PanelApp

Activity

Filter

Cancel
Date Panel Item Activity
3000 actions
Mendeliome v0.8484 STX3 Zornitza Stark edited their review of gene: STX3: Changed phenotypes: Microvillus inclusion disease, MIM#619445
Mendeliome v0.8484 C1QA Zornitza Stark Gene: c1qa has been classified as Green List (High Evidence).
Mendeliome v0.8481 CIITA Zornitza Stark Gene: ciita has been classified as Green List (High Evidence).
Mendeliome v0.8478 CD40LG Zornitza Stark Gene: cd40lg has been classified as Green List (High Evidence).
Mendeliome v0.8475 CD3G Zornitza Stark Gene: cd3g has been classified as Green List (High Evidence).
Mendeliome v0.8472 WDR26 Zornitza Stark Gene: wdr26 has been classified as Green List (High Evidence).
Mendeliome v0.8467 ABCD4 Zornitza Stark Gene: abcd4 has been classified as Green List (High Evidence).
Mendeliome v0.8464 ABCD1 Zornitza Stark Gene: abcd1 has been classified as Green List (High Evidence).
Mendeliome v0.8462 ABCD1 Zornitza Stark changed review comment from: Ataxia is a feature of this progressive disorder.
Sources: Expert list; to: Well established gene-disease association.
Sources: Expert list
Mendeliome v0.8460 CCBE1 Zornitza Stark Gene: ccbe1 has been classified as Green List (High Evidence).
Mendeliome v0.8460 CCBE1 Zornitza Stark Phenotypes for gene: CCBE1 were changed from to Hennekam lymphangiectasia- lymphoedema syndrome MIM# 235510; lymphangiectasia and lymphoedema; facial abnormalities; dysmorphic features; hypoalbuminaemia; intellectual disability; hypoglobulinaemia
Mendeliome v0.8457 CCBE1 Zornitza Stark reviewed gene: CCBE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19935664, 19911200, 19287381, 25925991, 27345729, 21778431; Phenotypes: Hennekam lymphangiectasia- lymphoedema syndrome MIM# 235510, lymphangiectasia and lymphoedema, facial abnormalities, dysmorphic features, hypoalbuminaemia, intellectual disability, hypoglobulinaemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8457 CD27 Zornitza Stark Gene: cd27 has been classified as Green List (High Evidence).
Mendeliome v0.8454 ZNF148 Zornitza Stark Gene: znf148 has been classified as Green List (High Evidence).
Mendeliome v0.8454 ZNF148 Zornitza Stark Classified gene: ZNF148 as Green List (high evidence)
Mendeliome v0.8454 ZNF148 Zornitza Stark Gene: znf148 has been classified as Green List (High Evidence).
Mendeliome v0.8453 RAC3 Zornitza Stark Gene: rac3 has been classified as Green List (High Evidence).
Mendeliome v0.8453 RAC3 Zornitza Stark Classified gene: RAC3 as Green List (high evidence)
Mendeliome v0.8453 RAC3 Zornitza Stark Gene: rac3 has been classified as Green List (High Evidence).
Mendeliome v0.8452 PCLO Zornitza Stark Phenotypes for gene: PCLO were changed from to Pontocerebellar hypoplasia, type 3, MIM#608027
Mendeliome v0.8449 ZNF148 Natalie Tan gene: ZNF148 was added
gene: ZNF148 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZNF148 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZNF148 were set to PMID: 27964749
Phenotypes for gene: ZNF148 were set to Global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies; MIM#617260
Review for gene: ZNF148 was set to GREEN
Added comment: Four unrelated individuals with de novo heterozygous nonsense or frameshift mutations (all resulting in premature termination codons in the last exon of ZNF148, predicted to escape nonsense-mediated mRNA decay and result in expression of a truncated protein). Phenotype characterised by underdevelopment of the corpus callosum, mild to moderate developmental delay and ID, variable microcephaly or mild macrocephaly, short stature, feeding problems, facial dysmorphisms, and cardiac and renal malformations. No functional studies to date.
Sources: Literature
Mendeliome v0.8449 CHRNA4 Zornitza Stark Gene: chrna4 has been classified as Green List (High Evidence).
Mendeliome v0.8445 ZIC3 Zornitza Stark Gene: zic3 has been classified as Green List (High Evidence).
Mendeliome v0.8442 VPS13B Zornitza Stark Gene: vps13b has been classified as Green List (High Evidence).
Mendeliome v0.8440 TULP1 Zornitza Stark Gene: tulp1 has been classified as Green List (High Evidence).
Mendeliome v0.8440 TULP1 Zornitza Stark Phenotypes for gene: TULP1 were changed from to Retinitis pigmentosa 14 M(MIM#600132); Leber congenital amaurosis 15, MIM# 613843
Mendeliome v0.8437 TULP1 Zornitza Stark reviewed gene: TULP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Leber congenital amaurosis 15, MIM# 613843; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8437 TOPORS Zornitza Stark Gene: topors has been classified as Green List (High Evidence).
Mendeliome v0.8434 SUFU Zornitza Stark Gene: sufu has been classified as Green List (High Evidence).
Mendeliome v0.8431 SUFU Zornitza Stark edited their review of gene: SUFU: Added comment: Mono-allelic variants are also associated with Basal cell nevus syndrome/predisposition to medulloblastoma.; Changed rating: GREEN; Changed publications: 28965847, 19533801, 31485359; Changed phenotypes: Joubert syndrome 32, MIM#617757, Basal cell nevus syndrome, MIM# 109400; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8431 SCNN1G Zornitza Stark Gene: scnn1g has been classified as Green List (High Evidence).
Mendeliome v0.8428 SCNN1G Zornitza Stark edited their review of gene: SCNN1G: Added comment: Variants resulting in constitutive activation of epithelial sodium channel activity have been demonstrated in the beta and gamma subunits as the cause of the autosomal dominant form of hypertension, Liddle syndrome, which is characterized by volume expansion, hypokalemia, and alkalosis.

Variants causing loss of epithelial sodium channel activity cause the converse phenotype of volume depletion, hyperkalaemia and acidosis characteristic of patients with pseudohypoaldosteronism type I.

Well established gene-disease associations.; Changed rating: GREEN; Changed phenotypes: Liddle syndrome 2, MIM# 618114, Pseudohypoaldosteronism, type I, MIM# 264350; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8428 SCLT1 Zornitza Stark Gene: sclt1 has been classified as Green List (High Evidence).
Mendeliome v0.8425 RPGR Zornitza Stark Gene: rpgr has been classified as Green List (High Evidence).
Mendeliome v0.8422 PRKCSH Zornitza Stark Gene: prkcsh has been classified as Green List (High Evidence).
Mendeliome v0.8418 POC1B Zornitza Stark Gene: poc1b has been classified as Green List (High Evidence).
Mendeliome v0.8415 PMM2 Zornitza Stark Gene: pmm2 has been classified as Green List (High Evidence).
Mendeliome v0.8412 PKHD1 Zornitza Stark Gene: pkhd1 has been classified as Green List (High Evidence).
Mendeliome v0.8410 PKHD1 Zornitza Stark changed review comment from: Included due to phenotypic overlap with nephronophthisis.; to: Well established gene-disease association.
Mendeliome v0.8410 MUC1 Zornitza Stark Gene: muc1 has been classified as Green List (High Evidence).
Mendeliome v0.8407 KIF7 Zornitza Stark Gene: kif7 has been classified as Green List (High Evidence).
Mendeliome v0.8404 KIAA0753 Zornitza Stark Gene: kiaa0753 has been classified as Green List (High Evidence).
Mendeliome v0.8401 KIAA0586 Zornitza Stark Gene: kiaa0586 has been classified as Green List (High Evidence).
Mendeliome v0.8401 KIAA0586 Zornitza Stark Phenotypes for gene: KIAA0586 were changed from to Joubert syndrome 23, MIM# 616490; Short-rib thoracic dysplasia 14 with polydactyly, MIM# 616546
Mendeliome v0.8398 KIAA0586 Zornitza Stark edited their review of gene: KIAA0586: Changed phenotypes: Short-rib thoracic dysplasia 14 with polydactyly, MIM# 616546, Joubert syndrome
Mendeliome v0.8398 IFT52 Zornitza Stark Gene: ift52 has been classified as Green List (High Evidence).
Mendeliome v0.8398 IFT52 Zornitza Stark Phenotypes for gene: IFT52 were changed from to Short-rib thoracic dysplasia 16 with or without polydactyly, MIM# 617102
Mendeliome v0.8395 IFT27 Zornitza Stark Gene: ift27 has been classified as Green List (High Evidence).
Mendeliome v0.8392 POLG2 Zornitza Stark Gene: polg2 has been classified as Green List (High Evidence).
Mendeliome v0.8392 POLG2 Zornitza Stark Phenotypes for gene: POLG2 were changed from to Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4, MIM# 610131; Mitochondrial DNA depletion syndrome 16 , MIM# 618528
Mendeliome v0.8389 POLG2 Zornitza Stark reviewed gene: POLG2: Rating: GREEN; 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
Mendeliome v0.8389 PCDHGC4 Zornitza Stark Gene: pcdhgc4 has been classified as Green List (High Evidence).
Mendeliome v0.8389 PCDHGC4 Zornitza Stark Classified gene: PCDHGC4 as Green List (high evidence)
Mendeliome v0.8389 PCDHGC4 Zornitza Stark Gene: pcdhgc4 has been classified as Green List (High Evidence).
Mendeliome v0.8388 PCDHGC4 Zornitza Stark gene: PCDHGC4 was added
gene: PCDHGC4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PCDHGC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCDHGC4 were set to 34244665
Phenotypes for gene: PCDHGC4 were set to Intellectual disability; Seizures
Review for gene: PCDHGC4 was set to GREEN
Added comment: Eight variants reported in 19 members of nine unreleted families with a neurodevelopmental syndrome. Severe or moderate intellectual disabilty in eight families and seizures in four families. Four of the variants were LoF, in silico analysis of the remaining missense (n=3) and splice variants were predicted to be pathogenic.
Sources: Literature
Mendeliome v0.8387 ATP6V0A4 Zornitza Stark Gene: atp6v0a4 has been classified as Green List (High Evidence).
Mendeliome v0.8387 ATP6V0A4 Zornitza Stark Phenotypes for gene: ATP6V0A4 were changed from to Renal tubular acidosis, distal, autosomal recessive, MIM#602722
Mendeliome v0.8384 ATP6V0A4 Zornitza Stark reviewed gene: ATP6V0A4: Rating: GREEN; Mode of pathogenicity: None; Publications: 12414817, 10973252; Phenotypes: Renal tubular acidosis, distal, autosomal recessive, MIM#602722; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8384 ICK Zornitza Stark Gene: ick has been classified as Green List (High Evidence).
Mendeliome v0.8384 ICK Zornitza Stark Phenotypes for gene: ICK were changed from to Endocrine-cerebroosteodysplasia (MIM#612651)
Mendeliome v0.8381 HNF1B Zornitza Stark Gene: hnf1b has been classified as Green List (High Evidence).
Mendeliome v0.8379 HNF1B Zornitza Stark changed review comment from: Included due to phenotypic overlap with nephronophthisis.; to: Well established gene-disease association, CNVs common.
Mendeliome v0.8379 GDF1 Zornitza Stark Gene: gdf1 has been classified as Green List (High Evidence).
Mendeliome v0.8376 GDF1 Zornitza Stark edited their review of gene: GDF1: Added comment: PMID: 32144877 - founder PTC in Arab population causing congenital heart detects AND right isomerism in 3 (unrelated?) families. Reviews other publications and reports additional chet (two PTC) or homozygous (missense) families with situs inversus and/or heart defects. No apparent genotype-phenotype correlation btw dominant and recessive disease.; Changed rating: GREEN; Changed publications: 32144877; Changed phenotypes: Congenital heart defects, multiple types, 6 613854, Right atrial isomerism (Ivemark) 208530; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8376 EVC2 Zornitza Stark Gene: evc2 has been classified as Green List (High Evidence).
Mendeliome v0.8373 EVC Zornitza Stark Gene: evc has been classified as Green List (High Evidence).
Mendeliome v0.8370 DCDC2 Zornitza Stark Gene: dcdc2 has been classified as Green List (High Evidence).
Mendeliome v0.8370 DCDC2 Zornitza Stark Phenotypes for gene: DCDC2 were changed from to Nephronophthisis 19, MIM# 616217; Sclerosing cholangitis, neonatal, MIM# 617394
Mendeliome v0.8367 DCDC2 Zornitza Stark changed review comment from: Only a single case with nephronophthisis, most reports are for cholangitis, though zebrafish model has renal cysts.; to: At least 5 families reported with cholangitis, and two with nephronophthisis, though zebrafish model has renal cysts.
Mendeliome v0.8367 DCDC2 Zornitza Stark edited their review of gene: DCDC2: Changed rating: GREEN; Changed publications: 25557784, 27319779, 27469900; Changed phenotypes: Nephronophthisis 19, MIM# 616217, Sclerosing cholangitis, neonatal, MIM# 617394; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8367 CRELD1 Zornitza Stark Gene: creld1 has been classified as Green List (High Evidence).
Mendeliome v0.8364 CRB2 Zornitza Stark Gene: crb2 has been classified as Green List (High Evidence).
Mendeliome v0.8364 CRB2 Zornitza Stark Phenotypes for gene: CRB2 were changed from to Ventriculomegaly with cystic kidney disease, MIM# 219730; Focal segmental glomerulosclerosis 9, MIM# 616220
Mendeliome v0.8361 CRB2 Zornitza Stark edited their review of gene: CRB2: Changed publications: 25557780, 33687977, 32051522, 30212996, 33575434, 31438467, 30593785, 25557779; Changed phenotypes: Ventriculomegaly with cystic kidney disease, MIM# 219730, Focal segmental glomerulosclerosis 9, MIM# 616220
Mendeliome v0.8361 CEP55 Zornitza Stark Gene: cep55 has been classified as Green List (High Evidence).
Mendeliome v0.8361 CEP55 Zornitza Stark Phenotypes for gene: CEP55 were changed from to Multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly, MIM# 236500
Mendeliome v0.8358 CEP55 Zornitza Stark reviewed gene: CEP55: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly, MIM# 236500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8358 CENPF Zornitza Stark Gene: cenpf has been classified as Green List (High Evidence).
Mendeliome v0.8355 C8orf37 Zornitza Stark Gene: c8orf37 has been classified as Green List (High Evidence).
Mendeliome v0.8352 C2CD3 Zornitza Stark Gene: c2cd3 has been classified as Green List (High Evidence).
Mendeliome v0.8348 CHRM3 Zornitza Stark Gene: chrm3 has been classified as Green List (High Evidence).
Mendeliome v0.8345 ARHGAP42 Zornitza Stark Gene: arhgap42 has been classified as Red List (Low Evidence).
Mendeliome v0.8345 ARHGAP42 Zornitza Stark gene: ARHGAP42 was added
gene: ARHGAP42 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARHGAP42 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARHGAP42 were set to 34232960
Phenotypes for gene: ARHGAP42 were set to Interstitial lung disease; systemic hypertension; immunological abnormalities
Review for gene: ARHGAP42 was set to RED
Added comment: Single individual reported with homozygous LoF variant, chILD disorder, systemic hypertension, and immunological findings.
Sources: Literature
Mendeliome v0.8344 KIAA0556 Zornitza Stark Gene: kiaa0556 has been classified as Green List (High Evidence).
Mendeliome v0.8341 IFT140 Zornitza Stark Phenotypes for gene: IFT140 were changed from Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920; Retinitis pigmentosa 80, MIM# 617781 to Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920; MONDO:0009964; Retinitis pigmentosa 80, MIM# 617781
Mendeliome v0.8340 IFT122 Zornitza Stark Phenotypes for gene: IFT122 were changed from Cranioectodermal dysplasia 1, MIM# MIM#218330 to Cranioectodermal dysplasia 1, MIM# MIM#218330; MONDO:0021093
Mendeliome v0.8339 LINGO4 Zornitza Stark Gene: lingo4 has been classified as Green List (High Evidence).
Mendeliome v0.8339 LINGO4 Zornitza Stark Classified gene: LINGO4 as Green List (high evidence)
Mendeliome v0.8339 LINGO4 Zornitza Stark Gene: lingo4 has been classified as Green List (High Evidence).
Mendeliome v0.8338 ARFGEF3 Zornitza Stark Gene: arfgef3 has been classified as Green List (High Evidence).
Mendeliome v0.8338 ARFGEF3 Zornitza Stark Classified gene: ARFGEF3 as Green List (high evidence)
Mendeliome v0.8338 ARFGEF3 Zornitza Stark Gene: arfgef3 has been classified as Green List (High Evidence).
Mendeliome v0.8337 IMPDH2 Zornitza Stark Gene: impdh2 has been classified as Green List (High Evidence).
Mendeliome v0.8336 IMPDH2 Zornitza Stark Classified gene: IMPDH2 as Green List (high evidence)
Mendeliome v0.8336 IMPDH2 Zornitza Stark Gene: impdh2 has been classified as Green List (High Evidence).
Mendeliome v0.8335 IMPDH2 Laura Raiti gene: IMPDH2 was added
gene: IMPDH2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IMPDH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IMPDH2 were set to PMID: 33098801
Phenotypes for gene: IMPDH2 were set to Dystonia
Review for gene: IMPDH2 was set to GREEN
Added comment: 6 unrelated individuals
1x individual in a dystonia cohort index case with infancy-onset dystonia and other neurological manifestations with a de-novo missense variant, c.338G>A (p.Gly113Glu) in IMPDH2, predicted to disrupt an invariant residue within the cystathionine-β-synthase (CBS) domain pair of the encoded protein.
IMPDH2 encodes IMPDH2, a key enzyme in the purine biosynthetic pathway, expressed throughout the brain and not linked previously to any human Mendelian condition.
1x individual with a de-novo substitution, c.337G>A (p.Gly113Arg), was found in in-house whole-exome sequencing data from 500 individuals with neurodevelopmental disorders. Through GeneMatcher, de novo variants identified:
3 x missense: c.729G>C (p.Gln243His), c.619G>C (p.Gly207Arg), and c.619G>A (p.Gly207Arg)
1 x deletion: c.478_480delTCC (p.Ser160del)
The six variants were predicted to be deleterious and none of them seen in control databases. All affected conserved amino acids and resided in and around the cystathionine-β-synthase domain pair.
The described variants are situated in and around the CBS domain pair, a regulatory element in which clustering of pathogenic missense variants has already been shown for the homologue of IMPDH2, IMPDH1.

The variant carriers shared similar neurodevelopmental phenotypes. Apart from the dystonia cohort index case, one participant had evidence of dystonic posturing. Modelling of the variants on 3D protein structures revealed spatial clustering near specific functional sites, predicted to result in deregulation of IMPDH2 activity. Additionally, thermal-shift assays showed that the c.619G>A (p.Gly207Arg) variant, identified as within the CBS domain pair, and c.729G>C (p.Gln243His), which is in close vicinity, affected the stability or folding behaviour of IMPDH2.
Sources: Literature
Mendeliome v0.8334 DYNC2H1 Zornitza Stark changed review comment from: More than 50 unrelated families reported.; to: More than 50 unrelated families reported with predominantly skeletal dysplasia.

Association with RP: - Five affected probands with homozygous and compound heterozygous missense and PTC variants - Associated with the NM_001080463.1 transcript (predominant isoform in retina from retinal organoid studies). PMID 32753734
Mendeliome v0.8334 DYNC2H1 Zornitza Stark edited their review of gene: DYNC2H1: Changed publications: 19442771, 19361615, 22499340, 23456818, 27925158, 32753734; Changed phenotypes: Short-rib thoracic dysplasia 3 with or without polydactyly, MIM# 613091, MONDO:0013127, Non-syndromic retinitis pigmentosa
Mendeliome v0.8334 STK36 Zornitza Stark Phenotypes for gene: STK36 were changed from Primary ciliary dyskinesia to Ciliary dyskinesia, primary, 46, MIM# 619436
Mendeliome v0.8333 STK36 Zornitza Stark edited their review of gene: STK36: Changed phenotypes: Ciliary dyskinesia, primary, 46, MIM# 619436
Mendeliome v0.8333 KIF20A Zornitza Stark Gene: kif20a has been classified as Red List (Low Evidence).
Mendeliome v0.8333 KIF20A Zornitza Stark gene: KIF20A was added
gene: KIF20A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIF20A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF20A were set to 29357359
Phenotypes for gene: KIF20A were set to Cardiomyopathy, familial restrictive, 6, MIM# 619433
Review for gene: KIF20A was set to GREEN
Added comment: Single family reported, two affected sibs, perinatal lethal cardiomyopathy, compound het variants in this gene.
Sources: Literature
Mendeliome v0.8332 ACTG2 Zornitza Stark Phenotypes for gene: ACTG2 were changed from Visceral myopathy, MIM#155310 to Visceral myopathy, MIM#155310; Megacystis-microcolon-intestinal hypoperistalsis syndrome 5, MIM# 619431
Mendeliome v0.8331 ACTG2 Zornitza Stark edited their review of gene: ACTG2: Changed phenotypes: Visceral myopathy, MIM#155310, Megacystis-microcolon-intestinal hypoperistalsis syndrome 5, MIM# 619431
Mendeliome v0.8331 B2M Zornitza Stark Gene: b2m has been classified as Green List (High Evidence).
Mendeliome v0.8331 B2M Zornitza Stark Phenotypes for gene: B2M were changed from to Immunodeficiency 43 MIM# 241600; Sinopulmonary infections; Purple-red skin lesions; Decreased serum IgG; Decreased B cells; Absent β2m associated proteins MHC-I, CD1a, CD1b, and CD1c; MONDO:0009434; Amyloidosis, familial visceral, MIM# 105200
Mendeliome v0.8328 B2M Zornitza Stark reviewed gene: B2M: Rating: GREEN; Mode of pathogenicity: None; Publications: 4186801, 16549777, 25702838, 11118151, 6165007, 22693999; Phenotypes: Immunodeficiency 43 MIM# 241600, Sinopulmonary infections, Purple-red skin lesions, Decreased serum IgG, Decreased B cells, Absent β2m associated proteins MHC-I, CD1a, CD1b, and CD1c, MONDO:0009434, Amyloidosis, familial visceral, MIM# 105200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8328 AK2 Zornitza Stark Phenotypes for gene: AK2 were changed from Reticular dysgenesis, MIM# 267500 to Reticular dysgenesis, MIM# 267500; MONDO:0009973
Mendeliome v0.8326 AK2 Zornitza Stark changed review comment from: Well established gene-disease association.; to: Well established gene-disease association.

PMID: 19043417 (2009). 6 affected individuals from 5 unrelated families (3 of the families showed evidence of consanguinity). Homozygous (5 individuals) and compound heterozygous (1 individual) variants in the AK2 gene. Variants included missense, deletion and inframe indel, resulting in protein LoF. Available parents were sequenced and found heterozygous for the variants, supporting bi-allelic inheritance.

PMID: 19043416 (2009). 7 affected individuals from 6 unrelated families (2 separate consanguineous & 4 non-consanguineous families). Homozygous and compound heterozygous variants detected (missense, deletion, inframe indel), resulting in protein LoF. Reticular dysgenesis phenotype including Leukopenia, lymphopenia and agranulocytosis in all affected individuals and sensorineural deafness in 7 individuals.
Mendeliome v0.8326 AK2 Zornitza Stark edited their review of gene: AK2: Changed phenotypes: Reticular dysgenesis, MIM# 267500, MONDO:0009973
Mendeliome v0.8326 TMEM126A Zornitza Stark Gene: tmem126a has been classified as Green List (High Evidence).
Mendeliome v0.8323 MYC Zornitza Stark Gene: myc has been classified as Red List (Low Evidence).
Mendeliome v0.8321 MYC Zornitza Stark Classified gene: MYC as Red List (low evidence)
Mendeliome v0.8321 MYC Zornitza Stark Gene: myc has been classified as Red List (Low Evidence).
Mendeliome v0.8318 ATG7 Zornitza Stark changed review comment from: 12 individuals from 5 unrelated families reported with a complex neurodevelopmental disorder and bi-allelic variants in this gene. Age range from 21 months to 71 years of age. Main clinical features included axial hypotonia, variably impaired intellectual development with poor or absent speech, and delayed walking (up to 7 years of age) or inability to walk. All had ataxia, often with tremor or dyskinesia, as well as dysarthria associated with cerebellar hypoplasia on brain imaging. Most had optic atrophy, and some had ptosis, chronic progressive external ophthalmoplegia, retinopathy, and strabismus; 1 had early-onset cataracts. The ore severely affected individuals had spastic paraplegia and inability to walk.

Functional data including mouse model.
Sources: Literature; to: 12 individuals from 5 unrelated families reported with a complex neurodevelopmental disorder and bi-allelic variants in this gene. Age range from 21 months to 71 years of age. Main clinical features included axial hypotonia, variably impaired intellectual development with poor or absent speech, and delayed walking (up to 7 years of age) or inability to walk. All had ataxia, often with tremor or dyskinesia, as well as dysarthria associated with cerebellar hypoplasia on brain imaging. Most had optic atrophy, and some had ptosis, chronic progressive external ophthalmoplegia, retinopathy, and strabismus; 1 had early-onset cataracts. The more severely affected individuals had spastic paraplegia and inability to walk.

Functional data including mouse model.
Sources: Literature
Mendeliome v0.8318 ATG7 Zornitza Stark changed review comment from: 12 individuals from 5 unrelated families reported with a complex neurodevelopmental disorder and bi-allelic variants in this gene. Age range from 21 months to 71 years of age. Main clinical features included axial hypotonia, variably impaired intellectual development with poor or absent speech, and delayed walking (up to 7 years of age) or inability to walk. All had ataxia, often with tremor or dyskinesia, as well as dysarthria associated with cerebellar hypoplasia on brain imaging. Most had optic atrophy, and some had ptosis, chronic progressive external ophthalmoplegia, retinopathy, and strabismus; 1 had early-onset cataracts. The ore severely affected individuals had spastic paraplegia and inability to walk.
Sources: Literature; to: 12 individuals from 5 unrelated families reported with a complex neurodevelopmental disorder and bi-allelic variants in this gene. Age range from 21 months to 71 years of age. Main clinical features included axial hypotonia, variably impaired intellectual development with poor or absent speech, and delayed walking (up to 7 years of age) or inability to walk. All had ataxia, often with tremor or dyskinesia, as well as dysarthria associated with cerebellar hypoplasia on brain imaging. Most had optic atrophy, and some had ptosis, chronic progressive external ophthalmoplegia, retinopathy, and strabismus; 1 had early-onset cataracts. The ore severely affected individuals had spastic paraplegia and inability to walk.

Functional data including mouse model.
Sources: Literature
Mendeliome v0.8318 ATG7 Zornitza Stark Gene: atg7 has been classified as Green List (High Evidence).
Mendeliome v0.8318 ATG7 Zornitza Stark Classified gene: ATG7 as Green List (high evidence)
Mendeliome v0.8318 ATG7 Zornitza Stark Gene: atg7 has been classified as Green List (High Evidence).
Mendeliome v0.8317 ATG7 Zornitza Stark gene: ATG7 was added
gene: ATG7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATG7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATG7 were set to 34161705
Phenotypes for gene: ATG7 were set to Spinocerebellar ataxia, SCAR31, MIM#619422
Review for gene: ATG7 was set to GREEN
Added comment: 12 individuals from 5 unrelated families reported with a complex neurodevelopmental disorder and bi-allelic variants in this gene. Age range from 21 months to 71 years of age. Main clinical features included axial hypotonia, variably impaired intellectual development with poor or absent speech, and delayed walking (up to 7 years of age) or inability to walk. All had ataxia, often with tremor or dyskinesia, as well as dysarthria associated with cerebellar hypoplasia on brain imaging. Most had optic atrophy, and some had ptosis, chronic progressive external ophthalmoplegia, retinopathy, and strabismus; 1 had early-onset cataracts. The ore severely affected individuals had spastic paraplegia and inability to walk.
Sources: Literature
Mendeliome v0.8316 ADA Zornitza Stark Gene: ada has been classified as Green List (High Evidence).
Mendeliome v0.8313 C2orf69 Zornitza Stark Gene: c2orf69 has been classified as Green List (High Evidence).
Mendeliome v0.8313 C2orf69 Zornitza Stark Classified gene: C2orf69 as Green List (high evidence)
Mendeliome v0.8313 C2orf69 Zornitza Stark Gene: c2orf69 has been classified as Green List (High Evidence).
Mendeliome v0.8312 C2orf69 Zornitza Stark gene: C2orf69 was added
gene: C2orf69 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: C2orf69 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C2orf69 were set to 34038740; 33945503
Phenotypes for gene: C2orf69 were set to Combined oxidative phosphorylation deficiency-53 (COXPD53), MIM#619423
Review for gene: C2orf69 was set to GREEN
Added comment: PMID 34038740: 20 affected children from 8 unrelated families reported, presenting with fatal syndrome consisting of severe autoinflammation and progredient leukoencephalopathy with recurrent seizures; 12 of these subjects, whose DNA was available, segregated homozygous loss-of-function C2orf69 variants. Endogenous C2ORF69 was found to be (1) loosely bound to mitochondria, (2) affects mitochondrial membrane potential and oxidative respiration in cultured neurons, and (3) controls the levels of the glycogen branching enzyme 1 (GBE1) consistent with a glycogen-storage-associated mitochondriopathy. Zebrafish model.

PMID 33945503: 8 individuals from 5 families reported with muscle hypotonia, developmental delay, progressive microcephaly, and brain MRI abnormalities. Age at onset ranged from birth to 6 months of age. Six patients had vision impairment, liver abnormalities, inflammation/inflammatory arthritis, and 5 patients had seizures.
Sources: Literature
Mendeliome v0.8310 NYNRIN Zornitza Stark Gene: nynrin has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8310 NYNRIN Zornitza Stark Phenotypes for gene: NYNRIN were changed from to Wilms tumour predisposition
Mendeliome v0.8309 NYNRIN Zornitza Stark Classified gene: NYNRIN as Amber List (moderate evidence)
Mendeliome v0.8309 NYNRIN Zornitza Stark Gene: nynrin has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8308 FBXW7 Zornitza Stark Phenotypes for gene: FBXW7 were changed from FBXW7-related neurodevelopmental syndrome to FBXW7-related neurodevelopmental syndrome; Wilms tumour predisposition
Mendeliome v0.8306 FBXW7 Zornitza Stark reviewed gene: FBXW7: Rating: GREEN; Mode of pathogenicity: None; Publications: 30885698, 26482194; Phenotypes: Wilms tumour predisposition; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8304 ZC3H14 Zornitza Stark edited their review of gene: ZC3H14: Added comment: Two families and a mouse model.; Changed phenotypes: Mental retardation, autosomal recessive 56, OMIM# 617125
Mendeliome v0.8302 ATP1A2 Zornitza Stark Gene: atp1a2 has been classified as Green List (High Evidence).
Mendeliome v0.8302 RNF2 Zornitza Stark Gene: rnf2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8302 RNF2 Zornitza Stark Classified gene: RNF2 as Amber List (moderate evidence)
Mendeliome v0.8302 RNF2 Zornitza Stark Gene: rnf2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8301 RING1 Zornitza Stark Gene: ring1 has been classified as Red List (Low Evidence).
Mendeliome v0.8301 RING1 Zornitza Stark Classified gene: RING1 as Red List (low evidence)
Mendeliome v0.8301 RING1 Zornitza Stark Gene: ring1 has been classified as Red List (Low Evidence).
Mendeliome v0.8300 IRX5 Zornitza Stark Gene: irx5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8297 IRX5 Zornitza Stark Classified gene: IRX5 as Amber List (moderate evidence)
Mendeliome v0.8297 IRX5 Zornitza Stark Gene: irx5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8296 IRX6 Zornitza Stark Gene: irx6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8296 IRX6 Zornitza Stark Classified gene: IRX6 as Amber List (moderate evidence)
Mendeliome v0.8296 IRX6 Zornitza Stark Gene: irx6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8293 RAB3GAP1 Zornitza Stark changed review comment from: Rare autosomal recessive syndrome characterized by microcephaly, microphthalmia, microcornea, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe mental retardation, spastic diplegia, and hypogonadism. Multiple families reported.; to: Warburg micro: Rare autosomal recessive syndrome characterized by microcephaly, microphthalmia, microcornea, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe ID, spastic diplegia, and hypogonadism. Multiple families reported.

Martsolf syndrome is characterised by cataracts, mild to severe ID, dysmorphic features. Two families reported.
Mendeliome v0.8293 CXCR2 Zornitza Stark Gene: cxcr2 has been classified as Red List (Low Evidence).
Mendeliome v0.8293 CXCR2 Zornitza Stark gene: CXCR2 was added
gene: CXCR2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CXCR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CXCR2 were set to 24777453
Phenotypes for gene: CXCR2 were set to WHIM syndrome 2, 619407
Review for gene: CXCR2 was set to RED
Added comment: 2 sisters with neutropaenia, myelokathexis, and recurrent bacterial infections and homozygous frameshift variant in this gene.
Sources: Expert list
Mendeliome v0.8292 IRX5 Eleanor Williams changed review comment from: Associated with Hamamy syndrome #611174 (AR) in OMIM. Hamamy syndrome is characterised by craniofacial dysmorphism, hearing loss, skeletal anomalies, microcytic hypochromic anemia and congenital heart defects. Severe myopia has also been reported. Homozygous missense variants in IRX5 were reported in 2 families with this condition.

Cone dystrophy
-------------------
PMID: 33891002 - Khol et al 2021 - report 3 unrelated families with duplications of a region covering the genes IRX5 and IRX6 completely, and the proximal exons of MMP2 and cone dystrophy. They propose that overexpression of IRX5 and IRX6 may be the cause of the disease, and this is supported by expression analysis in patient-derived fibroblasts and zebrafish experiments.

Initial family is a large 5 generation German family with 14 members with autosomal dominant cone dystrophy in which a 600kb duplicated region covering IRX5/IRX6 and part of MMP2 was identified. 2 additional families of Chinese and Dutch descent with copy number gains of ~700 and ~850 kb, covering the same region were then identified. The smallest region of overlap is 608kb. In addition another family of German decent is reported with adCD and the same duplication as the first German family. It is not known if they are distantly related. Segregation analysis on available members of all families showed the duplication in affected members and not in unaffected.

They find that IRX5, IRX6 and MMP2 are expressed in human adult retina. Several lincRNA within the locus are also expressed. In patient derived fibroblasts IRX5 and IRX6 showed increased expression levels. Over expression of IRX5 and IRX6 results in impaired visual performance in zebrafish larvae.; to: Associated with Hamamy syndrome #611174 (AR) in OMIM. Hamamy syndrome is characterised by craniofacial dysmorphism, hearing loss, skeletal anomalies, microcytic hypochromic anemia and congenital heart defects. Severe myopia has also been reported. Homozygous missense variants in IRX5 were reported in 2 families with this condition (PMID: 22581230;17230486)

Duplication of gene
-------------------
PMID: 33891002 - Kohl et al 2021 - report 3 unrelated families with duplications of a region covering the genes IRX5 and IRX6 completely, and the proximal exons of MMP2 and cone dystrophy. They propose that overexpression of IRX5 and IRX6 may be the cause of the disease, and this is supported by expression analysis in patient-derived fibroblasts and zebrafish experiments.

Initial family is a large 5 generation German family with 14 members with autosomal dominant cone dystrophy in which a 600kb duplicated region covering IRX5/IRX6 and part of MMP2 was identified. 2 additional families of Chinese and Dutch descent with copy number gains of ~700 and ~850 kb, covering the same region were then identified. The smallest region of overlap is 608kb. In addition another family of German decent is reported with adCD and the same duplication as the first German family. It is not known if they are distantly related. Segregation analysis on available members of all families showed the duplication in affected members and not in unaffected.

They find that IRX5, IRX6 and MMP2 are expressed in human adult retina. Several lincRNA within the locus are also expressed. In patient derived fibroblasts IRX5 and IRX6 showed increased expression levels. Over expression of IRX5 and IRX6 results in impaired visual performance in zebrafish larvae.

Loss of function/gene
---------
PMID: 28041643 - Carss et al 2017 - screened a cohort of 722 individuals with inherited retinal disease using WES/WGS. 1 case reported with a biallelic deletion in IRX5 reported which leads to a frameshift ENST00000394636.4; c.1362_1366delTAAAG, p.Lys455ProfsTer19 in a patient with retinitis pigmentosa.

PMID: 32045705 - Apuzzo et al 2020 - report 2 cases of loss of a region in 16q12.1q21 which encompasses IRX5 and IRX6 and many other genes, which together with 3 other previous reports of deletions in this region help define a syndrome with features that include dysmorphic features, short stature, microcephaly, global developmental delay/intellectual disability, autism spectrum disorder (ASD) and ocular abnormalities (nystagmus and strabismus).
Mendeliome v0.8292 IRX6 Eleanor Williams changed review comment from: Not associated with any disorder in OMIM or Gene2Phenotype.

PMID: 33891002 - Khol et al 2021 - report 3 unrelated families with duplications of a region covering the genes IRX5 and IRX6 completely, and the proximal exons of MMP2 and cone dystrophy. They propose that overexpression of IRX5 and IRX6 may be the cause of the disease, and this is supported by expression analysis in patient-derived fibroblasts and zebrafish experiments.

Initial family is a large 5 generation German family with 14 members with autosomal dominant cone dystrophy in which a 600kb duplicated region covering IRX5/IRX6 and part of MMP2 was identified. 2 additional families of Chinese and Dutch descent with copy number gains of ~700 and ~850 kb, covering the same region were then identified. The smallest region of overlap is 608kb. In addition another family of German decent is reported with adCD and the same duplication as the first German family. It is not known if they are distantly related. Segregation analysis on available members of all families showed the duplication in affected members and not in unaffected.

They find that IRX5, IRX6 and MMP2 are expressed in human adult retina. Several lincRNA within the locus are also expressed. In patient derived fibroblasts IRX5 and IRX6 showed increased expression levels. Over expression of IRX5 and IRX6 results in impaired visual performance in zebrafish larvae.
Sources: Literature; to: Not associated with any disorder in OMIM or Gene2Phenotype.

PMID: 33891002 - Kohl et al 2021 - report 3 unrelated families with duplications of a region covering the genes IRX5 and IRX6 completely, and the proximal exons of MMP2 and cone dystrophy. They propose that overexpression of IRX5 and IRX6 may be the cause of the disease, and this is supported by expression analysis in patient-derived fibroblasts and zebrafish experiments.

Initial family is a large 5 generation German family with 14 members with autosomal dominant cone dystrophy in which a 600kb duplicated region covering IRX5/IRX6 and part of MMP2 was identified. 2 additional families of Chinese and Dutch descent with copy number gains of ~700 and ~850 kb, covering the same region were then identified. The smallest region of overlap is 608kb. In addition another family of German decent is reported with adCD and the same duplication as the first German family. It is not known if they are distantly related. Segregation analysis on available members of all families showed the duplication in affected members and not in unaffected.

They find that IRX5, IRX6 and MMP2 are expressed in human adult retina. Several lincRNA within the locus are also expressed. In patient derived fibroblasts IRX5 and IRX6 showed increased expression levels. Over expression of IRX5 and IRX6 results in impaired visual performance in zebrafish larvae.
Sources: Literature
Mendeliome v0.8292 SLCO2A1 Zornitza Stark Gene: slco2a1 has been classified as Green List (High Evidence).
Mendeliome v0.8291 GNB2 Zornitza Stark Classified gene: GNB2 as Green List (high evidence)
Mendeliome v0.8291 GNB2 Zornitza Stark Gene: gnb2 has been classified as Green List (High Evidence).
Mendeliome v0.8290 HID1 Zornitza Stark Gene: hid1 has been classified as Green List (High Evidence).
Mendeliome v0.8290 HID1 Zornitza Stark Classified gene: HID1 as Green List (high evidence)
Mendeliome v0.8290 HID1 Zornitza Stark Gene: hid1 has been classified as Green List (High Evidence).
Mendeliome v0.8288 KIF1B Zornitza Stark Gene: kif1b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8288 KIF1B Zornitza Stark Phenotypes for gene: KIF1B were changed from to Charcot-Marie-Tooth disease, type 2A1 MIM#118210; Hypotonia, coloboma, hypoplasia of the corpus callosum, severe neurodevelopmental delay
Mendeliome v0.8285 NUF2 Zornitza Stark Gene: nuf2 has been classified as Red List (Low Evidence).
Mendeliome v0.8285 NUF2 Zornitza Stark Classified gene: NUF2 as Red List (low evidence)
Mendeliome v0.8285 NUF2 Zornitza Stark Gene: nuf2 has been classified as Red List (Low Evidence).
Mendeliome v0.8284 ERGIC3 Seb Lunke Gene: ergic3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8284 ERGIC3 Seb Lunke Classified gene: ERGIC3 as Amber List (moderate evidence)
Mendeliome v0.8284 ERGIC3 Seb Lunke Gene: ergic3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8283 FYCO1 Zornitza Stark Gene: fyco1 has been classified as Green List (High Evidence).
Mendeliome v0.8278 JPH3 Seb Lunke Gene: jph3 has been classified as Red List (Low Evidence).
Mendeliome v0.8277 MYT1 Zornitza Stark changed review comment from: Five unrelated individuals reported with variants in this gene and OAV spectrum.; to: Five unrelated individuals reported with variants in this gene and OAV spectrum.

Single individual reported with missense variant as part of an ID cohort, limited evidence for disease association.
Mendeliome v0.8277 JPH3 Seb Lunke Classified gene: JPH3 as Red List (low evidence)
Mendeliome v0.8277 JPH3 Seb Lunke Added comment: Comment on list classification: Only STRs disease causing, see separate STR list. No evidence for SNVs etc.
Mendeliome v0.8277 JPH3 Seb Lunke Gene: jph3 has been classified as Red List (Low Evidence).
Mendeliome v0.8276 MYT1 Zornitza Stark Gene: myt1 has been classified as Green List (High Evidence).
Mendeliome v0.8273 HEATR5B Seb Lunke Phenotypes for gene: HEATR5B were changed from pontocerebellar hypoplasia to pontocerebellar hypoplasia; intellectual disability; seizures
Mendeliome v0.8272 ATP1A2 Zornitza Stark Phenotypes for gene: ATP1A2 were changed from to Alternating hemiplegia of childhood 1, MIM#104290; Hydrops fetalis, microcephaly, arthrogryposis, extensive cortical malformations; Developmental and epileptic encephalopathy, polymicrogyria
Mendeliome v0.8269 ATP1A2 Zornitza Stark edited their review of gene: ATP1A2: Added comment: Association with alternating hemiplegia is well established.

PMID 31608932: Three individuals from two unrelated families reported with balleliic LoF variants in this gene and hydrops/congenital abnormalities. Mouse model is perinatal lethal.

PMID 33880529: six individuals with de novo missense variants reported and DD/EE/PMG.; Changed rating: GREEN; Changed publications: 31608932, 33880529; Changed phenotypes: Alternating hemiplegia of childhood 1, MIM#104290, Hydrops fetalis, microcephaly, arthrogryposis, extensive cortical malformations, Developmental and epileptic encephalopathy, polymicrogyria; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8269 HEATR5B Seb Lunke Gene: heatr5b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8269 HEATR5B Seb Lunke Classified gene: HEATR5B as Amber List (moderate evidence)
Mendeliome v0.8269 HEATR5B Seb Lunke Gene: heatr5b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8266 SAMD9L Zornitza Stark changed review comment from: At least three unrelated families reported, some postulate GoF whereas others postulate LoF as mechanism.; to: Ataxia-pancytopaenia: At least three unrelated families reported, some postulate GoF whereas others postulate LoF as mechanism.

ID: single individual reported, limited evidence of association.
Mendeliome v0.8266 PITRM1 Zornitza Stark Phenotypes for gene: PITRM1 were changed from Ataxia; Intellectual disability to Spinocerebellar ataxia-30 (SCAR30), MIM#619405; intellectual disability; cognitive decline; psychosis
Mendeliome v0.8265 VPS41 Zornitza Stark Phenotypes for gene: VPS41 were changed from Dystonia; intellectual disability to Spinocerebellar ataxia-29 (SCAR29), MIM#619389; Progressive neurodevelopmental disorder with ataxia, hypotonia, dystonia, intellectual disability and speech delay
Mendeliome v0.8264 IRX6 Eleanor Williams gene: IRX6 was added
gene: IRX6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IRX6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: IRX6 were set to 33891002
Phenotypes for gene: IRX6 were set to cone dystrophy, MONDO:0000455
Mode of pathogenicity for gene: IRX6 was set to Other
Review for gene: IRX6 was set to GREEN
Added comment: Not associated with any disorder in OMIM or Gene2Phenotype.

PMID: 33891002 - Khol et al 2021 - report 3 unrelated families with duplications of a region covering the genes IRX5 and IRX6 completely, and the proximal exons of MMP2 and cone dystrophy. They propose that overexpression of IRX5 and IRX6 may be the cause of the disease, and this is supported by expression analysis in patient-derived fibroblasts and zebrafish experiments.

Initial family is a large 5 generation German family with 14 members with autosomal dominant cone dystrophy in which a 600kb duplicated region covering IRX5/IRX6 and part of MMP2 was identified. 2 additional families of Chinese and Dutch descent with copy number gains of ~700 and ~850 kb, covering the same region were then identified. The smallest region of overlap is 608kb. In addition another family of German decent is reported with adCD and the same duplication as the first German family. It is not known if they are distantly related. Segregation analysis on available members of all families showed the duplication in affected members and not in unaffected.

They find that IRX5, IRX6 and MMP2 are expressed in human adult retina. Several lincRNA within the locus are also expressed. In patient derived fibroblasts IRX5 and IRX6 showed increased expression levels. Over expression of IRX5 and IRX6 results in impaired visual performance in zebrafish larvae.
Sources: Literature
Mendeliome v0.8264 EPHA7 Zornitza Stark Gene: epha7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8264 EPHA7 Zornitza Stark Classified gene: EPHA7 as Amber List (moderate evidence)
Mendeliome v0.8264 EPHA7 Zornitza Stark Gene: epha7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8263 EPHA7 Zornitza Stark gene: EPHA7 was added
gene: EPHA7 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: EPHA7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EPHA7 were set to 34176129
Phenotypes for gene: EPHA7 were set to Intellectual disability
Review for gene: EPHA7 was set to AMBER
Added comment: Lévy et al (2021 - PMID: 34176129) provide evidence that haploinssuficiency of EPHA7 results in a neurodevelopmental disorder.

The authors report on 12 individuals belonging to 9 unrelated families, all harboring with 6q microdeletions spanning EPHA7.

Overlapping features included DD (13/13), ID (10/10 - mild in most cases, individuals with larger CNVs/additional variants had more severe phenotype), speech delay and behavioral disorders. Variable other features incl. hypotonia (70%), non specific facial features, eye abnormalities (40%) and cardiac defects (25%).

The CNVs ranged from 152 kb to few Mb in size but in 4 subjects (P5-8) were only minimal, involving only EPHA7.

9 out of 12 individuals had inherited the deletion (5 subjects paternal, 4 maternal), in 1 subject (P12) this occured de novo, while for 2 others inheritance was not specified. Most deletions were inherited from an unaffected parent (in 6/7 families), with unclear contribution in a further one.

The authors discuss on previous studies suggesting an important role for EphA7 in brain development (modulation of cell-cell adhesion and repulsion, regulation of dendrite morphogenesis in early corticogenesis, role in dendritic spine formation later in development. EphA7 has also been proposed to drive neuronal maturation and synaptic function).

Haploinsufficiency for other ephrins or ephrin receptors has been implicated in other NDDs.

Overall Lévy et al promote incomplete penetrance and variable expressivity with haploinsufficiency of this gene being a risk factor for NDD. [The gene has also an %HI of 2.76% and a pLI of 1].
Sources: Expert Review
Mendeliome v0.8262 DNM1 Zornitza Stark Gene: dnm1 has been classified as Green List (High Evidence).
Mendeliome v0.8259 GRK2 Zornitza Stark Gene: grk2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8259 GRK2 Zornitza Stark Classified gene: GRK2 as Amber List (moderate evidence)
Mendeliome v0.8259 GRK2 Zornitza Stark Gene: grk2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8257 WDR60 Zornitza Stark Gene: wdr60 has been classified as Green List (High Evidence).
Mendeliome v0.8257 WDR60 Zornitza Stark Phenotypes for gene: WDR60 were changed from to Short-rib thoracic dysplasia 8 with or without polydactyly, MIM# 615503; Retinitis pigmentosa
Mendeliome v0.8254 WDR60 Zornitza Stark reviewed gene: WDR60: Rating: GREEN; Mode of pathogenicity: None; Publications: 23910462, 29271569, 26874042; Phenotypes: Short-rib thoracic dysplasia 8 with or without polydactyly, MIM# 615503, Retinitis pigmentosa; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8254 WDR34 Zornitza Stark Gene: wdr34 has been classified as Green List (High Evidence).
Mendeliome v0.8254 WDR34 Zornitza Stark Phenotypes for gene: WDR34 were changed from to Short-rib thoracic dysplasia 11 with or without polydactyly, MIM# 615633; Retinitis pigmentosa
Mendeliome v0.8251 WDR34 Zornitza Stark reviewed gene: WDR34: Rating: GREEN; Mode of pathogenicity: None; Publications: 24183449, 24183451, 33124039, 30649997, 29241935, 28379358; Phenotypes: Short-rib thoracic dysplasia 11 with or without polydactyly, MIM# 615633, Retinitis pigmentosa; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8251 WDR19 Zornitza Stark Gene: wdr19 has been classified as Green List (High Evidence).
Mendeliome v0.8251 WDR19 Zornitza Stark Phenotypes for gene: WDR19 were changed from to Nephronophthisis 13, MIM# 614377; Senior-Loken syndrome 8, MIM# 616307; Short-rib thoracic dysplasia 5 with or without polydactyly, MIM# 614376; Cranioectodermal dysplasia 4, MIM# 614378
Mendeliome v0.8248 WDR19 Zornitza Stark reviewed gene: WDR19: Rating: GREEN; Mode of pathogenicity: None; Publications: 33946315, 33875766, 33606107, 22019273, 23559409, 23683095, 32055034; Phenotypes: Nephronophthisis 13, MIM# 614377, Senior-Loken syndrome 8, MIM# 616307, Short-rib thoracic dysplasia 5 with or without polydactyly, MIM# 614376, Cranioectodermal dysplasia 4, MIM# 614378; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8248 TXNDC15 Zornitza Stark Gene: txndc15 has been classified as Green List (High Evidence).
Mendeliome v0.8245 TTC8 Zornitza Stark Gene: ttc8 has been classified as Green List (High Evidence).
Mendeliome v0.8242 TTC21B Zornitza Stark Gene: ttc21b has been classified as Green List (High Evidence).
Mendeliome v0.8242 TTC21B Zornitza Stark Phenotypes for gene: TTC21B were changed from to Nephronophthisis 12, MIM# 613820; Short-rib thoracic dysplasia 4 with or without polydactyly, MIM# 613819; Joubert syndrome
Mendeliome v0.8239 TTC21B Zornitza Stark reviewed gene: TTC21B: Rating: GREEN; Mode of pathogenicity: None; Publications: 21258341, 25492405, 18327258, 33875766; Phenotypes: Nephronophthisis 12, MIM# 613820, Short-rib thoracic dysplasia 4 with or without polydactyly, MIM# 613819, Joubert syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8239 TRAF3IP1 Zornitza Stark Gene: traf3ip1 has been classified as Green List (High Evidence).
Mendeliome v0.8236 ATP9A Zornitza Stark Classified gene: ATP9A as Amber List (moderate evidence)
Mendeliome v0.8236 ATP9A Zornitza Stark Gene: atp9a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8235 ATP2C2 Zornitza Stark Classified gene: ATP2C2 as Red List (low evidence)
Mendeliome v0.8235 ATP2C2 Zornitza Stark Gene: atp2c2 has been classified as Red List (Low Evidence).
Mendeliome v0.8229 ATP9A Arina Puzriakova gene: ATP9A was added
gene: ATP9A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATP9A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP9A were set to http://dx.doi.org/10.1136/jmedgenet-2021-107843
Phenotypes for gene: ATP9A were set to Neurodevelopmental delay; Postnatal microcephaly; Failure to thrive; Gastrointestinal symptoms
Review for gene: ATP9A was set to AMBER
Added comment: Vogt et al. 2021 report on 3 individuals from 2 unrelated consanguineous families with different homozygous truncating variants in ATP9A, presenting with DD/ID of variable degree (2 mild, 1 severe), postnatal microcephaly (OFC range: −2.33 SD to −3.58 SD), failure to thrive, and gastrointestinal symptoms. Patient-derived fibroblasts showed reduced expression of ATP9A, and consistent with previous findings also overexpression of interacting partners, ARPC3 and SNX3.
Sources: Literature
Mendeliome v0.8229 ATP2C2 Eleanor Williams gene: ATP2C2 was added
gene: ATP2C2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATP2C2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ATP2C2 were set to 33864365; 28440294
Phenotypes for gene: ATP2C2 were set to language impairment, HP:0002463
Review for gene: ATP2C2 was set to RED
Added comment: PMID: 33864365 - Martinelli et al 2021 - report a family with a missense variant NM_001286527.2:c.304G>A, p.(Val102Met) in ATP2C2 in a father and two siblings with specific language impairment. However two other affected siblings did not have this variant. This variant was also reported by Chen et al. They found that the variant had a higher frequency in language cases (1.8%, N = 360) compared with cohorts selected for dyslexia (0.8%, N = 520) and ADHD (0.7%, N = 150), which presented frequencies comparable to reference databases (0.9%, N = 24 046 gnomAD controls). They postulate that variant is not sufficient on its own to cause a disorder but is a susceptibility factor which increases the risk for language impairment.

PMID: 28440294 - Chen et al 2017 - report 2 probands with severe learning impairment, and missense variants in ATP2C2 (NM_001286527: c.G304A:p.V102M and NM_001291454:exon21: c.C1936T:p.R646W).
Sources: Literature
Mendeliome v0.8229 TMEM67 Zornitza Stark Gene: tmem67 has been classified as Green List (High Evidence).
Mendeliome v0.8229 TMEM67 Zornitza Stark Phenotypes for gene: TMEM67 were changed from to Joubert syndrome 6, MIM# 610688; Meckel syndrome 3, MIM# 607361; Nephronophthisis 11, MIM# 613550; COACH syndrome 1, MIM# 216360
Mendeliome v0.8226 TMEM67 Zornitza Stark edited their review of gene: TMEM67: Added comment: Bi-allelic variants in this gene are associated with a range of ciliopathies, including JBTS, Meckel syndrome and nephronophthisis. Multiple families with each.; Changed publications: 16415887, 17377820, 17160906, 19508969; Changed phenotypes: Joubert syndrome 6, MIM# 610688, Meckel syndrome 3, MIM# 607361, Nephronophthisis 11, MIM# 613550, COACH syndrome 1, MIM# 216360
Mendeliome v0.8226 XDH Zornitza Stark Gene: xdh has been classified as Green List (High Evidence).
Mendeliome v0.8223 TCTEX1D2 Zornitza Stark Gene: tctex1d2 has been classified as Green List (High Evidence).
Mendeliome v0.8223 TCTEX1D2 Zornitza Stark Phenotypes for gene: TCTEX1D2 were changed from to Short-rib thoracic dysplasia 17 with or without polydactyly, MIM# 617405
Mendeliome v0.8220 TCTEX1D2 Zornitza Stark reviewed gene: TCTEX1D2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26044572, 25830415; Phenotypes: Short-rib thoracic dysplasia 17 with or without polydactyly, MIM# 617405; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8220 TCTN3 Zornitza Stark Gene: tctn3 has been classified as Green List (High Evidence).
Mendeliome v0.8217 SDCCAG8 Zornitza Stark Gene: sdccag8 has been classified as Green List (High Evidence).
Mendeliome v0.8217 SDCCAG8 Zornitza Stark Phenotypes for gene: SDCCAG8 were changed from to Bardet-Biedl syndrome 16, MIM# 615993; MONDO:0014444; Senior-Loken syndrome 7, MIM# 613615; MONDO:0013326; Nephronophthisis
Mendeliome v0.8214 SDCCAG8 Zornitza Stark reviewed gene: SDCCAG8: Rating: GREEN; Mode of pathogenicity: None; Publications: 20835237, 22626039, 22626039, 32432520, 31534065, 26968886; Phenotypes: Bardet-Biedl syndrome 16, MIM# 615993, MONDO:0014444, Senior-Loken syndrome 7, MIM# 613615, MONDO:0013326, Nephronophthisis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8214 SBDS Zornitza Stark Gene: sbds has been classified as Green List (High Evidence).
Mendeliome v0.8212 RPGRIP1L Zornitza Stark Gene: rpgrip1l has been classified as Green List (High Evidence).
Mendeliome v0.8212 RPGRIP1L Zornitza Stark Phenotypes for gene: RPGRIP1L were changed from to Joubert syndrome 7, MIM# 611560; Meckel syndrome 5, MIM# 611561; COACH syndrome 3, MIM# 619113; Nephronophthisis
Mendeliome v0.8209 RPGRIP1L Zornitza Stark edited their review of gene: RPGRIP1L: Added comment: Bi-allelic variants in this gene are associated with a range of ciliopathies, including JBTS and Meckel syndrome. Mouse model.; Changed publications: 17558409, 17558407, 17960139, 26071364, 19574260, 29991045; Changed phenotypes: Joubert syndrome 7, MIM# 611560, Meckel syndrome 5, MIM# 611561, COACH syndrome 3, MIM# 619113, Nephronophthisis
Mendeliome v0.8209 NPHP4 Zornitza Stark Gene: nphp4 has been classified as Green List (High Evidence).
Mendeliome v0.8209 NPHP4 Zornitza Stark Phenotypes for gene: NPHP4 were changed from to Nephronophthisis 4, MIM# 606966; Senior-Loken syndrome 4, MIM# 606996
Mendeliome v0.8206 NPHP4 Zornitza Stark reviewed gene: NPHP4: Rating: GREEN; Mode of pathogenicity: None; Publications: 12244321, 12205563, 34013113; Phenotypes: Nephronophthisis 4, MIM# 606966, Senior-Loken syndrome 4, MIM# 606996; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8206 NPHP1 Zornitza Stark Gene: nphp1 has been classified as Green List (High Evidence).
Mendeliome v0.8206 NPHP1 Zornitza Stark Phenotypes for gene: NPHP1 were changed from to Joubert syndrome 4, MIM# 609583; Nephronophthisis 1, juvenile, MIM# 256100; Senior-Loken syndrome-1, MIM# 266900
Mendeliome v0.8203 NPHP1 Zornitza Stark reviewed gene: NPHP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15138899, 32139166, 28347285, 8852662, 9856524; Phenotypes: Joubert syndrome 4, MIM# 609583, Nephronophthisis 1, juvenile, MIM# 256100, Senior-Loken syndrome-1, MIM# 266900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8203 TIE1 Zornitza Stark Gene: tie1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8203 TIE1 Zornitza Stark Classified gene: TIE1 as Amber List (moderate evidence)
Mendeliome v0.8203 TIE1 Zornitza Stark Gene: tie1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8201 KIF1B Paul De Fazio reviewed gene: KIF1B: Rating: RED; Mode of pathogenicity: None; Publications: 33710394; Phenotypes: Hypotonia, coloboma, hypoplasia of the corpus callosum, severe neurodevelopmental delay; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.8201 NUF2 Dean Phelan gene: NUF2 was added
gene: NUF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NUF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NUF2 were set to PMID: 33721060
Phenotypes for gene: NUF2 were set to microcephaly; short stature; bilateral vocal cord paralysis; micrognathia; atrial septal defect
Review for gene: NUF2 was set to RED
Added comment: PMID: 33721060 - de novo missense variant identified in one male patient with microcephaly and short stature, with additional features, such as bilateral vocal cord paralysis, micrognathia and atrial septal defect.
Sources: Literature
Mendeliome v0.8201 ERGIC3 Elena Savva gene: ERGIC3 was added
gene: ERGIC3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ERGIC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERGIC3 were set to PMID: 33710394; 31585110
Phenotypes for gene: ERGIC3 were set to Intellectual disability
Review for gene: ERGIC3 was set to AMBER
Added comment: PMID: 33710394 - two homozygous sibs with mild ID, a novel canonical splice (c.717+1G>A). Absent in gnomAD, no splice studies. Classed as a VUS.

PMID: 31585110 - 1 hom (p.Gln233Argfs*10) in a male 8yo with Growth retardation, Microcephaly, Learning disability, Facial dysmorphism, Abnormal pigmentation.
Sources: Literature
Mendeliome v0.8201 HEATR5B Teresa Zhao gene: HEATR5B was added
gene: HEATR5B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HEATR5B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HEATR5B were set to PMID: 33824466
Phenotypes for gene: HEATR5B were set to pontocerebellar hypoplasia
Review for gene: HEATR5B was set to AMBER
Added comment: Four affected children from two families presenting with pontocerebellar hypoplasiawith neonatal seizures, severe ID and motor delay.

Two homozygous splice variants were reported ((c.5051–1G>A and c.5050+4A>G) in intron 31 of HEATR5B gene. Aberrant splicing was found in patient fibroblasts, which correlated
with reduced levels of HEATR5B protein.

Homozygous knockout mice were not viable.

*NOTE: gene (and alias) not found in OMIM
Sources: Literature
Mendeliome v0.8201 NEK8 Zornitza Stark Gene: nek8 has been classified as Green List (High Evidence).
Mendeliome v0.8201 NEK8 Zornitza Stark Phenotypes for gene: NEK8 were changed from to Renal-hepatic-pancreatic dysplasia 2, MIM# 615415; MONDO:0014174
Mendeliome v0.8198 NEK8 Zornitza Stark reviewed gene: NEK8: Rating: GREEN; Mode of pathogenicity: None; Publications: 33131162, 23418306, 26862157, 26697755, 26967905, 23274954, 31633649; Phenotypes: Renal-hepatic-pancreatic dysplasia 2, MIM# 615415, MONDO:0014174; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8198 MKKS Zornitza Stark Gene: mkks has been classified as Green List (High Evidence).
Mendeliome v0.8198 MKKS Zornitza Stark Phenotypes for gene: MKKS were changed from to Bardet-Biedl syndrome 6 (MIM#605231); McKusick-Kaufman syndrome, MIM# 236700; Retinitis pigmentosa
Mendeliome v0.8195 MKKS Zornitza Stark reviewed gene: MKKS: Rating: GREEN; Mode of pathogenicity: None; Publications: 10802661, 26900326, 10973251; Phenotypes: Bardet-Biedl syndrome 6 (MIM#605231), McKusick-Kaufman syndrome, MIM# 236700, Retinitis pigmentosa; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8195 IQCB1 Zornitza Stark Gene: iqcb1 has been classified as Green List (High Evidence).
Mendeliome v0.8192 IFT80 Zornitza Stark Gene: ift80 has been classified as Green List (High Evidence).
Mendeliome v0.8192 IFT80 Zornitza Stark Phenotypes for gene: IFT80 were changed from to Short-rib thoracic dysplasia 2 with or without polydactyly, MIM# 611263; MONDO:0012644
Mendeliome v0.8189 IFT80 Zornitza Stark reviewed gene: IFT80: Rating: GREEN; Mode of pathogenicity: None; Publications: 17468754, 19648123, 30767363; Phenotypes: Short-rib thoracic dysplasia 2 with or without polydactyly, MIM# 611263, MONDO:0012644; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8189 LZTFL1 Zornitza Stark Gene: lztfl1 has been classified as Green List (High Evidence).
Mendeliome v0.8186 TTC26 Zornitza Stark Gene: ttc26 has been classified as Green List (High Evidence).
Mendeliome v0.8186 TTC26 Zornitza Stark Classified gene: TTC26 as Green List (high evidence)
Mendeliome v0.8186 TTC26 Zornitza Stark Gene: ttc26 has been classified as Green List (High Evidence).
Mendeliome v0.8183 IFT43 Zornitza Stark changed review comment from: One family reported with cranioectodermal dysplasia, one with RP, and two with skeletal ciliopathy.; to: Two families reported with cranioectodermal dysplasia, one with RP, and two with skeletal ciliopathy.
Mendeliome v0.8183 IFT43 Zornitza Stark Gene: ift43 has been classified as Green List (High Evidence).
Mendeliome v0.8183 IFT43 Zornitza Stark Phenotypes for gene: IFT43 were changed from to Short-rib thoracic dysplasia 18 with polydactyly, MIM# 617866; Retinitis pigmentosa 81 , MIM#617871; Cranioectodermal dysplasia 3, MIM# 614099
Mendeliome v0.8180 IFT43 Zornitza Stark reviewed gene: IFT43: Rating: GREEN; Mode of pathogenicity: None; Publications: 28400947, 28973684, 21378380; Phenotypes: Short-rib thoracic dysplasia 18 with polydactyly, MIM# 617866, Retinitis pigmentosa 81 , MIM#617871, Cranioectodermal dysplasia 3, MIM# 614099; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8180 IFT140 Zornitza Stark Gene: ift140 has been classified as Green List (High Evidence).
Mendeliome v0.8180 IFT140 Zornitza Stark Phenotypes for gene: IFT140 were changed from to Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920; Retinitis pigmentosa 80, MIM# 617781
Mendeliome v0.8177 IFT140 Zornitza Stark reviewed gene: IFT140: Rating: GREEN; Mode of pathogenicity: None; Publications: 22503633, 23418020, 28288023, 28724397, 26216056, 26968735; Phenotypes: Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920, Retinitis pigmentosa 80, MIM# 617781; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8175 DYNC2H1 Zornitza Stark Gene: dync2h1 has been classified as Green List (High Evidence).
Mendeliome v0.8175 DYNC2H1 Zornitza Stark Phenotypes for gene: DYNC2H1 were changed from to Short-rib thoracic dysplasia 3 with or without polydactyly, MIM# 613091; MONDO:0013127
Mendeliome v0.8172 DYNC2H1 Zornitza Stark reviewed gene: DYNC2H1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19442771, 19361615, 22499340, 23456818, 27925158; Phenotypes: Short-rib thoracic dysplasia 3 with or without polydactyly, MIM# 613091, MONDO:0013127; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8172 DDX59 Zornitza Stark Gene: ddx59 has been classified as Green List (High Evidence).
Mendeliome v0.8169 CEP83 Zornitza Stark Gene: cep83 has been classified as Green List (High Evidence).
Mendeliome v0.8169 CEP83 Zornitza Stark Phenotypes for gene: CEP83 were changed from to Nephronophthisis 18, MIM# 615862; MONDO:0014374; Retinal dystrophy; ID
Mendeliome v0.8166 CEP83 Zornitza Stark reviewed gene: CEP83: Rating: GREEN; Mode of pathogenicity: None; Publications: 24882706, 33938610; Phenotypes: Nephronophthisis 18, MIM# 615862, MONDO:0014374, Retinal dystrophy, ID; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8166 RNU12 Bryony Thompson Gene: rnu12 has been classified as Green List (High Evidence).
Mendeliome v0.8166 RNU12 Bryony Thompson Classified gene: RNU12 as Green List (high evidence)
Mendeliome v0.8166 RNU12 Bryony Thompson Gene: rnu12 has been classified as Green List (High Evidence).
Mendeliome v0.8165 RNU12 Bryony Thompson gene: RNU12 was added
gene: RNU12 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RNU12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNU12 were set to 34085356; 27863452
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: 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. Also, limited evidence for an association with cerebellar ataxia with a single large consanguineous family reported with a homozygous variant.
Sources: Literature
Mendeliome v0.8164 FHOD3 Zornitza Stark Gene: fhod3 has been classified as Green List (High Evidence).
Mendeliome v0.8160 KCNJ16 Zornitza Stark Gene: kcnj16 has been classified as Green List (High Evidence).
Mendeliome v0.8160 KCNJ16 Zornitza Stark Classified gene: KCNJ16 as Green List (high evidence)
Mendeliome v0.8160 KCNJ16 Zornitza Stark Gene: kcnj16 has been classified as Green List (High Evidence).
Mendeliome v0.8158 KLHL7 Zornitza Stark Gene: klhl7 has been classified as Green List (High Evidence).
Mendeliome v0.8155 SLC34A3 Zornitza Stark Gene: slc34a3 has been classified as Green List (High Evidence).
Mendeliome v0.8152 TNC Zornitza Stark Gene: tnc has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8149 TNC Zornitza Stark Classified gene: TNC as Amber List (moderate evidence)
Mendeliome v0.8149 TNC Zornitza Stark Gene: tnc has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8148 RIPK4 Zornitza Stark Gene: ripk4 has been classified as Green List (High Evidence).
Mendeliome v0.8145 CEP290 Zornitza Stark Gene: cep290 has been classified as Green List (High Evidence).
Mendeliome v0.8145 CEP290 Zornitza Stark Phenotypes for gene: CEP290 were changed from to Bardet-Biedl syndrome 14, MIM# 615991; Joubert syndrome 5 610188; Leber congenital amaurosis 10, MIM# 611755; Meckel syndrome 4, MIM# 611134; Senior-Loken syndrome 6, MIM# 610189
Mendeliome v0.8142 CEP290 Zornitza Stark reviewed gene: CEP290: Rating: GREEN; Mode of pathogenicity: None; Publications: 18327255, 20690115, 16682973, 16682970, 17564967, 16909394, 17564974; Phenotypes: Bardet-Biedl syndrome 14, MIM# 615991, Joubert syndrome 5 610188, Leber congenital amaurosis 10, MIM# 611755, Meckel syndrome 4, MIM# 611134, Senior-Loken syndrome 6, MIM# 610189; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8142 CEP164 Zornitza Stark Gene: cep164 has been classified as Green List (High Evidence).
Mendeliome v0.8142 CEP164 Zornitza Stark Phenotypes for gene: CEP164 were changed from to Bardet-Biedl syndrome; Nephronophthisis 15, MIM# 614845; Oro-facio-digital syndrome
Mendeliome v0.8139 CEP164 Zornitza Stark reviewed gene: CEP164: Rating: GREEN; Mode of pathogenicity: None; Publications: 34132027, 34013113, 32055034, 27708425, 22863007; Phenotypes: Bardet-Biedl syndrome, Nephronophthisis 15, MIM# 614845, Oro-facio-digital syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8139 CEP120 Zornitza Stark Gene: cep120 has been classified as Green List (High Evidence).
Mendeliome v0.8139 CEP120 Zornitza Stark Phenotypes for gene: CEP120 were changed from to Joubert syndrome 31, MIM# 617761; Short-rib thoracic dysplasia 13 with or without polydactyly, MIM# 616300
Mendeliome v0.8136 CEP120 Zornitza Stark reviewed gene: CEP120: Rating: GREEN; Mode of pathogenicity: None; Publications: 27208211, 33486889, 29847808, 25361962, 27208211; Phenotypes: Joubert syndrome 31, MIM# 617761, Short-rib thoracic dysplasia 13 with or without polydactyly, MIM# 616300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8136 CEP104 Zornitza Stark Gene: cep104 has been classified as Green List (High Evidence).
Mendeliome v0.8133 C5orf42 Zornitza Stark Gene: c5orf42 has been classified as Green List (High Evidence).
Mendeliome v0.8130 C21orf2 Zornitza Stark changed review comment from: Axial spondylometaphyseal dysplasia (SMDAX) is characterized by postnatal growth failure, including rhizomelic short stature in early childhood that evolves into short trunk in late childhood, and thoracic hypoplasia that may cause mild to moderate respiratory problems in the neonatal period and later susceptibility to airway infection. Impaired visual acuity comes to medical attention in early life and vision rapidly deteriorates. Retinal changes are diagnosed as retinitis pigmentosa or pigmentary retinal degeneration on funduscopic examination and as cone-rod dystrophy on ERG. Radiologic hallmarks include short ribs with flared and cupped anterior ends, mild spondylar dysplasia, lacy iliac crests, and metaphyseal irregularities essentially confined to the proximal femora. At least 7 unrelated families reported.

7 families also reported with isolated retinal dystrophy.; to: Axial spondylometaphyseal dysplasia (SMDAX) is characterized by postnatal growth failure, including rhizomelic short stature in early childhood that evolves into short trunk in late childhood, and thoracic hypoplasia that may cause mild to moderate respiratory problems in the neonatal period and later susceptibility to airway infection. Impaired visual acuity comes to medical attention in early life and vision rapidly deteriorates. Retinal changes are diagnosed as retinitis pigmentosa or pigmentary retinal degeneration on funduscopic examination and as cone-rod dystrophy on ERG. Radiologic hallmarks include short ribs with flared and cupped anterior ends, mild spondylar dysplasia, lacy iliac crests, and metaphyseal irregularities essentially confined to the proximal femora. At least 7 unrelated families reported.

7 families also reported with isolated retinal dystrophy.

New HGNC approved name is CFAP410.
Mendeliome v0.8130 C21orf2 Zornitza Stark Gene: c21orf2 has been classified as Green List (High Evidence).
Mendeliome v0.8130 C21orf2 Zornitza Stark Phenotypes for gene: C21orf2 were changed from to Spondylometaphyseal dysplasia, axial, MIM# 602271; Retinal dystrophy with macular staphyloma, MIM# 617547
Mendeliome v0.8127 C21orf2 Zornitza Stark reviewed gene: C21orf2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26974433, 27548899, 28422394, 26294103, 23105016, 27548899; Phenotypes: Spondylometaphyseal dysplasia, axial, MIM# 602271, Retinal dystrophy with macular staphyloma, MIM# 617547; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8127 BBS9 Zornitza Stark Gene: bbs9 has been classified as Green List (High Evidence).
Mendeliome v0.8124 BBS7 Zornitza Stark Gene: bbs7 has been classified as Green List (High Evidence).
Mendeliome v0.8121 BBS5 Zornitza Stark Gene: bbs5 has been classified as Green List (High Evidence).
Mendeliome v0.8118 BBS4 Zornitza Stark Gene: bbs4 has been classified as Green List (High Evidence).
Mendeliome v0.8115 ARL6 Zornitza Stark Gene: arl6 has been classified as Green List (High Evidence).
Mendeliome v0.8111 SLCO2A1 Zornitza Stark Phenotypes for gene: SLCO2A1 were changed from to Hypertrophic osteoarthropathy, primary, autosomal dominant, MIM# 167100; Hypertrophic osteoarthropathy, primary, autosomal recessive 2, MIM# 614441
Mendeliome v0.8108 SLCO2A1 Zornitza Stark reviewed gene: SLCO2A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23509104, 27134495, 33852188, 22331663, 27134495]; Phenotypes: Hypertrophic osteoarthropathy, primary, autosomal dominant, MIM# 167100, Hypertrophic osteoarthropathy, primary, autosomal recessive 2, MIM# 614441; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8108 NDUFB11 Zornitza Stark Phenotypes for gene: NDUFB11 were changed from Linear skin defects with multiple congenital anomalies 3, XLD (MIM#300952); MONDO:0010494; Mitochondrial complex I deficiency, nuclear type 30, XLR (MIM#301021); MONDO:0026721 to Linear skin defects with multiple congenital anomalies 3, XLD (MIM#300952); MONDO:0010494; Mitochondrial complex I deficiency, nuclear type 30, XLR (MIM#301021); MONDO:0026721; X-linked sideroblastic anaemia
Mendeliome v0.8106 NDUFB11 Zornitza Stark reviewed gene: NDUFB11: Rating: GREEN; Mode of pathogenicity: None; Publications: 27488349; Phenotypes: X-linked sideroblastic anaemia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8106 PPP2R1A Zornitza Stark Gene: ppp2r1a has been classified as Green List (High Evidence).
Mendeliome v0.8106 PPP2R1A Zornitza Stark Phenotypes for gene: PPP2R1A were changed from to Mental retardation, autosomal dominant 36, MIM#616362; Microcephaly-corpus callosum hypoplasia-intellectual disability-facial dysmorphism syndrome, MONDO:0014605
Mendeliome v0.8103 PPP2R1A Zornitza Stark reviewed gene: PPP2R1A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, autosomal dominant 36, MIM#616362, Microcephaly-corpus callosum hypoplasia-intellectual disability-facial dysmorphism syndrome, MONDO:0014605; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8103 KIF1B Bryony Thompson Classified gene: KIF1B as Amber List (moderate evidence)
Mendeliome v0.8103 KIF1B Bryony Thompson Gene: kif1b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8102 ARHGEF10 Bryony Thompson Gene: arhgef10 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8102 ARHGEF10 Bryony Thompson Classified gene: ARHGEF10 as Amber List (moderate evidence)
Mendeliome v0.8102 ARHGEF10 Bryony Thompson Added comment: Comment on list classification: ClinGen gene-disease clinical validity classification is limited for this gene.
Mendeliome v0.8102 ARHGEF10 Bryony Thompson Gene: arhgef10 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8100 CLPB Zornitza Stark Gene: clpb has been classified as Green List (High Evidence).
Mendeliome v0.8096 PON1 Zornitza Stark Gene: pon1 has been classified as Red List (Low Evidence).
Mendeliome v0.8095 PON1 Zornitza Stark Classified gene: PON1 as Red List (low evidence)
Mendeliome v0.8095 PON1 Zornitza Stark Gene: pon1 has been classified as Red List (Low Evidence).
Mendeliome v0.8094 ABCB4 Zornitza Stark Gene: abcb4 has been classified as Green List (High Evidence).
Mendeliome v0.8094 ABCB4 Zornitza Stark Phenotypes for gene: ABCB4 were changed from to Cholestasis, progressive familial intrahepatic 3 MIM#602347; disorder of bile acid metabolism
Mendeliome v0.8091 OAS1 Zornitza Stark Gene: oas1 has been classified as Green List (High Evidence).
Mendeliome v0.8091 OAS1 Zornitza Stark Phenotypes for gene: OAS1 were changed from to Autoinflammatory immunodeficiency; infantile-onset pulmonary alveolar proteinosis; hypogammaglobulinaemia
Mendeliome v0.8087 OAS1 Zornitza Stark reviewed gene: OAS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34145065, 29455859; Phenotypes: Autoinflammatory immunodeficiency, infantile-onset pulmonary alveolar proteinosis, hypogammaglobulinaemia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.8087 SLIT3 Zornitza Stark Gene: slit3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8087 SLIT3 Zornitza Stark Classified gene: SLIT3 as Amber List (moderate evidence)
Mendeliome v0.8087 SLIT3 Zornitza Stark Gene: slit3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.8086 SLIT3 Zornitza Stark gene: SLIT3 was added
gene: SLIT3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLIT3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLIT3 were set to 33933663
Phenotypes for gene: SLIT3 were set to Congenital diaphragmatic hernia
Review for gene: SLIT3 was set to AMBER
Added comment: Two affected individuals, single family, supportive mouse model.
Sources: Literature
Mendeliome v0.8083 IQGAP3 Zornitza Stark Gene: iqgap3 has been classified as Red List (Low Evidence).
Mendeliome v0.8083 IQGAP3 Zornitza Stark gene: IQGAP3 was added
gene: IQGAP3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IQGAP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: IQGAP3 were set to Hereditary neuropathy
Review for gene: IQGAP3 was set to RED
Added comment: Single multiplex family, intronic variant, limited functional data.
Sources: Literature
Mendeliome v0.8082 TINF2 Zornitza Stark Gene: tinf2 has been classified as Green List (High Evidence).
Mendeliome v0.8082 TINF2 Zornitza Stark Phenotypes for gene: TINF2 were changed from to Dyskeratosis congenita, autosomal dominant 3, MIM# 613990; Revesz syndrome, MIM# 268130
Mendeliome v0.8079 TINF2 Zornitza Stark edited their review of gene: TINF2: Added comment: RS is a severe variant of DKC with early bone marrow failure and retinopathy. Well established gene-disease associations.; Changed publications: 18252230, 21477109, 18979121, 18669893, 21199492, 33097095; Changed phenotypes: Dyskeratosis congenita, autosomal dominant 3, MIM# 613990, Revesz syndrome, MIM# 268130
Mendeliome v0.8079 POPDC3 Zornitza Stark changed review comment from: 5 affected individuals from 3 unrelated families reported, supportive animal model data.
Sources: Literature; to: 5 affected individuals from 3 unrelated families reported, supportive animal model data. Presentation was between adolescence and 40s with proximal muscle weakness primarily affecting the lower limbs, resulting in increased falls and difficulty running. The disorder was slowly progressive, with later involvement of the upper limbs. MRI showed fatty replacement of the thigh muscles and medial gastrocnemius, with some paraspinal muscles also affected. Some patients had calf hypertrophy. Serum CK was markedly elevated.
Sources: Literature
Mendeliome v0.8079 POPDC3 Zornitza Stark Gene: popdc3 has been classified as Green List (High Evidence).
Mendeliome v0.8079 POPDC3 Zornitza Stark Classified gene: POPDC3 as Green List (high evidence)
Mendeliome v0.8079 POPDC3 Zornitza Stark Gene: popdc3 has been classified as Green List (High Evidence).
Mendeliome v0.8078 POPDC3 Zornitza Stark gene: POPDC3 was added
gene: POPDC3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: POPDC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POPDC3 were set to 31610034
Phenotypes for gene: POPDC3 were set to Muscular dystrophy, limb-girdle, autosomal recessive 26, MIM# 618848
Review for gene: POPDC3 was set to GREEN
Added comment: 5 affected individuals from 3 unrelated families reported, supportive animal model data.
Sources: Literature
Mendeliome v0.8077 ACD Zornitza Stark Gene: acd has been classified as Red List (Low Evidence).
Mendeliome v0.8077 ACD Zornitza Stark Phenotypes for gene: ACD were changed from to Dyskeratosis congenita, MIM# 616553
Mendeliome v0.8074 ACD Zornitza Stark Classified gene: ACD as Red List (low evidence)
Mendeliome v0.8074 ACD Zornitza Stark Gene: acd has been classified as Red List (Low Evidence).
Mendeliome v0.8073 ACD Zornitza Stark reviewed gene: ACD: Rating: RED; Mode of pathogenicity: None; Publications: 25205116, 25233904; Phenotypes: Dyskeratosis congenita, MIM# 616553; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8071 WRAP53 Zornitza Stark Gene: wrap53 has been classified as Green List (High Evidence).
Mendeliome v0.8071 WRAP53 Zornitza Stark Phenotypes for gene: WRAP53 were changed from to Dyskeratosis congenita, autosomal recessive 3, MIM# 613988
Mendeliome v0.8068 WRAP53 Zornitza Stark reviewed gene: WRAP53: Rating: GREEN; Mode of pathogenicity: None; Publications: 21205863, 32303682, 29514627; Phenotypes: Dyskeratosis congenita, autosomal recessive 3, MIM# 613988; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8068 EP300 Zornitza Stark Gene: ep300 has been classified as Green List (High Evidence).
Mendeliome v0.8065 PARN Zornitza Stark Gene: parn has been classified as Green List (High Evidence).
Mendeliome v0.8065 PARN Zornitza Stark Phenotypes for gene: PARN were changed from to Dyskeratosis congenita, autosomal recessive 6, MIM# 616353; Pulmonary fibrosis and/or bone marrow failure, telomere-related, 4, MIM# 616371
Mendeliome v0.8062 PARN Zornitza Stark reviewed gene: PARN: Rating: GREEN; Mode of pathogenicity: None; Publications: 25893599, 26342108, 25848748; Phenotypes: Dyskeratosis congenita, autosomal recessive 6, MIM# 616353, Pulmonary fibrosis and/or bone marrow failure, telomere-related, 4, MIM# 616371; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.8062 KLF1 Zornitza Stark Gene: klf1 has been classified as Green List (High Evidence).
Mendeliome v0.8059 SPAG17 Zornitza Stark Gene: spag17 has been classified as Red List (Low Evidence).
Mendeliome v0.8059 SPAG17 Zornitza Stark gene: SPAG17 was added
gene: SPAG17 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPAG17 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPAG17 were set to 28548327
Phenotypes for gene: SPAG17 were set to Spermatogenic failure 55, MIM#619380
Review for gene: SPAG17 was set to RED
Added comment: Single family reported with two affected brothers, homozygous missense variant.
Sources: Literature
Mendeliome v0.8058 CATIP Zornitza Stark Gene: catip has been classified as Red List (Low Evidence).
Mendeliome v0.8058 CATIP Zornitza Stark gene: CATIP was added
gene: CATIP was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CATIP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CATIP were set to 32503832
Phenotypes for gene: CATIP were set to Spermatogenic failure 54, MIM# 619379
Review for gene: CATIP was set to RED
Added comment: Homozygous missense variant reported in a single consanguineous family with 4 affecteds. Limited functional data.
Sources: Expert list
Mendeliome v0.8056 HAX1 Zornitza Stark Gene: hax1 has been classified as Green List (High Evidence).
Mendeliome v0.8056 HAX1 Zornitza Stark Phenotypes for gene: HAX1 were changed from to Neutropaenia, severe congenital 3, autosomal recessive, MIM# 610738; Kostmann syndrome MONDO:0012548
Mendeliome v0.8053 HAX1 Zornitza Stark reviewed gene: HAX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17187068, 18611981, 19036076; Phenotypes: Neutropaenia, severe congenital 3, autosomal recessive, MIM# 610738, Kostmann syndrome MONDO:0012548; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8050 MYL9 Zornitza Stark Phenotypes for gene: MYL9 were changed from Megacystis-microcolon-intestinal hypoperistalsis syndrome to Megacystis-microcolon-intestinal hypoperistalsis syndrome, MIM#619365
Mendeliome v0.8049 MYL9 Zornitza Stark edited their review of gene: MYL9: Changed phenotypes: Megacystis-microcolon-intestinal hypoperistalsis syndrome, MIM#619365
Mendeliome v0.8046 NBEAL2 Zornitza Stark Gene: nbeal2 has been classified as Green List (High Evidence).
Mendeliome v0.8043 GFI1 Zornitza Stark Gene: gfi1 has been classified as Green List (High Evidence).
Mendeliome v0.8040 SLC13A5 Zornitza Stark Gene: slc13a5 has been classified as Green List (High Evidence).
Mendeliome v0.8040 SLC13A5 Zornitza Stark Phenotypes for gene: SLC13A5 were changed from to Developmental and epileptic encephalopathy 25, with amelogenesis imperfecta MIM#615905; MONDO:0014392
Mendeliome v0.8037 SLC13A5 Zornitza Stark reviewed gene: SLC13A5: Rating: GREEN; Mode of pathogenicity: None; Publications: 24995870, 26384929; Phenotypes: Developmental and epileptic encephalopathy 25, with amelogenesis imperfecta MIM#615905, MONDO:0014392; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8037 GATA2 Zornitza Stark Gene: gata2 has been classified as Green List (High Evidence).
Mendeliome v0.8034 GATA1 Zornitza Stark Gene: gata1 has been classified as Green List (High Evidence).
Mendeliome v0.8032 ELANE Zornitza Stark Gene: elane has been classified as Green List (High Evidence).
Mendeliome v0.8029 EFL1 Zornitza Stark Gene: efl1 has been classified as Green List (High Evidence).
Mendeliome v0.8026 CXCR4 Zornitza Stark Gene: cxcr4 has been classified as Green List (High Evidence).
Mendeliome v0.8023 CTC1 Zornitza Stark Gene: ctc1 has been classified as Green List (High Evidence).
Mendeliome v0.8020 ANKRD26 Zornitza Stark Gene: ankrd26 has been classified as Green List (High Evidence).
Mendeliome v0.8017 AK2 Zornitza Stark Gene: ak2 has been classified as Green List (High Evidence).
Mendeliome v0.8017 AK2 Zornitza Stark Phenotypes for gene: AK2 were changed from to Reticular dysgenesis, MIM# 267500
Mendeliome v0.8014 AK2 Zornitza Stark reviewed gene: AK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 19043416; Phenotypes: Reticular dysgenesis, MIM# 267500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.8014 ADA2 Zornitza Stark Gene: ada2 has been classified as Green List (High Evidence).
Mendeliome v0.8011 ADA2 Zornitza Stark commented on gene: ADA2: Vasculitis, autoinflammation, immunodeficiency, and haematologic defects syndrome (VAIHS) is an autosomal recessive multisystem disorder with onset in childhood. The phenotype is highly variable, but most patients have features of a systemic vascular inflammatory disorder with skin ulceration and recurrent strokes affecting the small vessels of the brain resulting in neurologic dysfunction. Other features may include recurrent fever, elevated acute-phase proteins, myalgias, lesions resembling polyarteritis nodosa, and/or livedo racemosa or reticularis with an inflammatory vasculitis on biopsy. Some patients may have renal and/or gastrointestinal involvement, hypertension, aneurysms, or ischemic necrosis of the digits. Some affected individuals have immunodeficiency. At least 10 unrelated families reported, the p.Gly47Arg variant is a common founder variant in the Jewish population.
Mendeliome v0.8009 IFT74 Zornitza Stark edited their review of gene: IFT74: Added comment: PMID 33531668: Identified IFT74 as a JBTS-associated gene in 3 unrelated families through WES. All the affected individuals carried truncated variants and shared one missense variant (p.Q179E) found only in East Asians. The expression of the human p.Q179E-IFT74 variant displayed compromised rescue effects in zebrafish ift74 morphants. Attenuated ciliogenesis; altered distribution of IFT proteins and ciliary membrane proteins, including ARL13B, INPP5E, and GPR161; and disrupted hedgehog signaling were observed in patient fibroblasts with IFT74 variants.; Changed publications: 27486776, 32144365, 33531668; Changed phenotypes: Bardet-Biedl syndrome 20, MIM# 617119, Joubert syndrome
Mendeliome v0.8009 RFX4 Zornitza Stark Gene: rfx4 has been classified as Green List (High Evidence).
Mendeliome v0.8009 RFX4 Zornitza Stark Classified gene: RFX4 as Green List (high evidence)
Mendeliome v0.8009 RFX4 Zornitza Stark Gene: rfx4 has been classified as Green List (High Evidence).
Mendeliome v0.8008 RFX4 Zornitza Stark gene: RFX4 was added
gene: RFX4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RFX4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RFX4 were set to 33658631
Phenotypes for gene: RFX4 were set to ID, ASD, ADHD
Review for gene: RFX4 was set to GREEN
Added comment: Report of 38 individuals (from 33 unrelated families) with de novo or inherited loss of function variants in RFX3 (15 families), RFX4 (4 families), and RFX7 (14 families), identified through WES. Individuals share neurobehavioural features including ASD, intellectual disability, and/or ADHD; other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes. These genes are potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis.
Sources: Literature
Mendeliome v0.8007 RFX3 Zornitza Stark Gene: rfx3 has been classified as Green List (High Evidence).
Mendeliome v0.8007 RFX3 Zornitza Stark Classified gene: RFX3 as Green List (high evidence)
Mendeliome v0.8007 RFX3 Zornitza Stark Gene: rfx3 has been classified as Green List (High Evidence).
Mendeliome v0.8006 RFX3 Zornitza Stark gene: RFX3 was added
gene: RFX3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RFX3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RFX3 were set to 33658631
Phenotypes for gene: RFX3 were set to ID, ASD, ADHD
Review for gene: RFX3 was set to GREEN
Added comment: Report of 38 individuals (from 33 unrelated families) with de novo or inherited loss of function variants in RFX3 (15 families), RFX4 (4 families), and RFX7 (14 families), identified through WES. Individuals share neurobehavioural features including ASD, intellectual disability, and/or ADHD; other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes. These genes are potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis.
Sources: Literature
Mendeliome v0.8005 RFX7 Zornitza Stark Gene: rfx7 has been classified as Green List (High Evidence).
Mendeliome v0.8005 RFX7 Zornitza Stark Classified gene: RFX7 as Green List (high evidence)
Mendeliome v0.8005 RFX7 Zornitza Stark Gene: rfx7 has been classified as Green List (High Evidence).
Mendeliome v0.8004 RFX7 Zornitza Stark gene: RFX7 was added
gene: RFX7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RFX7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RFX7 were set to 33658631
Phenotypes for gene: RFX7 were set to ID, ASD, ADHD
Review for gene: RFX7 was set to GREEN
Added comment: Report of 38 individuals (from 33 unrelated families) with de novo or inherited loss of function variants in RFX3 (15 families), RFX4 (4 families), and RFX7 (14 families), identified through WES. Individuals share neurobehavioural features including ASD, intellectual disability, and/or ADHD; other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes. These genes are potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis.
Sources: Literature
Mendeliome v0.8003 SEMA3F Zornitza Stark Gene: sema3f has been classified as Green List (High Evidence).
Mendeliome v0.8003 SEMA3F Zornitza Stark Classified gene: SEMA3F as Green List (high evidence)
Mendeliome v0.8003 SEMA3F Zornitza Stark Gene: sema3f has been classified as Green List (High Evidence).
Mendeliome v0.8002 SEMA3F Zornitza Stark gene: SEMA3F was added
gene: SEMA3F was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SEMA3F was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SEMA3F were set to 33495532
Phenotypes for gene: SEMA3F were set to Hypogonadotropic hypogonadism
Review for gene: SEMA3F was set to GREEN
Added comment: Screened 216 patients with Idiopathic hypogonadotropic hypogonadism by exome sequencing. Identified 10 individuals from 7 families with heterozygous SEMA3F missense variants. In 4 of the kindreds, there was at least one more gene known to be associated with IHH (oligogenecity). Provide unequivocal human embryonic data showing the expression of SEMA3F along the developing human GnRH migratory pathway. SEMA3Fs harboring the P452T, T29M, and T724M missense variants showed impaired SEMA3F secretion in whole cell lysates.
Sources: Literature
Mendeliome v0.8001 PLXNA3 Zornitza Stark Gene: plxna3 has been classified as Green List (High Evidence).
Mendeliome v0.8001 PLXNA3 Zornitza Stark Classified gene: PLXNA3 as Green List (high evidence)
Mendeliome v0.8001 PLXNA3 Zornitza Stark Gene: plxna3 has been classified as Green List (High Evidence).
Mendeliome v0.8000 PLXNA3 Zornitza Stark gene: PLXNA3 was added
gene: PLXNA3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PLXNA3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PLXNA3 were set to 33495532
Phenotypes for gene: PLXNA3 were set to Hypogonadotropic hypogonadism
Review for gene: PLXNA3 was set to GREEN
Added comment: Screened 216 patients with Idiopathic hypogonadotropic hypogonadism by exome sequencing. Identified 7 individuals from 5 families with hemizygous PLXNA3 missense variants. In 2 of the kindreds, there was at least one more gene known to be associated with IHH (oligogenecity). Data provided with evidence that PLXNA3, a key component of the SEMA3F holoreceptor complex,31 is expressed by the human GnRH and olfactory/vomeronasal systems. S646P variant showed PLXNA3 localization exclusively in the ER, indicating that the variant S646P disrupts cell surface localization of PLXNA3.
Sources: Literature
Mendeliome v0.7997 GNAI1 Zornitza Stark Gene: gnai1 has been classified as Green List (High Evidence).
Mendeliome v0.7994 FARSA Zornitza Stark Classified gene: FARSA as Green List (high evidence)
Mendeliome v0.7994 FARSA Zornitza Stark Gene: farsa has been classified as Green List (High Evidence).
Mendeliome v0.7993 LAMA5 Bryony Thompson Phenotypes for gene: LAMA5 were changed from to bent bone dysplasia; nephrotic syndrome; Presynaptic congenital myasthenic syndrome; multisystem syndrome; developmental delay
Mendeliome v0.7990 LAMA5 Bryony Thompson reviewed gene: LAMA5: Rating: AMBER; Mode of pathogenicity: None; Publications: 33242826, 29534211, 16790509, 30589377, 28735299, 30631761; Phenotypes: bent bone dysplasia, nephrotic syndrome, Presynaptic congenital myasthenic syndrome, multisystem syndrome, developmental delay; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7990 ZNF81 Zornitza Stark Gene: znf81 has been classified as Red List (Low Evidence).
Mendeliome v0.7987 ZNF81 Zornitza Stark Classified gene: ZNF81 as Red List (low evidence)
Mendeliome v0.7987 ZNF81 Zornitza Stark Gene: znf81 has been classified as Red List (Low Evidence).
Mendeliome v0.7986 RELN Ee Ming Wong edited their review of gene: RELN: Added comment: - Six affected individuals carrying missense variants in RELN including
1. Two individuals with compound heterozygous variants
- One of the variants has 26 homozygotes in gnomAD and therefore pathogenicity of this variant is in question
- LoF demonstrated for three of the variants (reduced RELN secretion), except for p.Y1821H which demonstrated an apparently increased RELN secretion (GoF)
2. Two brothers carrying the maternally inherited variant (mother apparently healthy)
- LoF demonstrated for these variants
3. Two individuals de novo for RELN variants
- Dominant negative demonstrated for these variants where secretion of WT-RELN was impaired when co-transfected with mutant constructs in HEK293T cells; Changed rating: AMBER; Changed publications: Riva et al bioRxiv (pre-print, not peer-reviewed); Changed phenotypes: Pachygyria, Polymicrogyria, Heterotopia; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7986 NIID Bryony Thompson Str: niid has been classified as Green List (High Evidence).
Mendeliome v0.7986 NIID Bryony Thompson Classified STR: NIID as Green List (high evidence)
Mendeliome v0.7986 NIID Bryony Thompson Str: niid has been classified as Green List (High Evidence).
Mendeliome v0.7985 NIID Bryony Thompson STR: NIID was added
STR: NIID was added to Mendeliome. Sources: Literature
Mode of inheritance for STR: NIID was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: NIID were set to 31178126; 31332381; 31819945; 33887199; 33943039; 32250060; 31332380; 32852534; 32989102
Phenotypes for STR: NIID were set to Neuronal intranuclear inclusion disease MIM#603472; Tremor, hereditary essential, 6 MIM#618866
Review for STR: NIID was set to GREEN
STR: NIID was marked as clinically relevant
Added comment: NM_001364012.2:c.-164GGC[(66_517)]
Large number of families and sporadic cases reported with expansions, with a range of neurodegenerative phenotypes, including: dementia, Parkinsonism/tremor, peripheral neuropathy, leukoencephalopathy, myopathy, motor neurone disease.
Normal repeat range: 7-60
Pathogenic repeat range: >=61-500
Mechanism of disease is translation of repeat expansion into a toxic polyglycine protein, identified in both mouse models and tissue samples from affected individuals.
Sources: Literature
Mendeliome v0.7984 NOTCH2NL Bryony Thompson Classified gene: NOTCH2NL as No list
Mendeliome v0.7984 NOTCH2NL Bryony Thompson Added comment: Comment on list classification: STR is the only reported cause of disease for this gene. It has been added as an STR under NIID.
Mendeliome v0.7983 TRPM6 Zornitza Stark Gene: trpm6 has been classified as Green List (High Evidence).
Mendeliome v0.7981 CNTNAP1 Zornitza Stark Gene: cntnap1 has been classified as Green List (High Evidence).
Mendeliome v0.7978 GLDN Zornitza Stark Gene: gldn has been classified as Green List (High Evidence).
Mendeliome v0.7975 ZBTB42 Zornitza Stark Gene: zbtb42 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7975 ZBTB42 Zornitza Stark Classified gene: ZBTB42 as Amber List (moderate evidence)
Mendeliome v0.7975 ZBTB42 Zornitza Stark Gene: zbtb42 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7974 ZBTB42 Zornitza Stark gene: ZBTB42 was added
gene: ZBTB42 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: ZBTB42 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZBTB42 were set to 25055871
Phenotypes for gene: ZBTB42 were set to Lethal congenital contracture syndrome 6, MIM# 616248
Review for gene: ZBTB42 was set to AMBER
Added comment: Homozygous missense variant reported in a family with three stillbirths and a phenotype consistent with LCCS. Supportive zebrafish model.
Sources: Expert Review
Mendeliome v0.7973 MYBPC1 Zornitza Stark Gene: mybpc1 has been classified as Green List (High Evidence).
Mendeliome v0.7973 MYBPC1 Zornitza Stark Phenotypes for gene: MYBPC1 were changed from to Arthrogryposis, distal, type 1B 614335; Lethal congenital contracture syndrome 4, MIM# 614915; Myopathy, congenital, with tremor MIM#618524
Mendeliome v0.7970 MYBPC1 Zornitza Stark reviewed gene: MYBPC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20045868, 22610851, 23873045, 26661508, 31264822, 31025394; Phenotypes: Arthrogryposis, distal, type 1B 614335, Lethal congenital contracture syndrome 4, MIM# 614915, Myopathy, congenital, with tremor MIM#618524; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7970 ERBB3 Zornitza Stark Gene: erbb3 has been classified as Green List (High Evidence).
Mendeliome v0.7970 ERBB3 Zornitza Stark Phenotypes for gene: ERBB3 were changed from Lethal congenital contractural syndrome 2, MIM# 607598 to Lethal congenital contractural syndrome 2, MIM# 607598; Hirschsprung disease; Arthrogryposis
Mendeliome v0.7967 MUSK Zornitza Stark Gene: musk has been classified as Green List (High Evidence).
Mendeliome v0.7967 MUSK Zornitza Stark Phenotypes for gene: MUSK were changed from to Fetal akinesia deformation sequence 1, MIM# 208150; MONDO:0100101; Myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency, MIM# 616325; MONDO:0014587
Mendeliome v0.7964 MUSK Zornitza Stark reviewed gene: MUSK: Rating: GREEN; Mode of pathogenicity: None; Publications: 25537362, 25612909, 8653786, 31750350, 15496425, 19949040, 20371544, 32253145; Phenotypes: Fetal akinesia deformation sequence 1, MIM# 208150, MONDO:0100101, Myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency, MIM# 616325, MONDO:0014587; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7964 DOK7 Zornitza Stark Gene: dok7 has been classified as Green List (High Evidence).
Mendeliome v0.7964 DOK7 Zornitza Stark Phenotypes for gene: DOK7 were changed from to Myasthenic syndrome, congenital, 10, MIM# 254300; Fetal akinesia deformation sequence 3, MIM# 618389
Mendeliome v0.7961 DOK7 Zornitza Stark reviewed gene: DOK7: Rating: GREEN; Mode of pathogenicity: None; Publications: 16917026, 18626973, 20147321, 16794080, 31453852, 29395672, 32360404, 19261599, 31880392; Phenotypes: Myasthenic syndrome, congenital, 10, MIM# 254300, Fetal akinesia deformation sequence 3, MIM# 618389; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7961 TPM2 Zornitza Stark Gene: tpm2 has been classified as Green List (High Evidence).
Mendeliome v0.7961 TPM2 Zornitza Stark Phenotypes for gene: TPM2 were changed from to Arthrogryposis, distal, type 1A 108120; Arthrogryposis, distal, type 2B4 108120; CAP myopathy 2 609285; Nemaline myopathy 4, autosomal dominant 609285; Multiple pterygium syndrome
Mendeliome v0.7958 TPM2 Zornitza Stark reviewed gene: TPM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32092148, 27726070, 32092148, 24692096; Phenotypes: Arthrogryposis, distal, type 1A 108120, Arthrogryposis, distal, type 2B4 108120, CAP myopathy 2 609285, Nemaline myopathy 4, autosomal dominant 609285, Multiple pterygium syndrome; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7958 CHRNG Zornitza Stark Gene: chrng has been classified as Green List (High Evidence).
Mendeliome v0.7955 CD207 Zornitza Stark Gene: cd207 has been classified as Red List (Low Evidence).
Mendeliome v0.7952 CD207 Zornitza Stark Classified gene: CD207 as Red List (low evidence)
Mendeliome v0.7952 CD207 Zornitza Stark Gene: cd207 has been classified as Red List (Low Evidence).
Mendeliome v0.7951 KIF17 Zornitza Stark Gene: kif17 has been classified as Red List (Low Evidence).
Mendeliome v0.7951 KIF17 Zornitza Stark gene: KIF17 was added
gene: KIF17 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIF17 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF17 were set to 33922911; 30458707; 28341548
Phenotypes for gene: KIF17 were set to Microphthalmia; Coloboma
Review for gene: KIF17 was set to RED
Added comment: Two siblings reported with MAC spectrum and homozygous missense variant in this gene. Some pre-existing data linking KIF17 to eye development.
Sources: Literature
Mendeliome v0.7950 SASH3 Zornitza Stark Gene: sash3 has been classified as Green List (High Evidence).
Mendeliome v0.7950 SASH3 Zornitza Stark Classified gene: SASH3 as Green List (high evidence)
Mendeliome v0.7950 SASH3 Zornitza Stark Gene: sash3 has been classified as Green List (High Evidence).
Mendeliome v0.7949 SASH3 Zornitza Stark gene: SASH3 was added
gene: SASH3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SASH3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SASH3 were set to 33876203
Phenotypes for gene: SASH3 were set to Combined immunodeficiency; immune dysregulation
Review for gene: SASH3 was set to GREEN
Added comment: Four unrelated males reported presenting with combined immunodeficiency and immune dysregulation manifesting as recurrent sinopulmonary, cutaneous and mucosal infections, and refractory autoimmune cytopaenias. One missense variant, rest were nonsense.
Sources: Literature
Mendeliome v0.7945 MYBPC2 Zornitza Stark Gene: mybpc2 has been classified as Red List (Low Evidence).
Mendeliome v0.7945 MYBPC2 Zornitza Stark gene: MYBPC2 was added
gene: MYBPC2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MYBPC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYBPC2 were set to 32732226
Phenotypes for gene: MYBPC2 were set to Fetal akinesia; Hydrops; Hygroma; Multiple pterygium
Review for gene: MYBPC2 was set to RED
Added comment: Novel candidate gene identified in a fetus with fetal akinesia detected by ultrasound. Autopsy showed multiple congenital abnormalities including hydrops, hygroma, multiple pterygium. A homozygous variant (c.3394G>A/ p.Glu1132Lys) in MYBPC2 was found by exome sequencing with concordant segregation among one affected sib and two unaffected sibs.
Sources: Literature
Mendeliome v0.7944 SCN7A Zornitza Stark Gene: scn7a has been classified as Red List (Low Evidence).
Mendeliome v0.7944 SCN7A Zornitza Stark gene: SCN7A was added
gene: SCN7A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SCN7A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCN7A were set to 32732226
Phenotypes for gene: SCN7A were set to Holoprosencephaly
Review for gene: SCN7A was set to RED
Added comment: Novel candidate gene identified in a fetus with holoprosencephaly detected by ultrasound. Autopsy showed multiple congenital abnormalities including IUGR, microcephaly, bilateral, ablepharon, corpus callosum agenesis, myelomeningocele, tracheal atresia, absent nipples, unilateral simian crease, and hypoplastic phalanges. Compound heterozygous variants including a truncating variant were found by exome sequencing with concordant segregation.
Sources: Literature
Mendeliome v0.7943 SPTBN5 Zornitza Stark Gene: sptbn5 has been classified as Red List (Low Evidence).
Mendeliome v0.7943 SPTBN5 Zornitza Stark gene: SPTBN5 was added
gene: SPTBN5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPTBN5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPTBN5 were set to 32732226; 28007035
Phenotypes for gene: SPTBN5 were set to Sacral agenesis; congenital anomalies
Review for gene: SPTBN5 was set to RED
Added comment: Identified as a candidate gene in a sacral agenesis cohort.

PMID 32732226: compound het variants identified in a fetus with multicystic kidney and oligohydramnios detected by fetal ultrasound. Autopsy showed multiple congenital abnormalities including hygroma coli, spina bifida, polycystic kidneys, facial dysmorphism, common mesenterin, rachischisis, sacral vertebral agenesis.
Sources: Literature
Mendeliome v0.7942 WDR91 Zornitza Stark Phenotypes for gene: WDR91 were changed from to Hydrocephalus; cerebellar hypoplasia; hygroma
Mendeliome v0.7939 WDR91 Zornitza Stark Classified gene: WDR91 as Amber List (moderate evidence)
Mendeliome v0.7939 WDR91 Zornitza Stark Gene: wdr91 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7938 WDR91 Zornitza Stark commented on gene: WDR91: PMID 32732226: Novel candidate gene identified in a fetus with hygroma and hydrocephaly detected by fetal ultrasound. Autopsy showed multiple congenital abnormalities including hygroma, macrocephaly, abnormal ears, unilateral simian crease, hydrocephaly, cerebellar hypoplasia, and interventricular communication. A homozygous truncating variant was found by exome sequencing with concordant segregation among 4 affected fetus, 2 healthy sibs and both parents. Mouse models support role in brain development.
Mendeliome v0.7938 WDR91 Zornitza Stark reviewed gene: WDR91: Rating: AMBER; Mode of pathogenicity: None; Publications: 34028500, 28860274, 32732226; Phenotypes: Hydrocephalus, cerebellar hypoplasia, hygroma; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7938 PLEKHN1 Zornitza Stark Gene: plekhn1 has been classified as Red List (Low Evidence).
Mendeliome v0.7938 PLEKHN1 Zornitza Stark gene: PLEKHN1 was added
gene: PLEKHN1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PLEKHN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLEKHN1 were set to 33884296
Phenotypes for gene: PLEKHN1 were set to Sensory Neuropathy
Review for gene: PLEKHN1 was set to RED
Added comment: Hom missense variant in single patient with severely reduced/absent pain and temperature sensation
Sources: Literature
Mendeliome v0.7937 ZNF3 Zornitza Stark Gene: znf3 has been classified as Red List (Low Evidence).
Mendeliome v0.7937 SMPDL3A Seb Lunke changed review comment from: Hom missense variant in twin sisters with deverely reduced pain and temperature sensation
Sources: Literature; to: Hom missense variant in twin sisters with severely reduced pain and temperature sensation
Sources: Literature
Mendeliome v0.7937 ZNF3 Zornitza Stark gene: ZNF3 was added
gene: ZNF3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZNF3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF3 were set to 32732226
Phenotypes for gene: ZNF3 were set to Hydrocephalus; cleft palate; microphthalmia
Review for gene: ZNF3 was set to RED
Added comment: Novel candidate gene identified in a fetus with hydrocephaly and facial cleft detected by fetal ultrasound. Autopsy showed multiple congenital abnormalities including a median cleft palate, partial maxillar agenesis, bilateral severe microphthalmia, arhinencephaly, partial thalamic fusion. A homozygous truncating variant (c.396A>G/ p.*132Trpext*69) in ZNF3 was found by exome sequencing.
Sources: Literature
Mendeliome v0.7936 SMPDL3A Seb Lunke Gene: smpdl3a has been classified as Red List (Low Evidence).
Mendeliome v0.7936 WRAP73 Zornitza Stark Gene: wrap73 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7936 WRAP73 Zornitza Stark Classified gene: WRAP73 as Amber List (moderate evidence)
Mendeliome v0.7936 WRAP73 Zornitza Stark Gene: wrap73 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7936 SMPDL3A Seb Lunke gene: SMPDL3A was added
gene: SMPDL3A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SMPDL3A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMPDL3A were set to 33884296
Phenotypes for gene: SMPDL3A were set to Sensory Neuropathy
Added comment: Hom missense variant in twin sisters with deverely reduced pain and temperature sensation
Sources: Literature
Mendeliome v0.7934 EIF2AK2 Zornitza Stark Phenotypes for gene: EIF2AK2 were changed from Intellectual disability; white matter abnormalities; ataxia; regression with febrile illness to Intellectual disability; white matter abnormalities; ataxia; regression with febrile illness; Dystonia
Mendeliome v0.7932 EIF2AK2 Zornitza Stark edited their review of gene: EIF2AK2: Added comment: Four unrelated families reported with dystonia, recurrent variant, (p.Gly130Arg); Changed publications: 32197074, 33866603; Changed phenotypes: Intellectual disability, white matter abnormalities, ataxia, regression with febrile illness, Dystonia
Mendeliome v0.7932 SLC37A4 Zornitza Stark Gene: slc37a4 has been classified as Green List (High Evidence).
Mendeliome v0.7929 TUBA1A Zornitza Stark Gene: tuba1a has been classified as Green List (High Evidence).
Mendeliome v0.7929 TUBA1A Zornitza Stark Phenotypes for gene: TUBA1A were changed from to Lissencephaly 3, MIM# 611603; Congenital fibrosis of the extraocular muscles, AD
Mendeliome v0.7926 COL9A3 Zornitza Stark Phenotypes for gene: COL9A3 were changed from Epiphyseal dysplasia, multiple, 3, with or without myopathy, MIM# 600969; Stickler syndrome; Deafness to Epiphyseal dysplasia, multiple, 3, with or without myopathy, MIM# 600969; Stickler syndrome AR; Deafness AD; Peripheral vitreoretinal degeneration and retinal detachment, AD
Mendeliome v0.7921 ANGPTL8 Zornitza Stark Gene: angptl8 has been classified as Red List (Low Evidence).
Mendeliome v0.7921 ANGPTL8 Zornitza Stark Classified gene: ANGPTL8 as Red List (low evidence)
Mendeliome v0.7921 ANGPTL8 Zornitza Stark Gene: angptl8 has been classified as Red List (Low Evidence).
Mendeliome v0.7920 SRCAP Zornitza Stark Gene: srcap has been classified as Green List (High Evidence).
Mendeliome v0.7917 ADAMTSL2 Zornitza Stark Gene: adamtsl2 has been classified as Green List (High Evidence).
Mendeliome v0.7917 ADAMTSL2 Zornitza Stark Phenotypes for gene: ADAMTSL2 were changed from to Geleophysic dysplasia 1, MIM# 231050; Dermatosparaxic Ehlers Danlos syndrome
Mendeliome v0.7914 ADAMTSL2 Zornitza Stark reviewed gene: ADAMTSL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33369194, 26879370, 21415077; Phenotypes: Geleophysic dysplasia 1, MIM# 231050, Dermatosparaxic Ehlers Danlos syndrome; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7914 UNC45A Zornitza Stark Phenotypes for gene: UNC45A were changed from Cholestasis; Diarrhoea; Bone fragility; Impaired hearing to Osteootohepatoenteric syndrome, MIM# 619377; Cholestasis; Diarrhoea; Bone fragility; Impaired hearing
Mendeliome v0.7913 UNC45A Zornitza Stark edited their review of gene: UNC45A: Changed phenotypes: Osteootohepatoenteric syndrome, MIM# 619377, Cholestasis, Diarrhoea, Bone fragility, Impaired hearing
Mendeliome v0.7912 HS3ST6 Zornitza Stark Gene: hs3st6 has been classified as Red List (Low Evidence).
Mendeliome v0.7912 HS3ST6 Zornitza Stark gene: HS3ST6 was added
gene: HS3ST6 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: HS3ST6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HS3ST6 were set to 33508266
Phenotypes for gene: HS3ST6 were set to Hereditary angioedema-8 (HAE8), MIM#619367
Review for gene: HS3ST6 was set to RED
Added comment: Three affected individuals from a single family reported, missense variant, no functional data.
Sources: Expert list
Mendeliome v0.7911 MYOF Zornitza Stark Gene: myof has been classified as Red List (Low Evidence).
Mendeliome v0.7910 KNG1 Zornitza Stark Gene: kng1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7907 KNG1 Zornitza Stark Classified gene: KNG1 as Amber List (moderate evidence)
Mendeliome v0.7907 KNG1 Zornitza Stark Gene: kng1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7906 ANGPT1 Zornitza Stark Gene: angpt1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7905 PLG Zornitza Stark changed review comment from: Association between mono-allelic variants and HAE: Over 20 families reported with a recurrent variant, p.Lys330Glu. Single family reported with a different variant. Note bi-allelic variants are associated with a separate disorder.

Bi-allelic variants and plasminogen deficiency: congenital plasminogen deficiency is characterised clinically by chronic mucosal pseudomembranous lesions consisting of subepithelial fibrin deposition and inflammation. The most common clinical manifestation is ligneous ('wood-like') conjunctivitis, a redness and subsequent formation of pseudomembranes mostly on the palpebral surfaces of the eye that progress to white, yellow-white, or red thick masses with a wood-like consistency that replace the normal mucosa. The lesions may be triggered by local injury and/or infection and often recur after local excision. Pseudomembranous lesions of other mucous membranes often occur in the mouth, nasopharynx, trachea, and female genital tract. Some affected children also have congenital occlusive hydrocephalus. At least 3 unrelated families reported.; to: Association between mono-allelic variants and HAE: Over 20 families reported with a recurrent variant, p.Lys330Glu. Single family reported with a different variant. Note bi-allelic variants are associated with a separate disorder.

Bi-allelic variants and plasminogen deficiency: congenital plasminogen deficiency is characterised clinically by chronic mucosal pseudomembranous lesions consisting of subepithelial fibrin deposition and inflammation. The most common clinical manifestation is ligneous ('wood-like') conjunctivitis, a redness and subsequent formation of pseudomembranes mostly on the palpebral surfaces of the eye that progress to white, yellow-white, or red thick masses with a wood-like consistency that replace the normal mucosa. The lesions may be triggered by local injury and/or infection and often recur after local excision. Pseudomembranous lesions of other mucous membranes often occur in the mouth, nasopharynx, trachea, and female genital tract. Some affected children also have congenital occlusive hydrocephalus. Over 20 unrelated families reported.
Mendeliome v0.7905 PLG Zornitza Stark Gene: plg has been classified as Green List (High Evidence).
Mendeliome v0.7901 PRKD1 Zornitza Stark Phenotypes for gene: PRKD1 were changed from Congenital heart defects and ectodermal dysplasia, 617364 to Congenital heart defects and ectodermal dysplasia, 617364; Congenital heart disease, autosomal recessive
Mendeliome v0.7898 PIGF Zornitza Stark Phenotypes for gene: PIGF were changed from Glycosylphosphatidylinositol\ deficiency, onychodystrophy, osteodystrophy, intellectual disability, and seizures to Onychodystrophy, osteodystrophy, impaired intellectual development, and seizures syndrome, MIM# 619356
Mendeliome v0.7897 PRKD1 Zornitza Stark edited their review of gene: PRKD1: Added comment: Additional publications supporting association with bi-allelic disease:

PMID: 33919081: Three sisters with pulmonary stenosis, truncus arteriosis, and atrial septal defect were homozygous for c.265-1G>T. Their asymptomatic father was also homozygous, however he had two affected sisters (not genotyped), raising the possibility that PRKD1 may undergo autosomal recessive inheritance mode with gender limitation. PMID: 25713110: Two sisters with truncus arteriosis were homozygous for R618X.; Changed publications: 27479907, 32817298, 25713110, 33919081; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7897 ATXN2L Seb Lunke Gene: atxn2l has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7897 ATXN2L Seb Lunke Classified gene: ATXN2L as Amber List (moderate evidence)
Mendeliome v0.7897 ATXN2L Seb Lunke Gene: atxn2l has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7895 LTBP1 Seb Lunke Gene: ltbp1 has been classified as Green List (High Evidence).
Mendeliome v0.7895 LTBP1 Seb Lunke Classified gene: LTBP1 as Green List (high evidence)
Mendeliome v0.7895 LTBP1 Seb Lunke Gene: ltbp1 has been classified as Green List (High Evidence).
Mendeliome v0.7894 SLC30A5 Seb Lunke Classified gene: SLC30A5 as Amber List (moderate evidence)
Mendeliome v0.7894 SLC30A5 Seb Lunke Gene: slc30a5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7893 CADM3 Seb Lunke Added comment: Comment when marking as ready: Three families, but evidence not that great and missing segregation, so stays amber.
Mendeliome v0.7893 CADM3 Seb Lunke Gene: cadm3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7893 CADM3 Seb Lunke Classified gene: CADM3 as Amber List (moderate evidence)
Mendeliome v0.7893 CADM3 Seb Lunke Gene: cadm3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7892 PGM2L1 Sue White Gene: pgm2l1 has been classified as Green List (High Evidence).
Mendeliome v0.7892 PGM2L1 Sue White Classified gene: PGM2L1 as Green List (high evidence)
Mendeliome v0.7892 PGM2L1 Sue White Gene: pgm2l1 has been classified as Green List (High Evidence).
Mendeliome v0.7891 BCAS3 Sue White Gene: bcas3 has been classified as Green List (High Evidence).
Mendeliome v0.7891 TUBA1A Kristin Rigbye edited their review of gene: TUBA1A: Changed phenotypes: Congenital fibrosis of the extraocular muscles, AD
Mendeliome v0.7891 TUBA1A Kristin Rigbye reviewed gene: TUBA1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 30677308; Phenotypes: Congenital fibrosis of the extraocular muscles; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7891 LTBP1 Chern Lim gene: LTBP1 was added
gene: LTBP1 was added to Mendeliome. 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 syndrome
Review for gene: LTBP1 was set to GREEN
gene: LTBP1 was marked as current diagnostic
Added comment: PMID:33991472
- Premature truncating variants in multiple affected individuals from 4 unrelated consanguineous families.
- Affected individuals present with connective tissue features (cutis laxa and inguinal hernia), craniofacial dysmorphology, variable heart defects, and prominent skeletal features (craniosynostosis, short stature, brachydactyly, and syndactyly).
- Functional studies done on patient fibroblasts and zebrafish models.
Sources: Literature
Mendeliome v0.7891 SLC30A5 Melanie Marty gene: SLC30A5 was added
gene: SLC30A5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC30A5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC30A5 were set to 33547425; 12095919
Phenotypes for gene: SLC30A5 were set to Perinatal lethal cardiomyopathy
Review for gene: SLC30A5 was set to AMBER
Added comment: Four affected children from two unrelated families with cardiomyopathy, hydrops fetalis, or cystic hygroma that all deceased perinatally. 2 different homozygous PTCs variants found. Knockout of SLC30A5 in mouse models showed reduced body growth and reduced bone density. About 60% of the mice died due to bradyarrhythmia.
Sources: Literature
Mendeliome v0.7891 COL9A3 Kristin Rigbye reviewed gene: COL9A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 33633367; Phenotypes: Epiphyseal dysplasia, multiple, 3, with or without myopathy, AD, MIM# 600969, Stickler syndrome, AR, Deafness, AD, Peripheral vitreoretinal degeneration and retinal detachment, AD; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7891 CADM3 Teresa Zhao gene: CADM3 was added
gene: CADM3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CADM3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CADM3 were set to PMID: 33889941
Phenotypes for gene: CADM3 were set to Charcot-Marie-Tooth disease
Review for gene: CADM3 was set to AMBER
Added comment: Three families reported with the same missense variant in CADM3 p.Tyr172Cys (one family de novo), with mice work to show reduced expression of the mutant protein in axons and abnormal axonal organization.
Sources: Literature
Mendeliome v0.7891 PGM2L1 Chern Lim gene: PGM2L1 was added
gene: PGM2L1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PGM2L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PGM2L1 were set to 33979636
Phenotypes for gene: PGM2L1 were set to severe developmental and speech delay, dysmorphic facial features, ear anomalies, high arched palate, strabismus, hypotonia, and keratosis pilaris
Review for gene: PGM2L1 was set to GREEN
gene: PGM2L1 was marked as current diagnostic
Added comment: PMID: 33979636:
- Hom/chet PTVs in 4 unrelated individuals. All four affected individuals had severe developmental and speech delay, dysmorphic facial features, ear anomalies, high arched palate, strabismus, hypotonia, and keratosis pilaris. Early obesity and seizures were present in three individuals.
- Studies on patient fibroblasts and cell lines indicated that PGM2L1 deficiency causes a decrease, but not a disappearance, of the sugar bisphosphates needed for the formation of NDP-sugars and that there is no evidence that this leads to a glycosylation defect.
Sources: Literature
Mendeliome v0.7891 KCNB1 Zornitza Stark Gene: kcnb1 has been classified as Green List (High Evidence).
Mendeliome v0.7888 SYT1 Zornitza Stark Gene: syt1 has been classified as Green List (High Evidence).
Mendeliome v0.7885 UBTF Zornitza Stark Gene: ubtf has been classified as Green List (High Evidence).
Mendeliome v0.7882 ZEB2 Zornitza Stark Gene: zeb2 has been classified as Green List (High Evidence).
Mendeliome v0.7881 SLC9A6 Zornitza Stark Gene: slc9a6 has been classified as Green List (High Evidence).
Mendeliome v0.7875 SATB2 Zornitza Stark Gene: satb2 has been classified as Green List (High Evidence).
Mendeliome v0.7870 MBD5 Zornitza Stark Gene: mbd5 has been classified as Green List (High Evidence).
Mendeliome v0.7867 IQSEC2 Zornitza Stark Phenotypes for gene: IQSEC2 were changed from Mental retardation, X-linked 1/78, MIM#309530 to Mental retardation, X-linked 1/78, MIM# 309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347
Mendeliome v0.7865 IQSEC2 Zornitza Stark reviewed gene: IQSEC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33368194, 20473311, 23674175; Phenotypes: Mental retardation, X-linked 1/78, MIM# 309530, MONDO:0010656, Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mendeliome v0.7863 MASP1 Zornitza Stark Gene: masp1 has been classified as Green List (High Evidence).
Mendeliome v0.7860 BRPF1 Zornitza Stark Gene: brpf1 has been classified as Green List (High Evidence).
Mendeliome v0.7860 BRPF1 Zornitza Stark Phenotypes for gene: BRPF1 were changed from to Intellectual developmental disorder with dysmorphic facies and ptosis, MIM# 617333; MONDO:0015022
Mendeliome v0.7857 BRPF1 Zornitza Stark reviewed gene: BRPF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27939640, 27939639; Phenotypes: Intellectual developmental disorder with dysmorphic facies and ptosis, MIM# 617333, MONDO:0015022; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7857 TRAF7 Zornitza Stark Gene: traf7 has been classified as Green List (High Evidence).
Mendeliome v0.7854 UBE3B Zornitza Stark Gene: ube3b has been classified as Green List (High Evidence).
Mendeliome v0.7850 HSPG2 Zornitza Stark reviewed gene: HSPG2: Rating: GREEN; Mode of pathogenicity: None; Publications: 11101850, 16927315, 11279527; Phenotypes: Schwartz-Jampel syndrome, type 1, MIM# 255800, MONDO:0009717, Dyssegmental dysplasia, Silverman-Handmaker type, MIM# 224410, MONDO:0009140; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7850 HLA-DRB1 Zornitza Stark Gene: hla-drb1 has been classified as Red List (Low Evidence).
Mendeliome v0.7850 HLA-DRB1 Zornitza Stark Classified gene: HLA-DRB1 as Red List (low evidence)
Mendeliome v0.7850 HLA-DRB1 Zornitza Stark Gene: hla-drb1 has been classified as Red List (Low Evidence).
Mendeliome v0.7849 HLA-DRA Zornitza Stark Gene: hla-dra has been classified as Red List (Low Evidence).
Mendeliome v0.7849 HLA-DRA Zornitza Stark Classified gene: HLA-DRA as Red List (low evidence)
Mendeliome v0.7849 HLA-DRA Zornitza Stark Gene: hla-dra has been classified as Red List (Low Evidence).
Mendeliome v0.7848 HLA-C Zornitza Stark Gene: hla-c has been classified as Red List (Low Evidence).
Mendeliome v0.7848 HLA-C Zornitza Stark Classified gene: HLA-C as Red List (low evidence)
Mendeliome v0.7848 HLA-C Zornitza Stark Gene: hla-c has been classified as Red List (Low Evidence).
Mendeliome v0.7847 HLA-B Zornitza Stark Gene: hla-b has been classified as Red List (Low Evidence).
Mendeliome v0.7847 HLA-B Zornitza Stark Classified gene: HLA-B as Red List (low evidence)
Mendeliome v0.7847 HLA-B Zornitza Stark Gene: hla-b has been classified as Red List (Low Evidence).
Mendeliome v0.7846 HLA-A Zornitza Stark Gene: hla-a has been classified as Red List (Low Evidence).
Mendeliome v0.7846 HLA-A Zornitza Stark Classified gene: HLA-A as Red List (low evidence)
Mendeliome v0.7846 HLA-A Zornitza Stark Gene: hla-a has been classified as Red List (Low Evidence).
Mendeliome v0.7845 TAF6 Zornitza Stark Gene: taf6 has been classified as Green List (High Evidence).
Mendeliome v0.7841 SLC24A5 Zornitza Stark Gene: slc24a5 has been classified as Green List (High Evidence).
Mendeliome v0.7838 SLC45A2 Zornitza Stark Gene: slc45a2 has been classified as Green List (High Evidence).
Mendeliome v0.7835 TYR Zornitza Stark Gene: tyr has been classified as Green List (High Evidence).
Mendeliome v0.7833 TYRP1 Zornitza Stark Gene: tyrp1 has been classified as Green List (High Evidence).
Mendeliome v0.7830 MC1R Zornitza Stark Gene: mc1r has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7827 MC1R Zornitza Stark Classified gene: MC1R as Amber List (moderate evidence)
Mendeliome v0.7827 MC1R Zornitza Stark Gene: mc1r has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7826 LRMDA Zornitza Stark Gene: lrmda has been classified as Green List (High Evidence).
Mendeliome v0.7823 SERPINF2 Zornitza Stark Gene: serpinf2 has been classified as Green List (High Evidence).
Mendeliome v0.7820 SERPINE1 Zornitza Stark Gene: serpine1 has been classified as Green List (High Evidence).
Mendeliome v0.7817 TBXA2R Zornitza Stark Gene: tbxa2r has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7814 TBXA2R Zornitza Stark Classified gene: TBXA2R as Amber List (moderate evidence)
Mendeliome v0.7814 TBXA2R Zornitza Stark Gene: tbxa2r has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7813 P2RY12 Zornitza Stark Gene: p2ry12 has been classified as Green List (High Evidence).
Mendeliome v0.7810 MCFD2 Zornitza Stark Gene: mcfd2 has been classified as Green List (High Evidence).
Mendeliome v0.7807 LMAN1 Zornitza Stark Gene: lman1 has been classified as Green List (High Evidence).
Mendeliome v0.7804 ITGA2B Zornitza Stark Gene: itga2b has been classified as Green List (High Evidence).
Mendeliome v0.7801 LMOD1 Zornitza Stark Gene: lmod1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7801 LMOD1 Zornitza Stark Phenotypes for gene: LMOD1 were changed from to Megacystis-microcolon-intestinal hypoperistalsis syndrome 3, MIM# 619362
Mendeliome v0.7798 LMOD1 Zornitza Stark Classified gene: LMOD1 as Amber List (moderate evidence)
Mendeliome v0.7798 LMOD1 Zornitza Stark Gene: lmod1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7797 LMOD1 Zornitza Stark 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
Mendeliome v0.7797 POU4F1 Bryony Thompson Gene: pou4f1 has been classified as Green List (High Evidence).
Mendeliome v0.7797 POU4F1 Bryony Thompson Classified gene: POU4F1 as Green List (high evidence)
Mendeliome v0.7797 POU4F1 Bryony Thompson Gene: pou4f1 has been classified as Green List (High Evidence).
Mendeliome v0.7795 HPS6 Zornitza Stark Gene: hps6 has been classified as Green List (High Evidence).
Mendeliome v0.7792 HPS4 Zornitza Stark Gene: hps4 has been classified as Green List (High Evidence).
Mendeliome v0.7789 HPS3 Zornitza Stark Gene: hps3 has been classified as Green List (High Evidence).
Mendeliome v0.7786 HPS1 Zornitza Stark Gene: hps1 has been classified as Green List (High Evidence).
Mendeliome v0.7783 GP9 Zornitza Stark Gene: gp9 has been classified as Green List (High Evidence).
Mendeliome v0.7780 GP6 Zornitza Stark Gene: gp6 has been classified as Green List (High Evidence).
Mendeliome v0.7777 GP1BB Zornitza Stark Gene: gp1bb has been classified as Green List (High Evidence).
Mendeliome v0.7774 CREB3L3 Zornitza Stark Gene: creb3l3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7772 SCNN1B Zornitza Stark Gene: scnn1b has been classified as Green List (High Evidence).
Mendeliome v0.7772 SCNN1B Zornitza Stark Phenotypes for gene: SCNN1B were changed from to Liddle syndrome 1, MIM# 177200; Pseudohypoaldosteronism, type I, MIM# 264350; Bronchiectasis with or without elevated sweat chloride 1 (MIM#211400)
Mendeliome v0.7770 SCNN1B Zornitza Stark reviewed gene: SCNN1B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Liddle syndrome 1, MIM# 177200, Pseudohypoaldosteronism, type I, MIM# 264350, Bronchiectasis with or without elevated sweat chloride 1 (MIM#211400); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7770 FGB Zornitza Stark Gene: fgb has been classified as Green List (High Evidence).
Mendeliome v0.7767 F9 Zornitza Stark Gene: f9 has been classified as Green List (High Evidence).
Mendeliome v0.7764 F8 Zornitza Stark Gene: f8 has been classified as Green List (High Evidence).
Mendeliome v0.7761 F7 Zornitza Stark Gene: f7 has been classified as Green List (High Evidence).
Mendeliome v0.7758 F5 Zornitza Stark Gene: f5 has been classified as Green List (High Evidence).
Mendeliome v0.7758 F5 Zornitza Stark Phenotypes for gene: F5 were changed from to Factor V deficiency, MIM# 227400; MONDO:0009210; Thrombophilia due to activated protein C resistance, MIM# 188055; MONDO:0008560; {Thrombophilia, susceptibility to, due to factor V Leiden}, MIM# 188055
Mendeliome v0.7756 F5 Zornitza Stark reviewed gene: F5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Factor V deficiency, MIM# 227400, MONDO:0009210, Thrombophilia due to activated protein C resistance, MIM# 188055, MONDO:0008560, {Thrombophilia, susceptibility to, due to factor V Leiden}, MIM# 188055; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7756 F13A1 Zornitza Stark Gene: f13a1 has been classified as Green List (High Evidence).
Mendeliome v0.7753 F10 Zornitza Stark Gene: f10 has been classified as Green List (High Evidence).
Mendeliome v0.7750 F10 Zornitza Stark commented on gene: F10: Factor X deficiency shows variable phenotypic severity. Affected individuals can manifest prolonged nasal and mucosal haemorrhage, menorrhagia, haematuria, and occasionally haemarthrosis. More than 20 unrelated families reported.
Mendeliome v0.7750 MCM7 Zornitza Stark Gene: mcm7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7750 MCM7 Zornitza Stark Classified gene: MCM7 as Amber List (moderate evidence)
Mendeliome v0.7750 MCM7 Zornitza Stark Gene: mcm7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7749 MCM7 Arina Puzriakova gene: MCM7 was added
gene: MCM7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MCM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCM7 were set to 33654309; 34059554
Phenotypes for gene: MCM7 were set to Meier-Gorlin syndrome; Microcephaly; Intellectual disability; Lipodystrophy; Adrenal insufficiency
Review for gene: MCM7 was set to AMBER
Added comment: MCM7 is a component of the MCM complex, a DNA helicase which is essential for DNA replication. Other components have been linked to disease with phenotypes including microcephaly and ID. MCM7 is not associated with any phenotype in OMIM or G2P at present.
------
Currently there are 3 unrelated pedigrees in literature with different biallelic MCM7 variants associated with disease (see below). Although there is some functional data in support of variant-level deleteriousness or gene-level pathogenicity, the clinical gestalt is very different between the 3 families.

- PMID: 33654309 (2021) - Two unrelated individuals with different compound het variants in MCM7 but disparate clinical features. One patient had typical Meier-Gorlin syndrome (including growth retardation, microcephaly, congenital lung emphysema, absent breast development, microtia, facial dysmorphism) whereas the second case had a multi-system disorder with neonatal progeroid appearance, lipodystrophy and adrenal insufficiency. While small at birth, the second patient did not demonstrate reduced stature or microcephaly at age 14.5 years. Both individuals had normal neurodevelopment.
Functional studies using patient-derived fibroblasts demonstrate that the identified MCM7 variants were deleterious at either transcript or protein levels and through interfering with MCM complex formation, impact efficiency of S phase progression.

- PMID: 34059554 (2021) - Homozygous missense variant identified in three affected individuals from a consanguineous family with severe primary microcephaly, severe ID and behavioural abnormalities. Knockdown of Mcm7 in mouse neuroblastoma cells lead to reduced cell viability and proliferation with increased apoptosis, which were rescued by overexpression of wild-type but not mutant MCM7.
Sources: Literature
Mendeliome v0.7749 DTNBP1 Zornitza Stark Gene: dtnbp1 has been classified as Green List (High Evidence).
Mendeliome v0.7746 BLOC1S3 Zornitza Stark Gene: bloc1s3 has been classified as Green List (High Evidence).
Mendeliome v0.7743 AP3B1 Zornitza Stark Gene: ap3b1 has been classified as Green List (High Evidence).
Mendeliome v0.7740 LHCGR Zornitza Stark Gene: lhcgr has been classified as Green List (High Evidence).
Mendeliome v0.7740 LHCGR Zornitza Stark Phenotypes for gene: LHCGR were changed from to Luteinizing hormone resistance, female, (MIM#238320); Leydig cell hypoplasia with pseudohermaphroditism, (MIM#238320); Leydig cell hypoplasia with hypergonadotropic hypogonadism, (MIM#238320); Precocious puberty, male, (MIM#176410)
Mendeliome v0.7736 NEB Zornitza Stark Phenotypes for gene: NEB were changed from Nemaline myopathy 2, autosomal recessive 256030 to Nemaline myopathy 2, autosomal recessive 256030; MONDO:0009725; Arthrogryposis multiplex congenita 6, MIM# 619334
Mendeliome v0.7735 NEB Zornitza Stark reviewed gene: NEB: Rating: GREEN; Mode of pathogenicity: None; Publications: 10051637, 22367672, 26578207, 33376055; Phenotypes: Arthrogryposis multiplex congenita 6, MIM# 619334; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7735 LHCGR Ain Roesley reviewed gene: LHCGR: Rating: GREEN; Mode of pathogenicity: None; Publications: 11041448; Phenotypes: Luteinizing hormone resistance, female, (MIM#238320), Leydig cell hypoplasia with pseudohermaphroditism, (MIM#238320), Leydig cell hypoplasia with hypergonadotropic hypogonadism, (MIM#238320), Precocious puberty, male, (MIM#176410); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7735 GEMIN5 Zornitza Stark Gene: gemin5 has been classified as Green List (High Evidence).
Mendeliome v0.7735 GEMIN5 Zornitza Stark Classified gene: GEMIN5 as Green List (high evidence)
Mendeliome v0.7735 GEMIN5 Zornitza Stark Gene: gemin5 has been classified as Green List (High Evidence).
Mendeliome v0.7734 GEMIN5 Zornitza Stark gene: GEMIN5 was added
gene: GEMIN5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GEMIN5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GEMIN5 were set to 33963192
Phenotypes for gene: GEMIN5 were set to Neurodevelopmental disorder with cerebellar atrophy and motor dysfunction, MIM# 619333
Review for gene: GEMIN5 was set to GREEN
Added comment: Neurodevelopmental disorder with cerebellar atrophy and motor dysfunction (NEDCAM) is an autosomal recessive disorder characterized by global developmental delay with prominent motor abnormalities, mainly axial hypotonia, gait ataxia, and appendicular spasticity. Affected individuals have cognitive impairment and speech delay; brain imaging shows cerebellar atrophy. 30 individuals from 22 unrelated families reported.
Sources: Literature
Mendeliome v0.7733 ANO6 Zornitza Stark Gene: ano6 has been classified as Green List (High Evidence).
Mendeliome v0.7730 KLHL3 Zornitza Stark Gene: klhl3 has been classified as Green List (High Evidence).
Mendeliome v0.7727 KCNJ5 Zornitza Stark Gene: kcnj5 has been classified as Green List (High Evidence).
Mendeliome v0.7727 KCNJ5 Zornitza Stark Classified gene: KCNJ5 as Green List (high evidence)
Mendeliome v0.7727 KCNJ5 Zornitza Stark Gene: kcnj5 has been classified as Green List (High Evidence).
Mendeliome v0.7725 HSD11B2 Zornitza Stark Gene: hsd11b2 has been classified as Green List (High Evidence).
Mendeliome v0.7722 CLCN2 Zornitza Stark Gene: clcn2 has been classified as Green List (High Evidence).
Mendeliome v0.7719 CACNA1D Zornitza Stark Gene: cacna1d has been classified as Green List (High Evidence).
Mendeliome v0.7719 CACNA1D Zornitza Stark Phenotypes for gene: CACNA1D were changed from to Primary aldosteronism, seizures, and neurologic abnormalities, MIM# 615474; MONDO:0014200; Sinoatrial node dysfunction and deafness, MIM# 614896
Mendeliome v0.7716 CACNA1D Zornitza Stark reviewed gene: CACNA1D: Rating: GREEN; Mode of pathogenicity: None; Publications: 23913001, 32336187, 30698561, 21131953, 15357422, 22678062; Phenotypes: Primary aldosteronism, seizures, and neurologic abnormalities, MIM# 615474, MONDO:0014200, Sinoatrial node dysfunction and deafness, MIM# 614896; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7716 CACNA1H Zornitza Stark Gene: cacna1h has been classified as Green List (High Evidence).
Mendeliome v0.7713 COX16 Zornitza Stark Phenotypes for gene: COX16 were changed from Hypertrophic cardiomyopathy; encephalopathy; severe fatal lactic acidosis to Mitochondrial complex IV deficiency, nuclear type 22, MIM# 619355; Hypertrophic cardiomyopathy; encephalopathy; severe fatal lactic acidosis
Mendeliome v0.7712 NSF Zornitza Stark Phenotypes for gene: NSF were changed from Seizures; EEG with burst suppression; Global developmental delay; Intellectual disability to Developmental and epileptic encephalopathy 96, MIM# 619340; Seizures; EEG with burst suppression; Global developmental delay; Intellectual disability
Mendeliome v0.7711 NSF Zornitza Stark edited their review of gene: NSF: Changed phenotypes: Developmental and epileptic encephalopathy 96, MIM# 619340, Seizures, EEG with burst suppression, Global developmental delay, Intellectual disability
Mendeliome v0.7710 IPO8 Zornitza Stark Classified gene: IPO8 as Green List (high evidence)
Mendeliome v0.7710 IPO8 Zornitza Stark Gene: ipo8 has been classified as Green List (High Evidence).
Mendeliome v0.7709 NFU1 Zornitza Stark Gene: nfu1 has been classified as Green List (High Evidence).
Mendeliome v0.7706 RAB11B Zornitza Stark commented on gene: RAB11B: NDAGSCW is a neurodevelopmental disorder characterized by severely delayed psychomotor development apparent from infancy. Affected individuals have delayed and difficulty walking, intellectual disability, absent speech, and variable additional features, including hip dysplasia, tapering fingers, and seizures. Brain imaging shows decreased cortical white matter, often with decreased cerebellar white matter, thin corpus callosum, and thin brainstem.
Mendeliome v0.7706 RAB11B Zornitza Stark Gene: rab11b has been classified as Green List (High Evidence).
Mendeliome v0.7703 UFSP2 Zornitza Stark Gene: ufsp2 has been classified as Green List (High Evidence).
Mendeliome v0.7703 UFSP2 Zornitza Stark Phenotypes for gene: UFSP2 were changed from to Neurodevelopmental disorder; Hip dysplasia, Beukes type, MIM#142669; Spondyloepimetaphyseal dysplasia, Di Rocco type, MIM# 617974
Mendeliome v0.7700 UFSP2 Zornitza Stark changed review comment from: Ni et al (2021 - PMID: 33473208) describe the phenotype of 8 children (belonging to 4 families - 2 of which consanguineous) homozygous for a UFSP2 missense variant [NM_018359.5:c.344T>A; p.(Val115Glu)]. Likely founder variant in all.

Hip dysplasia: single 8 generation family reported.

Spondyloepimetaphyseal dysplasia, Di Rocco type: two families reported.; to: Ni et al (2021 - PMID: 33473208) describe the phenotype of 8 children (belonging to 4 families - 2 of which consanguineous) homozygous for a UFSP2 missense variant [NM_018359.5:c.344T>A; p.(Val115Glu)]. Likely founder variant in all. Additional cases identified through the 100,000 Genomes project.

Hip dysplasia: single 8 generation family reported.

Spondyloepimetaphyseal dysplasia, Di Rocco type: two families reported.
Mendeliome v0.7700 KLHL13 Zornitza Stark Gene: klhl13 has been classified as Red List (Low Evidence).
Mendeliome v0.7700 KLHL13 Zornitza Stark gene: KLHL13 was added
gene: KLHL13 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: KLHL13 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: KLHL13 were set to 24627108
Phenotypes for gene: KLHL13 were set to HMSN
Review for gene: KLHL13 was set to RED
Added comment: Single family (two affected males) with an inherited peripheral neuropathy, no functional analysis.
Sources: Expert Review
Mendeliome v0.7699 PRX Zornitza Stark Gene: prx has been classified as Green List (High Evidence).
Mendeliome v0.7696 PLEKHG5 Zornitza Stark Gene: plekhg5 has been classified as Green List (High Evidence).
Mendeliome v0.7696 PLEKHG5 Zornitza Stark Phenotypes for gene: PLEKHG5 were changed from to Charcot-Marie-Tooth disease, recessive intermediate C, MIM# 615376; Spinal muscular atrophy, distal, autosomal recessive, 4, MIM# 611067
Mendeliome v0.7693 PLEKHG5 Zornitza Stark reviewed gene: PLEKHG5: Rating: GREEN; Mode of pathogenicity: None; Publications: 17564964, 23777631, 23844677, 33492783, 33275839, 33220101, 23777631; Phenotypes: Charcot-Marie-Tooth disease, recessive intermediate C, MIM# 615376, Spinal muscular atrophy, distal, autosomal recessive, 4, MIM# 611067; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7693 NEFL Zornitza Stark Gene: nefl has been classified as Green List (High Evidence).
Mendeliome v0.7690 ADNP Zornitza Stark Gene: adnp has been classified as Green List (High Evidence).
Mendeliome v0.7687 CHUK Zornitza Stark Gene: chuk has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7684 CHUK Zornitza Stark Classified gene: CHUK as Amber List (moderate evidence)
Mendeliome v0.7684 CHUK Zornitza Stark Gene: chuk has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7683 TMEM251 Zornitza Stark Phenotypes for gene: TMEM251 were changed from Dysostosis multiplex‐like skeletal dysplasia; severe short stature to Dysostosis multiplex, Ain-Naz type 619345
Mendeliome v0.7682 TMEM251 Zornitza Stark reviewed gene: TMEM251: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Dysostosis multiplex, Ain-Naz type 619345; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7681 PARP6 Zornitza Stark Gene: parp6 has been classified as Green List (High Evidence).
Mendeliome v0.7681 PARP6 Zornitza Stark Classified gene: PARP6 as Green List (high evidence)
Mendeliome v0.7681 PARP6 Zornitza Stark Gene: parp6 has been classified as Green List (High Evidence).
Mendeliome v0.7680 PARP6 Zornitza Stark gene: PARP6 was added
gene: PARP6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PARP6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PARP6 were set to Cells 2021, 10(6), 1289; https://doi.org/10.3390/cells10061289
Phenotypes for gene: PARP6 were set to Intellectual disability; Epilepsy; Microcephaly
Review for gene: PARP6 was set to GREEN
Added comment: Four unrelated individuals reported with de novo variants in this gene and a neurodevelopmental phenotype. Supportive functional data. One pair of siblings with a homozygous missense: limited evidence for bi-allelic variants causing disease.
Sources: Literature
Mendeliome v0.7679 MAPKBP1 Zornitza Stark Gene: mapkbp1 has been classified as Green List (High Evidence).
Mendeliome v0.7679 MAPKBP1 Zornitza Stark Phenotypes for gene: MAPKBP1 were changed from to Nephronophthisis 20, MIM# 617271; MONDO:0014997
Mendeliome v0.7676 MAPKBP1 Zornitza Stark reviewed gene: MAPKBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28089251, 33623699, 32505465, 32055034; Phenotypes: Nephronophthisis 20, MIM# 617271, MONDO:0014997; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7675 DNAJB2 Zornitza Stark Gene: dnajb2 has been classified as Green List (High Evidence).
Mendeliome v0.7675 DNAJB2 Zornitza Stark Phenotypes for gene: DNAJB2 were changed from to Spinal muscular atrophy, distal, autosomal recessive, 5, MIM# 614881; MONDO:0014866
Mendeliome v0.7672 DNAJB2 Zornitza Stark reviewed gene: DNAJB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22522442, 25274842, 33369814, 22522442; Phenotypes: Spinal muscular atrophy, distal, autosomal recessive, 5, MIM# 614881, MONDO:0014866; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7672 ATP7A Zornitza Stark Phenotypes for gene: ATP7A were changed from Occipital horn syndrome, 304150; X-linked recessive Menkes disease, 309400 Spinal muscular atrophy, distal, X-linked 3, 300489 to Menkes disease MIM#309400; Occipital horn syndrome MIM#304150; Spinal muscular atrophy, distal, X-linked 3, MIM# 300489
Mendeliome v0.7670 UFSP2 Zornitza Stark changed review comment from: Ni et al (2021 - PMID: 33473208) describe the phenotype of 8 children (belonging to 4 families - 2 of which consanguineous) homozygous for a UFSP2 missense variant [NM_018359.5:c.344T>A; p.(Val115Glu)]. Likely founder variant in all.

Hip dysplasia: single 8 generation family reported.

Spondyloepimetaphyseal dysplasia, Di Rocco type: single 3-generation family reported.; to: Ni et al (2021 - PMID: 33473208) describe the phenotype of 8 children (belonging to 4 families - 2 of which consanguineous) homozygous for a UFSP2 missense variant [NM_018359.5:c.344T>A; p.(Val115Glu)]. Likely founder variant in all.

Hip dysplasia: single 8 generation family reported.

Spondyloepimetaphyseal dysplasia, Di Rocco type: two families reported.
Mendeliome v0.7670 UFSP2 Zornitza Stark reviewed gene: UFSP2: Rating: AMBER; Mode of pathogenicity: None; Publications: 33473208, 26428751, 28892125; Phenotypes: Neurodevelopmental disorder, Hip dysplasia, Beukes type, MIM#142669, Spondyloepimetaphyseal dysplasia, Di Rocco type, MIM# 617974; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7670 TRPV6 Zornitza Stark Gene: trpv6 has been classified as Green List (High Evidence).
Mendeliome v0.7670 TRPV6 Zornitza Stark Phenotypes for gene: TRPV6 were changed from to Hyperparathyroidism, transient neonatal, MIM# 618188; Early onset chronic pancreatitis susceptibility
Mendeliome v0.7667 TRPV6 Zornitza Stark reviewed gene: TRPV6: Rating: GREEN; Mode of pathogenicity: None; Publications: 32383311, 31930989, 29861107; Phenotypes: Hyperparathyroidism, transient neonatal, MIM# 618188, Early onset chronic pancreatitis susceptibility; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7667 FAR1 Zornitza Stark Phenotypes for gene: FAR1 were changed from Peroxisomal fatty acyl-CoA reductase 1 disorder, MIM#616154; spastic paraparesis and bilateral cataracts to Peroxisomal fatty acyl-CoA reductase 1 disorder, MIM#616154; Cataracts, spastic paraparesis, and speech delay, MIM#619338
Mendeliome v0.7666 FAR1 Zornitza Stark edited their review of gene: FAR1: Changed phenotypes: Peroxisomal fatty acyl-CoA reductase 1 disorder, MIM#616154, Cataracts, spastic paraparesis, and speech delay, MIM#619338
Mendeliome v0.7665 BICRA Zornitza Stark Phenotypes for gene: BICRA were changed from Developmental delay, intellectual disability, autism spectrum disorder,behavioral abnormalities, dysmorphic features to Coffin-Siris syndrome-12, MIM#619325; Developmental delay, intellectual disability, autism spectrum disorder,behavioral abnormalities, dysmorphic features
Mendeliome v0.7664 BICRA Zornitza Stark reviewed gene: BICRA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Coffin-Siris syndrome-12, MIM#619325; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7664 RETREG1 Zornitza Stark Gene: retreg1 has been classified as Green List (High Evidence).
Mendeliome v0.7661 SBF1 Zornitza Stark Gene: sbf1 has been classified as Green List (High Evidence).
Mendeliome v0.7658 SBF2 Zornitza Stark Gene: sbf2 has been classified as Green List (High Evidence).
Mendeliome v0.7655 SCN10A Zornitza Stark Gene: scn10a has been classified as Green List (High Evidence).
Mendeliome v0.7651 COL5A1 Zornitza Stark Gene: col5a1 has been classified as Green List (High Evidence).
Mendeliome v0.7651 COL5A1 Zornitza Stark Phenotypes for gene: COL5A1 were changed from to Ehlers-Danlos syndrome, classic type, 1, MIM# 130000; Fibromuscular dysplasia, multifocal, MIM# 619329
Mendeliome v0.7648 COL5A1 Zornitza Stark reviewed gene: COL5A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30071989, 32938213; Phenotypes: Ehlers-Danlos syndrome, classic type, 1, MIM# 130000, Fibromuscular dysplasia, multifocal, MIM# 619329; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7648 SCN1A Zornitza Stark Phenotypes for gene: SCN1A were changed from Epileptic encephalopathy, early infantile, 6 (Dravet syndrome), MIM# 607208; Genetic Epilepsy Febrile Seizures plus (GEFS+) Syndrome; Febrile seizures; Arthrogryposis multiplex congenita to Epileptic encephalopathy, early infantile, 6 (Dravet syndrome), MIM# 607208; Developmental and epileptic encephalopathy 6B, non-Dravet, MIM# 619317; Genetic Epilepsy Febrile Seizures plus (GEFS+) Syndrome; Febrile seizures; Arthrogryposis multiplex congenita
Mendeliome v0.7647 SCN1A Zornitza Stark edited their review of gene: SCN1A: Changed phenotypes: Epileptic encephalopathy, early infantile, 6 (Dravet syndrome), MIM# 607208, Developmental and epileptic encephalopathy 6B, non-Dravet, MIM# 619317, Genetic Epilepsy Febrile Seizures plus (GEFS+) Syndrome, Febrile seizures, Arthrogryposis multiplex congenita
Mendeliome v0.7646 DKC1 Zornitza Stark Gene: dkc1 has been classified as Green List (High Evidence).
Mendeliome v0.7646 DKC1 Zornitza Stark Phenotypes for gene: DKC1 were changed from to Dyskeratosis congenita, X-linked 305000; Hoyeraal-Hreidarsson Syndrome
Mendeliome v0.7643 DKC1 Zornitza Stark reviewed gene: DKC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31269755, 26951492, 29081935, 25940403; Phenotypes: Dyskeratosis congenita, X-linked 305000, Hoyeraal-Hreidarsson Syndrome; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.7643 THOC2 Zornitza Stark Gene: thoc2 has been classified as Green List (High Evidence).
Mendeliome v0.7640 FGA Zornitza Stark Gene: fga has been classified as Green List (High Evidence).
Mendeliome v0.7640 FGA Zornitza Stark Phenotypes for gene: FGA were changed from to Afibrinogenemia, congenital (MIM#202400), AR; Amyloidosis, familial visceral (MIM#105200), AD
Mendeliome v0.7637 FGA Chern Lim reviewed gene: FGA: Rating: GREEN; Mode of pathogenicity: None; Publications: 31064749, 17295221, 19073821, 11739173; Phenotypes: Afibrinogenemia, congenital (MIM#202400), AR, Amyloidosis, familial visceral (MIM#105200), AD; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.7637 GRHL2 Zornitza Stark Gene: grhl2 has been classified as Green List (High Evidence).
Mendeliome v0.7637 GRHL2 Zornitza Stark Phenotypes for gene: GRHL2 were changed from to Ectodermal dysplasia/short stature syndrome MIM#616029; Corneal dystrophy, posterior polymorphous, 4, MIM# 618031; Deafness, autosomal dominant 28, MIM# 608641
Mendeliome v0.7634 GRHL2 Zornitza Stark reviewed gene: GRHL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25152456, 29499165; Phenotypes: Ectodermal dysplasia/short stature syndrome MIM#616029, Corneal dystrophy, posterior polymorphous, 4, MIM# 618031, Deafness, autosomal dominant 28, MIM# 608641; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7634 ST14 Zornitza Stark Gene: st14 has been classified as Green List (High Evidence).
Mendeliome v0.7634 ST14 Zornitza Stark Phenotypes for gene: ST14 were changed from to Ichthyosis, congenital, autosomal recessive 11, MIM# MIM#602400
Mendeliome v0.7631 ST14 Zornitza Stark reviewed gene: ST14: Rating: GREEN; Mode of pathogenicity: None; Publications: 18843291, 29611532, 17273967; Phenotypes: Ichthyosis, congenital, autosomal recessive 11 MIM#602400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7631 CPE Zornitza Stark Gene: cpe has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7631 CPE Zornitza Stark Classified gene: CPE as Amber List (moderate evidence)
Mendeliome v0.7631 CPE Zornitza Stark Gene: cpe has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7629 CELSR1 Zornitza Stark Gene: celsr1 has been classified as Green List (High Evidence).
Mendeliome v0.7629 CELSR1 Zornitza Stark Classified gene: CELSR1 as Green List (high evidence)
Mendeliome v0.7629 CELSR1 Zornitza Stark Gene: celsr1 has been classified as Green List (High Evidence).
Mendeliome v0.7627 SLC2A4RG Zornitza Stark Gene: slc2a4rg has been classified as Red List (Low Evidence).
Mendeliome v0.7627 SLC2A4RG Zornitza Stark Classified gene: SLC2A4RG as Red List (low evidence)
Mendeliome v0.7627 SLC2A4RG Zornitza Stark Gene: slc2a4rg has been classified as Red List (Low Evidence).
Mendeliome v0.7626 SLCO1B1 Zornitza Stark Gene: slco1b1 has been classified as Red List (Low Evidence).
Mendeliome v0.7624 SLCO1B1 Zornitza Stark Classified gene: SLCO1B1 as Red List (low evidence)
Mendeliome v0.7624 SLCO1B1 Zornitza Stark Gene: slco1b1 has been classified as Red List (Low Evidence).
Mendeliome v0.7623 SIAH1 Zornitza Stark Phenotypes for gene: SIAH1 were changed from Developmental delay; Infantile hypotonia; Dysmorphic features; Laryngomalacia to Buratti-Harel syndrome, MIM# 619314; Developmental delay; Infantile hypotonia; Dysmorphic features; Laryngomalacia
Mendeliome v0.7622 SIAH1 Zornitza Stark reviewed gene: SIAH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Buratti-Harel syndrome, MIM# 619314; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7622 SMARCA5 Zornitza Stark Gene: smarca5 has been classified as Green List (High Evidence).
Mendeliome v0.7622 SMARCA5 Zornitza Stark Classified gene: SMARCA5 as Green List (high evidence)
Mendeliome v0.7622 SMARCA5 Zornitza Stark Gene: smarca5 has been classified as Green List (High Evidence).
Mendeliome v0.7619 FBXW7 Zornitza Stark Classified gene: FBXW7 as Green List (high evidence)
Mendeliome v0.7619 FBXW7 Zornitza Stark Gene: fbxw7 has been classified as Green List (High Evidence).
Mendeliome v0.7615 SLC5A7 Zornitza Stark Gene: slc5a7 has been classified as Green List (High Evidence).
Mendeliome v0.7611 NR3C2 Zornitza Stark Gene: nr3c2 has been classified as Green List (High Evidence).
Mendeliome v0.7608 SCNN1A Zornitza Stark Gene: scnn1a has been classified as Green List (High Evidence).
Mendeliome v0.7608 SCNN1A Zornitza Stark Phenotypes for gene: SCNN1A were changed from to Liddle syndrome 3 618126, MIM# AD, MONDO:0029132; Bronchiectasis with or without elevated sweat chloride 2, MIM# 613021 AD, MONDO:0013087; Pseudohypoaldosteronism, type I, MIM# 264350 AR, MIM#0009917
Mendeliome v0.7605 SCNN1A Zornitza Stark reviewed gene: SCNN1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 31301676, 28710092, 19462466, 19017867; Phenotypes: Liddle syndrome 3 618126, MIM# AD, MONDO:0029132, Bronchiectasis with or without elevated sweat chloride 2, MIM# 613021 AD, MONDO:0013087, Pseudohypoaldosteronism, type I, MIM# 264350 AR, MIM#0009917; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7605 SPTLC1 Zornitza Stark Gene: sptlc1 has been classified as Green List (High Evidence).
Mendeliome v0.7605 SPTLC1 Zornitza Stark Phenotypes for gene: SPTLC1 were changed from to Neuropathy, hereditary sensory and autonomic, type IA, MIM# 162400; Serine palmitoyl transferase deficiency (Disorders of complex lipid synthesis)
Mendeliome v0.7602 SPTLC2 Zornitza Stark Gene: sptlc2 has been classified as Green List (High Evidence).
Mendeliome v0.7602 SPTLC2 Zornitza Stark Phenotypes for gene: SPTLC2 were changed from to Neuropathy, hereditary sensory and autonomic, type IC, 613640; MONDO:0013337; Serine palmitoyl transferase deficiency (Disorders of complex lipid synthesis)
Mendeliome v0.7599 ZPR1 Zornitza Stark Gene: zpr1 has been classified as Red List (Low Evidence).
Mendeliome v0.7598 SPEN Zornitza Stark Gene: spen has been classified as Green List (High Evidence).
Mendeliome v0.7596 AFF3 Zornitza Stark Gene: aff3 has been classified as Green List (High Evidence).
Mendeliome v0.7593 KDR Zornitza Stark Gene: kdr has been classified as Green List (High Evidence).
Mendeliome v0.7593 KDR Zornitza Stark Phenotypes for gene: KDR were changed from to Pulmonary hypertension; Haemangioma, capillary infantile, somatic 602089
Mendeliome v0.7590 KDR Zornitza Stark reviewed gene: KDR: Rating: GREEN; Mode of pathogenicity: None; Publications: 31980491, 29650961, 18931684; Phenotypes: Pulmonary hypertension, Haemangioma, capillary infantile, somatic 602089; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7590 TRIM2 Zornitza Stark Gene: trim2 has been classified as Green List (High Evidence).
Mendeliome v0.7587 RAB7A Zornitza Stark Gene: rab7a has been classified as Green List (High Evidence).
Mendeliome v0.7584 PRDM12 Zornitza Stark Gene: prdm12 has been classified as Green List (High Evidence).
Mendeliome v0.7581 FIP1L1 Zornitza Stark Gene: fip1l1 has been classified as Red List (Low Evidence).
Mendeliome v0.7581 FIP1L1 Zornitza Stark Classified gene: FIP1L1 as Red List (low evidence)
Mendeliome v0.7581 FIP1L1 Zornitza Stark Gene: fip1l1 has been classified as Red List (Low Evidence).
Mendeliome v0.7580 THBS2 Zornitza Stark Gene: thbs2 has been classified as Red List (Low Evidence).
Mendeliome v0.7579 THBS2 Zornitza Stark Classified gene: THBS2 as Red List (low evidence)
Mendeliome v0.7579 THBS2 Zornitza Stark Gene: thbs2 has been classified as Red List (Low Evidence).
Mendeliome v0.7578 ADIPOQ Zornitza Stark Gene: adipoq has been classified as Red List (Low Evidence).
Mendeliome v0.7576 ADIPOQ Zornitza Stark Classified gene: ADIPOQ as Red List (low evidence)
Mendeliome v0.7576 ADIPOQ Zornitza Stark Gene: adipoq has been classified as Red List (Low Evidence).
Mendeliome v0.7575 INTU Zornitza Stark Gene: intu has been classified as Green List (High Evidence).
Mendeliome v0.7575 INTU Zornitza Stark Phenotypes for gene: INTU were changed from to ?Orofaciodigital syndrome XVII MIM#617926; ?Short-rib thoracic dysplasia 20 with polydactyly
Mendeliome v0.7572 INTU Elena Savva reviewed gene: INTU: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27158779, 29451301, 20067783; Phenotypes: ?Orofaciodigital syndrome XVII MIM#617926, ?Short-rib thoracic dysplasia 20 with polydactyly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7572 NGF Zornitza Stark Gene: ngf has been classified as Green List (High Evidence).
Mendeliome v0.7567 NDUFB3 Zornitza Stark Gene: ndufb3 has been classified as Green List (High Evidence).
Mendeliome v0.7563 EXOSC1 Zornitza Stark Phenotypes for gene: EXOSC1 were changed from Pontocerebellar hypoplasia to Pontocerebellar hypoplasia, type 1F, MIM# 619304
Mendeliome v0.7562 EXOSC1 Zornitza Stark edited their review of gene: EXOSC1: Changed phenotypes: Pontocerebellar hypoplasia, type 1F, MIM# 619304
Mendeliome v0.7562 SLC25A46 Zornitza Stark Phenotypes for gene: SLC25A46 were changed from Neuropathy, hereditary motor and sensory, type VIB, MIM# 616505 to Neuropathy, hereditary motor and sensory, type VIB, MIM# 616505; Pontocerebellar hypoplasia, type 1E, MIM# 619303
Mendeliome v0.7561 SLC25A46 Zornitza Stark changed review comment from: Hereditary motor and sensory neuropathy type VIB is an autosomal recessive complex progressive neurologic disorder characterized mainly by early-onset optic atrophy resulting in progressive visual loss and peripheral axonal sensorimotor neuropathy with highly variable age at onset and severity. Affected individuals also have cerebellar or pontocerebellar atrophy on brain imaging, and they show abnormal movements, such as ataxia, dysmetria, and myoclonus.

At least 10 unrelated families reported, supportive functional data.; to: Hereditary motor and sensory neuropathy type VIB is an autosomal recessive complex progressive neurologic disorder characterized mainly by early-onset optic atrophy resulting in progressive visual loss and peripheral axonal sensorimotor neuropathy with highly variable age at onset and severity. Affected individuals also have cerebellar or pontocerebellar atrophy on brain imaging, and they show abnormal movements, such as ataxia, dysmetria, and myoclonus. New disease entity added by OMIM in 2021 to reflect this more severe end of the spectrum.

At least 10 unrelated families reported, supportive functional data.
Mendeliome v0.7561 SLC25A46 Zornitza Stark edited their review of gene: SLC25A46: Changed phenotypes: Neuropathy, hereditary motor and sensory, type VIB, MIM# 616505, Pontocerebellar hypoplasia, type 1E, MIM# 619303
Mendeliome v0.7559 EXOC2 Zornitza Stark Phenotypes for gene: EXOC2 were changed from Global developmental delay; Intellectual disability; Abnormality of the face; Abnormality of brain morphology to Neurodevelopmental disorder with dysmorphic facies and cerebellar hypoplasia, MIM# 619306; Global developmental delay; Intellectual disability; Abnormality of the face; Abnormality of brain morphology
Mendeliome v0.7558 EXOC2 Zornitza Stark edited their review of gene: EXOC2: Changed phenotypes: Neurodevelopmental disorder with dysmorphic facies and cerebellar hypoplasia, MIM# 619306, Global developmental delay, Intellectual disability, Abnormality of the face, Abnormality of brain morphology
Mendeliome v0.7558 SPI1 Zornitza Stark Gene: spi1 has been classified as Green List (High Evidence).
Mendeliome v0.7558 SPI1 Zornitza Stark Classified gene: SPI1 as Green List (high evidence)
Mendeliome v0.7558 SPI1 Zornitza Stark Gene: spi1 has been classified as Green List (High Evidence).
Mendeliome v0.7557 SPI1 Zornitza Stark gene: SPI1 was added
gene: SPI1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPI1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPI1 were set to 33951726
Phenotypes for gene: SPI1 were set to Agammaglobulinaemia
Review for gene: SPI1 was set to GREEN
Added comment: Six unrelated individuals reported, four with de novo variants, two unphased. Some functional data.
Sources: Literature
Mendeliome v0.7556 NDRG1 Zornitza Stark Gene: ndrg1 has been classified as Green List (High Evidence).
Mendeliome v0.7553 MTMR2 Zornitza Stark Gene: mtmr2 has been classified as Green List (High Evidence).
Mendeliome v0.7550 TMEM222 Zornitza Stark Gene: tmem222 has been classified as Green List (High Evidence).
Mendeliome v0.7550 TMEM222 Zornitza Stark Classified gene: TMEM222 as Green List (high evidence)
Mendeliome v0.7550 TMEM222 Zornitza Stark Gene: tmem222 has been classified as Green List (High Evidence).
Mendeliome v0.7549 TMEM222 Zornitza Stark gene: TMEM222 was added
gene: TMEM222 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TMEM222 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM222 were set to 33824500
Phenotypes for gene: TMEM222 were set to Intellectual disability; Epilepsy; Microcephaly
Review for gene: TMEM222 was set to GREEN
Added comment: Polla et al (2021 - PMID: 33824500) report 17 individuals from 9 unrelated families, with biallelic TMEM222 pathogenic variants. The phenotype included motor, speech delay and moderate to severe ID (as universal features). Other manifestations included hypotonia (10/15), broad gait (5/12), seizures (7/17 - belonging to 6/9 families), MRI abnormalities (5/8). Variable behavioral abnormalities were observed (aggressive behavior, shy character, stereotypic movements etc). Abnormal OFC was a feature in several with microcephaly in 7 subjects from 4 families (measurements not available for all 17). Nonspecific facial features were reported in 10/17.
Sources: Literature
Mendeliome v0.7548 CHD5 Zornitza Stark Gene: chd5 has been classified as Green List (High Evidence).
Mendeliome v0.7548 CHD5 Zornitza Stark Classified gene: CHD5 as Green List (high evidence)
Mendeliome v0.7548 CHD5 Zornitza Stark Gene: chd5 has been classified as Green List (High Evidence).
Mendeliome v0.7546 MME Zornitza Stark Gene: mme has been classified as Green List (High Evidence).
Mendeliome v0.7543 FBXO31 Zornitza Stark Phenotypes for gene: FBXO31 were changed from Mental retardation, autosomal recessive 45, MIM#615979; Cerebral palsy, intellectual disability, autosomal dominant to Mental retardation, autosomal recessive 45, MIM#615979; Spastic-dystonic cerebral palsy, intellectual disability, de novo dominant
Mendeliome v0.7542 FBXO31 Zornitza Stark Classified gene: FBXO31 as Green List (high evidence)
Mendeliome v0.7542 FBXO31 Zornitza Stark Gene: fbxo31 has been classified as Green List (High Evidence).
Mendeliome v0.7541 FBXO31 Zornitza Stark changed review comment from: Single consanguineous family reported with homozygous truncating variant, limited functional evidence.
Sources: Expert list; to: AR intellectual disability: Single consanguineous family reported with homozygous truncating variant, limited functional evidence.
Sources: Expert list
Mendeliome v0.7541 FBXO31 Zornitza Stark edited their review of gene: FBXO31: Added comment: PMIDs 33675180; 32989326: three unrelated individuals with de novo missense variant, (p.Asp334Asn) and spastic-dystonic CP.; Changed rating: GREEN; Changed publications: 24623383, 33675180, 32989326; Changed phenotypes: Mental retardation, autosomal recessive 45, MIM#615979, Spastic-dystonic cerebral palsy, de novo dominant; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7541 RCAN1 Zornitza Stark Gene: rcan1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7541 RCAN1 Zornitza Stark Classified gene: RCAN1 as Amber List (moderate evidence)
Mendeliome v0.7541 RCAN1 Zornitza Stark Gene: rcan1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7539 ZNFX1 Zornitza Stark Gene: znfx1 has been classified as Green List (High Evidence).
Mendeliome v0.7539 ZNFX1 Zornitza Stark Phenotypes for gene: ZNFX1 were changed from Multisystem inflammation; susceptibility to viral infections to Multisystem inflammation; susceptibility to viral infections; monocytosis; susceptibility to mycobacterial infection
Mendeliome v0.7538 ZNFX1 Zornitza Stark Classified gene: ZNFX1 as Green List (high evidence)
Mendeliome v0.7538 ZNFX1 Zornitza Stark Gene: znfx1 has been classified as Green List (High Evidence).
Mendeliome v0.7537 ZNFX1 Zornitza Stark gene: ZNFX1 was added
gene: ZNFX1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZNFX1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNFX1 were set to 33872655; 33876776
Phenotypes for gene: ZNFX1 were set to Multisystem inflammation; susceptibility to viral infections
Review for gene: ZNFX1 was set to GREEN
Added comment: 15 individuals from 8 families reported with multi-system inflammation and susceptibility to viral infections.

In addition, four indviduals from two unrelated kindreds reported with intermittent monocytosis and mycobacterial disease, including bacillus Calmette-Guérin-osis and disseminated tuberculosis.
Sources: Literature
Mendeliome v0.7536 STXBP3 Zornitza Stark Gene: stxbp3 has been classified as Green List (High Evidence).
Mendeliome v0.7536 STXBP3 Zornitza Stark Classified gene: STXBP3 as Green List (high evidence)
Mendeliome v0.7536 STXBP3 Zornitza Stark Gene: stxbp3 has been classified as Green List (High Evidence).
Mendeliome v0.7534 IL21R Zornitza Stark Gene: il21r has been classified as Green List (High Evidence).
Mendeliome v0.7531 SCD Zornitza Stark Gene: scd has been classified as Red List (Low Evidence).
Mendeliome v0.7531 SCD Zornitza Stark Classified gene: SCD as Red List (low evidence)
Mendeliome v0.7531 SCD Zornitza Stark Gene: scd has been classified as Red List (Low Evidence).
Mendeliome v0.7530 DPYSL5 Zornitza Stark Gene: dpysl5 has been classified as Green List (High Evidence).
Mendeliome v0.7530 DPYSL5 Zornitza Stark Classified gene: DPYSL5 as Green List (high evidence)
Mendeliome v0.7530 DPYSL5 Zornitza Stark Gene: dpysl5 has been classified as Green List (High Evidence).
Mendeliome v0.7529 SIN3B Zornitza Stark Marked gene: SIN3B as ready
Mendeliome v0.7529 SIN3B Zornitza Stark Gene: sin3b has been classified as Green List (High Evidence).
Mendeliome v0.7529 SIN3B Zornitza Stark Mode of inheritance for gene: SIN3B was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7528 SIN3B Zornitza Stark Classified gene: SIN3B as Green List (high evidence)
Mendeliome v0.7528 SIN3B Zornitza Stark Gene: sin3b has been classified as Green List (High Evidence).
Mendeliome v0.7526 VPS41 Zornitza Stark Classified gene: VPS41 as Green List (high evidence)
Mendeliome v0.7526 VPS41 Zornitza Stark Gene: vps41 has been classified as Green List (High Evidence).
Mendeliome v0.7524 ANKRD17 Zornitza Stark Classified gene: ANKRD17 as Green List (high evidence)
Mendeliome v0.7524 ANKRD17 Zornitza Stark Gene: ankrd17 has been classified as Green List (High Evidence).
Mendeliome v0.7523 JAG2 Zornitza Stark Gene: jag2 has been classified as Green List (High Evidence).
Mendeliome v0.7523 JAG2 Zornitza Stark Classified gene: JAG2 as Green List (high evidence)
Mendeliome v0.7523 JAG2 Zornitza Stark Gene: jag2 has been classified as Green List (High Evidence).
Mendeliome v0.7522 NEPRO Zornitza Stark Gene: nepro has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7522 NEPRO Zornitza Stark Classified gene: NEPRO as Amber List (moderate evidence)
Mendeliome v0.7522 NEPRO Zornitza Stark Gene: nepro has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7521 LRSAM1 Zornitza Stark Gene: lrsam1 has been classified as Green List (High Evidence).
Mendeliome v0.7518 LITAF Zornitza Stark Gene: litaf has been classified as Green List (High Evidence).
Mendeliome v0.7515 SLC3A1 Zornitza Stark Gene: slc3a1 has been classified as Green List (High Evidence).
Mendeliome v0.7512 LSM7 Bryony Thompson Gene: lsm7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7512 LSM7 Bryony Thompson Classified gene: LSM7 as Amber List (moderate evidence)
Mendeliome v0.7512 LSM7 Bryony Thompson Gene: lsm7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7510 PTPN4 Bryony Thompson Gene: ptpn4 has been classified as Green List (High Evidence).
Mendeliome v0.7510 PTPN4 Bryony Thompson Classified gene: PTPN4 as Green List (high evidence)
Mendeliome v0.7510 PTPN4 Bryony Thompson Gene: ptpn4 has been classified as Green List (High Evidence).
Mendeliome v0.7509 PTPN4 Bryony Thompson gene: PTPN4 was added
gene: PTPN4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PTPN4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTPN4 were set to 17953619; 25424712; 30238967; DOI: https://doi.org/10.1016/j.xhgg.2021.100033
Phenotypes for gene: PTPN4 were set to Intellectual disability; developmental delay
Review for gene: PTPN4 was set to GREEN
Added comment: >3 unrelated probands and supporting mouse model
PMID: 17953619 - knockout mouse model has impaired motor learning and cerebellar synaptic plasticity
PMID: 25424712 - twins with a de novo whole gene deletion and a Rett-like neurodevelopmental disorder
PMID: 30238967 - mosaic de novo variant (p.Leu72Ser) identified in a child with developmental delay, autistic features, hypotonia, increased immunoglobulin E and dental problems. Also supporting mouse assays demonstrating loss of protein expression in dendritic spines
DOI: https://doi.org/10.1016/j.xhgg.2021.100033 - missense and truncating variants in six unrelated individuals with varying degrees of intellectual disability or developmental delay. 5 were able to undergo segregation analysis and found to be de novo.
Sources: Literature
Mendeliome v0.7507 POLR3K Zornitza Stark Gene: polr3k has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7507 POLR3K Zornitza Stark Classified gene: POLR3K as Amber List (moderate evidence)
Mendeliome v0.7507 POLR3K Zornitza Stark Gene: polr3k has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7506 POLR3K Zornitza Stark gene: POLR3K was added
gene: POLR3K was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: POLR3K was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3K were set to 30584594; 33659930
Phenotypes for gene: POLR3K were set to Hypomyelinating leukodystrophy-21, MIM#619310
Review for gene: POLR3K was set to AMBER
Added comment: Two individuals from same ethnic background reported with a common homozygous missense variant in this gene, suggestive of founder effect. Some functional evidence, and note other gene family members are linked to similar phenotypes. Neurodegenerative phenotype: global developmental delay apparent from infancy with loss of motor, speech, and cognitive milestones in the first decades of life.
Sources: Expert Review
Mendeliome v0.7505 SAG Zornitza Stark Gene: sag has been classified as Green List (High Evidence).
Mendeliome v0.7502 YWHAG Zornitza Stark Gene: ywhag has been classified as Green List (High Evidence).
Mendeliome v0.7498 OCRL Zornitza Stark Gene: ocrl has been classified as Green List (High Evidence).
Mendeliome v0.7495 APOL1 Zornitza Stark Phenotypes for gene: APOL1 were changed from {Glomerulosclerosis, focal segmental, 4, susceptibility to} 612551 to {Glomerulosclerosis, focal segmental, 4, susceptibility to} 612551; {End-stage renal disease, nondiabetic, susceptibility to} OMIM:612551
Mendeliome v0.7493 PDGFRB Zornitza Stark Phenotypes for gene: PDGFRB were changed from Premature aging syndrome, Penttinen type, 601812 to Basal ganglia calcification, idiopathic, 4, MIM# 615007; Kosaki overgrowth syndrome, MIM# 616592; Myeloproliferative disorder with eosinophilia, MIM# 131440; Myofibromatosis, infantile, 1, MIM# 228550; Premature ageing syndrome, Penttinen type, MIM# 601812
Mendeliome v0.7491 PDGFRB Zornitza Stark reviewed gene: PDGFRB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Basal ganglia calcification, idiopathic, 4, MIM# 615007, Kosaki overgrowth syndrome, MIM# 616592, Myeloproliferative disorder with eosinophilia, MIM# 131440, Myofibromatosis, infantile, 1, MIM# 228550, Premature ageing syndrome, Penttinen type, MIM# 601812; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7491 NEK1 Zornitza Stark Gene: nek1 has been classified as Green List (High Evidence).
Mendeliome v0.7491 NEK1 Zornitza Stark Phenotypes for gene: NEK1 were changed from to Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520; Amyotrophic lateral sclerosis, susceptibility to, 24, MIM# 617892
Mendeliome v0.7488 NEK1 Zornitza Stark reviewed gene: NEK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21211617, 22499340, 25492405, 28123176; Phenotypes: Short-rib thoracic dysplasia 6 with or without polydactyly, MIM# 263520, Amyotrophic lateral sclerosis, susceptibility to, 24, MIM# 617892; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7488 OCRL Eleanor Williams changed review comment from: PMID: 33517444 - Ramadesikan et al 2021 - studied the cellular effect of 7 OCRL1 (OCRL) variants identified in Lowe Syndrome patients in kidney epithelial cells. Differences in cell spreading, ciliogenesis, protein localization and degree of Golgi apparatus fragmentation were observed. The results help provide a framework to explains symptom heterogeneity and may help stratify patients.; to: Genotype/Phenotype information:
PMID: 33517444 - Ramadesikan et al 2021 - studied the cellular effect of 7 OCRL1 (OCRL) variants identified in Lowe Syndrome patients in kidney epithelial cells. Differences in cell spreading, ciliogenesis, protein localization and degree of Golgi apparatus fragmentation were observed. The results help provide a framework to explains symptom heterogeneity and may help stratify patients.
Mendeliome v0.7488 APOL1 Eleanor Williams reviewed gene: APOL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 33517446; Phenotypes: {Focal Segmental Glomerulosclerosis 4, Susceptibility to} OMIM:612551, {End-stage renal disease, nondiabetic, susceptibility to} OMIM:612551; Mode of inheritance: None
Mendeliome v0.7488 PDGFRB Eleanor Williams reviewed gene: PDGFRB: Rating: ; Mode of pathogenicity: None; Publications: 33450762; Phenotypes: Ocular pterygium-digital keloid dysplasia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.7488 NEK1 Eleanor Williams reviewed gene: NEK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33445179; Phenotypes: {Amyotrophic lateral sclerosis, susceptibility to, 24}, OMIM:617892; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.7488 INF2 Zornitza Stark Gene: inf2 has been classified as Green List (High Evidence).
Mendeliome v0.7488 INF2 Zornitza Stark Phenotypes for gene: INF2 were changed from to Charcot-Marie-Tooth disease, dominant intermediate E, MIM# 614455; Glomerulosclerosis, focal segmental, 5, MIM# 613237
Mendeliome v0.7485 INF2 Zornitza Stark reviewed gene: INF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22187985, 30680856, 25943269, 20023659; Phenotypes: Charcot-Marie-Tooth disease, dominant intermediate E, MIM# 614455, Glomerulosclerosis, focal segmental, 5, MIM# 613237; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7485 MED25 Zornitza Stark changed review comment from: Basel-Vanagaite-Smirin-Yosef syndrome is an autosomal recessive multiple congenital anomaly disorder characterized by severely delayed psychomotor development resulting in mental retardation, as well as variable eye, brain, cardiac, and palatal abnormalities.

7 individuals from 4 families reported initially, founder variant p.Tyr39Cys. Over 20 individuals reported since, including other variants.; to: Basel-Vanagaite-Smirin-Yosef syndrome is an autosomal recessive multiple congenital anomaly disorder characterized by severely delayed psychomotor development resulting in intellectual disability, as well as variable eye, brain, cardiac, and palatal abnormalities.

7 individuals from 4 families reported initially, founder variant p.Tyr39Cys. Over 20 individuals reported since, including other variants.
Mendeliome v0.7485 MED25 Zornitza Stark Gene: med25 has been classified as Green List (High Evidence).
Mendeliome v0.7482 HSPB1 Zornitza Stark Gene: hspb1 has been classified as Green List (High Evidence).
Mendeliome v0.7479 HINT1 Zornitza Stark Gene: hint1 has been classified as Green List (High Evidence).
Mendeliome v0.7479 HINT1 Zornitza Stark Phenotypes for gene: HINT1 were changed from to Neuromyotonia and axonal neuropathy, autosomal recessive, MIM# 137200; Gamstorp-Wohlfart syndrome, MONDO:0007646
Mendeliome v0.7476 HINT1 Zornitza Stark reviewed gene: HINT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22961002, 33663550, 33404983, 31848916; Phenotypes: Neuromyotonia and axonal neuropathy, autosomal recessive, MIM# 137200, Gamstorp-Wohlfart syndrome, MONDO:0007646; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7476 GNB4 Zornitza Stark Gene: gnb4 has been classified as Green List (High Evidence).
Mendeliome v0.7473 GJB1 Zornitza Stark Gene: gjb1 has been classified as Green List (High Evidence).
Mendeliome v0.7473 GJB1 Zornitza Stark Phenotypes for gene: GJB1 were changed from to Charcot-Marie-Tooth neuropathy, X-linked dominant, 1, MIM# 302800; MONDO:0010549; reversible posterior leukoencephalopathy
Mendeliome v0.7470 NEPRO Chern Lim gene: NEPRO was added
gene: NEPRO was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NEPRO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEPRO were set to 26633546; 29620724; 31250547
Phenotypes for gene: NEPRO were set to Anauxetic dysplasia 3, MIM618853
Review for gene: NEPRO was set to AMBER
Added comment: PMIDs 26633546, 29620724: 2 families with the same homozygous missense variant, haplotype analysis confirmed the founder nature of the variant.

PMID 31250547: 1 family with homozygous novel missense

All 5 affected individuals have severe short stature, brachydactyly, skin laxity, joint hypermobility, and joint dislocations. They also have short metacarpals, broad middle phalanges, and metaphyseal irregularities. No functional studies.
Sources: Literature
Mendeliome v0.7470 GJB1 Zornitza Stark reviewed gene: GJB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 8266101, 17100997, 17353473, 31842800; Phenotypes: Charcot-Marie-Tooth neuropathy, X-linked dominant, 1, MIM# 302800, MONDO:0010549, reversible posterior leukoencephalopathy; 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 v0.7470 FGD4 Zornitza Stark Gene: fgd4 has been classified as Green List (High Evidence).
Mendeliome v0.7467 COX6A1 Zornitza Stark Gene: cox6a1 has been classified as Green List (High Evidence).
Mendeliome v0.7467 COX6A1 Zornitza Stark Phenotypes for gene: COX6A1 were changed from to Charcot Marie Tooth disease, recessive intermediate D, MIM# 616039; MONDO:0014467
Mendeliome v0.7464 COX6A1 Zornitza Stark reviewed gene: COX6A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25152455, 26302975, 25152455; Phenotypes: Charcot Marie Tooth disease, recessive intermediate D, MIM# 616039, MONDO:0014467; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7464 JAG2 Belinda Chong gene: JAG2 was added
gene: JAG2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: JAG2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: JAG2 were set to PMID: 33861953
Phenotypes for gene: JAG2 were set to muscular dystrophy
Review for gene: JAG2 was set to GREEN
Added comment: Whole-exome sequencing identified 13 families with rare homozygous or compound heterozygous JAG2 variants. Bi-allelic variants include 10 missense variants that disrupt highly conserved amino acids, a nonsense variant, two frameshift variants, an in-frame deletion, and a microdeletion encompassing JAG2. Onset of muscle weakness occurred from infancy to young adulthood. Serum creatine kinase (CK) levels were normal or mildly elevated. Muscle histology was primarily dystrophic. MRI of the lower extremities revealed a distinct, slightly asymmetric pattern of muscle involvement with cores of preserved and affected muscles in quadriceps and tibialis anterior, in some cases resembling patterns seen in POGLUT1-associated muscular dystrophy.
Sources: Literature
Mendeliome v0.7464 VPS41 Kristin Rigbye edited their review of gene: VPS41: Changed phenotypes: Progressive neurodevelopmental disorder with ataxia, hypotonia, dystonia, intellectual disability and speech delay
Mendeliome v0.7464 VPS41 Kristin Rigbye changed review comment from: "Five unrelated families with nine affected individuals, all carrying homozygous variants in VPS41 that we show impact protein function. All affected individuals presented with a progressive neurodevelopmental disorder consisting of cognitive impairment, cerebellar atrophy/hypoplasia, motor dysfunction with ataxia and dystonia, and nystagmus. Zebrafish disease modelling supports the involvement of VPS41 dysfunction in the disorder, indicating lysosomal dysregulation throughout the brain and providing support for cerebellar and microglial abnormalities when vps41 was mutated. This provides the first example of human disease linked to the HOPS-specific subunit VPS41 and suggests the importance of HOPS complex activity for cerebellar function."; to: "Five unrelated families with nine affected individuals, all carrying homozygous variants in VPS41 that we show impact protein function. All affected individuals presented with a progressive neurodevelopmental disorder consisting of cognitive impairment, cerebellar atrophy/hypoplasia, motor dysfunction with ataxia and dystonia, and nystagmus. Zebrafish disease modelling supports the involvement of VPS41 dysfunction in the disorder, indicating lysosomal dysregulation throughout the brain and providing support for cerebellar and microglial abnormalities when vps41 was mutated. This provides the first example of human disease linked to the HOPS-specific subunit VPS41 and suggests the importance of HOPS complex activity for cerebellar function."

"Affected individuals were born after uneventful pregnancies and presented in most cases early in life with developmental delay. Various degrees of ataxia, hypotonia, and dystonia were present in all affected individuals, preventing independent ambulation. Likewise, nystagmus was commonly described. In addition, all affected individuals displayed intellectual disability and speech delay. Two siblings further presented with therapy-resistant epilepsy. No major dysmorphic features were found. In two individuals, retinal pigment alterations were noticed. Brain MRI revealed mild cerebellar atrophy and vermian atrophy without other major structural abnormalities in most affected individuals while in one case (Subject 9) bilateral hyperintensities at the nucleus caudatus area were noted. No hearing or vision problems were noted and in cases where nerve conduction studies were performed, these were normal. Transmission electron microscopy (TEM) on peripheral blood lymphocytes from Subject 2 and lymphoblastoid cells from Subject 3 revealed more multilayered vesicles compared to control cells."
Mendeliome v0.7464 SIN3B Elena Savva gene: SIN3B was added
gene: SIN3B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SIN3B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SIN3B were set to PMID: 33811806
Phenotypes for gene: SIN3B were set to Syndromic intellectual disability/autism spectrum disorder
Review for gene: SIN3B was set to GREEN
Added comment: PMID: 33811806
- 9 affected patients, all de novo (2 PTCs, 2 missense, multigenic CNVs)
- syndrome hallmarked by intellectual disability, developmental delay, and dysmorphic facial features with variably penetrant ASD, congenital malformations, corpus callosum defects, and impaired growth.
- CNVs encompassing the gene have been found
Sources: Literature
Mendeliome v0.7464 DPYSL5 Michelle Torres gene: DPYSL5 was added
gene: DPYSL5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DPYSL5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DPYSL5 were set to 33894126
Phenotypes for gene: DPYSL5 were set to Neurodevelopmental disorder with corpus callosum agenesis and cerebellar abnormalities
Review for gene: DPYSL5 was set to GREEN
Added comment: Nine individuals with brain malformations, including corpus callosum agenesis and/or posterior fossa abnormalities, associated with variable degrees of intellectual disability. The recurrent de novo p.Glu41Lys was found in eight unrelated patients, and a p.Gly47Arg variant was identified in one individual from the first family reported with Ritscher-Schinzel syndrome. Both impaired DPYSL5 function on dendritic outgrowth regulation by preventing the formation of the ternary complex with MAP2 and βIII-tubulin, ultimately leading to abnormal brain development
Sources: Literature
Mendeliome v0.7464 VPS41 Kristin Rigbye reviewed gene: VPS41: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33764426; Phenotypes: Progressive neurodevelopmental disorder; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7464 CDC40 Zornitza Stark Phenotypes for gene: CDC40 were changed from Pontocerebellar hypoplasia; microcephaly; seizures to Pontocerebellar hypoplasia, type 15, MIM# 619302; microcephaly; seizures
Mendeliome v0.7463 CDC40 Zornitza Stark edited their review of gene: CDC40: Changed phenotypes: Pontocerebellar hypoplasia, type 15, MIM# 619302, microcephaly, seizures
Mendeliome v0.7463 PPIL1 Zornitza Stark Phenotypes for gene: PPIL1 were changed from Pontocerebellar hypoplasia; microcephaly; seizures to Pontocerebellar hypoplasia, type 14, MIM# 619301; microcephaly; seizures
Mendeliome v0.7462 PPIL1 Zornitza Stark edited their review of gene: PPIL1: Changed phenotypes: Pontocerebellar hypoplasia, type 14, MIM# 619301, microcephaly, seizures
Mendeliome v0.7462 BICD2 Zornitza Stark Gene: bicd2 has been classified as Green List (High Evidence).
Mendeliome v0.7459 SMARCA2 Zornitza Stark Phenotypes for gene: SMARCA2 were changed from Nicolaides-Baraitser syndrome, MIM #601358; Blepharophimosis-intellectual disability syndrome to Nicolaides-Baraitser syndrome, MIM #601358; Blepharophimosis-intellectual disability syndrome, MIM#619293
Mendeliome v0.7457 KCNQ5 Zornitza Stark Gene: kcnq5 has been classified as Green List (High Evidence).
Mendeliome v0.7454 KCNK9 Zornitza Stark Gene: kcnk9 has been classified as Green List (High Evidence).
Mendeliome v0.7451 ATL1 Zornitza Stark Gene: atl1 has been classified as Green List (High Evidence).
Mendeliome v0.7447 COQ2 Zornitza Stark Gene: coq2 has been classified as Green List (High Evidence).
Mendeliome v0.7444 COA6 Zornitza Stark Gene: coa6 has been classified as Green List (High Evidence).
Mendeliome v0.7441 CARS2 Zornitza Stark Gene: cars2 has been classified as Green List (High Evidence).
Mendeliome v0.7438 PPP2R5C Zornitza Stark Gene: ppp2r5c has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7438 PPP2R5C Sue White Classified gene: PPP2R5C as Amber List (moderate evidence)
Mendeliome v0.7438 PPP2R5C Sue White Gene: ppp2r5c has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7437 PPP2R5C Sue White gene: PPP2R5C was added
gene: PPP2R5C was added to Mendeliome. Sources: Research
Mode of inheritance for gene: PPP2R5C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PPP2R5C were set to macrocephaly; intellectual disability
Penetrance for gene: PPP2R5C were set to Complete
Review for gene: PPP2R5C was set to AMBER
Added comment: Emerging unpublished evidence of monoallelic missense variants causing intellectual disability and macrocephaly
Sources: Research
Mendeliome v0.7436 SLX4 Zornitza Stark Gene: slx4 has been classified as Green List (High Evidence).
Mendeliome v0.7432 SGCE Zornitza Stark Gene: sgce has been classified as Green List (High Evidence).
Mendeliome v0.7429 PRKRA Zornitza Stark Gene: prkra has been classified as Green List (High Evidence).
Mendeliome v0.7426 KMT2B Zornitza Stark Gene: kmt2b has been classified as Green List (High Evidence).
Mendeliome v0.7423 CIZ1 Zornitza Stark Gene: ciz1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7420 CIZ1 Zornitza Stark Classified gene: CIZ1 as Amber List (moderate evidence)
Mendeliome v0.7420 CIZ1 Zornitza Stark Gene: ciz1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7419 NPAS2 Zornitza Stark Gene: npas2 has been classified as Red List (Low Evidence).
Mendeliome v0.7416 NPAS2 Zornitza Stark Classified gene: NPAS2 as Red List (low evidence)
Mendeliome v0.7416 NPAS2 Zornitza Stark Gene: npas2 has been classified as Red List (Low Evidence).
Mendeliome v0.7415 NPAS2 Alison Compton changed review comment from: The brothers with NOA from consanguineous Turkish family, homozygous NM_002518.3(NPAS2) c.1363C>G; p.(Pro455Ala) variant identified. Heterozygous in mother, and fertile brother and sister. Not present in 1000 Genomes, EVS or gnomAD. Predicted to be “benign” by Polyphen2, and "neutral" by both SIFT and Mutation taster. Not predicted to in a functional domain. Not listed as a disease-gene in OMIM, no other 'pathogenic' or 'likely pathogenic' variants listed in ClinVar. Paper did not include any functional work.; to: Three brothers with NOA from consanguineous Turkish family, homozygous NM_002518.3(NPAS2) c.1363C>G; p.(Pro455Ala) variant identified. Found to be heterozygous in mother, and fertile brother and sister. Not present in 1000 Genomes, EVS or gnomAD. Predicted to be “benign” by Polyphen2, and "neutral" by both SIFT and Mutation taster. Not predicted to be within a functional domain. Gene not listed as a disease-gene in OMIM, no other 'pathogenic' or 'likely pathogenic' variants listed in ClinVar. Publication did not include any functional work as support.
Mendeliome v0.7415 PNKD Zornitza Stark Gene: pnkd has been classified as Green List (High Evidence).
Mendeliome v0.7415 PNKD Zornitza Stark Phenotypes for gene: PNKD were changed from to Paroxysmal nonkinesigenic dyskinesia 1, MIM# 118800; MONDO:0007326
Mendeliome v0.7412 PNKD Zornitza Stark reviewed gene: PNKD: Rating: GREEN; Mode of pathogenicity: None; Publications: 15262732, 15496428, 15824259, 19124534, 21487022; Phenotypes: Paroxysmal nonkinesigenic dyskinesia 1, MIM# 118800, MONDO:0007326; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7412 MECR Zornitza Stark Gene: mecr has been classified as Green List (High Evidence).
Mendeliome v0.7409 HPCA Zornitza Stark Gene: hpca has been classified as Green List (High Evidence).
Mendeliome v0.7409 HPCA Zornitza Stark Phenotypes for gene: HPCA were changed from to Dystonia 2, torsion, autosomal recessive, MIM# 224500; MONDO:0009141
Mendeliome v0.7406 HPCA Zornitza Stark reviewed gene: HPCA: Rating: GREEN; Mode of pathogenicity: None; Publications: 25799108, 30991467, 30145809; Phenotypes: Dystonia 2, torsion, autosomal recessive, MIM# 224500, MONDO:0009141; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7406 GNAL Zornitza Stark Gene: gnal has been classified as Green List (High Evidence).
Mendeliome v0.7403 ADCY5 Zornitza Stark Gene: adcy5 has been classified as Green List (High Evidence).
Mendeliome v0.7403 ADCY5 Zornitza Stark Phenotypes for gene: ADCY5 were changed from to Dyskinesia, familial, with facial myokymia, MIM# 606703; MONDO:0011707
Mendeliome v0.7400 ADCY5 Zornitza Stark reviewed gene: ADCY5: Rating: GREEN; Mode of pathogenicity: None; Publications: 22782511, 24700542, 33051786, 32647899, 33704598; Phenotypes: Dyskinesia, familial, with facial myokymia, MIM# 606703, MONDO:0011707; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7400 XPNPEP3 Zornitza Stark Classified gene: XPNPEP3 as Green List (high evidence)
Mendeliome v0.7400 XPNPEP3 Zornitza Stark Gene: xpnpep3 has been classified as Green List (High Evidence).
Mendeliome v0.7399 THAP1 Zornitza Stark Gene: thap1 has been classified as Green List (High Evidence).
Mendeliome v0.7399 THAP1 Zornitza Stark Phenotypes for gene: THAP1 were changed from to Dystonia 6, torsion, 602629; MONDO:0011264
Mendeliome v0.7396 THAP1 Zornitza Stark reviewed gene: THAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21793105, 22377579; Phenotypes: Dystonia 6, torsion, 602629, MONDO:0011264; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7395 CHST11 Zornitza Stark Gene: chst11 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7395 CHST11 Zornitza Stark Classified gene: CHST11 as Amber List (moderate evidence)
Mendeliome v0.7395 CHST11 Zornitza Stark Gene: chst11 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7394 CHST11 Zornitza Stark gene: CHST11 was added
gene: CHST11 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: CHST11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHST11 were set to 26436107; 29514872
Phenotypes for gene: CHST11 were set to Osteochondrodysplasia, brachydactyly, and overlapping malformed digits, MIM# 618167
Review for gene: CHST11 was set to AMBER
Added comment: Osteochondrodysplasia, brachydactyly, and overlapping malformed digits (OCBMD) is characterized by bilateral symmetric skeletal defects that primarily affect the limbs. Affected individuals have mild short stature due to shortening of the lower leg bones, as well as hand and foot malformations, predominantly brachydactyly and overlapping digits. Other skeletal defects include scoliosis, dislocated patellae and fibulae, and pectus excavatum.

Two unrelated families reported, note one had a homozygous deletion. One family had 10 affected individuals.
Sources: Expert Review
Mendeliome v0.7392 PSMB8 Zornitza Stark Gene: psmb8 has been classified as Green List (High Evidence).
Mendeliome v0.7388 EFEMP1 Zornitza Stark edited their review of gene: EFEMP1: Added comment: PMID 33807164: third unrelated family reported with CTD phenotype, single affected individual with bi-alllelic LoF variant, cutis laxa and multiple herniations.; Changed publications: 32006683, 31792352, 33807164
Mendeliome v0.7388 PPARG Zornitza Stark Gene: pparg has been classified as Green List (High Evidence).
Mendeliome v0.7385 POLD1 Zornitza Stark Gene: pold1 has been classified as Green List (High Evidence).
Mendeliome v0.7385 POLD1 Zornitza Stark Phenotypes for gene: POLD1 were changed from to Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, MIM# 615381; MONDO:0014157
Mendeliome v0.7382 POLD1 Zornitza Stark reviewed gene: POLD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23770608, 33618333, 33369179, 32826474, 30023403, 29199204, 28791128; Phenotypes: Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, MIM# 615381, MONDO:0014157; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7382 PLIN1 Zornitza Stark Gene: plin1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7379 PLIN1 Zornitza Stark Classified gene: PLIN1 as Amber List (moderate evidence)
Mendeliome v0.7379 PLIN1 Zornitza Stark Gene: plin1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7378 PCYT1A Zornitza Stark Gene: pcyt1a has been classified as Green List (High Evidence).
Mendeliome v0.7378 PCYT1A Zornitza Stark Phenotypes for gene: PCYT1A were changed from to Spondylometaphyseal dysplasia with cone-rod dystrophy, MIM# 608940; Congenital lipodystrophy
Mendeliome v0.7375 PCYT1A Zornitza Stark reviewed gene: PCYT1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 24387990, 24387991, 24889630; Phenotypes: Spondylometaphyseal dysplasia with cone-rod dystrophy, MIM# 608940, Congenital lipodystrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7374 KCNJ6 Zornitza Stark Gene: kcnj6 has been classified as Green List (High Evidence).
Mendeliome v0.7371 EIF4G1 Zornitza Stark Gene: eif4g1 has been classified as Red List (Low Evidence).
Mendeliome v0.7368 EIF4G1 Zornitza Stark Classified gene: EIF4G1 as Red List (low evidence)
Mendeliome v0.7368 EIF4G1 Zornitza Stark Gene: eif4g1 has been classified as Red List (Low Evidence).
Mendeliome v0.7367 CIDEC Zornitza Stark Gene: cidec has been classified as Red List (Low Evidence).
Mendeliome v0.7364 CIDEC Zornitza Stark Classified gene: CIDEC as Red List (low evidence)
Mendeliome v0.7364 CIDEC Zornitza Stark Gene: cidec has been classified as Red List (Low Evidence).
Mendeliome v0.7363 LIG3 Zornitza Stark Gene: lig3 has been classified as Green List (High Evidence).
Mendeliome v0.7363 LIG3 Zornitza Stark Classified gene: LIG3 as Green List (high evidence)
Mendeliome v0.7363 LIG3 Zornitza Stark Gene: lig3 has been classified as Green List (High Evidence).
Mendeliome v0.7361 HNRNPDL Bryony Thompson Gene: hnrnpdl has been classified as Green List (High Evidence).
Mendeliome v0.7361 HNRNPDL Bryony Thompson Classified gene: HNRNPDL as Green List (high evidence)
Mendeliome v0.7361 HNRNPDL Bryony Thompson Gene: hnrnpdl has been classified as Green List (High Evidence).
Mendeliome v0.7359 JMJD1C Zornitza Stark Gene: jmjd1c has been classified as Green List (High Evidence).
Mendeliome v0.7359 JMJD1C Zornitza Stark Classified gene: JMJD1C as Green List (high evidence)
Mendeliome v0.7359 JMJD1C Zornitza Stark Gene: jmjd1c has been classified as Green List (High Evidence).
Mendeliome v0.7357 CAVIN1 Zornitza Stark Gene: cavin1 has been classified as Green List (High Evidence).
Mendeliome v0.7354 CAV1 Zornitza Stark Gene: cav1 has been classified as Green List (High Evidence).
Mendeliome v0.7354 CAV1 Zornitza Stark Phenotypes for gene: CAV1 were changed from to Lipodystrophy, familial partial, type 7, autosomal dominant MIM# 606721; Lipodystrophy, congenital generalized, type 3, autosomal recessive, MIM# 612526
Mendeliome v0.7351 CAV1 Zornitza Stark reviewed gene: CAV1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18237401, 25898808, 11739396, 18211975, 27717241, 26176221, 33836561, 33776068, 32502478, 22474227, 28768485; Phenotypes: Lipodystrophy, familial partial, type 7, autosomal dominant MIM# 606721, Lipodystrophy, congenital generalized, type 3, autosomal recessive, MIM# 612526; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7351 AFF4 Zornitza Stark Gene: aff4 has been classified as Green List (High Evidence).
Mendeliome v0.7348 DNAJB13 Zornitza Stark Classified gene: DNAJB13 as Green List (high evidence)
Mendeliome v0.7348 DNAJB13 Zornitza Stark Gene: dnajb13 has been classified as Green List (High Evidence).
Mendeliome v0.7347 GCGR Zornitza Stark Gene: gcgr has been classified as Green List (High Evidence).
Mendeliome v0.7347 GCGR Zornitza Stark Classified gene: GCGR as Green List (high evidence)
Mendeliome v0.7347 GCGR Zornitza Stark Gene: gcgr has been classified as Green List (High Evidence).
Mendeliome v0.7346 GCGR Zornitza Stark gene: GCGR was added
gene: GCGR was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: GCGR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GCGR were set to 19657311; 25695890; 27933176; 30032256; 30294546
Phenotypes for gene: GCGR were set to Mahvash disease, MIM# 619290
Review for gene: GCGR was set to GREEN
Added comment: Mahvash disease (MVAH) is caused by inactivating mutations in the glucagon receptor, leading to alpha-cell hyperplasia of the pancreas, hyperglucagonaemia without glucagonoma syndrome, and occasional hypoglycaemia. The disease may lead to glucagonomas and/or primitive neuroectodermal tumours.

More than 5 unrelated families reported.
Sources: Expert list
Mendeliome v0.7344 MED27 Zornitza Stark Phenotypes for gene: MED27 were changed from Intellectual disability; cerebellar hypoplasia; dystonia to Neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia, MIM# 619286
Mendeliome v0.7343 MED27 Zornitza Stark reviewed gene: MED27: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia, MIM# 619286; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7343 ABCB6 Zornitza Stark Gene: abcb6 has been classified as Green List (High Evidence).
Mendeliome v0.7343 ABCB6 Zornitza Stark Phenotypes for gene: ABCB6 were changed from to Pseudohyperkalemia, familial, 2, due to red cell leak, MIM# 609153; Microphthalmia, isolated, with coloboma 7, MIM# 614497; Dyschromatosis universalis hereditaria 3, MIM# 615402
Mendeliome v0.7340 ABCB6 Zornitza Stark reviewed gene: ABCB6: Rating: GREEN; Mode of pathogenicity: None; Publications: 23180570; Phenotypes: Pseudohyperkalemia, familial, 2, due to red cell leak, MIM# 609153, Microphthalmia, isolated, with coloboma 7, MIM# 614497, Dyschromatosis universalis hereditaria 3, MIM# 615402; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7340 ABCA1 Zornitza Stark Gene: abca1 has been classified as Green List (High Evidence).
Mendeliome v0.7340 PRDM15 Zornitza Stark Gene: prdm15 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7340 PRDM15 Zornitza Stark Classified gene: PRDM15 as Amber List (moderate evidence)
Mendeliome v0.7340 PRDM15 Zornitza Stark Gene: prdm15 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7339 PRDM15 Zornitza Stark gene: PRDM15 was added
gene: PRDM15 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRDM15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRDM15 were set to 31950080
Phenotypes for gene: PRDM15 were set to Steroid resistant nephrotic syndrome; Holoprosencephaly
Review for gene: PRDM15 was set to AMBER
Added comment: Four consanguineous families reported with same homozygous variant, C844Y, shown to be LoF. Syndromic SRNS including HPE, brain malformations, polydactyly, congenital heart disease. Mouse model, extensive functional data focused on the brain phenotype. Two additional homozygous missense identified with isolated SRNS.
Sources: Literature
Mendeliome v0.7338 ZIC2 Zornitza Stark Gene: zic2 has been classified as Green List (High Evidence).
Mendeliome v0.7335 TGIF1 Zornitza Stark Gene: tgif1 has been classified as Green List (High Evidence).
Mendeliome v0.7332 SIX3 Zornitza Stark Marked gene: SIX3 as ready
Mendeliome v0.7332 SIX3 Zornitza Stark Gene: six3 has been classified as Green List (High Evidence).
Mendeliome v0.7332 SIX3 Zornitza Stark Phenotypes for gene: SIX3 were changed from to Holoprosencephaly 2, MIM# 157170; MONDO:0007999
Mendeliome v0.7331 SIX3 Zornitza Stark Publications for gene: SIX3 were set to
Mendeliome v0.7330 SIX3 Zornitza Stark Mode of inheritance for gene: SIX3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7329 SIX3 Zornitza Stark reviewed gene: SIX3: Rating: GREEN; Mode of pathogenicity: None; Publications: 10369266, 16323008, 19346217; Phenotypes: Holoprosencephaly 2, MIM# 157170, MONDO:0007999; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.7329 DISP1 Zornitza Stark Gene: disp1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7326 DISP1 Zornitza Stark Classified gene: DISP1 as Amber List (moderate evidence)
Mendeliome v0.7326 DISP1 Zornitza Stark Gene: disp1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7325 TBX3 Zornitza Stark Gene: tbx3 has been classified as Green List (High Evidence).
Mendeliome v0.7322 SALL1 Zornitza Stark Gene: sall1 has been classified as Green List (High Evidence).
Mendeliome v0.7317 HELLS Zornitza Stark Gene: hells has been classified as Green List (High Evidence).
Mendeliome v0.7314 ZBTB24 Zornitza Stark Gene: zbtb24 has been classified as Green List (High Evidence).
Mendeliome v0.7311 CDCA7 Zornitza Stark Gene: cdca7 has been classified as Green List (High Evidence).
Mendeliome v0.7307 XPC Zornitza Stark Gene: xpc has been classified as Green List (High Evidence).
Mendeliome v0.7304 XPA Zornitza Stark Gene: xpa has been classified as Green List (High Evidence).
Mendeliome v0.7301 RMI2 Zornitza Stark Gene: rmi2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7298 RMI2 Zornitza Stark Classified gene: RMI2 as Amber List (moderate evidence)
Mendeliome v0.7298 RMI2 Zornitza Stark Gene: rmi2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7297 RAD51 Zornitza Stark Gene: rad51 has been classified as Green List (High Evidence).
Mendeliome v0.7294 POLH Zornitza Stark Gene: polh has been classified as Green List (High Evidence).
Mendeliome v0.7289 MRE11 Zornitza Stark Gene: mre11 has been classified as Green List (High Evidence).
Mendeliome v0.7289 MRE11 Zornitza Stark Phenotypes for gene: MRE11 were changed from to Ataxia-telangiectasia-like disorder 1, MIM# 604391; MONDO:0024557
Mendeliome v0.7286 MRE11 Zornitza Stark reviewed gene: MRE11: Rating: GREEN; Mode of pathogenicity: None; Publications: 10612394, 11371508, 15269180, 22863007, 24332946, 21227757; Phenotypes: Ataxia-telangiectasia-like disorder 1, MIM# 604391, MONDO:0024557; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7286 MPLKIP Zornitza Stark Gene: mplkip has been classified as Green List (High Evidence).
Mendeliome v0.7286 MPLKIP Zornitza Stark Phenotypes for gene: MPLKIP were changed from to Trichothiodystrophy 4, nonphotosensitive, MIM# 234050; MONDO:0021013
Mendeliome v0.7283 MPLKIP Zornitza Stark reviewed gene: MPLKIP: Rating: GREEN; Mode of pathogenicity: None; Publications: 15645389, 16977596; Phenotypes: Trichothiodystrophy 4, nonphotosensitive, MIM# 234050, MONDO:0021013; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7283 PIK3CD Zornitza Stark Gene: pik3cd has been classified as Green List (High Evidence).
Mendeliome v0.7283 PIK3CD Zornitza Stark Phenotypes for gene: PIK3CD were changed from to Immunodeficiency 14B, autosomal recessive, MIM# 619281; Immunodeficiency 14A, autosomal dominant, MIM# 615513
Mendeliome v0.7280 PIK3CD Zornitza Stark reviewed gene: PIK3CD: Rating: GREEN; Mode of pathogenicity: None; Publications: 30040974, 30336224, 29180244, 16984281, 24136356, 24165795, 24610295; Phenotypes: Immunodeficiency 14B, autosomal recessive, MIM# 619281, Immunodeficiency 14A, autosomal dominant, MIM# 615513; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7280 GTF2H5 Zornitza Stark Gene: gtf2h5 has been classified as Green List (High Evidence).
Mendeliome v0.7280 GTF2H5 Zornitza Stark Phenotypes for gene: GTF2H5 were changed from to Trichothiodystrophy 3, photosensitive, MIM# 616395; MONDO:0014619
Mendeliome v0.7277 GTF2H5 Zornitza Stark reviewed gene: GTF2H5: Rating: GREEN; Mode of pathogenicity: None; Publications: 15220921, 30359777, 24986372; Phenotypes: Trichothiodystrophy 3, photosensitive, MIM# 616395, MONDO:0014619; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7277 GTF2E2 Zornitza Stark Gene: gtf2e2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7277 GTF2E2 Zornitza Stark Phenotypes for gene: GTF2E2 were changed from to Trichothiodystrophy 6, nonphotosensitive, MIM# 616943; MONDO:0014841
Mendeliome v0.7274 GTF2E2 Zornitza Stark Classified gene: GTF2E2 as Amber List (moderate evidence)
Mendeliome v0.7274 GTF2E2 Zornitza Stark Gene: gtf2e2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7273 GTF2E2 Zornitza Stark reviewed gene: GTF2E2: Rating: AMBER; Mode of pathogenicity: None; Publications: 26996949; Phenotypes: Trichothiodystrophy 6, nonphotosensitive, MIM# 616943, MONDO:0014841; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7273 FANCL Zornitza Stark Gene: fancl has been classified as Green List (High Evidence).
Mendeliome v0.7270 FANCI Zornitza Stark Gene: fanci has been classified as Green List (High Evidence).
Mendeliome v0.7267 FANCG Zornitza Stark Gene: fancg has been classified as Green List (High Evidence).
Mendeliome v0.7264 FANCF Zornitza Stark Gene: fancf has been classified as Green List (High Evidence).
Mendeliome v0.7261 FANCE Zornitza Stark Gene: fance has been classified as Green List (High Evidence).
Mendeliome v0.7258 MDM2 Zornitza Stark Gene: mdm2 has been classified as Red List (Low Evidence).
Mendeliome v0.7255 MDM2 Zornitza Stark Classified gene: MDM2 as Red List (low evidence)
Mendeliome v0.7255 MDM2 Zornitza Stark Gene: mdm2 has been classified as Red List (Low Evidence).
Mendeliome v0.7252 NDUFB11 Zornitza Stark Gene: ndufb11 has been classified as Green List (High Evidence).
Mendeliome v0.7249 NDUFB11 Kristin Rigbye changed review comment from: Variable syndromic features have been observed in affected individuals, however anaemia and cardiomyopathy appear to be consistent features in males and females, respectively (PMID: 28050600, PMID: 30423443, PMID: 27488349).

Affected females have previously been reported with inherited pathogenic variants from their unaffected mothers. It has been suggested that this may be due to patterns of somatic X-chromosome inactivation, mosaicism or additional genetic or external factors (PMID: 28050600).

Affected females have been reported with null alleles, whereas affected males have only been identified with missense variants or a recurrent single residue in-frame deletion, suggesting that some residual enzyme activity is required for males to be viable, whereas complete loss of function variants may be lethal when hemizygous (PMID: 30423443).
Note: female carriers of missense variants have not been reported as clinically affected.

Western blots from cells of male patients with the recurrent F93del variant showed reduced protein levels, and recombinant cells demonstrated a proliferation defect, consistent with the anaemia phenotype (PMID: 27488349).; to: Variable syndromic features have been observed in affected individuals, however anaemia and cardiomyopathy appear to be consistent features in males and females, respectively (PMID: 28050600, PMID: 30423443, PMID: 27488349).

It has been suggested that heterozygous females do not display the severe phenotype associated with mitochondrial complex 1 deficiency due to highly skewed XCI favouring expression of the wild type allele, whereas these null variants result in a severe lethal disorder in hemizygous males (PMID: 25772934).

Affected females have previously been reported with inherited pathogenic variants from their unaffected mothers. It has been suggested that this may be due to patterns of somatic X-chromosome inactivation, mosaicism or additional genetic or external factors (PMID: 28050600).

Affected females have been reported with null alleles, whereas affected males have only been identified with missense variants or a recurrent single residue in-frame deletion, suggesting that some residual enzyme activity is required for males to be viable, whereas complete loss of function variants may be lethal when hemizygous (PMID: 30423443).
Note: female carriers of missense variants have not been reported as clinically affected.

Western blots from cells of male patients with the recurrent F93del variant showed reduced protein levels, and recombinant cells demonstrated a proliferation defect, consistent with the anaemia phenotype (PMID: 27488349).
Mendeliome v0.7249 FANCC Zornitza Stark Gene: fancc has been classified as Green List (High Evidence).
Mendeliome v0.7243 MFAP5 Zornitza Stark Classified gene: MFAP5 as Amber List (moderate evidence)
Mendeliome v0.7243 MFAP5 Zornitza Stark Gene: mfap5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7242 FANCB Zornitza Stark Gene: fancb has been classified as Green List (High Evidence).
Mendeliome v0.7238 FANCA Zornitza Stark Gene: fanca has been classified as Green List (High Evidence).
Mendeliome v0.7235 ERCC8 Zornitza Stark Gene: ercc8 has been classified as Green List (High Evidence).
Mendeliome v0.7235 ERCC8 Zornitza Stark Phenotypes for gene: ERCC8 were changed from to Cockayne syndrome, type A, MIM# 216400; MONDO:0019569; UV-sensitive syndrome 2, MIM# 614621; MONDO:0013829
Mendeliome v0.7232 ERCC8 Zornitza Stark reviewed gene: ERCC8: Rating: GREEN; Mode of pathogenicity: None; Publications: 7664335, 19894250; Phenotypes: Cockayne syndrome, type A, MIM# 216400, MONDO:0019569, UV-sensitive syndrome 2, MIM# 614621, MONDO:0013829; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7231 GP1BA Zornitza Stark Gene: gp1ba has been classified as Green List (High Evidence).
Mendeliome v0.7231 GP1BA Zornitza Stark Phenotypes for gene: GP1BA were changed from to Bernard-Soulier syndrome, type A1 (recessive), (MIM#231200), AR (AR BSS); von Willebrand disease, platelet-type, (MIM#177820), AD (VWD); MONDO:0008332; Bernard-Soulier syndrome, type A2 (dominant), (MIM#153670) (AD BSS); MONDO:0007930
Mendeliome v0.7229 GP1BA Zornitza Stark reviewed gene: GP1BA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Bernard-Soulier syndrome, type A1 (recessive), (MIM#231200), AR (AR BSS), von Willebrand disease, platelet-type, (MIM#177820), AD (VWD), MONDO:0008332, Bernard-Soulier syndrome, type A2 (dominant), (MIM#153670) (AD BSS), MONDO:0007930; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7229 GP1BA Ain Roesley reviewed gene: GP1BA: Rating: GREEN; Mode of pathogenicity: None; Publications: 24934643; Phenotypes: Bernard-Soulier syndrome, type A1 (recessive), (MIM#231200), AR (AR BSS), von Willebrand disease, platelet-type, (MIM#177820), AD (VWD), Bernard-Soulier syndrome, type A2 (dominant), (MIM#153670) (AD BSS); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7227 ERCC4 Zornitza Stark Gene: ercc4 has been classified as Green List (High Evidence).
Mendeliome v0.7224 ERCC3 Zornitza Stark Gene: ercc3 has been classified as Green List (High Evidence).
Mendeliome v0.7224 ERCC3 Zornitza Stark Phenotypes for gene: ERCC3 were changed from to Trichothiodystrophy 2, photosensitive, MIM# 616390; Xeroderma pigmentosum, group B 61, MIM#0651
Mendeliome v0.7221 ERCC3 Zornitza Stark reviewed gene: ERCC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 2167179, 10447254, 16947863, 9012405, 32557569, 27004399; Phenotypes: Trichothiodystrophy 2, photosensitive, MIM# 616390, Xeroderma pigmentosum, group B 61, MIM#0651; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7221 DAAM2 Zornitza Stark Phenotypes for gene: DAAM2 were changed from steroid-resistant nephrotic syndrome (SRNS) to Nephrotic syndrome, type 24, MIM# 619263; steroid-resistant nephrotic syndrome (SRNS)
Mendeliome v0.7220 DAAM2 Zornitza Stark edited their review of gene: DAAM2: Changed phenotypes: Nephrotic syndrome, type 24, MIM# 619263, Steroid-resistant nephrotic syndrome (SRNS)
Mendeliome v0.7219 SDHA Zornitza Stark Gene: sdha has been classified as Green List (High Evidence).
Mendeliome v0.7217 SLC19A1 Zornitza Stark Gene: slc19a1 has been classified as Red List (Low Evidence).
Mendeliome v0.7217 SLC19A1 Zornitza Stark gene: SLC19A1 was added
gene: SLC19A1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SLC19A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC19A1 were set to 32276275
Phenotypes for gene: SLC19A1 were set to Megaloblastic anemia, folate-responsive, MIM# 601775
Review for gene: SLC19A1 was set to RED
Added comment: Single individual reported with in-frame deletion, some functional data.
Sources: Expert list
Mendeliome v0.7216 ERCC2 Zornitza Stark Gene: ercc2 has been classified as Green List (High Evidence).
Mendeliome v0.7216 ERCC2 Zornitza Stark Phenotypes for gene: ERCC2 were changed from to Cerebrooculofacioskeletal syndrome 2, MIM# 610756; MONDO:0012553; Trichothiodystrophy 1, photosensitive, MIM# 601675; MONDO:0011125; Xeroderma pigmentosum, group D, MIM# 278730; MONDO:0010212
Mendeliome v0.7213 ERCC2 Zornitza Stark reviewed gene: ERCC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 7849702, 9758621, 11443545, 33733458; Phenotypes: Cerebrooculofacioskeletal syndrome 2, MIM# 610756, MONDO:0012553, Trichothiodystrophy 1, photosensitive, MIM# 601675, MONDO:0011125, Xeroderma pigmentosum, group D, MIM# 278730, MONDO:0010212; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7212 ERCC1 Zornitza Stark changed review comment from: Three unrelated families reported, variable severity reported from a Cockayne phenotype with congenital onset and early mortality, through to adolescent presentation with short stature, photosensitivity and progressive liver and renal dysfunction.; to: More than three unrelated families reported, variable severity reported from a Cockayne phenotype with congenital onset and early mortality, through to adolescent presentation with short stature, photosensitivity and progressive liver and renal dysfunction.
Mendeliome v0.7210 NDUFA8 Zornitza Stark Classified gene: NDUFA8 as Amber List (moderate evidence)
Mendeliome v0.7210 NDUFA8 Zornitza Stark Gene: ndufa8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7209 NDUFA8 Zornitza Stark commented on gene: NDUFA8: Second family reported with pair of affected siblings and homozygous missense variant, some functional data.
Mendeliome v0.7206 KCNH1 Zornitza Stark Gene: kcnh1 has been classified as Green List (High Evidence).
Mendeliome v0.7203 GREB1L Zornitza Stark Phenotypes for gene: GREB1L were changed from Renal hypodysplasia/aplasia 3, OMIM# 617805 to Renal hypodysplasia/aplasia 3, OMIM# 617805; Deafness, autosomal dominant 80, MIM# 619274
Mendeliome v0.7201 GREB1L Zornitza Stark edited their review of gene: GREB1L: Added comment: DFNA80 is characterized by nonsyndromic congenital deafness associated with absent or malformed cochleae and eighth cranial nerves. Four unrelated families reported, no comment on a renal phenotype. Note variants in this gene are also associated with renal agenesis.; Changed publications: 29100091, 29955957, 32585897; Changed phenotypes: Renal hypodysplasia/aplasia 3, OMIM# 617805, Deafness, autosomal dominant 80, MIM# 619274
Mendeliome v0.7200 EMC10 Zornitza Stark Classified gene: EMC10 as Green List (high evidence)
Mendeliome v0.7200 EMC10 Zornitza Stark Gene: emc10 has been classified as Green List (High Evidence).
Mendeliome v0.7199 ITGB3 Zornitza Stark Gene: itgb3 has been classified as Green List (High Evidence).
Mendeliome v0.7196 KRT8 Seb Lunke reviewed gene: KRT8: Rating: RED; Mode of pathogenicity: None; Publications: 15235035, 11372009, 12724528; Phenotypes: CIRRHOSIS, FAMILIAL, MIM #215600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.7194 UNC50 Zornitza Stark Gene: unc50 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7194 UNC50 Zornitza Stark Classified gene: UNC50 as Amber List (moderate evidence)
Mendeliome v0.7194 UNC50 Zornitza Stark Gene: unc50 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7192 ADCY6 Zornitza Stark changed review comment from: Laquerriere et al. (2014): 2 sibs from a consanguineous family with an axoglial form of lethal congenital contracture syndrome, and homozygous missense ADCY6 mutation (R1116C). The parents were heterozygous for the mutation. Knocked down ADCY6 orthologs in zebrafish showed a loss of myelin basic protein expression in the peripheral nervous system but no defects in Schwann cell migration and axonal growth. Gonzaga‐Jauregui et al. (2015): 1 patient with congenital hypotonia, distal joint contractures, hypomyelinating neuropathy, and vocal cord paralysis, and a homozygous missense ADCY6 variant. No functional studies. Deceased sister with a similar phenotype with hypotonia, areflexia, and hypomyelinating neuropathy who died at 18 months of respiratory insufficiency. Agolini et al. (2020): 1 patient with severe form of AMC, with two novel compound heterozygous variants in ADCY6 (parents confirmed carriers), but no functional studies.
Sources: Literature; to: - PMID: 33820833 (2021) - Further 2 sibs reported with a homozygous c.3346C>T:p.Arg1116Cys variant in the ADCY6 gene. The family was identified from a cohort of 315 genetically undiagnosed and unrelated AMC families. Arthrogryposis and IUGR were detected prenatally.

Laquerriere et al. (2014): 2 sibs from a consanguineous family with an axoglial form of lethal congenital contracture syndrome, and homozygous missense ADCY6 mutation (R1116C). The parents were heterozygous for the mutation. Knocked down ADCY6 orthologs in zebrafish showed a loss of myelin basic protein expression in the peripheral nervous system but no defects in Schwann cell migration and axonal growth. Gonzaga‐Jauregui et al. (2015): 1 patient with congenital hypotonia, distal joint contractures, hypomyelinating neuropathy, and vocal cord paralysis, and a homozygous missense ADCY6 variant. No functional studies. Deceased sister with a similar phenotype with hypotonia, areflexia, and hypomyelinating neuropathy who died at 18 months of respiratory insufficiency. Agolini et al. (2020): 1 patient with severe form of AMC, with two novel compound heterozygous variants in ADCY6 (parents confirmed carriers), but no functional studies.
Sources: Literature
Mendeliome v0.7192 PLCH1 Zornitza Stark Gene: plch1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7192 PLCH1 Zornitza Stark Classified gene: PLCH1 as Amber List (moderate evidence)
Mendeliome v0.7192 PLCH1 Zornitza Stark Gene: plch1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7191 UNC50 Arina Puzriakova gene: UNC50 was added
gene: UNC50 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: UNC50 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UNC50 were set to 29016857; 33820833
Phenotypes for gene: UNC50 were set to Arthrogryposis multiplex congenita
Review for gene: UNC50 was set to AMBER
Added comment: UNC50 is currently not associated with any phenotype in OMIM (last edited on 02/01/2018) or Gene2Phenotype.

- PMID: 29016857 (2017) - Homozygosity mapping of disease loci combined with WES in a single male from a consanguineous family presenting with lethal AMC revealed a homozygous frameshift deletion in UNC50 gene (c.750_751del:p.Cys251Phefs*4). Functional studies in C. elegans showed the variant caused loss of acetylcholine receptor expression in the muscle.

- PMID: 33820833 (2021) - Single individual reported with the same homozygous c.750_751del:p.Cys251Phefs*4 variant in UNC50 as previously described. The case was identified from a cohort of 315 genetically undiagnosed and unrelated AMC families. Arthrogryposis and tetra ventricular dilation were detected prenatally.

-- Note: it isn't definitively clear whether these are different individuals. Both are singleton males born to consanguineous parents, with the same variant and similar phenotype. Also both infants died at 28 w.g. However, the 2021 paper (PMID:33820833) states their patient was selected from a cohort of cases without a molecular diagnosis and indicate the UNC50 gene had already previously been identified in relation to this phenotype, highlighting the earlier paper (PMID:29016857). There is also no mention of tetra ventricular dilation in the first case, so it is likely that these do represent distinct individuals. Additional cases needed to provide clarity.
Sources: Literature
Mendeliome v0.7191 PLCH1 Arina Puzriakova gene: PLCH1 was added
gene: PLCH1 was added to Mendeliome. 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: PLCH1 is currently not associated with any phenotype in OMIM (last edited on 16/06/2009) or Gene2Phenotype.

- 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
Mendeliome v0.7191 DDX11 Zornitza Stark Gene: ddx11 has been classified as Green List (High Evidence).
Mendeliome v0.7188 PDIA6 Zornitza Stark Gene: pdia6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7188 PDIA6 Zornitza Stark Classified gene: PDIA6 as Amber List (moderate evidence)
Mendeliome v0.7188 PDIA6 Zornitza Stark Gene: pdia6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7187 PDIA6 Zornitza Stark gene: PDIA6 was added
gene: PDIA6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PDIA6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PDIA6 were set to Asphyxiating thoracic dystrophy (ATD) syndrome and infantile‐onset diabetes
Review for gene: PDIA6 was set to AMBER
Added comment: Amber in view of the good quality functional data.

1 case with asphyxiating thoracic dystrophy (ATD) syndrome and infantile‐onset diabetes. Whole exome sequencing revealed a homozygous frameshift variant in the PDIA6 gene. RNA expression was reduced in a gene dosage‐dependent manner, supporting a loss‐of‐function effect of this variant. Phenotypic correlation with the previously reported mouse model recapitulated the growth defect and delay, early lethality, coagulation, diabetes, immunological, and polycystic kidney disease phenotypes. The phenotype of the current patient is consistent with phenotypes associated with the disruption of PDIA6 and the sensors of UPR in mice and humans.
Sources: Literature
Mendeliome v0.7186 EXOSC1 Zornitza Stark Gene: exosc1 has been classified as Red List (Low Evidence).
Mendeliome v0.7186 EXOSC1 Zornitza Stark gene: EXOSC1 was added
gene: EXOSC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EXOSC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOSC1 were set to 33463720
Phenotypes for gene: EXOSC1 were set to Pontocerebellar hypoplasia
Review for gene: EXOSC1 was set to RED
Added comment: An 8‐months‐old male with developmental delay, microcephaly, subtle dysmorphism, hypotonia, pontocerebellar hypoplasia and delayed myelination. Similarly affected elder sibling succumbed at the age of 4‐years 6‐months. Exome sequencing revealed a homozygous missense variant (c.104C >T, p.Ser35Leu) in EXOSC1. In silico mutagenesis revealed loss of a polar contact with neighbouring Leu37 residue. Quantitative real‐time PCR indicated no appreciable differences in EXOSC1 transcript levels. Immunoblotting and blue native PAGE revealed reduction in the EXOSC1 protein levels and EXO9 complex in the proband, respectively. Of note, bi‐allelic variants in other exosome subunits EXOSC3, EXOSC8 and EXOSC9 have been reported to cause pontocerebellar hypoplasia type 1B, type 1C and type 1D, respectively.
Sources: Literature
Mendeliome v0.7183 UBE4A Zornitza Stark Gene: ube4a has been classified as Green List (High Evidence).
Mendeliome v0.7183 UBE4A Zornitza Stark Classified gene: UBE4A as Green List (high evidence)
Mendeliome v0.7183 UBE4A Zornitza Stark Gene: ube4a has been classified as Green List (High Evidence).
Mendeliome v0.7182 UBE4A Zornitza Stark gene: UBE4A was added
gene: UBE4A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: UBE4A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UBE4A were set to 33420346
Phenotypes for gene: UBE4A were set to Intellectual disability and global developmental delay
Review for gene: UBE4A was set to GREEN
Added comment: 8 individuals, from 4 unrelated families, with syndromic intellectual disability and global developmental delay (other clinical features included hypotonia, short stature, seizures, and behaviour disorder. Exome sequencing identified biallelic loss-of-function variants in UBE4A in the 4 families, with variants segregating with disease and parents carriers. They demonstrated that UBE4A loss-of-function variants reduced RNA expression and protein levels in clinical samples. Mice generated to mimic patient-specific Ube4a loss-of-function variant exhibited muscular and neurological/behavioural abnormalities, some of which are suggestive of the clinical abnormalities seen in the affected individuals.
Sources: Literature
Mendeliome v0.7181 MAPKAPK5 Zornitza Stark Gene: mapkapk5 has been classified as Green List (High Evidence).
Mendeliome v0.7181 MAPKAPK5 Zornitza Stark Classified gene: MAPKAPK5 as Green List (high evidence)
Mendeliome v0.7181 MAPKAPK5 Zornitza Stark Gene: mapkapk5 has been classified as Green List (High Evidence).
Mendeliome v0.7180 MAPKAPK5 Zornitza Stark gene: MAPKAPK5 was added
gene: MAPKAPK5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MAPKAPK5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAPKAPK5 were set to 3344202
Phenotypes for gene: MAPKAPK5 were set to Developmental delay, variable brain anomalies, congenital heart defects, dysmorphic
Review for gene: MAPKAPK5 was set to GREEN
Added comment: 3 individuals from 2 families with severe developmental delay, variable brain anomalies, congenital heart defects, dysmorphic facial features, and a distinctive type of synpolydactyly with an additional hypoplastic digit between the fourth and fifth digits of hands and/or feet. Exome sequencing identified different homozygous truncating variants in MAPKAPK5 in both families, segregating with disease and unaffected parents as carriers.

Patient-derived cells showed no expression of MAPKAPK5 protein isoforms and reduced levels of the MAPKAPK5-interacting protein ERK3. F-actin recovery after latrunculin B treatment was found to be less efficient in patient-derived fibroblasts than in control cells, supporting a role of MAPKAPK5 in F-actin polymerization.
Sources: Literature
Mendeliome v0.7179 FAR1 Zornitza Stark Phenotypes for gene: FAR1 were changed from Peroxisomal fatty acyl-CoA reductase 1 disorder, MIM#616154 to Peroxisomal fatty acyl-CoA reductase 1 disorder, MIM#616154; spastic paraparesis and bilateral cataracts
Mendeliome v0.7176 FAR1 Zornitza Stark Classified gene: FAR1 as Green List (high evidence)
Mendeliome v0.7176 FAR1 Zornitza Stark Gene: far1 has been classified as Green List (High Evidence).
Mendeliome v0.7175 FAR1 Zornitza Stark edited their review of gene: FAR1: Added comment: PMID33239752: 12 patients with paediatric onset spastic paraparesis and bilateral congenital/juvenile cataracts. Most also had speech and gross motor developmental delay and truncal hypotonia. Exome sequencing identified de novo variants affecting the Arg480 residue in FAR1 (p.Arg480Cys/His/Leu). Further functional studies in fibroblasts showed that these variants cause a disruption of the plasmalogen-dependent feedback regulation of FAR1 protein levels leading to uncontrolled ether lipid production.; Changed rating: GREEN; Changed publications: 25439727, 33239752; Changed phenotypes: Peroxisomal fatty acyl-CoA reductase 1 disorder, MIM#616154, spastic paraparesis and bilateral cataracts; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7175 GRIA3 Zornitza Stark Gene: gria3 has been classified as Green List (High Evidence).
Mendeliome v0.7172 SLC17A5 Zornitza Stark Gene: slc17a5 has been classified as Green List (High Evidence).
Mendeliome v0.7172 SLC17A5 Zornitza Stark Phenotypes for gene: SLC17A5 were changed from to Salla disease 604369; MONDO:0011449; Sialic acid storage disorder, infantile 269920; MONDO:0010027
Mendeliome v0.7169 SLC17A5 Zornitza Stark edited their review of gene: SLC17A5: Added comment: Sialic acid storage diseases are autosomal recessive neurodegenerative disorders that may present as a severe infantile form or a slowly progressive adult form, which is prevalent in Finland and referred to as Salla disease. p.Arg39Cys is a founder Finnish variant. Multiple families reported.; Changed publications: 10581036, 10947946; Changed phenotypes: Salla disease 604369, MONDO:0011449, Sialic acid storage disorder, infantile 269920, MONDO:0010027
Mendeliome v0.7169 SGSH Zornitza Stark Gene: sgsh has been classified as Green List (High Evidence).
Mendeliome v0.7169 SGSH Zornitza Stark Phenotypes for gene: SGSH were changed from to Mucopolysaccharidosis type IIIA (Sanfilippo A), MIM# 252900; MONDO:0009655
Mendeliome v0.7166 SGSH Zornitza Stark reviewed gene: SGSH: Rating: GREEN; Mode of pathogenicity: None; Publications: 7493035, 9158154, 9401012, 9554748; Phenotypes: Mucopolysaccharidosis type IIIA (Sanfilippo A), MIM# 252900, MONDO:0009655; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7166 SMPD1 Zornitza Stark changed review comment from: Well established gene-disease association.; to: Niemann-Pick disease (NPD) refers to a group of disorders that present with varying degrees of lipid storage and foam cell infiltration in tissues, as well as overlapping clinical features including hepatosplenomegaly, pulmonary insufficiency and/or central nervous system (CNS) involvement. Type A NPD patients exhibit hepatosplenomegaly in infancy and profound CNS involvement. They rarely survive beyond 2-3years of age. Type B patients also have hepatosplenomegaly and pathologic alterations of their lungs, but there are usually no CNS signs. The age of onset and rate of disease progression varies greatly among type B patients, and they frequently live into adulthood. Intermediate patients also have been reported with mild to moderate neurological findings.

Well established gene-disease association.
Mendeliome v0.7166 SMPD1 Zornitza Stark Gene: smpd1 has been classified as Green List (High Evidence).
Mendeliome v0.7163 TPP1 Zornitza Stark Phenotypes for gene: TPP1 were changed from Ceroid lipofuscinosis, neuronal, 2, MIM# 204500; Spinocerebellar ataxia, autosomal recessive 7, MIM# 609270 to Ceroid lipofuscinosis, neuronal, 2, MIM# 204500; MONDO:0008769; Spinocerebellar ataxia, autosomal recessive 7, MIM# 609270; MONDO:0012235
Mendeliome v0.7161 TPP1 Zornitza Stark reviewed gene: TPP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9295267, 18684116, 23418007, 26224725, 31283065; Phenotypes: Ceroid lipofuscinosis, neuronal, 2, MIM# 204500, MONDO:0008769, Spinocerebellar ataxia, autosomal recessive 7, MIM# 609270, MONDO:0012235; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7161 PSAP Zornitza Stark changed review comment from: Well established gene-disease association for bi-allelic variants. Early-onset PD reported with mono-allelic variants.; to: Well established gene-disease association for bi-allelic variants. Early-onset PD reported with mono-allelic variants.

The PSAP gene encodes saposins A, B, C and D. Variants resulting in PSAP null allele can be shared in patients with the deficit of other saposins (A-D) or whole prosaposin. The patient's phenotype depends then on the nature of the second allele - atypical Gaucher disease in case of saposin A, MLD in case of saposin B, and Krabbe disease in case of saposin C impairing mutations. The clinically most severe prosaposin deficit is caused by the presence of two PSAP null alleles.
Mendeliome v0.7161 PSAP Zornitza Stark Phenotypes for gene: PSAP were changed from Parkinson disease, AD; Combined SAP deficiency 611721; Gaucher disease, atypical, MIM# 610539; Krabbe disease, atypical, MIM# 611722; Metachromatic leukodystrophy due to SAP-b deficiency, MIM# 249900 to Parkinson disease, AD; Combined SAP deficiency, MIM# 611721; Encephalopathy due to prosaposin deficiency, MONDO:0012719; Krabbe disease, atypical, MIM# 611722; MONDO:0012720; Metachromatic leukodystrophy due to SAP-b deficiency, MIM# 249900; MONDO:0009590; Gaucher disease, atypical, MIM# 610539; MONDO:0012517
Mendeliome v0.7160 PSAP Zornitza Stark edited their review of gene: PSAP: Changed phenotypes: Combined SAP deficiency, MIM# 611721, Encephalopathy due to prosaposin deficiency, MONDO:0012719, Krabbe disease, atypical, MIM# 611722, MONDO:0012720, Metachromatic leukodystrophy due to SAP-b deficiency, MIM# 249900, MONDO:0009590, Gaucher disease, atypical, MIM# 610539, MONDO:0012517
Mendeliome v0.7160 PPT1 Zornitza Stark Gene: ppt1 has been classified as Green List (High Evidence).
Mendeliome v0.7160 PPT1 Zornitza Stark Phenotypes for gene: PPT1 were changed from to Ceroid lipofuscinosis, neuronal, 1, MIM# 256730; MONDO:0009744
Mendeliome v0.7157 PPT1 Zornitza Stark reviewed gene: PPT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 7637805, 9425237, 9664077; Phenotypes: Ceroid lipofuscinosis, neuronal, 1, MIM# 256730, MONDO:0009744; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7157 NEU1 Zornitza Stark Gene: neu1 has been classified as Green List (High Evidence).
Mendeliome v0.7157 NEU1 Zornitza Stark Phenotypes for gene: NEU1 were changed from to Sialidosis, type I and type II, MIM# 256550; MONDO:0009738
Mendeliome v0.7154 NEU1 Zornitza Stark reviewed gene: NEU1: Rating: GREEN; Mode of pathogenicity: None; Publications: 8985184, 9054950, 11063730; Phenotypes: Sialidosis, type I and type II, MIM# 256550, MONDO:0009738; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7154 NAGLU Zornitza Stark Phenotypes for gene: NAGLU were changed from Mucopolysaccharidosis type IIIB (Sanfilippo B), MIM# 252920; Charcot-Marie-Tooth disease, axonal, type 2V MIM#616491 to Mucopolysaccharidosis type IIIB (Sanfilippo B), MIM# 252920; MONDO:0009656; Charcot-Marie-Tooth disease, axonal, type 2V MIM#616491; MONDO:0014665
Mendeliome v0.7153 NAGLU Zornitza Stark Gene: naglu has been classified as Green List (High Evidence).
Mendeliome v0.7153 NAGLU Zornitza Stark Phenotypes for gene: NAGLU were changed from to Mucopolysaccharidosis type IIIB (Sanfilippo B), MIM# 252920; Charcot-Marie-Tooth disease, axonal, type 2V MIM#616491
Mendeliome v0.7150 NAGLU Zornitza Stark reviewed gene: NAGLU: Rating: GREEN; Mode of pathogenicity: None; Publications: 25818867, 8650226; Phenotypes: Mucopolysaccharidosis type IIIB (Sanfilippo B), MIM# 252920, Charcot-Marie-Tooth disease, axonal, type 2V MIM#616491; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7148 MIA3 Zornitza Stark Gene: mia3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7148 MIA3 Zornitza Stark Classified gene: MIA3 as Amber List (moderate evidence)
Mendeliome v0.7148 MIA3 Zornitza Stark Gene: mia3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7147 MIA3 Zornitza Stark changed review comment from: Odontochondrodysplasia-2 with hearing loss and diabetes (ODCD2) is characterized by growth retardation with proportionate short stature, dentinogenesis imperfecta, sensorineural hearing loss, insulin-dependent diabetes, and mild intellectual disability.

Four affected siblings reported. Mouse model has absence of bone mineralization.
Sources: Expert list; to: Odontochondrodysplasia-2 with hearing loss and diabetes (ODCD2) is characterized by growth retardation with proportionate short stature, dentinogenesis imperfecta, sensorineural hearing loss, insulin-dependent diabetes, and mild intellectual disability.

Four affected siblings reported, homozygous variant affecting splicing. Mouse model has absence of bone mineralization.
Sources: Expert list
Mendeliome v0.7147 MIA3 Zornitza Stark gene: MIA3 was added
gene: MIA3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MIA3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MIA3 were set to 32101163; 33778321
Phenotypes for gene: MIA3 were set to Ondontochondrodysplasia 2 with hearing loss and diabetes , MIM#619269
Review for gene: MIA3 was set to AMBER
Added comment: Odontochondrodysplasia-2 with hearing loss and diabetes (ODCD2) is characterized by growth retardation with proportionate short stature, dentinogenesis imperfecta, sensorineural hearing loss, insulin-dependent diabetes, and mild intellectual disability.

Four affected siblings reported. Mouse model has absence of bone mineralization.
Sources: Expert list
Mendeliome v0.7146 MFSD8 Zornitza Stark Phenotypes for gene: MFSD8 were changed from Ceroid lipofuscinosis, neuronal, 7 610951; Macular dystrophy with central cone involvement 616170 to Ceroid lipofuscinosis, neuronal, 7, MIM# 610951; MONDO:0012588; Macular dystrophy with central cone involvement, MIM# 616170; MONDO:0014515
Mendeliome v0.7144 MFSD8 Zornitza Stark reviewed gene: MFSD8: Rating: GREEN; Mode of pathogenicity: None; Publications: 17564970, 19201763, 25227500; Phenotypes: Ceroid lipofuscinosis, neuronal, 7, MIM# 610951, MONDO:0012588, Macular dystrophy with central cone involvement, MIM# 616170, MONDO:0014515; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7144 MCOLN1 Zornitza Stark Gene: mcoln1 has been classified as Green List (High Evidence).
Mendeliome v0.7144 MCOLN1 Zornitza Stark Phenotypes for gene: MCOLN1 were changed from to Mucolipidosis IV, MIM# 252650; MONDO:0009653
Mendeliome v0.7142 MCOLN1 Zornitza Stark reviewed gene: MCOLN1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mucolipidosis IV, MIM# 252650, MONDO:0009653; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7142 MANBA Zornitza Stark Gene: manba has been classified as Green List (High Evidence).
Mendeliome v0.7142 MANBA Zornitza Stark Phenotypes for gene: MANBA were changed from to Mannosidosis, beta, MIM# 248510; MONDO:0009562
Mendeliome v0.7140 MANBA Zornitza Stark reviewed gene: MANBA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mannosidosis, beta, MIM# 248510, MONDO:0009562; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7140 MAN2B1 Zornitza Stark Gene: man2b1 has been classified as Green List (High Evidence).
Mendeliome v0.7140 MAN2B1 Zornitza Stark Phenotypes for gene: MAN2B1 were changed from to Mannosidosis, alpha-, types I and II, MIM# 248500; MONDO:0009561
Mendeliome v0.7138 MAN2B1 Zornitza Stark reviewed gene: MAN2B1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mannosidosis, alpha-, types I and II, MIM# 248500, MONDO:0009561; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7138 LIPA Zornitza Stark Gene: lipa has been classified as Green List (High Evidence).
Mendeliome v0.7135 LAMP2 Zornitza Stark changed review comment from: XLD. Vacuolar cardiomyopathy and myopathy. Gene encodes lysosome-associated membrane protein-2.; to: XLD. Gene encodes lysosome-associated membrane protein-2.

Danon disease is an X-linked dominant disorder predominantly affecting cardiac muscle. Skeletal muscle involvement and mental retardation are variable features. The accumulation of glycogen in muscle and lysosomes originally led to the classification of Danon disease as a variant of glycogen storage disease II (Pompe disease) with 'normal acid maltase' or alpha-glucosidase, however, it may be more accurately classified as a lysosomal disorder.
Mendeliome v0.7135 LAMP2 Zornitza Stark Gene: lamp2 has been classified as Green List (High Evidence).
Mendeliome v0.7133 IDUA Zornitza Stark Phenotypes for gene: IDUA were changed from Mucopolysaccharidosis Ih (MIM#607014); Mucopolysaccharidosis Ih/s (MIM#607015); Mucopolysaccharidosis Is (MIM#6070) to Mucopolysaccharidosis Ih (MIM#607014); Mucopolysaccharidosis Ih/s (MIM#607015); Mucopolysaccharidosis Is (MIM#6070); Mucopolysaccharidosis type 1, MONDO:0001586
Mendeliome v0.7132 IDUA Zornitza Stark reviewed gene: IDUA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mucopolysaccharidosis type 1, MONDO:0001586; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7132 IDS Zornitza Stark Gene: ids has been classified as Green List (High Evidence).
Mendeliome v0.7132 IDS Zornitza Stark Phenotypes for gene: IDS were changed from to Mucopolysaccharidosis II, MIM# 309900; MONDO:0010674; Hunter syndrome
Mendeliome v0.7129 IDS Zornitza Stark reviewed gene: IDS: Rating: GREEN; Mode of pathogenicity: None; Publications: 9921913, 9762601, 8940265, 1901826; Phenotypes: Mucopolysaccharidosis II, MIM# 309900, MONDO:0010674, Hunter syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7129 ERBB2 Alison Yeung Classified gene: ERBB2 as Red List (low evidence)
Mendeliome v0.7129 ERBB2 Alison Yeung Gene: erbb2 has been classified as Red List (Low Evidence).
Mendeliome v0.7128 VWA1 Alison Yeung Gene: vwa1 has been classified as Green List (High Evidence).
Mendeliome v0.7128 VWA1 Alison Yeung Classified gene: VWA1 as Green List (high evidence)
Mendeliome v0.7128 VWA1 Alison Yeung Gene: vwa1 has been classified as Green List (High Evidence).
Mendeliome v0.7127 VWA1 Melanie Marty gene: VWA1 was added
gene: VWA1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: VWA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VWA1 were set to 33459760; 33693694; 33559681
Phenotypes for gene: VWA1 were set to Hereditary motor neuropathy
Review for gene: VWA1 was set to GREEN
Added comment: Six different truncating variants identified in 15 affected individuals from six families (biallelic inheritance). Disease manifested in childhood or adulthood with proximal and distal muscle weakness predominantly of the lower limbs. Myopathological and neurophysiological findings were indicative of combined neurogenic and myopathic pathology. Early childhood foot deformity was frequent, but no sensory signs were observed.

An additional 17 individuals from 15 families with hereditary motor neuropathy were identified. A 10-bp repeat expansion at the end of exon 1 was observed in 14 families and was homozygous in 10 of them. This mutation, c.62_71dup [p.Gly25Argfs*74], leads to a frameshift that results in a reduction in VWA1 transcript levels via nonsense-mediated decay.
Sources: Literature
Mendeliome v0.7127 GIPC1 Alison Yeung Classified gene: GIPC1 as Amber List (moderate evidence)
Mendeliome v0.7127 GIPC1 Alison Yeung Gene: gipc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7126 TSPOAP1 Tiong Tan Gene: tspoap1 has been classified as Green List (High Evidence).
Mendeliome v0.7126 TSPOAP1 Tiong Tan Classified gene: TSPOAP1 as Green List (high evidence)
Mendeliome v0.7126 TSPOAP1 Tiong Tan Added comment: Comment on list classification: Need to add to HSP gene lists too - dystonia/HSP
Mendeliome v0.7126 TSPOAP1 Tiong Tan Gene: tspoap1 has been classified as Green List (High Evidence).
Mendeliome v0.7125 CLDN11 Alison Yeung Gene: cldn11 has been classified as Green List (High Evidence).
Mendeliome v0.7125 CLDN11 Alison Yeung Classified gene: CLDN11 as Green List (high evidence)
Mendeliome v0.7125 CLDN11 Alison Yeung Gene: cldn11 has been classified as Green List (High Evidence).
Mendeliome v0.7124 ERBB3 Alison Yeung Classified gene: ERBB3 as Green List (high evidence)
Mendeliome v0.7124 ERBB3 Alison Yeung Gene: erbb3 has been classified as Green List (High Evidence).
Mendeliome v0.7123 SYK Alison Yeung Gene: syk has been classified as Green List (High Evidence).
Mendeliome v0.7123 SYK Alison Yeung Classified gene: SYK as Green List (high evidence)
Mendeliome v0.7123 SYK Alison Yeung Gene: syk has been classified as Green List (High Evidence).
Mendeliome v0.7122 NCDN Alison Yeung Gene: ncdn has been classified as Green List (High Evidence).
Mendeliome v0.7122 NCDN Alison Yeung Classified gene: NCDN as Green List (high evidence)
Mendeliome v0.7122 NCDN Alison Yeung Gene: ncdn has been classified as Green List (High Evidence).
Mendeliome v0.7121 TSPOAP1 Ain Roesley gene: TSPOAP1 was added
gene: TSPOAP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TSPOAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TSPOAP1 were set to 33539324
Phenotypes for gene: TSPOAP1 were set to Dystonia, intellectual disability and cerebellar atrophy
Penetrance for gene: TSPOAP1 were set to unknown
Review for gene: TSPOAP1 was set to GREEN
Added comment: 7 affecteds from 3 families (1 consanguineous)
2x null, 1x missense

Affecteds with the null variants presented with juvenile-onset progressive generalized dystonia, associated with intellectual disability and cerebellar atrophy while those with the missense p.(Gly1808Ser) presented with isolated adult-onset focal dystonia (mild cognitive impairment noted)

mice KO models were investigated
Sources: Literature
Mendeliome v0.7121 CLDN11 Melanie Marty gene: CLDN11 was added
gene: CLDN11 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CLDN11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CLDN11 were set to 33313762
Phenotypes for gene: CLDN11 were set to Hypomyelinating leukodystrophy
Review for gene: CLDN11 was set to GREEN
Added comment: In three unrelated individuals with early-onset spastic movement disorder, expressive speech disorder and eye abnormalities including hypermetropia, 2 different heterozygous de novo stop-loss variants were identified. One of the variants did not lead to a loss of CLDN11 expression on RNA level in fibroblasts indicating this transcript is not subject to nonsense-mediated decay and most likely translated into an extended protein.
Sources: Literature
Mendeliome v0.7121 SLC5A5 Zornitza Stark Gene: slc5a5 has been classified as Green List (High Evidence).
Mendeliome v0.7121 SLC5A5 Zornitza Stark Phenotypes for gene: SLC5A5 were changed from to Thyroid dyshormonogenesis 1, MIM# 274400; MONDO:0020716
Mendeliome v0.7118 SLC5A5 Zornitza Stark reviewed gene: SLC5A5: Rating: GREEN; Mode of pathogenicity: None; Publications: 9745458, 9171822, 33815280, 32319661; Phenotypes: Thyroid dyshormonogenesis 1, MIM# 274400, MONDO:0020716; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7118 SLC45A1 Zornitza Stark Gene: slc45a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7115 SLC45A1 Zornitza Stark Classified gene: SLC45A1 as Amber List (moderate evidence)
Mendeliome v0.7115 SLC45A1 Zornitza Stark Gene: slc45a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7114 MESP1 Zornitza Stark Gene: mesp1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7114 MESP1 Zornitza Stark Classified gene: MESP1 as Amber List (moderate evidence)
Mendeliome v0.7114 MESP1 Zornitza Stark Gene: mesp1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7113 MESP1 Zornitza Stark gene: MESP1 was added
gene: MESP1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MESP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MESP1 were set to 28677747; 28050627; 27185833; 26694203
Phenotypes for gene: MESP1 were set to Congenital heart disease
Review for gene: MESP1 was set to AMBER
Added comment: Rare/novel variants reported in at least 7 unrelated individuals with congenital heart disease, in-silicos conflicting, familial segregation only available for some (one de novo, three inherited, others unresolved). Functional data implicates gene in cardiac development.
Sources: Expert list
Mendeliome v0.7112 HYAL1 Zornitza Stark Gene: hyal1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7112 HYAL1 Zornitza Stark Phenotypes for gene: HYAL1 were changed from to Mucopolysaccharidosis type IX, MIM# 601492; MONDO:0011093
Mendeliome v0.7109 HYAL1 Zornitza Stark Classified gene: HYAL1 as Amber List (moderate evidence)
Mendeliome v0.7109 HYAL1 Zornitza Stark Gene: hyal1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7108 HYAL1 Zornitza Stark reviewed gene: HYAL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 10339581, 18344557, 21559944; Phenotypes: Mucopolysaccharidosis type IX, MIM# 601492, MONDO:0011093; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7108 HGSNAT Zornitza Stark Phenotypes for gene: HGSNAT were changed from Mucopolysaccharidosis type IIIC (Sanfilippo C), MIM# 252930 MONDO:0009657 Retinitis pigmentosa 73, MIM# 616544 MONDO:0014687 to Mucopolysaccharidosis type IIIC (Sanfilippo C), MIM# 252930; MONDO:0009657; Retinitis pigmentosa 73, MIM# 616544; MONDO:0014687
Mendeliome v0.7106 HGSNAT Zornitza Stark Phenotypes for gene: HGSNAT were changed from Mucopolysaccharidosis type IIIC (Sanfilippo C) (MIM #252930); Retinitis pigmentosa 73 (MIM # 616544) to Mucopolysaccharidosis type IIIC (Sanfilippo C), MIM# 252930 MONDO:0009657 Retinitis pigmentosa 73, MIM# 616544 MONDO:0014687
Mendeliome v0.7105 HEXB Zornitza Stark Gene: hexb has been classified as Green List (High Evidence).
Mendeliome v0.7103 HEXA Zornitza Stark Phenotypes for gene: HEXA were changed from GM2-gangliosidosis, several forms 272800; Tay-Sachs disease 272800 to GM2-gangliosidosis, several forms 272800; Tay-Sachs disease 272800; MONDO:0010100
Mendeliome v0.7102 GUSB Zornitza Stark Gene: gusb has been classified as Green List (High Evidence).
Mendeliome v0.7102 GUSB Zornitza Stark Phenotypes for gene: GUSB were changed from to Mucopolysaccharidosis VII, MIM# 253220; MONDO:0009662
Mendeliome v0.7100 GUSB Zornitza Stark reviewed gene: GUSB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mucopolysaccharidosis VII, MIM# 253220, MONDO:0009662; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7100 GNS Zornitza Stark Gene: gns has been classified as Green List (High Evidence).
Mendeliome v0.7100 GNS Zornitza Stark Phenotypes for gene: GNS were changed from to Mucopolysaccharidosis type IIID, MIM# 252940; Sanfilippo syndrome type D, MONDO:0009658
Mendeliome v0.7097 GNS Zornitza Stark reviewed gene: GNS: Rating: GREEN; Mode of pathogenicity: None; Publications: 12573255, 12624138, 31536183, 25851924; Phenotypes: Mucopolysaccharidosis type IIID, MIM# 252940, Sanfilippo syndrome type D, MONDO:0009658; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7097 GNPTG Zornitza Stark Gene: gnptg has been classified as Green List (High Evidence).
Mendeliome v0.7097 GNPTG Zornitza Stark Phenotypes for gene: GNPTG were changed from to Mucolipidosis III gamma, MIM# 252605; MONDO:0009652
Mendeliome v0.7094 GNPTG Zornitza Stark reviewed gene: GNPTG: Rating: GREEN; Mode of pathogenicity: None; Publications: 10712439, 19370764, 19659762, 33507475, 33023972, 32651481; Phenotypes: Mucolipidosis III gamma, MIM# 252605, MONDO:0009652; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7094 CHD7 Zornitza Stark Gene: chd7 has been classified as Green List (High Evidence).
Mendeliome v0.7091 ALDH1A2 Bryony Thompson Phenotypes for gene: ALDH1A2 were changed from to congenital heart defects; diaphragmatic eventration; pulmonary hypoplasia; dysmorphic features
Mendeliome v0.7089 NDUFA12 Bryony Thompson Classified gene: NDUFA12 as Green List (high evidence)
Mendeliome v0.7089 NDUFA12 Bryony Thompson Gene: ndufa12 has been classified as Green List (High Evidence).
Mendeliome v0.7088 ALDH1A2 Bryony Thompson Gene: aldh1a2 has been classified as Green List (High Evidence).
Mendeliome v0.7086 ALDH1A2 Bryony Thompson reviewed gene: ALDH1A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33565183, 10192400; Phenotypes: congenital heart defects, diaphragmatic eventration, pulmonary hypoplasia, dysmorphic features; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7086 MMP20 Bryony Thompson Gene: mmp20 has been classified as Green List (High Evidence).
Mendeliome v0.7084 FBN2 Zornitza Stark edited their review of gene: FBN2: Added comment: The association between mono-allelic variants in FBN2 and CCA is well established. Recent report of bi-allelic variants, Kloth (2021): biallelic FBN2 variants (PTC/missense) in a teenager with severe CCA, including cardiac defects, mild scoliosis and muscular involvement. Carrier parents both "healthy/unaffected". Phenotype matches mouse K/O. Authors performed a lit review and identified an additional 2 homozygous patients (both missense variants) with - fetal akinesia, brain ischemia and neonatal death - severe muscle weakness with bilateral clubfeet, a pronounced gait disturbance, recurrent patellar dislocations, flexion contractures, camptodactyly, widespread striae and an unusual myofibrillar disorganization, variation in fiber size and atrophic fibers in muscle biopsy.

Evidence for association with Macular degeneration, early-onset MIM#616118 is limited. One family reported, plus some rare variants reported in cohort studies. The familial variant p.Glu1144Lys is present in 11 hets in gnomad and has benign in silicos. The second variant reported in the paper, p.Met1247Thr is present in >20 hets.; Changed rating: GREEN; Changed publications: 33571691; Changed phenotypes: Contractural arachnodactyly, congenital MIM#121050, Macular degeneration, early-onset MIM#616118; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7084 MMP20 Bryony Thompson Phenotypes for gene: MMP20 were changed from to Amelogenesis imperfecta, type IIA2 MIM#612529
Mendeliome v0.7081 MMP20 Bryony Thompson reviewed gene: MMP20: Rating: GREEN; Mode of pathogenicity: None; Publications: 15744043, 33600052; Phenotypes: Amelogenesis imperfecta, type IIA2 MIM#612529; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.7081 NDUFB7 Bryony Thompson Gene: ndufb7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7081 NDUFB7 Bryony Thompson Classified gene: NDUFB7 as Amber List (moderate evidence)
Mendeliome v0.7081 NDUFB7 Bryony Thompson Gene: ndufb7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7080 NDUFB7 Bryony Thompson gene: NDUFB7 was added
gene: NDUFB7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NDUFB7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFB7 were set to 33502047; 27626371
Phenotypes for gene: NDUFB7 were set to Congenital lactic acidosis; hypertrophic cardiomyopathy
Review for gene: NDUFB7 was set to AMBER
Added comment: Single patient with a homozygous variant impacting RNA splicing (c.113-10C>G) with intrauterine growth restriction and anaemia, which displayed postpartum hypertrophic cardiomyopathy, lactic acidosis, encephalopathy, and a severe complex I defect with fatal outcome. Also, a supporting knockout cell line model demonstrating impaired complex I assembly.
Sources: Literature
Mendeliome v0.7079 CELA3B Bryony Thompson Gene: cela3b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7079 CELA3B Bryony Thompson Classified gene: CELA3B as Amber List (moderate evidence)
Mendeliome v0.7079 CELA3B Bryony Thompson Gene: cela3b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7078 CDH11 Zornitza Stark Gene: cdh11 has been classified as Green List (High Evidence).
Mendeliome v0.7074 SLC10A1 Zornitza Stark Gene: slc10a1 has been classified as Green List (High Evidence).
Mendeliome v0.7074 SLC10A1 Zornitza Stark Classified gene: SLC10A1 as Green List (high evidence)
Mendeliome v0.7074 SLC10A1 Zornitza Stark Gene: slc10a1 has been classified as Green List (High Evidence).
Mendeliome v0.7073 SLC10A1 Zornitza Stark gene: SLC10A1 was added
gene: SLC10A1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SLC10A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC10A1 were set to 24867799; 27882152; 28835676; 29290974; 31201272
Phenotypes for gene: SLC10A1 were set to Familial hypercholanemia-2, MIM#619256
Review for gene: SLC10A1 was set to GREEN
Added comment: IEM characterised by persistently increased plasma levels of conjugated bile salts apparent from infancy. Most patients are asymptomatic and have no liver dysfunction, although some neonates may have transient jaundice or transiently elevated liver enzymes. These abnormalities improve with age. The bile acid defect can result in impaired absorption of fat-soluble vitamins, including D and K, causing decreased bone mineral density or prolonged prothrobin time (PT). Some variants are recurrent (founder effect likely) but at least 3 different variants reported, mouse model.
Sources: Expert list
Mendeliome v0.7072 GALNS Zornitza Stark Gene: galns has been classified as Green List (High Evidence).
Mendeliome v0.7072 GALNS Zornitza Stark Phenotypes for gene: GALNS were changed from to Mucopolysaccharidosis IVA, MIM# 253000; MONDO:0009659
Mendeliome v0.7069 GALNS Zornitza Stark reviewed gene: GALNS: Rating: GREEN; Mode of pathogenicity: None; Publications: 9298823; Phenotypes: Mucopolysaccharidosis IVA, MIM# 253000, MONDO:0009659; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7069 GALC Zornitza Stark Gene: galc has been classified as Green List (High Evidence).
Mendeliome v0.7065 FUCA1 Zornitza Stark Gene: fuca1 has been classified as Green List (High Evidence).
Mendeliome v0.7065 FUCA1 Zornitza Stark Phenotypes for gene: FUCA1 were changed from to Fucosidosis, MIM# 230000; MONDO:0009254
Mendeliome v0.7062 FUCA1 Zornitza Stark reviewed gene: FUCA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10094192; Phenotypes: Fucosidosis, MIM# 230000, MONDO:0009254; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7062 CTSD Zornitza Stark Gene: ctsd has been classified as Green List (High Evidence).
Mendeliome v0.7062 CTSD Zornitza Stark Phenotypes for gene: CTSD were changed from to Ceroid lipofuscinosis, neuronal, 10, MIM# 610127; MONDO:0012414
Mendeliome v0.7059 CTSD Zornitza Stark reviewed gene: CTSD: Rating: GREEN; Mode of pathogenicity: None; Publications: 16685649, 16670177, 25298308, 33681191, 29284168, 27072142; Phenotypes: Ceroid lipofuscinosis, neuronal, 10, MIM# 610127, MONDO:0012414; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7059 CCDC88C Zornitza Stark Phenotypes for gene: CCDC88C were changed from Spinocerebellar ataxia 40, MIM#616053; Hydrocephalus, nonsyndromic, autosomal recessive 236600; Eearly-onset pure hereditary spastic paraplegia to Spinocerebellar ataxia 40, MIM#616053; Hydrocephalus, nonsyndromic, autosomal recessive 236600; Early-onset pure hereditary spastic paraplegia
Mendeliome v0.7058 CCDC88C Zornitza Stark Phenotypes for gene: CCDC88C were changed from Spinocerebellar ataxia 40, MIM#616053; Hydrocephalus, nonsyndromic, autosomal recessive 236600 AR to Spinocerebellar ataxia 40, MIM#616053; Hydrocephalus, nonsyndromic, autosomal recessive 236600; Eearly-onset pure hereditary spastic paraplegia
Mendeliome v0.7056 CCDC88C Paul De Fazio changed review comment from: Heterozygous missense variant (gnomad: 1 het) reported in a 48-year-old Sudanese female presented with pure early onset hereditary spastic paraplegia. In contrast to previous reports, she developed neurological symptoms in early childhood and showed neither features of cerebellar ataxia, extrapyramidal signs, nor evidence of intellectual involvement. Functional studies showed the varaint induced JNK hyper-phosphorylation and enhanced apoptosis. 4 unaffected family members did not have the variant.

This phenotype appears to be sufficiently dissimilar to the 2 previously reported SCA families to not constitute a 3rd supporting report in that context.; to: Heterozygous missense variant (gnomad: 1 het) reported in a 48-year-old Sudanese female presented with pure early onset hereditary spastic paraplegia. In contrast to previous reports, she developed neurological symptoms in early childhood and showed neither features of cerebellar ataxia, extrapyramidal signs, nor evidence of intellectual involvement. Functional studies showed the varaint induced JNK hyper-phosphorylation and enhanced apoptosis. 4 unaffected family members did not have the variant.

NB: Rated Amber as this phenotype appears to be sufficiently dissimilar to the 2 previously reported SCA families to not constitute a 3rd supporting report in that context. Gene remains Green for the AR ID phenotype.
Mendeliome v0.7055 NMNAT1 Zornitza Stark Phenotypes for gene: NMNAT1 were changed from to Spondyloepiphyseal dysplasia, sensorineural hearing loss, intellectual disability, and Leber congenital amaurosis (SHILCA), MIM#619260; Leber congenital amaurosis 9, MIM# 608553
Mendeliome v0.7053 NMNAT1 Zornitza Stark Gene: nmnat1 has been classified as Green List (High Evidence).
Mendeliome v0.7053 NMNAT1 Zornitza Stark reviewed gene: NMNAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32533184, 33668384, 22842230, 22842229; Phenotypes: Spondyloepiphyseal dysplasia, sensorineural hearing loss, intellectual disability, and Leber congenital amaurosis (SHILCA), MIM#619260, Leber congenital amaurosis 9, MIM# 608553; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7053 ZMPSTE24 Zornitza Stark Phenotypes for gene: ZMPSTE24 were changed from Mandibuloacral dysplasia with type B lipodystrophy, MIM# 608612; MONDO:0012074; Restrictive dermopathy, lethal, MIM# 275210 to Mandibuloacral dysplasia with type B lipodystrophy, MIM# 608612; MONDO:0012074; Restrictive dermopathy, lethal, MIM# 275210; MONDO:0010143
Mendeliome v0.7052 ZMPSTE24 Zornitza Stark Gene: zmpste24 has been classified as Green List (High Evidence).
Mendeliome v0.7052 ZMPSTE24 Zornitza Stark Phenotypes for gene: ZMPSTE24 were changed from to Mandibuloacral dysplasia with type B lipodystrophy, MIM# 608612; MONDO:0012074; Restrictive dermopathy, lethal, MIM# 275210
Mendeliome v0.7049 ZMPSTE24 Zornitza Stark reviewed gene: ZMPSTE24: Rating: GREEN; Mode of pathogenicity: None; Publications: 11923874, 22718200, 29794150, 29208544, 12913070, 27410998, 27409638, 15937076, 16671095, 22718200, 29794150, 24169522; Phenotypes: Mandibuloacral dysplasia with type B lipodystrophy, MIM# 608612, MONDO:0012074, Restrictive dermopathy, lethal, MIM# 275210; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7049 WDR35 Zornitza Stark reviewed gene: WDR35: Rating: GREEN; Mode of pathogenicity: None; Publications: 33421337, 29134781, 28870638, 26691894, 24027799, 21473986; Phenotypes: Cranioectodermal dysplasia 2, MIM#613610, MONDO:0013323, Short-rib thoracic dysplasia 7 with or without polydactyly, MIM#614091, MONDO:0013569; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7049 WDR35 Zornitza Stark Phenotypes for gene: WDR35 were changed from Cranioectodermal dysplasia 2, MIM#613610; Short-rib thoracic dysplasia 7 with or without polydactyly, MIM#614091 to Cranioectodermal dysplasia 2, MIM#613610; MONDO:0013323; Short-rib thoracic dysplasia 7 with or without polydactyly, MIM#614091; MONDO:0013569
Mendeliome v0.7048 EDN1 Zornitza Stark Gene: edn1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7045 EDN1 Zornitza Stark Classified gene: EDN1 as Amber List (moderate evidence)
Mendeliome v0.7045 EDN1 Zornitza Stark Gene: edn1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7044 CLN5 Zornitza Stark Gene: cln5 has been classified as Green List (High Evidence).
Mendeliome v0.7044 CLN5 Zornitza Stark Phenotypes for gene: CLN5 were changed from to Ceroid lipofuscinosis, neuronal, 5, MIM# 256731; MONDO:0009745
Mendeliome v0.7041 CLN5 Zornitza Stark reviewed gene: CLN5: Rating: GREEN; Mode of pathogenicity: None; Publications: 20157158; Phenotypes: Ceroid lipofuscinosis, neuronal, 5, MIM# 256731, MONDO:0009745; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7041 CLN3 Zornitza Stark Gene: cln3 has been classified as Green List (High Evidence).
Mendeliome v0.7041 CLN3 Zornitza Stark Phenotypes for gene: CLN3 were changed from to Ceroid lipofuscinosis, neuronal, 3, MIM# 204200; MONDO:0008767
Mendeliome v0.7038 CLN3 Zornitza Stark reviewed gene: CLN3: Rating: GREEN; Mode of pathogenicity: None; Publications: 7553855; Phenotypes: Ceroid lipofuscinosis, neuronal, 3, MIM# 204200, MONDO:0008767; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7038 ARSB Zornitza Stark Gene: arsb has been classified as Green List (High Evidence).
Mendeliome v0.7038 ARSB Zornitza Stark Phenotypes for gene: ARSB were changed from to Mucopolysaccharidosis type VI (Maroteaux-Lamy), MIM# 253200; MONDO:0009661
Mendeliome v0.7035 ARSB Zornitza Stark reviewed gene: ARSB: Rating: GREEN; Mode of pathogenicity: None; Publications: 11668612; Phenotypes: Mucopolysaccharidosis type VI (Maroteaux-Lamy), MIM# 253200, MONDO:0009661; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7035 AGA Zornitza Stark Gene: aga has been classified as Green List (High Evidence).
Mendeliome v0.7032 AGA Zornitza Stark edited their review of gene: AGA: Added comment: Aspartylglucosaminuria (AGU) is a severe autosomal recessive lysosomal storage disorder that involves the central nervous system and causes skeletal abnormalities as well as connective tissue lesions. The most characteristic feature is progressive mental retardation. Multiple families and mouse model.; Changed publications: 1703489, 1904874, 8064811, 8946839; Changed phenotypes: Aspartylglucosaminuria, MIM# 208400, MONDO:0008830
Mendeliome v0.7032 ATCAY Zornitza Stark Gene: atcay has been classified as Green List (High Evidence).
Mendeliome v0.7028 ARAP3 Zornitza Stark Gene: arap3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7028 ARAP3 Zornitza Stark Classified gene: ARAP3 as Amber List (moderate evidence)
Mendeliome v0.7028 ARAP3 Zornitza Stark Gene: arap3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7026 RORC Zornitza Stark edited their review of gene: RORC: Added comment: Association with lymphoedema: Two individuals reported with LoF variants as part of a large cohort. Note gene is depleted for LoF in gnomad, and bi-allelic variants have been associated with immunodeficiency.; Changed publications: 26160376, 32960152; Changed phenotypes: Immunodeficiency 42, MIM# 616622, Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency, MONDO:0014710, Lymphoedema; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.7026 RORC Zornitza Stark Gene: rorc has been classified as Green List (High Evidence).
Mendeliome v0.7026 RORC Zornitza Stark Phenotypes for gene: RORC were changed from to Immunodeficiency 42, MIM# 616622; Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency, MONDO:0014710
Mendeliome v0.7023 RORC Zornitza Stark reviewed gene: RORC: Rating: GREEN; Mode of pathogenicity: None; Publications: 26160376; Phenotypes: Immunodeficiency 42, MIM# 616622, Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency, MONDO:0014710; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7023 IL17RC Zornitza Stark Gene: il17rc has been classified as Green List (High Evidence).
Mendeliome v0.7023 IL17RC Zornitza Stark Phenotypes for gene: IL17RC were changed from to Candidiasis, familial, 9, MIM# 616445; MONDO:0014642
Mendeliome v0.7020 IL17RC Zornitza Stark reviewed gene: IL17RC: Rating: GREEN; Mode of pathogenicity: None; Publications: 25918342; Phenotypes: Candidiasis, familial, 9, MIM# 616445, MONDO:0014642; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7018 IL17RA Zornitza Stark Gene: il17ra has been classified as Green List (High Evidence).
Mendeliome v0.7017 CARD9 Zornitza Stark Gene: card9 has been classified as Green List (High Evidence).
Mendeliome v0.7017 CARD9 Zornitza Stark Phenotypes for gene: CARD9 were changed from to Candidiasis, familial, 2, autosomal recessive, MIM# 212050; Predisposition to invasive fungal disease, MONDO:0008905
Mendeliome v0.7014 CARD9 Zornitza Stark reviewed gene: CARD9: Rating: GREEN; Mode of pathogenicity: None; Publications: 19864672, 23335372, 24131138, 33789983, 33558980, 33180249; Phenotypes: Candidiasis, familial, 2, autosomal recessive, MIM# 212050, Predisposition to invasive fungal disease, MONDO:0008905; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.7014 CYP24A1 Zornitza Stark Gene: cyp24a1 has been classified as Green List (High Evidence).
Mendeliome v0.7009 ABCB7 Zornitza Stark Gene: abcb7 has been classified as Green List (High Evidence).
Mendeliome v0.7009 ABCB7 Zornitza Stark Phenotypes for gene: ABCB7 were changed from to Anaemia, sideroblastic, with ataxia, MIM# 301310
Mendeliome v0.7006 ABCB7 Zornitza Stark reviewed gene: ABCB7: Rating: GREEN; Mode of pathogenicity: None; Publications: 10196363, 10196363, 33157103, 31772327, 31511561, 26242992; Phenotypes: Anaemia, sideroblastic, with ataxia, MIM# 301310; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.7006 PORCN Zornitza Stark Gene: porcn has been classified as Green List (High Evidence).
Mendeliome v0.7006 PORCN Zornitza Stark Phenotypes for gene: PORCN were changed from to Focal dermal hypoplasia, MIM# 305600
Mendeliome v0.7004 PORCN Zornitza Stark reviewed gene: PORCN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Focal dermal hypoplasia, MIM# 305600; 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 v0.7004 PRIM1 Zornitza Stark changed review comment from: - PMID: 33060134 (2020) - From a cohort of 220 families with microcephalic dwarfism spectrum disorders (OFC ≤−4 SD; height ≤−2 SD), three families (4 individuals) were identified with the same homozygous intronic variant (c.638+36C>G) in PRIM1. This variant was present in gnomAD in 2 individuals across all populations, but only in a heterozygous state. Haplotype analysis indicated that all three families share a distant common ancestor - i.e. confirmed founder variant.
Authors subsequently identified a single individual with compound heterozygous PRIM1 variants (c.103+1G>T, c.901T>C) from the DDD study, who also presented microcephaly and short stature (OFC ≤−3 SD; height ≤−3 SD).

Clinical overlap was evident in all 5 individuals, presenting extreme pre- and postnatal growth restriction, severe microcephaly (OFC −6.0 ± 1.5 SD) with simplified gyri appearance, hypothyroidism, hypo/agammaglobulinaemia, and lymphopaenia accompanied by intermittent anaemia/thrombocytopaenia. All had chronic respiratory symptoms, and four died in early childhood from respiratory or GI infections.

Functional studies demonstrated reduced PRIM1 protein levels, replication fork defects and prolonged S-phase duration in PRIM1-deficient cells. The resulting delay to the cell cycle and inability to sustain sufficient cell proliferation provides a likely mechanism for the presenting phenotype.
Sources: Literature; to: - PMID: 33060134 (2020) - From a cohort of 220 families with microcephalic dwarfism spectrum disorders (OFC ≤−4 SD; height ≤−2 SD), three families (4 individuals) were identified with the same homozygous intronic variant (c.638+36C>G) in PRIM1. This variant was present in gnomAD in 2 individuals across all populations, but only in a heterozygous state. Haplotype analysis indicated that all three families share a distant common ancestor - i.e. confirmed founder variant.
Authors subsequently identified a single individual with compound heterozygous PRIM1 variants (c.103+1G>T, c.901T>C) from the DDD study, who also presented microcephaly and short stature (OFC ≤−3 SD; height ≤−3 SD).

Clinical overlap was evident in all 5 individuals, presenting extreme pre- and postnatal growth restriction, severe microcephaly (OFC −6.0 ± 1.5 SD) with simplified gyri appearance, hypothyroidism, hypo/agammaglobulinaemia, and lymphopaenia accompanied by intermittent anaemia/thrombocytopaenia. All had chronic respiratory symptoms, and four died in early childhood from respiratory or GI infections.

Functional studies demonstrated reduced PRIM1 protein levels, replication fork defects and prolonged S-phase duration in PRIM1-deficient cells. The resulting delay to the cell cycle and inability to sustain sufficient cell proliferation provides a likely mechanism for the presenting phenotype.
Sources: Literature
Mendeliome v0.7004 PRIM1 Zornitza Stark Gene: prim1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7004 PRIM1 Zornitza Stark Classified gene: PRIM1 as Amber List (moderate evidence)
Mendeliome v0.7004 PRIM1 Zornitza Stark Gene: prim1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.7003 PRIM1 Zornitza Stark changed review comment from: - PMID: 33060134 (2020) - From a cohort of 220 families with microcephalic dwarfism spectrum disorders (OFC ≤−4 SD; height ≤−2 SD), three families (4 individuals) were identified with the same homozygous intronic variant (c.638+36C>G) in PRIM1. This variant was present in gnomAD in 2 individuals across all populations, but only in a heterozygous state. Haplotype analysis indicated that all three families share a distant common ancestor - i.e. confirmed founder variant.
Authors subsequently identified a single individual with compound heterozygous PRIM1 variants (c.103+1G>T, c.901T>C) from the DDD study, who also presented microcephaly and short stature (OFC ≤−3 SD; height ≤−3 SD).

Clinical overlap was evident in all 5 individuals, presenting extreme pre- and postnatal growth restriction, severe microcephaly (OFC −6.0 ± 1.5 SD) with simplified gyri appearance, hypothyroidism, hypo/agammaglobulinemia, and lymphopenia accompanied by intermittent anaemia/thrombocytopaenia. All had chronic respiratory symptoms, and four died in early childhood from respiratory or GI infections.

Functional studies demonstrated reduced PRIM1 protein levels, replication fork defects and prolonged S-phase duration in PRIM1-deficient cells. The resulting delay to the cell cycle and inability to sustain sufficient cell proliferation provides a likely mechanism for the presenting phenotype.
Sources: Literature; to: - PMID: 33060134 (2020) - From a cohort of 220 families with microcephalic dwarfism spectrum disorders (OFC ≤−4 SD; height ≤−2 SD), three families (4 individuals) were identified with the same homozygous intronic variant (c.638+36C>G) in PRIM1. This variant was present in gnomAD in 2 individuals across all populations, but only in a heterozygous state. Haplotype analysis indicated that all three families share a distant common ancestor - i.e. confirmed founder variant.
Authors subsequently identified a single individual with compound heterozygous PRIM1 variants (c.103+1G>T, c.901T>C) from the DDD study, who also presented microcephaly and short stature (OFC ≤−3 SD; height ≤−3 SD).

Clinical overlap was evident in all 5 individuals, presenting extreme pre- and postnatal growth restriction, severe microcephaly (OFC −6.0 ± 1.5 SD) with simplified gyri appearance, hypothyroidism, hypo/agammaglobulinaemia, and lymphopaenia accompanied by intermittent anaemia/thrombocytopaenia. All had chronic respiratory symptoms, and four died in early childhood from respiratory or GI infections.

Functional studies demonstrated reduced PRIM1 protein levels, replication fork defects and prolonged S-phase duration in PRIM1-deficient cells. The resulting delay to the cell cycle and inability to sustain sufficient cell proliferation provides a likely mechanism for the presenting phenotype.
Sources: Literature
Mendeliome v0.7003 PRIM1 Zornitza Stark changed review comment from: - PMID: 33060134 (2020) - From a cohort of 220 families with microcephalic dwarfism spectrum disorders (OFC ≤−4 SD; height ≤−2 SD), three families (4 individuals) were identified with the same homozygous intronic variant (c.638+36C>G) in PRIM1. This variant was present in gnomAD in 2 individuals across all populations, but only in a heterozygous state. Haplotype analysis indicated that all three families share a distant common ancestor - i.e. confirmed founder variant.
Authors subsequently identified a single individual with compound heterozygous PRIM1 variants (c.103+1G>T, c.901T>C) from the DDD study, who also presented microcephaly and short stature (OFC ≤−3 SD; height ≤−3 SD).

Clinical overlap was evident in all 5 individuals, presenting extreme pre- and postnatal growth restriction, severe microcephaly (OFC −6.0 ± 1.5 SD) with simplified gyri appearance, hypothyroidism, hypo/agammaglobulinemia, and lymphopenia accompanied by intermittent anaemia/thrombocytopenia. All had chronic respiratory symptoms, and four died in early childhood from respiratory or GI infections.

Functional studies demonstrated reduced PRIM1 protein levels, replication fork defects and prolonged S-phase duration in PRIM1-deficient cells. The resulting delay to the cell cycle and inability to sustain sufficient cell proliferation provides a likely mechanism for the presenting phenotype.
Sources: Literature; to: - PMID: 33060134 (2020) - From a cohort of 220 families with microcephalic dwarfism spectrum disorders (OFC ≤−4 SD; height ≤−2 SD), three families (4 individuals) were identified with the same homozygous intronic variant (c.638+36C>G) in PRIM1. This variant was present in gnomAD in 2 individuals across all populations, but only in a heterozygous state. Haplotype analysis indicated that all three families share a distant common ancestor - i.e. confirmed founder variant.
Authors subsequently identified a single individual with compound heterozygous PRIM1 variants (c.103+1G>T, c.901T>C) from the DDD study, who also presented microcephaly and short stature (OFC ≤−3 SD; height ≤−3 SD).

Clinical overlap was evident in all 5 individuals, presenting extreme pre- and postnatal growth restriction, severe microcephaly (OFC −6.0 ± 1.5 SD) with simplified gyri appearance, hypothyroidism, hypo/agammaglobulinemia, and lymphopenia accompanied by intermittent anaemia/thrombocytopaenia. All had chronic respiratory symptoms, and four died in early childhood from respiratory or GI infections.

Functional studies demonstrated reduced PRIM1 protein levels, replication fork defects and prolonged S-phase duration in PRIM1-deficient cells. The resulting delay to the cell cycle and inability to sustain sufficient cell proliferation provides a likely mechanism for the presenting phenotype.
Sources: Literature
Mendeliome v0.7003 PRIM1 Zornitza Stark gene: PRIM1 was added
gene: PRIM1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRIM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRIM1 were set to 33060134
Phenotypes for gene: PRIM1 were set to Microcephalic primordial dwarfism, MONDO:0017950
Review for gene: PRIM1 was set to AMBER
Added comment: - PMID: 33060134 (2020) - From a cohort of 220 families with microcephalic dwarfism spectrum disorders (OFC ≤−4 SD; height ≤−2 SD), three families (4 individuals) were identified with the same homozygous intronic variant (c.638+36C>G) in PRIM1. This variant was present in gnomAD in 2 individuals across all populations, but only in a heterozygous state. Haplotype analysis indicated that all three families share a distant common ancestor - i.e. confirmed founder variant.
Authors subsequently identified a single individual with compound heterozygous PRIM1 variants (c.103+1G>T, c.901T>C) from the DDD study, who also presented microcephaly and short stature (OFC ≤−3 SD; height ≤−3 SD).

Clinical overlap was evident in all 5 individuals, presenting extreme pre- and postnatal growth restriction, severe microcephaly (OFC −6.0 ± 1.5 SD) with simplified gyri appearance, hypothyroidism, hypo/agammaglobulinemia, and lymphopenia accompanied by intermittent anaemia/thrombocytopenia. All had chronic respiratory symptoms, and four died in early childhood from respiratory or GI infections.

Functional studies demonstrated reduced PRIM1 protein levels, replication fork defects and prolonged S-phase duration in PRIM1-deficient cells. The resulting delay to the cell cycle and inability to sustain sufficient cell proliferation provides a likely mechanism for the presenting phenotype.
Sources: Literature
Mendeliome v0.6998 MCM10 Zornitza Stark edited their review of gene: MCM10: Added comment: PMID 33712616: second family reported, three affected sibs with restrictive cardiomyopathy and hypoplasia of the spleen and thymus. Functional data suggested that MCM10 deficiency causes chronic replication stress that reduces cell viability due to increased genomic instability and telomere erosion.; Changed publications: 32865517, 33712616; Changed phenotypes: Susceptibility to CMV, Restrictive cardiomyopathy
Mendeliome v0.6998 CYBA Zornitza Stark Gene: cyba has been classified as Green List (High Evidence).
Mendeliome v0.6998 CYBA Zornitza Stark Phenotypes for gene: CYBA were changed from to Chronic granulomatous disease 4, autosomal recessive, MIM# 233690; MONDO:0009308
Mendeliome v0.6995 CYBA Zornitza Stark reviewed gene: CYBA: Rating: GREEN; Mode of pathogenicity: None; Publications: 2770793; Phenotypes: Chronic granulomatous disease 4, autosomal recessive, MIM# 233690, MONDO:0009308; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6995 NUP37 Zornitza Stark Phenotypes for gene: NUP37 were changed from Nephrotic syndrome to Nephrotic syndrome; Microcephaly 24, primary, autosomal recessive, MIM# 618179
Mendeliome v0.6994 NUP37 Zornitza Stark changed review comment from: Single family reported with nephrotic syndrome.
Sources: Literature; to: Single family reported with nephrotic syndrome and microcephaly.
Sources: Literature
Mendeliome v0.6994 NUP37 Zornitza Stark edited their review of gene: NUP37: Changed phenotypes: Nephrotic syndrome, Microcephaly 24, primary, autosomal recessive, MIM# 618179
Mendeliome v0.6994 COPB2 Zornitza Stark Gene: copb2 has been classified as Red List (Low Evidence).
Mendeliome v0.6994 COPB2 Zornitza Stark gene: COPB2 was added
gene: COPB2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: COPB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COPB2 were set to 29036432
Phenotypes for gene: COPB2 were set to Microcephaly 19, primary, autosomal recessive, MIM# 617800
Review for gene: COPB2 was set to RED
Added comment: Two sibs with homozygous missense variant in this gene, mice homozygous for this variant had normal brain size however. Mice compound het for null allele and missense variant had some brain features, suggesting the missense variant is hypomorphic.
Sources: Expert list
Mendeliome v0.6993 WDR62 Zornitza Stark Gene: wdr62 has been classified as Green List (High Evidence).
Mendeliome v0.6993 WDR62 Zornitza Stark Phenotypes for gene: WDR62 were changed from to Microcephaly 2, primary, autosomal recessive, with or without cortical malformations, MIM# 604317; MONDO:0011435
Mendeliome v0.6990 WDR62 Zornitza Stark reviewed gene: WDR62: Rating: GREEN; Mode of pathogenicity: None; Publications: 20890279, 20729831, 20890278, 21496009, 21834044, 22775483, 32677750, 31788460; Phenotypes: Microcephaly 2, primary, autosomal recessive, with or without cortical malformations, MIM# 604317, MONDO:0011435; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6990 TRMT10A Zornitza Stark Gene: trmt10a has been classified as Green List (High Evidence).
Mendeliome v0.6987 TRAIP Zornitza Stark Gene: traip has been classified as Green List (High Evidence).
Mendeliome v0.6983 TOP3A Zornitza Stark Gene: top3a has been classified as Green List (High Evidence).
Mendeliome v0.6983 TOP3A Zornitza Stark Phenotypes for gene: TOP3A were changed from to Microcephaly, growth restriction, and increased sister chromatid exchange 2, MIM# 618097; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 5, MIM#618098
Mendeliome v0.6980 TOP3A Zornitza Stark reviewed gene: TOP3A: Rating: GREEN; Mode of pathogenicity: None; Publications: 30057030, 33631320; Phenotypes: Microcephaly, growth restriction, and increased sister chromatid exchange 2, MIM# 618097, Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 5, MIM#618098; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6980 STIL Zornitza Stark Gene: stil has been classified as Green List (High Evidence).
Mendeliome v0.6980 STIL Zornitza Stark Phenotypes for gene: STIL were changed from to Microcephaly 7, primary, autosomal recessive, MIM# 612703; MONDO:0012989
Mendeliome v0.6977 STIL Zornitza Stark reviewed gene: STIL: Rating: GREEN; Mode of pathogenicity: None; Publications: 19215732, 22989186, 25218063, 33132204, 32677750, 29230157; Phenotypes: Microcephaly 7, primary, autosomal recessive, MIM# 612703, MONDO:0012989; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6975 STAMBP Zornitza Stark Gene: stambp has been classified as Green List (High Evidence).
Mendeliome v0.6972 PCNT Zornitza Stark Gene: pcnt has been classified as Green List (High Evidence).
Mendeliome v0.6969 NHEJ1 Zornitza Stark Gene: nhej1 has been classified as Green List (High Evidence).
Mendeliome v0.6969 NHEJ1 Zornitza Stark Phenotypes for gene: NHEJ1 were changed from to Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, MIM# 611291; Cernunnos-XLF deficiency MONDO:0012650
Mendeliome v0.6966 NHEJ1 Zornitza Stark reviewed gene: NHEJ1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30898087, 30666249, 28741180, 25288157, 24511403, 21721379, 21535335; Phenotypes: Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, MIM# 611291, Cernunnos-XLF deficiency MONDO:0012650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6966 NBN Zornitza Stark Gene: nbn has been classified as Green List (High Evidence).
Mendeliome v0.6963 MSMO1 Zornitza Stark Gene: msmo1 has been classified as Green List (High Evidence).
Mendeliome v0.6963 MSMO1 Zornitza Stark Phenotypes for gene: MSMO1 were changed from to Microcephaly, congenital cataract, and psoriasiform dermatitis, MIM# 616834; MONDO:0014793; Disorders of the metabolism of sterols
Mendeliome v0.6960 MSMO1 Zornitza Stark reviewed gene: MSMO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21285510, 24144731, 28673550, 33161406; Phenotypes: Microcephaly, congenital cataract, and psoriasiform dermatitis, MIM# 616834, MONDO:0014793; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6960 MCPH1 Zornitza Stark Gene: mcph1 has been classified as Green List (High Evidence).
Mendeliome v0.6960 MCPH1 Zornitza Stark Phenotypes for gene: MCPH1 were changed from to Microcephaly 1, primary, autosomal recessive, MIM# 251200; MONDO:0009617
Mendeliome v0.6957 MCPH1 Zornitza Stark reviewed gene: MCPH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12046007, 15199523, 16311745, 20978018, 32294449, 30351297, 29026105; Phenotypes: Microcephaly 1, primary, autosomal recessive, MIM# 251200, MONDO:0009617; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6957 ATP1A3 Zornitza Stark Gene: atp1a3 has been classified as Green List (High Evidence).
Mendeliome v0.6953 LARP7 Zornitza Stark Gene: larp7 has been classified as Green List (High Evidence).
Mendeliome v0.6950 KNL1 Zornitza Stark Gene: knl1 has been classified as Green List (High Evidence).
Mendeliome v0.6950 KNL1 Zornitza Stark Phenotypes for gene: KNL1 were changed from to Microcephaly 4, primary, autosomal recessive, MIM# 604321; MONDO:0011437
Mendeliome v0.6947 KNL1 Zornitza Stark reviewed gene: KNL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22983954, 26626498, 27149178, 30304678, 27784895; Phenotypes: Microcephaly 4, primary, autosomal recessive, MIM# 604321, MONDO:0011437; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6946 BAAT Zornitza Stark Gene: baat has been classified as Green List (High Evidence).
Mendeliome v0.6943 KIF11 Zornitza Stark Gene: kif11 has been classified as Green List (High Evidence).
Mendeliome v0.6940 IER3IP1 Zornitza Stark Gene: ier3ip1 has been classified as Green List (High Evidence).
Mendeliome v0.6937 EFTUD2 Zornitza Stark Gene: eftud2 has been classified as Green List (High Evidence).
Mendeliome v0.6937 EFTUD2 Zornitza Stark Phenotypes for gene: EFTUD2 were changed from to Mandibulofacial dysostosis, Guion-Almeida type, MIM# 610536; Mandibulofacial dysostosis-microcephaly syndrome MONDO:0012516
Mendeliome v0.6934 EFTUD2 Zornitza Stark reviewed gene: EFTUD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22305528, 23188108, 33601405, 33262786, 26507355; Phenotypes: Mandibulofacial dysostosis, Guion-Almeida type, MIM# 610536, Mandibulofacial dysostosis-microcephaly syndrome MONDO:0012516; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.6934 CEP152 Zornitza Stark Gene: cep152 has been classified as Green List (High Evidence).
Mendeliome v0.6934 CEP152 Zornitza Stark Phenotypes for gene: CEP152 were changed from to Microcephaly 9, primary, autosomal recessive, MIM# 614852; MONDO:0013923; Seckel syndrome 5, MIM# 613823; MONDO:0013443
Mendeliome v0.6931 CEP152 Zornitza Stark reviewed gene: CEP152: Rating: GREEN; Mode of pathogenicity: None; Publications: 20598275, 22775483, 21131973, 23199753; Phenotypes: Microcephaly 9, primary, autosomal recessive, MIM# 614852, MONDO:0013923, Seckel syndrome 5, MIM# 613823, MONDO:0013443; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6931 GNPAT Zornitza Stark Gene: gnpat has been classified as Green List (High Evidence).
Mendeliome v0.6931 GNPAT Zornitza Stark Phenotypes for gene: GNPAT were changed from to Rhizomelic chondrodysplasia punctata, type 2, MIM# 222765; MONDO:0009112
Mendeliome v0.6928 GNPAT Zornitza Stark reviewed gene: GNPAT: Rating: GREEN; Mode of pathogenicity: None; Publications: 9536089, 11152660, 21990100; Phenotypes: Rhizomelic chondrodysplasia punctata, type 2, MIM# 222765, MONDO:0009112; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6927 CD4 Zornitza Stark Gene: cd4 has been classified as Green List (High Evidence).
Mendeliome v0.6927 CD4 Zornitza Stark Phenotypes for gene: CD4 were changed from to Immunodeficiency 79, MIM# 619238; Absence of CD4+ T cells; exuberant, relapsing, treatment-refractory warts
Mendeliome v0.6924 CD4 Zornitza Stark changed review comment from: Single individual reported, functional data, emerging gene.; to: Two individuals reported, functional data.
Mendeliome v0.6924 CD4 Zornitza Stark edited their review of gene: CD4: Changed rating: GREEN; Changed publications: 31781092, 33471124; Changed phenotypes: Immunodeficiency 79, MIM# 619238, Absence of CD4+ T cells, exuberant, relapsing, treatment-refractory warts
Mendeliome v0.6924 TMEM231 Zornitza Stark Gene: tmem231 has been classified as Green List (High Evidence).
Mendeliome v0.6921 TMEM216 Zornitza Stark Gene: tmem216 has been classified as Green List (High Evidence).
Mendeliome v0.6918 TMEM138 Zornitza Stark Gene: tmem138 has been classified as Green List (High Evidence).
Mendeliome v0.6915 TCTN2 Zornitza Stark Gene: tctn2 has been classified as Green List (High Evidence).
Mendeliome v0.6912 TCTN1 Zornitza Stark Gene: tctn1 has been classified as Green List (High Evidence).
Mendeliome v0.6908 SMCHD1 Zornitza Stark edited their review of gene: SMCHD1: Added comment: Bosma arhinia microphthalmia syndrome (BAMS) is characterized by severe hypoplasia of the nose and eyes, palatal abnormalities, deficient taste and smell, inguinal hernias, hypogonadotropic hypogonadism with cryptorchidism, and normal intelligence. Choanal atresia is a feature. More than 30 unrelated individuals reported. Caused by gain of function missense variants with the extended ATPase domain.; Changed rating: GREEN; Changed mode of pathogenicity: Other; Changed publications: 28067909; Changed phenotypes: Bosma arhinia microphthalmia syndrome, MIM# 603457, Arhinia, choanal atresia, microphthalmia MONDO:0011323; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.6908 SMCHD1 Zornitza Stark Phenotypes for gene: SMCHD1 were changed from Bosma arhinia microphthalmia syndrome, MIM 603457; Fascioscapulohumeral muscular dystrophy 2, digenic to Bosma arhinia microphthalmia syndrome, MIM 603457; Arhinia, choanal atresia, microphthalmia MONDO:0011323; Fascioscapulohumeral muscular dystrophy 2, digenic
Mendeliome v0.6906 TXNL4A Zornitza Stark Gene: txnl4a has been classified as Green List (High Evidence).
Mendeliome v0.6906 TXNL4A Zornitza Stark Phenotypes for gene: TXNL4A were changed from to Burn-McKeown syndrome, MIM# 608572; Choanal atresia - deafness - cardiac defects - dysmorphism syndrome, MONDO:0012064
Mendeliome v0.6903 TXNL4A Zornitza Stark reviewed gene: TXNL4A: Rating: GREEN; Mode of pathogenicity: None; Publications: 25434003; Phenotypes: Burn-McKeown syndrome, MIM# 608572, Choanal atresia - deafness - cardiac defects - dysmorphism syndrome, MONDO:0012064; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6901 SPINT2 Zornitza Stark changed review comment from: More than 15 unrelated families reported.; to: Well established gene-disease association. PMID 30445423 reviews 34 patients from 26 families: 13 different variants in SPINT2 were seen, including 3 premature termination codons, 2 start codon removals, and 3 canonical splice site variants, supporting loss of function as the pathogenic mechanism. The most commonly observed variant was Y163C, observed in 40 (59%) of 68 disease alleles. Seven unrelated patients with the Y163C mutation had a shared haplotype, suggesting that it is a founder mutation. Choanal atresia (20/34) and keratitis of infantile onset (26/34) were the most common findings. All patients presented with intractable diarrhoea, with onset typically in the first 2 weeks of life. Episodes of intestinal pseudoobstruction sometimes preceded the onset of diarrhoea. Characteristic epithelial tufts on intestinal histology were seen in 13 of the 34 patients.
Mendeliome v0.6901 FOXE1 Zornitza Stark Gene: foxe1 has been classified as Green List (High Evidence).
Mendeliome v0.6898 MIB1 Zornitza Stark Gene: mib1 has been classified as Green List (High Evidence).
Mendeliome v0.6897 ANO3 Zornitza Stark Gene: ano3 has been classified as Green List (High Evidence).
Mendeliome v0.6894 IPO8 Zornitza Stark Gene: ipo8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6894 IPO8 Zornitza Stark Classified gene: IPO8 as Amber List (moderate evidence)
Mendeliome v0.6894 IPO8 Zornitza Stark Gene: ipo8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6893 IPO8 Zornitza Stark gene: IPO8 was added
gene: IPO8 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: IPO8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IPO8 were set to Loeys-Dietz syndrome-like; cardiovascular, neurologic, skeletal and immunologic abnormalities
Review for gene: IPO8 was set to AMBER
Added comment: 12 individuals from 9 unrelated families in a cohort submitted for publication with bi-allelic IPO8 variants. Variants were nonsense/splice and some missense. Patients displayed a phenotype reminiscent of Loeys Dietz syndrome that variably combined cardiovascular, neurologic, skeletal and immunologic abnormalities along with dysmorphic features. Western blot on patient cells (4 individuals) showed reduced IPO8 expression. Disruption of IPO8 homologue in zebrafish associated with cardiac anomalies. Transcriptome analysis in zebrafish showed that IPO8-deficient zebrafish had abnormal TGFbeta pathway expression.
Sources: Expert Review
Mendeliome v0.6891 FAM20C Zornitza Stark Gene: fam20c has been classified as Green List (High Evidence).
Mendeliome v0.6886 ANKS6 Zornitza Stark Gene: anks6 has been classified as Green List (High Evidence).
Mendeliome v0.6886 ANKS6 Zornitza Stark Phenotypes for gene: ANKS6 were changed from to Nephronophthisis 16, MIM# 615382; MONDO:0014158
Mendeliome v0.6883 ANKS6 Zornitza Stark reviewed gene: ANKS6: Rating: GREEN; Mode of pathogenicity: None; Publications: 23793029, 31678577, 31635528, 26039630, 24610927; Phenotypes: Nephronophthisis 16, MIM# 615382, MONDO:0014158; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6883 GLIS2 Zornitza Stark Phenotypes for gene: GLIS2 were changed from Nephronophthisis 7, OMIM#611498 to Nephronophthisis 7, OMIM#611498; MONDO:0012680
Mendeliome v0.6881 GLIS2 Zornitza Stark edited their review of gene: GLIS2: Changed publications: 17618285, 23559409, 31676329; Changed phenotypes: Nephronophthisis 7, OMIM#611498, MONDO:0012680
Mendeliome v0.6881 CLDN2 Zornitza Stark Phenotypes for gene: CLDN2 were changed from Susceptibility to pancreatitis to Susceptibility to pancreatitis; Azoospermia, obstructive, with nephrolithiasis, MIM# 301060
Mendeliome v0.6878 CLDN2 Zornitza Stark edited their review of gene: CLDN2: Added comment: Azoospermia: single multigenerational family reported.; Changed publications: 29884332, 31163246, 31320686; Changed phenotypes: Susceptibility to pancreatitis, Azoospermia, obstructive, with nephrolithiasis, MIM# 301060; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.6877 FLII Zornitza Stark Classified gene: FLII as Green List (high evidence)
Mendeliome v0.6877 FLII Zornitza Stark Gene: flii has been classified as Green List (High Evidence).
Mendeliome v0.6876 POLR3A Elena Savva commented on gene: POLR3A: c.1909+22G>A is a recurring variant that results in a leaky splice site

Bi-allelic variants associated with Leukodystrophy and with Wiedemann-Rautenstrauch syndrome; note association between mono-allelic variants and susceptibility to severe VZV infection.

Deep intronic variants commonly pathogenic

No clear gen-phen correlation
Mendeliome v0.6876 HSF2BP Zornitza Stark Gene: hsf2bp has been classified as Red List (Low Evidence).
Mendeliome v0.6876 HSF2BP Zornitza Stark gene: HSF2BP was added
gene: HSF2BP was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: HSF2BP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HSF2BP were set to 32845237
Phenotypes for gene: HSF2BP were set to Premature ovarian failure, OMIM#619245
Review for gene: HSF2BP was set to RED
Added comment: Single family reported where homozygous missense variant segregated with POF in three sisters.
Sources: Expert list
Mendeliome v0.6875 COL4A6 Zornitza Stark Gene: col4a6 has been classified as Red List (Low Evidence).
Mendeliome v0.6872 COL4A6 Zornitza Stark Classified gene: COL4A6 as Red List (low evidence)
Mendeliome v0.6872 COL4A6 Zornitza Stark Gene: col4a6 has been classified as Red List (Low Evidence).
Mendeliome v0.6871 RNF6 Zornitza Stark Gene: rnf6 has been classified as Red List (Low Evidence).
Mendeliome v0.6871 RNF6 Zornitza Stark Classified gene: RNF6 as Red List (low evidence)
Mendeliome v0.6871 RNF6 Zornitza Stark Gene: rnf6 has been classified as Red List (Low Evidence).
Mendeliome v0.6870 MED12 Zornitza Stark Gene: med12 has been classified as Green List (High Evidence).
Mendeliome v0.6867 BMPR2 Zornitza Stark Gene: bmpr2 has been classified as Green List (High Evidence).
Mendeliome v0.6867 BMPR2 Zornitza Stark Phenotypes for gene: BMPR2 were changed from to Pulmonary venoocclusive disease 1 MIM#265450; Pulmonary hypertension, familial primary, 1, with or without HHT MIM#178600; Pulmonary hypertension, primary, fenfluramine or dexfenfluramine-associated MIM#178600
Mendeliome v0.6863 BMPR2 Elena Savva reviewed gene: BMPR2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 33380512; Phenotypes: Pulmonary venoocclusive disease 1 MIM#265450, Pulmonary hypertension, familial primary, 1, with or without HHT MIM#178600, Pulmonary hypertension, primary, fenfluramine or dexfenfluramine-associated MIM#178600; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.6863 ZNF711 Zornitza Stark Gene: znf711 has been classified as Green List (High Evidence).
Mendeliome v0.6860 SLC35A2 Zornitza Stark Gene: slc35a2 has been classified as Green List (High Evidence).
Mendeliome v0.6860 SLC35A2 Zornitza Stark Phenotypes for gene: SLC35A2 were changed from to Congenital disorder of glycosylation, type IIm (MIM #300896) 30817854; Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE)
Mendeliome v0.6857 SLC35A2 Zornitza Stark reviewed gene: SLC35A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23561849, 24115232, 27743886, 25778940, 33407896; Phenotypes: Congenital disorder of glycosylation, type IIm (MIM #300896) 30817854, Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE); 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 v0.6856 MEF2A Zornitza Stark Gene: mef2a has been classified as Red List (Low Evidence).
Mendeliome v0.6855 MEF2A Zornitza Stark Classified gene: MEF2A as Red List (low evidence)
Mendeliome v0.6855 MEF2A Zornitza Stark Gene: mef2a has been classified as Red List (Low Evidence).
Mendeliome v0.6854 FN1 Zornitza Stark Gene: fn1 has been classified as Green List (High Evidence).
Mendeliome v0.6854 FN1 Zornitza Stark Phenotypes for gene: FN1 were changed from to Glomerulopathy with fibronectin deposits 2 (MIM#601894); Spondylometaphyseal dysplasia, corner fracture type (MIM#184255)
Mendeliome v0.6851 IL37 Zornitza Stark Gene: il37 has been classified as Red List (Low Evidence).
Mendeliome v0.6851 IL37 Zornitza Stark gene: IL37 was added
gene: IL37 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IL37 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL37 were set to 33674380
Phenotypes for gene: IL37 were set to Infantile inflammatory bowel disease
Review for gene: IL37 was set to RED
Added comment: Single family reported with homozygous truncating variant this gene and infantile-onset of IBD, some functional data.
Sources: Literature
Mendeliome v0.6850 PEX10 Teresa Zhao reviewed gene: PEX10: Rating: GREEN; Mode of pathogenicity: None; Publications: 30640048; Phenotypes: Peroxisome biogenesis disorder 6A (Zellweger) (MIM#614870), Peroxisome biogenesis disorder 6B (MIM#614871); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6850 FN1 Ain Roesley reviewed gene: FN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29100092; Phenotypes: Glomerulopathy with fibronectin deposits 2 (MIM#601894), Spondylometaphyseal dysplasia, corner fracture type (MIM#184255); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.6850 CHRDL1 Zornitza Stark Gene: chrdl1 has been classified as Green List (High Evidence).
Mendeliome v0.6847 HDL2 Bryony Thompson Str: hdl2 has been classified as Green List (High Evidence).
Mendeliome v0.6847 HDL2 Bryony Thompson Classified STR: HDL2 as Green List (high evidence)
Mendeliome v0.6847 HDL2 Bryony Thompson Str: hdl2 has been classified as Green List (High Evidence).
Mendeliome v0.6846 HDL2 Bryony Thompson STR: HDL2 was added
STR: HDL2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for STR: HDL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: HDL2 were set to 20301701
Phenotypes for STR: HDL2 were set to Huntington disease-like 2 MIM#606438
Review for STR: HDL2 was set to GREEN
STR: HDL2 was marked as clinically relevant
Added comment: NM_001271604.2:c.431CTG[X] or NM_020655.4:c.382+760CTG[X]
In an alternatively spliced exon, the repeat can be transcribed in both directions, leading to CUG (more common) or CAG (less common) repeat-containing transcripts. While a dominant RNA toxic effect may occur, the repeat expansion also reduces levels of the Junctophilin-3 protein
Normal: ≤28 repeats
Questionable significance: 29-39 repeats, mutable normal or reduced penetrance included
Full penetrance: ≥40 repeats
Sources: Expert list
Mendeliome v0.6845 JPH3 Bryony Thompson Classified gene: JPH3 as No list
Mendeliome v0.6845 JPH3 Bryony Thompson Added comment: Comment on list classification: See STRs for this panel
Mendeliome v0.6844 DM2 Bryony Thompson Str: dm2 has been classified as Green List (High Evidence).
Mendeliome v0.6844 DM2 Bryony Thompson Classified STR: DM2 as Green List (high evidence)
Mendeliome v0.6844 DM2 Bryony Thompson Str: dm2 has been classified as Green List (High Evidence).
Mendeliome v0.6843 DM2 Bryony Thompson STR: DM2 was added
STR: DM2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for STR: DM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: DM2 were set to 20301639; 29325606
Phenotypes for STR: DM2 were set to Myotonic dystrophy 2 MIM#602668
Review for STR: DM2 was set to GREEN
STR: DM2 was marked as clinically relevant
Added comment: HGVS nomenclature: NM_003418.4:c.-14-833_-14-830[X]
Toxic gain of function RNA expected mechanism of disease
Normal: ≤30 uninterrupted CCTG repeats, 11-26 CCTG repeats with any GCTC or TCTG interruptions
Unknown significance (normal vs. mutable): 27-29 CCTG repeats
Mutable normal (premutation) alleles. ~30-~54 CCTG repeats
Unknown significance (premutation vs pathogenic): ~55-74 CCTG repeats
Pathogenic: ~75-11,000 CCTG repeats
Sources: Expert list
Mendeliome v0.6842 CNBP Bryony Thompson Classified gene: CNBP as No list
Mendeliome v0.6842 CNBP Bryony Thompson Added comment: Comment on list classification: Condition is caused by a CCTG expansion in intron 1. No reported SNVs or indels reported in association with disease. Present under STRs on this panel
Mendeliome v0.6841 DM1 Bryony Thompson Str: dm1 has been classified as Green List (High Evidence).
Mendeliome v0.6841 DM1 Bryony Thompson Classified STR: DM1 as Green List (high evidence)
Mendeliome v0.6841 DM1 Bryony Thompson Str: dm1 has been classified as Green List (High Evidence).
Mendeliome v0.6840 DM1 Bryony Thompson STR: DM1 was added
STR: DM1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for STR: DM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: DM1 were set to 20301344; 29325606
Phenotypes for STR: DM1 were set to Myotonic dystrophy 1 MIM#160900
Review for STR: DM1 was set to GREEN
STR: DM1 was marked as clinically relevant
Added comment: HGVS nomenclature: NM_001081560.2:c.*224_*226CTG[X]
RNA toxic gain of function is mechanism of disease
Premutation: 35-49 repeats, no clinical signs
Mild: 50-~150 repeats, age of onset 20-70 yrs, clinical signs - cataracts, mild myotonia
Classic: ~100-~1,000 repeats, age of onset 10-30 yrs, clinical signs - weakness, myotonia, cataracts, balding, cardiac arrhythmia
Congenital: >1,000 repeats, age of onset birth-10 yrs , clinical signs - infantile hypotonia, respiratory deficits, intellectual disability, classic signs in adults
Sources: Expert list
Mendeliome v0.6839 DMPK Bryony Thompson Classified gene: DMPK as No list
Mendeliome v0.6839 DMPK Bryony Thompson Added comment: Comment on list classification: STR is the only cause of condition for this gene and is present in STRs for this panel.
Mendeliome v0.6838 SCA17 Bryony Thompson Str: sca17 has been classified as Green List (High Evidence).
Mendeliome v0.6838 SCA17 Bryony Thompson Classified STR: SCA17 as Green List (high evidence)
Mendeliome v0.6838 SCA17 Bryony Thompson Str: sca17 has been classified as Green List (High Evidence).
Mendeliome v0.6836 TBP Bryony Thompson Classified gene: TBP as No list
Mendeliome v0.6836 TBP Bryony Thompson Added comment: Comment on list classification: See STRs
Mendeliome v0.6835 SCA12 Bryony Thompson Str: sca12 has been classified as Green List (High Evidence).
Mendeliome v0.6835 SCA12 Bryony Thompson Classified STR: SCA12 as Green List (high evidence)
Mendeliome v0.6835 SCA12 Bryony Thompson Str: sca12 has been classified as Green List (High Evidence).
Mendeliome v0.6834 SCA12 Bryony Thompson STR: SCA12 was added
STR: SCA12 was added to Mendeliome. Sources: Expert list
Mode of inheritance for STR: SCA12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: SCA12 were set to 29325606; 20301381
Phenotypes for STR: SCA12 were set to Spinocerebellar ataxia 12 MIM#604326
Review for STR: SCA12 was set to GREEN
STR: SCA12 was marked as clinically relevant
Added comment: NM_181675.3:c.27CAG[X]
Uncertain if CAG repeat encodes polyglutamine or instead effects expression of specific splice variants of the encoded phosphatase
Normal: ≤32 repeats
Reduced penetrance: ~40-66 repeats
Full penetrance: ≥66 repeats
Sources: Expert list
Mendeliome v0.6833 PPP2R2B Bryony Thompson Classified gene: PPP2R2B as No list
Mendeliome v0.6832 SCA36 Bryony Thompson Str: sca36 has been classified as Green List (High Evidence).
Mendeliome v0.6832 SCA36 Bryony Thompson Classified STR: SCA36 as Green List (high evidence)
Mendeliome v0.6832 SCA36 Bryony Thompson Str: sca36 has been classified as Green List (High Evidence).
Mendeliome v0.6831 SCA36 Bryony Thompson STR: SCA36 was added
STR: SCA36 was added to Mendeliome. Sources: Expert list
Mode of inheritance for STR: SCA36 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: SCA36 were set to 25101480
Phenotypes for STR: SCA36 were set to Spinocerebellar ataxia 36 MIM#614153
Review for STR: SCA36 was set to GREEN
STR: SCA36 was marked as clinically relevant
Added comment: NM_006392​.3:c.3+71GGCCTG[X]
Toxic RNA effect is suggested mechanism of disease
Normal: 3-14 repeats
Uncertain significance: 15-650 repeats
Pathogenic: ≥650 repeats
Sources: Expert list
Mendeliome v0.6830 NOP56 Bryony Thompson Classified gene: NOP56 as No list
Mendeliome v0.6830 NOP56 Bryony Thompson Added comment: Comment on list classification: A hexanucleotide (GGCCTG) repeat expansion in the first intron of the NOP56 gene is the only reported cause of disease. See STRS
Mendeliome v0.6829 SCA37 Bryony Thompson Str: sca37 has been classified as Green List (High Evidence).
Mendeliome v0.6829 SCA37 Bryony Thompson Classified STR: SCA37 as Green List (high evidence)
Mendeliome v0.6829 SCA37 Bryony Thompson Str: sca37 has been classified as Green List (High Evidence).
Mendeliome v0.6828 SCA37 Bryony Thompson STR: SCA37 was added
STR: SCA37 was added to Mendeliome. Sources: Expert list
Mode of inheritance for STR: SCA37 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: SCA37 were set to 28686858; 31145571
Phenotypes for STR: SCA37 were set to Spinocerebellar ataxia 37 MIM#615945
Review for STR: SCA37 was set to GREEN
STR: SCA37 was marked as clinically relevant
Added comment: NC_000001.10:g.57832716_57832797ins[(ATTTT)60-79(ATTTC)31-75(ATTTT)58-90]
Located in a 5'UTR intron, flanked by (ATTTT)n on both sides
Non-pathogenic allele: (ATTTT)7–400
Pathogenic allele: [(ATTTT)60–79(ATTTC)31–75(ATTTT)58–90]
Sources: Expert list
Mendeliome v0.6827 DAB1 Bryony Thompson Classified gene: DAB1 as No list
Mendeliome v0.6826 SCA31 Bryony Thompson Str: sca31 has been classified as Green List (High Evidence).
Mendeliome v0.6826 SCA31 Bryony Thompson Classified STR: SCA31 as Green List (high evidence)
Mendeliome v0.6826 SCA31 Bryony Thompson Str: sca31 has been classified as Green List (High Evidence).
Mendeliome v0.6825 SCA31 Bryony Thompson STR: SCA31 was added
STR: SCA31 was added to Mendeliome. Sources: Expert list
Mode of inheritance for STR: SCA31 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: SCA31 were set to 19878914; 31755042
Phenotypes for STR: SCA31 were set to Spinocerebellar ataxia 31 MIM#117210
Review for STR: SCA31 was set to GREEN
STR: SCA31 was marked as clinically relevant
Added comment: Complex repeat insertion (TGGAA)n, (TAGAA)n, (TAAAA)n, (TAAAATAGAA)n, TGGAA is present only in affected cases. Sequencing showed that the insertion consisted of a preceding TCAC sequence, and 3 pentanucleotide repeat components (TGGAA)n, (TAGAA)n, and (TAAAA)n in all patients tested.
2.5-3.8 KB insertion is associated with disease and RNA toxicity expected to be mechanism of disease
Normal and pathogenic cut-offs are based on animal model experiments (PMID: 31755042)
Sources: Expert list
Mendeliome v0.6824 BEAN1 Bryony Thompson Classified gene: BEAN1 as No list
Mendeliome v0.6823 SCA7 Bryony Thompson Str: sca7 has been classified as Green List (High Evidence).
Mendeliome v0.6823 SCA7 Bryony Thompson Classified STR: SCA7 as Green List (high evidence)
Mendeliome v0.6823 SCA7 Bryony Thompson Str: sca7 has been classified as Green List (High Evidence).
Mendeliome v0.6821 ATXN7 Bryony Thompson Classified gene: ATXN7 as No list
Mendeliome v0.6820 SCA3 Bryony Thompson Str: sca3 has been classified as Green List (High Evidence).
Mendeliome v0.6820 SCA3 Bryony Thompson Classified STR: SCA3 as Green List (high evidence)
Mendeliome v0.6820 SCA3 Bryony Thompson Str: sca3 has been classified as Green List (High Evidence).
Mendeliome v0.6819 SCA3 Bryony Thompson STR: SCA3 was added
STR: SCA3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for STR: SCA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: SCA3 were set to 20301375; 29325606
Phenotypes for STR: SCA3 were set to Machado-Joseph disease MIM#109150; Spinocerebellar ataxia type 3
Review for STR: SCA3 was set to GREEN
STR: SCA3 was marked as clinically relevant
Added comment: NM_004993​.5:c.886_888CAG[X]
Toxic aggregation and mislocalization in neurons is mechanism of disease
Normal: ≤44 repeats, mostly <31 repeats
Intermediate: 45-59 repeats, some intermediate alleles are not associated with classic clinical features of SCA3
Pathogenic (full penetrance): ≥60 repeats
Sources: Expert list
Mendeliome v0.6818 ATXN3 Bryony Thompson Classified gene: ATXN3 as No list
Mendeliome v0.6817 SCA2 Bryony Thompson Str: sca2 has been classified as Green List (High Evidence).
Mendeliome v0.6817 SCA2 Bryony Thompson Classified STR: SCA2 as Green List (high evidence)
Mendeliome v0.6817 SCA2 Bryony Thompson Str: sca2 has been classified as Green List (High Evidence).
Mendeliome v0.6816 SCA2 Bryony Thompson STR: SCA2 was added
STR: SCA2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for STR: SCA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: SCA2 were set to 29325606; 20301452
Phenotypes for STR: SCA2 were set to Spinocerebellar ataxia 2 MIM#183090
Review for STR: SCA2 was set to GREEN
STR: SCA2 was marked as clinically relevant
Added comment: NM_002973​.3:c.496_498CAG[X]
Toxic protein aggregation is mechanism of disease
Benign: ≤31 repeats (homozygous 31/31 repeats reported for recessive SCA2)
Uncertain: 32 repeats
ALS risk allele: 30-32 repeats
Reduced penetrance: 33-34 repeats, may not develop symptoms or only very late in life
Full penetrance: ≥35 repeats
Interruption of a CAG expanded allele by a CAA repeat does not mitigate the pathogenicity of the repeat size, but may enhance the meiotic stability of the repeat
Sources: Expert list
Mendeliome v0.6815 ATXN2 Bryony Thompson Classified gene: ATXN2 as No list
Mendeliome v0.6814 SCA10 Bryony Thompson Str: sca10 has been classified as Green List (High Evidence).
Mendeliome v0.6814 SCA10 Bryony Thompson Classified STR: SCA10 as Green List (high evidence)
Mendeliome v0.6814 SCA10 Bryony Thompson Str: sca10 has been classified as Green List (High Evidence).
Mendeliome v0.6813 SCA10 Bryony Thompson STR: SCA10 was added
STR: SCA10 was added to Mendeliome. Sources: Expert list
Mode of inheritance for STR: SCA10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: SCA10 were set to 20301354
Phenotypes for STR: SCA10 were set to Spinocerebellar ataxia 10 MIM#603516
Review for STR: SCA10 was set to GREEN
STR: SCA10 was marked as clinically relevant
Added comment: NM_013236​.2:c.1430+54822ATTCT[X]
Toxic RNA gain-of-function mechanism of disease
Normal alleles: 10-32 ATTCT repeats
Alleles of questionable significance: 33-280 ATTCT repeats
Reduced-penetrance alleles: 33-850 repeats
Full-penetrance alleles: 800-4,500 ATTCT repeats
Sources: Expert list
Mendeliome v0.6812 ATXN10 Bryony Thompson Classified gene: ATXN10 as No list
Mendeliome v0.6811 INPP4A Zornitza Stark Gene: inpp4a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6811 INPP4A Zornitza Stark Classified gene: INPP4A as Amber List (moderate evidence)
Mendeliome v0.6811 INPP4A Zornitza Stark Gene: inpp4a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6810 INPP4A Zornitza Stark gene: INPP4A was added
gene: INPP4A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: INPP4A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INPP4A were set to 31978615; 31938306; 25338135; 20011524
Phenotypes for gene: INPP4A were set to Intellectual disability
Review for gene: INPP4A was set to AMBER
Added comment: Two families reported with bi-allelic variants and a neurological phenotype. Supportive mouse model and expression data.
Sources: Literature
Mendeliome v0.6808 SATB1 Zornitza Stark edited their review of gene: SATB1: Added comment: Kohlschutter-Tonz syndrome-like (KTZSL) is characterized by global developmental delay with moderately to severely impaired intellectual development, poor or absent speech, and delayed motor skills. Although the severity of the disorder varies, many patients are nonverbal and have hypotonia with inability to sit or walk. Early-onset epilepsy is common and may be refractory to treatment, leading to epileptic encephalopathy and further interruption of developmental progress. Most patients have feeding difficulties with poor overall growth and dysmorphic facial features, as well as significant dental anomalies resembling amelogenesis imperfecta. This phenotype was reported in 28 patients (patients 13 to 40, PMID 33513338), including 9 patients from 3 families. Most variants were de novo, though some were inherited, suggestive of incomplete penetrance and variable expressivity.; Changed phenotypes: Developmental delay with dysmorphic facies and dental anomalies, MIM# 619228, Kohlschutter-Tonz syndrome-like, MIM# 619229
Mendeliome v0.6808 SATB1 Zornitza Stark commented on gene: SATB1: Developmental delay with dysmorphic facies and dental anomalies (DEFDA) is characterized by generally mild global developmental delay with variably impaired intellectual development, walking by 2 to 3 years, and slow language acquisition. The severity of the disorder ranges from moderate cognitive deficits to mild learning difficulties or behavioral abnormalities. Most patients have dysmorphic facial features, often with abnormal dentition and nonspecific visual defects, such as myopia, astigmatism, and strabismus. Although rare, involvement of other systems, such as skeletal, cardiac, and gastrointestinal, may be present. 12 individuals from 11 families reported (one inherited variant, affected parent).
Mendeliome v0.6805 MKS1 Zornitza Stark Gene: mks1 has been classified as Green List (High Evidence).
Mendeliome v0.6802 FLII Zornitza Stark Gene: flii has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6802 FLII Zornitza Stark Classified gene: FLII as Amber List (moderate evidence)
Mendeliome v0.6802 FLII Zornitza Stark Gene: flii has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6800 RHBDF1 Zornitza Stark Gene: rhbdf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6800 RHBDF1 Zornitza Stark Classified gene: RHBDF1 as Amber List (moderate evidence)
Mendeliome v0.6800 RHBDF1 Zornitza Stark Gene: rhbdf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6798 MYLK3 Zornitza Stark Gene: mylk3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6798 MYLK3 Zornitza Stark Classified gene: MYLK3 as Amber List (moderate evidence)
Mendeliome v0.6798 MYLK3 Zornitza Stark Gene: mylk3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6797 MYLK3 Zornitza Stark gene: MYLK3 was added
gene: MYLK3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MYLK3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: MYLK3 were set to 29235529; 31244672; 32213617; 32870709
Phenotypes for gene: MYLK3 were set to Dilated cardiomyopathy
Review for gene: MYLK3 was set to AMBER
Added comment: Two families reported with mono-allelic variants (one extension, one frameshift), and three consanguineous families reported with bi-allelic variants (two hmz frameshift, one hmz missense). Supportive mouse models.
Sources: Literature
Mendeliome v0.6796 NRAP Zornitza Stark Gene: nrap has been classified as Green List (High Evidence).
Mendeliome v0.6796 NRAP Zornitza Stark Classified gene: NRAP as Green List (high evidence)
Mendeliome v0.6796 NRAP Zornitza Stark Gene: nrap has been classified as Green List (High Evidence).
Mendeliome v0.6794 MPEG1 Zornitza Stark Gene: mpeg1 has been classified as Green List (High Evidence).
Mendeliome v0.6794 MPEG1 Zornitza Stark Classified gene: MPEG1 as Green List (high evidence)
Mendeliome v0.6794 MPEG1 Zornitza Stark Gene: mpeg1 has been classified as Green List (High Evidence).
Mendeliome v0.6793 MPEG1 Zornitza Stark gene: MPEG1 was added
gene: MPEG1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MPEG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MPEG1 were set to 33224153; 33692780; 28422754
Phenotypes for gene: MPEG1 were set to Immunodeficiency 77, MIM# 619223
Review for gene: MPEG1 was set to GREEN
Added comment: Immunodeficiency-77 (IMD77) is an immunologic disorder characterized by recurrent and persistent polymicrobial infections with multiple unusual organisms. Skin and pulmonary infections are the most common, consistent with increased susceptibility to epithelial cell infections. The age at onset is highly variable: some patients have recurrent infections from childhood, whereas others present in late adulthood. The limited number of reported patients are all female, suggesting incomplete penetrance or a possible sex-influenced trait. Patient cells, mainly macrophages, show impaired killing of intracellular bacteria and organisms, including nontubercular mycobacteria, although there is also impaired killing of other organisms, such as Pseudomonas, Candida, and Aspergillus.

Four individuals reported, functional data, including animal model.
Sources: Expert list
Mendeliome v0.6791 INPP5E Zornitza Stark Gene: inpp5e has been classified as Green List (High Evidence).
Mendeliome v0.6791 INPP5E Zornitza Stark Phenotypes for gene: INPP5E were changed from to Joubert syndrome 1, MIM# 213300; MONDO:0008944; Mental retardation, truncal obesity, retinal dystrophy, and micropenis, MIM# 610156; MONDO:0012423
Mendeliome v0.6788 INPP5E Zornitza Stark reviewed gene: INPP5E: Rating: GREEN; Mode of pathogenicity: None; Publications: 19668216, 32139166, 29230161, 29052317, 27998989, 27401686; Phenotypes: Joubert syndrome 1, MIM# 213300, MONDO:0008944, Mental retardation, truncal obesity, retinal dystrophy, and micropenis, MIM# 610156, MONDO:0012423; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6788 CSPP1 Zornitza Stark Gene: cspp1 has been classified as Green List (High Evidence).
Mendeliome v0.6785 CSPP1 Zornitza Stark changed review comment from: More than 20 unrelated families reported.; to: More than 20 unrelated families reported. Classically associated with Joubert syndrome; however, note 4 individuals reported with features consistent with Jeune asphyxiating thoracic dystrophy, including short ribs, bell-shaped chest, and pulmonary hypoplasia.
Mendeliome v0.6785 CEP41 Zornitza Stark Gene: cep41 has been classified as Green List (High Evidence).
Mendeliome v0.6782 SCA1 Bryony Thompson Str: sca1 has been classified as Green List (High Evidence).
Mendeliome v0.6782 SCA1 Bryony Thompson Classified STR: SCA1 as Green List (high evidence)
Mendeliome v0.6782 SCA1 Bryony Thompson Str: sca1 has been classified as Green List (High Evidence).
Mendeliome v0.6780 ATXN1 Bryony Thompson Classified gene: ATXN1 as No list
Mendeliome v0.6779 RANBP2 Bryony Thompson Gene: ranbp2 has been classified as Green List (High Evidence).
Mendeliome v0.6779 NCSTN Bryony Thompson Gene: ncstn has been classified as Green List (High Evidence).
Mendeliome v0.6779 PSENEN Bryony Thompson Gene: psenen has been classified as Green List (High Evidence).
Mendeliome v0.6776 ALDH1L2 Zornitza Stark Gene: aldh1l2 has been classified as Red List (Low Evidence).
Mendeliome v0.6776 ALDH1L2 Zornitza Stark Classified gene: ALDH1L2 as Red List (low evidence)
Mendeliome v0.6776 ALDH1L2 Zornitza Stark Gene: aldh1l2 has been classified as Red List (Low Evidence).
Mendeliome v0.6775 ESCO2 Zornitza Stark Gene: esco2 has been classified as Green List (High Evidence).
Mendeliome v0.6771 RNF113A Bryony Thompson Classified gene: RNF113A as Green List (high evidence)
Mendeliome v0.6771 RNF113A Bryony Thompson Added comment: Comment on list classification: Additional cases published
Mendeliome v0.6771 RNF113A Bryony Thompson Gene: rnf113a has been classified as Green List (High Evidence).
Mendeliome v0.6769 ALDH1L2 Naomi Baker gene: ALDH1L2 was added
gene: ALDH1L2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ALDH1L2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALDH1L2 were set to PMID: 31341639; 33168096
Phenotypes for gene: ALDH1L2 were set to pruritic ichthyosis, severe diffuse hypomyelination seen on MRI, and abnormal lipid peaks
Review for gene: ALDH1L2 was set to RED
Added comment: Individual reported with bialleleic ALDH1L2 variants (non-canonical splice and a frameshift mutation), who also has a de novo hemizygous RPS6KA3 frameshift mutation. Authors state that not all features of the individual could be explained by the RPS6KA3 variant, and that consideration of Coffin-Lowry sysndrome was only made after identification of the RPS6KA3 variant. Therefore individual has there is a blended phenotype of Coffin–Lowry syndrome and Sjögren–Larsson syndrome. From functional studies authors propose that the ALDH1L2 loss induces mitochondrial dysfunction due to reduced NADPH and increased oxidative stress (PMID: 31341639). Knockout mouse model was viable and did not show an apparent phenotype, however metabolomic analysis showed vastly changed metabotypes in the liver and plasma in these mice suggesting channeling of fatty acids away from β-oxidation. Authors therefore postulate that the role of ALDH1L2 in the lipid metabolism explains why the loss of this enzyme is associated with neuro-cutaneous disease.
Sources: Literature
Mendeliome v0.6769 FAM57B Zornitza Stark Gene: fam57b has been classified as Green List (High Evidence).
Mendeliome v0.6769 FAM57B Zornitza Stark Classified gene: FAM57B as Green List (high evidence)
Mendeliome v0.6769 FAM57B Zornitza Stark Gene: fam57b has been classified as Green List (High Evidence).
Mendeliome v0.6768 FAM57B Zornitza Stark gene: FAM57B was added
gene: FAM57B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FAM57B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM57B were set to 33077892
Phenotypes for gene: FAM57B were set to Cone–rod dystrophy; Maculopathy
Review for gene: FAM57B was set to GREEN
Added comment: 4 patients with cone-rod dystrophy or maculopathy from 3 families, with LOF pathogenic variants in TLCD3B (ceramide synthase gene). Ceramide is a proapoptotic lipid as high levels of ceramides can lead to apoptosis of neuronal cells, including photoreceptors. Variants segregated with disease. TLCD3B showed high expression in the adult retina with higher expression in the macular than in the peripheral region. Tlcd3bKO/KO mice exhibited a significant reduction of the cone photoreceptor light responses, thinning of the outer nuclear layer, and loss of cone photoreceptors across the retina.
Sources: Literature
Mendeliome v0.6767 LRRC8A Bryony Thompson Gene: lrrc8a has been classified as Red List (Low Evidence).
Mendeliome v0.6767 LRRC8A Bryony Thompson Classified gene: LRRC8A as Red List (low evidence)
Mendeliome v0.6767 LRRC8A Bryony Thompson Gene: lrrc8a has been classified as Red List (Low Evidence).
Mendeliome v0.6766 LRRC8A Bryony Thompson changed review comment from: A single case reported with a reciprocal translocation, t(9;20)(q33.2;q12), and demonstrated truncation of the LRRC8A gene. No other supporting evidence; to: A single case reported with a reciprocal translocation, t(9;20)(q33.2;q12), and demonstrated truncation of the LRRC8A gene. No other supporting evidence could be identified.
Mendeliome v0.6766 SIAE Bryony Thompson Marked gene: SIAE as ready
Mendeliome v0.6766 SIAE Bryony Thompson Gene: siae has been classified as Red List (Low Evidence).
Mendeliome v0.6766 SIAE Bryony Thompson Classified gene: SIAE as Red List (low evidence)
Mendeliome v0.6766 SIAE Bryony Thompson Gene: siae has been classified as Red List (Low Evidence).
Mendeliome v0.6765 SIAE Bryony Thompson reviewed gene: SIAE: Rating: RED; Mode of pathogenicity: None; Publications: 20555325, 28900629, 22200769; Phenotypes: {Autoimmune disease, susceptibility to, 6} MIM#613551; Mode of inheritance: Unknown
Mendeliome v0.6765 TAOK2 Bryony Thompson Gene: taok2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6765 TAOK2 Bryony Thompson edited their review of gene: TAOK2: Changed phenotypes: Generalized verrucosis, abnormal T cell activation, autism
Mendeliome v0.6765 TAOK2 Bryony Thompson Phenotypes for gene: TAOK2 were changed from Generalized verrucosis; abnormal T cell activation to Generalized verrucosis; abnormal T cell activation; autism
Mendeliome v0.6764 TAOK2 Bryony Thompson Classified gene: TAOK2 as Amber List (moderate evidence)
Mendeliome v0.6764 TAOK2 Bryony Thompson Gene: taok2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6763 TAOK2 Bryony Thompson gene: TAOK2 was added
gene: TAOK2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TAOK2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TAOK2 were set to 28385331; 29467497
Phenotypes for gene: TAOK2 were set to Generalized verrucosis; abnormal T cell activation
Review for gene: TAOK2 was set to AMBER
Added comment: PMID: 28385331 - A single consanguineous family with generalized verrucosis and abnormal T cell activation, and a homozygous missense (p.R700C), with some assays on patient fibroblasts.
PMID: 29467497 - One of the several genes in the 16p11.2 microdeletion region associated with autism. Taok2 heterozygous and knockout mice had gene dosage-dependent impairments in cognition, anxiety, social interaction, brain size, and neural connectivity. 3 de novo variants and 3 predicted loss of function variants identified in 6 unrelated autism cases. 2 of the de novo variants have supporting functional assays, but 1 of them co-occurs in an individual with a CHD8 frameshift. 1 of the predicted loss of function variants was also identified in the unaffected father and sibling.
Sources: Literature
Mendeliome v0.6762 CC2D2A Zornitza Stark Gene: cc2d2a has been classified as Green List (High Evidence).
Mendeliome v0.6759 POLR3GL Zornitza Stark Phenotypes for gene: POLR3GL were changed from endosteal hyperostosis; oligodontia; growth retardation; facial dysmorphisms; lipodystrophy to Short stature, oligodontia, dysmorphic facies, and motor delay (SOFM), MIM#619234; endosteal hyperostosis; oligodontia; growth retardation; facial dysmorphisms; lipodystrophy
Mendeliome v0.6758 INVS Zornitza Stark Gene: invs has been classified as Green List (High Evidence).
Mendeliome v0.6758 INVS Zornitza Stark Phenotypes for gene: INVS were changed from to Nephronophthisis 2, infantile, (MIM#602088)
Mendeliome v0.6755 INVS Paul De Fazio reviewed gene: INVS: Rating: GREEN; Mode of pathogenicity: None; Publications: 12872123, 19177160; Phenotypes: Nephronophthisis 2, infantile, (MIM#602088); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.6755 ZCCHC8 Bryony Thompson Gene: zcchc8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6755 ZCCHC8 Bryony Thompson Classified gene: ZCCHC8 as Amber List (moderate evidence)
Mendeliome v0.6755 ZCCHC8 Bryony Thompson Gene: zcchc8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6754 ZCCHC8 Bryony Thompson gene: ZCCHC8 was added
gene: ZCCHC8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZCCHC8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZCCHC8 were set to 31488579
Phenotypes for gene: ZCCHC8 were set to Pulmonary fibrosis
Review for gene: ZCCHC8 was set to AMBER
Added comment: A missense variant (P186L) segregates over 3 generations in a single family, and supporting in vitro assays and mouse model.
Sources: Literature
Mendeliome v0.6753 KDM5B Zornitza Stark reviewed gene: KDM5B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, autosomal recessive 65 MIM#618109, Intellectual disability and/or autism, autosomal dominant; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.6753 KDM5B Zornitza Stark Gene: kdm5b has been classified as Green List (High Evidence).
Mendeliome v0.6753 KDM5B Zornitza Stark Phenotypes for gene: KDM5B were changed from to Mental retardation, autosomal recessive 65 MIM#618109; Intellectual disability and/or autism, autosomal dominant
Mendeliome v0.6750 TPP2 Zornitza Stark Gene: tpp2 has been classified as Green List (High Evidence).
Mendeliome v0.6747 DOCK7 Zornitza Stark Gene: dock7 has been classified as Green List (High Evidence).
Mendeliome v0.6742 UBAP1 Zornitza Stark changed review comment from: PMID 31696996: Five unrelated families reported with childhood-onset HSP. A recurrent two‐base pair deletion (c.426_427delGA, p.K143Sfs*15) in the UBAP1 gene was found in four families, and a similar variant (c.475_476delTT, p.F159*) was detected in a fifth family. The variant was confirmed to be de novo in two families and inherited from an affected parent in two other families. RNA studies performed in lymphocytes from one patient with the de novo c.426_427delGA variant demonstrated escape of nonsense‐mediated decay of the UBAP1 mutant transcript, suggesting the generation of a truncated protein. Both variants identified are predicted to result in truncated proteins losing the capacity of binding to ubiquitinated proteins, hence appearing to exhibit a dominant‐negative effect on the normal function of the endosome‐specific endosomal sorting complexes required for the transport‐I complex.; to: PMID 31696996: Five unrelated families reported with childhood-onset HSP. A recurrent two‐base pair deletion (c.426_427delGA, p.K143Sfs*15) in the UBAP1 gene was found in four families, and a similar variant (c.475_476delTT, p.F159*) was detected in a fifth family. The variant was confirmed to be de novo in two families and inherited from an affected parent in two other families. RNA studies performed in lymphocytes from one patient with the de novo c.426_427delGA variant demonstrated escape of nonsense‐mediated decay of the UBAP1 mutant transcript, suggesting the generation of a truncated protein. Both variants identified are predicted to result in truncated proteins losing the capacity of binding to ubiquitinated proteins, hence appearing to exhibit a dominant‐negative effect on the normal function of the endosome‐specific endosomal sorting complexes required for the transport‐I complex.

PMID 32934340: additional 7 families. Median age of onset 10yrs.
Mendeliome v0.6742 RTN2 Zornitza Stark Gene: rtn2 has been classified as Green List (High Evidence).
Mendeliome v0.6739 KDM5B Elena Savva reviewed gene: KDM5B: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29276005, 30217758, 30409806; Phenotypes: Mental retardation, autosomal recessive 65 MIM#618109, autosomal dominant autism spectrum disorder or intellectual disability; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.6739 NIPA1 Zornitza Stark Gene: nipa1 has been classified as Green List (High Evidence).
Mendeliome v0.6736 DDHD1 Zornitza Stark Gene: ddhd1 has been classified as Green List (High Evidence).
Mendeliome v0.6736 DDHD1 Zornitza Stark Phenotypes for gene: DDHD1 were changed from to Spastic paraplegia 28, autosomal recessive, 609340; MONDO:0012256
Mendeliome v0.6733 DDHD1 Zornitza Stark reviewed gene: DDHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23176821; Phenotypes: Spastic paraplegia 28, autosomal recessive, 609340, MONDO:0012256; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6730 CAPN1 Zornitza Stark Phenotypes for gene: CAPN1 were changed from Spastic paraplegia 76, autosomal recessive, MIM#616907 to Spastic paraplegia 76, autosomal recessive, MIM#616907; MONDO:0014827
Mendeliome v0.6729 AP5Z1 Zornitza Stark Gene: ap5z1 has been classified as Green List (High Evidence).
Mendeliome v0.6729 AP5Z1 Zornitza Stark Phenotypes for gene: AP5Z1 were changed from to Spastic paraplegia 48, autosomal recessive, MIM# 613647; MONDO:0013342
Mendeliome v0.6726 AP5Z1 Zornitza Stark reviewed gene: AP5Z1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26085577, 33543803, 27606357; Phenotypes: Spastic paraplegia 48, autosomal recessive, MIM# 613647, MONDO:0013342; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6726 COPB1 Zornitza Stark Gene: copb1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6726 COPB1 Zornitza Stark Classified gene: COPB1 as Amber List (moderate evidence)
Mendeliome v0.6726 COPB1 Zornitza Stark Gene: copb1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6724 SLC1A4 Zornitza Stark Phenotypes for gene: SLC1A4 were changed from Spastic tetraplegia, thin corpus callosum, and progressive microcephaly, MIM# 616657 to Spastic tetraplegia, thin corpus callosum, and progressive microcephaly, MIM# 616657; MONDO:0014725
Mendeliome v0.6723 SLC1A4 Zornitza Stark Gene: slc1a4 has been classified as Green List (High Evidence).
Mendeliome v0.6723 SLC1A4 Zornitza Stark Phenotypes for gene: SLC1A4 were changed from to Spastic tetraplegia, thin corpus callosum, and progressive microcephaly, MIM# 616657
Mendeliome v0.6720 TFG Zornitza Stark Gene: tfg has been classified as Green List (High Evidence).
Mendeliome v0.6720 TFG Zornitza Stark Phenotypes for gene: TFG were changed from to Hereditary motor and sensory neuropathy, Okinawa type, MIM# 604484; Spastic paraplegia 57, autosomal recessive, MIM# 615658
Mendeliome v0.6718 TFG Zornitza Stark reviewed gene: TFG: Rating: GREEN; Mode of pathogenicity: None; Publications: 30467354, 30157421, 28124177, 27601211, 27492651, 23479643, 25098539, 23553329, 22883144, 31449671, 31111683; Phenotypes: Hereditary motor and sensory neuropathy, Okinawa type, MIM# 604484, Spastic paraplegia 57, autosomal recessive, MIM# 615658; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.6718 WDR45B Zornitza Stark Gene: wdr45b has been classified as Green List (High Evidence).
Mendeliome v0.6715 REEP2 Zornitza Stark Gene: reep2 has been classified as Green List (High Evidence).
Mendeliome v0.6715 REEP2 Zornitza Stark Phenotypes for gene: REEP2 were changed from to Spastic paraplegia 72, dominant and recessive, MIM# 615625; MONDO:0014282
Mendeliome v0.6712 REEP2 Zornitza Stark reviewed gene: REEP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33526816, 28491902, 24388663; Phenotypes: Spastic paraplegia 72, dominant and recessive, MIM# 615625, MONDO:0014282; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.6712 NT5C2 Zornitza Stark Gene: nt5c2 has been classified as Green List (High Evidence).
Mendeliome v0.6712 NT5C2 Zornitza Stark Phenotypes for gene: NT5C2 were changed from to Spastic paraplegia 45, autosomal recessive, MIM# 613162; MONDO:0013165
Mendeliome v0.6709 NT5C2 Zornitza Stark reviewed gene: NT5C2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24482476, 32153630, 29123918, 28884889, 28327087; Phenotypes: Spastic paraplegia 45, autosomal recessive, MIM# 613162, MONDO:0013165; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6709 HACE1 Zornitza Stark Gene: hace1 has been classified as Green List (High Evidence).
Mendeliome v0.6706 NKX6-2 Zornitza Stark Gene: nkx6-2 has been classified as Green List (High Evidence).
Mendeliome v0.6706 NKX6-2 Zornitza Stark Phenotypes for gene: NKX6-2 were changed from to Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy, MIM# 617560; MONDO:0033043
Mendeliome v0.6703 NKX6-2 Zornitza Stark reviewed gene: NKX6-2: Rating: GREEN; Mode of pathogenicity: None; Publications: 28575651, 15601927, 32246862, 32004679; Phenotypes: Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy, MIM# 617560, MONDO:0033043; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6703 ARPC1B Zornitza Stark Gene: arpc1b has been classified as Green List (High Evidence).
Mendeliome v0.6703 ARPC1B Zornitza Stark Phenotypes for gene: ARPC1B were changed from to Platelet abnormalities with eosinophilia and immune-mediated inflammatory disease 617718
Mendeliome v0.6700 ARPC1B Zornitza Stark reviewed gene: ARPC1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 28368018, 33679784; Phenotypes: Platelet abnormalities with eosinophilia and immune-mediated inflammatory disease 617718; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6699 KDM5C Zornitza Stark changed review comment from: Progressive lower limb spasticity is a feature of this ID syndrome. More than 5 unrelated families reported.; to: Intellectual disability, progressive lower limb spasticity, epilepsy and a number of other more variable features. Affected females reported PMID 32279304.
Mendeliome v0.6699 KDM5C Zornitza Stark Gene: kdm5c has been classified as Green List (High Evidence).
Mendeliome v0.6696 ENTPD1 Zornitza Stark Gene: entpd1 has been classified as Green List (High Evidence).
Mendeliome v0.6696 ENTPD1 Zornitza Stark Phenotypes for gene: ENTPD1 were changed from to Spastic paraplegia 64, autosomal recessive MIM#615683
Mendeliome v0.6693 ENTPD1 Zornitza Stark reviewed gene: ENTPD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24482476, 30652007; Phenotypes: Spastic paraplegia 64, autosomal recessive MIM#615683; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6693 C12orf65 Zornitza Stark Gene: c12orf65 has been classified as Green List (High Evidence).
Mendeliome v0.6693 C12orf65 Zornitza Stark Phenotypes for gene: C12orf65 were changed from to Spastic paraplegia 55, autosomal recessive, MIM#615035; Combined oxidative phosphorylation deficiency 7, MIM# 613559
Mendeliome v0.6690 C12orf65 Zornitza Stark reviewed gene: C12orf65: Rating: GREEN; Mode of pathogenicity: None; Publications: 23188110, 24080142, 24198383, 20598281, 32808965, 32478789, 28804760; Phenotypes: Spastic paraplegia 55, autosomal recessive, MIM#615035, Combined oxidative phosphorylation deficiency 7, MIM# 613559; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6690 C19orf12 Zornitza Stark Gene: c19orf12 has been classified as Green List (High Evidence).
Mendeliome v0.6690 C19orf12 Zornitza Stark Phenotypes for gene: C19orf12 were changed from to Neurodegeneration with brain iron accumulation 4, MIM# 614298; Spastic paraplegia 43, autosomal recessive, MIM# 615043
Mendeliome v0.6687 C19orf12 Zornitza Stark reviewed gene: C19orf12: Rating: GREEN; Mode of pathogenicity: None; Publications: 33688131, 21981780, 22508347, 23269600, 31804703, 30088953, 20039086; Phenotypes: Neurodegeneration with brain iron accumulation 4, MIM# 614298, Spastic paraplegia 43, autosomal recessive, MIM# 615043; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.6687 CYP2U1 Zornitza Stark Gene: cyp2u1 has been classified as Green List (High Evidence).
Mendeliome v0.6687 CYP2U1 Zornitza Stark Phenotypes for gene: CYP2U1 were changed from to Spastic paraplegia 56, autosomal recessive, MIM#615030
Mendeliome v0.6684 CYP2U1 Zornitza Stark edited their review of gene: CYP2U1: Added comment: SPG56 is an autosomal recessive neurodegenerative disorder characterized by early-onset progressive lower-limb spasticity resulting in walking difficulties. Upper limbs are often also affected, and some patients may have a subclinical axonal neuropathy. Onset is typically in the first decade. More than 5 unrelated families reported.; Changed rating: GREEN; Changed publications: 23176821, 32006740, 29034544
Mendeliome v0.6684 IFRD1 Zornitza Stark Gene: ifrd1 has been classified as Red List (Low Evidence).
Mendeliome v0.6684 IFRD1 Zornitza Stark gene: IFRD1 was added
gene: IFRD1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: IFRD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IFRD1 were set to 29362493
Phenotypes for gene: IFRD1 were set to Hereditary spastic paraplegia; peripheral neuropathy; ataxia
Review for gene: IFRD1 was set to RED
Added comment: A variant segregated with slowly progressing gait ataxia, pyramidal tract signs and peripheral neuropathy in three siblings from a single Chinese family. No functional analyses of the variant has been conducted. The variant (c.514 A>G, p.I172V) is too common (0.3%) for a dominant condition in the African population in gnomAD.
Sources: Expert Review
Mendeliome v0.6684 IFRD1 Zornitza Stark gene: IFRD1 was added
gene: IFRD1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: IFRD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IFRD1 were set to 29362493
Phenotypes for gene: IFRD1 were set to Hereditary spastic paraplegia; peripheral neuropathy; ataxia
Review for gene: IFRD1 was set to RED
Added comment: A variant segregated with slowly progressing gait ataxia, pyramidal tract signs and peripheral neuropathy in three siblings from a single Chinese family. No functional analyses of the variant has been conducted. The variant (c.514 A>G, p.I172V) is too common (0.3%) for a dominant condition in the African population in gnomAD.
Sources: Expert Review
Mendeliome v0.6683 KLC4 Zornitza Stark Gene: klc4 has been classified as Red List (Low Evidence).
Mendeliome v0.6683 KLC4 Zornitza Stark gene: KLC4 was added
gene: KLC4 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: KLC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KLC4 were set to 26423925
Phenotypes for gene: KLC4 were set to Complicated hereditary spastic paraplegia
Review for gene: KLC4 was set to RED
Added comment: Single family reported.
Sources: Expert Review
Mendeliome v0.6682 AP4M1 Zornitza Stark Gene: ap4m1 has been classified as Green List (High Evidence).
Mendeliome v0.6682 AP4M1 Zornitza Stark Phenotypes for gene: AP4M1 were changed from to Spastic paraplegia 50, autosomal recessive, MIM# 612936
Mendeliome v0.6679 AP4M1 Zornitza Stark reviewed gene: AP4M1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19559397, 21937992, 21937992, 32979048, 31915823, 29096665, 28464862, 25496299; Phenotypes: Spastic paraplegia 50, autosomal recessive, MIM# 612936; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6679 ADAMTS13 Zornitza Stark Gene: adamts13 has been classified as Green List (High Evidence).
Mendeliome v0.6676 AP4S1 Zornitza Stark Gene: ap4s1 has been classified as Green List (High Evidence).
Mendeliome v0.6676 AP4S1 Zornitza Stark Phenotypes for gene: AP4S1 were changed from to Spastic paraplegia 52, autosomal recessive, MIM# 614067
Mendeliome v0.6673 AP4S1 Zornitza Stark reviewed gene: AP4S1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21620353, 25552650, 32979048, 32216065, 31915823, 30283821, 27444738; Phenotypes: Spastic paraplegia 52, autosomal recessive, MIM# 614067; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6673 AIMP1 Zornitza Stark Gene: aimp1 has been classified as Green List (High Evidence).
Mendeliome v0.6667 CC2D1A Zornitza Stark Gene: cc2d1a has been classified as Green List (High Evidence).
Mendeliome v0.6667 CC2D1A Zornitza Stark Phenotypes for gene: CC2D1A were changed from to Autosomal recessive mental retardation, (MIM#608443)
Mendeliome v0.6664 CC2D1A Zornitza Stark reviewed gene: CC2D1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 25066123; Phenotypes: Autosomal recessive mental retardation, (MIM#608443); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6664 ZAP70 Zornitza Stark Gene: zap70 has been classified as Green List (High Evidence).
Mendeliome v0.6660 GDF5 Michelle Torres reviewed gene: GDF5: Rating: RED; Mode of pathogenicity: None; Publications: 8589725, 33333243; Phenotypes: ? Hunter-Thompson type acromesomelic dysplasia (MIM#201250) AR; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6660 CST3 Zornitza Stark Gene: cst3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6657 CST3 Zornitza Stark Classified gene: CST3 as Amber List (moderate evidence)
Mendeliome v0.6657 CST3 Zornitza Stark Gene: cst3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6656 NR3C1 Zornitza Stark Gene: nr3c1 has been classified as Green List (High Evidence).
Mendeliome v0.6656 NR3C1 Zornitza Stark Phenotypes for gene: NR3C1 were changed from to Glucocorticoid resistance, OMIM # 615962
Mendeliome v0.6653 NR3C1 Zornitza Stark reviewed gene: NR3C1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12754700, 1704018, 8445027, 31995340, 30158362; Phenotypes: Glucocorticoid resistance, OMIM # 615962; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.6652 YY1AP1 Zornitza Stark commented on gene: YY1AP1: Grange syndrome: multiple arterial stenoses, severe early onset hypertension, fibromuscular dysplasia, variable penetrance of brachydactyly, syndactyly, bone fragility, and learning disabilities. Missense variant reported PMID: 31633303 with moyamoya like phenotype in adult case; fibroblasts suggest that the p.Pro360Leu variant decreases the stability of the YY1AP1 protein but most LOF. PMID: 30556293 non coding variants reported (intronic variants leading to aberrant splicing)
Mendeliome v0.6652 NOS3 Zornitza Stark Gene: nos3 has been classified as Red List (Low Evidence).
Mendeliome v0.6652 NOS3 Zornitza Stark Phenotypes for gene: NOS3 were changed from to {Hypertension, susceptibility to}, MIM#145500; {Ischemic stroke, susceptibility to}, MIM# 601367; {Hypertension, pregnancy-induced}, MIM# 189800
Mendeliome v0.6650 NOS3 Zornitza Stark Classified gene: NOS3 as Red List (low evidence)
Mendeliome v0.6650 NOS3 Zornitza Stark Gene: nos3 has been classified as Red List (Low Evidence).
Mendeliome v0.6649 NOS3 Zornitza Stark reviewed gene: NOS3: Rating: RED; Mode of pathogenicity: None; Publications: 24986538, 28084234, 33652340; Phenotypes: {Hypertension, susceptibility to}, MIM#145500, {Ischemic stroke, susceptibility to}, MIM# 601367, {Hypertension, pregnancy-induced}, MIM# 189800; Mode of inheritance: Unknown
Mendeliome v0.6649 CDT1 Zornitza Stark Gene: cdt1 has been classified as Green List (High Evidence).
Mendeliome v0.6646 CDK5RAP2 Zornitza Stark Gene: cdk5rap2 has been classified as Green List (High Evidence).
Mendeliome v0.6646 CDK5RAP2 Zornitza Stark Phenotypes for gene: CDK5RAP2 were changed from to Microcephaly 3, primary, autosomal recessive, MIM# 604804; MONDO:0011488
Mendeliome v0.6643 CDK5RAP2 Zornitza Stark reviewed gene: CDK5RAP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 15793586, 22887808, 23995685, 23726037, 27761245, 20460369, 32677750, 32015000; Phenotypes: Microcephaly 3, primary, autosomal recessive, MIM# 604804, MONDO:0011488; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6643 UGT2B17 Zornitza Stark Gene: ugt2b17 has been classified as Red List (Low Evidence).
Mendeliome v0.6643 UGT2B17 Zornitza Stark Classified gene: UGT2B17 as Red List (low evidence)
Mendeliome v0.6643 UGT2B17 Zornitza Stark Gene: ugt2b17 has been classified as Red List (Low Evidence).
Mendeliome v0.6640 PLD1 Zornitza Stark Classified gene: PLD1 as Green List (high evidence)
Mendeliome v0.6640 PLD1 Zornitza Stark Gene: pld1 has been classified as Green List (High Evidence).
Mendeliome v0.6639 DONSON Zornitza Stark Gene: donson has been classified as Green List (High Evidence).
Mendeliome v0.6636 SQOR Zornitza Stark Gene: sqor has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6635 SQOR Zornitza Stark Classified gene: SQOR as Amber List (moderate evidence)
Mendeliome v0.6635 SQOR Zornitza Stark Gene: sqor has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6633 PGK1 Zornitza Stark Gene: pgk1 has been classified as Green List (High Evidence).
Mendeliome v0.6630 PGM1 Zornitza Stark Gene: pgm1 has been classified as Green List (High Evidence).
Mendeliome v0.6626 PHKA1 Zornitza Stark Gene: phka1 has been classified as Green List (High Evidence).
Mendeliome v0.6626 PHKA1 Zornitza Stark Phenotypes for gene: PHKA1 were changed from to Muscle glycogenosis, MIM# 300559
Mendeliome v0.6623 PHKA1 Zornitza Stark reviewed gene: PHKA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 7874115, 12825073, 9731190; Phenotypes: Muscle glycogenosis, MIM# 300559; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.6623 PHKB Zornitza Stark Gene: phkb has been classified as Green List (High Evidence).
Mendeliome v0.6623 PHKB Zornitza Stark Phenotypes for gene: PHKB were changed from to Phosphorylase kinase deficiency of liver and muscle, autosomal recessive 261750; Glycogen storage disease IXb, MONDO:0009868
Mendeliome v0.6620 PHKB Zornitza Stark reviewed gene: PHKB: Rating: GREEN; Mode of pathogenicity: None; Publications: 9215682, 25266922, 30659246; Phenotypes: Phosphorylase kinase deficiency of liver and muscle, autosomal recessive 261750, Glycogen storage disease IXb, MONDO:0009868; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6620 PHKG2 Zornitza Stark Gene: phkg2 has been classified as Green List (High Evidence).
Mendeliome v0.6617 PYGL Zornitza Stark Gene: pygl has been classified as Green List (High Evidence).
Mendeliome v0.6614 NHLRC1 Zornitza Stark Gene: nhlrc1 has been classified as Green List (High Evidence).
Mendeliome v0.6614 NHLRC1 Zornitza Stark Phenotypes for gene: NHLRC1 were changed from to Epilepsy, progressive myoclonic 2B (Lafora) 254780
Mendeliome v0.6611 NHLRC1 Zornitza Stark reviewed gene: NHLRC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21505799, 12958597; Phenotypes: Epilepsy, progressive myoclonic 2B (Lafora) 254780; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6611 LDHA Zornitza Stark Gene: ldha has been classified as Green List (High Evidence).
Mendeliome v0.6608 SIAH1 Zornitza Stark Marked gene: SIAH1 as ready
Mendeliome v0.6608 SIAH1 Zornitza Stark Gene: siah1 has been classified as Green List (High Evidence).
Mendeliome v0.6608 SIAH1 Zornitza Stark Classified gene: SIAH1 as Green List (high evidence)
Mendeliome v0.6608 SIAH1 Zornitza Stark Gene: siah1 has been classified as Green List (High Evidence).
Mendeliome v0.6607 RPL18 Zornitza Stark Gene: rpl18 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6607 RPL18 Zornitza Stark Classified gene: RPL18 as Amber List (moderate evidence)
Mendeliome v0.6607 RPL18 Zornitza Stark Gene: rpl18 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6605 RPS15A Zornitza Stark Gene: rps15a has been classified as Red List (Low Evidence).
Mendeliome v0.6605 RPS15A Zornitza Stark gene: RPS15A was added
gene: RPS15A was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: RPS15A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPS15A were set to 27909223
Phenotypes for gene: RPS15A were set to Diamond-Blackfan anemia 20, MIM# 618313
Review for gene: RPS15A was set to RED
Added comment: Single family reported.
Sources: Expert list
Mendeliome v0.6604 RPL35 Zornitza Stark Gene: rpl35 has been classified as Red List (Low Evidence).
Mendeliome v0.6604 RPL35 Zornitza Stark gene: RPL35 was added
gene: RPL35 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: RPL35 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPL35 were set to 28280134
Phenotypes for gene: RPL35 were set to Diamond-Blackfan anemia 19, MIM# 618312
Review for gene: RPL35 was set to RED
Added comment: Single family reported.
Sources: Expert list
Mendeliome v0.6603 RPS7 Zornitza Stark Gene: rps7 has been classified as Green List (High Evidence).
Mendeliome v0.6600 RPS26 Zornitza Stark Gene: rps26 has been classified as Green List (High Evidence).
Mendeliome v0.6597 RPS24 Zornitza Stark Gene: rps24 has been classified as Green List (High Evidence).
Mendeliome v0.6593 RPS19 Zornitza Stark Gene: rps19 has been classified as Green List (High Evidence).
Mendeliome v0.6590 ACKR3 Zornitza Stark Phenotypes for gene: ACKR3 were changed from Oculomotor synkinesis; Ptosis to Oculomotor-abducens synkinesis, MIM# 619215
Mendeliome v0.6589 ACKR3 Zornitza Stark reviewed gene: ACKR3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Oculomotor-abducens synkinesis, MIM# 619215; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6589 SIAH1 Arina Puzriakova gene: SIAH1 was added
gene: SIAH1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SIAH1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SIAH1 were set to 32430360
Phenotypes for gene: SIAH1 were set to Developmental delay; Infantile hypotonia; Dysmorphic features; Laryngomalacia
Review for gene: SIAH1 was set to GREEN
Added comment: - PMID: 32430360 (2021) - Five unrelated individuals with shared features of developmental delay, infantile hypotonia, dysmorphic features and laryngomalacia. All had speech delay and where cognitive assessment was age appropriate individuals exhibited learning difficulties. Trio WES revealed distinct de novo variants in SIAH1. In vitro assays demonstrated that SIAH1 mutants induce loss of Wnt stimulatory activity.
Sources: Literature
Mendeliome v0.6589 SYCP2L Zornitza Stark Gene: sycp2l has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6589 SYCP2L Zornitza Stark Classified gene: SYCP2L as Amber List (moderate evidence)
Mendeliome v0.6589 SYCP2L Zornitza Stark Gene: sycp2l has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6588 RPL5 Zornitza Stark Gene: rpl5 has been classified as Green List (High Evidence).
Mendeliome v0.6585 RPL35A Zornitza Stark Gene: rpl35a has been classified as Green List (High Evidence).
Mendeliome v0.6582 SYCP2L Arina Puzriakova gene: SYCP2L was added
gene: SYCP2L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SYCP2L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SYCP2L were set to 32303603
Phenotypes for gene: SYCP2L were set to Premature ovarian insufficiency
Review for gene: SYCP2L was set to AMBER
Added comment: - PMID: 32303603 (2021) - Two unrelated individuals with premature ovarian insufficiency and homozygous variants (c.150_151del (p.Ser52Profs*7), c.999A>G (p.Ile333Met)) in SYCP2L.
In vitro assays revealed that mutant SYCP2L proteins induced mislocalisation and reduced expression. Sycp2l knockout mice exhibit accelerated reproductive ageing.
Sources: Literature
Mendeliome v0.6582 RPL27 Zornitza Stark Gene: rpl27 has been classified as Red List (Low Evidence).
Mendeliome v0.6579 RPL27 Zornitza Stark Classified gene: RPL27 as Red List (low evidence)
Mendeliome v0.6579 RPL27 Zornitza Stark Gene: rpl27 has been classified as Red List (Low Evidence).
Mendeliome v0.6578 RPL11 Zornitza Stark Gene: rpl11 has been classified as Green List (High Evidence).
Mendeliome v0.6572 CLCN4 Zornitza Stark Gene: clcn4 has been classified as Green List (High Evidence).
Mendeliome v0.6572 CLCN4 Zornitza Stark Phenotypes for gene: CLCN4 were changed from to Raynaud-Claes syndrome, MIM#300114; intellectual disability; epilepsy; autistic features; mood disorders; cerebral white matter changes; progressive appendicular spasticity
Mendeliome v0.6569 CLCN4 Zornitza Stark reviewed gene: CLCN4: Rating: GREEN; Mode of pathogenicity: None; Publications: 27550844; Phenotypes: Raynaud-Claes syndrome, MIM#300114, intellectual disability, epilepsy, autistic features, mood disorders, cerebral white matter changes, progressive appendicular spasticity; 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 v0.6569 KIRREL1 Zornitza Stark Phenotypes for gene: KIRREL1 were changed from Steroid-resistant nephrotic syndrome to Nephrotic syndrome, type 23, MIM# 619201
Mendeliome v0.6567 EN1 Zornitza Stark changed review comment from: Three unrelated families reported (though two shown to be related by descent) with predominantly a skeletal phenotype comprising mesomelic shortening and deformation of the lower limbs due to severe hypoplasia of the tibia and fibula. This was accompanied by abnormalities of the digits of the hands and feet, with cutaneous and osseous syndactyly as well as dysplastic, missing, and/or volar nails. In addition, genitourinary anomalies were observed in some. Homozygous deletions identified in all, with the minimal deleted region being a 27-kb interval (chr2: 118,561,492-118,589,320) located approximately 300 kb upstream of the EN1 gene. Mouse model recapitulated the phenotype.
Sources: Literature; to: Three unrelated families reported (though two shown to be related by descent) with predominantly a skeletal phenotype comprising mesomelic shortening and deformation of the lower limbs due to severe hypoplasia of the tibia and fibula. This was accompanied by abnormalities of the digits of the hands and feet, with cutaneous and osseous syndactyly as well as dysplastic, missing, and/or volar nails. In addition, genitourinary anomalies were observed in some. Homozygous deletions identified in all, with the minimal deleted region being a 27-kb interval (chr2: 118,561,492-118,589,320) located approximately 300 kb upstream of the EN1 gene. Mouse model recapitulated the phenotype.

An additional fourth individual had cerebellar hypoplasia in addition to the skeletal phenotype, and a bi-allelic LoF variant.
Sources: Literature
Mendeliome v0.6567 EN1 Zornitza Stark Gene: en1 has been classified as Green List (High Evidence).
Mendeliome v0.6567 EN1 Zornitza Stark Classified gene: EN1 as Green List (high evidence)
Mendeliome v0.6567 EN1 Zornitza Stark Gene: en1 has been classified as Green List (High Evidence).
Mendeliome v0.6566 EN1 Zornitza Stark gene: EN1 was added
gene: EN1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EN1 were set to 33568816
Phenotypes for gene: EN1 were set to ENDOVE syndrome, limb-only type, MIM# 619217
Review for gene: EN1 was set to GREEN
Added comment: Three unrelated families reported (though two shown to be related by descent) with predominantly a skeletal phenotype comprising mesomelic shortening and deformation of the lower limbs due to severe hypoplasia of the tibia and fibula. This was accompanied by abnormalities of the digits of the hands and feet, with cutaneous and osseous syndactyly as well as dysplastic, missing, and/or volar nails. In addition, genitourinary anomalies were observed in some. Homozygous deletions identified in all, with the minimal deleted region being a 27-kb interval (chr2: 118,561,492-118,589,320) located approximately 300 kb upstream of the EN1 gene. Mouse model recapitulated the phenotype.
Sources: Literature
Mendeliome v0.6560 EEF2 Zornitza Stark Classified gene: EEF2 as Green List (high evidence)
Mendeliome v0.6560 EEF2 Zornitza Stark Gene: eef2 has been classified as Green List (High Evidence).
Mendeliome v0.6559 MKRN3 Zornitza Stark Gene: mkrn3 has been classified as Green List (High Evidence).
Mendeliome v0.6556 ACSL5 Zornitza Stark Gene: acsl5 has been classified as Red List (Low Evidence).
Mendeliome v0.6556 ACSL5 Zornitza Stark gene: ACSL5 was added
gene: ACSL5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ACSL5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACSL5 were set to 33191500
Phenotypes for gene: ACSL5 were set to severe FTT (no OMIM #)
Review for gene: ACSL5 was set to RED
Added comment: 6 individuals of a large consanguineous family presented in the neonatal period with recurrent vomiting and diarrhea, leading to severe FTT. Autozygosity mapping and WES identified homozygous variant (c.1358C>A:p.(Thr453Lys) in ACSL5. Segregated with affected individuals. Functional in vitro analysis of the ACSL5 variant by immunofluorescence, western blotting and enzyme assay suggested that Thr453Lys is a loss‐of‐function mutation without any remaining activity. Affected individuals were treated with total parenteral nutrition or medium‐chain triglyceride‐based formula restricted in long‐chain triglycerides. They responded well and follow up suggests that treatment is only required during early life.
Sources: Literature
Mendeliome v0.6555 GDF5 Zornitza Stark Gene: gdf5 has been classified as Green List (High Evidence).
Mendeliome v0.6555 GDF5 Zornitza Stark Phenotypes for gene: GDF5 were changed from to Type A1C brachydactyly (MIM#615072); Type A2 brachydactyly, (MIM#112600); Type C brachydactyly (MIM#113100); Grebe type chondrodysplasia (MIM#200700); Du Pan syndrome (MIM#228900); Multiple synostoses syndrome 2 (MIM#610017); Proximal Symphalangism 1B (MIM#615298)
Mendeliome v0.6554 GDF5 Zornitza Stark reviewed gene: GDF5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Type A1C brachydactyly (MIM#615072), Type A2 brachydactyly, (MIM#112600), Type C brachydactyly (MIM#113100), Grebe type chondrodysplasia (MIM#200700), Du Pan syndrome (MIM#228900), Multiple synostoses syndrome 2 (MIM#610017), Proximal Symphalangism 1B (MIM#615298); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.6552 KIDINS220 Zornitza Stark Gene: kidins220 has been classified as Green List (High Evidence).
Mendeliome v0.6552 KIDINS220 Zornitza Stark Phenotypes for gene: KIDINS220 were changed from to Spastic paraplegia, intellectual disability, nystagmus, and obesity, MIM# 617296; cerebral ventriculomegaly; limb contractures
Mendeliome v0.6549 KIDINS220 Zornitza Stark reviewed gene: KIDINS220: Rating: GREEN; Mode of pathogenicity: None; Publications: 27005418; Phenotypes: Spastic paraplegia, intellectual disability, nystagmus, and obesity, MIM# 617296; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.6549 MYO15A Zornitza Stark Phenotypes for gene: MYO15A were changed from Deafness, autosomal recessive 3, MIM# 600316 to Deafness, autosomal recessive 3, MIM# 600316; autosomal recessive nonsyndromic deafness 3 MONDO:0010860
Mendeliome v0.6547 MYO3A Zornitza Stark Phenotypes for gene: MYO3A were changed from to Deafness, autosomal recessive 30 OMIM:607101; autosomal recessive nonsyndromic deafness 30 MONDO:0011774; dominant deafness
Mendeliome v0.6544 MYO3A Zornitza Stark reviewed gene: MYO3A: Rating: GREEN; Mode of pathogenicity: None; Publications: 21165622, 26754646, 23990876; Phenotypes: Deafness, autosomal recessive 30, MIM# 607101; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.6544 COL9A3 Zornitza Stark Gene: col9a3 has been classified as Green List (High Evidence).
Mendeliome v0.6544 COL9A3 Zornitza Stark Phenotypes for gene: COL9A3 were changed from to Epiphyseal dysplasia, multiple, 3, with or without myopathy, MIM# 600969; Stickler syndrome; Deafness
Mendeliome v0.6541 COL9A3 Zornitza Stark reviewed gene: COL9A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 30450842, 31090205, 24273071, 10090888, 15551337; Phenotypes: Epiphyseal dysplasia, multiple, 3, with or without myopathy, MIM# 600969, Stickler syndrome, Deafness; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.6541 DLK1 Zornitza Stark Gene: dlk1 has been classified as Green List (High Evidence).
Mendeliome v0.6541 DLK1 Zornitza Stark Classified gene: DLK1 as Green List (high evidence)
Mendeliome v0.6541 DLK1 Zornitza Stark Gene: dlk1 has been classified as Green List (High Evidence).
Mendeliome v0.6540 DLK1 Zornitza Stark gene: DLK1 was added
gene: DLK1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: DLK1 was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Publications for gene: DLK1 were set to 28324015; 30462238
Phenotypes for gene: DLK1 were set to central precocious puberty
Review for gene: DLK1 was set to GREEN
Added comment: PMID: 30462238 "three frameshift mutations of DLK1 (p.Gly199Alafs*11, p.Val271Cysfs*14, and p.Pro160Leufs*50) in five women from three families with CPP. Segregation analysis was consistent with the maternal imprinting of DLK1". PMID: 28324015 single large family, only affected females, central precocious puberty all carrying paternally inherited LOF variant (del/dup of 5'UTR and exon 1) absent DLK1 expression in all affected. Unclear if males affected as none reported to date.
Sources: Expert Review
Mendeliome v0.6539 GDF5 Ain Roesley reviewed gene: GDF5: Rating: GREEN; Mode of pathogenicity: None; Publications: 33333243; Phenotypes: Type A1C brachydactyly (MIM#615072), Type A2 brachydactyly, (MIM#112600), Type C brachydactyly (MIM#113100), Grebe type chondrodysplasia (MIM#200700), Du Pan syndrome (MIM#228900), Multiple synostoses syndrome 2 (MIM#610017), Proximal Symphalangism 1B (MIM#615298); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.6539 MYO15A Eleanor Williams reviewed gene: MYO15A: Rating: ; Mode of pathogenicity: None; Publications: 33078831; Phenotypes: Deafness, autosomal recessive 3 OMIM:600316, autosomal recessive nonsyndromic deafness 3 MONDO:0010860; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6539 MYO3A Eleanor Williams reviewed gene: MYO3A: Rating: GREEN; Mode of pathogenicity: None; Publications: 33078831, 26841241, 29880844; Phenotypes: Deafness, autosomal recessive 30 OMIM:607101, autosomal recessive nonsyndromic deafness 30 MONDO:0011774; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6539 COL9A3 Eleanor Williams reviewed gene: COL9A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 33078831, 15917166; Phenotypes: autosomal recessive non-syndromic hearing impairment; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6539 EIF5A Zornitza Stark Gene: eif5a has been classified as Green List (High Evidence).
Mendeliome v0.6539 EIF5A Zornitza Stark Classified gene: EIF5A as Green List (high evidence)
Mendeliome v0.6539 EIF5A Zornitza Stark Gene: eif5a has been classified as Green List (High Evidence).
Mendeliome v0.6537 POLRMT Zornitza Stark Gene: polrmt has been classified as Green List (High Evidence).
Mendeliome v0.6537 POLRMT Zornitza Stark Classified gene: POLRMT as Green List (high evidence)
Mendeliome v0.6537 POLRMT Zornitza Stark Gene: polrmt has been classified as Green List (High Evidence).
Mendeliome v0.6536 POLRMT Zornitza Stark gene: POLRMT was added
gene: POLRMT was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: POLRMT was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: POLRMT were set to 33602924
Phenotypes for gene: POLRMT were set to Mitochondrial disorder; intellectual disability; hypotonia
Review for gene: POLRMT was set to GREEN
Added comment: 8 individuals from 7 families reported. 5 families with bi-allelic variants and 2 with heterozygous variants. Affected individuals presented with global developmental delay, hypotonia, short stature, and speech/intellectual disability in childhood; one subject displayed an indolent progressive external ophthalmoplegia phenotype.
Sources: Literature
Mendeliome v0.6535 PERP Zornitza Stark Phenotypes for gene: PERP were changed from Erythrokeratoderma, no OMIM # yet to Olmsted syndrome 2, MIM# 619208; Erythrokeratodermia variabilis et progressiva 7, MIM# 619209
Mendeliome v0.6532 PERP Zornitza Stark Classified gene: PERP as Green List (high evidence)
Mendeliome v0.6532 PERP Zornitza Stark Gene: perp has been classified as Green List (High Evidence).
Mendeliome v0.6531 PERP Zornitza Stark edited their review of gene: PERP: Added comment: Four families reported with heterozygous variants and Olmsted syndrome-2 (OLMS2), which is characterised by mutilating hyperkeratotic skin lesions, primarily on the palms and soles, but also extending onto dorsal surfaces of the hands and feet and distal extremities. The lesions are progressive, becoming thicker with verrucous fissures on the palms and soles over time. In addition, affected individuals exhibit perioral hyperkeratosis, and may have lesions around other orifices as well, such as the nostrils, perineum, and anus. Most patients also have hyperkeratotic nails and light-colored woolly hair.

Two families reported with bi-allelic variants and Erythrokeratodermia variabilis et progressiva-7 (EKVP7), which is characterised by palmoplantar keratoderma that extends to the dorsal surface of the hands and feet (transgrediens), as well as erythematous annular skin lesions. Pruritis, woolly hair, and dystrophic nails may also be present.; Changed rating: GREEN; Changed publications: 31898316, 30321533, 31361044; Changed phenotypes: Olmsted syndrome 2, MIM# 619208, Erythrokeratodermia variabilis et progressiva 7, MIM# 619209; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.6531 KARS Zornitza Stark edited their review of gene: KARS: Changed phenotypes: Leukoencephalopathy with or without deafness (LEPID), MIM#619147, Deafness, autosomal recessive 89, MIM# 613916, Congenital deafness and adult-onset progressive leukoencephalopathy (DEAPLE), MIM#619196
Mendeliome v0.6531 KARS Zornitza Stark Phenotypes for gene: KARS were changed from Leukoencephalopathy with or without deafness (LEPID), MIM#619147; Deafness, autosomal recessive 89, MIM# 613916 to Leukoencephalopathy with or without deafness (LEPID), MIM#619147; Deafness, autosomal recessive 89, MIM# 613916; Congenital deafness and adult-onset progressive leukoencephalopathy (DEAPLE), MIM#619196
Mendeliome v0.6530 KARS Zornitza Stark Gene: kars has been classified as Green List (High Evidence).
Mendeliome v0.6530 KARS Zornitza Stark Phenotypes for gene: KARS were changed from to Leukoencephalopathy with or without deafness (LEPID), MIM#619147; Deafness, autosomal recessive 89, MIM# 613916
Mendeliome v0.6527 KARS Zornitza Stark reviewed gene: KARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 26741492, 31618474, 28887846, 25330800, 29615062, 30252186, 28496994, 23768514, 14975237; Phenotypes: Leukoencephalopathy with or without deafness (LEPID), MIM#619147, Deafness, autosomal recessive 89, MIM# 613916; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6527 APOO Zornitza Stark reviewed gene: APOO: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental delay, Lactic acidosis, Muscle weakness, Hypotonia, Repetitive infections, Cognitive impairment, Autistic behaviour; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.6527 APOO Zornitza Stark Gene: apoo has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6527 APOO Zornitza Stark Classified gene: APOO as Amber List (moderate evidence)
Mendeliome v0.6527 APOO Zornitza Stark Gene: apoo has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6526 APOO Arina Puzriakova gene: APOO was added
gene: APOO was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: APOO 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: APOO were set to 32439808
Phenotypes for gene: APOO were set to Developmental delay; Lactic acidosis; Muscle weakness; Hypotonia; Repetitive infections; Cognitive impairment; Autistic behaviour
Review for gene: APOO was set to RED
Added comment: - PMID: 32439808 (2021) - Three generation family with c.350T>C variant in APOO, encoding a component of the MICOS complex which plays a role in maintaining inner mitochondrial membrane architecture.
Phenotypes include fatigue and muscle weakness (6/8), learning difficulties and cognitive impairment (4/8), and increased blood lactate (2/8). Four individuals were asymptomatic carriers, including one male (authors indicate variability in female carriers was due to skewed X-inactivation, although skewing studies were inconclusive in some cases). Variability in clinical presentation suggests reduced penetrance or possible contribution of additional factors.
Functional studies showed altered MICOS assembly and abnormalities in mitochondria ultrastructure in patient-derived fibroblasts. Knockdown studies in Drosophila and yeast demonstrated mitochondrial structural and functional deficiencies.
Sources: Literature
Mendeliome v0.6526 ECE1 Zornitza Stark Gene: ece1 has been classified as Red List (Low Evidence).
Mendeliome v0.6523 ECE1 Zornitza Stark Classified gene: ECE1 as Red List (low evidence)
Mendeliome v0.6523 ECE1 Zornitza Stark Gene: ece1 has been classified as Red List (Low Evidence).
Mendeliome v0.6522 AMH Seb Lunke Gene: amh has been classified as Green List (High Evidence).
Mendeliome v0.6522 AMH Seb Lunke Phenotypes for gene: AMH were changed from to Persistent Mullerian duct syndrome, type I (MIM#261550)
Mendeliome v0.6519 AMH Seb Lunke reviewed gene: AMH: Rating: GREEN; Mode of pathogenicity: None; Publications: 32172781; Phenotypes: Persistent Mullerian duct syndrome, type I (MIM#261550); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6519 PAX4 Zornitza Stark Gene: pax4 has been classified as Green List (High Evidence).
Mendeliome v0.6516 PCBD1 Zornitza Stark Gene: pcbd1 has been classified as Green List (High Evidence).
Mendeliome v0.6513 SPTAN1 Zornitza Stark Gene: sptan1 has been classified as Green List (High Evidence).
Mendeliome v0.6510 PSAP Zornitza Stark changed review comment from: Well established gene-disease association. Phenotype expansion with early-onset PD reported.; to: Well established gene-disease association for bi-allelic variants. Early-onset PD reported with mono-allelic variants.
Mendeliome v0.6508 PSAP Zornitza Stark changed review comment from: Well established gene-disease association. Phenotype expansion reported with early-onset PD reported.; to: Well established gene-disease association. Phenotype expansion with early-onset PD reported.
Mendeliome v0.6508 ACTL9 Zornitza Stark Gene: actl9 has been classified as Green List (High Evidence).
Mendeliome v0.6505 IRF4 Bryony Thompson Gene: irf4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6502 IRF4 Bryony Thompson Classified gene: IRF4 as Amber List (moderate evidence)
Mendeliome v0.6502 IRF4 Bryony Thompson Added comment: Comment on list classification: Single case and mouse model for recessive combined immunodeficiency
Mendeliome v0.6502 IRF4 Bryony Thompson Gene: irf4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6501 PCBD1 Michelle Torres edited their review of gene: PCBD1: Added comment: PMID: 24848070: one consanguineous family with early-onset nonautoimmune diabetes. The individual with early onset is biallelic, and 3 other carriers had later onset diabetes. In addition, 3 other patients with mild neonatal hyperphenylalaninemia with features similar to dominantly inherited HNF1A-diabetes.

PMID: 24204001: 2 out 3 patients with hypomagnesemia and renal magnesium wasting associated to biallelic PCBD1 variants developed MODY; Changed phenotypes: MODY, Hyperphenylalaninemia, BH4-deficient, D 264070
Mendeliome v0.6501 SPEN Alison Yeung Classified gene: SPEN as Green List (high evidence)
Mendeliome v0.6501 SPEN Alison Yeung Gene: spen has been classified as Green List (High Evidence).
Mendeliome v0.6500 SPTAN1 Alison Yeung Added comment: Comment on mode of inheritance: phenotype expansion
Mendeliome v0.6499 PSAP Seb Lunke Gene: psap has been classified as Green List (High Evidence).
Mendeliome v0.6497 ACTL9 Alison Yeung Classified gene: ACTL9 as Green List (high evidence)
Mendeliome v0.6497 ACTL9 Alison Yeung Gene: actl9 has been classified as Green List (High Evidence).
Mendeliome v0.6496 MAST2 Seb Lunke Gene: mast2 has been classified as Red List (Low Evidence).
Mendeliome v0.6496 MAST2 Seb Lunke Classified gene: MAST2 as Red List (low evidence)
Mendeliome v0.6496 MAST2 Seb Lunke Gene: mast2 has been classified as Red List (Low Evidence).
Mendeliome v0.6495 SPEN Chern Lim reviewed gene: SPEN: Rating: GREEN; Mode of pathogenicity: None; Publications: 33596411; Phenotypes: Developmental delay/intellectual disability, autism spectrum disorder, anxiety, aggressive behavior, attention deficit disorder, hypotonia, brain and spine anomalies, congenital heart defects, high/narrow palate, facial dysmorphisms, and obesity/increased BMI; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.6495 ANGPTL6 Alison Yeung Classified gene: ANGPTL6 as Green List (high evidence)
Mendeliome v0.6495 ANGPTL6 Alison Yeung Gene: angptl6 has been classified as Green List (High Evidence).
Mendeliome v0.6494 PCBD1 Michelle Torres changed review comment from: PMID: 24848070: one consanguineous family with early-onset nonautoimmune diabetes. The individual with early onset is biallelic, and 3 other carriers had later onset diabetes. In addition, 3 other patients with mild neonatal hyperphenylalaninemia with features similar to dominantly inherited HNF1A-diabetes.

PMID: 24204001: 2 out 3 patients with hypomagnesemia and renal magnesium wasting associated to biallelic PCBD1 variants developed MODY; to: PMID: 24848070: one consanguineous family with early-onset nonautoimmune diabetes. The individual with early onset is biallelic, and 3 other carriers had later onset diabetes. In addition, 3 other patients with mild neonatal hyperphenylalaninemia with features similar to dominantly inherited HNF1A-diabetes.

PMID: 24204001: 2 out 3 patients with hypomagnesemia and renal magnesium wasting associated to biallelic PCBD1 variants developed MODY
Mendeliome v0.6494 EPAS1 Seb Lunke Gene: epas1 has been classified as Green List (High Evidence).
Mendeliome v0.6494 EPAS1 Seb Lunke Phenotypes for gene: EPAS1 were changed from to Familial erythrocytosis (MIM#4611783), AD
Mendeliome v0.6492 NLRP3 Alison Yeung Classified gene: NLRP3 as Green List (high evidence)
Mendeliome v0.6492 NLRP3 Alison Yeung Gene: nlrp3 has been classified as Green List (High Evidence).
Mendeliome v0.6490 PCBD1 Michelle Torres changed review comment from: PMID: 24848070: one consanguineous family with early-onset nonautoimmune diabetes with features similar to dominantly inherited HNF1A-diabetes. The individual with early onset is biallelic, and 3 other carriers had later onset diabetes.

PMID: 24204001: 2 out 3 patients with hypomagnesemia and renal magnesium wasting associated to biallelic PCBD1 variants developed MODY; to: PMID: 24848070: one consanguineous family with early-onset nonautoimmune diabetes. The individual with early onset is biallelic, and 3 other carriers had later onset diabetes. In addition, 3 other patients with mild neonatal hyperphenylalaninemia with features similar to dominantly inherited HNF1A-diabetes.

PMID: 24204001: 2 out 3 patients with hypomagnesemia and renal magnesium wasting associated to biallelic PCBD1 variants developed MODY
Mendeliome v0.6487 NLRP3 Alison Yeung Gene: nlrp3 has been classified as Green List (High Evidence).
Mendeliome v0.6487 MED27 Alison Yeung Gene: med27 has been classified as Green List (High Evidence).
Mendeliome v0.6487 MED27 Alison Yeung Classified gene: MED27 as Green List (high evidence)
Mendeliome v0.6487 MED27 Alison Yeung Gene: med27 has been classified as Green List (High Evidence).
Mendeliome v0.6486 MED27 Alison Yeung gene: MED27 was added
gene: MED27 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MED27 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MED27 were set to 33443317
Phenotypes for gene: MED27 were set to Intellectual disability; cerebellar hypoplasia; dystonia
Review for gene: MED27 was set to GREEN
gene: MED27 was marked as current diagnostic
Added comment: 16 patients from 11 families with balletic variants
Sources: Literature
Mendeliome v0.6485 ACTL9 Elena Savva gene: ACTL9 was added
gene: ACTL9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ACTL9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACTL9 were set to PMID: 33626338
Phenotypes for gene: ACTL9 were set to Fertilization failure; male infertility
Review for gene: ACTL9 was set to GREEN
Added comment: Three families with homozygous pathogenic variants (two missense, one PTC). Single affected in each family. Functional analysis from patients shows all sperm had morphological defects, protein had reduced binding to ACTL7A
All variants very rare in gnomAD.
Sources: Literature
Mendeliome v0.6485 MAST2 Elena Savva gene: MAST2 was added
gene: MAST2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MAST2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MAST2 were set to PMID: 33465109
Phenotypes for gene: MAST2 were set to Thrombophilia; venous thrombosis
Review for gene: MAST2 was set to RED
Added comment: Single missense identified in a family with venous thrombosis and thrombophilia. Missense variant reviewed by in silicos only. Shown to affect regulation of TFP1 and SERPINE1 gene expression.

RNAi of MAST2 followed by RNAseq showed expression changes in many downstream targets
Sources: Literature
Mendeliome v0.6485 EPAS1 Teresa Zhao reviewed gene: EPAS1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 27292716, 19208626; Phenotypes: Familial erythrocytosis (MIM#4611783), AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.6485 AGPS Zornitza Stark Gene: agps has been classified as Green List (High Evidence).
Mendeliome v0.6485 AGPS Zornitza Stark Phenotypes for gene: AGPS were changed from to Rhizomelic chondrodysplasia punctata, type 3, MIM# 600121
Mendeliome v0.6482 AGPS Zornitza Stark reviewed gene: AGPS: Rating: GREEN; Mode of pathogenicity: None; Publications: 9553082, 8611652, 21990100; Phenotypes: Rhizomelic chondrodysplasia punctata, type 3, MIM# 600121; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6482 BANF1 Zornitza Stark Gene: banf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6479 BANF1 Zornitza Stark Classified gene: BANF1 as Amber List (moderate evidence)
Mendeliome v0.6479 BANF1 Zornitza Stark Gene: banf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6478 FOXP2 Zornitza Stark Gene: foxp2 has been classified as Green List (High Evidence).
Mendeliome v0.6475 GLI3 Zornitza Stark Gene: gli3 has been classified as Green List (High Evidence).
Mendeliome v0.6472 KIF22 Zornitza Stark Gene: kif22 has been classified as Green List (High Evidence).
Mendeliome v0.6471 KIF22 Zornitza Stark reviewed gene: KIF22: Rating: GREEN; Mode of pathogenicity: None; Publications: 25256152; Phenotypes: Spondyloepimetaphyseal dysplasia with joint laxity, type 2, MIM# 603546; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.6471 KIF22 Zornitza Stark Phenotypes for gene: KIF22 were changed from to Spondyloepimetaphyseal dysplasia with joint laxity, type 2 MIM#603546
Mendeliome v0.6468 ANKZF1 Bryony Thompson Gene: ankzf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6468 ANKZF1 Bryony Thompson Classified gene: ANKZF1 as Amber List (moderate evidence)
Mendeliome v0.6468 ANKZF1 Bryony Thompson Gene: ankzf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6466 ANGPT1 Bryony Thompson Classified gene: ANGPT1 as Amber List (moderate evidence)
Mendeliome v0.6466 ANGPT1 Bryony Thompson Gene: angpt1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6465 ANGPT1 Bryony Thompson gene: ANGPT1 was added
gene: ANGPT1 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: ANGPT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANGPT1 were set to 28601681; 24852101; 30689269; 10617467; 8980224
Phenotypes for gene: ANGPT1 were set to Hereditary angioedema
Review for gene: ANGPT1 was set to AMBER
Added comment: A missense variant (A119S) identified in 4 affected individuals in a single family. Supportive data in patient cells, functional assays of the variant, and animal models (both overexpression and null) for the gene.
Sources: Other
Mendeliome v0.6464 CLTCL1 Bryony Thompson Gene: cltcl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6464 CLTCL1 Bryony Thompson Classified gene: CLTCL1 as Amber List (moderate evidence)
Mendeliome v0.6464 CLTCL1 Bryony Thompson Added comment: Comment on list classification: A single family, but also some compelling functional data for an association with insensitivity to pain.
Mendeliome v0.6464 CLTCL1 Bryony Thompson Gene: cltcl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6463 CLTCL1 Bryony Thompson changed review comment from: PMID: 26068709 - Three siblings in a single consanguineous family with congenital insensitivity to pain, inability to feel touch, and cognitive delay and a homozygous rare missense variant (Glu330Lys - no homozygotes in gnomAD v2.1). In vitro functional assays of the variant suggested a deleterious effect on the protein. Additionally cellular assays suggested a role for the gene in neural crest development and in the genesis of pain and touch sensing neurons.

PMID: 29402896 - more in depth functional assays and proteomic analyses suggesting a role for the protein in regulating sensory neuron differentiation in the human peripheral system

Other reports of associations with limited evidence:
PMID: 22511880 - Identified as a candidate gene in an autism study, but the homozygous variant (reported as R125C, but actually R1165C) has 40 homozygotes in gnomAD v2.1. And many of the other compound heterozygous candidate variants in the study are too common in gnomAD v2.1, with many homozygotes present. The missense reported in the pain insensitivity family Glu330Lys was reported with another rare missense variant (Glu1310Lys) in one of the autism cases, but no other phenotype information was provided.

PMID: 31354784 - a single case with infantile spasm reported with compound het missense (Met1316Val & Arg1165Cys), but both are very common in gnomAD v2.1 with 33,000 and 40 homozygotes, respectively.
Sources: Literature; to: PMID: 26068709 - Three siblings in a single consanguineous family with congenital insensitivity to pain, inability to feel touch, and cognitive delay and a homozygous rare missense variant (Glu330Lys - no homozygotes in gnomAD v2.1). In vitro functional assays of the variant suggested a deleterious effect on the protein. Additionally cellular assays suggested a role for the gene in neural crest development and in the genesis of pain and touch sensing neurons.

PMID: 29402896 - more in depth functional assays and proteomic analyses suggesting a role for the protein in regulating sensory neuron differentiation in the human peripheral system.

Other reports of associations with limited evidence:
PMID: 22511880 - Identified as a candidate gene in an autism study, but the homozygous variant (reported as R125C, but actually R1165C) has 40 homozygotes in gnomAD v2.1. And many of the other compound heterozygous candidate variants in the study are too common in gnomAD v2.1, with many homozygotes present. The missense reported in the pain insensitivity family Glu330Lys was reported with another rare missense variant (Glu1310Lys) in one of the autism cases, but no other phenotype information was provided.

PMID: 31354784 - a single case with infantile spasm reported with compound het missense (Met1316Val & Arg1165Cys), but both are very common in gnomAD v2.1 with 33,000 and 40 homozygotes, respectively.
Sources: Literature
Mendeliome v0.6463 CLTCL1 Bryony Thompson gene: CLTCL1 was added
gene: CLTCL1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CLTCL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLTCL1 were set to 26068709; 29402896; 22511880; 31354784
Phenotypes for gene: CLTCL1 were set to Congenital insensitivity to pain
Review for gene: CLTCL1 was set to AMBER
Added comment: PMID: 26068709 - Three siblings in a single consanguineous family with congenital insensitivity to pain, inability to feel touch, and cognitive delay and a homozygous rare missense variant (Glu330Lys - no homozygotes in gnomAD v2.1). In vitro functional assays of the variant suggested a deleterious effect on the protein. Additionally cellular assays suggested a role for the gene in neural crest development and in the genesis of pain and touch sensing neurons.

PMID: 29402896 - more in depth functional assays and proteomic analyses suggesting a role for the protein in regulating sensory neuron differentiation in the human peripheral system

Other reports of associations with limited evidence:
PMID: 22511880 - Identified as a candidate gene in an autism study, but the homozygous variant (reported as R125C, but actually R1165C) has 40 homozygotes in gnomAD v2.1. And many of the other compound heterozygous candidate variants in the study are too common in gnomAD v2.1, with many homozygotes present. The missense reported in the pain insensitivity family Glu330Lys was reported with another rare missense variant (Glu1310Lys) in one of the autism cases, but no other phenotype information was provided.

PMID: 31354784 - a single case with infantile spasm reported with compound het missense (Met1316Val & Arg1165Cys), but both are very common in gnomAD v2.1 with 33,000 and 40 homozygotes, respectively.
Sources: Literature
Mendeliome v0.6462 KIF22 Elena Savva reviewed gene: KIF22: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22152677, 22152678; Phenotypes: Spondyloepimetaphyseal dysplasia with joint laxity, type 2 MIM#603546; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Mendeliome v0.6461 SLC7A6OS Zornitza Stark Phenotypes for gene: SLC7A6OS were changed from Progressive myoclonus epilepsy to Epilepsy, progressive myoclonic, 12, MIM# 619191
Mendeliome v0.6460 SLC7A6OS Zornitza Stark edited their review of gene: SLC7A6OS: Changed phenotypes: Epilepsy, progressive myoclonic, 12, MIM# 619191
Mendeliome v0.6460 G6PC Zornitza Stark Gene: g6pc has been classified as Green List (High Evidence).
Mendeliome v0.6457 ALPI Zornitza Stark Classified gene: ALPI as Amber List (moderate evidence)
Mendeliome v0.6457 ALPI Zornitza Stark Gene: alpi has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6456 NMNAT2 Bryony Thompson Gene: nmnat2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6456 NMNAT2 Bryony Thompson Gene: nmnat2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6456 NMNAT2 Bryony Thompson Classified gene: NMNAT2 as Amber List (moderate evidence)
Mendeliome v0.6456 NMNAT2 Bryony Thompson Gene: nmnat2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6455 NMNAT2 Bryony Thompson gene: NMNAT2 was added
gene: NMNAT2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NMNAT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NMNAT2 were set to 31132363; 25271157; 20126265
Phenotypes for gene: NMNAT2 were set to polyneuropathy; erythromelalgia
Review for gene: NMNAT2 was set to AMBER
Added comment: A single family with siblings with a homozygous variant that confers a partial loss of function. Strong supporting functional evidence that the gene plays a key role in axonal survival.
Sources: Literature
Mendeliome v0.6451 USF1 Bryony Thompson Gene: usf1 has been classified as Red List (Low Evidence).
Mendeliome v0.6451 USF1 Bryony Thompson Classified gene: USF1 as Red List (low evidence)
Mendeliome v0.6451 USF1 Bryony Thompson Gene: usf1 has been classified as Red List (Low Evidence).
Mendeliome v0.6449 PDXK Bryony Thompson Classified gene: PDXK as Green List (high evidence)
Mendeliome v0.6449 PDXK Bryony Thompson Added comment: Comment on list classification: Additional family published in 2020
Mendeliome v0.6449 PDXK Bryony Thompson Gene: pdxk has been classified as Green List (High Evidence).
Mendeliome v0.6447 LIPI Bryony Thompson Gene: lipi has been classified as Red List (Low Evidence).
Mendeliome v0.6447 LIPI Bryony Thompson Classified gene: LIPI as Red List (low evidence)
Mendeliome v0.6447 LIPI Bryony Thompson Gene: lipi has been classified as Red List (Low Evidence).
Mendeliome v0.6446 GALNT12 Bryony Thompson Gene: galnt12 has been classified as Red List (Low Evidence).
Mendeliome v0.6446 GALNT12 Bryony Thompson Classified gene: GALNT12 as Red List (low evidence)
Mendeliome v0.6446 GALNT12 Bryony Thompson Gene: galnt12 has been classified as Red List (Low Evidence).
Mendeliome v0.6445 ABCG2 Bryony Thompson Gene: abcg2 has been classified as Red List (Low Evidence).
Mendeliome v0.6445 ABCG2 Bryony Thompson Classified gene: ABCG2 as Red List (low evidence)
Mendeliome v0.6445 ABCG2 Bryony Thompson Gene: abcg2 has been classified as Red List (Low Evidence).
Mendeliome v0.6444 SAT1 Bryony Thompson Gene: sat1 has been classified as Red List (Low Evidence).
Mendeliome v0.6444 SAT1 Bryony Thompson Classified gene: SAT1 as Red List (low evidence)
Mendeliome v0.6444 SAT1 Bryony Thompson Gene: sat1 has been classified as Red List (Low Evidence).
Mendeliome v0.6443 SAT1 Bryony Thompson reviewed gene: SAT1: Rating: RED; Mode of pathogenicity: None; Publications: 12215835, 20672378, 9228047; Phenotypes: Keratosis follicularis spinulosa decalvans; 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 v0.6442 ALPI Zornitza Stark Classified gene: ALPI as Green List (high evidence)
Mendeliome v0.6442 ALPI Zornitza Stark Gene: alpi has been classified as Green List (High Evidence).
Mendeliome v0.6441 MIR5004 Bryony Thompson Gene: mir5004 has been classified as Red List (Low Evidence).
Mendeliome v0.6441 MIR5004 Bryony Thompson Classified gene: MIR5004 as Red List (low evidence)
Mendeliome v0.6441 MIR5004 Bryony Thompson Gene: mir5004 has been classified as Red List (Low Evidence).
Mendeliome v0.6440 TOGARAM1 Zornitza Stark Phenotypes for gene: TOGARAM1 were changed from Cleft of the lip and palate; Microphthalmia; Cerebral dysgenesis; Hydrocephalus to Joubert syndrome 37, MIM# 619185
Mendeliome v0.6438 TOGARAM1 Zornitza Stark Classified gene: TOGARAM1 as Green List (high evidence)
Mendeliome v0.6438 TOGARAM1 Zornitza Stark Gene: togaram1 has been classified as Green List (High Evidence).
Mendeliome v0.6437 ALDOA Zornitza Stark Gene: aldoa has been classified as Green List (High Evidence).
Mendeliome v0.6434 RDH5 Zornitza Stark Gene: rdh5 has been classified as Green List (High Evidence).
Mendeliome v0.6431 RPGRIP1 Zornitza Stark Gene: rpgrip1 has been classified as Green List (High Evidence).
Mendeliome v0.6431 RPGRIP1 Zornitza Stark Phenotypes for gene: RPGRIP1 were changed from to Cone-rod dystrophy 13 (MIM#608194) , Leber congenital amaurosis (MIM#61382)
Mendeliome v0.6428 RPGRIP1 Ain Roesley reviewed gene: RPGRIP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33308271, 31666973; Phenotypes: Cone-rod dystrophy 13 (MIM#608194) , Leber congenital amaurosis (MIM#61382); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6428 IRX4 Zornitza Stark Gene: irx4 has been classified as Red List (Low Evidence).
Mendeliome v0.6425 IRX4 Zornitza Stark Classified gene: IRX4 as Red List (low evidence)
Mendeliome v0.6425 IRX4 Zornitza Stark Gene: irx4 has been classified as Red List (Low Evidence).
Mendeliome v0.6424 AKAP6 Zornitza Stark Gene: akap6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6421 AKAP6 Zornitza Stark Classified gene: AKAP6 as Amber List (moderate evidence)
Mendeliome v0.6421 AKAP6 Zornitza Stark Gene: akap6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6420 ASCC3 Bryony Thompson Gene: ascc3 has been classified as Green List (High Evidence).
Mendeliome v0.6420 ASCC3 Bryony Thompson Classified gene: ASCC3 as Green List (high evidence)
Mendeliome v0.6420 ASCC3 Bryony Thompson Gene: ascc3 has been classified as Green List (High Evidence).
Mendeliome v0.6418 HS2ST1 Zornitza Stark Phenotypes for gene: HS2ST1 were changed from Intellectual disability; dysmorphic features; congenital anomalies to Neurofacioskeletal syndrome with or without renal agenesis, MIM#619194; Intellectual disability; dysmorphic features; congenital anomalies
Mendeliome v0.6417 HS2ST1 Zornitza Stark reviewed gene: HS2ST1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurofacioskeletal syndrome with or without renal agenesis, MIM#619194; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6414 ARSG Bryony Thompson Classified gene: ARSG as Green List (high evidence)
Mendeliome v0.6414 ARSG Bryony Thompson Added comment: Comment on list classification: 2 additional families reported, upgraded to green
Mendeliome v0.6414 ARSG Bryony Thompson Gene: arsg has been classified as Green List (High Evidence).
Mendeliome v0.6412 LMNB1 Zornitza Stark Phenotypes for gene: LMNB1 were changed from Global developmental delay, Intellectual disability, Microcephaly, Short stature, Seizures, Abnormality of the corpus callosum, Cortical gyral simplification, Feeding difficulties, Scoliosis; Leukodystrophy, adult-onset, autosomal dominant, MIM#169500 to Microcephaly 26, primary, autosomal dominant, MIM# 619179; Global developmental delay, Intellectual disability, Microcephaly, Short stature, Seizures, Abnormality of the corpus callosum, Cortical gyral simplification, Feeding difficulties, Scoliosis; Leukodystrophy, adult-onset, autosomal dominant, MIM#169500
Mendeliome v0.6411 LMNB1 Zornitza Stark edited their review of gene: LMNB1: Changed phenotypes: Microcephaly 26, primary, autosomal dominant, MIM# 619179, Global developmental delay, Intellectual disability, Microcephaly, Short stature, Seizures, Abnormality of the corpus callosum, Cortical gyral simplification, Feeding difficulties, Scoliosis, Leukodystrophy, adult-onset, autosomal dominant, MIM#169500
Mendeliome v0.6410 CRYM Zornitza Stark Gene: crym has been classified as Green List (High Evidence).
Mendeliome v0.6407 HARS Zornitza Stark Gene: hars has been classified as Green List (High Evidence).
Mendeliome v0.6401 PMVK Zornitza Stark Gene: pmvk has been classified as Green List (High Evidence).
Mendeliome v0.6401 PMVK Zornitza Stark Classified gene: PMVK as Green List (high evidence)
Mendeliome v0.6401 PMVK Zornitza Stark Gene: pmvk has been classified as Green List (High Evidence).
Mendeliome v0.6400 PMVK Zornitza Stark gene: PMVK was added
gene: PMVK was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: PMVK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PMVK were set to 26202976
Phenotypes for gene: PMVK were set to Porokeratosis 1, multiple types, MIM# 175800
Review for gene: PMVK was set to GREEN
Added comment: At least 9 individuals reported.
Sources: Expert Review
Mendeliome v0.6399 MVD Zornitza Stark Gene: mvd has been classified as Green List (High Evidence).
Mendeliome v0.6399 MVD Zornitza Stark Classified gene: MVD as Green List (high evidence)
Mendeliome v0.6399 MVD Zornitza Stark Gene: mvd has been classified as Green List (High Evidence).
Mendeliome v0.6398 MVD Zornitza Stark gene: MVD was added
gene: MVD was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MVD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MVD were set to 30942823; 33491095
Phenotypes for gene: MVD were set to Porokeratosis 7, multiple types, MIM# 614714
Review for gene: MVD was set to GREEN
Added comment: Porokeratoses are a heterogeneous group of keratinization disorders. For linear porokeratosis and disseminated superficial actinic porokeratosis, a heterozygous pathogenic germline variant in a mevalonate pathway gene and a postzygotic second hit mutation present in affected skin have been shown to be the patho-genetic mechanism for the development of the lesions. At least 5 individuals reported.
Sources: Expert list
Mendeliome v0.6396 UNC45B Zornitza Stark Phenotypes for gene: UNC45B were changed from Progressive Myopathy with Eccentric Cores to Myofibrillar myopathy 11, MIM# 619178; Progressive Myopathy with Eccentric Cores
Mendeliome v0.6395 SHROOM3 Zornitza Stark Gene: shroom3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6395 SHROOM3 Zornitza Stark Classified gene: SHROOM3 as Amber List (moderate evidence)
Mendeliome v0.6395 SHROOM3 Zornitza Stark Gene: shroom3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6394 SHROOM3 Zornitza Stark gene: SHROOM3 was added
gene: SHROOM3 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: SHROOM3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SHROOM3 were set to 32621286
Phenotypes for gene: SHROOM3 were set to Anencephaly; cleft lip and palate
Review for gene: SHROOM3 was set to AMBER
Added comment: Animal model and other functional data link SHROOM3 to neural tube development. Single family reported with bi-allelic LoF in a fetus with anencephaly and CL/P.
Sources: Expert Review
Mendeliome v0.6393 FLT3 Zornitza Stark Gene: flt3 has been classified as Red List (Low Evidence).
Mendeliome v0.6393 FLT3 Zornitza Stark Classified gene: FLT3 as Red List (low evidence)
Mendeliome v0.6393 FLT3 Zornitza Stark Gene: flt3 has been classified as Red List (Low Evidence).
Mendeliome v0.6392 MSL3 Zornitza Stark Gene: msl3 has been classified as Green List (High Evidence).
Mendeliome v0.6392 MSL3 Zornitza Stark Phenotypes for gene: MSL3 were changed from to Basilicata-Akhtar syndrome, OMIM # 301032
Mendeliome v0.6389 MSL3 Zornitza Stark reviewed gene: MSL3: Rating: GREEN; Mode of pathogenicity: None; Publications: 33173220; Phenotypes: Basilicata-Akhtar syndrome, OMIM # 301032; 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 v0.6389 TOE1 Zornitza Stark Gene: toe1 has been classified as Green List (High Evidence).
Mendeliome v0.6389 TOE1 Zornitza Stark Phenotypes for gene: TOE1 were changed from to Pontocerebellar hypoplasia, type 7, MIM# 614969
Mendeliome v0.6386 TOE1 Zornitza Stark reviewed gene: TOE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28092684; Phenotypes: Pontocerebellar hypoplasia, type 7, MIM# 614969; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6386 VRK1 Zornitza Stark Gene: vrk1 has been classified as Green List (High Evidence).
Mendeliome v0.6386 VRK1 Zornitza Stark Phenotypes for gene: VRK1 were changed from to Pontocerebellar hypoplasia type 1A, MIM# 607596; SMA
Mendeliome v0.6383 VRK1 Zornitza Stark edited their review of gene: VRK1: Changed rating: GREEN; Changed phenotypes: Pontocerebellar hypoplasia type 1A, MIM# 607596, SMA
Mendeliome v0.6383 SPTBN2 Zornitza Stark Gene: sptbn2 has been classified as Green List (High Evidence).
Mendeliome v0.6383 SPTBN2 Zornitza Stark Phenotypes for gene: SPTBN2 were changed from to Spinocerebellar ataxia, autosomal recessive 14, MIM# 615386; Spinocerebellar ataxia 5, MIM# 600224
Mendeliome v0.6380 SEPSECS Zornitza Stark Gene: sepsecs has been classified as Green List (High Evidence).
Mendeliome v0.6380 SEPSECS Zornitza Stark Phenotypes for gene: SEPSECS were changed from to Pontocerebellar hypoplasia type 2D, 613811; cerebellar ataxia and cognitive impairment
Mendeliome v0.6377 SEPSECS Zornitza Stark reviewed gene: SEPSECS: Rating: GREEN; Mode of pathogenicity: None; Publications: 20920667, 25044680, 31748115, 29464431; Phenotypes: Pontocerebellar hypoplasia type 2D, MIM# 613811; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6377 ITPR1 Zornitza Stark changed review comment from: Gillespie syndrome is usually diagnosed in the first year of life by the presence of fixed dilated pupils in a hypotonic infant. Affected individuals have a characteristic form of iris hypoplasia in which the pupillary border of the iris exhibits a scalloped or 'festooned' edge, with iris strands extending onto the anterior lens surface at regular intervals. The key extraocular features of Gillespie syndrome are congenital hypotonia, progressive cerebellar hypoplasia, and ataxia, as well as variable cognitive impairment that is usually mild. Multiple families reported with bi-allelic or de novo heterozygous variants.; to: Gillespie syndrome: usually diagnosed in the first year of life by the presence of fixed dilated pupils in a hypotonic infant. Affected individuals have a characteristic form of iris hypoplasia in which the pupillary border of the iris exhibits a scalloped or 'festooned' edge, with iris strands extending onto the anterior lens surface at regular intervals. The key extraocular features of Gillespie syndrome are congenital hypotonia, progressive cerebellar hypoplasia, and ataxia, as well as variable cognitive impairment that is usually mild. Multiple families reported with bi-allelic or de novo heterozygous variants.
Mendeliome v0.6377 ITPR1 Zornitza Stark Gene: itpr1 has been classified as Green List (High Evidence).
Mendeliome v0.6377 ITPR1 Zornitza Stark Phenotypes for gene: ITPR1 were changed from to Gillespie syndrome, MIM# 206700; Spinocerebellar ataxia 15 MIM#606658; Spinocerebellar ataxia 29, congenital nonprogressive MIM#117360
Mendeliome v0.6374 EXOSC8 Zornitza Stark Gene: exosc8 has been classified as Green List (High Evidence).
Mendeliome v0.6374 EXOSC8 Zornitza Stark Phenotypes for gene: EXOSC8 were changed from to Pontocerebellar hypoplasia, type 1C, MIM# 616081
Mendeliome v0.6371 EXOSC8 Zornitza Stark reviewed gene: EXOSC8: Rating: GREEN; Mode of pathogenicity: None; Publications: 24989451; Phenotypes: Pontocerebellar hypoplasia, type 1C, MIM# 616081; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6371 EXOSC3 Zornitza Stark Gene: exosc3 has been classified as Green List (High Evidence).
Mendeliome v0.6371 EXOSC3 Zornitza Stark Phenotypes for gene: EXOSC3 were changed from to Pontocerebellar hypoplasia, type 1B, MIM# 614678
Mendeliome v0.6368 EXOSC3 Zornitza Stark reviewed gene: EXOSC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 22544365, 23284067, 24524299; Phenotypes: Pontocerebellar hypoplasia, type 1B, MIM# 614678; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6368 CLP1 Zornitza Stark Gene: clp1 has been classified as Green List (High Evidence).
Mendeliome v0.6368 CLP1 Zornitza Stark Phenotypes for gene: CLP1 were changed from to Pontocerebellar hypoplasia type 10, MIM# 615803
Mendeliome v0.6365 CLP1 Zornitza Stark reviewed gene: CLP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24766809, 29307788; Phenotypes: Pontocerebellar hypoplasia type 10, MIM# 615803; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6365 CHMP1A Zornitza Stark Gene: chmp1a has been classified as Green List (High Evidence).
Mendeliome v0.6365 CHMP1A Zornitza Stark Phenotypes for gene: CHMP1A were changed from to Pontocerebellar hypoplasia, type 8, MIM# 614961
Mendeliome v0.6362 CHMP1A Zornitza Stark reviewed gene: CHMP1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 23023333; Phenotypes: Pontocerebellar hypoplasia, type 8, MIM# 614961; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6362 BRF1 Zornitza Stark Gene: brf1 has been classified as Green List (High Evidence).
Mendeliome v0.6359 DHODH Zornitza Stark Gene: dhodh has been classified as Green List (High Evidence).
Mendeliome v0.6356 ITGB4 Zornitza Stark Gene: itgb4 has been classified as Green List (High Evidence).
Mendeliome v0.6356 ITGB4 Zornitza Stark Phenotypes for gene: ITGB4 were changed from to Epidermolysis bullosa of hands and feet, MIM# 131800; Epidermolysis bullosa, junctional, non-Herlitz type, MIM# 226650; Epidermolysis bullosa, junctional, with pyloric atresia, MIM# 226730
Mendeliome v0.6353 ITGB4 Zornitza Stark reviewed gene: ITGB4: Rating: GREEN; Mode of pathogenicity: None; Publications: 11328943, 9670011, 33225458, 30079450, 29380424, 29198538, 28557647; Phenotypes: Epidermolysis bullosa of hands and feet, MIM# 131800, Epidermolysis bullosa, junctional, non-Herlitz type, MIM# 226650, Epidermolysis bullosa, junctional, with pyloric atresia, MIM# 226730; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.6353 LAMA3 Zornitza Stark Gene: lama3 has been classified as Green List (High Evidence).
Mendeliome v0.6353 LAMA3 Zornitza Stark Phenotypes for gene: LAMA3 were changed from to Epidermolysis bullosa, generalized atrophic benign, MIM# 226650; Epidermolysis bullosa, junctional, Herlitz type, MIM# 226700
Mendeliome v0.6350 LAMA3 Zornitza Stark reviewed gene: LAMA3: Rating: GREEN; Mode of pathogenicity: None; Publications: 7633458, 8530087, 11810295, 10366601; Phenotypes: Epidermolysis bullosa, generalized atrophic benign, MIM# 226650, Epidermolysis bullosa, junctional, Herlitz type, MIM# 226700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6350 LAMB3 Zornitza Stark Gene: lamb3 has been classified as Green List (High Evidence).
Mendeliome v0.6350 LAMB3 Zornitza Stark Phenotypes for gene: LAMB3 were changed from to Epidermolysis bullosa, junctional, Herlitz type, MIM# 226700; Epidermolysis bullosa, junctional, non-Herlitz type, MIM# 226650
Mendeliome v0.6347 LAMB3 Zornitza Stark reviewed gene: LAMB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 11023379, 7706760; Phenotypes: Epidermolysis bullosa, junctional, Herlitz type, MIM# 226700, Epidermolysis bullosa, junctional, non-Herlitz type, MIM# 226650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6347 LAMC2 Zornitza Stark Gene: lamc2 has been classified as Green List (High Evidence).
Mendeliome v0.6347 LAMC2 Zornitza Stark Phenotypes for gene: LAMC2 were changed from to Epidermolysis bullosa, junctional, Herlitz type, MIM# 226700; Epidermolysis bullosa, junctional, non-Herlitz type, MIM# 226650
Mendeliome v0.6344 LAMC2 Zornitza Stark reviewed gene: LAMC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 11810295, 25888738, 24533970; Phenotypes: Epidermolysis bullosa, junctional, Herlitz type, MIM# 226700, Epidermolysis bullosa, junctional, non-Herlitz type, MIM# 226650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6344 KRT5 Zornitza Stark Gene: krt5 has been classified as Green List (High Evidence).
Mendeliome v0.6344 KRT5 Zornitza Stark Phenotypes for gene: KRT5 were changed from to Dowling-Degos disease 1, MIM# 179850; Epidermolysis bullosa simplex-MCR, MIM# 609352; Epidermolysis bullosa simplex-MP 131960; Epidermolysis bullosa simplex, Dowling-Meara type, MIM# 131760; Epidermolysis bullosa simplex, Koebner type, MIM# 131900; Epidermolysis bullosa simplex, recessive 1, MIM# 601001; Epidermolysis bullosa simplex, Weber-Cockayne type, MIM# 131800
Mendeliome v0.6342 KRT5 Zornitza Stark reviewed gene: KRT5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dowling-Degos disease 1, MIM# 179850, Epidermolysis bullosa simplex-MCR, MIM# 609352, Epidermolysis bullosa simplex-MP 131960, Epidermolysis bullosa simplex, Dowling-Meara type, MIM# 131760, Epidermolysis bullosa simplex, Koebner type, MIM# 131900, Epidermolysis bullosa simplex, recessive 1, MIM# 601001, Epidermolysis bullosa simplex, Weber-Cockayne type, MIM# 131800; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.6340 ITGA6 Zornitza Stark Gene: itga6 has been classified as Green List (High Evidence).
Mendeliome v0.6340 ITGA6 Zornitza Stark Phenotypes for gene: ITGA6 were changed from to Epidermolysis bullosa, junctional, with pyloric stenosis, MIM# 226730
Mendeliome v0.6337 ITGA6 Zornitza Stark reviewed gene: ITGA6: Rating: GREEN; Mode of pathogenicity: None; Publications: 31502654, 27607025, 9158140; Phenotypes: Epidermolysis bullosa, junctional, with pyloric stenosis, MIM# 226730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6337 ITGA3 Zornitza Stark Gene: itga3 has been classified as Green List (High Evidence).
Mendeliome v0.6337 ITGA3 Zornitza Stark Phenotypes for gene: ITGA3 were changed from to Interstitial lung disease, nephrotic syndrome, and epidermolysis bullosa, congenital, MIM# 614748
Mendeliome v0.6334 ITGA3 Zornitza Stark reviewed gene: ITGA3: Rating: GREEN; Mode of pathogenicity: None; Publications: 22512483, 25810266, 27717396, 32198874, 26854491; Phenotypes: Interstitial lung disease, nephrotic syndrome, and epidermolysis bullosa, congenital, MIM# 614748; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6334 FERMT1 Zornitza Stark Gene: fermt1 has been classified as Green List (High Evidence).
Mendeliome v0.6331 EXPH5 Zornitza Stark Gene: exph5 has been classified as Green List (High Evidence).
Mendeliome v0.6331 EXPH5 Zornitza Stark Phenotypes for gene: EXPH5 were changed from to Epidermolysis bullosa, nonspecific, autosomal recessive, MIM# 615028
Mendeliome v0.6328 EXPH5 Zornitza Stark reviewed gene: EXPH5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23176819, 32176379, 27730671, 27384765; Phenotypes: Epidermolysis bullosa, nonspecific, autosomal recessive, MIM# 615028; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6328 COL7A1 Zornitza Stark Gene: col7a1 has been classified as Green List (High Evidence).
Mendeliome v0.6328 COL7A1 Zornitza Stark Phenotypes for gene: COL7A1 were changed from to EBD inversa, MIM# 226600; EBD, Bart type MIM# 132000; EBD, localisata variant; Epidermolysis bullosa dystrophica, MIM# 131750; Epidermolysis bullosa dystrophica, 226600; Epidermolysis bullosa pruriginosa 604129; Epidermolysis bullosa, pretibial, MIM# 131850; Transient bullous of the newborn 131705
Mendeliome v0.6326 COL7A1 Zornitza Stark reviewed gene: COL7A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: EBD inversa, MIM# 226600, EBD, Bart type MIM# 132000, EBD, localisata variant, Epidermolysis bullosa dystrophica, MIM# 131750, Epidermolysis bullosa dystrophica, 226600, Epidermolysis bullosa pruriginosa 604129, Epidermolysis bullosa, pretibial, MIM# 131850, Transient bullous of the newborn 131705; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.6326 IGSF1 Zornitza Stark Gene: igsf1 has been classified as Green List (High Evidence).
Mendeliome v0.6323 FSTL5 Zornitza Stark Gene: fstl5 has been classified as Red List (Low Evidence).
Mendeliome v0.6323 FSTL5 Zornitza Stark Classified gene: FSTL5 as Red List (low evidence)
Mendeliome v0.6323 FSTL5 Zornitza Stark Gene: fstl5 has been classified as Red List (Low Evidence).
Mendeliome v0.6322 NCOA3 Zornitza Stark Gene: ncoa3 has been classified as Red List (Low Evidence).
Mendeliome v0.6322 NCOA3 Zornitza Stark Classified gene: NCOA3 as Red List (low evidence)
Mendeliome v0.6322 NCOA3 Zornitza Stark Gene: ncoa3 has been classified as Red List (Low Evidence).
Mendeliome v0.6321 FCHO1 Zornitza Stark Phenotypes for gene: FCHO1 were changed from Combined immunodeficiency; T cells: low, poor proliferation; B cells: normal number; Recurrent infections (viral, mycobacteria, bacterial, fungal); lymphoproliferation; Failure to thrive; Increased activation-induced T-cell death; Defective clathrin-mediated endocytosis to Immunodeficiency 76, MIM# 619164; Combined immunodeficiency; T cells: low, poor proliferation; B cells: normal number; Recurrent infections (viral, mycobacteria, bacterial, fungal); lymphoproliferation; Failure to thrive; Increased activation-induced T-cell death; Defective clathrin-mediated endocytosis
Mendeliome v0.6320 FCHO1 Zornitza Stark edited their review of gene: FCHO1: Changed phenotypes: Immunodeficiency 76, MIM# 619164, Combined immunodeficiency, T cells: low, poor proliferation, B cells: normal number, Recurrent infections (viral, mycobacteria, bacterial, fungal), lymphoproliferation, Failure to thrive, Increased activation-induced T-cell death, Defective clathrin-mediated endocytosis
Mendeliome v0.6320 FSTL5 Eleanor Williams gene: FSTL5 was added
gene: FSTL5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FSTL5 was set to Unknown
Publications for gene: FSTL5 were set to 33105483
Phenotypes for gene: FSTL5 were set to isolated club-foot; iTEV; Talipes equinovarus
Review for gene: FSTL5 was set to RED
Added comment: PMID: 33105483 - Khanshour et al 20201 - GWAS study of isolated Talipes equinovarus (clubfoot, iTEV) identified an associated locus within FSTL5. They show that Fstl5 is expressed in the embryonic hindlimb in bats, chicks and mice. However, Fstl5 was expressed more highly in neural tissues in mice, and rats lacking Fstl5 showed no gross developmental malformations. Conditional overexpression of Fstl5 in osteochondroprogenitors resulted in sexually dimorphic differences in skeletal development in mice.
Sources: Literature
Mendeliome v0.6320 NCOA3 Eleanor Williams gene: NCOA3 was added
gene: NCOA3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NCOA3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NCOA3 were set to 33326993
Phenotypes for gene: NCOA3 were set to non-syndromic hearing loss
Review for gene: NCOA3 was set to RED
Added comment: PMID: 33326993 - Salazar da Silva et al 2020 - report a 5 generation Brazilian family with 15 individuals with non-syndromic, bilateral and progressive hearing loss. Using linkage analysis and then exome sequencing they identified a heterozygous variant in NCOA3 (NM_181659, c.2810C > G; p.Ser937Cys) that was found in the 7 analysed affected individuals. It was also found in 4 unaffected individuals but they are within the range of onset of hearing loss observed in the family. Expression of nco3 was found in the inner ear of mice and zebrafish. ncoa3-/- zebrafish showed subtle alterations in cartilage, mineral density and abnormal adult swimming behaviour, which may suggest the mechanism of pathogenicity.
Sources: Literature
Mendeliome v0.6320 CFHR3 Zornitza Stark Gene: cfhr3 has been classified as Green List (High Evidence).
Mendeliome v0.6317 CFHR1 Zornitza Stark Gene: cfhr1 has been classified as Green List (High Evidence).
Mendeliome v0.6312 OTUD5 Zornitza Stark Classified gene: OTUD5 as Green List (high evidence)
Mendeliome v0.6312 OTUD5 Zornitza Stark Gene: otud5 has been classified as Green List (High Evidence).
Mendeliome v0.6311 OTUD5 Zornitza Stark edited their review of gene: OTUD5: Added comment: PMID 33523931: Another 10 individuals from 7 families reported, promote to Green. X-linked multiple congenital anomalies-neurodevelopmental syndrome (MCAND) is an X-linked recessive congenital multisystemic disorder characterized by poor growth, global developmental delay with impaired intellectual development, and variable abnormalities of the cardiac, skeletal, and genitourinary systems. Most affected individuals also have hypotonia and dysmorphic craniofacial features. Brain imaging typically shows enlarged ventricles and thin corpus callosum; some have microcephaly, whereas others have hydrocephalus. The severity of the disorder is highly variable, ranging from death in early infancy to survival into the second or third decade.; Changed rating: GREEN; Changed publications: 33131077, 33523931; Changed phenotypes: Multiple congenital anomalies-neurodevelopmental syndrome, X-linked, MIM# 301056
Mendeliome v0.6311 SCARB1 Bryony Thompson Gene: scarb1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6311 SCARB1 Bryony Thompson Phenotypes for gene: SCARB1 were changed from to High density lipoprotein cholesterol level QTL6 MIM#610762; Scavenger receptor class B type I deficiency; Inherited hypolipidaemias
Mendeliome v0.6308 SCARB1 Bryony Thompson Classified gene: SCARB1 as Amber List (moderate evidence)
Mendeliome v0.6308 SCARB1 Bryony Thompson Added comment: Comment on list classification: Benign clinical phenotype
Mendeliome v0.6308 SCARB1 Bryony Thompson Gene: scarb1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6307 SCARB1 Bryony Thompson reviewed gene: SCARB1: Rating: ; Mode of pathogenicity: None; Publications: 21226579, 30720493, 21480869, 26965621, 27604308; Phenotypes: High density lipoprotein cholesterol level QTL6 MIM#610762, Scavenger receptor class B type I deficiency, Inherited hypolipidaemias; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.6307 CETP Bryony Thompson Gene: cetp has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6307 CETP Bryony Thompson Phenotypes for gene: CETP were changed from to Hyperalphalipoproteinemia MIM#143470; Disorders of high density lipoprotein metabolism
Mendeliome v0.6304 CETP Bryony Thompson Classified gene: CETP as Amber List (moderate evidence)
Mendeliome v0.6304 CETP Bryony Thompson Added comment: Comment on list classification: Benign metabolic condition
Mendeliome v0.6304 CETP Bryony Thompson Gene: cetp has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6303 CETP Bryony Thompson reviewed gene: CETP: Rating: ; Mode of pathogenicity: None; Publications: 12070157, 2586614, 27604308, 2215607, 2390095; Phenotypes: Hyperalphalipoproteinemia MIM#143470, Disorders of high density lipoprotein metabolism; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.6302 DMGDH Bryony Thompson Classified gene: DMGDH as Amber List (moderate evidence)
Mendeliome v0.6302 DMGDH Bryony Thompson Gene: dmgdh has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6301 CD320 Bryony Thompson Gene: cd320 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6301 CD320 Bryony Thompson Phenotypes for gene: CD320 were changed from to Methylmalonic aciduria, transient, due to transcobalamin receptor defect MIM#613646; Disorders of cobalamin absorption, transport and metabolism
Mendeliome v0.6299 CD320 Bryony Thompson Classified gene: CD320 as Amber List (moderate evidence)
Mendeliome v0.6299 CD320 Bryony Thompson Added comment: Comment on list classification: Benign clinical condition
Mendeliome v0.6299 CD320 Bryony Thompson Gene: cd320 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6298 CD320 Bryony Thompson reviewed gene: CD320: Rating: ; Mode of pathogenicity: None; Publications: 29663633, 27604308, 30303736; Phenotypes: Methylmalonic aciduria, transient, due to transcobalamin receptor defect MIM#613646, Disorders of cobalamin absorption, transport and metabolism; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6298 SHPK Bryony Thompson Gene: shpk has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6298 SHPK Bryony Thompson Classified gene: SHPK as Amber List (moderate evidence)
Mendeliome v0.6298 SHPK Bryony Thompson Added comment: Comment on list classification: Likely benign disorder
Mendeliome v0.6298 SHPK Bryony Thompson Gene: shpk has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6297 SHPK Bryony Thompson gene: SHPK was added
gene: SHPK was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SHPK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SHPK were set to 25647543; 27604308
Phenotypes for gene: SHPK were set to Sedoheptulokinase deficiency MIM#617213
Review for gene: SHPK was set to AMBER
Added comment: 2 unrelated cases reported, with elevated excretion of erythritol and sedoheptulose, and each had a homozygous nonsense variant. The first patient presented with neonatal cholestasis, hypoglycemia, and anemia, while the second patient presented with congenital arthrogryposis multiplex, multiple contractures, and dysmorphisms. Due to inconsistency in phenotypes, likely SHPK deficiency is a benign disorder.
Sources: Literature
Mendeliome v0.6296 PNLIP Bryony Thompson Gene: pnlip has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6296 PNLIP Bryony Thompson Classified gene: PNLIP as Amber List (moderate evidence)
Mendeliome v0.6296 PNLIP Bryony Thompson Added comment: Comment on list classification: Appears to be a clinically benign metabolic condition
Mendeliome v0.6296 PNLIP Bryony Thompson Gene: pnlip has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6294 TDO2 Zornitza Stark Gene: tdo2 has been classified as Red List (Low Evidence).
Mendeliome v0.6294 TDO2 Zornitza Stark gene: TDO2 was added
gene: TDO2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: TDO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TDO2 were set to 28285122; 27604308
Phenotypes for gene: TDO2 were set to Hypertryptophanemia MIM#600627; Disorders of histidine, tryptophan or lysine metabolism
Review for gene: TDO2 was set to RED
Added comment: Single case reported, biochemical phenotype of hypertryptophanemia and hyperserotoninemia does not appear to have significant clinical consequences
Sources: Expert list
Mendeliome v0.6293 SUGCT Zornitza Stark Gene: sugct has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6290 SUGCT Zornitza Stark Classified gene: SUGCT as Amber List (moderate evidence)
Mendeliome v0.6290 SUGCT Zornitza Stark Gene: sugct has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6289 SLC36A2 Zornitza Stark Gene: slc36a2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6286 SLC36A2 Zornitza Stark Classified gene: SLC36A2 as Amber List (moderate evidence)
Mendeliome v0.6286 SLC36A2 Zornitza Stark Gene: slc36a2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6285 SARDH Zornitza Stark Gene: sardh has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6285 SARDH Zornitza Stark Phenotypes for gene: SARDH were changed from to Sarcosinemia MIM#268900; Disorders of serine, glycine or glycerate metabolism
Mendeliome v0.6282 SARDH Zornitza Stark Classified gene: SARDH as Amber List (moderate evidence)
Mendeliome v0.6282 SARDH Zornitza Stark Gene: sardh has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6281 SARDH Zornitza Stark reviewed gene: SARDH: Rating: AMBER; Mode of pathogenicity: None; Publications: 22825317, 27604308; Phenotypes: Sarcosinemia MIM#268900, Disorders of serine, glycine or glycerate metabolism; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6281 OPLAH Zornitza Stark Gene: oplah has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6278 OPLAH Zornitza Stark Classified gene: OPLAH as Amber List (moderate evidence)
Mendeliome v0.6278 OPLAH Zornitza Stark Gene: oplah has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6277 KHK Zornitza Stark Gene: khk has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6274 KHK Zornitza Stark Classified gene: KHK as Amber List (moderate evidence)
Mendeliome v0.6274 KHK Zornitza Stark Gene: khk has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6273 HAL Zornitza Stark Gene: hal has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6273 HAL Zornitza Stark Phenotypes for gene: HAL were changed from to Histidinemia MIM#235800; Disorders of histidine, tryptophan or lysine metabolism
Mendeliome v0.6270 HAL Zornitza Stark Classified gene: HAL as Amber List (moderate evidence)
Mendeliome v0.6270 HAL Zornitza Stark Gene: hal has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6269 HAL Zornitza Stark reviewed gene: HAL: Rating: AMBER; Mode of pathogenicity: None; Publications: 27604308, 15806399, 20156889; Phenotypes: Histidinemia MIM#235800, Disorders of histidine, tryptophan or lysine metabolism; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.6268 GGT1 Zornitza Stark Classified gene: GGT1 as Amber List (moderate evidence)
Mendeliome v0.6268 GGT1 Zornitza Stark Gene: ggt1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6267 DCXR Zornitza Stark Gene: dcxr has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6267 DCXR Zornitza Stark Classified gene: DCXR as Amber List (moderate evidence)
Mendeliome v0.6267 DCXR Zornitza Stark Gene: dcxr has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6265 CTH Zornitza Stark Gene: cth has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6262 CTH Zornitza Stark Classified gene: CTH as Amber List (moderate evidence)
Mendeliome v0.6262 CTH Zornitza Stark Gene: cth has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6261 ACSF3 Zornitza Stark Gene: acsf3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6258 ACSF3 Zornitza Stark Classified gene: ACSF3 as Amber List (moderate evidence)
Mendeliome v0.6258 ACSF3 Zornitza Stark Gene: acsf3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6257 PHGDH Zornitza Stark Gene: phgdh has been classified as Green List (High Evidence).
Mendeliome v0.6253 PNP Zornitza Stark Gene: pnp has been classified as Green List (High Evidence).
Mendeliome v0.6253 PNP Zornitza Stark Phenotypes for gene: PNP were changed from to Immunodeficiency due to purine nucleoside phosphorylase deficiency, MIM# 613179
Mendeliome v0.6250 PNP Zornitza Stark reviewed gene: PNP: Rating: GREEN; Mode of pathogenicity: None; Publications: 3029074, 1384322, 11453975, 32695102, 32514656; Phenotypes: Immunodeficiency due to purine nucleoside phosphorylase deficiency, MIM# 613179; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6250 PNPLA2 Zornitza Stark Gene: pnpla2 has been classified as Green List (High Evidence).
Mendeliome v0.6247 ESRP2 Zornitza Stark Gene: esrp2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6244 ESRP2 Zornitza Stark Classified gene: ESRP2 as Amber List (moderate evidence)
Mendeliome v0.6244 ESRP2 Zornitza Stark Gene: esrp2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6243 ACBD5 Zornitza Stark Gene: acbd5 has been classified as Green List (High Evidence).
Mendeliome v0.6240 SAR1B Zornitza Stark Gene: sar1b has been classified as Green List (High Evidence).
Mendeliome v0.6237 SC5D Zornitza Stark Gene: sc5d has been classified as Green List (High Evidence).
Mendeliome v0.6237 SC5D Zornitza Stark Phenotypes for gene: SC5D were changed from to Lathosterolosis, MIM# 607330
Mendeliome v0.6234 SC5D Zornitza Stark reviewed gene: SC5D: Rating: GREEN; Mode of pathogenicity: None; Publications: 17853487, 12189593, 12812989, 24142275; Phenotypes: Lathosterolosis, MIM# 607330; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6234 SLC39A14 Zornitza Stark Gene: slc39a14 has been classified as Green List (High Evidence).
Mendeliome v0.6231 SLC46A1 Zornitza Stark Gene: slc46a1 has been classified as Green List (High Evidence).
Mendeliome v0.6228 SLC46A1 Zornitza Stark changed review comment from: Hereditary folate malabsorption is an autosomal recessive disorder characterized by signs and symptoms of folate deficiency that appear within a few months after birth. Infants exhibit low blood and cerebrospinal fluid folate levels with megaloblastic anemia, diarrhea, immune deficiency, infections, and neurologic deficits. Treatment with folate supplementation results in resolution of the signs and symptoms. The disorder is caused by impaired intestinal folate absorption and impaired transport of folate into the central nervous system. More than 5 unrelated families reported.; to: Hereditary folate malabsorption is an autosomal recessive disorder characterized by signs and symptoms of folate deficiency that appear within a few months after birth. Infants exhibit low blood and cerebrospinal fluid folate levels with megaloblastic anemia, diarrhoea, immune deficiency, infections, and neurologic deficits. Treatment with folate supplementation results in resolution of the signs and symptoms. The disorder is caused by impaired intestinal folate absorption and impaired transport of folate into the central nervous system. More than 5 unrelated families reported.
Mendeliome v0.6228 ST3GAL3 Zornitza Stark Gene: st3gal3 has been classified as Green List (High Evidence).
Mendeliome v0.6228 ST3GAL3 Zornitza Stark Phenotypes for gene: ST3GAL3 were changed from to Mental retardation, autosomal recessive 12 MIM# 611090
Mendeliome v0.6225 ST3GAL3 Zornitza Stark reviewed gene: ST3GAL3: Rating: GREEN; Mode of pathogenicity: None; Publications: 23252400, 21907012, 31584066; Phenotypes: Mental retardation, autosomal recessive 12 MIM# 611090; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6221 DDX58 Zornitza Stark edited their review of gene: DDX58: Added comment: Prasov et al. 2021 (PMID: 33495304) - A heterozygous DDX58 variant (c.1529A>T) was identified in 5 individuals from 2 unrelated families from different ethnic backgrounds. Phenotypes varied with some being severely affected by systemic features and others solely with glaucoma.Functional analysis demonstrated the variant confers a dominant gain-of-function effect on interferon activity.; Changed mode of pathogenicity: Other; Changed publications: 25620203, 33495304
Mendeliome v0.6221 KL Bryony Thompson Gene: kl has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6220 KL Bryony Thompson Phenotypes for gene: KL were changed from to Tumoral calcinosis, hyperphosphatemic, familial, 3 MIM#617994; Hyperphosphatemia
Mendeliome v0.6219 KL Bryony Thompson Classified gene: KL as Amber List (moderate evidence)
Mendeliome v0.6219 KL Bryony Thompson Gene: kl has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6218 KL Bryony Thompson reviewed gene: KL: Rating: AMBER; Mode of pathogenicity: None; Publications: 17710231, 31013726, 9363890; Phenotypes: Tumoral calcinosis, hyperphosphatemic, familial, 3 MIM#617994, Hyperphosphatemia; Mode of inheritance: None
Mendeliome v0.6218 GLRX2 Bryony Thompson Gene: glrx2 has been classified as Red List (Low Evidence).
Mendeliome v0.6218 GLRX2 Bryony Thompson Classified gene: GLRX2 as Red List (low evidence)
Mendeliome v0.6218 GLRX2 Bryony Thompson Gene: glrx2 has been classified as Red List (Low Evidence).
Mendeliome v0.6217 GLRX3 Bryony Thompson Classified gene: GLRX3 as Red List (low evidence)
Mendeliome v0.6217 GLRX3 Bryony Thompson Gene: glrx3 has been classified as Red List (Low Evidence).
Mendeliome v0.6216 GSTO2 Bryony Thompson Gene: gsto2 has been classified as Red List (Low Evidence).
Mendeliome v0.6216 GSTO2 Bryony Thompson Classified gene: GSTO2 as Red List (low evidence)
Mendeliome v0.6216 GSTO2 Bryony Thompson Gene: gsto2 has been classified as Red List (Low Evidence).
Mendeliome v0.6215 SIX1 Zornitza Stark changed review comment from: DEFINITIVE by ClinGen. Variable expressivity, some families reported with isolated deafness, however this likely represents a spectrum rather than a separate disorder.; to: Deafness/BOS: DEFINITIVE by ClinGen. Variable expressivity, some families reported with isolated deafness, however this likely represents a spectrum rather than a separate disorder.
Mendeliome v0.6215 SIX1 Zornitza Stark Phenotypes for gene: SIX1 were changed from Deafness, autosomal dominant 23, MIM# 605192; Branchiootic syndrome 3, MIM# 608389 to Deafness, autosomal dominant 23, MIM# 605192; Branchiootic syndrome 3, MIM# 608389; Sagittal synostosis; Multi-suture synostosis
Mendeliome v0.6214 SIX1 Zornitza Stark Publications for gene: SIX1 were set to 15141091; 18330911; 21254961; 17637804; 29500469; 21700001; 24164807
Mendeliome v0.6213 BMP7 Zornitza Stark Phenotypes for gene: BMP7 were changed from Non-syndromic metopic craniosynostosis; Congenital abnormalities of the kidneys and urinary tract to Non-syndromic metopic craniosynostosis; Congenital abnormalities of the kidneys and urinary tract; Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS)
Mendeliome v0.6211 BMP7 Zornitza Stark changed review comment from: Non-syndromic metopic craniosynostosis: PMID 32266521 reports rs6127972 as a susceptibility SNP for non-syndromic metopic craniosynostosis

CAKUT: PMID 24429398 1 family with mouse model in large cohort of CAKUT.
Sources: Literature; to: Non-syndromic metopic craniosynostosis: PMID 32266521 reports rs6127972 as a susceptibility SNP for non-syndromic metopic craniosynostosis

CAKUT: PMID 24429398 1 family with mouse model in large cohort of CAKUT.
Sources: Literature

PMID 33434492: Two individuals with likely deleterious variants identified in a cohort of individuals with MRKHS.
Mendeliome v0.6211 BMP7 Zornitza Stark edited their review of gene: BMP7: Changed phenotypes: Non-syndromic metopic craniosynostosis, Congenital abnormalities of the kidneys and urinary tract, Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS)
Mendeliome v0.6211 BMP7 Zornitza Stark Phenotypes for gene: BMP7 were changed from Non-syndromic metopic craniosynostosis to Non-syndromic metopic craniosynostosis; Congenital abnormalities of the kidneys and urinary tract
Mendeliome v0.6210 BMP7 Zornitza Stark edited their review of gene: BMP7: Changed phenotypes: Non-syndromic metopic craniosynostosis, Congenital abnormalities of the kidneys and urinary tract
Mendeliome v0.6210 SIX1 Arina Puzriakova reviewed gene: SIX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33436522; Phenotypes: Sagittal synostosis, Multi-suture synostosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.6210 WBP11 Zornitza Stark Gene: wbp11 has been classified as Green List (High Evidence).
Mendeliome v0.6210 WBP11 Zornitza Stark Classified gene: WBP11 as Green List (high evidence)
Mendeliome v0.6210 WBP11 Zornitza Stark Gene: wbp11 has been classified as Green List (High Evidence).
Mendeliome v0.6208 CLRN2 Zornitza Stark Gene: clrn2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6208 CLRN2 Zornitza Stark Phenotypes for gene: CLRN2 were changed from Non-syndromic hearing loss to Non-syndromic hearing loss; Deafness, autosomal recessive 117, MIM# 619174
Mendeliome v0.6207 WBP11 Eleanor Williams gene: WBP11 was added
gene: WBP11 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: WBP11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: WBP11 were set to 33276377
Phenotypes for gene: WBP11 were set to malformation syndrome affecting the cardiac, skeletal, gastrointestinal and renal systems
Review for gene: WBP11 was set to GREEN
Added comment: PMID: 33276377 - Martin et al 2020 - report 13 affected individuals from 7 unrelated families identified through various different cohort analysis (vertebral malformation, renal hypodysplasia, syndromic esophageal atresia, multiple congenital anomalies) in whom a WBP11 heterozygous variant is considered the top causative candidate. 5 identified variants were predicted to be protein truncating whilst the 6th was a missense variant. All variants are absent from population databases. In family 1, the variant was inherited from the apparently unaffected mother, indicating reduced penetrance, and phenotypic variance within families was observed. Phenotypes covered cardiac, vertebral, renal, craniofacial and gastrointestinal systems. At least at least 5 of the patients affected had features in three component organs so can be considered a VACTERL association. Wbp11 heterozygous null mice had vertebral and renal anomalies.
Sources: Literature
Mendeliome v0.6207 TTF2 Zornitza Stark Gene: ttf2 has been classified as Red List (Low Evidence).
Mendeliome v0.6207 TTF2 Zornitza Stark gene: TTF2 was added
gene: TTF2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: TTF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TTF2 were set to 30022773
Phenotypes for gene: TTF2 were set to congenital hypothyroidism, thyroid dysgenesis, No OMIM #
Review for gene: TTF2 was set to RED
Added comment: 1 case only
Sources: Expert Review
Mendeliome v0.6206 DUOXA1 Zornitza Stark Gene: duoxa1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6206 DUOXA1 Zornitza Stark Classified gene: DUOXA1 as Amber List (moderate evidence)
Mendeliome v0.6206 DUOXA1 Zornitza Stark Gene: duoxa1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6204 DUOX1 Zornitza Stark Gene: duox1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6204 DUOX1 Zornitza Stark Classified gene: DUOX1 as Amber List (moderate evidence)
Mendeliome v0.6204 DUOX1 Zornitza Stark Gene: duox1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6202 TTF1 Zornitza Stark Gene: ttf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6202 TTF1 Zornitza Stark Phenotypes for gene: TTF1 were changed from to congenital hypothyroidism, thyroid dysgenesis, No OMIM #
Mendeliome v0.6199 TTF1 Zornitza Stark Classified gene: TTF1 as Amber List (moderate evidence)
Mendeliome v0.6199 TTF1 Zornitza Stark Gene: ttf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6198 TTF1 Zornitza Stark reviewed gene: TTF1: Rating: AMBER; Mode of pathogenicity: None; Publications: 30022773; Phenotypes: congenital hypothyroidism, thyroid dysgenesis, No OMIM #; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.6198 CDCA8 Zornitza Stark Gene: cdca8 has been classified as Green List (High Evidence).
Mendeliome v0.6198 CDCA8 Zornitza Stark Classified gene: CDCA8 as Green List (high evidence)
Mendeliome v0.6198 CDCA8 Zornitza Stark Gene: cdca8 has been classified as Green List (High Evidence).
Mendeliome v0.6197 CDCA8 Zornitza Stark gene: CDCA8 was added
gene: CDCA8 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: CDCA8 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CDCA8 were set to 28025328; 29546359
Phenotypes for gene: CDCA8 were set to Congenital hypothyroidism, thyroid dysgenesis, no OMIM #
Mode of pathogenicity for gene: CDCA8 was set to Other
Review for gene: CDCA8 was set to GREEN
Added comment: 4 families (1 with bilallelic variants [parent affected as HTZ], 3 with monoallelic variants) with functional evidence of variants. GREEN for mono allelic, RED for biallelic.
Sources: Expert Review
Mendeliome v0.6196 DNAJC30 Zornitza Stark Gene: dnajc30 has been classified as Green List (High Evidence).
Mendeliome v0.6196 DNAJC30 Zornitza Stark Classified gene: DNAJC30 as Green List (high evidence)
Mendeliome v0.6196 DNAJC30 Zornitza Stark Gene: dnajc30 has been classified as Green List (High Evidence).
Mendeliome v0.6195 DNAJC30 Zornitza Stark gene: DNAJC30 was added
gene: DNAJC30 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DNAJC30 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNAJC30 were set to 33465056
Phenotypes for gene: DNAJC30 were set to Leber Hereditary Optic Neuropathy
Review for gene: DNAJC30 was set to GREEN
Added comment: 33 individuals from 29 families had homozygous DNAJC30 missense variants. Three different variants identified (one responsible for most cases). All three variants absent from gnomAD. Incomplete penetrance and male predominance in affected individuals both typical of LHON due to mtDNA mutations. All 3 variants in the J domain of the protein. Functional evidence.
Sources: Literature
Mendeliome v0.6194 NFS1 Zornitza Stark Classified gene: NFS1 as Green List (high evidence)
Mendeliome v0.6194 NFS1 Zornitza Stark Gene: nfs1 has been classified as Green List (High Evidence).
Mendeliome v0.6192 SLC7A6OS Zornitza Stark Gene: slc7a6os has been classified as Red List (Low Evidence).
Mendeliome v0.6192 SLC7A6OS Zornitza Stark gene: SLC7A6OS was added
gene: SLC7A6OS was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC7A6OS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC7A6OS were set to 33085104
Phenotypes for gene: SLC7A6OS were set to Progressive myoclonus epilepsy
Review for gene: SLC7A6OS was set to RED
Added comment: Two unrelated families reported with same homozygous splice site variant, shared haplotype (founder effect). Limited functional data.
Sources: Literature
Mendeliome v0.6191 TLR8 Zornitza Stark Gene: tlr8 has been classified as Green List (High Evidence).
Mendeliome v0.6191 TLR8 Zornitza Stark Classified gene: TLR8 as Green List (high evidence)
Mendeliome v0.6191 TLR8 Zornitza Stark Gene: tlr8 has been classified as Green List (High Evidence).
Mendeliome v0.6190 TLR8 Zornitza Stark gene: TLR8 was added
gene: TLR8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TLR8 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: TLR8 were set to 33512449
Phenotypes for gene: TLR8 were set to Immunodeficiency; bone marrow failure
Mode of pathogenicity for gene: TLR8 was set to Other
Review for gene: TLR8 was set to GREEN
Added comment: Six unrelated males reported with a phenotype comprising neutropaenia, infections, lymphoproliferation, humoral immune defects, and in some cases bone marrow failure. Three different variants reported, the variant was somatic in 5/6 individuals. GoF mechanism demonstrated.
Sources: Literature
Mendeliome v0.6189 PIGF Zornitza Stark Gene: pigf has been classified as Red List (Low Evidence).
Mendeliome v0.6189 PIGF Zornitza Stark Classified gene: PIGF as Red List (low evidence)
Mendeliome v0.6189 PIGF Zornitza Stark Gene: pigf has been classified as Red List (Low Evidence).
Mendeliome v0.6188 BRWD1 Zornitza Stark Gene: brwd1 has been classified as Green List (High Evidence).
Mendeliome v0.6188 BRWD1 Zornitza Stark Classified gene: BRWD1 as Green List (high evidence)
Mendeliome v0.6188 BRWD1 Zornitza Stark Gene: brwd1 has been classified as Green List (High Evidence).
Mendeliome v0.6187 PIGF Paul De Fazio changed review comment from: The same homozygous missense variant identified in 2 individuals from different families from the same region of India. Individuals had a phenotype similar to DOORS syndrome without deafness. Impaired glycosylphosphatidylinositol (GPI) biosynthesis was demonstrated.

Rated Red as the two families are likely to be related (founder mutation?).
Sources: Literature; to: The same homozygous missense variant identified in 2 individuals from different families from the same region of India. Individuals had a phenotype similar to DOORS syndrome without deafness - only one of the two had seizures (GTCS), the other was 14mo and noted to have tonic posturing.

Impaired glycosylphosphatidylinositol (GPI) biosynthesis was demonstrated by flow cytometry and a rescue assay. Alkaline phosphatase in both individuals was normal.

Rated Red as the two families are likely to be related (founder mutation?).
Sources: Literature
Mendeliome v0.6187 PIGF Paul De Fazio edited their review of gene: PIGF: Changed phenotypes: Glycosylphosphatidylinositol deficiency, onychodystrophy, osteodystrophy, intellectual disability, and seizures
Mendeliome v0.6187 PIGF Paul De Fazio changed review comment from: The same missense variant identified in 2 individuals from different families from the same region of India. Individuals had a phenotype similar to DOORS syndrome without deafness. Impaired glycosylphosphatidylinositol (GPI) biosynthesis was demonstrated.

Rated Red as the two families are likely to be related (founder mutation?).
Sources: Literature; to: The same homozygous missense variant identified in 2 individuals from different families from the same region of India. Individuals had a phenotype similar to DOORS syndrome without deafness. Impaired glycosylphosphatidylinositol (GPI) biosynthesis was demonstrated.

Rated Red as the two families are likely to be related (founder mutation?).
Sources: Literature
Mendeliome v0.6187 PIGF Paul De Fazio changed review comment from: Identified in 2 individuals with a phenotype similar to DOORS (syndrome
Sources: Literature; to: The same missense variant identified in 2 individuals from different families from the same region of India. Individuals had a phenotype similar to DOORS syndrome without deafness. Impaired glycosylphosphatidylinositol (GPI) biosynthesis was demonstrated.

Rated Red as the two families are likely to be related (founder mutation?).
Sources: Literature
Mendeliome v0.6187 PIGF Paul De Fazio gene: PIGF was added
gene: PIGF was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PIGF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGF were set to 33386993
Phenotypes for gene: PIGF were set to Glycosylphosphatidylinositol\ deficiency, onychodystrophy, osteodystrophy, intellectual disability, and seizures
Review for gene: PIGF was set to RED
gene: PIGF was marked as current diagnostic
Added comment: Identified in 2 individuals with a phenotype similar to DOORS (syndrome
Sources: Literature
Mendeliome v0.6187 BRWD1 Paul De Fazio gene: BRWD1 was added
gene: BRWD1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BRWD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BRWD1 were set to 33389130
Phenotypes for gene: BRWD1 were set to Asthenoteratozoospermia, likely primary ciliary dyskinesia
Review for gene: BRWD1 was set to GREEN
gene: BRWD1 was marked as current diagnostic
Added comment: Biallelic missense variants reported in 3 unrelated individuals. Apart from asthenoteratozoospermia, all 3 had PCD or "PCD-likely" symptoms of re-occurring airway infections, bronchiectasis, and rhinosinusitis. One individual had situs inversus. Studies on cells from one indivdidual showed abnormal respiratory cilia structure. BRWD1 staining was absent from respiratory cilia in this individual (present in controls).

Rated Green as there are three unrelated individuals reported.
Sources: Literature
Mendeliome v0.6187 HIRA Zornitza Stark Gene: hira has been classified as Green List (High Evidence).
Mendeliome v0.6187 HIRA Zornitza Stark Classified gene: HIRA as Green List (high evidence)
Mendeliome v0.6187 HIRA Zornitza Stark Gene: hira has been classified as Green List (High Evidence).
Mendeliome v0.6186 EYA3 Zornitza Stark Gene: eya3 has been classified as Red List (Low Evidence).
Mendeliome v0.6186 EYA3 Zornitza Stark Classified gene: EYA3 as Red List (low evidence)
Mendeliome v0.6186 EYA3 Zornitza Stark Gene: eya3 has been classified as Red List (Low Evidence).
Mendeliome v0.6185 CLRN2 Zornitza Stark Classified gene: CLRN2 as Amber List (moderate evidence)
Mendeliome v0.6185 CLRN2 Zornitza Stark Gene: clrn2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6184 POLR3B Zornitza Stark Gene: polr3b has been classified as Green List (High Evidence).
Mendeliome v0.6181 CFAP47 Zornitza Stark Gene: cfap47 has been classified as Green List (High Evidence).
Mendeliome v0.6181 CFAP47 Zornitza Stark Classified gene: CFAP47 as Green List (high evidence)
Mendeliome v0.6181 CFAP47 Zornitza Stark Gene: cfap47 has been classified as Green List (High Evidence).
Mendeliome v0.6180 C14orf39 Zornitza Stark Gene: c14orf39 has been classified as Green List (High Evidence).
Mendeliome v0.6180 C14orf39 Zornitza Stark Classified gene: C14orf39 as Green List (high evidence)
Mendeliome v0.6180 C14orf39 Zornitza Stark Gene: c14orf39 has been classified as Green List (High Evidence).
Mendeliome v0.6179 ENO1 Zornitza Stark Gene: eno1 has been classified as Red List (Low Evidence).
Mendeliome v0.6179 ENO1 Zornitza Stark Classified gene: ENO1 as Red List (low evidence)
Mendeliome v0.6179 ENO1 Zornitza Stark Gene: eno1 has been classified as Red List (Low Evidence).
Mendeliome v0.6178 HEY2 Zornitza Stark gene: HEY2 was added
gene: HEY2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HEY2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: HEY2 were set to 32820247
Phenotypes for gene: HEY2 were set to congenital heart defects and thoracic aortic aneurysms
Review for gene: HEY2 was set to RED
Added comment: A very large family affected by CHD and familial thoracic aortic aneurysms. Trio genome sequencing was carried out in an index patient with critical CHD, and family members had either exome or Sanger sequencing. Identified homozygous loss-of-function variant (c.318_319delAG, p.G108*) in HEY2 in 3 individuals in family with critical CHD, whereas the 20 heterozygous carriers show a spectrum of CVDs (CHD and FTAA, but varying expressivity and incomplete penetrance). Other studies show that knockout of HEY2 in mice results in cardiovascular defects (CVDs), including septal defects, cardiomyopathy, a thin-walled aorta, and valve anomalies.
Sources: Literature
Mendeliome v0.6177 FGF9 Zornitza Stark edited their review of gene: FGF9: Changed phenotypes: Multiple synostoses syndrome 3, OMIM # 612961, Craniosynostosis
Mendeliome v0.6177 FGF9 Zornitza Stark Gene: fgf9 has been classified as Green List (High Evidence).
Mendeliome v0.6177 FGF9 Zornitza Stark Phenotypes for gene: FGF9 were changed from to Multiple synostoses syndrome 3, OMIM # 612961; Craniosynostosis
Mendeliome v0.6174 OTUD5 Zornitza Stark Gene: otud5 has been classified as Red List (Low Evidence).
Mendeliome v0.6174 OTUD5 Zornitza Stark gene: OTUD5 was added
gene: OTUD5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: OTUD5 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: OTUD5 were set to 33131077
Phenotypes for gene: OTUD5 were set to X-linked severe neurodevelopmental delay, hydrocephalus, and early lethality
Review for gene: OTUD5 was set to RED
Added comment: 13 male patients from a single family with three generations affected. Patients presented prenatally or during the neonatal period with IUGR, ventriculomegaly, hydrocephalus, hypotonia, congenital heart defects, hypospadias, and severe neurodevelopmental delay. The disease is typically fatal during infancy, mainly due to sepsis (pneumonias). Female carriers are asymptomatic. WGS in four individuals identified a unique candidate variant in the OTUD5 gene (NM_017602.3:c.598G > A, p.Glu200Lys). The variant cosegregated with the disease in 10 tested individuals. No functional studies.
Sources: Literature
Mendeliome v0.6173 BCAT2 Bryony Thompson Gene: bcat2 has been classified as Green List (High Evidence).
Mendeliome v0.6173 BCAT2 Bryony Thompson Classified gene: BCAT2 as Green List (high evidence)
Mendeliome v0.6173 BCAT2 Bryony Thompson Gene: bcat2 has been classified as Green List (High Evidence).
Mendeliome v0.6172 BCAT2 Bryony Thompson changed review comment from: A single case reported with compound heterozygous variants with functional studies demonstrating that the two variants resulted in decreased BCAT2 enzyme activity. Also, a null mouse model has a phenotype similar to human maple syrup urine disease.
Sources: NHS GMS; to: 6 cases from 5 unrelated families with homozygous or compound heterozygous variant, and supporting functional studies demonstrating decreased BCAT2 enzyme activity for some of the variants. Also, a null mouse model has a phenotype similar to human maple syrup urine disease.
Sources: NHS GMS
Mendeliome v0.6172 BCAT2 Bryony Thompson gene: BCAT2 was added
gene: BCAT2 was added to Mendeliome. Sources: NHS GMS
Mode of inheritance for gene: BCAT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BCAT2 were set to 14755340; 25653144
Phenotypes for gene: BCAT2 were set to Hypervalinemia or hyperleucine-isoleucinemia MIM#618850; disorder of branched-chain amino acid metabolism
Review for gene: BCAT2 was set to AMBER
Added comment: A single case reported with compound heterozygous variants with functional studies demonstrating that the two variants resulted in decreased BCAT2 enzyme activity. Also, a null mouse model has a phenotype similar to human maple syrup urine disease.
Sources: NHS GMS
Mendeliome v0.6170 KCNN2 Sebastian Lunke Gene: kcnn2 has been classified as Green List (High Evidence).
Mendeliome v0.6169 SATB1 Zornitza Stark Classified gene: SATB1 as Green List (high evidence)
Mendeliome v0.6169 SATB1 Zornitza Stark Gene: satb1 has been classified as Green List (High Evidence).
Mendeliome v0.6168 KCNN2 Sebastian Lunke Classified gene: KCNN2 as Green List (high evidence)
Mendeliome v0.6168 KCNN2 Sebastian Lunke Gene: kcnn2 has been classified as Green List (High Evidence).
Mendeliome v0.6167 ENO1 Kristin Rigbye gene: ENO1 was added
gene: ENO1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ENO1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ENO1 were set to 32488097
Phenotypes for gene: ENO1 were set to Polymicrogyria
Review for gene: ENO1 was set to RED
Added comment: ENO1 identified as a polymicrogyria candidate gene from the smallest case of 1p36 duplication reported to date, in a 35yo F (onset at 8mo) presenting intellectual disability, microcephaly, epilepsy and perisylvian polymicrogyria. The duplication only encompassed 2 genes, ENO1 and RERE, and gene expression analysis performed using the patient cells revealed reduced expression, mimicking haploinsufficiency. Eno1 inactivation in rats was shown to cause a brain development defect. According to OMIM, ENO1 is deleted in glioblastoma, which is tolerated by the expression of ENO2.
Sources: Literature
Mendeliome v0.6167 METAP1 Zornitza Stark Gene: metap1 has been classified as Red List (Low Evidence).
Mendeliome v0.6167 METAP1 Zornitza Stark Classified gene: METAP1 as Red List (low evidence)
Mendeliome v0.6167 METAP1 Zornitza Stark Gene: metap1 has been classified as Red List (Low Evidence).
Mendeliome v0.6166 METAP1 Paul De Fazio gene: METAP1 was added
gene: METAP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: METAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: METAP1 were set to PMID: 32764695
Phenotypes for gene: METAP1 were set to Intellectual disability, aggression, neurodevelopmental delay
Review for gene: METAP1 was set to RED
gene: METAP1 was marked as current diagnostic
Added comment: Biallelic nonsense (NMD-predicted) variant identified in 4 sibs in a consanguineous family with dev delay. One sib had bilateral clinodactyly of her toes and her left 3rd finger, other sibs were not dysmorphic. Rated red due to single consanguineous family.
Sources: Literature
Mendeliome v0.6166 MYADML2 Zornitza Stark Gene: myadml2 has been classified as Red List (Low Evidence).
Mendeliome v0.6166 MYADML2 Zornitza Stark Classified gene: MYADML2 as Red List (low evidence)
Mendeliome v0.6166 MYADML2 Zornitza Stark Gene: myadml2 has been classified as Red List (Low Evidence).
Mendeliome v0.6165 CCDC186 Zornitza Stark Gene: ccdc186 has been classified as Red List (Low Evidence).
Mendeliome v0.6164 KCNN2 Ain Roesley gene: KCNN2 was added
gene: KCNN2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KCNN2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KCNN2 were set to 33242881
Phenotypes for gene: KCNN2 were set to neurodevelopmental movement disorders
Penetrance for gene: KCNN2 were set to unknown
Review for gene: KCNN2 was set to GREEN
Added comment: - 11 probands all de novo except for 1 mother-daughter pair.
- a mix of null and missense variants
- 2/11 with microcephaly, 10/11 motor delay, 7/11 language delay (excluding 2 with regression), all with varying degrees of ID, 3/11 seizures, 7/11 movement disorder, 4/11 cerebellar ataxia, 6/11 MRI anomalies

additional variants were noted in 2 patients: 1x cHet for variants in MED12L and 1x de novo TNK2 variant

patch clamp functional studies were also done
Sources: Literature
Mendeliome v0.6164 MYADML2 Paul De Fazio gene: MYADML2 was added
gene: MYADML2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MYADML2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYADML2 were set to 32778762
Phenotypes for gene: MYADML2 were set to Cranial asymmetry, reduced bone maturation, multiple dislocations, lumbar lordosis, and prominent clavicles
Review for gene: MYADML2 was set to RED
gene: MYADML2 was marked as current diagnostic
Added comment: 5 sibs from a consanguineous family identified to have biallelic deletion encompassing part of the PYCR1 gene and the coding region of the MYADML2 gene.

According to the authors: "All five affected sibs had the most common features of ARCL (autosomal recessive cutis laxa) but not many of the less common ones. We attributed the anomalies not typical for ARCL to MYADML2 deficit, because no other genetic defect possibly a candidate to underlie the skeletal phenotype was found."

Phenotype may still be explained by the PYCR1 deletion alone.
Sources: Literature
Mendeliome v0.6163 HYAL2 Zornitza Stark Gene: hyal2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6163 HYAL2 Zornitza Stark Classified gene: HYAL2 as Amber List (moderate evidence)
Mendeliome v0.6163 HYAL2 Zornitza Stark Gene: hyal2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6161 SLC6A20 Zornitza Stark Gene: slc6a20 has been classified as Green List (High Evidence).
Mendeliome v0.6158 SUOX Zornitza Stark Gene: suox has been classified as Green List (High Evidence).
Mendeliome v0.6155 PDE2A Zornitza Stark Phenotypes for gene: PDE2A were changed from Paroxysmal dyskinesia to Paroxysmal dyskinesia; Intellectual developmental disorder with paroxysmal dyskinesia or seizures, MIM# 619150Intellectual developmental disorder with paroxysmal dyskinesia or seizures, MIM# 619150
Mendeliome v0.6154 ADH5 Zornitza Stark Phenotypes for gene: ADH5 were changed from Aplastic anaemia; myelodysplasia; short stature to AMED syndrome, digenic, MIM# 619151; Aplastic anaemia; myelodysplasia; short stature
Mendeliome v0.6153 ADH5 Zornitza Stark edited their review of gene: ADH5: Changed phenotypes: AMED syndrome, digenic, MIM# 619151, Aplastic anaemia, myelodysplasia, short stature
Mendeliome v0.6153 PDE2A Zornitza Stark edited their review of gene: PDE2A: Changed phenotypes: Paroxysmal dyskinesia, Intellectual developmental disorder with paroxysmal dyskinesia or seizures, MIM# 619150Intellectual developmental disorder with paroxysmal dyskinesia or seizures, MIM# 619150
Mendeliome v0.6153 PRDM13 Zornitza Stark Phenotypes for gene: PRDM13 were changed from Retinal dystrophy to Retinal dystrophy; Chorioretinal atrophy, progressive bifocal, MIM# 600790
Mendeliome v0.6152 PRDM13 Zornitza Stark edited their review of gene: PRDM13: Changed phenotypes: Retinal dystrophy, Chorioretinal atrophy, progressive bifocal, MIM# 600790
Mendeliome v0.6150 NOS1AP Zornitza Stark Classified gene: NOS1AP as Green List (high evidence)
Mendeliome v0.6150 NOS1AP Zornitza Stark Gene: nos1ap has been classified as Green List (High Evidence).
Mendeliome v0.6149 NOS1AP Zornitza Stark edited their review of gene: NOS1AP: Added comment: Nephrotic syndrome type 22 (NPHS22) is an autosomal recessive renal disease characterized by onset of progressive kidney dysfunction in infancy. Affected individuals usually present with edema associated with hypoproteinemia, proteinuria, and microscopic hematuria. Renal biopsy shows effacement of the podocyte foot processes, glomerulosclerosis, and thickening of the glomerular basement membrane. The disease is steroid-resistant and progressive, resulting in end-stage renal disease usually necessitating kidney transplant.

Two unrelated families and animal model.

No PMID yet: https://advances.sciencemag.org/content/7/1/eabe1386; Changed rating: GREEN; Changed phenotypes: Nephrotic syndrome, type 22, MIM# 619155; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6148 DCT Zornitza Stark Gene: dct has been classified as Green List (High Evidence).
Mendeliome v0.6148 DCT Zornitza Stark Classified gene: DCT as Green List (high evidence)
Mendeliome v0.6148 DCT Zornitza Stark Gene: dct has been classified as Green List (High Evidence).
Mendeliome v0.6146 SDHAF1 Zornitza Stark Gene: sdhaf1 has been classified as Green List (High Evidence).
Mendeliome v0.6142 NDUFC2 Zornitza Stark Gene: ndufc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6142 NDUFC2 Zornitza Stark Classified gene: NDUFC2 as Amber List (moderate evidence)
Mendeliome v0.6142 NDUFC2 Zornitza Stark Gene: ndufc2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6141 NDUFC2 Zornitza Stark gene: NDUFC2 was added
gene: NDUFC2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: NDUFC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFC2 were set to 32969598
Phenotypes for gene: NDUFC2 were set to Mitochondrial complex I deficiency, nuclear type 36, MIM# 619170
Review for gene: NDUFC2 was set to AMBER
Added comment: Mitochondrial complex I deficiency nuclear type 36 (MC1DN36) is an autosomal recessive metabolic disorder characterized by global developmental delay, hypotonia, and failure to thrive apparent from infancy or early childhood. Affected individuals usually do not acquire ambulation, show progressive spasticity, and have impaired intellectual development with absent speech. More variable features may include pale optic discs, poor eye contact, seizures, and congenital heart defects. Laboratory studies show increased serum lactate; metabolic acidosis may occur during stress or infection. Brain imaging shows T2-weighted abnormalities in the basal ganglia and brainstem, consistent with a clinical diagnosis of Leigh syndrome. Two unrelated families reported, some functional data.
Sources: Expert list
Mendeliome v0.6140 UPB1 Zornitza Stark Gene: upb1 has been classified as Green List (High Evidence).
Mendeliome v0.6137 UROC1 Zornitza Stark Gene: uroc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6134 UROC1 Zornitza Stark Classified gene: UROC1 as Amber List (moderate evidence)
Mendeliome v0.6134 UROC1 Zornitza Stark Gene: uroc1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6133 DLX4 Zornitza Stark Gene: dlx4 has been classified as Red List (Low Evidence).
Mendeliome v0.6133 DLX4 Zornitza Stark gene: DLX4 was added
gene: DLX4 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: DLX4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DLX4 were set to 25954033; 29738288
Phenotypes for gene: DLX4 were set to Orofacial cleft 15, MIM# 616788
Review for gene: DLX4 was set to RED
Added comment: Single family reported and a SNP association study.
Sources: Expert list
Mendeliome v0.6132 DLG1 Zornitza Stark Gene: dlg1 has been classified as Red List (Low Evidence).
Mendeliome v0.6132 DLG1 Zornitza Stark gene: DLG1 was added
gene: DLG1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: DLG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DLG1 were set to 28926086
Phenotypes for gene: DLG1 were set to Non-syndromic cleft lip and palate
Review for gene: DLG1 was set to RED
Added comment: GWAS study PMID: 28926086 found genome-wide significance for several SNPs within this gene, identifying it as a candidate gene for non-syndromic cleft lip with or without cleft palate.
Sources: Expert list
Mendeliome v0.6131 PLEKHA7 Zornitza Stark Gene: plekha7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6128 PLEKHA7 Zornitza Stark Classified gene: PLEKHA7 as Amber List (moderate evidence)
Mendeliome v0.6128 PLEKHA7 Zornitza Stark Gene: plekha7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6127 GYS2 Zornitza Stark Gene: gys2 has been classified as Green List (High Evidence).
Mendeliome v0.6123 OPA3 Zornitza Stark Gene: opa3 has been classified as Green List (High Evidence).
Mendeliome v0.6119 FOXF1 Zornitza Stark changed review comment from: Congenital alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is characterized histologically by failure of formation and ingrowth of alveolar capillaries that then do not make contact with alveolar epithelium, medial muscular thickening of small pulmonary arterioles with muscularization of the intraacinar arterioles, thickened alveolar walls, and anomalously situated pulmonary veins running alongside pulmonary arterioles and sharing the same adventitial sheath. Less common features include a reduced number of alveoli and a patchy distribution of the histopathologic changes. The disorder is associated with persistent pulmonary hypertension of the neonate and shows varying degrees of lability and severity. Affected infants present with respiratory distress resulting from pulmonary hypertension in the early postnatal period, and the disease is uniformly fatal within the newborn period. Additional features of ACDMPV include multiple congenital anomalies affecting the cardiovascular, gastrointestinal, genitourinary, and musculoskeletal systems, as well as disruption of the normal right-left asymmetry of intrathoracic or intraabdominal organs.; to: Congenital alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is characterized histologically by failure of formation and ingrowth of alveolar capillaries that then do not make contact with alveolar epithelium, medial muscular thickening of small pulmonary arterioles with muscularization of the intraacinar arterioles, thickened alveolar walls, and anomalously situated pulmonary veins running alongside pulmonary arterioles and sharing the same adventitial sheath. Less common features include a reduced number of alveoli and a patchy distribution of the histopathologic changes. The disorder is associated with persistent pulmonary hypertension of the neonate and shows varying degrees of lability and severity. Affected infants present with respiratory distress resulting from pulmonary hypertension in the early postnatal period, and the disease is uniformly fatal within the newborn period. Additional features of ACDMPV include multiple congenital anomalies affecting the cardiovascular, gastrointestinal, genitourinary, and musculoskeletal systems, as well as disruption of the normal right-left asymmetry of intrathoracic or intraabdominal organs.

Over 50 families reported.
Mendeliome v0.6119 FOXF1 Zornitza Stark Gene: foxf1 has been classified as Green List (High Evidence).
Mendeliome v0.6119 FOXF1 Zornitza Stark Phenotypes for gene: FOXF1 were changed from to Alveolar capillary dysplasia with misalignment of pulmonary veins, MIM# 265380
Mendeliome v0.6116 FOXF1 Zornitza Stark reviewed gene: FOXF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19500772, 23505205; Phenotypes: Alveolar capillary dysplasia with misalignment of pulmonary veins, MIM# 265380; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.6116 FOXF1 Kristin Rigbye reviewed gene: FOXF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23505205, 27071622, 27855150; Phenotypes: Alveolar capillary dysplasia with misalignment of pulmonary veins (MIM#265380), AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.6116 STEAP3 Zornitza Stark Gene: steap3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6113 STEAP3 Zornitza Stark Classified gene: STEAP3 as Amber List (moderate evidence)
Mendeliome v0.6113 STEAP3 Zornitza Stark Gene: steap3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6112 FTH1 Zornitza Stark Gene: fth1 has been classified as Red List (Low Evidence).
Mendeliome v0.6112 FTH1 Zornitza Stark gene: FTH1 was added
gene: FTH1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: FTH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FTH1 were set to 11389486
Phenotypes for gene: FTH1 were set to Hemochromatosis, type 5, MIM# 615517
Review for gene: FTH1 was set to RED
Added comment: One multi-generational family with 5' UTR variant.
Sources: Expert list
Mendeliome v0.6111 CYBRD1 Zornitza Stark Gene: cybrd1 has been classified as Red List (Low Evidence).
Mendeliome v0.6110 BMP6 Zornitza Stark Gene: bmp6 has been classified as Green List (High Evidence).
Mendeliome v0.6110 BMP6 Zornitza Stark Classified gene: BMP6 as Green List (high evidence)
Mendeliome v0.6110 BMP6 Zornitza Stark Gene: bmp6 has been classified as Green List (High Evidence).
Mendeliome v0.6108 CREB3L3 Bryony Thompson Classified gene: CREB3L3 as Amber List (moderate evidence)
Mendeliome v0.6108 CREB3L3 Bryony Thompson Gene: creb3l3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6107 CREB3L3 Bryony Thompson gene: CREB3L3 was added
gene: CREB3L3 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CREB3L3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CREB3L3 were set to 32580631; 29954705; 27982131; 27291420; 26427795; 21666694
Phenotypes for gene: CREB3L3 were set to Hyperlipidaemia; hypertriglyceridemia
Review for gene: CREB3L3 was set to AMBER
Added comment: PMID: 26427795 - a loss of function variant (c.359delG p.K120fsX20) was identified in 2 affected adult siblings and a 13 yo normotriglyceridemic daughter of one of the siblings.
PMID: 21666694 - Lipoprotein profiles of the families of 4 individuals with CREB3L3 nonsense mutations showed a significantly elevated mean plasma TG level in 11 mutation carriers compared with 5 non-carrier first-degree relatives (9.67 ± 4.70 vs. 1.66 ± 0.55 mM, P = 0.021, Wilcoxon test). 3 of those families have the same variant - Lys245GlufsTer130, which has 126 (281,946 alleles) hets in gnomAD v2.1.
PMID: 32580631 - case-control analysis of nonmonogenic severe hypertriglyceridemia cases (N=265) vs normolipidemic controls (N=477), identified 5 cases with LoF variants (3 of whom had the Lys245GlufsTer130 frameshift) and none in controls. OR 20.2 (95% CI 1.11–366.1) p = 0.002, adjusted p = 0.03.
The frequency of Lys245GlufsTer130 is higher than expected for a dominant disorder, but other loss of function variants have been identified. The gene may be associated with variable penetrance. There are multiple supporting null mouse models with hyperlipidaemia.
Sources: Expert list
Mendeliome v0.6106 GPIHBP1 Bryony Thompson Gene: gpihbp1 has been classified as Green List (High Evidence).
Mendeliome v0.6106 GPIHBP1 Bryony Thompson Classified gene: GPIHBP1 as Green List (high evidence)
Mendeliome v0.6106 GPIHBP1 Bryony Thompson Gene: gpihbp1 has been classified as Green List (High Evidence).
Mendeliome v0.6103 CBY1 Bryony Thompson Gene: cby1 has been classified as Green List (High Evidence).
Mendeliome v0.6103 CBY1 Bryony Thompson Classified gene: CBY1 as Green List (high evidence)
Mendeliome v0.6103 CBY1 Bryony Thompson Gene: cby1 has been classified as Green List (High Evidence).
Mendeliome v0.6102 CBY1 Bryony Thompson gene: CBY1 was added
gene: CBY1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CBY1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CBY1 were set to 33131181; 25103236; 25220153
Phenotypes for gene: CBY1 were set to intellectual disability; cerebellar ataxia; molar tooth sign; polydactyly; Joubert syndrome
Review for gene: CBY1 was set to GREEN
Added comment: Three cases in two unrelated consanguineous families with homozygous loss of function variants. Multiple null model organisms recapitulate the human phenotype: Null mouse model had cystic kidneys, a phenotype common to ciliopathies. Reducing Cby levels in Xenopus laevis model reduced the density of multiciliated cells, the number of basal bodies per multiciliated cell, and the numbers of neural tube primary cilia; it also led to abnormal development of the neural crest, central nervous system, and pronephros. Depletion of cby1 in zebrafish results in ciliopathy‐related phenotypes.
Sources: Literature
Mendeliome v0.6101 ZMYND15 Bryony Thompson Gene: zmynd15 has been classified as Green List (High Evidence).
Mendeliome v0.6101 ZMYND15 Bryony Thompson Classified gene: ZMYND15 as Green List (high evidence)
Mendeliome v0.6101 ZMYND15 Bryony Thompson Gene: zmynd15 has been classified as Green List (High Evidence).
Mendeliome v0.6099 PNPLA1 Zornitza Stark Gene: pnpla1 has been classified as Green List (High Evidence).
Mendeliome v0.6099 PNPLA1 Zornitza Stark Phenotypes for gene: PNPLA1 were changed from to Ichthyosis, congenital, autosomal recessive 10, MIM# 615024
Mendeliome v0.6096 PNPLA1 Zornitza Stark reviewed gene: PNPLA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22246504, 24344921, 26691440; Phenotypes: Ichthyosis, congenital, autosomal recessive 10, MIM# 615024; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6096 TMEM251 Bryony Thompson Gene: tmem251 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6096 TMEM251 Bryony Thompson Classified gene: TMEM251 as Amber List (moderate evidence)
Mendeliome v0.6096 TMEM251 Bryony Thompson Gene: tmem251 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.6095 TMEM251 Bryony Thompson gene: TMEM251 was added
gene: TMEM251 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TMEM251 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM251 were set to 33252156
Phenotypes for gene: TMEM251 were set to Dysostosis multiplex‐like skeletal dysplasia; severe short stature
Review for gene: TMEM251 was set to AMBER
Added comment: Two unrelated consanguineous families with homozygous variants (c.133C>T; p.Arg45Trp and c.215dupA; p.Tyr72Ter), with co-segregation data in one family. Preliminary in vitro functional assays conducted - Tmem251 knockdown by small interfering RNA induced dedifferentiation of rat primary chondrocytes.
Sources: Literature
Mendeliome v0.6094 LOR Zornitza Stark Gene: lor has been classified as Green List (High Evidence).
Mendeliome v0.6094 LOR Zornitza Stark Phenotypes for gene: LOR were changed from to Vohwinkel syndrome with ichthyosis, MIM# 604117
Mendeliome v0.6091 LOR Zornitza Stark reviewed gene: LOR: Rating: GREEN; Mode of pathogenicity: None; Publications: 8673107, 9326398, 9326323, 25234742, 25142840; Phenotypes: Vohwinkel syndrome with ichthyosis, MIM# 604117; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.6091 CYP4F22 Zornitza Stark Gene: cyp4f22 has been classified as Green List (High Evidence).
Mendeliome v0.6091 CYP4F22 Zornitza Stark Phenotypes for gene: CYP4F22 were changed from to Ichthyosis, congenital, autosomal recessive 5, MIM# 604777
Mendeliome v0.6088 CYP4F22 Zornitza Stark reviewed gene: CYP4F22: Rating: GREEN; Mode of pathogenicity: None; Publications: 16436457; Phenotypes: Ichthyosis, congenital, autosomal recessive 5, MIM# 604777; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6088 CERS3 Zornitza Stark Gene: cers3 has been classified as Green List (High Evidence).
Mendeliome v0.6088 CERS3 Zornitza Stark Phenotypes for gene: CERS3 were changed from to Ichthyosis, congenital, autosomal recessive 9, MIM# 615023
Mendeliome v0.6085 CERS3 Zornitza Stark reviewed gene: CERS3: Rating: GREEN; Mode of pathogenicity: None; Publications: 23754960, 23549421, 31168818, 30578701; Phenotypes: Ichthyosis, congenital, autosomal recessive 9, MIM# 615023; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6085 ALOX12B Zornitza Stark Gene: alox12b has been classified as Green List (High Evidence).
Mendeliome v0.6085 ALOX12B Zornitza Stark Phenotypes for gene: ALOX12B were changed from to Ichthyosis, congenital, autosomal recessive 2, MIM# 242100
Mendeliome v0.6082 ALOX12B Zornitza Stark reviewed gene: ALOX12B: Rating: GREEN; Mode of pathogenicity: None; Publications: 16116617, 11773004; Phenotypes: Ichthyosis, congenital, autosomal recessive 2, MIM# 242100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6082 ALX3 Zornitza Stark Gene: alx3 has been classified as Green List (High Evidence).
Mendeliome v0.6082 ALX3 Zornitza Stark Phenotypes for gene: ALX3 were changed from to Frontonasal dysplasia 1, MIM#136760
Mendeliome v0.6079 ALX1 Zornitza Stark Gene: alx1 has been classified as Green List (High Evidence).
Mendeliome v0.6079 ALX1 Zornitza Stark Phenotypes for gene: ALX1 were changed from to Frontonasal dysplasia 3, MIM#613456
Mendeliome v0.6076 ALX1 Zornitza Stark reviewed gene: ALX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27324866, 20451171, 23059813; Phenotypes: Frontonasal dysplasia 3, MIM#613456; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6076 HIST1H1E Zornitza Stark Gene: hist1h1e has been classified as Green List (High Evidence).
Mendeliome v0.6073 EED Zornitza Stark Gene: eed has been classified as Green List (High Evidence).
Mendeliome v0.6070 CLCN1 Zornitza Stark Gene: clcn1 has been classified as Green List (High Evidence).
Mendeliome v0.6070 CLCN1 Zornitza Stark Phenotypes for gene: CLCN1 were changed from to Myotonia congenita, dominant 160800; Myotonia congenita, recessive 255700
Mendeliome v0.6067 CLCN1 Zornitza Stark reviewed gene: CLCN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 1379744, 7981750, 8533761; Phenotypes: Myotonia congenita, dominant 160800, Myotonia congenita, recessive 255700; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.6067 TUBG1 Zornitza Stark Gene: tubg1 has been classified as Green List (High Evidence).
Mendeliome v0.6067 TUBG1 Zornitza Stark Phenotypes for gene: TUBG1 were changed from to Cortical dysplasia, complex, with other brain malformations 4, MIM# 615412
Mendeliome v0.6064 TUBG1 Zornitza Stark reviewed gene: TUBG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23603762, 31086189; Phenotypes: Cortical dysplasia, complex, with other brain malformations 4, MIM# 615412; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.6064 TUBB3 Zornitza Stark Gene: tubb3 has been classified as Green List (High Evidence).
Mendeliome v0.6064 TUBB3 Zornitza Stark Phenotypes for gene: TUBB3 were changed from to Cortical dysplasia, complex, with other brain malformations 1, MIM# 614039; Fibrosis of extraocular muscles, congenital, 3A, MIM# 600638
Mendeliome v0.6061 TUBB3 Zornitza Stark reviewed gene: TUBB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 20829227, 25059107, 33318778, 20074521; Phenotypes: Cortical dysplasia, complex, with other brain malformations 1, MIM# 614039, Fibrosis of extraocular muscles, congenital, 3A, MIM# 600638; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.6061 TUBB2B Zornitza Stark Gene: tubb2b has been classified as Green List (High Evidence).
Mendeliome v0.6061 TUBB2B Zornitza Stark Phenotypes for gene: TUBB2B were changed from to Cortical dysplasia, complex, with other brain malformations 7, MIM# 610031
Mendeliome v0.6058 TUBB2B Zornitza Stark reviewed gene: TUBB2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 19465910, 22333901, 26732629, 33082561; Phenotypes: Cortical dysplasia, complex, with other brain malformations 7, MIM# 610031; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.6058 TUBB Zornitza Stark Gene: tubb has been classified as Green List (High Evidence).
Mendeliome v0.6058 TUBB Zornitza Stark Phenotypes for gene: TUBB were changed from to Cortical dysplasia, complex, with other brain malformations 6, MIM# 615771
Mendeliome v0.6055 TUBB Zornitza Stark reviewed gene: TUBB: Rating: GREEN; Mode of pathogenicity: None; Publications: 23246003, 32085672; Phenotypes: Cortical dysplasia, complex, with other brain malformations 6, MIM# 615771; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.6055 FZD4 Zornitza Stark Gene: fzd4 has been classified as Green List (High Evidence).
Mendeliome v0.6052 TSPAN12 Zornitza Stark Gene: tspan12 has been classified as Green List (High Evidence).
Mendeliome v0.6049 PPP2R5D Zornitza Stark Gene: ppp2r5d has been classified as Green List (High Evidence).
Mendeliome v0.6045 KAT6B Zornitza Stark Gene: kat6b has been classified as Green List (High Evidence).
Mendeliome v0.6041 DVL1 Zornitza Stark Gene: dvl1 has been classified as Green List (High Evidence).
Mendeliome v0.6037 ZFP36L1 Zornitza Stark Gene: zfp36l1 has been classified as Red List (Low Evidence).
Mendeliome v0.6037 ZFP36L1 Zornitza Stark Classified gene: ZFP36L1 as Red List (low evidence)
Mendeliome v0.6037 ZFP36L1 Zornitza Stark Gene: zfp36l1 has been classified as Red List (Low Evidence).
Mendeliome v0.6035 SCAMP5 Zornitza Stark edited their review of gene: SCAMP5: Added comment: PMID 33390987: Four unrelated individuals reported with same de novo missense variant, p. Gly180Trp. The onset age of seizures was ranged from 6 to 15 months. Patients had different types of seizures, including focal seizures, generalized tonic-clonic seizures and tonic seizure. One patient showed typical autism spectrum disorder (ASD) symptoms. Electroencephalogram (EEG) findings presented as focal or multifocal discharges, sometimes spreading to generalization. Brain magnetic resonance imaging (MRI) abnormalities were present in each patient. Severe intellectual disability and language and motor developmental disorders were found in our patients, with all patients having poor language development and were nonverbal at last follow-up. All but one of the patients could walk independently in childhood, but the ability to walk independently in one patient had deteriorated with age. All patients had abnormal neurological exam findings, mostly signs of extrapyramidal system involvement. Dysmorphic features were found in 2/4 patients, mainly in the face and trunk.; Changed publications: 31439720, 33390987
Mendeliome v0.6035 TSPYL1 Zornitza Stark Phenotypes for gene: TSPYL1 were changed from Sudden infant death with dysgenesis of the testes syndrome (MIM#608800) to Sudden infant death with dysgenesis of the testes syndrome (MIM#608800); sudden infant death-dysgenesis of the testes syndrome MONDO:0012124
Mendeliome v0.6033 TSPYL1 Zornitza Stark Classified gene: TSPYL1 as Green List (high evidence)
Mendeliome v0.6033 TSPYL1 Zornitza Stark Gene: tspyl1 has been classified as Green List (High Evidence).
Mendeliome v0.6029 ZNF526 Zornitza Stark Classified gene: ZNF526 as Green List (high evidence)
Mendeliome v0.6029 ZNF526 Zornitza Stark Gene: znf526 has been classified as Green List (High Evidence).
Mendeliome v0.6028 CYLD Zornitza Stark Phenotypes for gene: CYLD were changed from Brooke-Spiegler syndrome, 605041; Cylindromatosis, familial, 132700; Trichoepithelioma, multiple familial, 1, 601606; Frontotemporal dementia and amyotrophic lateral sclerosis to Brooke-Spiegler syndrome, 605041; Cylindromatosis, familial, 132700; Trichoepithelioma, multiple familial, 1, 601606; Frontotemporal dementia and/or amytrophic lateral sclerosis 8, MIM# 619132
Mendeliome v0.6027 CYLD Zornitza Stark reviewed gene: CYLD: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Frontotemporal dementia and/or amytrophic lateral sclerosis 8, MIM# 619132; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.6026 TSPYL1 Eleanor Williams reviewed gene: TSPYL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32885560, 33075815; Phenotypes: Sudden infant death with dysgenesis of the testes syndrome OMIM:608800, sudden infant death-dysgenesis of the testes syndrome MONDO:0012124; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6026 INTS6 Zornitza Stark Gene: ints6 has been classified as Red List (Low Evidence).
Mendeliome v0.6026 INTS6 Zornitza Stark Classified gene: INTS6 as Red List (low evidence)
Mendeliome v0.6026 INTS6 Zornitza Stark Gene: ints6 has been classified as Red List (Low Evidence).
Mendeliome v0.6025 BCS1L Zornitza Stark Gene: bcs1l has been classified as Green List (High Evidence).
Mendeliome v0.6022 MRPS22 Zornitza Stark Gene: mrps22 has been classified as Green List (High Evidence).
Mendeliome v0.6022 MRPS22 Zornitza Stark Phenotypes for gene: MRPS22 were changed from to Combined oxidative phosphorylation deficiency 5 MIM#611719; Ovarian dysgenesis 7 MIM#618117
Mendeliome v0.6019 KRT10 Elena Savva reviewed gene: KRT10: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 26176760, 20798280, 31638346, 18219278, 16505000; Phenotypes: Epidermolytic hyperkeratosis, MIM#113800, Ichthyosis with confetti, MIM#609165, Ichthyosis, cyclic, with epidermolytic hyperkeratosis, MIM#607602; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.6019 BRPF1 Elena Savva reviewed gene: BRPF1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32652122, 27939640; Phenotypes: Intellectual developmental disorder with dysmorphic facies and ptosis MIM#617333; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.6019 MRPS22 Elena Savva reviewed gene: MRPS22: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29566152; Phenotypes: Combined oxidative phosphorylation deficiency 5 MIM#611719, Ovarian dysgenesis 7 MIM#618117; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.6019 CELF2 Zornitza Stark Gene: celf2 has been classified as Green List (High Evidence).
Mendeliome v0.6019 CELF2 Zornitza Stark Classified gene: CELF2 as Green List (high evidence)
Mendeliome v0.6019 CELF2 Zornitza Stark Gene: celf2 has been classified as Green List (High Evidence).
Mendeliome v0.6018 CELF2 Zornitza Stark gene: CELF2 was added
gene: CELF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CELF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CELF2 were set to 33131106
Phenotypes for gene: CELF2 were set to Developmental and epileptic encephalopathy
Review for gene: CELF2 was set to GREEN
Added comment: Five unrelated individuals reported. Four with de novo variants, and one inherited from a mosaic mother. Notably, all identified variants, except for c.272‐1G>C, were clustered within 20 amino acid residues of the C‐terminus, which might be a nuclear localization signal.
Sources: Literature
Mendeliome v0.6017 FGF13 Zornitza Stark Gene: fgf13 has been classified as Green List (High Evidence).
Mendeliome v0.6017 FGF13 Zornitza Stark Classified gene: FGF13 as Green List (high evidence)
Mendeliome v0.6017 FGF13 Zornitza Stark Gene: fgf13 has been classified as Green List (High Evidence).
Mendeliome v0.6016 FGF13 Zornitza Stark gene: FGF13 was added
gene: FGF13 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FGF13 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: FGF13 were set to 33245860
Phenotypes for gene: FGF13 were set to Intellectual disability; epilepsy
Mode of pathogenicity for gene: FGF13 was set to Other
Review for gene: FGF13 was set to GREEN
Added comment: Two sibling pairs and three unrelated males reported who presented in infancy with intractable focal seizures and severe developmental delay.

The variants were located in the N-terminal domain of the A isoform of FGF13/FHF2 (FHF2A). The X-linked FHF2 gene (also known as FGF13) has alternative first exons which produce multiple protein isoforms that differ in their N-terminal sequence. The variants were located at highly conserved residues in the FHF2A inactivation particle that competes with the intrinsic fast inactivation mechanism of Nav channels. Functional characterization of mutant FHF2A co-expressed with wild-type Nav1.6 (SCN8A) revealed that mutant FHF2A proteins lost the ability to induce rapid-onset, long-term blockade of the channel while retaining pro-excitatory properties. These gain-of-function effects are likely to increase neuronal excitability consistent with the epileptic potential of FHF2 variants.
Sources: Literature
Mendeliome v0.6015 SCUBE3 Zornitza Stark Gene: scube3 has been classified as Green List (High Evidence).
Mendeliome v0.6015 SCUBE3 Zornitza Stark Classified gene: SCUBE3 as Green List (high evidence)
Mendeliome v0.6015 SCUBE3 Zornitza Stark Gene: scube3 has been classified as Green List (High Evidence).
Mendeliome v0.6014 SCUBE3 Zornitza Stark changed review comment from: Eighteen affected individuals from nine unrelated families reported with a consistent phenotype characterised by reduced growth, skeletal features, distinctive craniofacial appearance, and dental anomalies.
Sources: Literature; to: Eighteen affected individuals from nine unrelated families reported with a consistent phenotype characterised by reduced growth, skeletal features, distinctive craniofacial appearance, and dental anomalies. Mouse model recapitulated phenotype.
Sources: Literature
Mendeliome v0.6014 SCUBE3 Zornitza Stark gene: SCUBE3 was added
gene: SCUBE3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SCUBE3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCUBE3 were set to 33308444
Phenotypes for gene: SCUBE3 were set to Short stature; skeletal abnormalities; craniofacial abnormalities; dental anomalies
Review for gene: SCUBE3 was set to GREEN
Added comment: Eighteen affected individuals from nine unrelated families reported with a consistent phenotype characterised by reduced growth, skeletal features, distinctive craniofacial appearance, and dental anomalies.
Sources: Literature
Mendeliome v0.6013 UBR7 Zornitza Stark Gene: ubr7 has been classified as Green List (High Evidence).
Mendeliome v0.6013 UBR7 Zornitza Stark Classified gene: UBR7 as Green List (high evidence)
Mendeliome v0.6013 UBR7 Zornitza Stark Gene: ubr7 has been classified as Green List (High Evidence).
Mendeliome v0.6012 UBR7 Zornitza Stark gene: UBR7 was added
gene: UBR7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: UBR7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UBR7 were set to 33340455
Phenotypes for gene: UBR7 were set to Intellectual disability; epilepsy; hypothyroidism; congenital anomalies; dysmorphic features
Review for gene: UBR7 was set to GREEN
Added comment: Seven individuals from 6 unrelated families. All had developmental delay, and all males had urogenital anomalies, namely cryptorchidism in 5/6 and small penis in 1/6. Six individuals had seizures and hypotonia. Hypothyroidism was present in 4/7 individuals, and ptosis was noted in 6/7 individuals. Five individuals exhibited cardiac abnormalities: two had ventricular septal defect, one had atrial septal defect, one had a patent ductus arteriosus requiring surgery, and the other had a patent ductus arteriosus and a patent foramen ovale that both closed spontaneously. Five individuals had short stature (height < 3rd percentile). Physical examination revealed various dysmorphic features, including prominent forehead (3/7), hypertelorism (4/7), telecanthus (1/7), epicanthus(1/7), downslanting palpebral fissures (3/7), thick eyebrow (1/7), low-set ears (3/7), long philtrum (2/7), unilateral single transverse palmar crease (1/7), and hypertrichosis (1/7).
Sources: Literature
Mendeliome v0.6011 RNU7-1 Zornitza Stark Gene: rnu7-1 has been classified as Green List (High Evidence).
Mendeliome v0.6010 RNU7-1 Zornitza Stark Classified gene: RNU7-1 as Green List (high evidence)
Mendeliome v0.6010 RNU7-1 Zornitza Stark Gene: rnu7-1 has been classified as Green List (High Evidence).
Mendeliome v0.6009 RABL2A Zornitza Stark Gene: rabl2a has been classified as Red List (Low Evidence).
Mendeliome v0.6007 RABL2A Zornitza Stark Classified gene: RABL2A as Red List (low evidence)
Mendeliome v0.6007 RABL2A Zornitza Stark Gene: rabl2a has been classified as Red List (Low Evidence).
Mendeliome v0.6006 AKT1 Zornitza Stark Classified gene: AKT1 as Green List (high evidence)
Mendeliome v0.6006 AKT1 Zornitza Stark Gene: akt1 has been classified as Green List (High Evidence).
Mendeliome v0.6005 CEP250 Zornitza Stark Gene: cep250 has been classified as Green List (High Evidence).
Mendeliome v0.6002 RABL2A Eleanor Williams gene: RABL2A was added
gene: RABL2A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RABL2A was set to Unknown
Publications for gene: RABL2A were set to 33075816
Phenotypes for gene: RABL2A were set to male infertility; ciliopathy
Review for gene: RABL2A was set to RED
Added comment: PMID: 33075816 - Ding et al 2020 - with the aim of identifying variants that affect male fertility, the authors report on mice expressing two RABL2A SNPs found to be rare (MAF between 2% and 0.02% in gnomAD, with a deleterious prediction from SIFT and PolyPhen-2, and to affect protein stability. Mice homozygous for these variants (p.L119F and p.V158F) were found to be show ciliopathy-associated disorders including male infertility, early growth retardation, excessive weight gain in adulthood, heterotaxia, pre-axial polydactyly, neural tube defects and hydrocephalus.
Sources: Literature
Mendeliome v0.6002 VCAN Zornitza Stark Gene: vcan has been classified as Green List (High Evidence).
Mendeliome v0.5999 CAPN5 Zornitza Stark Gene: capn5 has been classified as Green List (High Evidence).
Mendeliome v0.5996 UBIAD1 Zornitza Stark Gene: ubiad1 has been classified as Green List (High Evidence).
Mendeliome v0.5993 TGFBI Zornitza Stark Gene: tgfbi has been classified as Green List (High Evidence).
Mendeliome v0.5990 TACSTD2 Zornitza Stark Gene: tacstd2 has been classified as Green List (High Evidence).
Mendeliome v0.5987 KIF27 Zornitza Stark Gene: kif27 has been classified as Red List (Low Evidence).
Mendeliome v0.5987 KIF27 Zornitza Stark Classified gene: KIF27 as Red List (low evidence)
Mendeliome v0.5987 KIF27 Zornitza Stark Gene: kif27 has been classified as Red List (Low Evidence).
Mendeliome v0.5986 ZEB1 Zornitza Stark Gene: zeb1 has been classified as Green List (High Evidence).
Mendeliome v0.5983 ZNF469 Zornitza Stark Gene: znf469 has been classified as Green List (High Evidence).
Mendeliome v0.5980 PIKFYVE Zornitza Stark Gene: pikfyve has been classified as Green List (High Evidence).
Mendeliome v0.5977 OVOL2 Zornitza Stark Gene: ovol2 has been classified as Green List (High Evidence).
Mendeliome v0.5974 KRT3 Zornitza Stark Gene: krt3 has been classified as Green List (High Evidence).
Mendeliome v0.5971 DCN Zornitza Stark Gene: dcn has been classified as Green List (High Evidence).
Mendeliome v0.5968 COL8A2 Zornitza Stark Gene: col8a2 has been classified as Green List (High Evidence).
Mendeliome v0.5965 STX3 Zornitza Stark Gene: stx3 has been classified as Green List (High Evidence).
Mendeliome v0.5965 STX3 Zornitza Stark Phenotypes for gene: STX3 were changed from to Microvillus inclusion disease
Mendeliome v0.5962 STX3 Zornitza Stark reviewed gene: STX3: Rating: GREEN; Mode of pathogenicity: None; Publications: 24726755, 29266534, 25358429, 29282386, 30909251, 29282386; Phenotypes: Microvillus inclusion disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5962 SPINT2 Zornitza Stark Gene: spint2 has been classified as Green List (High Evidence).
Mendeliome v0.5959 SLC9A3 Zornitza Stark Gene: slc9a3 has been classified as Green List (High Evidence).
Mendeliome v0.5956 SLC5A1 Zornitza Stark Gene: slc5a1 has been classified as Green List (High Evidence).
Mendeliome v0.5953 SLC39A4 Zornitza Stark Gene: slc39a4 has been classified as Green List (High Evidence).
Mendeliome v0.5950 SLC26A3 Zornitza Stark Gene: slc26a3 has been classified as Green List (High Evidence).
Mendeliome v0.5947 SLC51B Zornitza Stark Gene: slc51b has been classified as Red List (Low Evidence).
Mendeliome v0.5947 SLC51B Zornitza Stark gene: SLC51B was added
gene: SLC51B was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: SLC51B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC51B were set to 28898457
Phenotypes for gene: SLC51B were set to Congenital diarrhoea; Cholestasis
Review for gene: SLC51B was set to RED
Added comment: Two siblings reported with homozygous LOF variant in this gene and congenital diarrhoea/cholestasis.
Sources: Expert Review
Mendeliome v0.5946 SLC10A2 Zornitza Stark Gene: slc10a2 has been classified as Red List (Low Evidence).
Mendeliome v0.5943 SLC10A2 Zornitza Stark Classified gene: SLC10A2 as Red List (low evidence)
Mendeliome v0.5943 SLC10A2 Zornitza Stark Gene: slc10a2 has been classified as Red List (Low Evidence).
Mendeliome v0.5942 PLVAP Zornitza Stark Gene: plvap has been classified as Green List (High Evidence).
Mendeliome v0.5942 PLVAP Zornitza Stark Phenotypes for gene: PLVAP were changed from to Diarrhoea 10, protein-losing enteropathy type, MIM# 618183
Mendeliome v0.5939 PLVAP Zornitza Stark reviewed gene: PLVAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 29875123, 29661969, 26207260, 31215290; Phenotypes: Diarrhoea 10, protein-losing enteropathy type, MIM# 618183; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5939 NEUROG3 Zornitza Stark Gene: neurog3 has been classified as Green List (High Evidence).
Mendeliome v0.5936 TMPRSS15 Zornitza Stark Gene: tmprss15 has been classified as Green List (High Evidence).
Mendeliome v0.5933 TTC37 Zornitza Stark Gene: ttc37 has been classified as Green List (High Evidence).
Mendeliome v0.5930 WNT2B Zornitza Stark Gene: wnt2b has been classified as Green List (High Evidence).
Mendeliome v0.5927 MYO5B Zornitza Stark Gene: myo5b has been classified as Green List (High Evidence).
Mendeliome v0.5927 MYO5B Zornitza Stark Phenotypes for gene: MYO5B were changed from to Microvillus inclusion disease, MIM# 251850; Cholestasis
Mendeliome v0.5924 MYO5B Zornitza Stark reviewed gene: MYO5B: Rating: GREEN; Mode of pathogenicity: None; Publications: 30564347, 29266534, 28027573, 27532546; Phenotypes: Microvillus inclusion disease, MIM# 251850, Cholestasis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5924 LCT Zornitza Stark Gene: lct has been classified as Green List (High Evidence).
Mendeliome v0.5922 FBRSL1 Zornitza Stark Gene: fbrsl1 has been classified as Green List (High Evidence).
Mendeliome v0.5922 CAMK2B Zornitza Stark Gene: camk2b has been classified as Green List (High Evidence).
Mendeliome v0.5919 FBRSL1 Sue White Classified gene: FBRSL1 as Green List (high evidence)
Mendeliome v0.5919 FBRSL1 Sue White Gene: fbrsl1 has been classified as Green List (High Evidence).
Mendeliome v0.5918 RALGAPB Seb Lunke Gene: ralgapb has been classified as Green List (High Evidence).
Mendeliome v0.5918 RALGAPB Seb Lunke Classified gene: RALGAPB as Green List (high evidence)
Mendeliome v0.5918 RALGAPB Seb Lunke Gene: ralgapb has been classified as Green List (High Evidence).
Mendeliome v0.5917 RALGAPB Elena Savva gene: RALGAPB was added
gene: RALGAPB was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RALGAPB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RALGAPB were set to PMID: 32853829
Phenotypes for gene: RALGAPB were set to Neurodevelopmental disorders, autism
Review for gene: RALGAPB was set to GREEN
Added comment: PMID: 32853829 - 2 patients with de novo missense variants, 1 patient with a de novo PTC with autism spectrum disorder from a large cohort.
Reviews previous publications and identifies 10 de novo variants (5 PTCs, 5 missense) in patients with ASD (7/10), epilepsy (2/10) and developmental delay (1/10).
Functional studies of patient cells show reduced mRNA expression (PTC).
Sources: Literature
Mendeliome v0.5917 RPL3L Seb Lunke Gene: rpl3l has been classified as Green List (High Evidence).
Mendeliome v0.5917 RPL3L Seb Lunke Classified gene: RPL3L as Green List (high evidence)
Mendeliome v0.5917 RPL3L Seb Lunke Gene: rpl3l has been classified as Green List (High Evidence).
Mendeliome v0.5916 LSM11 Seb Lunke changed review comment from: Comment on list classification: Very little evidence at this stage, just one consanguineous family with a some functional data.; to: Comment on list classification: Very little evidence at this stage, just one consanguineous family with some functional data.
Mendeliome v0.5916 LSM11 Seb Lunke Gene: lsm11 has been classified as Red List (Low Evidence).
Mendeliome v0.5916 LSM11 Seb Lunke Classified gene: LSM11 as Red List (low evidence)
Mendeliome v0.5916 LSM11 Seb Lunke Added comment: Comment on list classification: Very little evidence at this stage, just one consanguineous family with a some functional data.
Mendeliome v0.5916 LSM11 Seb Lunke Gene: lsm11 has been classified as Red List (Low Evidence).
Mendeliome v0.5915 DPH2 Seb Lunke Gene: dph2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5915 DPH2 Seb Lunke Classified gene: DPH2 as Amber List (moderate evidence)
Mendeliome v0.5915 DPH2 Seb Lunke Gene: dph2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5914 RPL3L Elena Savva gene: RPL3L was added
gene: RPL3L was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RPL3L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RPL3L were set to PMID: 32514796; 32870709
Phenotypes for gene: RPL3L were set to Neonatal dilated cardiomyopathy
Review for gene: RPL3L was set to GREEN
Added comment: PMID: 32514796 - 5 hom/chet individuals from three independent families who presented with severe neonatal dilated cardiomyopathy. Unaffected sibs were either carriers of a single variant or homozygous wildtype.

PMID: 32870709 - 1 hom patient w/ neonatal DCM
Sources: Literature
Mendeliome v0.5914 LSM11 Ee Ming Wong gene: LSM11 was added
gene: LSM11 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LSM11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LSM11 were set to PMID: 33230297
Phenotypes for gene: LSM11 were set to type I interferonopathy Aicardi–Goutières syndrome
Review for gene: LSM11 was set to AMBER
gene: LSM11 was marked as current diagnostic
Added comment: - Two affected siblings from a consanguineous family carrying a homozygous variant in LSM11
- Compared to control fibroblasts, patient fibroblasts were enriched for misprocessed forms of
replication-dependent histone (RDH) mRNAs
- Knockdown of LSM11 in THP-1 cells results in an increase in misprocessed RDH mRNA and
interferon signaling
Sources: Literature
Mendeliome v0.5914 DPH2 Paul De Fazio changed review comment from: One family reported (PMID:32576952) with biallelic (one missense, one nonsense) variants in DPH2, with phenotype similar to DPH1 deficiency.

Another family was previously reported with biallelic nonsense variants (PMID:27421267) with a comparable phenotype, this family also has biallelic variants in KALRN and the authors thought those variants more likely causative.

In vitro functional assays support reduced diphthamide synthesis activity for the variants identified in PMID:32576952.
Sources: Literature; to: One 19 month old reported (PMID:32576952) with biallelic (one missense, one nonsense) variants in DPH2, with phenotype similar to DPH1 deficiency (gross motor delay, not walking, fine motor and expressive language delays, macrocephaly)

Another family (sibs) was previously reported with biallelic nonsense variants (PMID:27421267) with a comparable phenotype, this family also has biallelic variants in KALRN and the authors thought those variants more likely causative. Patients had ID and microcephaly (in contrast to the 19 month old above).

In vitro functional assays support reduced diphthamide synthesis activity for the variants identified in PMID:32576952.
Sources: Literature
Mendeliome v0.5914 DPH2 Paul De Fazio gene: DPH2 was added
gene: DPH2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DPH2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DPH2 were set to 32576952; 27421267
Phenotypes for gene: DPH2 were set to Diphthamide-deficiency syndrome
Review for gene: DPH2 was set to AMBER
gene: DPH2 was marked as current diagnostic
Added comment: One family reported (PMID:32576952) with biallelic (one missense, one nonsense) variants in DPH2, with phenotype similar to DPH1 deficiency.

Another family was previously reported with biallelic nonsense variants (PMID:27421267) with a comparable phenotype, this family also has biallelic variants in KALRN and the authors thought those variants more likely causative.

In vitro functional assays support reduced diphthamide synthesis activity for the variants identified in PMID:32576952.
Sources: Literature
Mendeliome v0.5914 EPCAM Zornitza Stark Gene: epcam has been classified as Green List (High Evidence).
Mendeliome v0.5911 DGAT1 Zornitza Stark Gene: dgat1 has been classified as Green List (High Evidence).
Mendeliome v0.5911 DGAT1 Zornitza Stark Phenotypes for gene: DGAT1 were changed from to Diarrhoea 7, protein-losing enteropathy type, MIM# 615863
Mendeliome v0.5908 DGAT1 Zornitza Stark reviewed gene: DGAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33261563, 32786057, 31778854, 28373485, 29604290; Phenotypes: Diarrhoea 7, protein-losing enteropathy type, MIM# 615863; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5908 CPA6 Zornitza Stark Gene: cpa6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5905 CPA6 Zornitza Stark Classified gene: CPA6 as Amber List (moderate evidence)
Mendeliome v0.5905 CPA6 Zornitza Stark Gene: cpa6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5904 CPA6 Zornitza Stark edited their review of gene: CPA6: Added comment: Homozygous p.A270V variant reported in four siblings with Febrile seizures, familial, 11 (MIM 614418)(PMID:21922598), some functional data. Present in gnomad as hets but no homs. Also note one of the heterozygous individuals initially reported was subsequently found to have a second missense variant, PMID 23105115.

Disputed association between mono allelic variants and disease: variants reported have high frequency in gnomad, not in keeping with Mendelian disorder.; Changed rating: AMBER; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5904 HSD17B10 Zornitza Stark Gene: hsd17b10 has been classified as Green List (High Evidence).
Mendeliome v0.5902 HMGCS2 Zornitza Stark Gene: hmgcs2 has been classified as Green List (High Evidence).
Mendeliome v0.5899 HMGCL Zornitza Stark Gene: hmgcl has been classified as Green List (High Evidence).
Mendeliome v0.5896 GLUD1 Zornitza Stark Gene: glud1 has been classified as Green List (High Evidence).
Mendeliome v0.5891 AGPAT2 Zornitza Stark Gene: agpat2 has been classified as Green List (High Evidence).
Mendeliome v0.5888 LPIN1 Zornitza Stark Gene: lpin1 has been classified as Green List (High Evidence).
Mendeliome v0.5888 LPIN1 Zornitza Stark Phenotypes for gene: LPIN1 were changed from to Myoglobinuria, acute recurrent, autosomal recessive, MIM# 268200
Mendeliome v0.5885 LPIN1 Zornitza Stark reviewed gene: LPIN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18817903, 32549891, 32522502, 32410653; Phenotypes: Myoglobinuria, acute recurrent, autosomal recessive, MIM# 268200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5885 MLYCD Zornitza Stark Gene: mlycd has been classified as Green List (High Evidence).
Mendeliome v0.5882 SLC25A20 Zornitza Stark Gene: slc25a20 has been classified as Green List (High Evidence).
Mendeliome v0.5879 GABRD Zornitza Stark Gene: gabrd has been classified as Red List (Low Evidence).
Mendeliome v0.5876 GABRD Zornitza Stark Classified gene: GABRD as Red List (low evidence)
Mendeliome v0.5876 GABRD Zornitza Stark Gene: gabrd has been classified as Red List (Low Evidence).
Mendeliome v0.5875 SPR Zornitza Stark Gene: spr has been classified as Green List (High Evidence).
Mendeliome v0.5875 SPR Zornitza Stark Phenotypes for gene: SPR were changed from to Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, MIM# 612716
Mendeliome v0.5872 PRRT2 Zornitza Stark Gene: prrt2 has been classified as Green List (High Evidence).
Mendeliome v0.5872 PRRT2 Zornitza Stark Phenotypes for gene: PRRT2 were changed from to Convulsions, familial infantile, with paroxysmal choreoathetosis 602066; Episodic kinesigenic dyskinesia 1 128200; Seizures, benign familial infantile, 2 605751
Mendeliome v0.5869 PRRT2 Zornitza Stark reviewed gene: PRRT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33126500; Phenotypes: Convulsions, familial infantile, with paroxysmal choreoathetosis 602066, Episodic kinesigenic dyskinesia 1 128200, Seizures, benign familial infantile, 2 605751; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5869 KCNQ3 Zornitza Stark Gene: kcnq3 has been classified as Green List (High Evidence).
Mendeliome v0.5866 PRKACB Zornitza Stark Gene: prkacb has been classified as Green List (High Evidence).
Mendeliome v0.5866 PRKACB Zornitza Stark Phenotypes for gene: PRKACB were changed from Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability to Cardioacrofacial dysplasia 2, MIM# 619143; Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability
Mendeliome v0.5865 PRKACB Zornitza Stark reviewed gene: PRKACB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardioacrofacial dysplasia 2, MIM# 619143; Mode of inheritance: None
Mendeliome v0.5865 PRKACA Zornitza Stark Phenotypes for gene: PRKACA were changed from Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth to Cardioacrofacial dysplasia 1, MIM# 619142; Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability
Mendeliome v0.5864 PRKACA Zornitza Stark reviewed gene: PRKACA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cardioacrofacial dysplasia 1, MIM# 619142; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5864 SCARF2 Zornitza Stark Gene: scarf2 has been classified as Green List (High Evidence).
Mendeliome v0.5860 GSTO1 Zornitza Stark Gene: gsto1 has been classified as Red List (Low Evidence).
Mendeliome v0.5858 GSTO1 Zornitza Stark Classified gene: GSTO1 as Red List (low evidence)
Mendeliome v0.5858 GSTO1 Zornitza Stark Gene: gsto1 has been classified as Red List (Low Evidence).
Mendeliome v0.5857 PRR12 Zornitza Stark Gene: prr12 has been classified as Green List (High Evidence).
Mendeliome v0.5854 PRSS56 Zornitza Stark Gene: prss56 has been classified as Green List (High Evidence).
Mendeliome v0.5851 GJA8 Zornitza Stark Gene: gja8 has been classified as Green List (High Evidence).
Mendeliome v0.5848 ATIC Zornitza Stark Gene: atic has been classified as Green List (High Evidence).
Mendeliome v0.5848 ATIC Zornitza Stark Phenotypes for gene: ATIC were changed from to AICA-ribosiduria due to ATIC deficiency, MIM# 608688
Mendeliome v0.5845 ATIC Zornitza Stark reviewed gene: ATIC: Rating: GREEN; Mode of pathogenicity: None; Publications: 15114530, 32557644; Phenotypes: AICA-ribosiduria due to ATIC deficiency, MIM# 608688; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5845 FZD5 Zornitza Stark Gene: fzd5 has been classified as Green List (High Evidence).
Mendeliome v0.5845 FZD5 Zornitza Stark Classified gene: FZD5 as Green List (high evidence)
Mendeliome v0.5845 FZD5 Zornitza Stark Gene: fzd5 has been classified as Green List (High Evidence).
Mendeliome v0.5843 STRA6 Zornitza Stark Gene: stra6 has been classified as Green List (High Evidence).
Mendeliome v0.5840 SOX2 Zornitza Stark Gene: sox2 has been classified as Green List (High Evidence).
Mendeliome v0.5840 SOX2 Zornitza Stark Phenotypes for gene: SOX2 were changed from to Microphthalmia, syndromic 3, MIM# 206900; Optic nerve hypoplasia and abnormalities of the central nervous system, MIM# 206900
Mendeliome v0.5837 SOX2 Zornitza Stark reviewed gene: SOX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30450772, 28121235, 25542770, 24498598, 24211324, 24033328, 21326281; Phenotypes: Microphthalmia, syndromic 3, MIM# 206900, Optic nerve hypoplasia and abnormalities of the central nervous system, MIM# 206900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5837 SIX6 Zornitza Stark Marked gene: SIX6 as ready
Mendeliome v0.5837 SIX6 Zornitza Stark Gene: six6 has been classified as Green List (High Evidence).
Mendeliome v0.5837 SIX6 Zornitza Stark Phenotypes for gene: SIX6 were changed from to Optic disc anomalies with retinal and/or macular dystrophy, MIM# 212550
Mendeliome v0.5836 SIX6 Zornitza Stark Publications for gene: SIX6 were set to
Mendeliome v0.5835 SIX6 Zornitza Stark Mode of inheritance for gene: SIX6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5834 SIX6 Zornitza Stark reviewed gene: SIX6: Rating: GREEN; Mode of pathogenicity: None; Publications: 23167593, 24702266, 33108933, 31207931, 24702266; Phenotypes: Optic disc anomalies with retinal and/or macular dystrophy, MIM# 212550; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5834 RERE Zornitza Stark Gene: rere has been classified as Green List (High Evidence).
Mendeliome v0.5830 RAX Zornitza Stark Gene: rax has been classified as Green List (High Evidence).
Mendeliome v0.5826 RARB Zornitza Stark Gene: rarb has been classified as Green List (High Evidence).
Mendeliome v0.5819 RARA Zornitza Stark edited their review of gene: RARA: Added comment: Single case report of de novo missense variant in association with syndromic coloboma.; Changed publications: 31343737; Changed phenotypes: Syndromic chorioretinal coloboma
Mendeliome v0.5819 PXDN Zornitza Stark Gene: pxdn has been classified as Green List (High Evidence).
Mendeliome v0.5819 PXDN Zornitza Stark Phenotypes for gene: PXDN were changed from to Anterior segment dysgenesis 7, with sclerocornea, MIM# 269400
Mendeliome v0.5816 PXDN Zornitza Stark reviewed gene: PXDN: Rating: GREEN; Mode of pathogenicity: None; Publications: 21907015, 24939590, 32499604, 32224865, 32015378, 31817535; Phenotypes: Anterior segment dysgenesis 7, with sclerocornea, MIM# 269400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5816 SMOC1 Zornitza Stark Gene: smoc1 has been classified as Green List (High Evidence).
Mendeliome v0.5813 MFRP Zornitza Stark Gene: mfrp has been classified as Green List (High Evidence).
Mendeliome v0.5810 MAB21L2 Zornitza Stark Gene: mab21l2 has been classified as Green List (High Evidence).
Mendeliome v0.5810 MAB21L2 Zornitza Stark Phenotypes for gene: MAB21L2 were changed from to Microphthalmia/coloboma and skeletal dysplasia syndrome, MIM# 615877
Mendeliome v0.5807 MAB21L2 Zornitza Stark reviewed gene: MAB21L2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24906020, 25719200, 31037784, 30375740, 30073347, 26116559; Phenotypes: Microphthalmia/coloboma and skeletal dysplasia syndrome, MIM# 615877; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5807 PDSS1 Zornitza Stark Gene: pdss1 has been classified as Green List (High Evidence).
Mendeliome v0.5804 POLR1A Zornitza Stark Gene: polr1a has been classified as Green List (High Evidence).
Mendeliome v0.5804 POLR1A Zornitza Stark Phenotypes for gene: POLR1A were changed from Acrofacial dysostosis, Cincinnati type, (MIM#616462) to Acrofacial dysostosis, Cincinnati type, (MIM#616462); Leukodystrophy
Mendeliome v0.5803 POLR1A Zornitza Stark Phenotypes for gene: POLR1A were changed from to Acrofacial dysostosis, Cincinnati type, (MIM#616462)
Mendeliome v0.5800 POLR1A Ain Roesley 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
Mendeliome v0.5800 LOXL3 Zornitza Stark Gene: loxl3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5800 LOXL3 Zornitza Stark Classified gene: LOXL3 as Amber List (moderate evidence)
Mendeliome v0.5800 LOXL3 Zornitza Stark Gene: loxl3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5798 RBP4 Zornitza Stark Gene: rbp4 has been classified as Green List (High Evidence).
Mendeliome v0.5795 VAX1 Zornitza Stark Gene: vax1 has been classified as Red List (Low Evidence).
Mendeliome v0.5792 VAX1 Zornitza Stark Classified gene: VAX1 as Red List (low evidence)
Mendeliome v0.5792 VAX1 Zornitza Stark Gene: vax1 has been classified as Red List (Low Evidence).
Mendeliome v0.5791 VSX2 Zornitza Stark Gene: vsx2 has been classified as Green List (High Evidence).
Mendeliome v0.5788 WDR37 Zornitza Stark Gene: wdr37 has been classified as Green List (High Evidence).
Mendeliome v0.5785 ALDH1A3 Zornitza Stark Gene: aldh1a3 has been classified as Green List (High Evidence).
Mendeliome v0.5781 VEGFC Zornitza Stark Gene: vegfc has been classified as Green List (High Evidence).
Mendeliome v0.5778 KDELR2 Zornitza Stark Phenotypes for gene: KDELR2 were changed from Increased susceptibility to fractures; joint hypermobility; Scoliosis; Bowing of the legs; Bowing of the arms to Osteogenesis imperfecta 21, MIM# 619131; Increased susceptibility to fractures; joint hypermobility; Scoliosis; Bowing of the legs; Bowing of the arms
Mendeliome v0.5777 KDELR2 Zornitza Stark edited their review of gene: KDELR2: Changed phenotypes: Osteogenesis imperfecta 21, MIM# 619131, Increased susceptibility to fractures, joint hypermobility, Scoliosis, Bowing of the legs, Bowing of the arms
Mendeliome v0.5775 RNASEH2B Zornitza Stark Gene: rnaseh2b has been classified as Green List (High Evidence).
Mendeliome v0.5772 PDGFB Zornitza Stark Gene: pdgfb has been classified as Green List (High Evidence).
Mendeliome v0.5769 XYLT1 Zornitza Stark reviewed gene: XYLT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30554721, 24581741, 23982343; Phenotypes: Desbuquois dysplasia 2, MIM# 615777, Baratela-Scott syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5769 TUSC3 Zornitza Stark Gene: tusc3 has been classified as Green List (High Evidence).
Mendeliome v0.5769 TUSC3 Zornitza Stark Phenotypes for gene: TUSC3 were changed from to Mental retardation, autosomal recessive 7, MIM# 611093, MONDO:0012615; TUSC3-CDG (Disorders of protein N-glycosylation)
Mendeliome v0.5766 TUSC3 Zornitza Stark reviewed gene: TUSC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 18452889, 18455129, 21739581, 27148795, 31606977; Phenotypes: Mental retardation, autosomal recessive 7, MIM# 611093, MONDO:0012615, TUSC3-CDG (Disorders of protein N-glycosylation); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5766 TMEM165 Zornitza Stark Gene: tmem165 has been classified as Green List (High Evidence).
Mendeliome v0.5763 SLC35D1 Zornitza Stark Phenotypes for gene: SLC35D1 were changed from Schneckenbecken dysplasia, MIM 269250 to Schneckenbecken dysplasia, MIM 269250, MONDO:0010013; O-xylosyl/N-acetylgalactosaminylglycan synthesis deficiencies (Disorders of protein O-glycosylation)
Mendeliome v0.5761 SLC35D1 Zornitza Stark reviewed gene: SLC35D1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17952091, 19508970, 31423530; Phenotypes: Schneckenbecken dysplasia 269250, O-xylosyl/N-acetylgalactosaminylglycan synthesis deficiencies (Disorders of protein O-glycosylation); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5761 SLC35C1 Zornitza Stark Gene: slc35c1 has been classified as Green List (High Evidence).
Mendeliome v0.5756 GNE Zornitza Stark Gene: gne has been classified as Green List (High Evidence).
Mendeliome v0.5756 GNE Zornitza Stark Phenotypes for gene: GNE were changed from to Nonaka myopathy 605820; Sialuria MIM#269921; ADUDP-GlcNAc epimerase/kinase deficiency (Disorders of multiple glycosylation and other glycosylation pathways)
Mendeliome v0.5753 GNE Zornitza Stark reviewed gene: GNE: Rating: GREEN; Mode of pathogenicity: None; Publications: 12177386, 12473753, 32053088, 29923088, 10356312, 11326336, 11486897, 27142465; Phenotypes: Nonaka myopathy 605820, Sialuria MIM#269921, ADUDP-GlcNAc epimerase/kinase deficiency (Disorders of multiple glycosylation and other glycosylation pathways); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5753 EXT2 Zornitza Stark Gene: ext2 has been classified as Green List (High Evidence).
Mendeliome v0.5752 TBL1X Zornitza Stark Gene: tbl1x has been classified as Green List (High Evidence).
Mendeliome v0.5752 TBL1X Zornitza Stark Classified gene: TBL1X as Green List (high evidence)
Mendeliome v0.5752 TBL1X Zornitza Stark Gene: tbl1x has been classified as Green List (High Evidence).
Mendeliome v0.5751 CHSY1 Zornitza Stark edited their review of gene: CHSY1: Changed phenotypes: Temtamy preaxial brachydactyly syndrome, MIM# 605282, MONDO:0011533, CHSY1-CDG (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies)
Mendeliome v0.5751 CHSY1 Zornitza Stark Gene: chsy1 has been classified as Green List (High Evidence).
Mendeliome v0.5751 CHSY1 Zornitza Stark Phenotypes for gene: CHSY1 were changed from to Temtamy preaxial brachydactyly syndrome, MIM# 605282, MONDO:0011533; CHSY1-CDG (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies)
Mendeliome v0.5748 CHSY1 Zornitza Stark reviewed gene: CHSY1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21129728, 21129727, 24269551; Phenotypes: VTemtamy preaxial brachydactyly syndrome, MIM# 605282, MONDO:0011533, CHSY1-CDG (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5748 DHDDS Zornitza Stark Gene: dhdds has been classified as Green List (High Evidence).
Mendeliome v0.5743 FBLN1 Zornitza Stark Gene: fbln1 has been classified as Red List (Low Evidence).
Mendeliome v0.5740 FBLN1 Zornitza Stark Classified gene: FBLN1 as Red List (low evidence)
Mendeliome v0.5740 FBLN1 Zornitza Stark Gene: fbln1 has been classified as Red List (Low Evidence).
Mendeliome v0.5739 ST3GAL5 Zornitza Stark Gene: st3gal5 has been classified as Green List (High Evidence).
Mendeliome v0.5739 ST3GAL5 Zornitza Stark Phenotypes for gene: ST3GAL5 were changed from to Salt and pepper developmental regression syndrome 609056; GM3 synthase deficiency, MONDO:0018274; Lactosylceramide alpha-2,3-sialyltransferase deficiency (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation)
Mendeliome v0.5736 ST3GAL5 Zornitza Stark reviewed gene: ST3GAL5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23436467, 22990144, 15502825, 27232954, 30691927, 30688114, 30576498; Phenotypes: Salt and pepper developmental regression syndrome 609056, GM3 synthase deficiency, MONDO:0018274, Lactosylceramide alpha-2,3-sialyltransferase deficiency (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5736 SUCLA2 Zornitza Stark Gene: sucla2 has been classified as Green List (High Evidence).
Mendeliome v0.5733 RFT1 Zornitza Stark Gene: rft1 has been classified as Green List (High Evidence).
Mendeliome v0.5730 CHST6 Zornitza Stark Gene: chst6 has been classified as Green List (High Evidence).
Mendeliome v0.5727 MGAT2 Zornitza Stark Gene: mgat2 has been classified as Green List (High Evidence).
Mendeliome v0.5724 MPI Zornitza Stark Gene: mpi has been classified as Green List (High Evidence).
Mendeliome v0.5721 PGM3 Zornitza Stark Gene: pgm3 has been classified as Green List (High Evidence).
Mendeliome v0.5718 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.
Mendeliome v0.5718 PGAP3 Zornitza Stark Gene: pgap3 has been classified as Green List (High Evidence).
Mendeliome v0.5718 PGAP3 Zornitza Stark Phenotypes for gene: PGAP3 were changed from to Hyperphosphatasia with mental retardation syndrome 4, MIM# 615716, MONDO:0014318
Mendeliome v0.5715 PGAP3 Zornitza Stark reviewed gene: PGAP3: Rating: GREEN; Mode of pathogenicity: None; Publications: 24439110, 29620724, 30345601, 30217754; Phenotypes: Hyperphosphatasia with mental retardation syndrome 4, MIM# 615716, MONDO:0014318; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5715 PGAP2 Zornitza Stark Gene: pgap2 has been classified as Green List (High Evidence).
Mendeliome v0.5715 PGAP2 Zornitza Stark Phenotypes for gene: PGAP2 were changed from to Hyperphosphatasia with mental retardation syndrome 3, MIM# 614207, MONDO:0013628
Mendeliome v0.5712 PGAP2 Zornitza Stark reviewed gene: PGAP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23561846, 23561847, 31805394, 29119105, 27871432; Phenotypes: Hyperphosphatasia with mental retardation syndrome 3, MIM# 614207, MONDO:0013628; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5712 PIGV Zornitza Stark Gene: pigv has been classified as Green List (High Evidence).
Mendeliome v0.5712 PIGV Zornitza Stark Phenotypes for gene: PIGV were changed from to Hyperphosphatasia with mental retardation syndrome 1, MIM# 239300, MONDO:0009398
Mendeliome v0.5709 PIGV Zornitza Stark reviewed gene: PIGV: Rating: GREEN; Mode of pathogenicity: None; Publications: 20802478, 22315194, 28817240, 24129430; Phenotypes: Hyperphosphatasia with mental retardation syndrome 1, MIM# 239300, MONDO:0009398; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5708 PIGO Zornitza Stark Gene: pigo has been classified as Green List (High Evidence).
Mendeliome v0.5708 PIGO Zornitza Stark Phenotypes for gene: PIGO were changed from to Hyperphosphatasia with mental retardation syndrome 2, MIM# 614749, MONDO:0013882
Mendeliome v0.5705 PIGO Zornitza Stark reviewed gene: PIGO: Rating: GREEN; Mode of pathogenicity: None; Publications: 22683086, 31698102, 28900819, 28545593, 28337824; Phenotypes: Hyperphosphatasia with mental retardation syndrome 2, MIM# 614749, MONDO:0013882; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5705 PIGN Zornitza Stark Gene: pign has been classified as Green List (High Evidence).
Mendeliome v0.5702 PIGA Zornitza Stark Gene: piga has been classified as Green List (High Evidence).
Mendeliome v0.5699 PIGL Zornitza Stark Gene: pigl has been classified as Green List (High Evidence).
Mendeliome v0.5696 B3GALT6 Zornitza Stark Gene: b3galt6 has been classified as Green List (High Evidence).
Mendeliome v0.5696 B3GALT6 Zornitza Stark Phenotypes for gene: B3GALT6 were changed from to Al-Gazali syndrome, MIM# 609465; Ehlers-Danlos syndrome, spondylodysplastic type, 2, MIM# 615349, MONDO:0014139; Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures, MIM# 271640, MONDO:0010075
Mendeliome v0.5693 B3GALT6 Zornitza Stark reviewed gene: B3GALT6: Rating: GREEN; Mode of pathogenicity: None; Publications: 25149931, 29443383, 23664117, 29931299, 23664117, 23664118, 31614862; Phenotypes: Al-Gazali syndrome, MIM# 609465, Ehlers-Danlos syndrome, spondylodysplastic type, 2, MIM# 615349, MONDO:0014139, Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures, MIM# 271640, MONDO:0010075; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5693 B3GALNT2 Zornitza Stark Gene: b3galnt2 has been classified as Green List (High Evidence).
Mendeliome v0.5690 MPDU1 Zornitza Stark Gene: mpdu1 has been classified as Green List (High Evidence).
Mendeliome v0.5687 DPAGT1 Zornitza Stark Gene: dpagt1 has been classified as Green List (High Evidence).
Mendeliome v0.5684 DPAGT1 Zornitza Stark changed review comment from: Type I CDG. More than 20 unrelated families reported. Most affected individuals have a very severe disease course, where common findings are pronounced muscular hypotonia, intractable epilepsy, global developmental delay/intellectual disability, and early death. Additional features that may be observed include apnoea and respiratory deficiency, cataracts, joint contractures, vermian hypoplasia, dysmorphic features (esotropia, arched palate, micrognathia, finger clinodactyly, single flexion creases) and feeding difficulties.

Myasthenic syndrome, congenital, 13, with tubular aggregates, MIM 614750 is a milder allelic disorder.; to: Type I CDG. More than 20 unrelated families reported. Most affected individuals have a very severe disease course, where common findings are pronounced muscular hypotonia, intractable epilepsy, global developmental delay/intellectual disability, and early death. Additional features that may be observed include apnoea and respiratory deficiency, cataracts, joint contractures, vermian hypoplasia, dysmorphic features (esotropia, arched palate, micrognathia, finger clinodactyly, single flexion creases) and feeding difficulties.

Myasthenic syndrome, congenital, 13, with tubular aggregates, MIM 614750 is a milder allelic disorder. More than 5 unrelated families reported with this presentation.
Mendeliome v0.5684 DOLK Zornitza Stark Gene: dolk has been classified as Green List (High Evidence).
Mendeliome v0.5681 SLC2A1 Zornitza Stark Gene: slc2a1 has been classified as Green List (High Evidence).
Mendeliome v0.5681 SLC2A1 Zornitza Stark Phenotypes for gene: SLC2A1 were changed from to GLUT1 deficiency syndrome 1, infantile onset, severe, MIM#606777; Dystonia 9, MIM#601042; Stomatin-deficient cryohydrocytosis with neurologic defects, MIM#608885; GLUT1 deficiency syndrome 2, childhood onset, MIM#612126; {Epilepsy, idiopathic generalized, susceptibility to, 12}, MIM#614847
Mendeliome v0.5678 MTX2 Zornitza Stark Phenotypes for gene: MTX2 were changed from Mandibuloacral dysplasia; lipodystrophy; arterial calcification to Mandibuloacral dysplasia progeroid syndrome, MIM# 619127; Mandibuloacral dysplasia; lipodystrophy; arterial calcification
Mendeliome v0.5677 MTX2 Zornitza Stark edited their review of gene: MTX2: Changed phenotypes: Mandibuloacral dysplasia progeroid syndrome, MIM# 619127, Mandibuloacral dysplasia, lipodystrophy, arterial calcification
Mendeliome v0.5677 SLC2A1 Elena Savva reviewed gene: SLC2A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:18451999, 20129935, 10980529, 20221955, 31196579; Phenotypes: GLUT1 deficiency syndrome 1, infantile onset, severe, MIM#606777, Dystonia 9, MIM#601042, Stomatin-deficient cryohydrocytosis with neurologic defects, MIM#608885, GLUT1 deficiency syndrome 2, childhood onset, MIM#612126, {Epilepsy, idiopathic generalized, susceptibility to, 12}, MIM#614847; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.5677 ERCC1 Zornitza Stark Gene: ercc1 has been classified as Green List (High Evidence).
Mendeliome v0.5674 POR Zornitza Stark Gene: por has been classified as Green List (High Evidence).
Mendeliome v0.5674 POR Zornitza Stark Phenotypes for gene: POR were changed from to Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis, MIM#201750; Disordered steroidogenesis due to cytochrome P450 oxidoreductase, MIM#613571
Mendeliome v0.5671 MYH6 Zornitza Stark Gene: myh6 has been classified as Green List (High Evidence).
Mendeliome v0.5671 MYH6 Zornitza Stark Phenotypes for gene: MYH6 were changed from to Atrial septal defect 3 MIM#614089; Congenital heart disease; Cardiomyopathy, dilated, 1EE MIM#613252; Cardiomyopathy, hypertrophic, 14 MIM#613251; {Sick sinus syndrome 3} MIM#614090
Mendeliome v0.5668 MYH6 Zornitza Stark reviewed gene: MYH6: Rating: GREEN; Mode of pathogenicity: None; Publications: 32656206, 31638415, 29969989, 29536580, 29332214, 30681346; Phenotypes: Atrial septal defect 3 MIM#614089, Congenital heart disease, Cardiomyopathy, dilated, 1EE MIM#613252, Cardiomyopathy, hypertrophic, 14 MIM#613251, {Sick sinus syndrome 3} MIM#614090; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5668 EZH2 Zornitza Stark Gene: ezh2 has been classified as Green List (High Evidence).
Mendeliome v0.5665 POR Elena Savva reviewed gene: POR: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27068427; Phenotypes: Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis, MIM#201750, Disordered steroidogenesis due to cytochrome P450 oxidoreductase, MIM#613571; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.5665 MYH6 Elena Savva reviewed gene: MYH6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Atrial septal defect 3 MIM#614089, Cardiomyopathy, dilated, 1EE MIM#613252, Cardiomyopathy, hypertrophic, 14 MIM#613251, {Sick sinus syndrome 3} MIM#614090; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.5665 COG6 Zornitza Stark Gene: cog6 has been classified as Green List (High Evidence).
Mendeliome v0.5662 COG5 Zornitza Stark Gene: cog5 has been classified as Green List (High Evidence).
Mendeliome v0.5659 FIGLA Zornitza Stark Gene: figla has been classified as Green List (High Evidence).
Mendeliome v0.5656 ESR1 Zornitza Stark Gene: esr1 has been classified as Green List (High Evidence).
Mendeliome v0.5656 ESR1 Zornitza Stark Phenotypes for gene: ESR1 were changed from to Estrogen resistance, MIM# 615363
Mendeliome v0.5653 ESR1 Zornitza Stark reviewed gene: ESR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27754803, 23841731, 24152274; Phenotypes: Estrogen resistance, MIM# 615363; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5653 SHMT2 Zornitza Stark Phenotypes for gene: SHMT2 were changed from Congenital microcephaly; Infantile axial hypotonia; Spastic paraparesis; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum; Abnormal cortical gyration; Hypertrophic cardiomyopathy; Abnormality of the face; Proximal placement of thumb; 2-3 toe syndactyly to Neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities (NEDCASB), MIM#619121; Congenital microcephaly; Infantile axial hypotonia; Spastic paraparesis; Global developmental delay; Intellectual disability; Abnormality of the corpus callosum; Abnormal cortical gyration; Hypertrophic cardiomyopathy; Abnormality of the face; Proximal placement of thumb; 2-3 toe syndactyly
Mendeliome v0.5652 SHMT2 Zornitza Stark edited their review of gene: SHMT2: Changed phenotypes: Neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities (NEDCASB), MIM#619121, Congenital microcephaly, Infantile axial hypotonia, Spastic paraparesis, Global developmental delay, Intellectual disability, Abnormality of the corpus callosum, Abnormal cortical gyration, Hypertrophic cardiomyopathy, Abnormality of the face, Proximal placement of thumb, 2-3 toe syndactyly
Mendeliome v0.5652 BMP15 Zornitza Stark Gene: bmp15 has been classified as Green List (High Evidence).
Mendeliome v0.5652 BMP15 Zornitza Stark Phenotypes for gene: BMP15 were changed from to Ovarian dysgenesis 2, MIM# 300510; Premature ovarian failure 4, MIM# 300510
Mendeliome v0.5649 BMP15 Zornitza Stark reviewed gene: BMP15: Rating: GREEN; Mode of pathogenicity: None; Publications: 15136966, 16508750, 16464940; Phenotypes: Ovarian dysgenesis 2, MIM# 300510, Premature ovarian failure 4, MIM# 300510; Mode of inheritance: Other
Mendeliome v0.5649 PANX1 Zornitza Stark Gene: panx1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5649 PANX1 Zornitza Stark Classified gene: PANX1 as Amber List (moderate evidence)
Mendeliome v0.5649 PANX1 Zornitza Stark Gene: panx1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5647 NANOS3 Bryony Thompson Gene: nanos3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5647 NANOS3 Bryony Thompson Classified gene: NANOS3 as Amber List (moderate evidence)
Mendeliome v0.5647 NANOS3 Bryony Thompson Gene: nanos3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5646 NANOS3 Bryony Thompson gene: NANOS3 was added
gene: NANOS3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NANOS3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: NANOS3 were set to 25054146; 24091668
Phenotypes for gene: NANOS3 were set to Primary ovarian insufficiency
Review for gene: NANOS3 was set to AMBER
Added comment: A homozygous missense (p.Glu120Lys) was identified in two Brazillian sisters with primary amenorrhea, and supporting in vitro functional assays. A heterozygous missense (p.Arg153Trp) was identified in a Chinese woman with POI, with supporting in vitro functional assays. Also, supporting null mouse model.
Sources: Literature
Mendeliome v0.5645 MSH5 Bryony Thompson Gene: msh5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5645 MSH5 Bryony Thompson Classified gene: MSH5 as Amber List (moderate evidence)
Mendeliome v0.5645 MSH5 Bryony Thompson Gene: msh5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5644 MSH5 Bryony Thompson gene: MSH5 was added
gene: MSH5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MSH5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MSH5 were set to 28175301; 9916805; 24970489
Phenotypes for gene: MSH5 were set to Premature ovarian failure 13 MIM#617442
Review for gene: MSH5 was set to AMBER
Added comment: A homozygous missense mutation (p.D487Y) in two sisters with POI. Also, homologous mutation in mice results in atrophic ovaries without oocytes, and in vitro functional study revealed that mutant MSH5 impaired DNA homologous recombination repair. Null mouse model is viable, but sterile. A case with congenital adrenal hyperplasia, ovarian failure and Ehlers-Danlos syndrome had a de novo t(6;14)(p21;q32) translocation, including CYP21A2,TNXB and MSH5.
Sources: Literature
Mendeliome v0.5643 PATL2 Zornitza Stark Gene: patl2 has been classified as Green List (High Evidence).
Mendeliome v0.5643 PATL2 Zornitza Stark Classified gene: PATL2 as Green List (high evidence)
Mendeliome v0.5643 PATL2 Zornitza Stark Gene: patl2 has been classified as Green List (High Evidence).
Mendeliome v0.5639 FANCM Bryony Thompson Classified gene: FANCM as Green List (high evidence)
Mendeliome v0.5639 FANCM Bryony Thompson Added comment: Comment on list classification: Green for POI
Mendeliome v0.5639 FANCM Bryony Thompson Gene: fancm has been classified as Green List (High Evidence).
Mendeliome v0.5638 EIF4ENIF1 Bryony Thompson Gene: eif4enif1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5638 PGRMC1 Zornitza Stark Gene: pgrmc1 has been classified as Red List (Low Evidence).
Mendeliome v0.5637 EIF4ENIF1 Bryony Thompson Classified gene: EIF4ENIF1 as Amber List (moderate evidence)
Mendeliome v0.5637 EIF4ENIF1 Bryony Thompson Gene: eif4enif1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5635 POF1B Zornitza Stark Gene: pof1b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5632 POF1B Zornitza Stark Classified gene: POF1B as Amber List (moderate evidence)
Mendeliome v0.5632 POF1B Zornitza Stark Gene: pof1b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5631 DIAPH2 Bryony Thompson Gene: diaph2 has been classified as Red List (Low Evidence).
Mendeliome v0.5631 DIAPH2 Bryony Thompson Classified gene: DIAPH2 as Red List (low evidence)
Mendeliome v0.5631 DIAPH2 Bryony Thompson Gene: diaph2 has been classified as Red List (Low Evidence).
Mendeliome v0.5630 CCDC141 Bryony Thompson Gene: ccdc141 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5630 POU5F1 Zornitza Stark gene: POU5F1 was added
gene: POU5F1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: POU5F1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POU5F1 were set to 21273125
Phenotypes for gene: POU5F1 were set to Premature ovarian failure
Review for gene: POU5F1 was set to RED
Added comment: Single individual reported in 2011 and a missense variant.
Sources: Expert list
Mendeliome v0.5629 CCDC141 Bryony Thompson Classified gene: CCDC141 as Amber List (moderate evidence)
Mendeliome v0.5629 CCDC141 Bryony Thompson Gene: ccdc141 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5627 SGO2 Zornitza Stark Gene: sgo2 has been classified as Red List (Low Evidence).
Mendeliome v0.5627 SGO2 Zornitza Stark gene: SGO2 was added
gene: SGO2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SGO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SGO2 were set to 27629923
Phenotypes for gene: SGO2 were set to Perrault syndrome
Review for gene: SGO2 was set to RED
Added comment: Single affected individual reported, though deafness was thought to be explained by a CLDN14 variant. Protein is known to be involved in meiosis.
Sources: Expert list
Mendeliome v0.5626 SOHLH2 Zornitza Stark Gene: sohlh2 has been classified as Red List (Low Evidence).
Mendeliome v0.5625 SYCE1 Zornitza Stark Gene: syce1 has been classified as Green List (High Evidence).
Mendeliome v0.5625 SYCE1 Zornitza Stark Classified gene: SYCE1 as Green List (high evidence)
Mendeliome v0.5625 SYCE1 Zornitza Stark Gene: syce1 has been classified as Green List (High Evidence).
Mendeliome v0.5624 SYCE1 Zornitza Stark gene: SYCE1 was added
gene: SYCE1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SYCE1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SYCE1 were set to 25062452; 32917591; 32741963; 32402064; 31925770; 31916078
Phenotypes for gene: SYCE1 were set to Premature ovarian failure 12, MIM# 616947; Spermatogenic failure 15 ,MIM#616950
Review for gene: SYCE1 was set to GREEN
Added comment: More than 5 families reported with POF/SF and bi-allelic variants in this gene. Mechanism is thought to be disruption of meiosis, mouse model data also supports gene-disease association.
Sources: Expert list
Mendeliome v0.5623 DACH2 Zornitza Stark Gene: dach2 has been classified as Red List (Low Evidence).
Mendeliome v0.5622 TUBB8 Zornitza Stark Gene: tubb8 has been classified as Green List (High Evidence).
Mendeliome v0.5619 WEE2 Zornitza Stark Gene: wee2 has been classified as Green List (High Evidence).
Mendeliome v0.5616 ZP1 Zornitza Stark Gene: zp1 has been classified as Green List (High Evidence).
Mendeliome v0.5616 ZP1 Zornitza Stark Classified gene: ZP1 as Green List (high evidence)
Mendeliome v0.5616 ZP1 Zornitza Stark Gene: zp1 has been classified as Green List (High Evidence).
Mendeliome v0.5613 ZP3 Zornitza Stark Gene: zp3 has been classified as Green List (High Evidence).
Mendeliome v0.5613 ZP3 Zornitza Stark Classified gene: ZP3 as Green List (high evidence)
Mendeliome v0.5613 ZP3 Zornitza Stark Gene: zp3 has been classified as Green List (High Evidence).
Mendeliome v0.5611 ECEL1P2 Zornitza Stark Gene: ecel1p2 has been classified as Red List (Low Evidence).
Mendeliome v0.5611 ECEL1P2 Zornitza Stark Classified gene: ECEL1P2 as Red List (low evidence)
Mendeliome v0.5611 ECEL1P2 Zornitza Stark Gene: ecel1p2 has been classified as Red List (Low Evidence).
Mendeliome v0.5609 CDC40 Zornitza Stark Gene: cdc40 has been classified as Red List (Low Evidence).
Mendeliome v0.5609 CDC40 Zornitza Stark gene: CDC40 was added
gene: CDC40 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CDC40 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDC40 were set to 33220177
Phenotypes for gene: CDC40 were set to Pontocerebellar hypoplasia; microcephaly; seizures
Review for gene: CDC40 was set to RED
Added comment: Single individual reported with bi-allelic variants in the gene and PCH, microcephaly, hypotonia, seizures, severe DD/ID, thrombocytopaenia, anaemia. Interaction with PPIL1 and mouse model support gene-disease association. Gene referred to as PRP17 in paper.
Sources: Literature
Mendeliome v0.5608 PPIL1 Zornitza Stark Gene: ppil1 has been classified as Green List (High Evidence).
Mendeliome v0.5608 PPIL1 Zornitza Stark Classified gene: PPIL1 as Green List (high evidence)
Mendeliome v0.5608 PPIL1 Zornitza Stark Gene: ppil1 has been classified as Green List (High Evidence).
Mendeliome v0.5607 PPIL1 Zornitza Stark gene: PPIL1 was added
gene: PPIL1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PPIL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPIL1 were set to 33220177
Phenotypes for gene: PPIL1 were set to Pontocerebellar hypoplasia; microcephaly; seizures
Review for gene: PPIL1 was set to GREEN
Added comment: 17 individuals from 9 unrelated families reported with bi-allelic variants in the gene and PCH, microcephaly, hypotonia, seizures, severe DD/ID. Mouse models support gene-disease association.
Sources: Literature
Mendeliome v0.5606 FRA12A Bryony Thompson Classified STR: FRA12A as Amber List (moderate evidence)
Mendeliome v0.5606 FRA12A Bryony Thompson Str: fra12a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5605 FRA12A Bryony Thompson STR: FRA12A was added
STR: FRA12A was added to Mendeliome. Sources: Other
5'UTR tags were added to STR: FRA12A.
Mode of inheritance for STR: FRA12A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: FRA12A were set to 17236128
Phenotypes for STR: FRA12A were set to Mental retardation, FRA12A type MIM#136630
Review for STR: FRA12A was set to AMBER
Added comment: NM_173602.2:c.-137CGG[X]
All individuals expressing FRA12A had CGG-repeat expansion. The length of the expanded allele in 3 unaffected FRA12A carriers was 650–850 bp. In the two affected patients from 2 families with FRA12A, the length of the expanded allele was ∼1,050-1,150 bp.
70 controls used to determine the "normal" repeat range.
Sources: Other
Mendeliome v0.5604 DIP2B Bryony Thompson Classified gene: DIP2B as No list
Mendeliome v0.5604 DIP2B Bryony Thompson Added comment: Comment on list classification: Only repeat expansion reported. Added as an STR
Mendeliome v0.5603 DIP2B Bryony Thompson Classified gene: DIP2B as No list
Mendeliome v0.5603 DIP2B Bryony Thompson Added comment: Comment on list classification: Only repeat expansion reported. Added as an STR
Mendeliome v0.5601 CANVAS_ACAGG Bryony Thompson changed review comment from: A novel RFC1 repeat expansion motif, (ACAGG)exp, identified in three affected individuals from 2 families in an Asian-Pacific cohort for CANVAS. Southern blot was used to identify the repeat was ~1000kb in one of the cases, equivalent to ~1000 repeats.
Sources: Literature; to: A novel RFC1 repeat expansion motif, (ACAGG)exp, identified homozygous in three affected individuals from 2 families in an Asian-Pacific cohort for CANVAS. Southern blot was used to identify the repeat was ~1000kb in one of the cases, equivalent to ~1000 repeats.
Sources: Literature
Mendeliome v0.5601 CANVAS_ACAGG Bryony Thompson Str: canvas_acagg has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5601 CANVAS_ACAGG Bryony Thompson Classified STR: CANVAS_ACAGG as Amber List (moderate evidence)
Mendeliome v0.5601 CANVAS_ACAGG Bryony Thompson Added comment: Comment on list classification: Used the pathogenic cut-off of 400 repeats from original CANVAS repeat
Mendeliome v0.5601 CANVAS_ACAGG Bryony Thompson Str: canvas_acagg has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5600 CANVAS_ACAGG Bryony Thompson STR: CANVAS_ACAGG was added
STR: CANVAS_ACAGG was added to Mendeliome. Sources: Literature
Mode of inheritance for STR: CANVAS_ACAGG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for STR: CANVAS_ACAGG were set to 33103729
Phenotypes for STR: CANVAS_ACAGG were set to Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome; fasciculations; elevated serum creatine kinase levels; denervation
Review for STR: CANVAS_ACAGG was set to AMBER
Added comment: A novel RFC1 repeat expansion motif, (ACAGG)exp, identified in three affected individuals from 2 families in an Asian-Pacific cohort for CANVAS. Southern blot was used to identify the repeat was ~1000kb in one of the cases, equivalent to ~1000 repeats.
Sources: Literature
Mendeliome v0.5599 CANVAS Bryony Thompson Str: canvas has been classified as Green List (High Evidence).
Mendeliome v0.5599 CANVAS Bryony Thompson Classified STR: CANVAS as Green List (high evidence)
Mendeliome v0.5599 CANVAS Bryony Thompson Str: canvas has been classified as Green List (High Evidence).
Mendeliome v0.5598 CANVAS Bryony Thompson STR: CANVAS was added
STR: CANVAS was added to Mendeliome. Sources: Expert list
Mode of inheritance for STR: CANVAS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for STR: CANVAS were set to 30926972; 32851396
Phenotypes for STR: CANVAS were set to Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome MIM#614575
Review for STR: CANVAS was set to GREEN
STR: CANVAS was marked as clinically relevant
Added comment: Simple tandem repeat (AAAAG)11 replaced with (AAGGG)n in intron 2 of RFC1. Loss of function is not the mechanism of disease. Maori population-specific CANVAS configuration (AAAGG)10-25(AAGGG)exp. (AAAGG)n repeat alone is not pathogenic.
Sources: Expert list
Mendeliome v0.5597 RFC1 Bryony Thompson Classified gene: RFC1 as No list
Mendeliome v0.5595 RNASEH2C Zornitza Stark Gene: rnaseh2c has been classified as Green List (High Evidence).
Mendeliome v0.5592 CFAP52 Zornitza Stark Gene: cfap52 has been classified as Green List (High Evidence).
Mendeliome v0.5592 CFAP52 Zornitza Stark Classified gene: CFAP52 as Green List (high evidence)
Mendeliome v0.5592 CFAP52 Zornitza Stark Gene: cfap52 has been classified as Green List (High Evidence).
Mendeliome v0.5591 CFAP45 Zornitza Stark Gene: cfap45 has been classified as Green List (High Evidence).
Mendeliome v0.5591 CFAP45 Zornitza Stark Classified gene: CFAP45 as Green List (high evidence)
Mendeliome v0.5591 CFAP45 Zornitza Stark Gene: cfap45 has been classified as Green List (High Evidence).
Mendeliome v0.5590 LMX1B Zornitza Stark Phenotypes for gene: LMX1B were changed from Nail-patella syndrome (MIM#161200), MONDO:0008061; LMX1B-related nephropathy to Nail-patella syndrome (MIM#161200), MONDO:0008061; LMX1B-related nephropathy; Focal segmental glomerulosclerosis-10 (FSGS10), MIM#256020
Mendeliome v0.5589 LMX1B Zornitza Stark edited their review of gene: LMX1B: Changed phenotypes: Nail-patella syndrome (MIM#161200), MONDO:0008061, LMX1B-related nephropathy, Focal segmental glomerulosclerosis-10 (FSGS10), MIM#256020
Mendeliome v0.5589 RAP1A Zornitza Stark Gene: rap1a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5586 RAP1A Zornitza Stark Classified gene: RAP1A as Amber List (moderate evidence)
Mendeliome v0.5586 RAP1A Zornitza Stark Gene: rap1a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5584 RAP1B Zornitza Stark Classified gene: RAP1B as Green List (high evidence)
Mendeliome v0.5584 RAP1B Zornitza Stark Gene: rap1b has been classified as Green List (High Evidence).
Mendeliome v0.5583 RAP1B Zornitza Stark Gene: rap1b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5580 RAP1B Zornitza Stark Classified gene: RAP1B as Amber List (moderate evidence)
Mendeliome v0.5580 RAP1B Zornitza Stark Gene: rap1b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5579 EMC10 Zornitza Stark Gene: emc10 has been classified as Red List (Low Evidence).
Mendeliome v0.5579 EMC10 Zornitza Stark gene: EMC10 was added
gene: EMC10 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EMC10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EMC10 were set to 32869858
Phenotypes for gene: EMC10 were set to Intellectual disability
Review for gene: EMC10 was set to RED
Added comment: Homozygous variants of EMC1 are associated with GDD, scoliosis, and cerebellar atrophy, indicating the relevance of this pathway for neurogenetic disorders.

One Saudi family with 2 affected individuals with mild ID, speech delay, and GDD.
WES and Sanger sequencing revealed a homozygous splice acceptor site variant (c.679‐1G>A) in EMC10 . Variant segregated within the family. RT‐qPCR showed a substantial decrease in the relative EMC10 gene expression in the patients.
Sources: Literature
Mendeliome v0.5578 FBXO28 Zornitza Stark Gene: fbxo28 has been classified as Green List (High Evidence).
Mendeliome v0.5578 FBXO28 Zornitza Stark Classified gene: FBXO28 as Green List (high evidence)
Mendeliome v0.5578 FBXO28 Zornitza Stark Gene: fbxo28 has been classified as Green List (High Evidence).
Mendeliome v0.5577 FBXO28 Zornitza Stark gene: FBXO28 was added
gene: FBXO28 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FBXO28 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FBXO28 were set to 33280099
Phenotypes for gene: FBXO28 were set to Developmental and epileptic encephalopathy
Review for gene: FBXO28 was set to GREEN
Added comment: Nine new individuals with FBXO28 pathogenic variants (four missense, including one recurrent, three nonsense, and one frameshift) and all 10 known cases reviewed to delineate the phenotypic spectrum. All had epilepsy and 9 of 10 had DEE, including infantile spasms (3) and a progressive myoclonic epilepsy (1). Median age at seizure onset was 22.5 months (range 8 months to 5 years). Nine of 10 patients had intellectual disability, which was profound in six of nine and severe in three of nine. Movement disorders occurred in eight of 10 patients, six of 10 had hypotonia, four of 10 had acquired microcephaly, and five of 10 had dysmorphic features.
Sources: Literature
Mendeliome v0.5575 CFAP45 Zornitza Stark gene: CFAP45 was added
gene: CFAP45 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CFAP45 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP45 were set to 33139725
Phenotypes for gene: CFAP45 were set to Situs inversus; asthenospermia
Review for gene: CFAP45 was set to GREEN
Added comment: Three unrelated individuals reported with bi-alleic LOF variants, mouse model recapitulated phenotype.
Sources: Literature
Mendeliome v0.5573 CLCN6 Zornitza Stark Classified gene: CLCN6 as Green List (high evidence)
Mendeliome v0.5573 CLCN6 Zornitza Stark Gene: clcn6 has been classified as Green List (High Evidence).
Mendeliome v0.5572 CLCN6 Zornitza Stark edited their review of gene: CLCN6: Added comment: Three unrelated families reported with recurrent GOF de novo c.1658A>G (p.Tyr553Cys) and severe developmental delay with pronounced generalized hypotonia, respiratory insufficiency, and variable neurodegeneration and diffusion restriction in cerebral peduncles, midbrain, and/or brainstem in MRI scans.; Changed rating: GREEN; Changed publications: 25794116, 21107136, 33217309; Changed phenotypes: Neurodegeneration, Benign partial epilepsy, febrile seizures, NCL; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5572 GDF6 Zornitza Stark Phenotypes for gene: GDF6 were changed from Klippel-Feil syndrome 1, autosomal dominant 118100; Leber congenital amaurosis 17 615360; Microphthalmia with coloboma 6, digenic 613703; Microphthalmia, isolated 4 613094; Multiple synostoses syndrome 4 617898 to Klippel-Feil syndrome 1, autosomal dominant 118100; Leber congenital amaurosis 17 615360; Microphthalmia with coloboma 6, digenic 613703; Microphthalmia, isolated 4 613094; Multiple synostoses syndrome 4 617898; CAKUT
Mendeliome v0.5571 GDF6 Zornitza Stark Gene: gdf6 has been classified as Green List (High Evidence).
Mendeliome v0.5571 GDF6 Zornitza Stark Phenotypes for gene: GDF6 were changed from to Klippel-Feil syndrome 1, autosomal dominant 118100; Leber congenital amaurosis 17 615360; Microphthalmia with coloboma 6, digenic 613703; Microphthalmia, isolated 4 613094; Multiple synostoses syndrome 4 617898
Mendeliome v0.5567 GDF6 Belinda Chong reviewed gene: GDF6: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32737436; Phenotypes: Klippel-Feil syndrome 1, autosomal dominant 118100, Leber congenital amaurosis 17 615360, Microphthalmia with coloboma 6, digenic 613703, Microphthalmia, isolated 4 613094, Multiple synostoses syndrome 4 617898; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.5567 VPS4A Kristin Rigbye changed review comment from: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain.
1x homozygous missense in the MIT domain (milder phenotype and unaffected parents).
Demonstrated defective CD71 trafficking in all 3 patients.

PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly).
Demonstrated that the variants had a dominant-negative effect on VPS4A function.
"The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life."
Sources: Literature; to: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain.
1x homozygous missense in the MIT domain (milder phenotype and unaffected parents - possibly just a simple LoF mechanism for AR inheritance).
Demonstrated defective CD71 trafficking in all 3 patients.

PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly).
Demonstrated that the variants had a dominant-negative effect on VPS4A function.

"The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life."
Mendeliome v0.5567 VPS4A Elena Savva changed review comment from: Comment when marking as ready: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents). Demonstrated defective CD71 trafficking in all 3 patients. PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. "The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life."; to: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain.
1x homozygous missense in the MIT domain (milder phenotype and unaffected parents).
Demonstrated defective CD71 trafficking in all 3 patients.

Comment when marking as ready: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents). Demonstrated defective CD71 trafficking in all 3 patients. PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. "The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life."
Mendeliome v0.5567 VPS4A Elena Savva Added comment: Comment when marking as ready: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain. 1x homozygous missense in the MIT domain (milder phenotype and unaffected parents). Demonstrated defective CD71 trafficking in all 3 patients. PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly). Demonstrated that the variants had a dominant-negative effect on VPS4A function. "The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life."
Mendeliome v0.5567 VPS4A Elena Savva Gene: vps4a has been classified as Green List (High Evidence).
Mendeliome v0.5566 VPS4A Elena Savva Classified gene: VPS4A as Green List (high evidence)
Mendeliome v0.5566 VPS4A Elena Savva Gene: vps4a has been classified as Green List (High Evidence).
Mendeliome v0.5565 DAAM2 Zornitza Stark reviewed gene: DAAM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33232676; Phenotypes: Steroid-resistant nephrotic syndrome (SRNS); Mode of inheritance: None
Mendeliome v0.5565 DAAM2 Zornitza Stark Gene: daam2 has been classified as Green List (High Evidence).
Mendeliome v0.5564 DAAM2 Zornitza Stark Classified gene: DAAM2 as Green List (high evidence)
Mendeliome v0.5564 DAAM2 Zornitza Stark Gene: daam2 has been classified as Green List (High Evidence).
Mendeliome v0.5563 HS2ST1 Zornitza Stark Gene: hs2st1 has been classified as Green List (High Evidence).
Mendeliome v0.5563 BICRA Elena Savva Gene: bicra has been classified as Green List (High Evidence).
Mendeliome v0.5563 BICRA Elena Savva Classified gene: BICRA as Green List (high evidence)
Mendeliome v0.5563 BICRA Elena Savva Gene: bicra has been classified as Green List (High Evidence).
Mendeliome v0.5562 HS2ST1 Zornitza Stark Classified gene: HS2ST1 as Green List (high evidence)
Mendeliome v0.5562 HS2ST1 Zornitza Stark Gene: hs2st1 has been classified as Green List (High Evidence).
Mendeliome v0.5561 KDM4B Zornitza Stark Gene: kdm4b has been classified as Green List (High Evidence).
Mendeliome v0.5561 KDM4B Zornitza Stark Classified gene: KDM4B as Green List (high evidence)
Mendeliome v0.5561 KDM4B Zornitza Stark Gene: kdm4b has been classified as Green List (High Evidence).
Mendeliome v0.5560 SMG8 Zornitza Stark Classified gene: SMG8 as Green List (high evidence)
Mendeliome v0.5560 SMG8 Zornitza Stark Gene: smg8 has been classified as Green List (High Evidence).
Mendeliome v0.5559 UNC45B Zornitza Stark Gene: unc45b has been classified as Green List (High Evidence).
Mendeliome v0.5559 UNC45B Zornitza Stark Classified gene: UNC45B as Green List (high evidence)
Mendeliome v0.5559 UNC45B Zornitza Stark Gene: unc45b has been classified as Green List (High Evidence).
Mendeliome v0.5558 VPS4A Kristin Rigbye gene: VPS4A was added
gene: VPS4A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: VPS4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VPS4A were set to PMID: 33186543; 33186545
Phenotypes for gene: VPS4A were set to Neurodevelopmental disorder
Review for gene: VPS4A was set to GREEN
Added comment: PMID: 33186543 - 2x de novo hetorozygous missense variants in the AAA (large ATPase) domain.
1x homozygous missense in the MIT domain (milder phenotype and unaffected parents).
Demonstrated defective CD71 trafficking in all 3 patients.

PMID: 33186545 - 6x probands with de novo missense variants in the AAA domain. 5 of the variants were at amino acid position 284 (changes to Trp and Gly).
Demonstrated that the variants had a dominant-negative effect on VPS4A function.
"The six probands with de novo substitutions affecting Glu206 or Arg284 had a consistent phenotype characterized by severe DD, profound ID, and dystonia. Children were very delayed in establishing head control and none achieved independent walking. Other common findings were cerebellar hypoplasia (five individuals out of six, the other showing uncharacterized severe cerebral atrophy) with a variable degree of corpus callosum hypoplasia. One individual also had bilateral polymicrogyria. Epilepsy was present in three and dystonia in five subjects. Eye involvement was also a common finding, including congenital cataract, retinal dystrophy, and in one case congenital Leber amaurosis. Four individuals were diagnosed with hepatosplenomegaly and/or steatosis. Three subjects had anemia, which was characterized as dyserythropoietic in two. Severe feeding difficulties were present in four individuals, requiring assisted feeding in three. Two had sensorineural deafness. Severe growth retardation, generally for all parameters, was present in most cases. Notably, severe microcephaly (typically with Z scores < −5) was universal. Overall, the disorder seems to have a poor prognosis as two affected individuals died in childhood or early adult life."
Sources: Literature
Mendeliome v0.5558 AGO2 Zornitza Stark Gene: ago2 has been classified as Green List (High Evidence).
Mendeliome v0.5558 AGO2 Zornitza Stark Classified gene: AGO2 as Green List (high evidence)
Mendeliome v0.5558 AGO2 Zornitza Stark Gene: ago2 has been classified as Green List (High Evidence).
Mendeliome v0.5556 DAAM2 Ain Roesley gene: DAAM2 was added
gene: DAAM2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DAAM2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DAAM2 were set to steroid-resistant nephrotic syndrome (SRNS)
Penetrance for gene: DAAM2 were set to unknown
Review for gene: DAAM2 was set to GREEN
Added comment: - steroid-resistant nephrotic syndrome (SRNS) with focal segmental glomerulosclerosis on histologic analysis of kidney biopsies and foot process effacement shown by electron microscopy (authors have suggested the term nephrotic syndrome type 22 (NPHS22))
- 4 unrelated families, 3 of which were consanguineous
- 4 unique missense and 1 stop
- in vitro studies done for the missense variants
Sources: Literature
Mendeliome v0.5556 RRP7A Zornitza Stark Gene: rrp7a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5556 RRP7A Zornitza Stark Classified gene: RRP7A as Amber List (moderate evidence)
Mendeliome v0.5556 RRP7A Zornitza Stark Gene: rrp7a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5555 RRP7A Zornitza Stark gene: RRP7A was added
gene: RRP7A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RRP7A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RRP7A were set to 33199730
Phenotypes for gene: RRP7A were set to Microcephaly
Review for gene: RRP7A was set to AMBER
Added comment: 10 affected individuals from a single large consanguineous family where bi-allelic variant segregated with severe microcephaly (-6-8SD), variable ID. Supportive functional data from mouse and zebrafish.
Sources: Literature
Mendeliome v0.5554 HS2ST1 Ain Roesley gene: HS2ST1 was added
gene: HS2ST1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HS2ST1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HS2ST1 were set to 33159882
Penetrance for gene: HS2ST1 were set to unknown
Review for gene: HS2ST1 was set to GREEN
Added comment: - 4 affected from 3 unrelated families
- 3 unique missense and 2 PTCs
- Developmental Delay, Corpus Callosum Hypoplasia or Aplasia, and Skeletal and Renal Abnormalities
Sources: Literature
Mendeliome v0.5554 MINPP1 Zornitza Stark Gene: minpp1 has been classified as Green List (High Evidence).
Mendeliome v0.5554 MINPP1 Zornitza Stark Classified gene: MINPP1 as Green List (high evidence)
Mendeliome v0.5554 MINPP1 Zornitza Stark Gene: minpp1 has been classified as Green List (High Evidence).
Mendeliome v0.5553 KDM4B Kristin Rigbye gene: KDM4B was added
gene: KDM4B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KDM4B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KDM4B were set to PMID: 33232677
Phenotypes for gene: KDM4B were set to Global developmental delay, intellectual disability and neuroanatomical defects
Review for gene: KDM4B was set to GREEN
Added comment: Nine individuals with mono-allelic de novo or inherited variants in KDM4B.

All individuals presented with dysmorphic features and global developmental delay (GDD) with language and motor skills most affected. Three individuals had a history of seizures, and four had anomalies on brain imaging ranging from agenesis of the corpus callosum with hydrocephalus to cystic formations, abnormal hippocampi, and polymicrogyria.

In a knockout mouse the total brain volume was significantly reduced with decreased
size of the hippocampal dentate gyrus, partial agenesis of the corpus callosum, and ventriculomegaly.
Sources: Literature
Mendeliome v0.5553 MINPP1 Zornitza Stark gene: MINPP1 was added
gene: MINPP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MINPP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MINPP1 were set to 33257696
Phenotypes for gene: MINPP1 were set to Pontocerebellar hypoplasia
Review for gene: MINPP1 was set to GREEN
Added comment: 8 individuals from 6 unrelated families reported with bi-allelic LOF variants. All presented with almost complete absence of motor and cognitive development, progressive or congenital microcephaly, spastic tetraplegia or dystonia, and vision impairments. For most, the first symptoms included neonatal severe axial hypotonia and epilepsy that started during the first months or years of life. Prenatal symptoms of microcephaly associated with increased thalami echogenicity were detected in one, while the seven other individuals presented with progressive microcephaly. Some exhibited rapidly progressive phenotype and the affected children died in their infancy or middle-childhood. Strikingly, all the affected children had a unique brain MRI showing a mild to severe PCH, fluid-filled posterior fossa, with dilated lateral ventricles. In addition, severe atrophy at the level of the basal ganglia or thalami often associated with typical T2 hypersignal were identified in all the patients MRI.

Supportive functional data showing accumulation of highly phosphorylated inositols, mostly inositol hexakisphosphate (IP6), detected in HEK293 cells, fibroblasts, iPSCs and differentiating neurons lacking MINPP1. In mutant cells, higher IP6 level is expected to be associated with an increased chelation of intracellular cations, such as iron or calcium, resulting in decreased levels of available ions.
Sources: Literature
Mendeliome v0.5552 UNC45B Paul De Fazio gene: UNC45B was added
gene: UNC45B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: UNC45B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UNC45B were set to 33217308
Phenotypes for gene: UNC45B were set to Progressive Myopathy with Eccentric Cores
Review for gene: UNC45B was set to GREEN
gene: UNC45B was marked as current diagnostic
Added comment: 10 individuals from 8 families reported with biallelic variants clinically manifesting with childhood-onset, progressive proximal and axial muscle weakness and various degrees of respiratory insufficiency. 4 missense variants and a +5 splice variant reported, p.Arg754Gln is recurrent. Functional studies support pathogenicity.
Sources: Literature
Mendeliome v0.5549 DNAJB11 Zornitza Stark edited their review of gene: DNAJB11: Added comment: Single family reported with bi-allelic variant and severe, fetal onset renal cystic disease, dilation and proliferation of pancreatic duct cells, and liver ductal plate malformation, an association known as Ivemark II syndrome.; Changed publications: 29706351, 29777155, 33129895; Changed phenotypes: Polycystic kidney disease 6 with or without polycystic liver disease, MIM#618061, Ivermark II syndrome.; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.5549 MYLPF Zornitza Stark Phenotypes for gene: MYLPF were changed from Distal arthrogryoposis to Distal arthrogryposis type 1C (DA1C), MIM#619110
Mendeliome v0.5548 MYLPF Zornitza Stark edited their review of gene: MYLPF: Changed rating: AMBER; Changed phenotypes: Distal arthrogryposis type 1C (DA1C), MIM#619110; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5548 HHAT Zornitza Stark Gene: hhat has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5548 HHAT Zornitza Stark Classified gene: HHAT as Amber List (moderate evidence)
Mendeliome v0.5548 HHAT Zornitza Stark Gene: hhat has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5547 HHAT Zornitza Stark gene: HHAT was added
gene: HHAT was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: HHAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HHAT were set to 24784881; 30912300
Phenotypes for gene: HHAT were set to Nivelon-Nivelon-Mabille syndrome 600092
Review for gene: HHAT was set to AMBER
Added comment: Two unrelated families reported. Clinical features include progressive microcephaly, cerebellar vermis hypoplasia, and skeletal dysplasia. Variable features include infantile-onset seizures, dwarfism, generalized chondrodysplasia, and micromelia.
Sources: Expert list
Mendeliome v0.5545 H3F3B Zornitza Stark Phenotypes for gene: H3F3B were changed from to Intellectual disability; regression; seizures
Mendeliome v0.5542 H3F3B Zornitza Stark Classified gene: H3F3B as Green List (high evidence)
Mendeliome v0.5542 H3F3B Zornitza Stark Gene: h3f3b has been classified as Green List (High Evidence).
Mendeliome v0.5541 H3F3B Zornitza Stark edited their review of gene: H3F3B: Added comment: 13 unrelated individuals reported with missense variants in H3F3B. Phenotype primarily comprised intellectual disability and minor congenital anomalies, regression in significant proportion. Seizures in 50%.; Changed rating: GREEN; Changed publications: 33268356; Changed phenotypes: Intellectual disability, regression, seizures; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5541 H3F3A Zornitza Stark Phenotypes for gene: H3F3A were changed from to Intellectual disability; regression; seizures
Mendeliome v0.5538 H3F3A Zornitza Stark Classified gene: H3F3A as Green List (high evidence)
Mendeliome v0.5538 H3F3A Zornitza Stark Gene: h3f3a has been classified as Green List (High Evidence).
Mendeliome v0.5537 H3F3A Zornitza Stark edited their review of gene: H3F3A: Changed phenotypes: Intellectual disability, regression, seizures
Mendeliome v0.5537 H3F3A Zornitza Stark edited their review of gene: H3F3A: Added comment: 33 unrelated individuals reported with missense variants in H3F3A. Phenotype primarily comprised intellectual disability and minor congenital anomalies, regression in significant proportion. Seizures in 50%.; Changed rating: GREEN; Changed publications: 33268356; Changed phenotypes: Intellectual disability, regression; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5537 ALDH7A1 Zornitza Stark Gene: aldh7a1 has been classified as Green List (High Evidence).
Mendeliome v0.5534 PRPS1 Zornitza Stark Gene: prps1 has been classified as Green List (High Evidence).
Mendeliome v0.5534 PRPS1 Zornitza Stark Phenotypes for gene: PRPS1 were changed from to Arts syndrome MIM#301835; Charcot-Marie-Tooth disease, X-linked recessive, 5 MIM#311070; Deafness, X-linked 1 MIM#304500; Gout, PRPS-related MIM#300661; Phosphoribosylpyrophosphate synthetase superactivity MIM#300661
Mendeliome v0.5530 HIVEP2 Zornitza Stark Gene: hivep2 has been classified as Green List (High Evidence).
Mendeliome v0.5527 PRPS1 Elena Savva reviewed gene: PRPS1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 32781272, 17701896, 7593598; Phenotypes: Arts syndrome MIM#301835, Charcot-Marie-Tooth disease, X-linked recessive, 5 MIM#311070, Deafness, X-linked 1 MIM#304500, Gout, PRPS-related MIM#300661, Phosphoribosylpyrophosphate synthetase superactivity MIM#300661; 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 v0.5527 YIPF5 Zornitza Stark Gene: yipf5 has been classified as Green List (High Evidence).
Mendeliome v0.5527 YIPF5 Zornitza Stark Classified gene: YIPF5 as Green List (high evidence)
Mendeliome v0.5527 YIPF5 Zornitza Stark Gene: yipf5 has been classified as Green List (High Evidence).
Mendeliome v0.5526 YIPF5 Zornitza Stark gene: YIPF5 was added
gene: YIPF5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: YIPF5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YIPF5 were set to 33164986
Phenotypes for gene: YIPF5 were set to Neonatal diabetes; microcephaly; seizures
Review for gene: YIPF5 was set to GREEN
Added comment: Six individuals from 5 unrelated consanguineous families reported with bi-allelic variants in this gene and neonatal/early-onset diabetes, severe microcephaly, and epilepsy. Functional data supports gene-disease association.
Sources: Literature
Mendeliome v0.5523 SLC38A8 Zornitza Stark Gene: slc38a8 has been classified as Green List (High Evidence).
Mendeliome v0.5523 SLC38A8 Zornitza Stark Phenotypes for gene: SLC38A8 were changed from to Foveal hypoplasia 2, with or without optic nerve misrouting and/or anterior segment dysgenesis OMIM:609218; foveal hypoplasia - optic nerve decussation defect - anterior segment dysgenesis syndrome MONDO:0012216
Mendeliome v0.5520 CAPN15 Zornitza Stark Gene: capn15 has been classified as Green List (High Evidence).
Mendeliome v0.5520 CAPN15 Zornitza Stark Classified gene: CAPN15 as Green List (high evidence)
Mendeliome v0.5520 CAPN15 Zornitza Stark Gene: capn15 has been classified as Green List (High Evidence).
Mendeliome v0.5519 TONSL Zornitza Stark Gene: tonsl has been classified as Green List (High Evidence).
Mendeliome v0.5519 TONSL Zornitza Stark Phenotypes for gene: TONSL were changed from to Spondyloepimetaphyseal dysplasia, sponastrime type OMIM:271510; spondyloepimetaphyseal dysplasia, sponastrime type MONDO:0010068
Mendeliome v0.5516 FKBP8 Zornitza Stark Gene: fkbp8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5516 FKBP8 Zornitza Stark Classified gene: FKBP8 as Amber List (moderate evidence)
Mendeliome v0.5516 FKBP8 Zornitza Stark Gene: fkbp8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5515 NPPA Zornitza Stark Classified gene: NPPA as Amber List (moderate evidence)
Mendeliome v0.5515 NPPA Zornitza Stark Gene: nppa has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5514 NPPA Zornitza Stark Gene: nppa has been classified as Green List (High Evidence).
Mendeliome v0.5511 FOXA2 Zornitza Stark Gene: foxa2 has been classified as Green List (High Evidence).
Mendeliome v0.5511 FOXA2 Zornitza Stark Classified gene: FOXA2 as Green List (high evidence)
Mendeliome v0.5511 FOXA2 Zornitza Stark Gene: foxa2 has been classified as Green List (High Evidence).
Mendeliome v0.5507 USP7 Zornitza Stark edited their review of gene: USP7: Added comment: Hao-Fountain syndrome (HAFOUS) is a neurodevelopmental disorder characterized by global developmental delay, variably impaired intellectual development with significant speech delay, behavioral abnormalities, such as autism, and mild dysmorphic facies. Additional features are variable, but may include hypotonia, feeding problems, delayed walking with unsteady gait, hypogonadism in males, and ocular anomalies, such as strabismus. Some patients develop seizures and some have mild white matter abnormalities on brain imaging.; Changed publications: 26365382, 30679821; Changed phenotypes: Hao-Fountain syndrome, MIM# 616863, Intellectual disability, Autism
Mendeliome v0.5507 FKBP8 Eleanor Williams gene: FKBP8 was added
gene: FKBP8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FKBP8 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FKBP8 were set to 32969478
Phenotypes for gene: FKBP8 were set to spina bifida HP:0002414
Review for gene: FKBP8 was set to AMBER
Added comment: Not associated with a phenotype in OMIM.

PMID: 32969478 - Tian et al 2020 - performed Sanger sequencing of FKBP8 on DNA samples from 472 spina bifida (SB) affected fetuses and 565 unaffected controls. 5 different rare heterozygous variants (MAF ≤ 0.001) were identified among the SB patients, while no deleterious rare variants were identified in the controls. 4 of the variants are missense, the other is a stop-gain. 2 cases were in white-Hispanic patients while the other 3 were non-white Hispanic. Functional studies showed that p.Glu140* affected FKBP8 localization to the mitochondria and impaired its interaction with BCL2 ultimately leading to an increase in cellular apoptosis. p.Ser3Leu, p.Lys315Asn and p.Ala292Ser variants decreased FKBP8 protein level. Gene expression was studied in mouse Fkbp8-/- embryos and found to be abnormal. Previous mouse models have shown neural tube defects.

Sufficient cases to rate green, but only the FKBP8 gene looked at so perhaps some caution required while further evidence is gathered.
Sources: Literature
Mendeliome v0.5507 TONSL Eleanor Williams reviewed gene: TONSL: Rating: GREEN; Mode of pathogenicity: None; Publications: 30773277, 30773278, 32959051; Phenotypes: Spondyloepimetaphyseal dysplasia, sponastrime type OMIM:271510, spondyloepimetaphyseal dysplasia, sponastrime type MONDO:0010068; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5507 CAPN15 Eleanor Williams changed review comment from: PMID: 32885237 - Zha et al 2020 - report 5 individuals with microphthalmia and/or coloboma from 4 independent families who, through WES, were identified as carrying homozygous or compound heterozygous missense variants in CAPN15 that are predicted to be damanging. the variants segregated with the disease in all 4 families, with parents being unaffected heterozygous carriers. Several individuals had additional phenotypes including growth deficits (2 families), developmental delay (2 families) and hearing loss (2 families).
Sources: Literature; to: PMID: 32885237 - Zha et al 2020 - report 5 individuals with microphthalmia and/or coloboma from 4 independent families who, through WES, were identified as carrying homozygous or compound heterozygous missense variants in CAPN15 that are predicted to be damanging. the variants segregated with the disease in all 4 families, with parents being unaffected heterozygous carriers. Several individuals had additional phenotypes including growth deficits (2 families), developmental delay (2 families) and hearing loss (2 families). Capn15 knockout mice showed similar severe developmental eye defects, including anophthalmia, microphthalmia and cataract, and diminished growth.

Sources: Literature
Mendeliome v0.5507 SLC38A8 Eleanor Williams reviewed gene: SLC38A8: Rating: GREEN; Mode of pathogenicity: None; Publications: 32744312; Phenotypes: Foveal hypoplasia 2, with or without optic nerve misrouting and/or anterior segment dysgenesis OMIM:609218, foveal hypoplasia - optic nerve decussation defect - anterior segment dysgenesis syndrome MONDO:0012216; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5507 MYF5 Zornitza Stark Gene: myf5 has been classified as Green List (High Evidence).
Mendeliome v0.5503 TARS2 Zornitza Stark edited their review of gene: TARS2: Added comment: Second family reported, single affected individual, compound heterozygous missense variants, computational data only in support of pathogenicity.; Changed publications: 24827421, 26811336, 33153448
Mendeliome v0.5503 COX16 Bryony Thompson Gene: cox16 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5503 COX16 Bryony Thompson Classified gene: COX16 as Amber List (moderate evidence)
Mendeliome v0.5503 COX16 Bryony Thompson Gene: cox16 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5502 COX16 Bryony Thompson gene: COX16 was added
gene: COX16 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: COX16 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COX16 were set to 33169484
Phenotypes for gene: COX16 were set to Hypertrophic cardiomyopathy; encephalopathy; severe fatal lactic acidosis
Review for gene: COX16 was set to AMBER
Added comment: 2 unrelated patients with the same homozygous (non-consanguineous) nonsense variant c.244C>T (p.Arg82*), and isolated complex IV deficiency present in both patient fibroblasts/skeletal muscle biopsy. COX16 is involved in the biogenesis of complex IV, the terminal complex of the mitochondrial respiratory chain (RC)
Sources: Literature
Mendeliome v0.5501 THBD Bryony Thompson Classified gene: THBD as Green List (high evidence)
Mendeliome v0.5501 THBD Bryony Thompson Gene: thbd has been classified as Green List (High Evidence).
Mendeliome v0.5500 KCNJ18 Zornitza Stark Gene: kcnj18 has been classified as Red List (Low Evidence).
Mendeliome v0.5500 KCNJ18 Zornitza Stark gene: KCNJ18 was added
gene: KCNJ18 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: KCNJ18 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNJ18 were set to 20074522; 27008341
Phenotypes for gene: KCNJ18 were set to {Thyrotoxic periodic paralysis, susceptibility to, 2}, MIM# 613239
Review for gene: KCNJ18 was set to RED
Added comment: Six variants reported in original publication, however note lack of segregation data and limited functional data. Subsequently, concerns raised about high nucleotide sequence homology between multiple potassium channel genes, with variant misattribution.
Sources: Expert Review
Mendeliome v0.5499 DPM3 Zornitza Stark Gene: dpm3 has been classified as Green List (High Evidence).
Mendeliome v0.5496 B3GAT3 Zornitza Stark Gene: b3gat3 has been classified as Green List (High Evidence).
Mendeliome v0.5493 SLC10A7 Zornitza Stark Gene: slc10a7 has been classified as Green List (High Evidence).
Mendeliome v0.5493 SLC10A7 Zornitza Stark Phenotypes for gene: SLC10A7 were changed from to Short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis, MIM# 618363
Mendeliome v0.5490 SLC10A7 Zornitza Stark reviewed gene: SLC10A7: Rating: GREEN; Mode of pathogenicity: None; Publications: 30082715, 29878199, 31191616; Phenotypes: Short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis, MIM# 618363; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5486 GPAA1 Zornitza Stark Gene: gpaa1 has been classified as Green List (High Evidence).
Mendeliome v0.5486 GPAA1 Zornitza Stark Phenotypes for gene: GPAA1 were changed from to Glycosylphosphatidylinositol biosynthesis defect 15, MIM#617810
Mendeliome v0.5483 GPAA1 Zornitza Stark edited their review of gene: GPAA1: Added comment: 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.; Changed publications: 29100095
Mendeliome v0.5483 ATP7A Zornitza Stark Gene: atp7a has been classified as Green List (High Evidence).
Mendeliome v0.5483 ATP7A Zornitza Stark Phenotypes for gene: ATP7A were changed from to Occipital horn syndrome, 304150; X-linked recessive Menkes disease, 309400 Spinal muscular atrophy, distal, X-linked 3, 300489
Mendeliome v0.5480 PEX1 Zornitza Stark Gene: pex1 has been classified as Green List (High Evidence).
Mendeliome v0.5480 PEX1 Zornitza Stark Phenotypes for gene: PEX1 were changed from to Heimler syndrome 1 234580; Peroxisome biogenesis disorder 1A (Zellweger) 214100; . Peroxisome biogenesis disorder 1B (NALD/IRD) 601539
Mendeliome v0.5476 HDAC4 Bryony Thompson Classified gene: HDAC4 as Green List (high evidence)
Mendeliome v0.5476 HDAC4 Bryony Thompson Gene: hdac4 has been classified as Green List (High Evidence).
Mendeliome v0.5474 ATP7A Elena Savva reviewed gene: ATP7A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 21221114; Phenotypes: Occipital horn syndrome, 304150, X-linked recessive Menkes disease, 309400 Spinal muscular atrophy, distal, X-linked 3, 300489; 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 v0.5474 PEX1 Elena Savva reviewed gene: PEX1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26387595; Phenotypes: Heimler syndrome 1 234580, Peroxisome biogenesis disorder 1A (Zellweger) 214100, . Peroxisome biogenesis disorder 1B (NALD/IRD) 601539; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5474 TMEM218 Bryony Thompson Gene: tmem218 has been classified as Green List (High Evidence).
Mendeliome v0.5474 TMEM218 Bryony Thompson Classified gene: TMEM218 as Green List (high evidence)
Mendeliome v0.5474 TMEM218 Bryony Thompson Gene: tmem218 has been classified as Green List (High Evidence).
Mendeliome v0.5473 TMEM218 Bryony Thompson gene: TMEM218 was added
gene: TMEM218 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TMEM218 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM218 were set to https://doi.org/10.1016/j.xhgg.2020.100016; 25161209
Phenotypes for gene: TMEM218 were set to Joubert syndrome; retinal dystrophy; polycystic kidneys; occipital encephalocele
Review for gene: TMEM218 was set to GREEN
Added comment: 11 cases in 6 families with homozygous or compound heterozygous missense and nonsense (1) variants, with a Joubert/Meckel syndrome phenotype. Clinical features included the molar tooth sign (N=2), occipital encephalocele (N=5, all fetuses), retinal dystrophy (N=4, all living individuals), polycystic kidneys (N=2), and polydactyly (N=2), without liver involvement. A null mouse model had nephronophthisis and retinal degeneration. No OMIM entry.
Sources: Literature
Mendeliome v0.5472 AGBL1 Zornitza Stark Gene: agbl1 has been classified as Red List (Low Evidence).
Mendeliome v0.5471 TLE6 Zornitza Stark Gene: tle6 has been classified as Green List (High Evidence).
Mendeliome v0.5471 TLE6 Zornitza Stark Classified gene: TLE6 as Green List (high evidence)
Mendeliome v0.5471 TLE6 Zornitza Stark Gene: tle6 has been classified as Green List (High Evidence).
Mendeliome v0.5469 OGT Zornitza Stark Gene: ogt has been classified as Green List (High Evidence).
Mendeliome v0.5466 EXTL3 Zornitza Stark Gene: extl3 has been classified as Green List (High Evidence).
Mendeliome v0.5466 EXTL3 Zornitza Stark Phenotypes for gene: EXTL3 were changed from to Immunoskeletal dysplasia with neurodevelopmental abnormalities, MIM# 617425
Mendeliome v0.5463 EXTL3 Zornitza Stark reviewed gene: EXTL3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28132690, 28148688, 28331220; Phenotypes: Immunoskeletal dysplasia with neurodevelopmental abnormalities, MIM# 617425; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5463 SSR3 Zornitza Stark Gene: ssr3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5463 SSR3 Zornitza Stark Classified gene: SSR3 as Amber List (moderate evidence)
Mendeliome v0.5463 SSR3 Zornitza Stark Gene: ssr3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5462 SSR3 Zornitza Stark gene: SSR3 was added
gene: SSR3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SSR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SSR3 were set to 30945312
Phenotypes for gene: SSR3 were set to Congenital disorder of glycosylation
Review for gene: SSR3 was set to AMBER
Added comment: Single individual reported with an unsolved type I CDG, intellectual disability, homozygous LOF variant in SSR3, supportive functional evidence.
Sources: Literature
Mendeliome v0.5461 LCP2 Zornitza Stark Gene: lcp2 has been classified as Red List (Low Evidence).
Mendeliome v0.5459 DPM2 Zornitza Stark Classified gene: DPM2 as Green List (high evidence)
Mendeliome v0.5459 DPM2 Zornitza Stark Gene: dpm2 has been classified as Green List (High Evidence).
Mendeliome v0.5458 ATP6V0A2 Zornitza Stark Gene: atp6v0a2 has been classified as Green List (High Evidence).
Mendeliome v0.5458 ATP6V0A2 Zornitza Stark Phenotypes for gene: ATP6V0A2 were changed from to Cutis laxa, autosomal recessive, type IIA, MIM# 219200; Wrinkly skin syndrome, MIM#278250
Mendeliome v0.5455 ATP6V0A2 Zornitza Stark reviewed gene: ATP6V0A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29952037, 22773132; Phenotypes: Cutis laxa, autosomal recessive, type IIA, MIM# 219200, Wrinkly skin syndrome, MIM#278250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5455 ALG9 Zornitza Stark Gene: alg9 has been classified as Green List (High Evidence).
Mendeliome v0.5449 ALG8 Zornitza Stark changed review comment from: Review of 15 reported individuals in PMID: 26066342: multiple prenatal abnormalities were present in 6/12 patients. In 13/15, there were symptoms at birth, 9/15 died within 12 months. Birth weight was appropriate in 11/12, only one was small for gestational age. Prematurity was reported in 7/12. Hydrops fetalis was noticed in 3, edemas in 11/13; gastrointestinal symptoms in 9/14; structural brain pathology, psychomental retardation, seizures, ataxia in 12/13, muscle hypotonia in 13/14. Common dysmorphic signs were: low set ears, macroglossia, hypertelorism, pes equinovarus, campto- and brachydactyly (13/15). In 10/11, there was coagulopathy, in 8/11 elevated transaminases; thrombocytopenia was present in 9/9. Eye involvement was reported in 9/14. CDG typical skin involvement was reported in 8/13.; to: Bi-allelic variants and CDG: Review of 15 reported individuals in PMID: 26066342. Multiple prenatal abnormalities were present in 6/12 patients. In 13/15, there were symptoms at birth, 9/15 died within 12 months. Birth weight was appropriate in 11/12, only one was small for gestational age. Prematurity was reported in 7/12. Hydrops fetalis was noticed in 3, edemas in 11/13; gastrointestinal symptoms in 9/14; structural brain pathology, psychomental retardation, seizures, ataxia in 12/13, muscle hypotonia in 13/14. Common dysmorphic signs were: low set ears, macroglossia, hypertelorism, pes equinovarus, campto- and brachydactyly (13/15). In 10/11, there was coagulopathy, in 8/11 elevated transaminases; thrombocytopenia was present in 9/9. Eye involvement was reported in 9/14. CDG typical skin involvement was reported in 8/13.
Mendeliome v0.5449 ALG8 Zornitza Stark Gene: alg8 has been classified as Green List (High Evidence).
Mendeliome v0.5446 ALG3 Zornitza Stark Gene: alg3 has been classified as Green List (High Evidence).
Mendeliome v0.5441 SLC3A2 Zornitza Stark Gene: slc3a2 has been classified as Red List (Low Evidence).
Mendeliome v0.5441 SLC3A2 Zornitza Stark Classified gene: SLC3A2 as Red List (low evidence)
Mendeliome v0.5441 SLC3A2 Zornitza Stark Gene: slc3a2 has been classified as Red List (Low Evidence).
Mendeliome v0.5440 HOXA4 Zornitza Stark Gene: hoxa4 has been classified as Red List (Low Evidence).
Mendeliome v0.5439 HOXA4 Zornitza Stark Phenotypes for gene: HOXA4 were changed from to Microtia-Atresia; CAKUT
Mendeliome v0.5436 HOXA4 Zornitza Stark Classified gene: HOXA4 as Red List (low evidence)
Mendeliome v0.5436 HOXA4 Zornitza Stark Gene: hoxa4 has been classified as Red List (Low Evidence).
Mendeliome v0.5435 ASTE1 Zornitza Stark Gene: aste1 has been classified as Red List (Low Evidence).
Mendeliome v0.5435 ASTE1 Zornitza Stark Phenotypes for gene: ASTE1 were changed from to palmar and plantar fibromatosis
Mendeliome v0.5432 ASTE1 Zornitza Stark Classified gene: ASTE1 as Red List (low evidence)
Mendeliome v0.5432 ASTE1 Zornitza Stark Gene: aste1 has been classified as Red List (Low Evidence).
Mendeliome v0.5431 HOXA4 Naomi Baker reviewed gene: HOXA4: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 33193662; Phenotypes: Microtia-Atresia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5431 ASTE1 Naomi Baker reviewed gene: ASTE1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 29104234; Phenotypes: palmar and plantar fibromatosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5431 SMARCA1 Zornitza Stark Gene: smarca1 has been classified as Red List (Low Evidence).
Mendeliome v0.5428 SMARCA1 Zornitza Stark Classified gene: SMARCA1 as Red List (low evidence)
Mendeliome v0.5428 SMARCA1 Zornitza Stark Gene: smarca1 has been classified as Red List (Low Evidence).
Mendeliome v0.5427 CDKAL1 Zornitza Stark Gene: cdkal1 has been classified as Red List (Low Evidence).
Mendeliome v0.5427 CDKAL1 Zornitza Stark Classified gene: CDKAL1 as Red List (low evidence)
Mendeliome v0.5427 CDKAL1 Zornitza Stark Gene: cdkal1 has been classified as Red List (Low Evidence).
Mendeliome v0.5426 TCHH Zornitza Stark Gene: tchh has been classified as Red List (Low Evidence).
Mendeliome v0.5423 TCHH Zornitza Stark Classified gene: TCHH as Red List (low evidence)
Mendeliome v0.5423 TCHH Zornitza Stark Gene: tchh has been classified as Red List (Low Evidence).
Mendeliome v0.5422 CRTAP Zornitza Stark Gene: crtap has been classified as Green List (High Evidence).
Mendeliome v0.5422 CRTAP Zornitza Stark Phenotypes for gene: CRTAP were changed from to Osteogenesis imperfecta, type VII MIM#610682
Mendeliome v0.5419 USP9X Zornitza Stark Gene: usp9x has been classified as Green List (High Evidence).
Mendeliome v0.5416 ALG6 Zornitza Stark Gene: alg6 has been classified as Green List (High Evidence).
Mendeliome v0.5412 RORB Zornitza Stark Gene: rorb has been classified as Green List (High Evidence).
Mendeliome v0.5412 RORB Zornitza Stark Phenotypes for gene: RORB were changed from to {Epilepsy, idiopathic generalized, susceptibility to, 15} (MIM#618357), AD; Genetic generalized epilepsy (GGE); Photosensitive generalized and occipital epilepsy
Mendeliome v0.5409 RORB Zornitza Stark reviewed gene: RORB: Rating: GREEN; Mode of pathogenicity: None; Publications: 27352968, 32162308; Phenotypes: {Epilepsy, idiopathic generalized, susceptibility to, 15} (MIM#618357), AD, Genetic generalized epilepsy (GGE), Photosensitive generalized and occipital epilepsy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5409 MYL9 Zornitza Stark Gene: myl9 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5409 MYL9 Zornitza Stark Classified gene: MYL9 as Amber List (moderate evidence)
Mendeliome v0.5409 MYL9 Zornitza Stark Gene: myl9 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5408 MYL9 Zornitza Stark gene: MYL9 was added
gene: MYL9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MYL9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYL9 were set to 29453416; 33031641
Phenotypes for gene: MYL9 were set to Megacystis-microcolon-intestinal hypoperistalsis syndrome
Review for gene: MYL9 was set to AMBER
Added comment: Two unrelated families reported.
Sources: Literature
Mendeliome v0.5407 CRTAP Paul De Fazio reviewed gene: CRTAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 21955071, 19846465, 17192541; Phenotypes: Osteogenesis imperfecta, type VII MIM#610682; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.5405 PHYKPL Zornitza Stark Gene: phykpl has been classified as Red List (Low Evidence).
Mendeliome v0.5405 PHYKPL Zornitza Stark Phenotypes for gene: PHYKPL were changed from to [?Phosphohydroxylysinuria] 615011
Mendeliome v0.5402 PHYKPL Zornitza Stark Classified gene: PHYKPL as Red List (low evidence)
Mendeliome v0.5402 PHYKPL Zornitza Stark Gene: phykpl has been classified as Red List (Low Evidence).
Mendeliome v0.5401 MTCL1 Bryony Thompson Classified gene: MTCL1 as Green List (high evidence)
Mendeliome v0.5401 MTCL1 Bryony Thompson Gene: mtcl1 has been classified as Green List (High Evidence).
Mendeliome v0.5400 MTCL1 Bryony Thompson edited their review of gene: MTCL1: Added comment: A new report of another case with a homozygous loss of function variant and a similar phenotype to the previously reported early onset homozygous Polish case (2 independent cases), and the supporting null mouse model.; Changed rating: GREEN; Changed publications: 30548255, 28283581, 32961396; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5400 PHYKPL Elena Savva reviewed gene: PHYKPL: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 23242558; Phenotypes: [?Phosphohydroxylysinuria] 615011; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5400 POLE Zornitza Stark Gene: pole has been classified as Green List (High Evidence).
Mendeliome v0.5396 OFD1 Zornitza Stark Gene: ofd1 has been classified as Green List (High Evidence).
Mendeliome v0.5396 OFD1 Zornitza Stark Phenotypes for gene: OFD1 were changed from to Joubert syndrome 10, 300804; Simpson-Golabi-Behmel syndrome, type 2, 300209; Orofaciodigital syndrome I, 311200; Retinitis pigmentosa 23, 300424
Mendeliome v0.5393 OFD1 Elena Savva reviewed gene: OFD1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31373179, 23033313, 16783569; Phenotypes: ?Retinitis pigmentosa 23, 300424, Joubert syndrome 10, 300804, Simpson-Golabi-Behmel syndrome, type 2, 300209, Orofaciodigital syndrome I, 311200; Mode of inheritance: Other
Mendeliome v0.5389 DZIP1 Zornitza Stark Gene: dzip1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5388 DZIP1 Zornitza Stark Classified gene: DZIP1 as Amber List (moderate evidence)
Mendeliome v0.5388 DZIP1 Zornitza Stark Gene: dzip1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5386 ADH5 Zornitza Stark Gene: adh5 has been classified as Green List (High Evidence).
Mendeliome v0.5386 ADH5 Zornitza Stark Classified gene: ADH5 as Green List (high evidence)
Mendeliome v0.5386 ADH5 Zornitza Stark Gene: adh5 has been classified as Green List (High Evidence).
Mendeliome v0.5385 ADH5 Zornitza Stark gene: ADH5 was added
gene: ADH5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ADH5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADH5 were set to 33147438
Phenotypes for gene: ADH5 were set to Aplastic anaemia; myelodysplasia; short stature
Review for gene: ADH5 was set to GREEN
Added comment: 7 individuals reported with bi-allelic variants in this gene and a Fanconi syndrome-like phenotype. All had aplastic anaemia, 4 developed a myelodysplastic syndrome, and one developed AML. Short stature and abnormal skin pigmentation were additional features.

Note, all also had the ALDH2*2 allele, which is common in East Asian populations, and may be contributory.

Extensive experimental data.
Sources: Literature
Mendeliome v0.5384 NPHS2 Zornitza Stark Gene: nphs2 has been classified as Green List (High Evidence).
Mendeliome v0.5381 LRIF1 Bryony Thompson changed review comment from: A single consanguineous case with a homozygous truncating variant. DZ4Z hypomethylation and increased DUX expression was present in patient cells. siRNA-mediated depletion of LRIF1L in immortalized myoblasts derepressed the DUX4 locus.
Sources: Literature; to: A single consanguineous case with a homozygous truncating variant, and D4Z4 repeat of 13 units on a 4qA haplotype (permissive haplotype). DZ4Z hypomethylation and increased DUX expression was present in patient cells. siRNA-mediated depletion of LRIF1L in immortalized myoblasts derepressed the DUX4 locus.
Sources: Literature
Mendeliome v0.5381 LRIF1 Bryony Thompson Classified gene: LRIF1 as Amber List (moderate evidence)
Mendeliome v0.5381 LRIF1 Bryony Thompson Gene: lrif1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5380 LRIF1 Bryony Thompson gene: LRIF1 was added
gene: LRIF1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: LRIF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRIF1 were set to 32467133
Phenotypes for gene: LRIF1 were set to Facioscapulohumeral muscular dystrophy
Review for gene: LRIF1 was set to AMBER
Added comment: A single consanguineous case with a homozygous truncating variant. DZ4Z hypomethylation and increased DUX expression was present in patient cells. siRNA-mediated depletion of LRIF1L in immortalized myoblasts derepressed the DUX4 locus.
Sources: Literature
Mendeliome v0.5379 DNAH8 Zornitza Stark Phenotypes for gene: DNAH8 were changed from Asthenozoospermia; primary ciliary dyskinesia to Spermatogenic failure 46, MIM#619095; Asthenozoospermia; primary ciliary dyskinesia
Mendeliome v0.5378 DNAH8 Zornitza Stark edited their review of gene: DNAH8: Changed phenotypes: Spermatogenic failure 46, MIM#619095, Asthenozoospermia, primary ciliary dyskinesia
Mendeliome v0.5378 MYRF Zornitza Stark Phenotypes for gene: MYRF were changed from Nanophthalmos; High hyperopia to Nanophthalmos and high hyperopia; Cardiac-urogenital syndrome, MIM# 618280; Encephalitis/encephalopathy, mild, with reversible myelin vacuolization, MIM# 618113
Mendeliome v0.5376 MYRF Zornitza Stark edited their review of gene: MYRF: Added comment: Association with Encephalitis/encephalopathy, mild, with reversible myelin vacuolization 618113: limited evidence, two multiplex families with same missense variant (likely founder effect) reported (p.Gln403Arg); Changed publications: 31048900, 31172260, 31266062, 31700225, 29446546, 29446546, 30532227, 31069960, 29265453; Changed phenotypes: Nanophthalmos and high hyperopia, Cardiac-urogenital syndrome, MIM# 618280, Encephalitis/encephalopathy, mild, with reversible myelin vacuolization, MIM# 618113
Mendeliome v0.5376 MYRF Zornitza Stark changed review comment from: Cardiac-urogenital syndrome is characterized by partial anomalous pulmonary venous return in association with tracheal anomalies, pulmonary hypoplasia, congenital diaphragmatic hernia, thyroid fibrosis, thymic involution, cleft spleen, penoscrotal hypospadias, and cryptorchidism. More than 10 unrelated individuals reported.; to: Cardiac-urogenital syndrome MIM# 618280 is characterized by partial anomalous pulmonary venous return in association with tracheal anomalies, pulmonary hypoplasia, congenital diaphragmatic hernia, thyroid fibrosis, thymic involution, cleft spleen, penoscrotal hypospadias, and cryptorchidism. More than 10 unrelated individuals reported.
Mendeliome v0.5376 MYRF Zornitza Stark edited their review of gene: MYRF: Added comment: Cardiac-urogenital syndrome is characterized by partial anomalous pulmonary venous return in association with tracheal anomalies, pulmonary hypoplasia, congenital diaphragmatic hernia, thyroid fibrosis, thymic involution, cleft spleen, penoscrotal hypospadias, and cryptorchidism. More than 10 unrelated individuals reported.; Changed publications: 31048900, 31172260, 31266062, 31700225, 29446546, 29446546, 30532227, 31069960; Changed phenotypes: Nanophthalmos and high hyperopia, Cardiac-urogenital syndrome, MIM# 618280
Mendeliome v0.5376 RLIM Zornitza Stark Gene: rlim has been classified as Green List (High Evidence).
Mendeliome v0.5373 DNAH2 Zornitza Stark Gene: dnah2 has been classified as Green List (High Evidence).
Mendeliome v0.5373 DNAH2 Zornitza Stark Classified gene: DNAH2 as Green List (high evidence)
Mendeliome v0.5373 DNAH2 Zornitza Stark Gene: dnah2 has been classified as Green List (High Evidence).
Mendeliome v0.5371 CLDN9 Zornitza Stark Phenotypes for gene: CLDN9 were changed from Deafness, autosomal recessive to Deafness, autosomal recessive 116, MIM#619093
Mendeliome v0.5370 CLDN9 Zornitza Stark edited their review of gene: CLDN9: Changed phenotypes: Deafness, autosomal recessive 116, MIM#619093
Mendeliome v0.5369 FGFR1 Zornitza Stark Gene: fgfr1 has been classified as Green List (High Evidence).
Mendeliome v0.5369 FGFR1 Zornitza Stark Phenotypes for gene: FGFR1 were changed from to Encephalocraniocutaneous lipomatosis, somatic mosaic 613001; Hartsfield syndrome 615465; Hypogonadotropic hypogonadism 2 with or without anosmia 147950; Jackson-Weiss syndrome 123150; Osteoglophonic dysplasia 166250; Pfeiffer syndrome 101600; Trigonocephaly 1 190440
Mendeliome v0.5365 B4GALT7 Zornitza Stark Gene: b4galt7 has been classified as Green List (High Evidence).
Mendeliome v0.5362 TBX6 Zornitza Stark Phenotypes for gene: TBX6 were changed from Skeletal dysplasia; spondylocostal dysostosis; congenital scoliosis to Spondylocostal dysostosis 5, 122600
Mendeliome v0.5361 KCNQ2 Zornitza Stark Gene: kcnq2 has been classified as Green List (High Evidence).
Mendeliome v0.5357 FGFR1 Elena Savva reviewed gene: FGFR1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 18034870, 23812909, 26942290; Phenotypes: Encephalocraniocutaneous lipomatosis, somatic mosaic 613001, Hartsfield syndrome 615465, Hypogonadotropic hypogonadism 2 with or without anosmia 147950, Jackson-Weiss syndrome 123150, Osteoglophonic dysplasia 166250, Pfeiffer syndrome 101600, Trigonocephaly 1 190440; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.5357 ADAR Zornitza Stark Gene: adar has been classified as Green List (High Evidence).
Mendeliome v0.5357 ADAR Zornitza Stark Phenotypes for gene: ADAR were changed from to Aicardi-Goutieres syndrome 6, MIM# 615010; Dyschromatosis symmetrica hereditaria, MIM# 127400
Mendeliome v0.5355 ADAR Zornitza Stark reviewed gene: ADAR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aicardi-Goutieres syndrome 6, MIM# 615010, Dyschromatosis symmetrica hereditaria, MIM# 127400; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5355 NDUFB10 Zornitza Stark Classified gene: NDUFB10 as Green List (high evidence)
Mendeliome v0.5355 NDUFB10 Zornitza Stark Gene: ndufb10 has been classified as Green List (High Evidence).
Mendeliome v0.5353 FOXJ1 Zornitza Stark Phenotypes for gene: FOXJ1 were changed from hydrocephalus; chronic destructive airway disease; randomization of left/right body asymmetry to Ciliary dyskinesia, primary, 43, MIM#618699; hydrocephalus; chronic destructive airway disease; randomization of left/right body asymmetry
Mendeliome v0.5352 FOXJ1 Zornitza Stark edited their review of gene: FOXJ1: Changed phenotypes: Ciliary dyskinesia, primary, 43, MIM#618699, hydrocephalus, chronic destructive airway disease, randomization of left/right body asymmetry
Mendeliome v0.5351 SCD5 Zornitza Stark Gene: scd5 has been classified as Red List (Low Evidence).
Mendeliome v0.5351 SCD5 Zornitza Stark gene: SCD5 was added
gene: SCD5 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: SCD5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SCD5 were set to 31972369
Phenotypes for gene: SCD5 were set to Deafness, autosomal dominant 79, MIM#619086
Review for gene: SCD5 was set to RED
Added comment: Single 5-generation family reported with a missense variant segregating in 19 affected individuals. Variant is found at a low frequency in ExAC.
Sources: Expert list
Mendeliome v0.5349 SLC12A2 Zornitza Stark edited their review of gene: SLC12A2: Changed phenotypes: Delpire-McNeill syndrome, MIM#619083, Kilquist syndrome, MIM#619080, deafness, intellectual disability, dysmorphic features, absent salivation, ectodermal dysplasia, constipation, intestinal malrotation, multiple congenital anomalies, Deafness, autosomal dominant 78, MIM# 619081
Mendeliome v0.5348 SLC12A2 Zornitza Stark edited their review of gene: SLC12A2: Changed phenotypes: Kilquist syndrome, MIM#619080, deafness, intellectual disability, dysmorphic features, absent salivation, ectodermal dysplasia, constipation, intestinal malrotation, multiple congenital anomalies, Deafness, autosomal dominant 78, MIM# 619081
Mendeliome v0.5347 SLC12A2 Zornitza Stark edited their review of gene: SLC12A2: Changed phenotypes: Kilquist syndrome, MIM#619080, deafness, intellectual disability, dysmorphic features, absent salivation, ectodermal dysplasia, constipation, intestinal malrotation, multiple congenital anomalies
Mendeliome v0.5347 OCLN Zornitza Stark Gene: ocln has been classified as Green List (High Evidence).
Mendeliome v0.5344 JAM3 Zornitza Stark Gene: jam3 has been classified as Green List (High Evidence).
Mendeliome v0.5341 NCKAP1 Zornitza Stark Gene: nckap1 has been classified as Green List (High Evidence).
Mendeliome v0.5338 ACAD9 Zornitza Stark Gene: acad9 has been classified as Green List (High Evidence).
Mendeliome v0.5334 ALDOB Zornitza Stark Gene: aldob has been classified as Green List (High Evidence).
Mendeliome v0.5330 MYO1A Zornitza Stark Gene: myo1a has been classified as Red List (Low Evidence).
Mendeliome v0.5330 MYO1A Zornitza Stark Classified gene: MYO1A as Red List (low evidence)
Mendeliome v0.5330 MYO1A Zornitza Stark Gene: myo1a has been classified as Red List (Low Evidence).
Mendeliome v0.5329 ARL2 Zornitza Stark Gene: arl2 has been classified as Red List (Low Evidence).
Mendeliome v0.5329 ARL2 Zornitza Stark gene: ARL2 was added
gene: ARL2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ARL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARL2 were set to 30945270
Phenotypes for gene: ARL2 were set to Microcornea, rod-cone dystrophy, cataract, and posterior staphyloma-1 (MRCS1), MIM#619082
Review for gene: ARL2 was set to RED
Added comment: Single family reported, missense variant segregating with structural eye abnormalities in 4 individuals (father and three daughters).
Sources: Expert list
Mendeliome v0.5327 LMX1B Zornitza Stark commented on gene: LMX1B: 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. Some variants in the homeodomain of LMX1B cause isolated nephropathy without nail, patellar or skeletal abnormality (LMX1B-associated nephropathy).

>300 families reported.
Mendeliome v0.5326 UNC80 Zornitza Stark Gene: unc80 has been classified as Green List (High Evidence).
Mendeliome v0.5323 ZFHX4 Zornitza Stark Classified gene: ZFHX4 as Green List (high evidence)
Mendeliome v0.5323 ZFHX4 Zornitza Stark Gene: zfhx4 has been classified as Green List (High Evidence).
Mendeliome v0.5321 AP2S1 Zornitza Stark Gene: ap2s1 has been classified as Green List (High Evidence).
Mendeliome v0.5320 CARD8 Zornitza Stark Gene: card8 has been classified as Red List (Low Evidence).
Mendeliome v0.5317 ZFHX4 Bryony Thompson Gene: zfhx4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5316 ZFHX4 Bryony Thompson Classified gene: ZFHX4 as Amber List (moderate evidence)
Mendeliome v0.5316 ZFHX4 Bryony Thompson Gene: zfhx4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5315 ZFHX4 Bryony Thompson changed review comment from: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 16 de novo variants (5 frameshift, 5 missense, 4 stopgain, 2 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature; to: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 16 de novo variants (5 frameshift, 5 missense, 4 stopgain, 2 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
PMID: 24038936 - a single case with developmental delay, macrocephaly, ventriculomegaly, hypermetropia, recurrent
infections, dysmorphism and a de novo deletion of the last 7 exons of the gene.
Sources: Literature
Mendeliome v0.5315 ZFHX4 Bryony Thompson gene: ZFHX4 was added
gene: ZFHX4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZFHX4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZFHX4 were set to 33057194
Phenotypes for gene: ZFHX4 were set to Developmental disorders
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 16 de novo variants (5 frameshift, 5 missense, 4 stopgain, 2 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5314 UPF1 Bryony Thompson Gene: upf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5314 UPF1 Bryony Thompson Classified gene: UPF1 as Amber List (moderate evidence)
Mendeliome v0.5314 UPF1 Bryony Thompson Gene: upf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5313 UPF1 Bryony Thompson gene: UPF1 was added
gene: UPF1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: UPF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UPF1 were set to 33057194
Phenotypes for gene: UPF1 were set to Developmental disorders
Review for gene: UPF1 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 16 de novo variants (1 frameshift, 11 missense, 4 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5312 U2AF2 Bryony Thompson Classified gene: U2AF2 as Amber List (moderate evidence)
Mendeliome v0.5312 U2AF2 Bryony Thompson Gene: u2af2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5311 U2AF2 Bryony Thompson gene: U2AF2 was added
gene: U2AF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: U2AF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: U2AF2 were set to 33057194
Phenotypes for gene: U2AF2 were set to Developmental disorders
Review for gene: U2AF2 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 10 de novo variants (1 in-frame, 8 missense, 1 synoymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5309 TCF7L2 Bryony Thompson Gene: tcf7l2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5306 TCF7L2 Bryony Thompson Classified gene: TCF7L2 as Amber List (moderate evidence)
Mendeliome v0.5306 TCF7L2 Bryony Thompson Gene: tcf7l2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5305 SRRM2 Bryony Thompson Gene: srrm2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5305 SRRM2 Bryony Thompson Classified gene: SRRM2 as Amber List (moderate evidence)
Mendeliome v0.5305 SRRM2 Bryony Thompson Gene: srrm2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5304 SRRM2 Bryony Thompson gene: SRRM2 was added
gene: SRRM2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SRRM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SRRM2 were set to 33057194
Phenotypes for gene: SRRM2 were set to Developmental disorders
Review for gene: SRRM2 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 28 de novo variants (11 frameshift, 7 missense, 1 splice acceptor, 5 stopgain, 4 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5303 SPEN Bryony Thompson Gene: spen has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5303 SPEN Bryony Thompson Classified gene: SPEN as Amber List (moderate evidence)
Mendeliome v0.5303 SPEN Bryony Thompson Gene: spen has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5302 SPEN Bryony Thompson gene: SPEN was added
gene: SPEN was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPEN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPEN were set to 33057194
Phenotypes for gene: SPEN were set to Developmental disorders
Review for gene: SPEN was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 25 de novo variants (6 frameshift, 1 in-frame, 7 missense, 8 stopgain, 3 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5301 SATB1 Bryony Thompson Gene: satb1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5301 SATB1 Bryony Thompson Classified gene: SATB1 as Amber List (moderate evidence)
Mendeliome v0.5301 SATB1 Bryony Thompson Gene: satb1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5300 SATB1 Bryony Thompson gene: SATB1 was added
gene: SATB1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SATB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SATB1 were set to 33057194
Phenotypes for gene: SATB1 were set to Developmental disorders
Review for gene: SATB1 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 12 de novo (2 frameshift, 7 missense, 1 stopgain, 2 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5299 RAB14 Bryony Thompson Gene: rab14 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5299 RAB14 Bryony Thompson Classified gene: RAB14 as Amber List (moderate evidence)
Mendeliome v0.5299 RAB14 Bryony Thompson Gene: rab14 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5298 RAB14 Bryony Thompson gene: RAB14 was added
gene: RAB14 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RAB14 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAB14 were set to 33057194
Phenotypes for gene: RAB14 were set to Developmental disorders
Review for gene: RAB14 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 8 de novo variants (1 in-frame, 7 missense) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5297 PSMC5 Bryony Thompson Gene: psmc5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5297 PSMC5 Bryony Thompson Classified gene: PSMC5 as Amber List (moderate evidence)
Mendeliome v0.5297 PSMC5 Bryony Thompson Gene: psmc5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5296 PSMC5 Bryony Thompson gene: PSMC5 was added
gene: PSMC5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PSMC5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSMC5 were set to 33057194
Phenotypes for gene: PSMC5 were set to Developmental disorders
Review for gene: PSMC5 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 10 de novo variants (1 in-frame, 9 missense) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5295 PRPF8 Bryony Thompson Gene: prpf8 has been classified as Green List (High Evidence).
Mendeliome v0.5295 PRPF8 Bryony Thompson Added comment: Comment on phenotypes: Established Retinitis pigmentosa gene.
PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 29 de novo variants (2 frameshift, 19 missense, 1 stopgain, 7 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Mendeliome v0.5292 MSL2 Bryony Thompson Gene: msl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5292 MSL2 Bryony Thompson Classified gene: MSL2 as Amber List (moderate evidence)
Mendeliome v0.5292 MSL2 Bryony Thompson Gene: msl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5290 MSL2 Bryony Thompson gene: MSL2 was added
gene: MSL2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MSL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MSL2 were set to 31332282; 33057194
Phenotypes for gene: MSL2 were set to Developmental disorders; autism
Review for gene: MSL2 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 13 de novo variants (9 frameshift, 4 missense) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
PMID: 31332282 - candidate gene in a single autism study, with recurrent de novo variants in a potential oligogenic model
Sources: Literature
Mendeliome v0.5289 MMGT1 Bryony Thompson Classified gene: MMGT1 as Amber List (moderate evidence)
Mendeliome v0.5289 MMGT1 Bryony Thompson Gene: mmgt1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5288 MMGT1 Bryony Thompson gene: MMGT1 was added
gene: MMGT1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MMGT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MMGT1 were set to 33057194
Phenotypes for gene: MMGT1 were set to Developmental disorders
Review for gene: MMGT1 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 3 de novo missense identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5286 MIB1 Bryony Thompson Added comment: Comment on phenotypes: Established congenital cardiac disease gene.
PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 11 de novo variants (1 frameshift, 2 missense, 2 splice acceptor, 1 splice donor, 5 stopgain) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Mendeliome v0.5284 MFN2 Bryony Thompson Added comment: Comment on phenotypes: Established cause of hereditary neuropathy.
PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 9 de novo variants (8 missense, 1 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Mendeliome v0.5282 KCNK3 Bryony Thompson Added comment: Comment on phenotypes: Established pulmonary hypertension gene.
PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 8 de novo variants (7 missense, 1 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Mendeliome v0.5282 KCNK3 Bryony Thompson Phenotypes for gene: KCNK3 were changed from to Pulmonary hypertension, primary, 4 MIM#615344
Mendeliome v0.5280 HNRNPD Bryony Thompson Gene: hnrnpd has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5280 HNRNPD Bryony Thompson Classified gene: HNRNPD as Amber List (moderate evidence)
Mendeliome v0.5280 HNRNPD Bryony Thompson Gene: hnrnpd has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5279 HNRNPD Bryony Thompson gene: HNRNPD was added
gene: HNRNPD was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HNRNPD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPD were set to 33057194
Phenotypes for gene: HNRNPD were set to Developmental disorders
Review for gene: HNRNPD was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 8 de novo variants (5 frameshift, 1 missense, 1 splice acceptor, 1 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5278 PRKG2 Zornitza Stark Gene: prkg2 has been classified as Green List (High Evidence).
Mendeliome v0.5278 PRKG2 Zornitza Stark Classified gene: PRKG2 as Green List (high evidence)
Mendeliome v0.5278 PRKG2 Zornitza Stark Gene: prkg2 has been classified as Green List (High Evidence).
Mendeliome v0.5277 PLXND1 Zornitza Stark Gene: plxnd1 has been classified as Green List (High Evidence).
Mendeliome v0.5277 PLXND1 Zornitza Stark Classified gene: PLXND1 as Green List (high evidence)
Mendeliome v0.5277 PLXND1 Zornitza Stark Gene: plxnd1 has been classified as Green List (High Evidence).
Mendeliome v0.5275 ECEL1 Zornitza Stark Gene: ecel1 has been classified as Green List (High Evidence).
Mendeliome v0.5275 ECEL1 Zornitza Stark Phenotypes for gene: ECEL1 were changed from to Arthrogryposis, distal, type 5D, MIM# 615065
Mendeliome v0.5274 MYMK Zornitza Stark changed review comment from: Sources: Expert list; to: Carey-Fineman-Ziter syndrome (CFZS) is a multisystem congenital disorder characterized by hypotonia, Moebius sequence (bilateral congenital facial palsy with impairment of ocular abduction), Pierre Robin complex (micrognathia, glossoptosis, and high-arched or cleft palate), delayed motor milestones, and failure to thrive. Intellect has been normal in molecularly confirmed cases. Defect in myoblast fusion. 6 unrelated families reported with CFZ phenotype and bi-allelic MYMK variants. p.Pro91Thr is a common founder variant, which is hypomorphic.
Mendeliome v0.5272 ECEL1 Zornitza Stark reviewed gene: ECEL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23261301, 23236030, 25099528, 24782201; Phenotypes: Arthrogryposis, distal, type 5D, MIM# 615065; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5272 PRKG2 Arina Puzriakova gene: PRKG2 was added
gene: PRKG2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRKG2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRKG2 were set to 33106379
Phenotypes for gene: PRKG2 were set to Acromesomelic dysplasia
Review for gene: PRKG2 was set to GREEN
Added comment: - PMID: 33106379 (2020) - Distinct homozygous variants in PRKG2 identified in two unrelated individuals, both with a skeletal dysplasia associated with severe short stature due to acromesomelic limb shortening, brachydactyly, mild to moderate platyspondyly and progressively increasing metaphyseal alterations of the long bones.

Functional studies showed both variants result in NMD and disrupt the downstream MAPK signalling pathway in response to FGF2. The role of cGKII, encoded by PRKG2, in skeletal growth has been established in several animal models (references provided in paper).
Sources: Literature
Mendeliome v0.5271 FOXP4 Zornitza Stark Gene: foxp4 has been classified as Green List (High Evidence).
Mendeliome v0.5271 FOXP4 Zornitza Stark Classified gene: FOXP4 as Green List (high evidence)
Mendeliome v0.5271 FOXP4 Zornitza Stark Gene: foxp4 has been classified as Green List (High Evidence).
Mendeliome v0.5270 FOXP4 Zornitza Stark gene: FOXP4 was added
gene: FOXP4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FOXP4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXP4 were set to 33110267
Phenotypes for gene: FOXP4 were set to Neurodevelopmental disorder; multiple congenital abnormalities
Review for gene: FOXP4 was set to GREEN
Added comment: Eight unrelated individuals reported, seven de novo missense, and one individual with a truncating variant. Detailed phenotypic information available on 6. Overlapping features included speech and language delays, growth abnormalities, congenital diaphragmatic hernia (2/6), cervical spine abnormalities, and ptosis. Intellectual disability described as mild in 2, some had normal intellect despite the early speech and language delays.
Sources: Literature
Mendeliome v0.5269 ASAH1 Zornitza Stark Gene: asah1 has been classified as Green List (High Evidence).
Mendeliome v0.5269 ASAH1 Zornitza Stark Phenotypes for gene: ASAH1 were changed from to Spinal muscular atrophy with progressive myoclonic epilepsy, MIM# 159950; Farber lipogranulomatosis, MIM# 228000
Mendeliome v0.5267 ASAH1 Zornitza Stark reviewed gene: ASAH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinal muscular atrophy with progressive myoclonic epilepsy, MIM# 159950, Farber lipogranulomatosis, MIM# 228000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5267 DHX32 Zornitza Stark Gene: dhx32 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5267 DHX32 Zornitza Stark Classified gene: DHX32 as Amber List (moderate evidence)
Mendeliome v0.5267 DHX32 Zornitza Stark Gene: dhx32 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5266 TNF Zornitza Stark Gene: tnf has been classified as Red List (Low Evidence).
Mendeliome v0.5265 TNF Zornitza Stark Classified gene: TNF as Red List (low evidence)
Mendeliome v0.5265 TNF Zornitza Stark Gene: tnf has been classified as Red List (Low Evidence).
Mendeliome v0.5264 ALK Zornitza Stark Gene: alk has been classified as Green List (High Evidence).
Mendeliome v0.5261 RHOB Zornitza Stark Gene: rhob has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5260 RHOB Zornitza Stark Classified gene: RHOB as Amber List (moderate evidence)
Mendeliome v0.5260 RHOB Zornitza Stark Gene: rhob has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5259 FBXO31 Zornitza Stark Phenotypes for gene: FBXO31 were changed from Mental retardation, autosomal recessive 45, MIM#615979 to Mental retardation, autosomal recessive 45, MIM#615979; Cerebral palsy, intellectual disability, autosomal dominant
Mendeliome v0.5255 FBXO31 Zornitza Stark Classified gene: FBXO31 as Amber List (moderate evidence)
Mendeliome v0.5255 FBXO31 Zornitza Stark Gene: fbxo31 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5254 FBXO31 Kristin Rigbye changed review comment from: 2 unrelated probands with CP harbouring the same de novo missense variant (p.Asp334Asn). The variant affects the cyclin D interaction site, leading to an apparent gain of function of cyclin D degradation, supported by Western blots from patient fibroblasts which showed decreased cyclin D expression.; to: 2 unrelated probands with CP harbouring the same de novo missense variant (p.Asp334Asn). The variant affects the cyclin D interaction site, leading to an apparent gain of function of cyclin D degradation, supported by Western blots from patient fibroblasts which showed decreased cyclin D expression.

Extended patient phenotypes: Spastic diplegia, with esotropia, ID, dysarthria, mixed receptive/expressive language disorder, ADHD, cleft palate, intestinal malrotation and midgut volvulus (patient 1); Spastic paraplegia with ventricular dilation and thin corpus callosum, ID, attention deficit, anxiety, language impairments, strabismus, severe constipation (patient 2).
Mendeliome v0.5254 NHLRC2 Zornitza Stark Gene: nhlrc2 has been classified as Green List (High Evidence).
Mendeliome v0.5254 NHLRC2 Zornitza Stark Phenotypes for gene: NHLRC2 were changed from to Fibrosis, neurodegeneration, and cerebral angiomatosis (FINCA) syndrome MIM#618278
Mendeliome v0.5251 RHOB Crystle Lee gene: RHOB was added
gene: RHOB was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: RHOB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RHOB were set to 32989326
Phenotypes for gene: RHOB were set to Cerebral Palsy (PMID:32989326)
Mode of pathogenicity for gene: RHOB was set to Other
Review for gene: RHOB was set to AMBER
Added comment: Candidate disease-causing gene for CP. Recurrent de novo missense variant reported in 2 unrelated families with supporting functional studies.
Sources: Expert list
Mendeliome v0.5251 CTLA4 Zornitza Stark Gene: ctla4 has been classified as Green List (High Evidence).
Mendeliome v0.5249 VIM Zornitza Stark Gene: vim has been classified as Green List (High Evidence).
Mendeliome v0.5249 VIM Zornitza Stark Phenotypes for gene: VIM were changed from to Cataract 30, pulverulent 116300; frontonasal dysostosis and premature aging
Mendeliome v0.5248 NHLRC2 Paul De Fazio changed review comment from: 3 families with compound het variants in total, all share one missense variant (p.Asp148Ty)

PMID 29423877: 3 patients from 2 Finnish families compound het for the same missense variant (122 hets 0 homs) and the same frameshift variant (12 hets 0 homs), main clinical features included progressive cerebropulmonary symptoms, malabsorption, progressive growth failure, recurrent infections, chronic haemolytic anaemia and transient liver dysfunction. Expression studies in patient-derived fibroblasts supported the frameshift variant leading to NMD. Zebrafish knockdown affected the integrity of cells in the midbrain region.

PMID 32435055: patient with the same phenotype from a Ukrainian family chet for two missense variants, one shared with the Finnish families and one novel.; to: 3 families with compound het variants in total, all share one missense variant (p.Asp148Ty)

PMID 29423877: 3 patients from 2 Finnish families compound het for the same missense variant (122 hets 0 homs) and the same frameshift variant (12 hets 0 homs), main clinical features included progressive cerebropulmonary symptoms, malabsorption, progressive growth failure, recurrent infections, chronic haemolytic anaemia and transient liver dysfunction. Expression studies in patient-derived fibroblasts supported the frameshift variant leading to NMD. Zebrafish knockdown affected the integrity of cells in the midbrain region.

PMID 32435055: patient with the same phenotype from a Ukrainian family chet for two missense variants, one shared with the Finnish families and one novel.
Mendeliome v0.5248 NHLRC2 Paul De Fazio changed review comment from: 3 families with compound het variants in total, all share one missense variant (p.Asp148Ty)

PMID 29423877: 3 patients from 2 Finnish families compound het for the same missense variant (122 hets 0 homs) and the same frameshift variant (12 hets 0 homs), main clinical features included progressive cerebropulmonary symptoms, malabsorption, progressive growth failure, recurrent infections, chronic haemolytic anaemia and transient liver dysfunction. Zebrafish knockdown affected the integrity of cells in the midbrain region.

PMID 32435055: patient with the same phenotype from a Ukrainian family chet for two missense variants, one shared with the Finnish families and one novel.; to: 3 families with compound het variants in total, all share one missense variant (p.Asp148Ty)

PMID 29423877: 3 patients from 2 Finnish families compound het for the same missense variant (122 hets 0 homs) and the same frameshift variant (12 hets 0 homs), main clinical features included progressive cerebropulmonary symptoms, malabsorption, progressive growth failure, recurrent infections, chronic haemolytic anaemia and transient liver dysfunction. Expression studies in patient-derived fibroblasts supported the frameshift variant leading to NMD. Zebrafish knockdown affected the integrity of cells in the midbrain region.

PMID 32435055: patient with the same phenotype from a Ukrainian family chet for two missense variants, one shared with the Finnish families and one novel.
Mendeliome v0.5246 NHLRC2 Paul De Fazio reviewed gene: NHLRC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29423877, 32435055; Phenotypes: Fibrosis, neurodegeneration, and cerebral angiomatosis (FINCA) syndrome MIM#618278; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.5245 STN1 Zornitza Stark Classified gene: STN1 as Green List (high evidence)
Mendeliome v0.5245 STN1 Zornitza Stark Gene: stn1 has been classified as Green List (High Evidence).
Mendeliome v0.5244 ITPR3 Zornitza Stark Gene: itpr3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5244 VIM Ee Ming Wong reviewed gene: VIM: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 32066935; Phenotypes: frontonasal dysostosis, premature aging; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5244 ITPR3 Zornitza Stark Classified gene: ITPR3 as Amber List (moderate evidence)
Mendeliome v0.5244 ITPR3 Zornitza Stark Gene: itpr3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5243 ITPR3 Zornitza Stark gene: ITPR3 was added
gene: ITPR3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ITPR3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ITPR3 were set to 32949214
Phenotypes for gene: ITPR3 were set to Charcot-Marie-Tooth disease
Review for gene: ITPR3 was set to AMBER
Added comment: Two unrelated families reported: variant segregated in four affected individuals in one family and was de novo in the second family where there was a single affected person. Some evidence for dominant-negative effect.
Sources: Literature
Mendeliome v0.5240 AMOTL1 Zornitza Stark Gene: amotl1 has been classified as Red List (Low Evidence).
Mendeliome v0.5239 KIRREL1 Zornitza Stark Gene: kirrel1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5239 KIRREL1 Zornitza Stark Classified gene: KIRREL1 as Amber List (moderate evidence)
Mendeliome v0.5239 KIRREL1 Zornitza Stark Gene: kirrel1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5238 KIRREL1 Zornitza Stark gene: KIRREL1 was added
gene: KIRREL1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIRREL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIRREL1 were set to 31472902
Phenotypes for gene: KIRREL1 were set to Steroid-resistant nephrotic syndrome
Review for gene: KIRREL1 was set to AMBER
Added comment: Two unrelated families reported with bi-allelic variants and limited functional data.
Sources: Literature
Mendeliome v0.5237 GFRA1 Zornitza Stark Gene: gfra1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5237 GFRA1 Zornitza Stark Classified gene: GFRA1 as Amber List (moderate evidence)
Mendeliome v0.5237 GFRA1 Zornitza Stark Gene: gfra1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5236 GFRA1 Zornitza Stark gene: GFRA1 was added
gene: GFRA1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GFRA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GFRA1 were set to 33020172
Phenotypes for gene: GFRA1 were set to Renal agenesis
Review for gene: GFRA1 was set to AMBER
Added comment: Two unrelated families reported with bi-allelic LOF variants identified in individuals with bilateral renal agenesis. GFRA1 gene encodes a receptor on the Wolffian duct that regulates ureteric bud outgrowth in the development of a functional renal system.
Sources: Literature
Mendeliome v0.5235 GNB2 Bryony Thompson reviewed gene: GNB2: Rating: AMBER; Mode of pathogenicity: None; Publications: 33057194; Phenotypes: Developmental disorder, sinus node dysfunction and atrioventricular block; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.5235 GIGYF1 Bryony Thompson Gene: gigyf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5235 GIGYF1 Bryony Thompson Classified gene: GIGYF1 as Amber List (moderate evidence)
Mendeliome v0.5235 GIGYF1 Bryony Thompson Gene: gigyf1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5234 GIGYF1 Bryony Thompson gene: GIGYF1 was added
gene: GIGYF1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GIGYF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GIGYF1 were set to 33057194
Phenotypes for gene: GIGYF1 were set to Developmental disorder
Review for gene: GIGYF1 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 14 de novo variants (4 frameshift, 5 missense, 1 splice donor, 3 stopgain, 1 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5233 FBXW7 Bryony Thompson Gene: fbxw7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5233 FBXW7 Bryony Thompson Classified gene: FBXW7 as Amber List (moderate evidence)
Mendeliome v0.5233 FBXW7 Bryony Thompson Gene: fbxw7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5232 FBXW7 Bryony Thompson gene: FBXW7 was added
gene: FBXW7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FBXW7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FBXW7 were set to 33057194
Phenotypes for gene: FBXW7 were set to Developmental disorder
Review for gene: FBXW7 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio developmental disorder study. 12 de novo missense and 1 de novo synonymous variant identified in ~10,000 cases with developmental disorders (no other phenotype info provided)
Sources: Literature
Mendeliome v0.5230 PRKAR1B Zornitza Stark Gene: prkar1b has been classified as Green List (High Evidence).
Mendeliome v0.5230 PRKAR1B Zornitza Stark Classified gene: PRKAR1B as Green List (high evidence)
Mendeliome v0.5230 PRKAR1B Zornitza Stark Gene: prkar1b has been classified as Green List (High Evidence).
Mendeliome v0.5229 PRKAR1B Konstantinos Varvagiannis gene: PRKAR1B was added
gene: PRKAR1B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRKAR1B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRKAR1B were set to https://doi.org/10.1101/2020.09.10.20190314; 25414040
Phenotypes for gene: PRKAR1B were set to Global developmental delay; Intellectual disability; Autism; Attention deficit hyperactivity disorder; Aggressive behavior; Abnormality of movement; Upslanted palpebral fissure
Penetrance for gene: PRKAR1B were set to unknown
Review for gene: PRKAR1B was set to AMBER
Added comment: Please consider inclusion of this gene with amber rating pending publication of the preprint and/or additional evidence.

Marbach et al. (2020 - medRxiv : https://doi.org/10.1101/2020.09.10.20190314 - last author : C. Schaaf) report 6 unrelated individuals with heterozygous missense PRKAR1B variants.

All presented formal ASD diagnosis (6/6), global developmental delay (6/6) and intellectual disability (all - formal evaluations were lacking though). Additional features included neurologic anomalies (movement disorders : dyspraxia, apraxia, clumsiness in all, with tremor/dystonia or involuntary movements as single occurrences). Three displayed high pain tolerance. Regression in speech was a feature in two. Additional behavior anomalies included ADHD (4-5/6) or aggression (3/6). There was no consistent pattern of malformations, physical anomalies or facial features (with the exception of uplsanted palpebral fissures reported in 4).

3 different missense variants were identified (NM_00116470:c.1003C>T - p.Arg335Trp, c.586G>A - p.Glu196Lys, c.500_501delAAinsTT - p.Gln167Leu) with Arg355Trp being a recurrent one within this cohort (4/6 subjects). A possible splicing effect may apply for the MNV. All variants are absent from gnomAD and the SNVs had CADD scores > 24.

In all cases were parental samples were available (5/6), the variant had occurred as a de novo event.

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

The functional consequences of the variants at cellular level were not studied.

Previous studies have demonstrated that downregulation of RIβ in murine hippocampal cultures, reduced phosphorylation of CREB, a transcription factor involved in long-term memory formation. The authors speculate that a similar effect on cAMP/PKA/CREB cascade may mediate the cognitive effects in humans. RIβ deficient mice also display diminished nociceptive pain, similar to the human phenotype. [Several refs provided].

The authors cite the study by Kaplanis et al (2020 - PMID: 33057194), where in a large sample of 31,058 trio exomes of children with developmental disorders, PRKAR1B was among the genes with significant enrichment for de novo missense variants. [The gene has a pLI score of 0.18 in gnomAD / o/e = 0.26 - so pLoF variants may not be deleterious].

Please note that a specific PRKAR1B variant (NM_002735.2:c.149T>G - p.Leu50Arg) has been previous reported to segregate with a late-onset neurodegenerative disorder characterized by dementia and/or parkinsonism within a large pedigree with 12 affected individuals [Wong et al 2014 - PMID: 25414040].
Sources: Literature
Mendeliome v0.5229 NR1H4 Zornitza Stark Gene: nr1h4 has been classified as Green List (High Evidence).
Mendeliome v0.5229 NR1H4 Zornitza Stark Phenotypes for gene: NR1H4 were changed from to Cholestasis, progressive familial intrahepatic, 5, MIM# 617049
Mendeliome v0.5226 NR1H4 Zornitza Stark reviewed gene: NR1H4: Rating: GREEN; Mode of pathogenicity: None; Publications: 26888176, 32443034; Phenotypes: Cholestasis, progressive familial intrahepatic, 5, MIM# 617049; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5226 PTF1A Zornitza Stark Gene: ptf1a has been classified as Green List (High Evidence).
Mendeliome v0.5226 PTF1A Zornitza Stark Phenotypes for gene: PTF1A were changed from to Pancreatic agenesis 2, MIM# 615935; Pancreatic and cerebellar agenesis, MIM# 609069
Mendeliome v0.5223 PTF1A Zornitza Stark reviewed gene: PTF1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 24212882, 21749365, 10507728, 15543146, 19650412; Phenotypes: Pancreatic agenesis 2, MIM# 615935, Pancreatic and cerebellar agenesis, MIM# 609069; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5223 MPP5 Zornitza Stark Gene: mpp5 has been classified as Green List (High Evidence).
Mendeliome v0.5223 MPP5 Zornitza Stark Classified gene: MPP5 as Green List (high evidence)
Mendeliome v0.5223 MPP5 Zornitza Stark Gene: mpp5 has been classified as Green List (High Evidence).
Mendeliome v0.5222 MPP5 Konstantinos Varvagiannis gene: MPP5 was added
gene: MPP5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MPP5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MPP5 were set to 33073849
Phenotypes for gene: MPP5 were set to Global developmental delay; Intellectual disability; Delayed speech and language development; Developmental regression; Behavioral abnormality
Penetrance for gene: MPP5 were set to unknown
Review for gene: MPP5 was set to GREEN
Added comment: Sterling et al (2020 - PMID: 33073849) provide information on the phenotype of 3 individuals with de novo MPP5 variants.

Common features included global developmental delay, intellectual disability (3/3 - severe in 2/3), speech delay/regression (the latter in at least 2) and behavioral abnormalities. Variable other features were reported, among others microcephaly (1/3), abnormal vision (1/3 : CVI, retinal dystrophy, nystagmus), brain MRI abnormalities (2/3), late-onset seizures (1/3). These subjects displayed variable and non-specific dysmorphic features.

All were investigated by exome sequencing (previous investigations not mentioned).

One subject was found to harbor a de novo mosaic (5/25 reads) stopgain variant, further confirmed by Sanger sequencing [NM_022474.4:c.1555C>T - p.(Arg519Ter). The specific variant is reported once in gnomAD (1/251338). Two de novo missense variants were identified in the remaining individuals [c.1289A>G - p.Glu430Gly / c.974A>C - p.His325Pro). All variants had in silico predictions in favor of a deleterious effect (CADD score >24).

The authors comment that MPP5 encodes an apical complex protein with asymmetric localization to the apical side of polarized cells. It is expressed in brain, peripheral nervous system and other tissues. MPP5 is a member of the membrane-associated guanylate kinase family of proteins (MAGUK p55 subfamily), determining cell polarity at tight junctions.

Previous animal models suggest that complete Mpp5(Pals1) KO in mice leads to near absence of cerebral cortical neurons. Htz KO display reduction in size of cerebral cortex and hippocampus. The gene is expressed in proliferating cell populations of cerebellum and important for establishment cerebellar architecture. Conditional KO of Mpp5(Pals1) in retinal progenitor cells mimics the retinal pathology observed in LCA. [Several refs. provided]

The authors studied a heterozygous CNS-specific Mpp5 KO mouse model. These mice presented microcephaly, decreased cerebellar volume and cortical thickness, decreased ependymal cells and Mpp5 at the apical surface of cortical vertrical zone. The proportion of cortical cells undergoing apoptotic cell death was increased. Mice displayed behavioral abnormalities (hyperactivity) and visual deficits, with ERG traces further suggesting retinal blindness.

Overall the mouse model was thought to recapitulate the behavioral abnormalities observed in affected subjects as well as individual rare features such as microcephaly and abnormal vision.

Haploinsufficiency (rather than a dominant negative effect) is favored as the underlying disease mechanism. This is also in line with a dose dependent effect observed in mice.
Sources: Literature
Mendeliome v0.5222 AKR1D1 Zornitza Stark Gene: akr1d1 has been classified as Green List (High Evidence).
Mendeliome v0.5222 AKR1D1 Zornitza Stark Phenotypes for gene: AKR1D1 were changed from to Bile acid synthesis defect, congenital, 2, MIM# 235555
Mendeliome v0.5219 AKR1D1 Zornitza Stark reviewed gene: AKR1D1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12970144, 20522910; Phenotypes: Bile acid synthesis defect, congenital, 2, MIM# 235555; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.5219 SCYL1 Zornitza Stark Gene: scyl1 has been classified as Green List (High Evidence).
Mendeliome v0.5219 SCYL1 Zornitza Stark Phenotypes for gene: SCYL1 were changed from to Spinocerebellar ataxia, autosomal recessive 21, MIM# 616719
Mendeliome v0.5216 SCYL1 Zornitza Stark commented on gene: SCYL1: Autosomal recessive spinocerebellar ataxia-21 is a neurologic disorder characterized by onset of cerebellar ataxia associated with cerebellar atrophy in early childhood. Affected individuals also have recurrent episodes of liver failure in the first decade, resulting in chronic liver fibrosis, as well as later onset of a peripheral neuropathy. Mild learning disabilities may also occur. More than 5 unrelated families reported.
Mendeliome v0.5216 SLC30A10 Zornitza Stark Gene: slc30a10 has been classified as Green List (High Evidence).
Mendeliome v0.5213 DDX23 Bryony Thompson Classified gene: DDX23 as Amber List (moderate evidence)
Mendeliome v0.5213 DDX23 Bryony Thompson Gene: ddx23 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5212 DDX23 Bryony Thompson gene: DDX23 was added
gene: DDX23 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DDX23 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DDX23 were set to 33057194
Phenotypes for gene: DDX23 were set to Developmental disorder
Review for gene: DDX23 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio developmental disorder study. 6 de novo missense identified in ~10,000 cases with developmental disorders (no other phenotype info provided)
Sources: Literature
Mendeliome v0.5211 ATP6V0A1 Bryony Thompson Classified gene: ATP6V0A1 as Amber List (moderate evidence)
Mendeliome v0.5211 ATP6V0A1 Bryony Thompson Gene: atp6v0a1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5210 ATP6V0A1 Bryony Thompson gene: ATP6V0A1 was added
gene: ATP6V0A1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATP6V0A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP6V0A1 were set to 30842224; 33057194
Phenotypes for gene: ATP6V0A1 were set to Developmental disorder; Rett syndrome-like
Review for gene: ATP6V0A1 was set to AMBER
Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio developmental disorder study. 11 de novo missense identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
PMID: 30842224 - identified a de novo missense variant in a single individual with atypical Rett syndrome phenotype
Sources: Literature
Mendeliome v0.5209 ARHGAP35 Bryony Thompson Gene: arhgap35 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5209 ARHGAP35 Bryony Thompson Classified gene: ARHGAP35 as Amber List (moderate evidence)
Mendeliome v0.5209 ARHGAP35 Bryony Thompson Gene: arhgap35 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5208 ARHGAP35 Bryony Thompson gene: ARHGAP35 was added
gene: ARHGAP35 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARHGAP35 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARHGAP35 were set to 33057194
Phenotypes for gene: ARHGAP35 were set to Developmental disorder
Review for gene: ARHGAP35 was set to AMBER
Added comment: Has been identified as a gene with significant de novo enrichment in a large trio developmental disorder study. 16 de novo variants (3 frameshift, 2 in-frame, 10 missense, 1 stopgain) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).
Sources: Literature
Mendeliome v0.5207 AP2S1 Bryony Thompson Added comment: Comment on phenotypes: Established hypercalcaemia gene.
PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio developmental disorder study. 5 de novo missense identified in ~10,000 cases with developmental disorders (no other phenotype info provided)
Mendeliome v0.5204 ASCL1 Zornitza Stark Gene: ascl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5201 ASCL1 Zornitza Stark Classified gene: ASCL1 as Amber List (moderate evidence)
Mendeliome v0.5201 ASCL1 Zornitza Stark Gene: ascl1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.5198 KDELR2 Zornitza Stark Gene: kdelr2 has been classified as Green List (High Evidence).
Mendeliome v0.5198 KDELR2 Zornitza Stark Classified gene: KDELR2 as Green List (high evidence)
Mendeliome v0.5198 KDELR2 Zornitza Stark Gene: kdelr2 has been classified as Green List (High Evidence).
Mendeliome v0.5197 KDELR2 Zornitza Stark gene: KDELR2 was added
gene: KDELR2 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: KDELR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KDELR2 were set to 33053334
Phenotypes for gene: KDELR2 were set to Increased susceptibility to fractures; joint hypermobility; Scoliosis; Bowing of the legs; Bowing of the arms
Review for gene: KDELR2 was set to GREEN
Added comment: 4 families with osteogenesis imperfecta reported with functional studies.
Sources: Expert list
Mendeliome v0.5196 SCN8A Zornitza Stark Gene: scn8a has been classified as Green List (High Evidence).
Mendeliome v0.5196 SCN8A Zornitza Stark Phenotypes for gene: SCN8A were changed from 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
Mendeliome v0.5192 SCN8A Zornitza Stark reviewed gene: SCN8A: Rating: GREEN; Mode of pathogenicity: Other; Publications: 31625145, 29726066, 27098556, 28702509, 16236810, 31904124, 31887642, 31675620; 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: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.5191 ALPK1 Zornitza Stark edited their review of gene: ALPK1: Changed phenotypes: Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome, Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache (ROSAH) syndrome, MIM#614979
Mendeliome v0.5190 ALPK1 Zornitza Stark Phenotypes for gene: ALPK1 were changed from Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome; Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome ROSAH syndrome, MIM#614979 to Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome; Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache (ROSAH) syndrome, MIM#614979
Mendeliome v0.5189 ALPK1 Zornitza Stark Phenotypes for gene: ALPK1 were changed from Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome; ROSAH syndrome; retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache to Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome; Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome ROSAH syndrome, MIM#614979
Mendeliome v0.5188 ALPK1 Zornitza Stark edited their review of gene: ALPK1: Changed phenotypes: Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome, Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndromeROSAH syndrome, MIM#614979
Mendeliome v0.5185 COG8 Zornitza Stark Gene: cog8 has been classified as Green List (High Evidence).
Mendeliome v0.5182 HBB Zornitza Stark Gene: hbb has been classified as Green List (High Evidence).
Mendeliome v0.5182 HBB Zornitza Stark Phenotypes for gene: HBB were changed from to Delta-beta thalassemia 141749; Erythrocytosis 6 617980; Heinz body anemia 140700; Hereditary persistence of fetal hemoglobin 141749; Methemoglobinemia, beta type 617971; Sickle cell anemia 603903; Thalassemia-beta, dominant inclusion-body 603902; Thalassemia, beta 613985
Mendeliome v0.5178 RAD51D Zornitza Stark Gene: rad51d has been classified as Red List (Low Evidence).
Mendeliome v0.5175 RAD51D Zornitza Stark Classified gene: RAD51D as Red List (low evidence)
Mendeliome v0.5175 RAD51D Zornitza Stark Gene: rad51d has been classified as Red List (Low Evidence).
Mendeliome v0.5174 HBB Elena Savva reviewed gene: HBB: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31788855, 20301599, 29700171; Phenotypes: {Malaria, resistance to} 611162, Delta-beta thalassemia 141749, Erythrocytosis 6 617980, Heinz body anemia 140700, Hereditary persistence of fetal hemoglobin 141749, Methemoglobinemia, beta type 617971, Sickle cell anemia 603903, Thalassemia-beta, dominant inclusion-body 603902, Thalassemia, beta 613985; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.5174 TPO Zornitza Stark Gene: tpo has been classified as Green List (High Evidence).