene: ERBB3 as ready
Fetal anomalies v0.2757 ERBB3 Zornitza Stark Gene: erbb3 has been classified as Green List (High Evidence).
Fetal anomalies v0.2757 ERBB3 Zornitza Stark Classified gene: ERBB3 as Green List (high evidence)
Fetal anomalies v0.2757 ERBB3 Zornitza Stark Gene: erbb3 has been classified as Green List (High Evidence).
Fetal anomalies v0.2756 ERGIC1 Krithika Murali gene: ERGIC1 was added
gene: ERGIC1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ERGIC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERGIC1 were set to 28317099; 34037256; 31230720
Phenotypes for gene: ERGIC1 were set to Arthrogryposis multiplex congenita 2, neurogenic type; OMIM # 208100
Review for gene: ERGIC1 was set to GREEN
Added comment: Recent Panelapp review by Z. Stark Oct 2021 - no new publications since

---

Pehlivan et al. 2019 (PMID:31230720) identified the third case of arthrogryposis in a child who harboured a previously unreported homozygous variant (c.782G>A; p.Gly261Asp) in this gene. Parents were heterozygous carriers. Functional studies were not performed.
Created: 14 Oct 2021, 7:23 a.m. | Last Modified: 14 Oct 2021, 7:23 a.m.
Panel Version: 0.9373

Reinstein et al. (2018) used WES in a large consanguineous Israeli Arab kindred consisting of 16 patients affected with the neurogenic type of arthrogryposis multiplex congenita. They identified a homozygous missense (V98E) mutation in ERGIC1 gene, which segregated with the disorder in the kindred, and was not found in the ExAC database or in 212 ethnically matched controls. Functional studies of the variant and studies of patient cells were not performed. ERGIC1 encodes a cycling membrane protein which has a possible role in transport between endoplasmic reticulum and Golgi.

Marconi et al (2021) used genome sequencing in a consanguineous family with 2 affected siblings presenting congenital arthrogryposis and some facial dysmorphism. They identified a homozygous 22.6 Kb deletion encompassing the promoter and first exon of ERGIC1. mRNA quantification showed the complete absence of ERGIC1 expression in the two affected siblings and a decrease in heterozygous parents.
Sources: Literature
Sources: Literature
Fetal anomalies v0.2756 ERBB3 Krithika Murali gene: ERBB3 was added
gene: ERBB3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ERBB3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERBB3 were set to 31752936; 17701904; 33720042
Phenotypes for gene: ERBB3 were set to Lethal congenital contractural syndrome 2, MIM# 607598; Hirschsprung disease (HSCR, aganglionic megacolon) MIM#142623
Review for gene: ERBB3 was set to GREEN
Added comment: Biallelic variants associated with multi-system disorder, including gut dysmotility/Hirschsprung disease; with or without contractures.
--

PMID 33497358: 6 individuals from 4 unrelated families reported with severe gut dysmotility and other features of neurocristinopathy including short-segment HSCR, progressive axonal peripheral neuropathy, dysautonomia, hypopigmentation, deafness. Note variants in this gene have also recently been linked to Hirschsprung's disease.

PMID 17701904: Lethal congenital contractual syndrome: Two families reported with contractures, positional approach used in gene discovery (2007).

PMID 33720042 - Seven variants (missense and frameshfit) from four independent families with Hirschsprung disease (HSCR) reported. All reported individuals variably associated with conditions such as HSCR, chronic intestinal pseudo-obstruction, peripheral neuropathy, and arthrogryposis. Functional study revealed mutant proteins reduced protein expression or altered phosphorylation of the mutant receptors.
Sources: Literature
Fetal anomalies v0.2756 INVS Zornitza Stark Marked gene: INVS as ready
Fetal anomalies v0.2756 INVS Zornitza Stark Gene: invs has been classified as Green List (High Evidence).
Fetal anomalies v0.2756 INVS Zornitza Stark Phenotypes for gene: INVS were changed from Nephronophthisis 2 602088 to Nephronophthisis 2, MIM# 602088
Fetal anomalies v0.2755 INVS Zornitza Stark Publications for gene: INVS were set to
Fetal anomalies v0.2754 INSR Zornitza Stark Marked gene: INSR as ready
Fetal anomalies v0.2754 INSR Zornitza Stark Gene: insr has been classified as Green List (High Evidence).
Fetal anomalies v0.2754 INSR Zornitza Stark Phenotypes for gene: INSR were changed from DONOHUE SYNDROME 246200; Diabetes mellitus, insulin-resistant, with acanthosis nigricans 610549; Hyperinsulinemic hypoglycemia, familial, 5 609968; Rabson-Mendenhall syndrome 262190 to Leprechaunism, MIM# 246200
Fetal anomalies v0.2753 INSR Zornitza Stark changed review comment from: ID is not part of the phenotype of Leprechaunism, and some of the individuals with Rabson-Mendenhall are described as 'mentally precocious'.; to: IUGR
Fetal anomalies v0.2753 INSR Zornitza Stark edited their review of gene: INSR: Changed phenotypes: Leprechaunism, MIM# 246200
Fetal anomalies v0.2753 INSR Zornitza Stark edited their review of gene: INSR: Changed rating: GREEN
Fetal anomalies v0.2753 INPP5E Zornitza Stark Marked gene: INPP5E as ready
Fetal anomalies v0.2753 INPP5E Zornitza Stark Gene: inpp5e has been classified as Green List (High Evidence).
Fetal anomalies v0.2753 INPP5E Zornitza Stark Phenotypes for gene: INPP5E were changed from MENTAL RETARDATION-TRUNCAL OBESITY-RETINAL DYSTROPHY-MICROPENIS; JOUBERT SYNDROME TYPE 1 to Joubert syndrome 1, MIM# 213300; MONDO:0008944
Fetal anomalies v0.2752 INPP5E Zornitza Stark Publications for gene: INPP5E were set to
Fetal anomalies v0.2751 IKBKG Zornitza Stark Marked gene: IKBKG as ready
Fetal anomalies v0.2751 IKBKG Zornitza Stark Gene: ikbkg has been classified as Green List (High Evidence).
Fetal anomalies v0.2751 IKBKG Zornitza Stark Phenotypes for gene: IKBKG were changed from ECTODERMAL DYSPLASIA ANHIDROTIC WITH IMMUNODEFICIENCY-OSTEOPETROSIS-LYMPHEDEMA; SUSCEPTIBILITY TO X-LINKED FAMILIAL ATYPICAL MICOBACTERIOSIS TYPE 1; ECTODERMAL DYSPLASIA ANHIDROTIC WITH IMMUNODEFICIENCY X-LINKED; INCONTINENTIA PIGMENTI; IMMUNODEFICIENCY NEMO-RELATED WITHOUT ANHIDROTIC ECTODERMAL DYSPLASIA to ncontinentia pigmenti, MIM# 308300
Fetal anomalies v0.2750 IKBKG Zornitza Stark Publications for gene: IKBKG were set to
Mendeliome v0.10786 KIF1B Zornitza Stark Classified gene: KIF1B as Red List (low evidence)
Mendeliome v0.10786 KIF1B Zornitza Stark Gene: kif1b has been classified as Red List (Low Evidence).
Mendeliome v0.10785 KIF1B Zornitza Stark edited their review of gene: KIF1B: Added comment: Limited for both phenotypes.; Changed rating: RED
Hereditary Neuropathy_CMT - isolated v1.13 KIF1B Zornitza Stark Publications for gene: KIF1B were set to
Hereditary Neuropathy_CMT - isolated v1.12 KIF1B Zornitza Stark Mode of inheritance for gene: KIF1B was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary Neuropathy_CMT - isolated v1.11 KIF1B Zornitza Stark Classified gene: KIF1B as Red List (low evidence)
Hereditary Neuropathy_CMT - isolated v1.11 KIF1B Zornitza Stark Gene: kif1b has been classified as Red List (Low Evidence).
Hereditary Neuropathy_CMT - isolated v1.10 KIF1B Zornitza Stark reviewed gene: KIF1B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Charcot-Marie-Tooth disease, type 2A1 MIM#118210; Mode of inheritance: None
Mendeliome v0.10785 CAMK2G Zornitza Stark Marked gene: CAMK2G as ready
Mendeliome v0.10785 CAMK2G Zornitza Stark Gene: camk2g has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10785 CAMK2G Zornitza Stark Classified gene: CAMK2G as Amber List (moderate evidence)
Mendeliome v0.10785 CAMK2G Zornitza Stark Gene: camk2g has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10784 CAMK2G Zornitza Stark gene: CAMK2G was added
gene: CAMK2G was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: CAMK2G was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CAMK2G were set to 30184290; 23033978
Phenotypes for gene: CAMK2G were set to Mental retardation, autosomal dominant 59, MIM# 618522
Review for gene: CAMK2G was set to AMBER
Added comment: Two unrelated individuals reported with de novo (p.Arg292Pro) variant. Functional data suggests GoF.
Sources: Expert Review
Intellectual disability syndromic and non-syndromic v0.4468 CAMK2G Zornitza Stark Publications for gene: CAMK2G were set to 30184290
Intellectual disability syndromic and non-syndromic v0.4467 CAMK2G Zornitza Stark Phenotypes for gene: CAMK2G were changed from Intellectual disability to Mental retardation, autosomal dominant 59, MIM# 618522
Intellectual disability syndromic and non-syndromic v0.4466 CAMK2G Zornitza Stark Marked gene: CAMK2G as ready
Intellectual disability syndromic and non-syndromic v0.4466 CAMK2G Zornitza Stark Gene: camk2g has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4466 CAMK2G Zornitza Stark Classified gene: CAMK2G as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.4466 CAMK2G Zornitza Stark Gene: camk2g has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.4465 CAMK2G Zornitza Stark edited their review of gene: CAMK2G: Changed publications: 30184290, 29100089
Intellectual disability syndromic and non-syndromic v0.4465 CAMK2G Zornitza Stark gene: CAMK2G was added
gene: CAMK2G was added to Intellectual disability syndromic and non-syndromic. Sources: Expert Review
Mode of inheritance for gene: CAMK2G was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CAMK2G were set to 30184290
Phenotypes for gene: CAMK2G were set to Intellectual disability
Mode of pathogenicity for gene: CAMK2G 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: CAMK2G was set to AMBER
Added comment: Two unrelated individuals reported with de novo (p.Arg292Pro) variant. Functional data suggests GoF.
Sources: Expert Review
Genetic Epilepsy v0.1430 CSNK2B Zornitza Stark Marked gene: CSNK2B as ready
Genetic Epilepsy v0.1430 CSNK2B Zornitza Stark Gene: csnk2b has been classified as Green List (High Evidence).
Genetic Epilepsy v0.1430 CSNK2B Zornitza Stark Phenotypes for gene: CSNK2B were changed from to Poirier-Bienvenu neurodevelopmental syndrome , MIM#618732
Genetic Epilepsy v0.1429 CSNK2B Zornitza Stark Publications for gene: CSNK2B were set to
Genetic Epilepsy v0.1428 CSNK2B Zornitza Stark Mode of inheritance for gene: CSNK2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v0.1427 CSNK2B Zornitza Stark reviewed gene: CSNK2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 28585349, 28762608; Phenotypes: Poirier-Bienvenu neurodevelopmental syndrome , MIM#618732; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4464 CSNK2B Zornitza Stark Marked gene: CSNK2B as ready
Intellectual disability syndromic and non-syndromic v0.4464 CSNK2B Zornitza Stark Gene: csnk2b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4464 CSNK2B Zornitza Stark Phenotypes for gene: CSNK2B were changed from to Poirier-Bienvenu neurodevelopmental syndrome , MIM#618732
Intellectual disability syndromic and non-syndromic v0.4463 CSNK2B Zornitza Stark Publications for gene: CSNK2B were set to
Intellectual disability syndromic and non-syndromic v0.4462 CSNK2B Zornitza Stark Mode of inheritance for gene: CSNK2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.4461 CSNK2B Zornitza Stark reviewed gene: CSNK2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 28585349, 28762608; Phenotypes: Poirier-Bienvenu neurodevelopmental syndrome , MIM#618732; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10783 CSNK2B Zornitza Stark Marked gene: CSNK2B as ready
Mendeliome v0.10783 CSNK2B Zornitza Stark Gene: csnk2b has been classified as Green List (High Evidence).
Mendeliome v0.10783 CSNK2B Zornitza Stark Phenotypes for gene: CSNK2B were changed from to Poirier-Bienvenu neurodevelopmental syndrome , MIM#618732
Mendeliome v0.10782 CSNK2B Zornitza Stark Publications for gene: CSNK2B were set to
Mendeliome v0.10781 CSNK2B Zornitza Stark Mode of inheritance for gene: CSNK2B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10780 CSNK2B Zornitza Stark reviewed gene: CSNK2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 28585349, 28762608; Phenotypes: Poirier-Bienvenu neurodevelopmental syndrome , MIM#618732; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Syndromic Retinopathy v0.185 RNU4ATAC Zornitza Stark Marked gene: RNU4ATAC as ready
Syndromic Retinopathy v0.185 RNU4ATAC Zornitza Stark Gene: rnu4atac has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.185 RNU4ATAC Zornitza Stark Marked gene: RNU4ATAC as ready
Syndromic Retinopathy v0.185 RNU4ATAC Zornitza Stark Gene: rnu4atac has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.185 RNU4ATAC Zornitza Stark Classified gene: RNU4ATAC as Green List (high evidence)
Syndromic Retinopathy v0.185 RNU4ATAC Zornitza Stark Gene: rnu4atac has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.184 RNU4ATAC Zornitza Stark gene: RNU4ATAC was added
gene: RNU4ATAC was added to Syndromic Retinopathy. Sources: Expert Review
Mode of inheritance for gene: RNU4ATAC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNU4ATAC were set to 2801768; 29265708; 30368667
Phenotypes for gene: RNU4ATAC were set to Roifman syndrome, MIM# 616651; Lowry-Wood syndrome, MIM# 226960
Review for gene: RNU4ATAC was set to GREEN
Added comment: Retinal dystrophy reported.
Sources: Expert Review
Anophthalmia_Microphthalmia_Coloboma v1.12 PACS1 Zornitza Stark Marked gene: PACS1 as ready
Anophthalmia_Microphthalmia_Coloboma v1.12 PACS1 Zornitza Stark Gene: pacs1 has been classified as Green List (High Evidence).
Anophthalmia_Microphthalmia_Coloboma v1.12 PACS1 Zornitza Stark Phenotypes for gene: PACS1 were changed from 615009 to Schuurs-Hoeijmakers syndrome, MIM# 615009
Anophthalmia_Microphthalmia_Coloboma v1.11 PACS1 Zornitza Stark Classified gene: PACS1 as Green List (high evidence)
Anophthalmia_Microphthalmia_Coloboma v1.11 PACS1 Zornitza Stark Gene: pacs1 has been classified as Green List (High Evidence).
Mendeliome v0.10780 NCAPD3 Zornitza Stark Marked gene: NCAPD3 as ready
Mendeliome v0.10780 NCAPD3 Zornitza Stark Gene: ncapd3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10780 NCAPD3 Zornitza Stark Phenotypes for gene: NCAPD3 were changed from to Microcephaly 22, primary, autosomal recessive, MIM# 617984
Mendeliome v0.10779 NCAPD3 Zornitza Stark Publications for gene: NCAPD3 were set to
Mendeliome v0.10778 NCAPD3 Zornitza Stark Mode of inheritance for gene: NCAPD3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10777 NCAPD3 Zornitza Stark Classified gene: NCAPD3 as Amber List (moderate evidence)
Mendeliome v0.10777 NCAPD3 Zornitza Stark Gene: ncapd3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10776 NCAPD3 Zornitza Stark reviewed gene: NCAPD3: Rating: AMBER; Mode of pathogenicity: None; Publications: 27737959; Phenotypes: Microcephaly 22, primary, autosomal recessive, MIM# 617984; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary Neuropathy - complex v0.119 SLC5A6 Zornitza Stark Marked gene: SLC5A6 as ready
Hereditary Neuropathy - complex v0.119 SLC5A6 Zornitza Stark Gene: slc5a6 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.119 SLC5A6 Zornitza Stark Classified gene: SLC5A6 as Green List (high evidence)
Hereditary Neuropathy - complex v0.119 SLC5A6 Zornitza Stark Gene: slc5a6 has been classified as Green List (High Evidence).
Hereditary Neuropathy - complex v0.118 SLC5A6 Zornitza Stark gene: SLC5A6 was added
gene: SLC5A6 was added to Hereditary Neuropathy - complex. Sources: Literature
Mode of inheritance for gene: SLC5A6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC5A6 were set to 35013551
Phenotypes for gene: SLC5A6 were set to Neurodegeneration, infantile-onset, biotin-responsive, MIM# 618973
Review for gene: SLC5A6 was set to GREEN
Added comment: Multi-system potentially treatable disorder.

Five individuals from three families reported with motor neuropathies.
Sources: Literature
Mendeliome v0.10776 CYP2C8 Zornitza Stark Marked gene: CYP2C8 as ready
Mendeliome v0.10776 CYP2C8 Zornitza Stark Gene: cyp2c8 has been classified as Red List (Low Evidence).
Mendeliome v0.10776 CYP2C8 Zornitza Stark Phenotypes for gene: CYP2C8 were changed from to {Drug metabolism, altered, CYP2C8-related} 618018
Mendeliome v0.10775 CYP2C8 Zornitza Stark Classified gene: CYP2C8 as Red List (low evidence)
Mendeliome v0.10775 CYP2C8 Zornitza Stark Gene: cyp2c8 has been classified as Red List (Low Evidence).
Mendeliome v0.10774 CYP2C8 Zornitza Stark reviewed gene: CYP2C8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Drug metabolism, altered, CYP2C8-related} 618018; Mode of inheritance: None
Fetal anomalies v0.2749 MED25 Zornitza Stark Marked gene: MED25 as ready
Fetal anomalies v0.2749 MED25 Zornitza Stark Gene: med25 has been classified as Green List (High Evidence).
Fetal anomalies v0.2749 MED25 Zornitza Stark Classified gene: MED25 as Green List (high evidence)
Fetal anomalies v0.2749 MED25 Zornitza Stark Gene: med25 has been classified as Green List (High Evidence).
Fetal anomalies v0.2748 SHMT2 Zornitza Stark Marked gene: SHMT2 as ready
Fetal anomalies v0.2748 SHMT2 Zornitza Stark Gene: shmt2 has been classified as Green List (High Evidence).
Fetal anomalies v0.2748 SHMT2 Zornitza Stark Classified gene: SHMT2 as Green List (high evidence)
Fetal anomalies v0.2748 SHMT2 Zornitza Stark Gene: shmt2 has been classified as Green List (High Evidence).
Fetal anomalies v0.2747 MAST1 Zornitza Stark Marked gene: MAST1 as ready
Fetal anomalies v0.2747 MAST1 Zornitza Stark Gene: mast1 has been classified as Green List (High Evidence).
Fetal anomalies v0.2747 MAST1 Zornitza Stark Classified gene: MAST1 as Green List (high evidence)
Fetal anomalies v0.2747 MAST1 Zornitza Stark Gene: mast1 has been classified as Green List (High Evidence).
Fetal anomalies v0.2746 MAPK8IP3 Zornitza Stark Marked gene: MAPK8IP3 as ready
Fetal anomalies v0.2746 MAPK8IP3 Zornitza Stark Gene: mapk8ip3 has been classified as Green List (High Evidence).
Fetal anomalies v0.2746 MAPK8IP3 Zornitza Stark Classified gene: MAPK8IP3 as Green List (high evidence)
Fetal anomalies v0.2746 MAPK8IP3 Zornitza Stark Gene: mapk8ip3 has been classified as Green List (High Evidence).
Fetal anomalies v0.2745 MAP1B Zornitza Stark Marked gene: MAP1B as ready
Fetal anomalies v0.2745 MAP1B Zornitza Stark Gene: map1b has been classified as Green List (High Evidence).
Fetal anomalies v0.2745 MAP1B Zornitza Stark Phenotypes for gene: MAP1B were changed from polymicrogyria; PVNH; Periventricular nodular heterotopia 9, MIM# 618918 to Polymicrogyria; Periventricular nodular heterotopia 9, MIM# 618918
Fetal anomalies v0.2744 MAP1B Zornitza Stark Classified gene: MAP1B as Green List (high evidence)
Fetal anomalies v0.2744 MAP1B Zornitza Stark Gene: map1b has been classified as Green List (High Evidence).
Fetal anomalies v0.2743 ASTN1 Zornitza Stark Marked gene: ASTN1 as ready
Fetal anomalies v0.2743 ASTN1 Zornitza Stark Gene: astn1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.2743 ASTN1 Zornitza Stark Publications for gene: ASTN1 were set to 29706646; 11861479
Fetal anomalies v0.2742 ASTN1 Zornitza Stark Classified gene: ASTN1 as Amber List (moderate evidence)
Fetal anomalies v0.2742 ASTN1 Zornitza Stark Gene: astn1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.2741 PDE3A Zornitza Stark Marked gene: PDE3A as ready
Fetal anomalies v0.2741 PDE3A Zornitza Stark Gene: pde3a has been classified as Green List (High Evidence).
Fetal anomalies v0.2741 PDE3A Zornitza Stark Classified gene: PDE3A as Green List (high evidence)
Fetal anomalies v0.2741 PDE3A Zornitza Stark Gene: pde3a has been classified as Green List (High Evidence).
Fetal anomalies v0.2740 HYAL1 Zornitza Stark Marked gene: HYAL1 as ready
Fetal anomalies v0.2740 HYAL1 Zornitza Stark Gene: hyal1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.2740 HYAL1 Zornitza Stark Phenotypes for gene: HYAL1 were changed from MUCOPOLYSACCHARIDOSIS TYPE 9 to Mucopolysaccharidosis type IX, MIM# 601492; MONDO:0011093
Fetal anomalies v0.2739 HYAL1 Zornitza Stark Publications for gene: HYAL1 were set to
Fetal anomalies v0.2738 FMN1 Zornitza Stark Marked gene: FMN1 as ready
Fetal anomalies v0.2738 FMN1 Zornitza Stark Gene: fmn1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.2738 FMN1 Zornitza Stark Classified gene: FMN1 as Amber List (moderate evidence)
Fetal anomalies v0.2738 FMN1 Zornitza Stark Gene: fmn1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.2737 HSD17B10 Zornitza Stark Marked gene: HSD17B10 as ready
Fetal anomalies v0.2737 HSD17B10 Zornitza Stark Gene: hsd17b10 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.2737 HSD17B10 Zornitza Stark Phenotypes for gene: HSD17B10 were changed from 2-METHYL-3-HYDROXYBUTYRYL-COA DEHYDROGENASE DEFICIENCY; MENTAL RETARDATION SYNDROMIC X-LINKED TYPE 10 to HSD10 mitochondrial disease, MIM# 300438
Fetal anomalies v0.2736 HSD17B10 Zornitza Stark Classified gene: HSD17B10 as Amber List (moderate evidence)
Fetal anomalies v0.2736 HSD17B10 Zornitza Stark Gene: hsd17b10 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.2735 HPGD Zornitza Stark Marked gene: HPGD as ready
Fetal anomalies v0.2735 HPGD Zornitza Stark Gene: hpgd has been classified as Red List (Low Evidence).
Fetal anomalies v0.2735 HPGD Zornitza Stark Phenotypes for gene: HPGD were changed from CRANIOOSTEOARTHROPATHY to Hypertrophic osteoarthropathy, primary, autosomal recessive 1 MIM#259100; Cranioosteoarthropathy MIM#259100
Fetal anomalies v0.2734 HPGD Zornitza Stark Publications for gene: HPGD were set to
Fetal anomalies v0.2733 FAT1 Zornitza Stark Marked gene: FAT1 as ready
Fetal anomalies v0.2733 FAT1 Zornitza Stark Gene: fat1 has been classified as Green List (High Evidence).
Fetal anomalies v0.2733 FAT1 Zornitza Stark Classified gene: FAT1 as Green List (high evidence)
Fetal anomalies v0.2733 FAT1 Zornitza Stark Gene: fat1 has been classified as Green List (High Evidence).
Mendeliome v0.10774 HPGD Zornitza Stark Marked gene: HPGD as ready
Mendeliome v0.10774 HPGD Zornitza Stark Gene: hpgd has been classified as Green List (High Evidence).
Mendeliome v0.10774 HPGD Zornitza Stark Phenotypes for gene: HPGD were changed from to Hypertrophic osteoarthropathy, primary, autosomal recessive 1 MIM#259100; Cranioosteoarthropathy MIM#259100
Mendeliome v0.10773 HPGD Zornitza Stark Publications for gene: HPGD were set to
Mendeliome v0.10772 HPGD Zornitza Stark Mode of inheritance for gene: HPGD was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10771 GLMN Zornitza Stark Marked gene: GLMN as ready
Mendeliome v0.10771 GLMN Zornitza Stark Gene: glmn has been classified as Green List (High Evidence).
Mendeliome v0.10771 GLMN Zornitza Stark Phenotypes for gene: GLMN were changed from to Glomuvenous malformations MIM#138000
Mendeliome v0.10770 GLMN Zornitza Stark Publications for gene: GLMN were set to
Mendeliome v0.10769 GLMN Zornitza Stark Mode of inheritance for gene: GLMN was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.2732 GLMN Zornitza Stark Marked gene: GLMN as ready
Fetal anomalies v0.2732 GLMN Zornitza Stark Gene: glmn has been classified as Red List (Low Evidence).
Fetal anomalies v0.2732 GLMN Zornitza Stark Phenotypes for gene: GLMN were changed from GLOMUVENOUS MALFORMATIONS to Glomuvenous malformations MIM#138000
Fetal anomalies v0.2731 GLMN Zornitza Stark Mode of inheritance for gene: GLMN was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.2730 GLMN Zornitza Stark reviewed gene: GLMN: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v0.2730 GK Zornitza Stark Marked gene: GK as ready
Fetal anomalies v0.2730 GK Zornitza Stark Gene: gk has been classified as Red List (Low Evidence).
Fetal anomalies v0.2730 GK Zornitza Stark Phenotypes for gene: GK were changed from GLYCEROL KINASE DEFICIENCY to Glycerol kinase deficiency MIM#307030
Intellectual disability syndromic and non-syndromic v0.4461 GDI1 Zornitza Stark Marked gene: GDI1 as ready
Intellectual disability syndromic and non-syndromic v0.4461 GDI1 Zornitza Stark Gene: gdi1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.4461 GDI1 Zornitza Stark Phenotypes for gene: GDI1 were changed from to Intellectual developmental disorder, X-linked 41 MIM#300849
Intellectual disability syndromic and non-syndromic v0.4460 GDI1 Zornitza Stark Publications for gene: GDI1 were set to
Fetal anomalies v0.2729 MED25 Krithika Murali gene: MED25 was added
gene: MED25 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: MED25 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MED25 were set to 25792360; 32816121; 32816121; 32324310
Phenotypes for gene: MED25 were set to multiple congenital anomalies; congenital heart defects; hypospadias, thin corpus callosum, cerebral ventricular dilatation; Basel-Vanagait-Smirin-Yosef syndrome - #616449; Congenital cataract-microcephaly-naevus flammeus syndrome MONDO:0014643
Review for gene: MED25 was set to GREEN
Added comment: Multiple individuals reported - biallelic variants associated with severe syndromic neurodevelopmental disorder diagnosed from infancy.

PMID 32324310 - report one patient with antenatal ultrasound demonstrating cleft lip and clenched hands.

Additional features associated wtih this condition that may be diagnosed antenatally include cleft palate, cardiac septal defects, hypospadias, polymicrogyria, thin corpus callosum, microcephaly and cerebral ventricular dilatation.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.4459 GDI1 Zornitza Stark Mode of inheritance for gene: GDI1 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)
Intellectual disability syndromic and non-syndromic v0.4458 GDI1 Zornitza Stark reviewed gene: GDI1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28863211, 22002931, 9620768, 9668174; Phenotypes: Intellectual developmental disorder, X-linked 41 MIM#300849; 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 v0.10768 GDI1 Zornitza Stark Marked gene: GDI1 as ready
Mendeliome v0.10768 GDI1 Zornitza Stark Gene: gdi1 has been classified as Green List (High Evidence).
Mendeliome v0.10768 GDI1 Zornitza Stark Phenotypes for gene: GDI1 were changed from to Intellectual developmental disorder, X-linked 41 MIM#300849
Mendeliome v0.10767 GDI1 Zornitza Stark Publications for gene: GDI1 were set to
Mendeliome v0.10766 GDI1 Zornitza Stark Mode of inheritance for gene: GDI1 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)
Fetal anomalies v0.2729 GDI1 Zornitza Stark Marked gene: GDI1 as ready
Fetal anomalies v0.2729 GDI1 Zornitza Stark Gene: gdi1 has been classified as Red List (Low Evidence).
Fetal anomalies v0.2729 GDI1 Zornitza Stark Phenotypes for gene: GDI1 were changed from MENTAL RETARDATION X-LINKED TYPE 41; MENTAL RETARDATION X-LINKED TYPE 48 to Intellectual developmental disorder, X-linked 41 MIM#300849
Fetal anomalies v0.2728 SHMT2 Krithika Murali gene: SHMT2 was added
gene: SHMT2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SHMT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SHMT2 were set to 33015733
Phenotypes for gene: SHMT2 were set to Polymicrogyria; corpus callosum anomalies; Microcephaly; Neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities - #619121
Review for gene: SHMT2 was set to GREEN
Added comment: Neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities particularly thin corpus callosum and polymicrogyria (NEDCASB) associated with biallelic SHMT2 variants. Antenatal detection of microcephaly reported.

--
Detailed PanelApp review Oct 2020 - no new evidence to add

García‑Cazorla et al. (2020 - PMID: 33015733) report 5 individuals (from 4 families) with a novel brain and heart developmental syndrome caused by biallelic SHMT2 pathogenic variants.

All affected subjects presented similar phenotype incl. microcephaly at birth (5/5 with OFC < -2 SD though in 2/5 cases N OFC was observed later), DD and ID (1/5 mild-moderate, 1/5 moderate, 3/5 severe), motor dysfunction in the form of spastic (5/5) paraparesis, ataxia/dysmetria (3/4), intention tremor (in 3/?) and/or peripheral neuropathy (2 sibs). They exhibited corpus callosum hypoplasia (5/5) and perisylvian microgyria-like pattern (4/5). Cardiac problems were reported in all, with hypertrophic cardiomyopathy in 4/5 (from 3 families) and atrial-SD in the 5th individual (1/5). Common dysmorphic features incl. long palpebral/fissures, eversion of lateral third of lower eylids, arched eyebrows, long eyelashes, thin upper lip, short Vth finger, fetal pads, mild 2-3 toe syndactyly, proximally placed thumbs.

Biallelic variants were identified following exome sequencing in all (other investigations not mentioned). Identified variants were in all cases missense SNVs or in-frame del, which together with evidence from population databases and mouse model might suggest a hypomorphic effect of variants and intolerance/embryonic lethality for homozygous LoF ones.

SHMT2 encodes the mitohondrial form of serine hydroxymethyltransferase. The enzyme transfers one-carbon units from serine to tetrahydrofolate (THF) and generates glycine and 5,10,methylene-THF.

Mitochondrial defect was suggested by presence of ragged red fibers in myocardial biopsy of one patient. Quadriceps and myocardial biopsies of the same individual were overall suggestive of myopathic changes.

While plasma metabolites were within N range and SHMT2 protein levels not significantly altered in patient fibroblasts, the authors provide evidence for impaired enzymatic function eg. presence of the SHMT2 substrate (THF) in patient but not control (mitochondria-enriched) fibroblasts , decrease in glycine/serine ratios, impared folate metabolism. Patient fibroblasts displayed impaired oxidative capacity (reduced ATP levels in a medium without glucose, diminished oxygen consumption rates). Mitochondrial membrane potential and ROS levels were also suggestive of redox malfunction.

Shmt2 ko in mice was previously shown to be embryonically lethal attributed to severe mitochondrial respiration defects, although there was no observed brain metabolic defect.

The authors performed Shmt2 knockdown in motoneurons in Drosophila, demonstrating neuromuscular junction (# of satellite boutons) and motility defects (climbing distance/velocity).
Sources: Literature
Fetal anomalies v0.2728 MAST1 Krithika Murali gene: MAST1 was added
gene: MAST1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: MAST1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAST1 were set to 32818970; 32198973; 31721002; 30449657
Phenotypes for gene: MAST1 were set to Mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations - #61827; corpus callosum anomalies; cortical malformations; cerebellar hypoplasia
Review for gene: MAST1 was set to GREEN
Added comment: Neurodevelopmental disorder with muscular hypotonia and varying brain anomalies which may be diagnosed antenatally.

Reported cases include x1 individual reported to have hydrocephalus antenatally (PMID 32818970). MRI-B at 17 months demonstrated polymicrogyria, hyperplastic corpus callosum, progressive pontine hypoplasia and enlarged ventricles.

Another female patient reported with antenatal findings of increased nuchal translucency in a pregnancy complicated by oligohydramnios, IUGR, pre-eclampsia and pre-term delivery at 32 weeks (PMID 32198973). Postnatally diagnosed with cortical malformations without cerebellar hypoplasia.

6 unrelated patients with mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations (MCCCHCM) with de novo heterozygous mutations in MAST1 gene (30449657). In vitro functional studies showed that 1 of the variants (lys276del) increased MAST1 binding to microtubules compared to controls. Mutant mice heterozygous for a Mast1 leu278del allele showed a thicker corpus callosum compared to wildtype, and an overall reduction in cortical volume and thickness and decreased cerebellar volume and number of granule and Purkinje cells due to increased apoptosis compared to controls.

1 Emirati patient with ID, microcephaly, and dysmorphic features, with missense variant in MAST1 (30449657)
Sources: Literature
Fetal anomalies v0.2728 MAPK8IP3 Krithika Murali gene: MAPK8IP3 was added
gene: MAPK8IP3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: MAPK8IP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAPK8IP3 were set to 30945334; 30612693
Phenotypes for gene: MAPK8IP3 were set to Neurodevelopmental disorder with or without variable brain abnormalities - #618443; cerebral atrophy; corpus callosum anomalies; polymicrogyria
Review for gene: MAPK8IP3 was set to GREEN
Added comment: 13 unrelated individuals and 5 individuals from 4 families identified with de novo heterozygous MAPK8IP3 variants. Brain anomalies such as perisylvian polymicrogyria, cerebral or cerebellar atrophy and hypoplasia of the corpus callosum consistently reported in affected individuals
Sources: Literature
Fetal anomalies v0.2728 MAP1B Krithika Murali gene: MAP1B was added
gene: MAP1B was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: MAP1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAP1B were set to 31317654; 33772511; 30150678; 30214071
Phenotypes for gene: MAP1B were set to polymicrogyria; PVNH; Periventricular nodular heterotopia 9, MIM# 618918
Review for gene: MAP1B was set to GREEN
Added comment: At least 5 families described with phenotypic features that include variable brain malformations potentially detectable antenatally.
Sources: Literature
Fetal anomalies v0.2728 ASTN1 Krithika Murali reviewed gene: ASTN1: Rating: AMBER; Mode of pathogenicity: None; Publications: 27431290, 26539891, 29706646, 11861479; Phenotypes: Polymicrogyria, hypoplastic corpus callosum; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.2728 GAMT Zornitza Stark Marked gene: GAMT as ready
Fetal anomalies v0.2728 GAMT Zornitza Stark Gene: gamt has been classified as Red List (Low Evidence).
Fetal anomalies v0.2728 GAMT Zornitza Stark Phenotypes for gene: GAMT were changed from GUANIDINOACETATE METHYLTRANSFERASE DEFICIENCY to Cerebral creatine deficiency syndrome 2 MIM#612736
Fetal anomalies v0.2727 NMNAT2 Zornitza Stark Marked gene: NMNAT2 as ready
Fetal anomalies v0.2727 NMNAT2 Zornitza Stark Gene: nmnat2 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.2727 NMNAT2 Zornitza Stark Phenotypes for gene: NMNAT2 were changed from hydropic placenta; hydrocephalus; micrognathia; bilateral hypoplastic lungs; hypoplastic cerebellum; severely reduced skeletal muscle mass or absence; cleft palate; hydrops fetalis; flexion contractures of all extremities; cystic hygroma to Hydrops fetalis and multiple fetal anomalies; polyneuropathy; erythromelalgia
Fetal anomalies v0.2726 NMNAT2 Zornitza Stark Publications for gene: NMNAT2 were set to 31132363; 23082226; 31136762
Mendeliome v0.10765 NMNAT2 Zornitza Stark Phenotypes for gene: NMNAT2 were changed from polyneuropathy; erythromelalgia to polyneuropathy; erythromelalgia; Hydrops fetalis and multiple fetal anomalies