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Mendeliome v0.13084 FAH Bryony Thompson Phenotypes for gene: FAH were changed from to Tyrosinemia type I MONDO:0010161
Mendeliome v0.13081 FAH Bryony Thompson reviewed gene: FAH: Rating: GREEN; Mode of pathogenicity: None; Publications: 8253378, 1401056, 8364576, 8318997, 25681080; Phenotypes: Tyrosinemia type I MONDO:0010161; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13080 F12 Bryony Thompson Gene: f12 has been classified as Green List (High Evidence).
Mendeliome v0.13078 POMP Zornitza Stark Gene: pomp has been classified as Green List (High Evidence).
Mendeliome v0.13078 POMP Zornitza Stark Phenotypes for gene: POMP were changed from to Keratosis linearis with ichthyosis congenita and sclerosing keratoderma MIM#601952; Proteasome-associated autoinflammatory syndrome 2, MIM# 618048
Mendeliome v0.13075 POMP Zornitza Stark reviewed gene: POMP: Rating: GREEN; Mode of pathogenicity: None; Publications: 20226437, 27503413, 29805043; Phenotypes: Keratosis linearis with ichthyosis congenita and sclerosing keratoderma MIM#601952, Proteasome-associated autoinflammatory syndrome 2, MIM# 618048; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.13075 POMT1 Zornitza Stark Gene: pomt1 has been classified as Green List (High Evidence).
Mendeliome v0.13073 POMT2 Zornitza Stark Gene: pomt2 has been classified as Green List (High Evidence).
Mendeliome v0.13071 PPARA Zornitza Stark Gene: ppara has been classified as Red List (Low Evidence).
Mendeliome v0.13069 PPARA Zornitza Stark Classified gene: PPARA as Red List (low evidence)
Mendeliome v0.13069 PPARA Zornitza Stark Gene: ppara has been classified as Red List (Low Evidence).
Mendeliome v0.13068 PPM1K Zornitza Stark Gene: ppm1k has been classified as Red List (Low Evidence).
Mendeliome v0.13065 PPM1K Zornitza Stark Classified gene: PPM1K as Red List (low evidence)
Mendeliome v0.13065 PPM1K Zornitza Stark Gene: ppm1k has been classified as Red List (Low Evidence).
Mendeliome v0.13064 PPOX Zornitza Stark Gene: ppox has been classified as Green List (High Evidence).
Mendeliome v0.13061 PPP1R15B Zornitza Stark Gene: ppp1r15b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13061 SGCG Samantha Ayres reviewed gene: SGCG: Rating: GREEN; Mode of pathogenicity: None; Publications: 18285821, 8923014, 7481775, 8968757, 27708273; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 5 MIM#253700, autosomal recessive limb-girdle muscular dystrophy MONDO:0015152; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13061 CFHR5 Ain Roesley Gene: cfhr5 has been classified as Green List (High Evidence).
Mendeliome v0.13059 CFH Ain Roesley Gene: cfh has been classified as Green List (High Evidence).
Mendeliome v0.13055 PPP1R15B Zornitza Stark Classified gene: PPP1R15B as Amber List (moderate evidence)
Mendeliome v0.13055 PPP1R15B Zornitza Stark Gene: ppp1r15b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13054 PPP1R3A Zornitza Stark Gene: ppp1r3a has been classified as Red List (Low Evidence).
Mendeliome v0.13054 PPP1R3A Zornitza Stark Phenotypes for gene: PPP1R3A were changed from to Insulin resistance, severe, digenic 125853
Mendeliome v0.13051 PPP1R3A Zornitza Stark Classified gene: PPP1R3A as Red List (low evidence)
Mendeliome v0.13051 PPP1R3A Zornitza Stark Gene: ppp1r3a has been classified as Red List (Low Evidence).
Mendeliome v0.13050 PPP1R3A Zornitza Stark reviewed gene: PPP1R3A: Rating: RED; Mode of pathogenicity: None; Publications: 29948331, 12118251, 18232732; Phenotypes: Insulin resistance, severe, digenic 125853; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13050 PRCD Zornitza Stark Gene: prcd has been classified as Green List (High Evidence).
Mendeliome v0.13047 PRDM16 Zornitza Stark Gene: prdm16 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13044 PRDM16 Zornitza Stark Classified gene: PRDM16 as Amber List (moderate evidence)
Mendeliome v0.13044 PRDM16 Zornitza Stark Gene: prdm16 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.13043 CFD Ain Roesley Gene: cfd has been classified as Green List (High Evidence).
Mendeliome v0.13040 CEP78 Ain Roesley Gene: cep78 has been classified as Green List (High Evidence).
Mendeliome v0.13038 CEBPA Ain Roesley Gene: cebpa has been classified as Red List (Low Evidence).
Mendeliome v0.13038 CEBPA Ain Roesley Classified gene: CEBPA as Red List (low evidence)
Mendeliome v0.13038 CEBPA Ain Roesley Gene: cebpa has been classified as Red List (Low Evidence).
Mendeliome v0.13037 CEACAM16 Ain Roesley Gene: ceacam16 has been classified as Green List (High Evidence).
Mendeliome v0.13037 CEACAM16 Ain Roesley Phenotypes for gene: CEACAM16 were changed from to Deafness, autosomal dominant 4B, MIM# 614614; Deafness, autosomal recessive 113, MIM# 618410
Mendeliome v0.13036 CEACAM16 Ain Roesley reviewed gene: CEACAM16: Rating: GREEN; Mode of pathogenicity: None; Publications: 21368133, 22544735, 29703829, 25589040, 31249509, 30514912; Phenotypes: Deafness, autosomal dominant 4B, MIM# 614614, Deafness, autosomal recessive 113, MIM# 618410; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13036 CDKN2A Ain Roesley Gene: cdkn2a has been classified as Red List (Low Evidence).
Mendeliome v0.13036 CDKN2A Ain Roesley Classified gene: CDKN2A as Red List (low evidence)
Mendeliome v0.13036 CDKN2A Ain Roesley Gene: cdkn2a has been classified as Red List (Low Evidence).
Mendeliome v0.13035 CDKN1B Ain Roesley Phenotypes for gene: CDKN1B were changed from to Multiple endocrine neoplasia type 4, MEN4, OMIM #610755
Mendeliome v0.13033 CDKN1B Ain Roesley reviewed gene: CDKN1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 24819502, 17030811, 23555276; Phenotypes: Multiple endocrine neoplasia type 4, MEN4, OMIM #610755; Mode of inheritance: None; Current diagnostic: yes
Mendeliome v0.13033 CDK4 Ain Roesley Gene: cdk4 has been classified as Red List (Low Evidence).
Mendeliome v0.13032 CDK4 Ain Roesley Classified gene: CDK4 as Red List (low evidence)
Mendeliome v0.13032 CDK4 Ain Roesley Gene: cdk4 has been classified as Red List (Low Evidence).
Mendeliome v0.13031 CDK10 Ain Roesley Gene: cdk10 has been classified as Green List (High Evidence).
Mendeliome v0.13031 CDK10 Ain Roesley Phenotypes for gene: CDK10 were changed from to Al Kaissi syndrome MIM#617694
Mendeliome v0.13030 CDK10 Ain Roesley reviewed gene: CDK10: Rating: GREEN; Mode of pathogenicity: None; Publications: 28886341, 34974531; Phenotypes: Al Kaissi syndrome MIM#617694; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13030 CDHR1 Ain Roesley Gene: cdhr1 has been classified as Green List (High Evidence).
Mendeliome v0.13028 CDC73 Ain Roesley Gene: cdc73 has been classified as Green List (High Evidence).
Mendeliome v0.13025 CDC42 Ain Roesley Gene: cdc42 has been classified as Green List (High Evidence).
Mendeliome v0.13024 CDC14A Ain Roesley Gene: cdc14a has been classified as Green List (High Evidence).
Mendeliome v0.13024 CDC14A Ain Roesley Phenotypes for gene: CDC14A were changed from to Deafness, autosomal recessive 32, with or without immotile sperm, MIM# 608653
Mendeliome v0.13022 CDC14A Ain Roesley reviewed gene: CDC14A: Rating: GREEN; Mode of pathogenicity: None; Publications: 29293958, 2725905; Phenotypes: Deafness, autosomal recessive 32, with or without immotile sperm, MIM# 608653; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.13022 CD79B Ain Roesley Gene: cd79b has been classified as Green List (High Evidence).
Mendeliome v0.13020 PRDM5 Zornitza Stark Gene: prdm5 has been classified as Green List (High Evidence).
Mendeliome v0.13017 PREPL Zornitza Stark Gene: prepl has been classified as Green List (High Evidence).
Mendeliome v0.13014 PRG4 Zornitza Stark Gene: prg4 has been classified as Green List (High Evidence).
Mendeliome v0.13010 PRICKLE1 Zornitza Stark Gene: prickle1 has been classified as Green List (High Evidence).
Mendeliome v0.13010 PRICKLE1 Zornitza Stark Phenotypes for gene: PRICKLE1 were changed from to Epilepsy, progressive myoclonic 1B, MIM# 612437
Mendeliome v0.13007 PRICKLE1 Zornitza Stark reviewed gene: PRICKLE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34597683, 30564977, 30345727, 29790814, 26727662, 31035234; Phenotypes: Epilepsy, progressive myoclonic 1B, MIM# 612437; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.13007 PRKAR1A Zornitza Stark Gene: prkar1a has been classified as Green List (High Evidence).
Mendeliome v0.13007 PRKAR1A Zornitza Stark Phenotypes for gene: PRKAR1A were changed from to Acrodysostosis 1, with or without hormone resistance, MIM# 101800; Carney complex, type 1, MIM# 160980; Myxoma, intracardiac, MIM# 255960; Pigmented nodular adrenocortical disease, primary, 1, MIM# 610489
Mendeliome v0.13004 PRKAR1A Zornitza Stark reviewed gene: PRKAR1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 10973256, 11115848, 12424709, 21651393; Phenotypes: Acrodysostosis 1, with or without hormone resistance, MIM# 101800, Carney complex, type 1, MIM# 160980, Myxoma, intracardiac, MIM# 255960, Pigmented nodular adrenocortical disease, primary, 1, MIM# 610489; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.13004 PRKCG Zornitza Stark Gene: prkcg has been classified as Green List (High Evidence).
Mendeliome v0.13001 PRKG1 Zornitza Stark Gene: prkg1 has been classified as Green List (High Evidence).
Mendeliome v0.12998 PRMT7 Zornitza Stark Gene: prmt7 has been classified as Green List (High Evidence).
Mendeliome v0.12995 PRODH Zornitza Stark Gene: prodh has been classified as Green List (High Evidence).
Mendeliome v0.12992 PROK2 Zornitza Stark Gene: prok2 has been classified as Green List (High Evidence).
Mendeliome v0.12989 PROM1 Zornitza Stark Gene: prom1 has been classified as Green List (High Evidence).
Mendeliome v0.12986 PROS1 Zornitza Stark Gene: pros1 has been classified as Green List (High Evidence).
Mendeliome v0.12986 PROS1 Zornitza Stark Phenotypes for gene: PROS1 were changed from to Thrombophilia 5 due to protein S deficiency, autosomal dominant, MIM# 612336; Thrombophilia 5 due to protein S deficiency, autosomal recessive, MIM# 614514
Mendeliome v0.12983 PROS1 Zornitza Stark reviewed gene: PROS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 7545463, 19466456, 10063989, 20484936, 19729839; Phenotypes: Thrombophilia 5 due to protein S deficiency, autosomal dominant, MIM# 612336, Thrombophilia 5 due to protein S deficiency, autosomal recessive, MIM# 614514; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12983 PRPF3 Zornitza Stark Gene: prpf3 has been classified as Green List (High Evidence).
Mendeliome v0.12980 PRPF4 Zornitza Stark Gene: prpf4 has been classified as Green List (High Evidence).
Mendeliome v0.12977 PRPF6 Zornitza Stark Gene: prpf6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12974 PRPF6 Zornitza Stark Classified gene: PRPF6 as Amber List (moderate evidence)
Mendeliome v0.12974 PRPF6 Zornitza Stark Gene: prpf6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12973 PRPH Zornitza Stark Gene: prph has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12973 PRPH Zornitza Stark Phenotypes for gene: PRPH were changed from to {Amyotrophic lateral sclerosis, susceptibility to}, 105400
Mendeliome v0.12970 PRPH Zornitza Stark Classified gene: PRPH as Amber List (moderate evidence)
Mendeliome v0.12970 PRPH Zornitza Stark Gene: prph has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12969 PRPH Zornitza Stark reviewed gene: PRPH: Rating: AMBER; Mode of pathogenicity: None; Publications: 20363051, 15322088, 15446584; Phenotypes: {Amyotrophic lateral sclerosis, susceptibility to}, 105400; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12969 PRSS1 Zornitza Stark Gene: prss1 has been classified as Green List (High Evidence).
Mendeliome v0.12966 PRSS12 Zornitza Stark Gene: prss12 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12963 PRSS12 Zornitza Stark Classified gene: PRSS12 as Amber List (moderate evidence)
Mendeliome v0.12963 PRSS12 Zornitza Stark Gene: prss12 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12962 PSMC2 Zornitza Stark Gene: psmc2 has been classified as Red List (Low Evidence).
Mendeliome v0.12962 PSMC2 Zornitza Stark Classified gene: PSMC2 as Red List (low evidence)
Mendeliome v0.12962 PSMC2 Zornitza Stark Gene: psmc2 has been classified as Red List (Low Evidence).
Mendeliome v0.12961 PSMC3IP Zornitza Stark Gene: psmc3ip has been classified as Green List (High Evidence).
Mendeliome v0.12961 PSMC3IP Zornitza Stark Phenotypes for gene: PSMC3IP were changed from to Ovarian dysgenesis 3, MIM# 614324
Mendeliome v0.12958 PSMC3IP Zornitza Stark reviewed gene: PSMC3IP: Rating: GREEN; Mode of pathogenicity: None; Publications: 21963259, 35352317, 34878148, 30406445, 29240891; Phenotypes: Ovarian dysgenesis 3, MIM# 614324; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12958 PSMD12 Zornitza Stark Gene: psmd12 has been classified as Green List (High Evidence).
Mendeliome v0.12958 PSMD12 Zornitza Stark Phenotypes for gene: PSMD12 were changed from to Stankiewicz-Isidor syndrome, MIM# 617516
Mendeliome v0.12955 PSMD12 Zornitza Stark reviewed gene: PSMD12: Rating: GREEN; Mode of pathogenicity: None; Publications: 28132691, 34906456; Phenotypes: Stankiewicz-Isidor syndrome, MIM# 617516; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12955 PSPH Zornitza Stark Gene: psph has been classified as Green List (High Evidence).
Mendeliome v0.12952 PSTPIP1 Zornitza Stark Gene: pstpip1 has been classified as Green List (High Evidence).
Mendeliome v0.12949 PTGDR Zornitza Stark Gene: ptgdr has been classified as Red List (Low Evidence).
Mendeliome v0.12947 PTGDR Zornitza Stark Classified gene: PTGDR as Red List (low evidence)
Mendeliome v0.12947 PTGDR Zornitza Stark Gene: ptgdr has been classified as Red List (Low Evidence).
Mendeliome v0.12946 PTH Zornitza Stark Gene: pth has been classified as Green List (High Evidence).
Mendeliome v0.12943 PTH1R Zornitza Stark Gene: pth1r has been classified as Green List (High Evidence).
Mendeliome v0.12943 PTH1R Zornitza Stark Phenotypes for gene: PTH1R were changed from to Failure of tooth eruption, primary MIM#125350; Eiken syndrome MIM#600002; Metaphyseal chondrodysplasia, Murk Jansen type MIM#156400; Chondrodysplasia, Blomstrand type MIM#215045
Mendeliome v0.12940 PTH1R Zornitza Stark reviewed gene: PTH1R: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Failure of tooth eruption, primary MIM#125350, Eiken syndrome MIM#600002, Metaphyseal chondrodysplasia, Murk Jansen type MIM#156400, Chondrodysplasia, Blomstrand type MIM#215045; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12940 PTHLH Zornitza Stark Gene: pthlh has been classified as Green List (High Evidence).
Mendeliome v0.12937 PTPN14 Zornitza Stark Gene: ptpn14 has been classified as Green List (High Evidence).
Mendeliome v0.12937 PTPN14 Zornitza Stark Phenotypes for gene: PTPN14 were changed from to Choanal atresia and lymphoedema, MIM# 613611
Mendeliome v0.12934 PTPN14 Zornitza Stark reviewed gene: PTPN14: Rating: GREEN; Mode of pathogenicity: None; Publications: 20826270; Phenotypes: Choanal atresia and lymphoedema, MIM# 613611; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12932 TCF3 Zornitza Stark Phenotypes for gene: TCF3 were changed from Agammaglobulinaemia 8, autosomal dominant, MIM# 616941 to Agammaglobulinaemia 8, autosomal dominant, MIM# 616941; Agammaglobulinaemia 8B, autosomal recessive, MIM# 619824
Mendeliome v0.12931 TCF3 Zornitza Stark edited their review of gene: TCF3: Changed phenotypes: Agammaglobulinaemia 8, autosomal dominant, MIM# 616941, Agammaglobulinaemia 8B, autosomal recessive, MIM# 619824
Mendeliome v0.12930 PTPN22 Zornitza Stark Gene: ptpn22 has been classified as Red List (Low Evidence).
Mendeliome v0.12929 PTPN22 Zornitza Stark Classified gene: PTPN22 as Red List (low evidence)
Mendeliome v0.12929 PTPN22 Zornitza Stark Gene: ptpn22 has been classified as Red List (Low Evidence).
Mendeliome v0.12928 PTPRO Zornitza Stark Gene: ptpro has been classified as Green List (High Evidence).
Mendeliome v0.12925 PTRH2 Zornitza Stark Gene: ptrh2 has been classified as Green List (High Evidence).
Mendeliome v0.12922 PTRH2 Zornitza Stark commented on gene: PTRH2: Infantile-onset multisystem neurologic, endocrine, and pancreatic disease-1 (IMNEPD1) is an autosomal recessive multisystemic disorder with variable expressivity. The core features usually include global developmental delay with impaired intellectual development and speech delay, ataxia, sensorineural hearing loss, and pancreatic insufficiency. Additional features may include peripheral neuropathy, postnatal microcephaly, dysmorphic facial features, and cerebellar atrophy.

More than 5 unrelated families reported. The Q85P missense variant is reported in several families, likely founder effect.
Mendeliome v0.12922 PTS Zornitza Stark Gene: pts has been classified as Green List (High Evidence).
Mendeliome v0.12920 PUM1 Zornitza Stark Gene: pum1 has been classified as Green List (High Evidence).
Mendeliome v0.12917 PYCR2 Zornitza Stark Gene: pycr2 has been classified as Green List (High Evidence).
Mendeliome v0.12913 PYROXD1 Zornitza Stark Gene: pyroxd1 has been classified as Green List (High Evidence).
Mendeliome v0.12910 F12 Bryony Thompson commented on gene: F12: Also associated with FXII deficiency - PMID: 29383625, 20022356, 18024408, 20386432, 26709783, 21264442, 28007010, 15205584, 30700128 - Biallalelic loss-of-function variants are a well-established cause of FXII deficiency. FXII deficiency is not associated with bleeding risk unlike other coagulation factors, it is either asymptomatic or characterized by a prolonged activated partial thromboplastin time. DEFINITIVE gene-disease validity classification by the ClinGen Hemostasis Thrombosis VCEP, Classification - 01/22/2020
Mendeliome v0.12910 SGCD Zornitza Stark Gene: sgcd has been classified as Green List (High Evidence).
Mendeliome v0.12910 SGCD Zornitza Stark Phenotypes for gene: SGCD were changed from to Muscular dystrophy, limb-girdle, autosomal recessive 6, MIM# 601287; autosomal recessive limb-girdle muscular dystrophy MONDO:0015152
Mendeliome v0.12907 SGCD Zornitza Stark reviewed gene: SGCD: Rating: GREEN; Mode of pathogenicity: None; Publications: 8841194, 19259135, 20623375, 10838250, 10735275, 9832045, 30733730; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 6, MIM# 601287, autosomal recessive limb-girdle muscular dystrophy MONDO:0015152; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12907 SGCB Zornitza Stark Gene: sgcb has been classified as Green List (High Evidence).
Mendeliome v0.12907 SGCB Zornitza Stark Phenotypes for gene: SGCB were changed from to Muscular dystrophy, limb-girdle, autosomal recessive 4 MIM#604286; autosomal recessive limb-girdle muscular dystrophy, MONDO:0015152
Mendeliome v0.12904 SGCA Zornitza Stark Gene: sgca has been classified as Green List (High Evidence).
Mendeliome v0.12904 SGCA Zornitza Stark Phenotypes for gene: SGCA were changed from to Muscular dystrophy, limb-girdle, autosomal recessive 3 MIM#608099; autosomal recessive limb-girdle muscular dystrophy, MONDO:0015152
Mendeliome v0.12901 SFXN4 Zornitza Stark Gene: sfxn4 has been classified as Green List (High Evidence).
Mendeliome v0.12898 SFRP4 Zornitza Stark Gene: sfrp4 has been classified as Green List (High Evidence).
Mendeliome v0.12895 RASGRP1 Zornitza Stark Gene: rasgrp1 has been classified as Green List (High Evidence).
Mendeliome v0.12892 PDCD1 Zornitza Stark Gene: pdcd1 has been classified as Red List (Low Evidence).
Mendeliome v0.12888 PDCD1 Zornitza Stark Classified gene: PDCD1 as Red List (low evidence)
Mendeliome v0.12888 PDCD1 Zornitza Stark Gene: pdcd1 has been classified as Red List (Low Evidence).
Mendeliome v0.12887 PCK2 Zornitza Stark Gene: pck2 has been classified as Red List (Low Evidence).
Mendeliome v0.12885 PCK2 Zornitza Stark Classified gene: PCK2 as Red List (low evidence)
Mendeliome v0.12885 PCK2 Zornitza Stark Gene: pck2 has been classified as Red List (Low Evidence).
Mendeliome v0.12883 PCCB Zornitza Stark Gene: pccb has been classified as Green List (High Evidence).
Mendeliome v0.12880 PCCA Zornitza Stark Gene: pcca has been classified as Green List (High Evidence).
Mendeliome v0.12877 FXR1 Bryony Thompson Phenotypes for gene: FXR1 were changed from Congenital multi-minicore myopathy; multiminicore myopathy MONDO:0018948 to Congenital multi-minicore myopathy; myopathy, congenital proximal, with minicore lesions MONDO:0032937
Mendeliome v0.12874 PC Zornitza Stark Gene: pc has been classified as Green List (High Evidence).
Mendeliome v0.12871 PAX9 Zornitza Stark Gene: pax9 has been classified as Green List (High Evidence).
Mendeliome v0.12871 PAX9 Zornitza Stark Phenotypes for gene: PAX9 were changed from to Tooth agenesis, selective, 3 - MIM#604625
Mendeliome v0.12866 SET Zornitza Stark Gene: set has been classified as Green List (High Evidence).
Mendeliome v0.12863 SERPING1 Zornitza Stark Gene: serping1 has been classified as Green List (High Evidence).
Mendeliome v0.12859 SGCD Samantha Ayres reviewed gene: SGCD: Rating: GREEN; Mode of pathogenicity: None; Publications: 8841194, 30733730, 10838250; Phenotypes: autosomal recessive limb-girdle muscular dystrophy MONDO:0015152, Muscular dystrophy, limb-girdle, autosomal recessive 6, MIM#601287; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12859 SGCB Samantha Ayres reviewed gene: SGCB: Rating: GREEN; Mode of pathogenicity: None; Publications: 18285821; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 4 MIM#604286, autosomal recessive limb-girdle muscular dystrophy, MONDO:0015152; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12859 SGCA Samantha Ayres reviewed gene: SGCA: Rating: GREEN; Mode of pathogenicity: None; Publications: 30007747, 9192266, 34404573; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 3 MIM#608099, autosomal recessive limb-girdle muscular dystrophy, MONDO:0015152; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12859 SERPIND1 Zornitza Stark Gene: serpind1 has been classified as Green List (High Evidence).
Mendeliome v0.12855 PDCD1 Krithika Murali changed review comment from: No OMIM gene disease association.

1 individual from a consanguineous family reported with PDCD1 deficiency.

PMID: 34183838 (Nat Medicine 2021) - proband is the son of consanguineous Turkish parents. He was diagnosed with type 1 diabetes (T1D), hypothyroidism, and juvenile idiopathic arthritis (JIA) at the age of three years. He developed abdominal TB age 10 and died from pulmonary alveolar haemorrhage age 11. WES identified homozygous intragenic PDCD1 gene duplication (c.105dupC p.T36Hfs*70). Absent from population databases and unaffected parents confirmed to be heterozygous. Supportive in vitro studies showing absent expression or function of PD-1 protein. Proband's older brother died at the age of 3 from unexplained pneumonitis and had a history of T1DM and juvenile idiopathic arthritis.; to: No OMIM gene disease association.

1 individual from a consanguineous family reported with PDCD1 deficiency.

PMID: 34183838 (Nat Medicine 2021) - proband is the son of consanguineous Turkish parents. He was diagnosed with type 1 diabetes (T1D), hypothyroidism, and juvenile idiopathic arthritis (JIA) at the age of three years. He developed abdominal TB age 10 and died from pulmonary alveolar haemorrhage age 11. WES identified homozygous intragenic PDCD1 gene duplication (c.105dupC p.T36Hfs*70). Absent from population databases and unaffected parents confirmed to be heterozygous. Supportive in vitro studies showing absent expression or function of PD-1 protein. Proband's older brother died at the age of 3 from unexplained pneumonitis and had a history of T1DM and juvenile idiopathic arthritis.
Mendeliome v0.12855 CD79A Ain Roesley Gene: cd79a has been classified as Green List (High Evidence).
Mendeliome v0.12853 CD70 Ain Roesley Gene: cd70 has been classified as Green List (High Evidence).
Mendeliome v0.12851 CD55 Ain Roesley Gene: cd55 has been classified as Green List (High Evidence).
Mendeliome v0.12851 CD55 Ain Roesley Phenotypes for gene: CD55 were changed from to Complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy, MIM# 226300
Mendeliome v0.12849 CD55 Ain Roesley reviewed gene: CD55: Rating: GREEN; Mode of pathogenicity: None; Publications: 28657829, 28657861; Phenotypes: Complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy, MIM# 226300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.12849 CD46 Ain Roesley Gene: cd46 has been classified as Green List (High Evidence).
Mendeliome v0.12848 CD40 Ain Roesley Gene: cd40 has been classified as Green List (High Evidence).
Mendeliome v0.12846 CD36 Ain Roesley Gene: cd36 has been classified as Green List (High Evidence).
Mendeliome v0.12844 CD209 Ain Roesley Gene: cd209 has been classified as Red List (Low Evidence).
Mendeliome v0.12844 CD209 Ain Roesley Phenotypes for gene: CD209 were changed from to {Dengue fever, protection against} MIM#614371; {HIV type 1, susceptibility to} MIM#609423; {Mycobacterium tuberculosis, susceptibility to} MIM#607948
Mendeliome v0.12844 CD209 Ain Roesley Classified gene: CD209 as Red List (low evidence)
Mendeliome v0.12844 CD209 Ain Roesley Gene: cd209 has been classified as Red List (Low Evidence).
Mendeliome v0.12843 CD209 Ain Roesley reviewed gene: CD209: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Dengue fever, protection against} MIM#614371, {HIV type 1, susceptibility to} MIM#609423, {Mycobacterium tuberculosis, susceptibility to} MIM#607948; Mode of inheritance: None; Current diagnostic: yes
Mendeliome v0.12843 CD151 Ain Roesley Gene: cd151 has been classified as Green List (High Evidence).
Mendeliome v0.12843 CD151 Ain Roesley Phenotypes for gene: CD151 were changed from to Nephropathy with pretibial epidermolysis bullosa and deafness, MIM#609057
Mendeliome v0.12841 CD151 Ain Roesley reviewed gene: CD151: Rating: GREEN; Mode of pathogenicity: None; Publications: 15265795, 29138120; Phenotypes: Nephropathy with pretibial epidermolysis bullosa and deafness, MIM#609057; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.12841 CCR5 Ain Roesley Gene: ccr5 has been classified as Green List (High Evidence).
Mendeliome v0.12841 CCR5 Ain Roesley Phenotypes for gene: CCR5 were changed from to {Hepatitis C virus, resistance to} 609532; {HIV infection, susceptibility/resistance to}; {West nile virus, susceptibility to}MIM# 610379
Mendeliome v0.12839 CCR5 Ain Roesley reviewed gene: CCR5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: {Hepatitis C virus, resistance to} 609532, {HIV infection, susceptibility/resistance to}, {West nile virus, susceptibility to}MIM# 610379; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.12839 CCR2 Ain Roesley Phenotypes for gene: CCR2 were changed from to {HIV infection, susceptibility/resistance to}
Mendeliome v0.12838 CCR2 Ain Roesley changed review comment from: Currently no mendelian gene-disease association; to: Vall64Ile has been associated with reduction in the progression to AIDS. Mutant results in normal expression levels of the CCR2 receptor and has no effect on the incidence of HIV infection. However, in contrast to normal CCR2 peptides, the mutant protein preferentially dimerizes with the CXCR4 polypeptide, isolating it in the endoplasmic reticulum. It is also thought that the inhibitory effect is dependent on the stages of HIV-1 infection and interactions with other genetic variants.
Mendeliome v0.12838 CCR2 Ain Roesley edited their review of gene: CCR2: Changed phenotypes: {HIV infection, susceptibility/resistance to}
Mendeliome v0.12838 CCR2 Ain Roesley Classified gene: CCR2 as Red List (low evidence)
Mendeliome v0.12838 CCR2 Ain Roesley Gene: ccr2 has been classified as Red List (Low Evidence).
Mendeliome v0.12837 CCR2 Ain Roesley Classified gene: CCR2 as Red List (low evidence)
Mendeliome v0.12837 CCR2 Ain Roesley Gene: ccr2 has been classified as Red List (Low Evidence).
Mendeliome v0.12836 CCR2 Ain Roesley Gene: ccr2 has been classified as Green List (High Evidence).
Mendeliome v0.12836 SLC25A12 Zornitza Stark Gene: slc25a12 has been classified as Green List (High Evidence).
Mendeliome v0.12833 SLC25A13 Zornitza Stark Gene: slc25a13 has been classified as Green List (High Evidence).
Mendeliome v0.12830 SLC25A15 Zornitza Stark Gene: slc25a15 has been classified as Green List (High Evidence).
Mendeliome v0.12827 SLC25A19 Zornitza Stark Gene: slc25a19 has been classified as Green List (High Evidence).
Mendeliome v0.12827 SLC25A19 Zornitza Stark Phenotypes for gene: SLC25A19 were changed from to Microcephaly, Amish type, MIM#607196; Thiamine metabolism dysfunction syndrome 4 (progressive polyneuropathy type), MIM#613710
Mendeliome v0.12824 SLC25A19 Zornitza Stark reviewed gene: SLC25A19: Rating: GREEN; Mode of pathogenicity: None; Publications: 31506564, 31295743, 12185364, 19798730; Phenotypes: Microcephaly, Amish type, MIM#607196, Thiamine metabolism dysfunction syndrome 4 (progressive polyneuropathy type), MIM#613710; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12824 SLC25A22 Zornitza Stark Gene: slc25a22 has been classified as Green List (High Evidence).
Mendeliome v0.12821 TRPM1 Zornitza Stark Gene: trpm1 has been classified as Green List (High Evidence).
Mendeliome v0.12821 TRPM1 Zornitza Stark Phenotypes for gene: TRPM1 were changed from to Night blindness, congenital stationary (complete), 1C, autosomal recessive, MIM# 613216
Mendeliome v0.12818 TRPM1 Zornitza Stark reviewed gene: TRPM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19878917, 19896113, 19896109; Phenotypes: Night blindness, congenital stationary (complete), 1C, autosomal recessive, MIM# 613216; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12818 TRPC6 Zornitza Stark Gene: trpc6 has been classified as Green List (High Evidence).
Mendeliome v0.12818 TRPC6 Zornitza Stark Phenotypes for gene: TRPC6 were changed from to Glomerulosclerosis, focal segmental, 2, MIM# 603965
Mendeliome v0.12815 TRPC6 Zornitza Stark reviewed gene: TRPC6: Rating: GREEN; Mode of pathogenicity: None; Publications: 15879175, 15924139, 34387384, 33918778, 32509715; Phenotypes: Glomerulosclerosis, focal segmental, 2, MIM# 603965; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12815 TRAPPC2 Zornitza Stark Gene: trappc2 has been classified as Green List (High Evidence).
Mendeliome v0.12815 TRAPPC2 Zornitza Stark Phenotypes for gene: TRAPPC2 were changed from to Spondyloepiphyseal dysplasia tarda, MIM# 313400
Mendeliome v0.12812 TRAPPC2 Zornitza Stark reviewed gene: TRAPPC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 10431248, 14755465, 33726005, 20301324, 32953644; Phenotypes: Spondyloepiphyseal dysplasia tarda, MIM# 313400; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.12812 TRAPPC12 Zornitza Stark Gene: trappc12 has been classified as Green List (High Evidence).
Mendeliome v0.12812 TRAPPC11 Zornitza Stark Gene: trappc11 has been classified as Green List (High Evidence).
Mendeliome v0.12812 TRAPPC11 Zornitza Stark Phenotypes for gene: TRAPPC11 were changed from to Muscular dystrophy, limb-girdle, autosomal recessive 18, MIM# 615356
Mendeliome v0.12809 TRAPPC11 Zornitza Stark reviewed gene: TRAPPC11: Rating: GREEN; Mode of pathogenicity: None; Publications: 23830518, 26322222, 29855340, 30105108; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 18, MIM# 615356; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12809 TRAK1 Zornitza Stark Gene: trak1 has been classified as Green List (High Evidence).
Mendeliome v0.12806 TPMT Zornitza Stark Gene: tpmt has been classified as Red List (Low Evidence).
Mendeliome v0.12805 TPMT Zornitza Stark Classified gene: TPMT as Red List (low evidence)
Mendeliome v0.12805 TPMT Zornitza Stark Gene: tpmt has been classified as Red List (Low Evidence).
Mendeliome v0.12804 TRNT1 Zornitza Stark Gene: trnt1 has been classified as Green List (High Evidence).
Mendeliome v0.12804 TRNT1 Zornitza Stark Phenotypes for gene: TRNT1 were changed from to Retinitis pigmentosa and erythrocytic microcytosis, MIM# 616959; Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay, MIM# 616084
Mendeliome v0.12801 TRNT1 Zornitza Stark reviewed gene: TRNT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25193871, 23553769, 29170023, 27389523, 26494905; Phenotypes: Retinitis pigmentosa and erythrocytic microcytosis, MIM# 616959, Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay, MIM# 616084; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12801 TRMU Zornitza Stark Gene: trmu has been classified as Green List (High Evidence).
Mendeliome v0.12801 TRMU Zornitza Stark Phenotypes for gene: TRMU were changed from to Liver failure, transient infantile, MIM# 613070
Mendeliome v0.12798 TRMU Zornitza Stark reviewed gene: TRMU: Rating: GREEN; Mode of pathogenicity: None; Publications: 19732863; Phenotypes: Liver failure, transient infantile, MIM# 613070; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12798 TRMT5 Zornitza Stark Gene: trmt5 has been classified as Green List (High Evidence).
Mendeliome v0.12793 ETV1 Bryony Thompson Gene: etv1 has been classified as Red List (Low Evidence).
Mendeliome v0.12791 ETV1 Bryony Thompson Classified gene: ETV1 as Red List (low evidence)
Mendeliome v0.12791 ETV1 Bryony Thompson Gene: etv1 has been classified as Red List (Low Evidence).
Mendeliome v0.12790 EXOC3L2 Bryony Thompson Phenotypes for gene: EXOC3L2 were changed from Dandy-Walker malformation; renal dysplasia; bone marrow failure to Dandy-Walker malformation, MONDO:0009072; renal dysplasia; bone marrow failure
Mendeliome v0.12789 ETFDH Bryony Thompson Gene: etfdh has been classified as Green List (High Evidence).
Mendeliome v0.12787 TRMT10C Zornitza Stark Gene: trmt10c has been classified as Green List (High Evidence).
Mendeliome v0.12784 PDHA2 Zornitza Stark Gene: pdha2 has been classified as Red List (Low Evidence).
Mendeliome v0.12783 TRDN Zornitza Stark Gene: trdn has been classified as Green List (High Evidence).
Mendeliome v0.12780 TRHR Zornitza Stark Gene: trhr has been classified as Green List (High Evidence).
Mendeliome v0.12777 TRIM37 Zornitza Stark Gene: trim37 has been classified as Green List (High Evidence).
Mendeliome v0.12774 TRIM32 Zornitza Stark Gene: trim32 has been classified as Green List (High Evidence).
Mendeliome v0.12774 TRIM32 Zornitza Stark Phenotypes for gene: TRIM32 were changed from to Bardet-Biedl syndrome 11, MIM# 615988; Muscular dystrophy, limb-girdle, autosomal recessive 8 MIM#254110
Mendeliome v0.12771 TRIM32 Zornitza Stark changed review comment from: Single family reported in 2006.; to: BBS: Single family reported in 2006. LIMITED.
Mendeliome v0.12771 TRIM32 Zornitza Stark edited their review of gene: TRIM32: Added comment: >3 unrelated cases with myopathy, adult onset reported; Changed rating: GREEN; Changed publications: 16606853, 31309175, 11822024; Changed phenotypes: Bardet-Biedl syndrome 11, MIM# 615988, Muscular dystrophy, limb-girdle, autosomal recessive 8 MIM#254110
Mendeliome v0.12771 TRPM4 Zornitza Stark Gene: trpm4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12771 TRPM4 Zornitza Stark Phenotypes for gene: TRPM4 were changed from to Progressive familial heart block, type IB, MIM# 604559; Erythrokeratodermia variabilis et progressiva 6, MIM# 618531
Mendeliome v0.12768 TRPM4 Zornitza Stark Classified gene: TRPM4 as Amber List (moderate evidence)
Mendeliome v0.12768 TRPM4 Zornitza Stark Gene: trpm4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12767 TRPM4 Zornitza Stark reviewed gene: TRPM4: Rating: AMBER; Mode of pathogenicity: None; Publications: 19726882, 20562447, 21887725, 20562447, 35205305, 34897640, 30528822; Phenotypes: Progressive familial heart block, type IB, MIM# 604559, Erythrokeratodermia variabilis et progressiva 6 618531; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12767 TRPV4 Zornitza Stark Gene: trpv4 has been classified as Green List (High Evidence).
Mendeliome v0.12765 TTPA Zornitza Stark Gene: ttpa has been classified as Green List (High Evidence).
Mendeliome v0.12762 TTC19 Zornitza Stark Gene: ttc19 has been classified as Green List (High Evidence).
Mendeliome v0.12759 TTC19 Zornitza Stark edited their review of gene: TTC19: Added comment: Mitochondrial complex III deficiency nuclear type 2 is an autosomal recessive severe neurodegenerative disorder that usually presents in childhood, but may show later onset, even in adulthood. Affected individuals have motor disability, with ataxia, apraxia, dystonia, and dysarthria, associated with necrotic lesions throughout the brain. Most patients also have cognitive impairment and axonal neuropathy and become severely disabled later in life. The disorder may present clinically as spinocerebellar ataxia or Leigh syndrome, or with psychiatric disturbances.

At least 4 unrelated families reported.; Changed publications: 21278747, 23532514, 24368687, 24397319
Mendeliome v0.12759 TSFM Zornitza Stark Gene: tsfm has been classified as Green List (High Evidence).
Mendeliome v0.12756 PAX9 Krithika Murali reviewed gene: PAX9: Rating: GREEN; Mode of pathogenicity: None; Publications: 10615120, 16479262; Phenotypes: Tooth agenesis, selective, 3 - MIM#604625; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12756 TPK1 Zornitza Stark Gene: tpk1 has been classified as Green List (High Evidence).
Mendeliome v0.12753 TP63 Zornitza Stark Gene: tp63 has been classified as Green List (High Evidence).
Mendeliome v0.12753 TP63 Zornitza Stark Phenotypes for gene: TP63 were changed from to ADULT syndrome, OMIM #103285; Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3, OMIM #604292; Hay-Wells syndrome, OMIM #106260; Limb-mammary syndrome, OMIM #603543; Orofacial cleft 8, OMIM #618149; Rapp-Hodgkin syndrome, OMIM #129400; Split-hand/foot malformation 4, OMIM #605289
Mendeliome v0.12750 TP63 Zornitza Stark reviewed gene: TP63: Rating: GREEN; Mode of pathogenicity: None; Publications: 20556892; Phenotypes: ADULT syndrome, OMIM #103285, Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3, OMIM #604292, Hay-Wells syndrome, OMIM #106260, Limb-mammary syndrome, OMIM #603543, Orofacial cleft 8, OMIM #618149, Rapp-Hodgkin syndrome, OMIM #129400, Split-hand/foot malformation 4, OMIM #605289; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12750 TOR1A Zornitza Stark Gene: tor1a has been classified as Green List (High Evidence).
Mendeliome v0.12750 TOR1A Zornitza Stark Phenotypes for gene: TOR1A were changed from to Arthrogryposis multiplex congenita, MIM#618947; Dystonia-1, torsion, MIM#128100
Mendeliome v0.12747 TOR1A Zornitza Stark reviewed gene: TOR1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 30244176, 9288096, 19955557, 18477710, 32243914, 31583275, 31347572; Phenotypes: Arthrogryposis multiplex congenita, MIM#618947, Dystonia-1, torsion, MIM#128100; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12747 TNXB Zornitza Stark Gene: tnxb has been classified as Green List (High Evidence).
Mendeliome v0.12747 TNXB Zornitza Stark Phenotypes for gene: TNXB were changed from to Ehlers-Danlos syndrome, classic-like, 1 MIM# 606408
Mendeliome v0.12744 TNXB Zornitza Stark reviewed gene: TNXB: Rating: GREEN; Mode of pathogenicity: None; Publications: 28306229, 28306225, 23620400; Phenotypes: Ehlers-Danlos syndrome, classic-like, 1 MIM# 606408; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12744 TNPO3 Zornitza Stark Gene: tnpo3 has been classified as Green List (High Evidence).
Mendeliome v0.12741 RSPO2 Zornitza Stark Gene: rspo2 has been classified as Green List (High Evidence).
Mendeliome v0.12738 PIGA Zornitza Stark changed review comment from: PIGA 34875027: variants in PIGA causing a neurodevelopment disorder and a juvenile form of hereditary hemochromatosis reported in > three unrelated patients. All patients had increased serum iron, ferritin and transferrin saturation levels, high ALP and low hepcidin. All patients had generalised seizures and intellectual disability. A subpopulation of patient blood cells showed a slight reduction of GPI-anchored proteins, suggesting that the mutations were hypomorphic and retained some residual activity. CRISPR/Cas12a-mediated knockdown of PIGA in Hep3B liver cells eliminated the cell surface expression of GPI-anchored proteins CD59 and hemojuvelin (HJV; 608374), as well as caused decreased expression of hepcidin (606464) compared to controls. These hypomorphic alleles could explain the milder neurologic phenotype, which allowed for sufficiently long survival for the iron overload phenotype to manifest.; to: PMID 34875027: variants in PIGA causing a neurodevelopment disorder and a juvenile form of hereditary hemochromatosis reported in > three unrelated patients. All patients had increased serum iron, ferritin and transferrin saturation levels, high ALP and low hepcidin. All patients had generalised seizures and intellectual disability. A subpopulation of patient blood cells showed a slight reduction of GPI-anchored proteins, suggesting that the mutations were hypomorphic and retained some residual activity. CRISPR/Cas12a-mediated knockdown of PIGA in Hep3B liver cells eliminated the cell surface expression of GPI-anchored proteins CD59 and hemojuvelin (HJV; 608374), as well as caused decreased expression of hepcidin (606464) compared to controls. These hypomorphic alleles could explain the milder neurologic phenotype, which allowed for sufficiently long survival for the iron overload phenotype to manifest.
Mendeliome v0.12738 PIGA Zornitza Stark Phenotypes for gene: PIGA were changed from Multiple congenital anomalies-hypotonia-seizures syndrome 2, MIM# 300868, MONDO:0010466 to Multiple congenital anomalies-hypotonia-seizures syndrome 2, MIM# 300868, MONDO:0010466; Neurodevelopmental disorder with epilepsy and haemochromatosis, MIM# 301072
Mendeliome v0.12737 PIGA Zornitza Stark edited their review of gene: PIGA: Added comment: PIGA 34875027: variants in PIGA causing a neurodevelopment disorder and a juvenile form of hereditary hemochromatosis reported in > three unrelated patients. All patients had increased serum iron, ferritin and transferrin saturation levels, high ALP and low hepcidin. All patients had generalised seizures and intellectual disability. A subpopulation of patient blood cells showed a slight reduction of GPI-anchored proteins, suggesting that the mutations were hypomorphic and retained some residual activity. CRISPR/Cas12a-mediated knockdown of PIGA in Hep3B liver cells eliminated the cell surface expression of GPI-anchored proteins CD59 and hemojuvelin (HJV; 608374), as well as caused decreased expression of hepcidin (606464) compared to controls. These hypomorphic alleles could explain the milder neurologic phenotype, which allowed for sufficiently long survival for the iron overload phenotype to manifest.; Changed publications: 22305531, 24357517, 24706016, 26545172, 33333793, 32694024, 34875027; Changed phenotypes: Multiple congenital anomalies-hypotonia-seizures syndrome 2, MIM# 300868, MONDO:0010466, Neurodevelopmental disorder with epilepsy and haemochromatosis, MIM# 301072
Mendeliome v0.12737 SLC35B2 Zornitza Stark Phenotypes for gene: SLC35B2 were changed from chondrodysplasia with hypomyelinating leukodystrophy, intellectual disability to Leukodystrophy, MONDO:0019046, SLC35B2-related
Mendeliome v0.12733 TNNC1 Zornitza Stark Gene: tnnc1 has been classified as Green List (High Evidence).
Mendeliome v0.12733 CACNA2D1 Alison Yeung Gene: cacna2d1 has been classified as Green List (High Evidence).
Mendeliome v0.12732 CACNA2D1 Alison Yeung Classified gene: CACNA2D1 as Green List (high evidence)
Mendeliome v0.12732 CACNA2D1 Alison Yeung Gene: cacna2d1 has been classified as Green List (High Evidence).
Mendeliome v0.12731 CACNA2D1 Michelle Torres gene: CACNA2D1 was added
gene: CACNA2D1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CACNA2D1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CACNA2D1 were set to 35293990
Phenotypes for gene: CACNA2D1 were set to developmental and epileptic encephalopathy disorder MONDO:0100062 CACNA2D1-related
Review for gene: CACNA2D1 was set to GREEN
Added comment: PMID 35293990: WES of 2x unrelated individuals with early-onset developmental epileptic encephalopathy, microcephaly, severe hypotonia, absent speech, spasticity, choreiform movements, orofacial dyskinesia, and 2 cortical visual impairment, corpus callosum hypoplasia and progressive volume loss. Patient 2 also had a tiny patent foramen ovale.

Patient 1 is homozygous for p.(Ser275Asnfs*13). mRNA and protein expression were reduced to ~10% of WT in fibroblasts

Patient 2 is cHet for p.(Leu9Alafs*5) and p.(Gly209Asp). mRNA expression in patients fibroblasts was similar to controls, and protein expression reduced to 31-38%. Functional of the p.(Gly209Asp) showed impaired localization and mutagenesis showed complete loss of channel function.
Sources: Literature
Mendeliome v0.12731 TRAPPC10 Zornitza Stark Gene: trappc10 has been classified as Green List (High Evidence).
Mendeliome v0.12731 TRAPPC10 Zornitza Stark Classified gene: TRAPPC10 as Green List (high evidence)
Mendeliome v0.12731 TRAPPC10 Zornitza Stark Gene: trappc10 has been classified as Green List (High Evidence).
Mendeliome v0.12729 TTC21B Zornitza Stark Phenotypes for gene: TTC21B were changed from Nephronophthisis 12, MIM# 613820; Short-rib thoracic dysplasia 4 with or without polydactyly, MIM# 613819; Joubert syndrome to Nephronophthisis 12, MIM# 613820; Short-rib thoracic dysplasia 4 with or without polydactyly, MIM# 613819; Joubert syndrome; Glomerular disorder MONDO:0019722, TTC21B-related
Mendeliome v0.12728 FUZ Zornitza Stark Phenotypes for gene: FUZ were changed from {Neural tube defects, susceptibility to} MIM#182940 to {Neural tube defects, susceptibility to} MIM#182940; craniosynostosis, FUZ-related MONDO#0015469
Mendeliome v0.12726 FUZ Anna Ritchie reviewed gene: FUZ: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 34719684; Phenotypes: craniosynostosis, FUZ-related MONDO#0015469; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12726 TNNI1 Zornitza Stark Gene: tnni1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12726 TNNI1 Zornitza Stark Classified gene: TNNI1 as Amber List (moderate evidence)
Mendeliome v0.12726 TNNI1 Zornitza Stark Gene: tnni1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12725 TNNI1 Zornitza Stark Phenotypes for gene: TNNI1 were changed from arthrogryposis; joint contractures to Arthrogryposis MONDO:0008779, TNNI1-related
Mendeliome v0.12724 SLC35B2 Alison Yeung Gene: slc35b2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12724 SLC35B2 Alison Yeung Classified gene: SLC35B2 as Amber List (moderate evidence)
Mendeliome v0.12724 SLC35B2 Alison Yeung Gene: slc35b2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12723 ATP2B1 Zornitza Stark Gene: atp2b1 has been classified as Green List (High Evidence).
Mendeliome v0.12723 ATP2B1 Zornitza Stark Classified gene: ATP2B1 as Green List (high evidence)
Mendeliome v0.12723 ATP2B1 Zornitza Stark Gene: atp2b1 has been classified as Green List (High Evidence).
Mendeliome v0.12722 SLC35B2 Melanie Marty changed review comment from: 2 x individuals with homozygous variants (c.1218_1220del and c.1224_1225del) in SLC35B2. Phenotypes included pre- and postnatal growth retardation, scoliosis, severe motor and intellectual disabilities and hypomyelinating leukodystrophy.

Functional analysis on patient cells showed that the variants result in a decreased expression of mRNA and affect protein subcellular localization leading to functional impairment of the protein.
Sources: Literature; to: 2 x individuals with homozygous variants (c.1218_1220del and c.1224_1225del) in SLC35B2. Phenotypes included pre- and postnatal growth retardation, scoliosis, severe motor and intellectual disabilities and hypomyelinating leukodystrophy.

Functional analysis on patient cells showed that the variants result in a decreased expression of mRNA and affect protein subcellular localization leading to functional impairment of the protein.
Sources: Literature
Mendeliome v0.12720 MDFIC Zornitza Stark Gene: mdfic has been classified as Green List (High Evidence).
Mendeliome v0.12720 TTC21B Dean Phelan reviewed gene: TTC21B: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 35289079; Phenotypes: early onset hypertension, proteinuria, progressive kidney disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12720 FUZ Anna Ritchie changed review comment from: Novel missense p.(Arg284Pro) mutation in FUZ identified in twins presenting with craniosynostosis. Loss of Fuz resulted in increased mineralisation in both in vitro embryonic primary osteoblast cultures and in fibroblasts undergoing an osteogenic challenge. No previous reports have implicated changes in human FUZ in craniosynostosis. However, variations in FUZ have been found in patients with neural tube defects.; to: Novel missense p.(Arg284Pro) mutation in FUZ identified in twins presenting with craniosynostosis. Loss of Fuz resulted in increased mineralisation in both in vitro embryonic primary osteoblast cultures and in fibroblasts undergoing an osteogenic challenge. No previous reports have implicated changes in human FUZ in craniosynostosis. However, variations in FUZ have been found in patients with neural tube defects.
Mendeliome v0.12719 ADAM22 Alison Yeung Classified gene: ADAM22 as Green List (high evidence)
Mendeliome v0.12719 ADAM22 Alison Yeung Gene: adam22 has been classified as Green List (High Evidence).
Mendeliome v0.12717 MDFIC Zornitza Stark Classified gene: MDFIC as Green List (high evidence)
Mendeliome v0.12717 MDFIC Zornitza Stark Gene: mdfic has been classified as Green List (High Evidence).
Mendeliome v0.12716 FUZ Anna Ritchie reviewed gene: FUZ: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 34719684; Phenotypes: Craniosynostosis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12714 TNNI1 Krithika Murali gene: TNNI1 was added
gene: TNNI1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TNNI1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TNNI1 were set to 34934811
Phenotypes for gene: TNNI1 were set to arthrogryposis; joint contractures
Review for gene: TNNI1 was set to AMBER
Added comment: No OMIM gene disease association reported

PMID 34934811 Nishimori et al report 2 individuals from a Japanese family with joint contractures, elevated CK and a novel heterozygous TNNI1 variant.

The proband was born with clasped thumbs (gestational age not stated) requiring surgical correction at 5 months of age. At age 14 was diagnosed with contractures of the neck, trunk, hip and knee with elevated serum CK (1689 IU/L). No muscle weakness noted. Muscle biopsy showed moth-eaten appearance of type I fibres and electron microscopy showed type 1 fibre Z disk streaming.

Trio exome sequencing identified a paternally heterozygous nonsense TNNI1 variant (c.523A>T p.K175*). The proband's father and paternal grandfather (not genotyped) also have a history of joint contractures with elevated CK.

The affected amino acid residue is in the tropomyosin binding site near the C-terminus and is highly conserved. The variant is absent from gnomAD. rt-PCR products of mRNA from the patient's muscle biopsy showed presence of both mutated and normal transcripts.
Sources: Literature
Mendeliome v0.12714 SLC35B2 Melanie Marty gene: SLC35B2 was added
gene: SLC35B2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLC35B2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC35B2 were set to PMID: 35325049
Phenotypes for gene: SLC35B2 were set to chondrodysplasia with hypomyelinating leukodystrophy, intellectual disability
Review for gene: SLC35B2 was set to AMBER
Added comment: 2 x individuals with homozygous variants (c.1218_1220del and c.1224_1225del) in SLC35B2. Phenotypes included pre- and postnatal growth retardation, scoliosis, severe motor and intellectual disabilities and hypomyelinating leukodystrophy.

Functional analysis on patient cells showed that the variants result in a decreased expression of mRNA and affect protein subcellular localization leading to functional impairment of the protein.
Sources: Literature
Mendeliome v0.12714 AHSG Elena Savva gene: AHSG was added
gene: AHSG was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AHSG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AHSG were set to PMID: 28054173; 9395485; 31288248; 17389622
Phenotypes for gene: AHSG were set to ?Alopecia-intellectual disability syndrome 1 MIM#203650; infantile cortical hyperostosis
Review for gene: AHSG was set to RED
Added comment: PMID: 28054173 - 7 relatives within a large consanguinous fam w/ alopecia and ID, and a hom missense (p.Arg317His). Modelling predicts this variant to be a phosphorylation site, functional studies show a difference in protein size. Unclear biological significance.
Alt change with stronger GS (p.(Arg317Cys)) is a common poly with 19 homozygotes in gnomAD.

No hom PTCs in gnomAD

PMID: 9395485 - K/O mouse model shows no gross anatomical abnormalities, were fertile and "healthy". No mentioned of ID, alopecia
PMID: 17389622 - K/O mouse model on the calcification resistant genetic background C57BL/6, shows uraemia and phosphate challenge. No mentioned of ID, alopecia

PMID: 31288248 - 1 hom infant (p.K2*, within 5' NMD escape region) with infantile cortical hyperostosis, loss of enzyme in patient serum shown by ELISA. No mentioned of ID, alopecia
Sources: Literature
Mendeliome v0.12713 VPS16 Ain Roesley Phenotypes for gene: VPS16 were changed from Dystonia 30, MIM#619291 to Dystonia 30, MIM#619291; mucopolysaccharidosis-like disorder, VPS16-related MONDO#0100365
Mendeliome v0.12711 MDFIC Belinda Chong gene: MDFIC was added
gene: MDFIC was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MDFIC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MDFIC were set to 35235341
Phenotypes for gene: MDFIC were set to Central conducting lymphatic anomaly with lymphedema
Review for gene: MDFIC was set to GREEN
Added comment: Central conducting lymphatic anomaly (CCLA), characterized by the dysfunction of core collecting lymphatic vessels including the thoracic duct and cisterna chyli, and presenting as chylothorax, pleural effusions, chylous ascites, and lymphedema, is a severe disorder often resulting in fetal or perinatal demise.

Seven individuals with CCLA from six independent families. Clinical manifestations of affected fetuses and children included nonimmune hydrops fetalis (NIHF), pleural and pericardial effusions, and lymphedema. Generation of a mouse model of human MDFIC truncation variants revealed that homozygous mutant mice died perinatally exhibiting chylothorax.
Sources: Literature
Mendeliome v0.12711 ATP2B1 Daniel Flanagan gene: ATP2B1 was added
gene: ATP2B1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ATP2B1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP2B1 were set to PMID: 35358416
Phenotypes for gene: ATP2B1 were set to Neurodevelopmental delay; autism; seizures; distal limb abnormalities
Review for gene: ATP2B1 was set to GREEN
Added comment: 12 unrelated individuals with variants in ATP2B1 and an overlapping phenotype of mild to moderate global development delay. Additional common symptoms include autism (5), dissimilar forms of seizures (6), and distal limb abnormalities (4). 9 variants proven to be de novo, other 3 variants had unknown inheritance. 9 missense and 3 nonsense reported. Supporting functional analysis for missense.
Sources: Expert list
Mendeliome v0.12711 TNFSF4 Zornitza Stark Gene: tnfsf4 has been classified as Red List (Low Evidence).
Mendeliome v0.12709 VPS16 Ain Roesley reviewed gene: VPS16: Rating: GREEN; Mode of pathogenicity: None; Publications: 33938619, 34013567; Phenotypes: mucopolysaccharidosis-like disorder, VPS16-related MONDO#0100365; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.12709 TNFSF4 Zornitza Stark Classified gene: TNFSF4 as Red List (low evidence)
Mendeliome v0.12709 TNFSF4 Zornitza Stark Gene: tnfsf4 has been classified as Red List (Low Evidence).
Mendeliome v0.12708 TNFSF11 Zornitza Stark Gene: tnfsf11 has been classified as Green List (High Evidence).
Mendeliome v0.12708 TNFSF11 Zornitza Stark Phenotypes for gene: TNFSF11 were changed from to Osteopetrosis, autosomal recessive 2, MIM# 259710
Mendeliome v0.12705 TNFSF11 Zornitza Stark reviewed gene: TNFSF11: Rating: GREEN; Mode of pathogenicity: None; Publications: 17632511; Phenotypes: Osteopetrosis, autosomal recessive 2, MIM# 259710; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12705 TNFRSF11B Zornitza Stark Gene: tnfrsf11b has been classified as Green List (High Evidence).
Mendeliome v0.12702 TMEM240 Zornitza Stark Gene: tmem240 has been classified as Green List (High Evidence).
Mendeliome v0.12699 TMEM127 Zornitza Stark Gene: tmem127 has been classified as Green List (High Evidence).
Mendeliome v0.12697 TMEM126B Zornitza Stark Gene: tmem126b has been classified as Green List (High Evidence).
Mendeliome v0.12694 TMEM106B Zornitza Stark Gene: tmem106b has been classified as Green List (High Evidence).
Mendeliome v0.12691 TMEM106B Zornitza Stark changed review comment from: Cerebellar signs including ataxia prominent.; to: Hypomyelinating leukodystrophy-16 is an autosomal dominant neurologic disorder characterized by onset of hypotonia, nystagmus, and mildly delayed motor development in infancy. Affected individuals have motor disabilities, including ataxic or broad-based gait, hyperreflexia, intention tremor, dysmetria, and a mild pyramidal syndrome. Some patients have cognitive impairment, whereas others may have normal cognition or mild intellectual disability with speech difficulties. Brain imaging typically shows hypomyelination, leukodystrophy, and thin corpus callosum.

At least 5 unrelated individuals reported.
Mendeliome v0.12691 RAPSN Zornitza Stark Gene: rapsn has been classified as Green List (High Evidence).
Mendeliome v0.12691 RAPSN Zornitza Stark Phenotypes for gene: RAPSN were changed from to Fetal akinesia deformation sequence 2 (MIM#618388); Myasthenic syndrome, congenital, 11, associated with acetylcholine receptor deficiency (MIM#616326)
Mendeliome v0.12688 RAD51C Zornitza Stark Gene: rad51c has been classified as Green List (High Evidence).
Mendeliome v0.12684 SLC25A26 Zornitza Stark Gene: slc25a26 has been classified as Green List (High Evidence).
Mendeliome v0.12684 GGN Zornitza Stark Gene: ggn has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12684 GGN Zornitza Stark Classified gene: GGN as Amber List (moderate evidence)
Mendeliome v0.12684 GGN Zornitza Stark Gene: ggn has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12679 SLC25A3 Zornitza Stark Gene: slc25a3 has been classified as Green List (High Evidence).
Mendeliome v0.12676 RAPSN Crystle Lee reviewed gene: RAPSN: Rating: GREEN; Mode of pathogenicity: None; Publications: 18252226, 19620612, 22482962, 28495245, 18179903, 28495245; Phenotypes: Fetal akinesia deformation sequence 2 (MIM#618388), Myasthenic syndrome, congenital, 11, associated with acetylcholine receptor deficiency (MIM#616326); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12676 SLC25A4 Zornitza Stark Gene: slc25a4 has been classified as Green List (High Evidence).
Mendeliome v0.12676 SLC25A4 Zornitza Stark Phenotypes for gene: SLC25A4 were changed from to Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) AD, MIM#617184; Mitochondrial DNA depletion syndrome 12B (cardiomyopathic type) AR, MIM#615418; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 2, MIM#609283
Mendeliome v0.12673 SLC25A4 Zornitza Stark reviewed gene: SLC25A4: Rating: GREEN; Mode of pathogenicity: None; Publications: 30046662, 30013777, 29654543, 28823815; Phenotypes: Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) AD, MIM#617184, Mitochondrial DNA depletion syndrome 12B (cardiomyopathic type) AR, MIM#615418, Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 2, MIM#609283; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12673 SLC25A42 Zornitza Stark Gene: slc25a42 has been classified as Green List (High Evidence).
Mendeliome v0.12673 SLC25A42 Zornitza Stark Phenotypes for gene: SLC25A42 were changed from to Metabolic crises, recurrent, with variable encephalomyopathic features and neurologic regression , MIM#618416
Mendeliome v0.12670 SLC25A42 Zornitza Stark reviewed gene: SLC25A42: Rating: GREEN; Mode of pathogenicity: None; Publications: 26541337, 29327420, 29923093, 34258143; Phenotypes: Metabolic crises, recurrent, with variable encephalomyopathic features and neurologic regression , MIM#618416; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12670 SLC2A10 Zornitza Stark Gene: slc2a10 has been classified as Green List (High Evidence).
Mendeliome v0.12670 SLC2A10 Zornitza Stark Phenotypes for gene: SLC2A10 were changed from to Arterial tortuosity syndrome, MIM# 208050
Mendeliome v0.12667 SLC2A10 Zornitza Stark reviewed gene: SLC2A10: Rating: GREEN; Mode of pathogenicity: None; Publications: 30071989, 16550171, 17935213; Phenotypes: Arterial tortuosity syndrome, MIM# 208050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12667 SLC2A2 Zornitza Stark changed review comment from: Fanconi-Bickel syndrome is a rare but well-defined clinical entity, inherited in an autosomal recessive mode and characterized by hepatorenal glycogen accumulation, proximal renal tubular dysfunction, and impaired utilization of glucose and galactose.

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

> 5 patients previously reported with the associated condition, which is a glycogen storage disease. SLC2A2 encodes for the glucose transporter, GLUT2.
Mendeliome v0.12667 SLC2A2 Zornitza Stark Gene: slc2a2 has been classified as Green List (High Evidence).
Mendeliome v0.12664 SLC2A3 Zornitza Stark Gene: slc2a3 has been classified as Red List (Low Evidence).
Mendeliome v0.12664 SLC2A3 Zornitza Stark Classified gene: SLC2A3 as Red List (low evidence)
Mendeliome v0.12664 SLC2A3 Zornitza Stark Gene: slc2a3 has been classified as Red List (Low Evidence).
Mendeliome v0.12663 SLC2A4 Zornitza Stark Gene: slc2a4 has been classified as Red List (Low Evidence).
Mendeliome v0.12663 SLC2A4 Zornitza Stark Classified gene: SLC2A4 as Red List (low evidence)
Mendeliome v0.12663 SLC2A4 Zornitza Stark Gene: slc2a4 has been classified as Red List (Low Evidence).
Mendeliome v0.12662 SORT1 Zornitza Stark Gene: sort1 has been classified as Red List (Low Evidence).
Mendeliome v0.12662 SORT1 Zornitza Stark Phenotypes for gene: SORT1 were changed from to Low density lipoprotein cholesterol level QTL6] 613589
Mendeliome v0.12660 SORT1 Zornitza Stark Classified gene: SORT1 as Red List (low evidence)
Mendeliome v0.12660 SORT1 Zornitza Stark Gene: sort1 has been classified as Red List (Low Evidence).
Mendeliome v0.12659 SORT1 Zornitza Stark reviewed gene: SORT1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: [Low density lipoprotein cholesterol level QTL6] 613589; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12659 SOX10 Zornitza Stark Gene: sox10 has been classified as Green List (High Evidence).
Mendeliome v0.12656 SOX17 Zornitza Stark Gene: sox17 has been classified as Green List (High Evidence).
Mendeliome v0.12656 SOX17 Zornitza Stark Phenotypes for gene: SOX17 were changed from to Vesicoureteral reflux 3 MIM#613674; Pulmonary arterial hypertension, MONDO:0015924
Mendeliome v0.12653 SOX17 Zornitza Stark reviewed gene: SOX17: Rating: GREEN; Mode of pathogenicity: None; Publications: 29650961, 31406341, 20960469; Phenotypes: Vesicoureteral reflux 3 MIM#613674, Pulmonary arterial hypertension, MONDO:0015924; Mode of inheritance: None
Mendeliome v0.12653 SOX18 Zornitza Stark Gene: sox18 has been classified as Green List (High Evidence).
Mendeliome v0.12653 SOX18 Zornitza Stark Phenotypes for gene: SOX18 were changed from to Hypotrichosis-lymphedema-telangiectasia syndrome, MIM# 607823; Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome, MIM# 137940
Mendeliome v0.12650 SOX18 Zornitza Stark reviewed gene: SOX18: Rating: GREEN; Mode of pathogenicity: None; Publications: 12740761, 24697860, 2484451, 26148450, 33851505; Phenotypes: Hypotrichosis-lymphedema-telangiectasia syndrome, MIM# 607823, Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome, MIM# 137940; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12650 SOX5 Zornitza Stark Gene: sox5 has been classified as Green List (High Evidence).
Mendeliome v0.12647 SOX9 Zornitza Stark Gene: sox9 has been classified as Green List (High Evidence).
Mendeliome v0.12647 SOX9 Zornitza Stark Phenotypes for gene: SOX9 were changed from to Campomelic dysplasia, MIM# 114290; Campomelic dysplasia, MONDO:0007251
Mendeliome v0.12644 SOX9 Zornitza Stark reviewed gene: SOX9: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Campomelic dysplasia, MIM# 114290, Campomelic dysplasia, MONDO:0007251; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12644 NKX2-1 Zornitza Stark reviewed gene: NKX2-1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Choreoathetosis, hypothyroidism, and neonatal respiratory distress MIM#610978, Chorea, hereditary benign MIM#118700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12644 SP7 Zornitza Stark Gene: sp7 has been classified as Green List (High Evidence).
Mendeliome v0.12644 SP7 Zornitza Stark Phenotypes for gene: SP7 were changed from to Osteogenesis imperfecta type 12, MONDO:0013460; Osteogenesis imperfecta, type XII, OMIM:613849
Mendeliome v0.12641 SP7 Zornitza Stark reviewed gene: SP7: Rating: GREEN; Mode of pathogenicity: None; Publications: 20579626, 29382611, 35367406, 34091789, 32413570; Phenotypes: Osteogenesis imperfecta type 12, MONDO:0013460, Osteogenesis imperfecta, type XII, OMIM:613849; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12641 SPAG7 Zornitza Stark Gene: spag7 has been classified as Red List (Low Evidence).
Mendeliome v0.12638 SPAG7 Zornitza Stark Classified gene: SPAG7 as Red List (low evidence)
Mendeliome v0.12638 SPAG7 Zornitza Stark Gene: spag7 has been classified as Red List (Low Evidence).
Mendeliome v0.12637 SPATA5 Zornitza Stark Gene: spata5 has been classified as Green List (High Evidence).
Mendeliome v0.12634 SPECC1L Zornitza Stark Gene: specc1l has been classified as Green List (High Evidence).
Mendeliome v0.12631 SPECC1L Zornitza Stark edited their review of gene: SPECC1L: Added comment: Well established gene-disease associations with Teebi and Opitz GBBB.

Single individual reported with oblique facial cleft, some supportive functional data.; Changed publications: 25412741, 26111080, 21703590; Changed phenotypes: Hypertelorism, Teebi type, MIM# 145420, Opitz GBBB syndrome, type II, MIM#145410
Mendeliome v0.12631 SPECC1L Zornitza Stark edited their review of gene: SPECC1L: Changed phenotypes: Hypertelorism, Teebi type, MIM# 145420, Opitz GBBB syndrome, type II, MIM#145410, Craniosynostosis
Mendeliome v0.12631 SSR4 Zornitza Stark Gene: ssr4 has been classified as Green List (High Evidence).
Mendeliome v0.12628 SRY Zornitza Stark Gene: sry has been classified as Green List (High Evidence).
Mendeliome v0.12625 SRP54 Zornitza Stark Gene: srp54 has been classified as Green List (High Evidence).
Mendeliome v0.12622 SRD5A2 Zornitza Stark Gene: srd5a2 has been classified as Green List (High Evidence).
Mendeliome v0.12619 SPRY1 Zornitza Stark Gene: spry1 has been classified as Red List (Low Evidence).
Mendeliome v0.12619 SPRY1 Zornitza Stark Classified gene: SPRY1 as Red List (low evidence)
Mendeliome v0.12619 SPRY1 Zornitza Stark Gene: spry1 has been classified as Red List (Low Evidence).
Mendeliome v0.12618 SPINK5 Zornitza Stark Gene: spink5 has been classified as Green List (High Evidence).
Mendeliome v0.12615 SPINK1 Zornitza Stark Gene: spink1 has been classified as Green List (High Evidence).
Mendeliome v0.12612 SPG7 Zornitza Stark Phenotypes for gene: SPG7 were changed from Spastic paraplegia 7, autosomal recessive, MIM# 607259 to Spastic paraplegia 7, autosomal recessive, MIM# 607259; Autosomal dominant optic atrophy, MONDO:0020250
Mendeliome v0.12610 SPG7 Zornitza Stark changed review comment from: SPG7 mutations most often lead to spastic paraparesis (HSP) and/or hereditary cerebellar ataxia (HCA), frequently with mixed phenotypes.

Well established for bi-allelic variants.

Enrichment of mono-allelic variants reported in a couple of cohorts, although a recent one suggests digenic inheritance.; to: SPG7 mutations most often lead to spastic paraparesis (HSP) and/or hereditary cerebellar ataxia (HCA), frequently with mixed phenotypes.

Well established for bi-allelic variants.

Enrichment of mono-allelic variants reported in a couple of cohorts, although a recent one suggests digenic inheritance.

Association with OA: 7 families reported for AD OA, including 5 missense and 2 frameshift variants, PMID 32548275
Mendeliome v0.12610 SPG7 Zornitza Stark edited their review of gene: SPG7: Changed publications: 9635427, 9635427, 16534102, 18799786, 22571692, 34500365, 33598982, 32548275; Changed phenotypes: Spastic paraplegia 7, autosomal recessive, MIM# 607259, Autosomal dominant optic atrophy, MONDO:0020250; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12610 SPG7 Zornitza Stark Gene: spg7 has been classified as Green List (High Evidence).
Mendeliome v0.12610 SPG7 Zornitza Stark Phenotypes for gene: SPG7 were changed from to Spastic paraplegia 7, autosomal recessive, MIM# 607259
Mendeliome v0.12607 SPG7 Zornitza Stark reviewed gene: SPG7: Rating: GREEN; Mode of pathogenicity: None; Publications: 9635427, 9635427, 16534102, 18799786, 22571692, 34500365, 33598982; Phenotypes: Spastic paraplegia 7, autosomal recessive, MIM# 607259; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12607 RSPO4 Zornitza Stark Gene: rspo4 has been classified as Green List (High Evidence).
Mendeliome v0.12604 RTN4IP1 Zornitza Stark Gene: rtn4ip1 has been classified as Green List (High Evidence).
Mendeliome v0.12601 RUNX1 Zornitza Stark Gene: runx1 has been classified as Green List (High Evidence).
Mendeliome v0.12598 PAX6 Zornitza Stark Gene: pax6 has been classified as Green List (High Evidence).
Mendeliome v0.12598 PAX6 Zornitza Stark Phenotypes for gene: PAX6 were changed from to Coloboma of optic nerve - MIM# 120430; Coloboma, ocular - MIM#120200; Morning glory disc anomaly - MIM#120430; Aniridia - MIM#106210; Anterior segment dysgenesis 5, multiple subtypes - MIM#604229; Cataract with late-onset corneal dystrophy - MIM#106210; Foveal hypoplasia 1- MIM#136520; Keratitis - MIM#148190; Optic nerve hypoplasia - MIM#165550
Mendeliome v0.12595 PAX2 Zornitza Stark Gene: pax2 has been classified as Green List (High Evidence).
Mendeliome v0.12595 PAX2 Zornitza Stark Phenotypes for gene: PAX2 were changed from to Papillorenal syndrome, MIM# 120330; Renal coloboma syndrome, MONDO:0007352; Glomerulosclerosis, focal segmental, 7 - MIM#616002
Mendeliome v0.12592 TSEN15 Zornitza Stark Gene: tsen15 has been classified as Green List (High Evidence).
Mendeliome v0.12592 TSEN15 Zornitza Stark Phenotypes for gene: TSEN15 were changed from to Pontocerebellar hypoplasia, type 2F, MIM # 617026, MONDO:0014874
Mendeliome v0.12589 TSEN15 Zornitza Stark reviewed gene: TSEN15: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pontocerebellar hypoplasia, type 2F, MIM # 617026, MONDO:0014874; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12589 RAB33B Zornitza Stark Gene: rab33b has been classified as Green List (High Evidence).
Mendeliome v0.12589 RAB33B Zornitza Stark Phenotypes for gene: RAB33B were changed from to Smith-McCort dysplasia 2 (MIM#615222)
Mendeliome v0.12586 RAB28 Zornitza Stark Gene: rab28 has been classified as Green List (High Evidence).
Mendeliome v0.12583 PAM16 Zornitza Stark Gene: pam16 has been classified as Green List (High Evidence).
Mendeliome v0.12583 PAM16 Zornitza Stark Phenotypes for gene: PAM16 were changed from to Spondylometaphyseal dysplasia, Megarbane-Dagher-Melike type, OMIM # 613320
Mendeliome v0.12580 PALLD Zornitza Stark Gene: palld has been classified as Red List (Low Evidence).
Mendeliome v0.12580 PALLD Zornitza Stark Classified gene: PALLD as Red List (low evidence)
Mendeliome v0.12580 PALLD Zornitza Stark Gene: palld has been classified as Red List (Low Evidence).
Mendeliome v0.12578 AMPD3 Zornitza Stark Gene: ampd3 has been classified as Red List (Low Evidence).
Mendeliome v0.12575 AMPD3 Zornitza Stark Classified gene: AMPD3 as Red List (low evidence)
Mendeliome v0.12575 AMPD3 Zornitza Stark Gene: ampd3 has been classified as Red List (Low Evidence).
Mendeliome v0.12573 PAX6 Krithika Murali reviewed gene: PAX6: Rating: GREEN; Mode of pathogenicity: None; Publications: 31700164, 30986449, 29930474, 22171686; Phenotypes: ?Coloboma of optic nerve - MIM# 120430, ?Coloboma, ocular - MIM#120200, ?Morning glory disc anomaly - MIM#120430, Aniridia - MIM#106210, Anterior segment dysgenesis 5, multiple subtypes - MIM#604229, Cataract with late-onset corneal dystrophy - MIM#106210, Foveal hypoplasia 1- MIM#136520, Keratitis - MIM#148190, Optic nerve hypoplasia - MIM#165550; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12573 PAX2 Krithika Murali reviewed gene: PAX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21654726, 24676634, 31060108, 32203253; Phenotypes: Papillorenal syndrome, MIM# 120330, Renal coloboma syndrome, MONDO:0007352, Glomerulosclerosis, focal segmental, 7 - MIM#616002; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12573 TSEN15 Manny Jacobs reviewed gene: TSEN15: Rating: ; Mode of pathogenicity: None; Publications: PMID: 25558065, 27392077; Phenotypes: Pontocerebellar hypoplasia, type 2F, MIM # 617026, MONDO:0014874; Mode of inheritance: None
Mendeliome v0.12573 RAB33B Crystle Lee reviewed gene: RAB33B: Rating: GREEN; Mode of pathogenicity: None; Publications: 22652534, 28127940, 23042644, 34284742; Phenotypes: Smith-McCort dysplasia 2 (MIM#615222); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12571 SERPINC1 Zornitza Stark Gene: serpinc1 has been classified as Green List (High Evidence).
Mendeliome v0.12568 SERPINB8 Zornitza Stark Gene: serpinb8 has been classified as Green List (High Evidence).
Mendeliome v0.12565 SERPINB6 Zornitza Stark Gene: serpinb6 has been classified as Green List (High Evidence).
Mendeliome v0.12565 SERPINB6 Zornitza Stark Phenotypes for gene: SERPINB6 were changed from to Deafness, autosomal recessive 91, MIM# 613453
Mendeliome v0.12561 PAM16 Krithika Murali reviewed gene: PAM16: Rating: GREEN; Mode of pathogenicity: None; Publications: 24786642, 27354339; Phenotypes: Spondylometaphyseal dysplasia, Megarbane-Dagher-Melike type, OMIM # 613320; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12561 CCM2 Ain Roesley Gene: ccm2 has been classified as Green List (High Evidence).
Mendeliome v0.12559 CCL2 Ain Roesley Gene: ccl2 has been classified as Red List (Low Evidence).
Mendeliome v0.12559 CCL2 Ain Roesley Phenotypes for gene: CCL2 were changed from to {HIV-1, resistance to} MIM#609423; {Mycobacterium tuberculosis, susceptibility to} MIM#607948; {Spina bifida, susceptibility to} MIM#182940
Mendeliome v0.12559 CCL2 Ain Roesley Classified gene: CCL2 as Red List (low evidence)
Mendeliome v0.12559 CCL2 Ain Roesley Gene: ccl2 has been classified as Red List (Low Evidence).
Mendeliome v0.12558 CCL2 Ain Roesley reviewed gene: CCL2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {HIV-1, resistance to} MIM#609423, {Mycobacterium tuberculosis, susceptibility to} MIM#607948, {Spina bifida, susceptibility to} MIM#182940; Mode of inheritance: None; Current diagnostic: yes
Mendeliome v0.12558 ANK1 Elena Savva Phenotypes for gene: ANK1 were changed from Spherocytosis, type 1 MIM#182900 to Spherocytosis, type 1 MIM#182900
Mendeliome v0.12557 CCDC88A Ain Roesley Gene: ccdc88a has been classified as Green List (High Evidence).
Mendeliome v0.12556 ANK1 Elena Savva Phenotypes for gene: ANK1 were changed from to Spherocytosis, type 1 MIM#182900
Mendeliome v0.12555 ANK1 Elena Savva Gene: ank1 has been classified as Green List (High Evidence).
Mendeliome v0.12554 ANK1 Elena Savva reviewed gene: ANK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 8640229; Phenotypes: Spherocytosis, type 1 MIM#182900; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12554 ANKH Elena Savva Gene: ankh has been classified as Green List (High Evidence).
Mendeliome v0.12554 CCDC50 Ain Roesley Gene: ccdc50 has been classified as Green List (High Evidence).
Mendeliome v0.12553 ANKLE2 Elena Savva Phenotypes for gene: ANKLE2 were changed from Microcephaly 16, primary, autosomal recessive, MIM# 616681 to Microcephaly 16, primary, autosomal recessive, MIM# 616681
Mendeliome v0.12552 ANKLE2 Elena Savva Phenotypes for gene: ANKLE2 were changed from Microcephaly 16, primary, autosomal recessive, MIM# 616681 to Microcephaly 16, primary, autosomal recessive, MIM# 616681
Mendeliome v0.12550 ANKH Elena Savva Phenotypes for gene: ANKH were changed from to Chondrocalcinosis 2 MIM#118600; Craniometaphyseal dysplasia MIM#123000
Mendeliome v0.12548 ANKLE2 Elena Savva Phenotypes for gene: ANKLE2 were changed from to Microcephaly 16, primary, autosomal recessive, MIM# 616681
Mendeliome v0.12547 ANKLE2 Elena Savva Gene: ankle2 has been classified as Green List (High Evidence).
Mendeliome v0.12546 ANKH Elena Savva reviewed gene: ANKH: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32366894; Phenotypes: Chondrocalcinosis 2 MIM#118600, Craniometaphyseal dysplasia MIM#123000; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.12546 CAV3 Ain Roesley Gene: cav3 has been classified as Green List (High Evidence).
Mendeliome v0.12542 CATSPER2 Ain Roesley Gene: catsper2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12542 CATSPER2 Ain Roesley Classified gene: CATSPER2 as Amber List (moderate evidence)
Mendeliome v0.12542 CATSPER2 Ain Roesley Gene: catsper2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12539 ANGPTL3 Elena Savva Gene: angptl3 has been classified as Green List (High Evidence).
Mendeliome v0.12536 CATSPER1 Ain Roesley Gene: catsper1 has been classified as Green List (High Evidence).
Mendeliome v0.12534 ETFA Bryony Thompson Gene: etfa has been classified as Green List (High Evidence).
Mendeliome v0.12533 ERLIN2 Bryony Thompson Gene: erlin2 has been classified as Green List (High Evidence).
Mendeliome v0.12532 TSHB Zornitza Stark Gene: tshb has been classified as Green List (High Evidence).
Mendeliome v0.12528 TSHR Zornitza Stark Gene: tshr has been classified as Green List (High Evidence).
Mendeliome v0.12525 CAT Ain Roesley Gene: cat has been classified as Green List (High Evidence).
Mendeliome v0.12523 TSPAN7 Zornitza Stark Gene: tspan7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12520 TSPAN7 Zornitza Stark Classified gene: TSPAN7 as Amber List (moderate evidence)
Mendeliome v0.12520 TSPAN7 Zornitza Stark Gene: tspan7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12518 AMT Elena Savva Gene: amt has been classified as Green List (High Evidence).
Mendeliome v0.12518 EPX Bryony Thompson Gene: epx has been classified as Red List (Low Evidence).
Mendeliome v0.12518 EPX Bryony Thompson Phenotypes for gene: EPX were changed from to [Eosinophil peroxidase deficiency] MIM#261500
Mendeliome v0.12516 AMHR2 Elena Savva Gene: amhr2 has been classified as Green List (High Evidence).
Mendeliome v0.12516 AMHR2 Elena Savva Phenotypes for gene: AMHR2 were changed from to Persistent Mullerian duct syndrome, type II MIM#261550
Mendeliome v0.12514 ALX4 Elena Savva Gene: alx4 has been classified as Green List (High Evidence).
Mendeliome v0.12514 AMHR2 Elena Savva reviewed gene: AMHR2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34810374; Phenotypes: Persistent Mullerian duct syndrome, type II MIM#261550; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12512 ALX4 Elena Savva Phenotypes for gene: ALX4 were changed from to Frontonasal dysplasia 2 MIM# 613451; Parietal foramina 2 MIM# 609597; {Craniosynostosis 5, susceptibility to} MIM#615529
Mendeliome v0.12511 EPX Bryony Thompson Classified gene: EPX as Red List (low evidence)
Mendeliome v0.12511 EPX Bryony Thompson Gene: epx has been classified as Red List (Low Evidence).
Mendeliome v0.12510 EPX Bryony Thompson reviewed gene: EPX: Rating: RED; Mode of pathogenicity: None; Publications: 7809065, 11241847; Phenotypes: [Eosinophil peroxidase deficiency] MIM#261500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12510 ALX4 Elena Savva reviewed gene: ALX4: Rating: GREEN; Mode of pathogenicity: None; Publications: 22829454, 34586326; Phenotypes: Frontonasal dysplasia 2 MIM# 613451, Parietal foramina 2 MIM# 609597, {Craniosynostosis 5, susceptibility to} MIM#615529; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12508 ALMS1 Elena Savva Gene: alms1 has been classified as Green List (High Evidence).
Mendeliome v0.12508 ALDH6A1 Elena Savva Gene: aldh6a1 has been classified as Green List (High Evidence).
Mendeliome v0.12508 ALDH18A1 Elena Savva Phenotypes for gene: ALDH18A1 were changed from Cutis laxa, autosomal recessive, type IIIA MIM#219150; Spastic paraplegia 9A, autosomal dominant MIM#601162; Spastic paraplegia 9B, autosomal recessive MIM#616586; Cutis laxa, autosomal dominant 3 MIM#616603; disorders of ornithine or proline metabolism to Cutis laxa, autosomal recessive, type IIIA MIM#219150; Spastic paraplegia 9A, autosomal dominant MIM#601162; Spastic paraplegia 9B, autosomal recessive MIM#616586; Cutis laxa, autosomal dominant 3 MIM#616603; disorders of ornithine or proline metabolism
Mendeliome v0.12505 ALDH18A1 Elena Savva Phenotypes for gene: ALDH18A1 were changed from to Cutis laxa, autosomal recessive, type IIIA MIM#219150; Spastic paraplegia 9A, autosomal dominant MIM#601162; Spastic paraplegia 9B, autosomal recessive MIM#616586; Cutis laxa, autosomal dominant 3 MIM#616603; disorders of ornithine or proline metabolism
Mendeliome v0.12504 ALDH18A1 Elena Savva Gene: aldh18a1 has been classified as Green List (High Evidence).
Mendeliome v0.12503 CASR Ain Roesley Gene: casr has been classified as Green List (High Evidence).
Mendeliome v0.12500 CASQ1 Ain Roesley Gene: casq1 has been classified as Green List (High Evidence).
Mendeliome v0.12498 SERPINB6 Samantha Ayres reviewed gene: SERPINB6: Rating: GREEN; Mode of pathogenicity: None; Publications: 20451170, 25719458, 23669344; Phenotypes: Deafness, autosomal recessive 91, MIM# 613453; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12498 TMEM98 Zornitza Stark Gene: tmem98 has been classified as Green List (High Evidence).
Mendeliome v0.12495 TMEM70 Zornitza Stark Gene: tmem70 has been classified as Green List (High Evidence).
Mendeliome v0.12492 TMEM38B Zornitza Stark Gene: tmem38b has been classified as Green List (High Evidence).
Mendeliome v0.12492 TMEM38B Zornitza Stark Phenotypes for gene: TMEM38B were changed from to Osteogenesis imperfecta, type XIV, MIM# 615066
Mendeliome v0.12489 TMEM38B Zornitza Stark reviewed gene: TMEM38B: Rating: GREEN; Mode of pathogenicity: None; Publications: 23054245; Phenotypes: Osteogenesis imperfecta, type XIV, MIM# 615066; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12489 TMEM199 Zornitza Stark Gene: tmem199 has been classified as Green List (High Evidence).
Mendeliome v0.12486 TMEM173 Zornitza Stark Gene: tmem173 has been classified as Green List (High Evidence).
Mendeliome v0.12483 TMC6 Zornitza Stark Gene: tmc6 has been classified as Green List (High Evidence).
Mendeliome v0.12483 TMC6 Zornitza Stark Phenotypes for gene: TMC6 were changed from to Epidermodysplasia verruciformis, MIM# 226400
Mendeliome v0.12480 TMC6 Zornitza Stark reviewed gene: TMC6: Rating: GREEN; Mode of pathogenicity: None; Publications: 12426567, 15042430]; Phenotypes: Epidermodysplasia verruciformis, MIM# 226400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12480 TLR5 Zornitza Stark Gene: tlr5 has been classified as Red List (Low Evidence).
Mendeliome v0.12480 TLR5 Zornitza Stark Classified gene: TLR5 as Red List (low evidence)
Mendeliome v0.12480 TLR5 Zornitza Stark Gene: tlr5 has been classified as Red List (Low Evidence).
Mendeliome v0.12479 TLR3 Zornitza Stark Gene: tlr3 has been classified as Green List (High Evidence).
Mendeliome v0.12476 TLR2 Zornitza Stark Gene: tlr2 has been classified as Red List (Low Evidence).
Mendeliome v0.12476 TLR2 Zornitza Stark Classified gene: TLR2 as Red List (low evidence)
Mendeliome v0.12476 TLR2 Zornitza Stark Gene: tlr2 has been classified as Red List (Low Evidence).
Mendeliome v0.12475 FTCD Zornitza Stark Gene: ftcd has been classified as Green List (High Evidence).
Mendeliome v0.12475 FTCD Zornitza Stark Phenotypes for gene: FTCD were changed from Glutamate formiminotransferase deficiency MIM#229100; Disorders of histidine, tryptophan or lysine metabolism to Glutamate formiminotransferase deficiency MIM#229100; Disorders of histidine, tryptophan or lysine metabolism
Mendeliome v0.12472 FTCD Zornitza Stark Gene: ftcd has been classified as Green List (High Evidence).
Mendeliome v0.12472 FTCD Zornitza Stark Phenotypes for gene: FTCD were changed from to Glutamate formiminotransferase deficiency MIM#229100; Disorders of histidine, tryptophan or lysine metabolism
Mendeliome v0.12469 FGF14 Zornitza Stark Gene: fgf14 has been classified as Green List (High Evidence).
Mendeliome v0.12467 FAT4 Zornitza Stark Gene: fat4 has been classified as Green List (High Evidence).
Mendeliome v0.12467 FAT4 Zornitza Stark Phenotypes for gene: FAT4 were changed from to Hennekam lymphangiectasia-lymphedema syndrome 2 MIM#616006; Van Maldergem syndrome 2 MIM#615546
Mendeliome v0.12464 ERLIN1 Zornitza Stark Gene: erlin1 has been classified as Green List (High Evidence).
Mendeliome v0.12464 ERCC6 Zornitza Stark Gene: ercc6 has been classified as Green List (High Evidence).
Mendeliome v0.12460 SLC30A2 Zornitza Stark Gene: slc30a2 has been classified as Green List (High Evidence).
Mendeliome v0.12460 SLC30A2 Zornitza Stark Phenotypes for gene: SLC30A2 were changed from to Zinc deficiency, transient neonatal , MIM#608118
Mendeliome v0.12457 SLC30A2 Zornitza Stark reviewed gene: SLC30A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 17065149, 22733820, 32278324, 30450693, 28665435; Phenotypes: Zinc deficiency, transient neonatal , MIM#608118; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12457 SLC2A9 Zornitza Stark Gene: slc2a9 has been classified as Green List (High Evidence).
Mendeliome v0.12454 RIPOR2 Zornitza Stark Phenotypes for gene: RIPOR2 were changed from Deafness, autosomal recessive 104, MIM# 616515; Deafness, autosomal dominant to Deafness, autosomal recessive 104, MIM# 616515; Deafness, autosomal dominant 21, MIM# 607017
Mendeliome v0.12453 RIPOR2 Zornitza Stark edited their review of gene: RIPOR2: Changed phenotypes: Deafness, autosomal recessive 104, MIM# 616515, Deafness, autosomal dominant 21, MIM# 607017
Mendeliome v0.12451 EPS8 Bryony Thompson reviewed gene: EPS8: Rating: GREEN; Mode of pathogenicity: None; Publications: 24741995, 27344577, 30303587, 34637946, 21526224; Phenotypes: Autosomal recessive nonsyndromic hearing loss 102 MONDO:0014428; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12449 SLC30A8 Zornitza Stark Gene: slc30a8 has been classified as Red List (Low Evidence).
Mendeliome v0.12446 SLC30A8 Zornitza Stark Classified gene: SLC30A8 as Red List (low evidence)
Mendeliome v0.12446 SLC30A8 Zornitza Stark Gene: slc30a8 has been classified as Red List (Low Evidence).
Mendeliome v0.12445 SLC34A1 Zornitza Stark changed review comment from: Infantile hypercalcaemia and bi-allelic variants: More than 5 unrelated families reported.

Nephrolithiasis and mono-allelic variants: multiple families reported.; to: Infantile hypercalcaemia and bi-allelic variants: More than 5 unrelated families reported.

Nephrolithiasis and mono-allelic variants: multiple families reported.

Single family reported with renal Fanconi and homozygous variant.
Mendeliome v0.12445 SLC34A1 Zornitza Stark Gene: slc34a1 has been classified as Green List (High Evidence).
Mendeliome v0.12445 SLC34A1 Zornitza Stark Phenotypes for gene: SLC34A1 were changed from to Hypercalcaemia, infantile, 2 MIM#616963; Nephrolithiasis/osteoporosis, hypophosphatemic, 1 612286
Mendeliome v0.12442 SLC34A1 Zornitza Stark reviewed gene: SLC34A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26047794, 33516786, 33099630, 32866123, 31188746, 30943683, 12324554, 32216560, 30778725; Phenotypes: Hypercalcaemia, infantile, 2 MIM#616963, Nephrolithiasis/osteoporosis, hypophosphatemic, 1 612286; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12442 SLC34A2 Zornitza Stark Gene: slc34a2 has been classified as Green List (High Evidence).
Mendeliome v0.12442 SLC34A2 Zornitza Stark Phenotypes for gene: SLC34A2 were changed from to Pulmonary alveolar microlithiasis, MIM# 265100
Mendeliome v0.12439 SLC34A2 Zornitza Stark reviewed gene: SLC34A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 16960801, 34581165, 33884208, 32328294, 31941744; Phenotypes: Pulmonary alveolar microlithiasis, MIM# 265100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12439 SLC35A1 Zornitza Stark Gene: slc35a1 has been classified as Green List (High Evidence).
Mendeliome v0.12439 EPO Bryony Thompson Gene: epo has been classified as Green List (High Evidence).
Mendeliome v0.12436 EPO Bryony Thompson Phenotypes for gene: EPO were changed from to erythrocytosis, familial, 5 MONDO:0033483
Mendeliome v0.12435 SLC39A13 Zornitza Stark Gene: slc39a13 has been classified as Green List (High Evidence).
Mendeliome v0.12432 SLC39A5 Zornitza Stark Gene: slc39a5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12430 EPO Bryony Thompson changed review comment from: PMID: 27651169, 29514032, 25985138 - At least 4 families reported with heterozygous variants segregating with erythrocytosis. Mechanism of disease is gain-of-function. Frameshift variants identified (c.32delG, c.19delC) use of an alternative promoter (P2) in intron 1 causing the production of functional transcripts and increased amounts of biologically active EPO compared to controls, and 5’UTR conserved variant (c.‐136G>A) and expected to have a similar mechanism.

PMID: 28283061 - single proband from a consanguineous family with severe anaemia (Diamond-Blackfan anaemia phenotype) reported with a homozygous missense (R150Q) showing a mild reduction in its affinity for the EPO receptor; to: PMID: 27651169, 29514032, 25985138 - At least 4 families reported with heterozygous variants segregating with erythrocytosis. Mechanism of disease is gain-of-function. Frameshift variants identified (c.32delG, c.19delC) use of an alternative promoter (P2) in intron 1 causing the production of functional transcripts and increased amounts of biologically active EPO compared to controls, and 5’UTR conserved variant (c.‐136G>A) expected to have a similar mechanism.

PMID: 28283061 - single proband from a consanguineous family with severe anaemia (Diamond-Blackfan anaemia phenotype) reported with a homozygous missense (R150Q) showing a mild reduction in its affinity for the EPO receptor
Mendeliome v0.12429 SLC39A5 Zornitza Stark Classified gene: SLC39A5 as Amber List (moderate evidence)
Mendeliome v0.12429 SLC39A5 Zornitza Stark Gene: slc39a5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12426 EPM2A Bryony Thompson Gene: epm2a has been classified as Green List (High Evidence).
Mendeliome v0.12425 EPO Bryony Thompson reviewed gene: EPO: Rating: GREEN; Mode of pathogenicity: Other; Publications: 27651169, 29514032, 25985138, 28283061; Phenotypes: erythrocytosis, familial, 5 MONDO:0033483; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12422 EPHA3 Bryony Thompson Gene: epha3 has been classified as Red List (Low Evidence).
Mendeliome v0.12422 EPHA3 Bryony Thompson Classified gene: EPHA3 as Red List (low evidence)
Mendeliome v0.12422 EPHA3 Bryony Thompson Gene: epha3 has been classified as Red List (Low Evidence).
Mendeliome v0.12421 EPHA2 Bryony Thompson Gene: epha2 has been classified as Green List (High Evidence).
Mendeliome v0.12420 SLC40A1 Zornitza Stark Gene: slc40a1 has been classified as Green List (High Evidence).
Mendeliome v0.12420 SLC40A1 Zornitza Stark Phenotypes for gene: SLC40A1 were changed from to Haemochromatosis, type 4, MIM# 606069
Mendeliome v0.12417 SLC40A1 Zornitza Stark reviewed gene: SLC40A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11431687, 11518736, 15956209, 16351644; Phenotypes: Haemochromatosis, type 4 606069; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12415 SLC4A11 Zornitza Stark Gene: slc4a11 has been classified as Green List (High Evidence).
Mendeliome v0.12415 SLC4A11 Zornitza Stark Phenotypes for gene: SLC4A11 were changed from to Corneal dystrophy, Fuchs endothelial, 4, MIM# 613268; Corneal endothelial dystrophy and perceptive deafness, MIM# 217400; Corneal endothelial dystrophy, autosomal recessive, MIM# 217700
Mendeliome v0.12413 SLC4A11 Zornitza Stark reviewed gene: SLC4A11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Corneal dystrophy, Fuchs endothelial, 4, MIM# 613268, Corneal endothelial dystrophy and perceptive deafness, MIM# 217400, Corneal endothelial dystrophy, autosomal recessive, MIM# 217700; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12413 SLC4A4 Zornitza Stark Gene: slc4a4 has been classified as Green List (High Evidence).
Mendeliome v0.12413 SLC4A4 Zornitza Stark Phenotypes for gene: SLC4A4 were changed from to Renal tubular acidosis, proximal, with ocular abnormalities, MIM# 604278; Hemiplegic migraine
Mendeliome v0.12410 SLC4A4 Zornitza Stark reviewed gene: SLC4A4: Rating: GREEN; Mode of pathogenicity: None; Publications: 10545938, 11274232, 35260236, 33439394, 29914390; Phenotypes: Renal tubular acidosis, proximal, with ocular abnormalities, MIM# 604278, Hemiplegic migraine; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12410 ENO3 Bryony Thompson Gene: eno3 has been classified as Green List (High Evidence).
Mendeliome v0.12407 ENG Bryony Thompson Gene: eng has been classified as Green List (High Evidence).
Mendeliome v0.12407 ENG Bryony Thompson Phenotypes for gene: ENG were changed from to hereditary hemorrhagic telangiectasia MONDO:0019180
Mendeliome v0.12404 ENG Bryony Thompson reviewed gene: ENG: Rating: GREEN; Mode of pathogenicity: None; Publications: 34012068, 30336550, 7894484, 10751092, 20414677, 30763665, 17384219, 20364125; Phenotypes: hereditary hemorrhagic telangiectasia MONDO:0019180; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.12404 EMP2 Bryony Thompson Gene: emp2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12401 EMP2 Bryony Thompson Classified gene: EMP2 as Amber List (moderate evidence)
Mendeliome v0.12401 EMP2 Bryony Thompson Gene: emp2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12400 ELP2 Bryony Thompson Gene: elp2 has been classified as Green List (High Evidence).
Mendeliome v0.12400 ELP2 Bryony Thompson Phenotypes for gene: ELP2 were changed from to intellectual disability, autosomal recessive 58 MONDO:0014996
Mendeliome v0.12397 ELP2 Bryony Thompson reviewed gene: ELP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21937992, 25847581, 32573669, 34653680; Phenotypes: intellectual disability, autosomal recessive 58 MONDO:0014996; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12397 ELOVL4 Bryony Thompson Gene: elovl4 has been classified as Green List (High Evidence).
Mendeliome v0.12397 ELOVL5 Bryony Thompson Gene: elovl5 has been classified as Green List (High Evidence).
Mendeliome v0.12396 ELOVL4 Bryony Thompson Phenotypes for gene: ELOVL4 were changed from to congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome MONDO:0013760; spinocerebellar ataxia type 34 MONDO:0007574; Stargardt disease MONDO:0019353
Mendeliome v0.12390 ELOVL4 Bryony Thompson reviewed gene: ELOVL4: Rating: GREEN; Mode of pathogenicity: None; Publications: 11138005, 15028284, 11726641, 17208947, 22100072, 24566826, 34227061, 24571530, 26010696; Phenotypes: congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome MONDO:0013760, spinocerebellar ataxia type 34 MONDO:0007574, Stargardt disease MONDO:0019353; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.12390 ELN Bryony Thompson Gene: eln has been classified as Green List (High Evidence).
Mendeliome v0.12390 ELN Bryony Thompson Phenotypes for gene: ELN were changed from to cutis laxa, autosomal dominant 1 MONDO:0007411; supravalvular aortic stenosis MONDO:0008504
Mendeliome v0.12387 ELN Bryony Thompson reviewed gene: ELN: Rating: GREEN; Mode of pathogenicity: None; Publications: 8132745, 9580666, 9873040, 10190324, 10190538, 22573328, 28383366; Phenotypes: cutis laxa, autosomal dominant 1 MONDO:0007411, supravalvular aortic stenosis MONDO:0008504; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.12386 SLC52A2 Zornitza Stark Gene: slc52a2 has been classified as Green List (High Evidence).
Mendeliome v0.12384 SLC52A3 Zornitza Stark Gene: slc52a3 has been classified as Green List (High Evidence).
Mendeliome v0.12382 DVL2 Bryony Thompson Gene: dvl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12382 DVL2 Bryony Thompson Classified gene: DVL2 as Amber List (moderate evidence)
Mendeliome v0.12382 DVL2 Bryony Thompson Gene: dvl2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12381 SLC5A2 Zornitza Stark Gene: slc5a2 has been classified as Green List (High Evidence).
Mendeliome v0.12381 DVL2 Bryony Thompson gene: DVL2 was added
gene: DVL2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DVL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DVL2 were set to 35047859; 33599851; 30521570
Phenotypes for gene: DVL2 were set to Robinow syndrome MONDO:0019978
Review for gene: DVL2 was set to AMBER
Added comment: A single case with Robinow syndrome identified with a de novo frameshift variant in the last exon of the gene (c.2105dupC, p.Pro703Serfs*103). Also, a canine DVL2 frameshift variant has been associated with a Robinow-like syndrome in dogs, contributing to the brachycephalic phenotype and caudal vertebral anomalies.
Sources: Literature
Mendeliome v0.12379 SLC6A17 Zornitza Stark Gene: slc6a17 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12379 TAMM41 Bryony Thompson Gene: tamm41 has been classified as Green List (High Evidence).
Mendeliome v0.12379 TAMM41 Bryony Thompson Classified gene: TAMM41 as Green List (high evidence)
Mendeliome v0.12379 TAMM41 Bryony Thompson Gene: tamm41 has been classified as Green List (High Evidence).
Mendeliome v0.12378 TAMM41 Bryony Thompson gene: TAMM41 was added
gene: TAMM41 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TAMM41 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAMM41 were set to 35321494; 29253589
Phenotypes for gene: TAMM41 were set to inborn mitochondrial metabolism disorder MONDO:0004069; hypotonia; developmental delay; myopathy; ptosis
Review for gene: TAMM41 was set to GREEN
Added comment: Three unrelated individuals with mitochondrial disease that share clinical features, including lethargy at birth, hypotonia, developmental delay, myopathy, and ptosis with biallelic variants. Tissue-specific observations on OXPHOS were identified, cardiolipin levels were unchanged in subject fibroblasts but significantly decreased in the skeletal muscle of affected individuals. The missense variants identified were defective in yeast models. In an in vitro cell model knockdown of TAMM41 resulted in decreased mitochondrial CDP diacylglycerol synthase activity, decreased cardiolipin levels and a decrease in oxygen consumption.
Sources: Literature
Mendeliome v0.12377 SLC6A17 Zornitza Stark Phenotypes for gene: SLC6A17 were changed from to Mental retardation, autosomal recessive 48, MIM# 616269
Mendeliome v0.12374 SLC6A17 Zornitza Stark Classified gene: SLC6A17 as Amber List (moderate evidence)
Mendeliome v0.12374 SLC6A17 Zornitza Stark Gene: slc6a17 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12373 SLC6A17 Zornitza Stark reviewed gene: SLC6A17: Rating: AMBER; Mode of pathogenicity: None; Publications: 25704603, 23672601; Phenotypes: Mental retardation, autosomal recessive 48, MIM# 616269; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12373 SLC6A19 Zornitza Stark Gene: slc6a19 has been classified as Green List (High Evidence).
Mendeliome v0.12371 BNIP1 Bryony Thompson Gene: bnip1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12371 BNIP1 Bryony Thompson Classified gene: BNIP1 as Amber List (moderate evidence)
Mendeliome v0.12371 BNIP1 Bryony Thompson Gene: bnip1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12370 BNIP1 Bryony Thompson gene: BNIP1 was added
gene: BNIP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BNIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BNIP1 were set to 35266227; 31344970
Phenotypes for gene: BNIP1 were set to spondyloepiphyseal dysplasia MONDO:0016761
Review for gene: BNIP1 was set to AMBER
Added comment: Two apparently unrelated cases with spondyloepiphyseal dysplasia from India were identified with the same variant (c.84+3A>T). The kindred coefficient comparison of the 2 cases exome data suggested they were unrelated, however there was a stretch of shared homozygosity suggesting remote consanguinity. ~80% aberrantly spliced BNIP1 pre-mRNAs, reduced BNIP1 mRNA level to ~80%, and BNIP1 protein level reduction by ~50% were detected in one of the cases fibroblasts. A block at the terminal stage of autolysosome formation and/or clearance in patient fibroblasts was suggested based on the data. A drosophila model of the BNIP1 orthologue Sec20 also demonstrated defective autolysosome formation.
Sources: Literature
Mendeliome v0.12369 EIF4E Bryony Thompson Gene: eif4e has been classified as Red List (Low Evidence).
Mendeliome v0.12367 EIF4E Bryony Thompson Classified gene: EIF4E as Red List (low evidence)
Mendeliome v0.12367 EIF4E Bryony Thompson Gene: eif4e has been classified as Red List (Low Evidence).
Mendeliome v0.12366 TLL1 Zornitza Stark Gene: tll1 has been classified as Green List (High Evidence).
Mendeliome v0.12365 TK2 Zornitza Stark Gene: tk2 has been classified as Green List (High Evidence).
Mendeliome v0.12365 TK2 Zornitza Stark Phenotypes for gene: TK2 were changed from to Mitochondrial DNA depletion syndrome 2 (myopathic type), MIM# 609560; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3; MIM# 617069
Mendeliome v0.12362 TK2 Zornitza Stark reviewed gene: TK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 11687801, 12391347, 12873860, 35286480, 35280287, 35094997; Phenotypes: Mitochondrial DNA depletion syndrome 2 (myopathic type), MIM# 609560, Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3, MIM# 617069; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12362 TJP2 Zornitza Stark Gene: tjp2 has been classified as Green List (High Evidence).
Mendeliome v0.12362 TJP2 Zornitza Stark Phenotypes for gene: TJP2 were changed from to Cholestasis, progressive familial intrahepatic 4, MIM# 615878; Hypercholanemia, familial 1, MIM# 607748
Mendeliome v0.12359 TJP2 Zornitza Stark reviewed gene: TJP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24614073, 25921221, 31696999, 12704386; Phenotypes: Cholestasis, progressive familial intrahepatic 4, MIM# 615878, Hypercholanemia, familial 1, MIM# 607748; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12359 TIMP3 Zornitza Stark Gene: timp3 has been classified as Green List (High Evidence).
Mendeliome v0.12356 TIMM50 Zornitza Stark Gene: timm50 has been classified as Green List (High Evidence).
Mendeliome v0.12353 TIMM44 Zornitza Stark Gene: timm44 has been classified as Red List (Low Evidence).
Mendeliome v0.12353 TIMM44 Zornitza Stark Classified gene: TIMM44 as Red List (low evidence)
Mendeliome v0.12353 TIMM44 Zornitza Stark Gene: timm44 has been classified as Red List (Low Evidence).
Mendeliome v0.12352 TICAM1 Zornitza Stark Gene: ticam1 has been classified as Green List (High Evidence).
Mendeliome v0.12349 TTBK2 Zornitza Stark Gene: ttbk2 has been classified as Green List (High Evidence).
Mendeliome v0.12346 TTLL5 Zornitza Stark Gene: ttll5 has been classified as Green List (High Evidence).
Mendeliome v0.12343 TTR Zornitza Stark Gene: ttr has been classified as Green List (High Evidence).
Mendeliome v0.12343 TTR Zornitza Stark Phenotypes for gene: TTR were changed from to Amyloidosis, hereditary, transthyretin-related, MIM #105210; Carpal tunnel syndrome, familial, MIM# 115430
Mendeliome v0.12338 PADI6 Zornitza Stark Gene: padi6 has been classified as Green List (High Evidence).
Mendeliome v0.12335 PADI3 Zornitza Stark Gene: padi3 has been classified as Green List (High Evidence).
Mendeliome v0.12332 PACS2 Zornitza Stark Gene: pacs2 has been classified as Green List (High Evidence).
Mendeliome v0.12329 PABPN1 Zornitza Stark Gene: pabpn1 has been classified as Green List (High Evidence).
Mendeliome v0.12326 AGK Zornitza Stark Gene: agk has been classified as Green List (High Evidence).
Mendeliome v0.12323 EIF2B5 Bryony Thompson Gene: eif2b5 has been classified as Green List (High Evidence).
Mendeliome v0.12323 TTR Manny Jacobs reviewed gene: TTR: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID:1570831, 1626570, 16115295, 16194874, 26537620; Phenotypes: Amyloidosis, hereditary, transthyretin-related, MIM #105210, Carpal tunnel syndrome, familial, MIM# 115430; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12321 P3H2 Zornitza Stark Gene: p3h2 has been classified as Green List (High Evidence).
Mendeliome v0.12316 AKT3 Elena Savva Gene: akt3 has been classified as Green List (High Evidence).
Mendeliome v0.12316 EIF2B4 Bryony Thompson Gene: eif2b4 has been classified as Green List (High Evidence).
Mendeliome v0.12311 EIF2B3 Bryony Thompson Gene: eif2b3 has been classified as Green List (High Evidence).
Mendeliome v0.12311 AFP Zornitza Stark Added comment: Comment when marking as ready: Raised or low levels of AFP are observed in some medical conditions, kept Amber due to possible phenotypic overlap.
Mendeliome v0.12311 AFP Zornitza Stark Gene: afp has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12311 AFP Zornitza Stark Phenotypes for gene: AFP were changed from to Alpha-fetoprotein deficiency MIM#615969; [Hereditary persistence of alpha-fetoprotein] MIM#615970
Mendeliome v0.12308 AFP Zornitza Stark Classified gene: AFP as Amber List (moderate evidence)
Mendeliome v0.12308 AFP Zornitza Stark Gene: afp has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12304 AHCY Elena Savva Gene: ahcy has been classified as Green List (High Evidence).
Mendeliome v0.12302 EIF2B1 Bryony Thompson Gene: eif2b1 has been classified as Green List (High Evidence).
Mendeliome v0.12302 AGL Elena Savva Gene: agl has been classified as Green List (High Evidence).
Mendeliome v0.12298 EIF2AK3 Bryony Thompson Gene: eif2ak3 has been classified as Green List (High Evidence).
Mendeliome v0.12297 TIA1 Zornitza Stark Classified gene: TIA1 as Amber List (moderate evidence)
Mendeliome v0.12297 TIA1 Zornitza Stark Gene: tia1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12296 EIF2AK3 Bryony Thompson Phenotypes for gene: EIF2AK3 were changed from to Wolcott-Rallison syndrome MONDO:0009192; neonatal diabetes mellitus; epiphyseal dysplasia/osteopenia; hepatic/renal dysfunction; intellectual disability/developmental delay
Mendeliome v0.12295 TIA1 Zornitza Stark reviewed gene: TIA1: Rating: AMBER; Mode of pathogenicity: None; Publications: 29235362, 29886022, 29773329, 29699721, 29216908, 24659297, 29457785, 28817800, 23401021, 23401021; Phenotypes: Amyotrophic lateral sclerosis 26 with or without frontotemporal dementia, MIM# 619133, Welander distal myopathy (MIM#604454); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.12293 THSD1 Zornitza Stark Gene: thsd1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12290 THSD1 Zornitza Stark Classified gene: THSD1 as Amber List (moderate evidence)
Mendeliome v0.12290 THSD1 Zornitza Stark Gene: thsd1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12289 EFNA4 Bryony Thompson Gene: efna4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12289 EIF2AK3 Bryony Thompson reviewed gene: EIF2AK3: Rating: GREEN; Mode of pathogenicity: None; Publications: 10932183, 12960215, 16813601, 11997520, 20202148; Phenotypes: Wolcott-Rallison syndrome MONDO:0009192, neonatal diabetes mellitus, epiphyseal dysplasia/osteopenia, hepatic/renal dysfunction, intellectual disability/developmental delay; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.12289 EFNA4 Bryony Thompson Phenotypes for gene: EFNA4 were changed from to craniosynostosis MONDO:0015469
Mendeliome v0.12288 RBMX Zornitza Stark Gene: rbmx has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12288 RBMX Zornitza Stark Classified gene: RBMX as Amber List (moderate evidence)
Mendeliome v0.12288 RBMX Zornitza Stark Gene: rbmx has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12287 RBMX Zornitza Stark gene: RBMX was added
gene: RBMX was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: RBMX was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: RBMX were set to 25256757; 34260915
Phenotypes for gene: RBMX were set to Intellectual developmental disorder, syndromic 11, Shashi type, MIM#300238
Review for gene: RBMX was set to AMBER
Added comment: Hemizygous truncating variant reported segregating in multiple affected individuals in a single family. Some supportive functional data.
Sources: Expert Review
Mendeliome v0.12284 EHBP1 Bryony Thompson Gene: ehbp1 has been classified as Red List (Low Evidence).
Mendeliome v0.12283 EHBP1 Bryony Thompson Classified gene: EHBP1 as Red List (low evidence)
Mendeliome v0.12283 EHBP1 Bryony Thompson Gene: ehbp1 has been classified as Red List (Low Evidence).
Mendeliome v0.12282 EDNRB Bryony Thompson Gene: ednrb has been classified as Green List (High Evidence).
Mendeliome v0.12282 EFNA4 Bryony Thompson Classified gene: EFNA4 as Amber List (moderate evidence)
Mendeliome v0.12282 EFNA4 Bryony Thompson Gene: efna4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12281 EFNA4 Bryony Thompson reviewed gene: EFNA4: Rating: AMBER; Mode of pathogenicity: None; Publications: 16540516, 19201948, 19772933, 23983218, 29168297, 29215649, 33065355, 34586326; Phenotypes: craniosynostosis MONDO:0015469; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12281 AFP Elena Savva reviewed gene: AFP: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 15280901, 18854864; Phenotypes: Alpha-fetoprotein deficiency MIM#615969, [Hereditary persistence of alpha-fetoprotein] MIM#615970; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12281 ADRB2 Elena Savva Gene: adrb2 has been classified as Red List (Low Evidence).
Mendeliome v0.12281 ADRB2 Elena Savva Phenotypes for gene: ADRB2 were changed from to Beta-2-adrenoreceptor agonist, reduced response to; {Asthma, nocturnal, susceptibility to} MIM#600807; {Obesity, susceptibility to} MIM#601665
Mendeliome v0.12280 ADRB2 Elena Savva Classified gene: ADRB2 as Red List (low evidence)
Mendeliome v0.12280 ADRB2 Elena Savva Gene: adrb2 has been classified as Red List (Low Evidence).
Mendeliome v0.12279 THRB Zornitza Stark Gene: thrb has been classified as Green List (High Evidence).
Mendeliome v0.12279 THRB Zornitza Stark Phenotypes for gene: THRB were changed from to Thyroid hormone resistance, MIM# 188570; Thyroid hormone resistance, autosomal recessive, MIM# 274300; Thyroid hormone resistance, selective pituitary, MIM# 145650
Mendeliome v0.12276 THRB Zornitza Stark reviewed gene: THRB: Rating: GREEN; Mode of pathogenicity: None; Publications: 25135573, 31590893; Phenotypes: Thyroid hormone resistance, MIM# 188570, Thyroid hormone resistance, autosomal recessive, MIM# 274300, Thyroid hormone resistance, selective pituitary, MIM# 145650; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.12276 ADRB2 Elena Savva reviewed gene: ADRB2: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 15724149; Phenotypes: Beta-2-adrenoreceptor agonist, reduced response to, {Asthma, nocturnal, susceptibility to} MIM#600807, {Obesity, susceptibility to} MIM#601665; Mode of inheritance: Unknown
Mendeliome v0.12276 SLC6A2 Zornitza Stark Gene: slc6a2 has been classified as Red List (Low Evidence).
Mendeliome v0.12273 SLC6A2 Zornitza Stark Classified gene: SLC6A2 as Red List (low evidence)
Mendeliome v0.12273 SLC6A2 Zornitza Stark Gene: slc6a2 has been classified as Red List (Low Evidence).
Mendeliome v0.12272 SMARCAD1 Zornitza Stark Gene: smarcad1 has been classified as Green List (High Evidence).
Mendeliome v0.12268 SMARCB1 Zornitza Stark Gene: smarcb1 has been classified as Green List (High Evidence).
Mendeliome v0.12268 SMARCB1 Zornitza Stark Phenotypes for gene: SMARCB1 were changed from to Coffin-Siris syndrome 3, MIM# 614608
Mendeliome v0.12265 SMARCB1 Zornitza Stark reviewed gene: SMARCB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34205270, 31530938, 25168959; Phenotypes: Coffin-Siris syndrome 3, MIM# 614608; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12265 SMN2 Zornitza Stark Gene: smn2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12263 SMN2 Zornitza Stark Classified gene: SMN2 as Amber List (moderate evidence)
Mendeliome v0.12263 SMN2 Zornitza Stark Gene: smn2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12262 OTOG Zornitza Stark Gene: otog has been classified as Green List (High Evidence).
Mendeliome v0.12262 OTOG Zornitza Stark Phenotypes for gene: OTOG were changed from to Deafness, autosomal recessive 18B - MIM#614945
Mendeliome v0.12255 OTC Zornitza Stark Gene: otc has been classified as Green List (High Evidence).
Mendeliome v0.12253 OSTM1 Zornitza Stark Gene: ostm1 has been classified as Green List (High Evidence).
Mendeliome v0.12253 OSTM1 Zornitza Stark Phenotypes for gene: OSTM1 were changed from to Osteopetrosis, autosomal recessive 5 (MIM#259720)
Mendeliome v0.12250 OSMR Zornitza Stark Gene: osmr has been classified as Green List (High Evidence).
Mendeliome v0.12250 OSMR Zornitza Stark Phenotypes for gene: OSMR were changed from to Amyloidosis, primary localized cutaneous, 1 - MIM#105250
Mendeliome v0.12247 OSBPL2 Zornitza Stark Gene: osbpl2 has been classified as Green List (High Evidence).
Mendeliome v0.12244 OR2J3 Zornitza Stark Gene: or2j3 has been classified as Red List (Low Evidence).
Mendeliome v0.12244 OR2J3 Zornitza Stark Classified gene: OR2J3 as Red List (low evidence)
Mendeliome v0.12244 OR2J3 Zornitza Stark Gene: or2j3 has been classified as Red List (Low Evidence).
Mendeliome v0.12243 OPN1SW Zornitza Stark Gene: opn1sw has been classified as Green List (High Evidence).
Mendeliome v0.12240 OPN1MW Zornitza Stark Gene: opn1mw has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12237 OPN1MW Zornitza Stark Classified gene: OPN1MW as Amber List (moderate evidence)
Mendeliome v0.12237 OPN1MW Zornitza Stark Gene: opn1mw has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12236 OPN1LW Zornitza Stark Gene: opn1lw has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12234 BLOC1S6 Bryony Thompson Classified gene: BLOC1S6 as Green List (high evidence)
Mendeliome v0.12234 BLOC1S6 Bryony Thompson Gene: bloc1s6 has been classified as Green List (High Evidence).
Mendeliome v0.12231 OPN1LW Zornitza Stark Classified gene: OPN1LW as Amber List (moderate evidence)
Mendeliome v0.12231 OPN1LW Zornitza Stark Gene: opn1lw has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12230 SERPINA6 Zornitza Stark Gene: serpina6 has been classified as Green List (High Evidence).
Mendeliome v0.12227 SERPINA1 Zornitza Stark Gene: serpina1 has been classified as Green List (High Evidence).
Mendeliome v0.12227 SERPINA1 Zornitza Stark Phenotypes for gene: SERPINA1 were changed from to Emphysema due to AAT deficiency, MIM#613490; Emphysema-cirrhosis, due to AAT deficiency, MIM#613490; Hemorrhagic diathesis due to antithrombin Pittburgh, MIM#613490; alpha 1-antitrypsin deficiency, MONDO#0013282
Mendeliome v0.12224 OTOG Krithika Murali reviewed gene: OTOG: Rating: GREEN; Mode of pathogenicity: None; Publications: 29800624, 23122587; Phenotypes: Deafness, autosomal recessive 18B - MIM#614945; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12224 OSTM1 Krithika Murali reviewed gene: OSTM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 12627228, 15108279, 16813530, 23772242, 32048120; Phenotypes: Osteopetrosis, autosomal recessive 5 (MIM#259720); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12224 OSMR Krithika Murali reviewed gene: OSMR: Rating: GREEN; Mode of pathogenicity: None; Publications: 19375894, 19528426, 25054142, 20507362, 19690585; Phenotypes: Amyloidosis, primary localized cutaneous, 1 - MIM#105250; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12224 SERPINA1 Samantha Ayres changed review comment from: Well established gene-disease relationship

Rated as C by babyseq due to low penetrance in childhood. Can cause hepatic dysfunction in infancy. Identification would prevent further investigation and potentially lead to optimising respiratory health due to adult onset respiratory involvement.; to: Well established gene-disease relationship

Rated as C by babyseq due to low penetrance in childhood. Can cause hepatic dysfunction in infancy. Identification would prevent further investigation and potentially lead to optimising respiratory health due to adult onset respiratory involvement.

MUTATIONAL & CLINICAL SPECTRUM
ZZ genotype: 2% have severe, neonatal/early-onset liver disease (potentially fatal/requiring liver transplantation), up to 6% have childhood onset liver disease. Also associated with adult-onset lung disease particularly emphysema (50%+ penetrance) - smoking is an important risk factor (close to 100% penetrance).

TREATMENT
There is no specific treatment for liver disease beyond transplant. There is treatment (AAT augmentation therapy) available to delay progression of lung disease phenotype.
Mendeliome v0.12224 SERPINA1 Samantha Ayres changed review comment from: Well established gene-disease association

Rated as C by babyseq due to low penetrance in childhood. Can cause hepatic dysfunction in infancy. Identification would prevent further investigation and potentially lead to optimising respiratory health due to adult onset respiratory involvement.; to: Well established gene-disease relationship

Rated as C by babyseq due to low penetrance in childhood. Can cause hepatic dysfunction in infancy. Identification would prevent further investigation and potentially lead to optimising respiratory health due to adult onset respiratory involvement.
Mendeliome v0.12224 SERPINA1 Samantha Ayres reviewed gene: SERPINA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301692, 9041988, 34408829; Phenotypes: Emphysema due to AAT deficiency, MIM#613490, Emphysema-cirrhosis, due to AAT deficiency, MIM#613490, Hemorrhagic diathesis due to antithrombin Pittburgh, MIM#613490, alpha 1-antitrypsin deficiency, MONDO#0013282; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12224 THRA Zornitza Stark Gene: thra has been classified as Green List (High Evidence).
Mendeliome v0.12221 TGM1 Zornitza Stark Gene: tgm1 has been classified as Green List (High Evidence).
Mendeliome v0.12221 TGM1 Zornitza Stark Phenotypes for gene: TGM1 were changed from to Ichthyosis, congenital, autosomal recessive 1, MIM#242300
Mendeliome v0.12218 TGM1 Zornitza Stark reviewed gene: TGM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19890349, 24261627, 30302839; Phenotypes: Ichthyosis, congenital, autosomal recessive 1, MIM#242300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12218 TGM3 Zornitza Stark Gene: tgm3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12215 TGM3 Zornitza Stark Classified gene: TGM3 as Amber List (moderate evidence)
Mendeliome v0.12215 TGM3 Zornitza Stark Gene: tgm3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12214 OAT Zornitza Stark Gene: oat has been classified as Green List (High Evidence).
Mendeliome v0.12211 NUP93 Zornitza Stark Gene: nup93 has been classified as Green List (High Evidence).
Mendeliome v0.12208 NUP62 Zornitza Stark Gene: nup62 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12205 NUP62 Zornitza Stark Classified gene: NUP62 as Amber List (moderate evidence)
Mendeliome v0.12205 NUP62 Zornitza Stark Gene: nup62 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12204 ADH1B Zornitza Stark Gene: adh1b has been classified as Red List (Low Evidence).
Mendeliome v0.12203 CASP8 Zornitza Stark Gene: casp8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12200 CASP8 Zornitza Stark Classified gene: CASP8 as Amber List (moderate evidence)
Mendeliome v0.12200 CASP8 Zornitza Stark Gene: casp8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12198 ADCY3 Zornitza Stark Gene: adcy3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12198 ADCY3 Zornitza Stark Phenotypes for gene: ADCY3 were changed from to {Obesity, susceptibility to, BMIQ19} MIM#617885
Mendeliome v0.12195 ADCY3 Zornitza Stark Classified gene: ADCY3 as Amber List (moderate evidence)
Mendeliome v0.12195 ADCY3 Zornitza Stark Gene: adcy3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12194 TGFB3 Zornitza Stark Gene: tgfb3 has been classified as Green List (High Evidence).
Mendeliome v0.12191 TGFB2 Zornitza Stark Gene: tgfb2 has been classified as Green List (High Evidence).
Mendeliome v0.12189 TGFB1 Zornitza Stark Gene: tgfb1 has been classified as Green List (High Evidence).
Mendeliome v0.12186 TG Zornitza Stark Gene: tg has been classified as Green List (High Evidence).
Mendeliome v0.12186 TG Zornitza Stark Phenotypes for gene: TG were changed from to Thyroid dyshormonogenesis 3, MIM# 274700
Mendeliome v0.12183 TG Zornitza Stark reviewed gene: TG: Rating: GREEN; Mode of pathogenicity: None; Publications: 33832185, 19169491, 28620499, 18631008, 12915634; Phenotypes: Thyroid dyshormonogenesis 3, MIM# 274700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12181 ADRB1 Elena Savva Gene: adrb1 has been classified as Red List (Low Evidence).
Mendeliome v0.12181 ADRB1 Elena Savva Classified gene: ADRB1 as Red List (low evidence)
Mendeliome v0.12181 ADRB1 Elena Savva Gene: adrb1 has been classified as Red List (Low Evidence).
Mendeliome v0.12180 NTN1 Zornitza Stark Gene: ntn1 has been classified as Green List (High Evidence).
Mendeliome v0.12177 NSD1 Zornitza Stark Gene: nsd1 has been classified as Green List (High Evidence).
Mendeliome v0.12174 NRCAM Zornitza Stark Gene: nrcam has been classified as Green List (High Evidence).
Mendeliome v0.12174 NR4A3 Zornitza Stark Gene: nr4a3 has been classified as Red List (Low Evidence).
Mendeliome v0.12174 NR4A3 Zornitza Stark Classified gene: NR4A3 as Red List (low evidence)
Mendeliome v0.12174 NR4A3 Zornitza Stark Gene: nr4a3 has been classified as Red List (Low Evidence).
Mendeliome v0.12173 NKX2-5 Zornitza Stark Gene: nkx2-5 has been classified as Green List (High Evidence).
Mendeliome v0.12169 NKX2-1 Zornitza Stark Gene: nkx2-1 has been classified as Green List (High Evidence).
Mendeliome v0.12169 NKX2-1 Zornitza Stark Phenotypes for gene: NKX2-1 were changed from to Choreoathetosis, hypothyroidism, and neonatal respiratory distress MIM#610978; Chorea, hereditary benign MIM#118700
Mendeliome v0.12166 NDUFAF5 Zornitza Stark Gene: ndufaf5 has been classified as Green List (High Evidence).
Mendeliome v0.12163 NDUFS4 Zornitza Stark Gene: ndufs4 has been classified as Green List (High Evidence).
Mendeliome v0.12160 NDUFV2 Zornitza Stark Gene: ndufv2 has been classified as Green List (High Evidence).
Mendeliome v0.12158 ADH1B Elena Savva Classified gene: ADH1B as Red List (low evidence)
Mendeliome v0.12158 ADH1B Elena Savva Gene: adh1b has been classified as Red List (Low Evidence).
Mendeliome v0.12154 CA2 Zornitza Stark Phenotypes for gene: CA2 were changed from to Osteopetrosis, autosomal recessive 3, with renal tubular acidosis, MIM#259730
Mendeliome v0.12152 CASP8 Ain Roesley changed review comment from: Boderline red/amber

1 family (the 2nd family reported in PMID:25814141 was found to be distantly related to the one in PMID:12353035)

Mice with targeted T cell and B cell caspase-8 deficiency present normal thymocyte development but a marked decrease in peripheral blood T-cells. Besides, when challenged with the lymphocytic choriomeningitis virus (LCMV), these animals showed a significantly impaired immune response to the infection that included impaired CD8 cell expansion and an abrogated ability to generate virus-specific CD8+ cytotoxic T-cells.; to: Borderline red/amber

1 family (the 2nd family reported in PMID:25814141 was found to be distantly related to the one in PMID:12353035)

Mice with targeted T cell and B cell caspase-8 deficiency present normal thymocyte development but a marked decrease in peripheral blood T-cells. Besides, when challenged with the lymphocytic choriomeningitis virus (LCMV), these animals showed a significantly impaired immune response to the infection that included impaired CD8 cell expansion and an abrogated ability to generate virus-specific CD8+ cytotoxic T-cells.
Mendeliome v0.12151 ADGRV1 Elena Savva Gene: adgrv1 has been classified as Green List (High Evidence).
Mendeliome v0.12150 ADCY3 Elena Savva reviewed gene: ADCY3: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 11055432, 29311636, 29311637; Phenotypes: {Obesity, susceptibility to, BMIQ19} MIM#617885; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12149 CASP10 Ain Roesley Gene: casp10 has been classified as Green List (High Evidence).
Mendeliome v0.12148 NUBPL Zornitza Stark Gene: nubpl has been classified as Green List (High Evidence).
Mendeliome v0.12145 NTRK1 Zornitza Stark Gene: ntrk1 has been classified as Green List (High Evidence).
Mendeliome v0.12145 NTRK1 Zornitza Stark Phenotypes for gene: NTRK1 were changed from to Insensitivity to pain, congenital, with anhidrosis - MIM#256800
Mendeliome v0.12142 NTF4 Zornitza Stark Gene: ntf4 has been classified as Red List (Low Evidence).
Mendeliome v0.12139 CASK Ain Roesley Phenotypes for gene: CASK were changed from FG syndrome 4 MIM#300422; Intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia MIM#300749; Mental retardation, with or without nystagmus MIM#300422 to FG syndrome 4 MIM#300422; Intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia MIM#300749; Mental retardation, with or without nystagmus MIM#300422
Mendeliome v0.12139 NTF4 Zornitza Stark Classified gene: NTF4 as Red List (low evidence)
Mendeliome v0.12139 NTF4 Zornitza Stark Gene: ntf4 has been classified as Red List (Low Evidence).
Mendeliome v0.12138 CASK Ain Roesley Phenotypes for gene: CASK were changed from to FG syndrome 4 MIM#300422; Intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia MIM#300749; Mental retardation, with or without nystagmus MIM#300422
Mendeliome v0.12137 CASK Ain Roesley Gene: cask has been classified as Green List (High Evidence).
Mendeliome v0.12137 CASK Ain Roesley Gene: cask has been classified as Green List (High Evidence).
Mendeliome v0.12135 NSUN2 Zornitza Stark Gene: nsun2 has been classified as Green List (High Evidence).
Mendeliome v0.12135 NSUN2 Zornitza Stark Phenotypes for gene: NSUN2 were changed from to Mental retardation, autosomal recessive 5 - MIM#611091
Mendeliome v0.12134 CASK Ain Roesley reviewed gene: CASK: Rating: GREEN; Mode of pathogenicity: None; Publications: 24278995; Phenotypes: FG syndrome 4 MIM#300422, Intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia MIM#300749, Mental retardation, with or without nystagmus MIM#300422; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes
Mendeliome v0.12132 NSUN2 Zornitza Stark reviewed gene: NSUN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22541559, 22541562, 21063731, 22577224, 35126837; Phenotypes: Mental retardation, autosomal recessive 5 - MIM#611091; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12132 NRXN1 Zornitza Stark Gene: nrxn1 has been classified as Green List (High Evidence).
Mendeliome v0.12129 CARD11 Ain Roesley Phenotypes for gene: CARD11 were changed from Immunodeficiency 11A, autosomal recessive, MIM# 615206; Immunodeficiency 11B with atopic dermatitis, autosomal dominant, MIM# 617638 to Immunodeficiency 11A, autosomal recessive, MIM# 615206; Immunodeficiency 11B with atopic dermatitis, autosomal dominant, MIM# 617638
Mendeliome v0.12128 CARD11 Ain Roesley Phenotypes for gene: CARD11 were changed from to Immunodeficiency 11A, autosomal recessive, MIM# 615206; Immunodeficiency 11B with atopic dermatitis, autosomal dominant, MIM# 617638
Mendeliome v0.12128 CARD11 Ain Roesley Gene: card11 has been classified as Green List (High Evidence).
Mendeliome v0.12127 CARD11 Ain Roesley reviewed gene: CARD11: Rating: GREEN; Mode of pathogenicity: None; Publications: 23561803, 12818158, 23374270, 28628108; Phenotypes: Immunodeficiency 11A, autosomal recessive, MIM# 615206, Immunodeficiency 11B with atopic dermatitis, autosomal dominant, MIM# 617638; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.12127 CALM3 Ain Roesley Gene: calm3 has been classified as Green List (High Evidence).
Mendeliome v0.12126 CALM2 Ain Roesley Gene: calm2 has been classified as Green List (High Evidence).
Mendeliome v0.12124 CALM1 Ain Roesley Gene: calm1 has been classified as Green List (High Evidence).
Mendeliome v0.12122 NRL Zornitza Stark Gene: nrl has been classified as Green List (High Evidence).
Mendeliome v0.12122 NRL Zornitza Stark Phenotypes for gene: NRL were changed from to Retinitis pigmentosa 27 - MIM#613750; Retinal degeneration, autosomal recessive, clumped pigment type
Mendeliome v0.12118 CACNA2D4 Ain Roesley Gene: cacna2d4 has been classified as Green List (High Evidence).
Mendeliome v0.12117 NR2F2 Zornitza Stark Gene: nr2f2 has been classified as Green List (High Evidence).
Mendeliome v0.12115 SERAC1 Zornitza Stark Gene: serac1 has been classified as Green List (High Evidence).
Mendeliome v0.12112 SEMA3A Zornitza Stark Gene: sema3a has been classified as Green List (High Evidence).
Mendeliome v0.12109 SCP2 Zornitza Stark Gene: scp2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12108 SCP2 Zornitza Stark Classified gene: SCP2 as Amber List (moderate evidence)
Mendeliome v0.12108 SCP2 Zornitza Stark Gene: scp2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12103 CACNA2D2 Ain Roesley Gene: cacna2d2 has been classified as Green List (High Evidence).
Mendeliome v0.12102 SCP2 Zornitza Stark Classified gene: SCP2 as Red List (low evidence)
Mendeliome v0.12102 SCP2 Zornitza Stark Gene: scp2 has been classified as Red List (Low Evidence).
Mendeliome v0.12099 CACNA1F Ain Roesley Gene: cacna1f has been classified as Green List (High Evidence).
Mendeliome v0.12099 TUBB1 Zornitza Stark Gene: tubb1 has been classified as Green List (High Evidence).
Mendeliome v0.12096 SCARB2 Zornitza Stark Gene: scarb2 has been classified as Green List (High Evidence).
Mendeliome v0.12096 SCARB2 Zornitza Stark Phenotypes for gene: SCARB2 were changed from to Progressive Myoclonus Epilepsy, MONDO:0020074; Epilepsy, progressive myoclonic 4, with or without renal failure, MIM #254900
Mendeliome v0.12093 SASH1 Zornitza Stark Gene: sash1 has been classified as Green List (High Evidence).
Mendeliome v0.12093 SASH1 Zornitza Stark Phenotypes for gene: SASH1 were changed from to Dyschromatosis universalis hereditaria 1, MIM #127500; familial generalized lentiginosis MONDO:007891
Mendeliome v0.12090 SASH1 Zornitza Stark reviewed gene: SASH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Dyschromatosis universalis hereditaria 1, MIM# 127500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12090 CABP2 Ain Roesley Gene: cabp2 has been classified as Green List (High Evidence).
Mendeliome v0.12090 TUBB4B Zornitza Stark Gene: tubb4b has been classified as Green List (High Evidence).
Mendeliome v0.12090 CABP2 Ain Roesley Phenotypes for gene: CABP2 were changed from to Deafness, autosomal recessive 93, MIM# 614899
Mendeliome v0.12090 TUBB4B Zornitza Stark Phenotypes for gene: TUBB4B were changed from to Leber congenital amaurosis with early onset deafness, LCAEOD, OMIM #617879; MONDO:0060650
Mendeliome v0.12089 CABP2 Ain Roesley reviewed gene: CABP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22981119, 31661684, 28183797; Phenotypes: Deafness, autosomal recessive 93, MIM# 614899; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.12088 TUBB4B Zornitza Stark reviewed gene: TUBB4B: Rating: GREEN; Mode of pathogenicity: None; Publications: 35240325; Phenotypes: Leber congenital amaurosis with early onset deafness, LCAEOD, OMIM #617879, MONDO:0060650; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12086 TUFM Zornitza Stark Gene: tufm has been classified as Green List (High Evidence).
Mendeliome v0.12083 CA2 Ain Roesley Gene: ca2 has been classified as Green List (High Evidence).
Mendeliome v0.12083 CA2 Ain Roesley reviewed gene: CA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34624559, 33555497, 12566520, 7627193; Phenotypes: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis, MIM#259730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.12082 CA12 Ain Roesley Gene: ca12 has been classified as Green List (High Evidence).
Mendeliome v0.12082 CA12 Ain Roesley Phenotypes for gene: CA12 were changed from to Hyperchlorhidrosis, isolated MIM#143860
Mendeliome v0.12080 NR2E3 Zornitza Stark Gene: nr2e3 has been classified as Green List (High Evidence).
Mendeliome v0.12080 CA12 Ain Roesley reviewed gene: CA12: Rating: GREEN; Mode of pathogenicity: None; Publications: 21035102, 21184099, 26911677; Phenotypes: Hyperchlorhidrosis, isolated MIM#143860; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.12077 NR0B2 Zornitza Stark Gene: nr0b2 has been classified as Red List (Low Evidence).
Mendeliome v0.12076 NR0B2 Zornitza Stark Phenotypes for gene: NR0B2 were changed from to Obesity, mild, early-onset, MIM# 601665
Mendeliome v0.12075 NR0B2 Zornitza Stark Classified gene: NR0B2 as Red List (low evidence)
Mendeliome v0.12075 NR0B2 Zornitza Stark Gene: nr0b2 has been classified as Red List (Low Evidence).
Mendeliome v0.12074 NPSR1 Zornitza Stark Gene: npsr1 has been classified as Red List (Low Evidence).
Mendeliome v0.12072 NPSR1 Zornitza Stark Classified gene: NPSR1 as Red List (low evidence)
Mendeliome v0.12072 NPSR1 Zornitza Stark Gene: npsr1 has been classified as Red List (Low Evidence).
Mendeliome v0.12071 ACER3 Zornitza Stark edited their review of gene: ACER3: Added comment: Additional publication (Dehvani et al., 2021; PMID: 34281620) detailing three further unrelated cases, each with novel homozygous variants in the ACER3 gene. All individuals displayed features of progressive leukoencephalopathy, developmental delay, hypotonia, appendicular spasticity, and dystonia. Early development is apparently normal followed by symptoms of stagnation and neurologic regression (onset within first year of life).; Changed rating: GREEN; Changed publications: 32816236, 26792856, 34281620; Changed phenotypes: Leukodystrophy, progressive, early childhood-onset, MIM:617762
Mendeliome v0.12071 LIAS Alison Yeung Gene: lias has been classified as Green List (High Evidence).
Mendeliome v0.12071 LIAS Alison Yeung Phenotypes for gene: LIAS were changed from to Hyperglycinemia, lactic acidosis, and seizures, MIM# 614462
Mendeliome v0.12068 LIAS Alison Yeung reviewed gene: LIAS: Rating: GREEN; Mode of pathogenicity: None; Publications: 22152680, 24334290, 26108146; Phenotypes: Hyperglycinemia, lactic acidosis, and seizures, MIM# 614462; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.12067 LHX4 Alison Yeung Gene: lhx4 has been classified as Green List (High Evidence).
Mendeliome v0.12066 LHX3 Alison Yeung Gene: lhx3 has been classified as Green List (High Evidence).
Mendeliome v0.12064 LHB Alison Yeung Gene: lhb has been classified as Green List (High Evidence).
Mendeliome v0.12062 SCARB2 Samantha Ayres reviewed gene: SCARB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 18308289, 18424452, 23659519, 19847901, 18022370, 19933215; Phenotypes: Progressive Myoclonus Epilepsy, MONDO:0020074, Epilepsy, progressive myoclonic 4, with or without renal failure, MIM #254900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12062 SASH1 Samantha Ayres reviewed gene: SASH1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23333244, 27885802, 32981204; Phenotypes: Dyschromatosis universalis hereditaria 1, MIM #127500, familial generalized lentiginosis MONDO:007891; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.12062 TUBB4B Manny Jacobs reviewed gene: TUBB4B: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29198720; Phenotypes: Leber congenital amaurosis with early onset deafness, LCAEOD, OMIM #617879, MONDO:0060650; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12062 LGI1 Alison Yeung Gene: lgi1 has been classified as Green List (High Evidence).
Mendeliome v0.12059 NTRK1 Krithika Murali reviewed gene: NTRK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10233776, 19250380, 10861667, 10982191, 20301726, 20089052; Phenotypes: Insensitivity to pain, congenital, with anhidrosis - MIM#256800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12059 LEMD3 Alison Yeung Gene: lemd3 has been classified as Green List (High Evidence).
Mendeliome v0.12059 LEMD3 Alison Yeung Phenotypes for gene: LEMD3 were changed from to Buschke-Ollendorff syndrome MIM#166700; Osteopoikilosis with or without melorheostosis MIM#166700
Mendeliome v0.12056 NRL Krithika Murali reviewed gene: NRL: Rating: GREEN; Mode of pathogenicity: None; Publications: 15591106, 29385733, 21981118, 10192380, 9344665; Phenotypes: Retinitis pigmentosa 27 - MIM#613750, Retinal degeneration, autosomal recessive, clumped pigment type; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.12056 LDLRAP1 Alison Yeung Gene: ldlrap1 has been classified as Green List (High Evidence).
Mendeliome v0.12053 LDHB Alison Yeung Gene: ldhb has been classified as Red List (Low Evidence).
Mendeliome v0.12050 LDHB Alison Yeung Classified gene: LDHB as Red List (low evidence)
Mendeliome v0.12050 LDHB Alison Yeung Added comment: Comment on list classification: Not associated with clinical disease
Mendeliome v0.12050 LDHB Alison Yeung Gene: ldhb has been classified as Red List (Low Evidence).
Mendeliome v0.12049 LCAT Alison Yeung Gene: lcat has been classified as Green List (High Evidence).
Mendeliome v0.12046 LCA5 Alison Yeung Gene: lca5 has been classified as Green List (High Evidence).
Mendeliome v0.12046 LCA5 Alison Yeung Phenotypes for gene: LCA5 were changed from to Leber Congenital Amaurosis 5, MIM# 604537
Mendeliome v0.12043 LCA5 Alison Yeung reviewed gene: LCA5: Rating: GREEN; Mode of pathogenicity: None; Publications: 17546029; Phenotypes: Leber Congenital Amaurosis 5, MIM# 604537; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12043 MSMB Zornitza Stark Gene: msmb has been classified as Red List (Low Evidence).
Mendeliome v0.12041 MSMB Zornitza Stark Classified gene: MSMB as Red List (low evidence)
Mendeliome v0.12041 MSMB Zornitza Stark Gene: msmb has been classified as Red List (Low Evidence).
Mendeliome v0.12040 SON Zornitza Stark Gene: son has been classified as Green List (High Evidence).
Mendeliome v0.12037 SNX3 Zornitza Stark Gene: snx3 has been classified as Red List (Low Evidence).
Mendeliome v0.12037 SNX3 Zornitza Stark Classified gene: SNX3 as Red List (low evidence)
Mendeliome v0.12037 SNX3 Zornitza Stark Gene: snx3 has been classified as Red List (Low Evidence).
Mendeliome v0.12036 SMARCE1 Zornitza Stark Phenotypes for gene: SMARCE1 were changed from Coffin-Siris syndrome 5, MIM# 616938 to Coffin-Siris syndrome 5, MIM# 616938; {Meningioma, familial, susceptibility to} 607174
Mendeliome v0.12035 SMARCE1 Zornitza Stark changed review comment from: Coffin-Siris syndrome is a rare congenital disorder characterized by delayed psychomotor development, intellectual disability, coarse facial features, and hypoplasia of the distal phalanges, particularly the fifth digit. Other features may also be observed, including congenital heart defects, hypoplasia of the corpus callosum, and poor overall growth with short stature and microcephaly.

Accounts for ~2% of Coffin Siris syndrome.; to: Coffin-Siris syndrome is a rare congenital disorder characterized by delayed psychomotor development, intellectual disability, coarse facial features, and hypoplasia of the distal phalanges, particularly the fifth digit. Other features may also be observed, including congenital heart defects, hypoplasia of the corpus callosum, and poor overall growth with short stature and microcephaly.

Accounts for ~2% of Coffin Siris syndrome.

Germline LoF variants also linked to familial meningioma.
Mendeliome v0.12035 SMARCE1 Zornitza Stark edited their review of gene: SMARCE1: Changed publications: 23377182, 22426308, 23906836, 23929686, 32732226, 32436246, 32410215, 34205270; Changed phenotypes: Coffin-Siris syndrome 5, MIM# 616938, {Meningioma, familial, susceptibility to} 607174
Mendeliome v0.12034 SMARCE1 Zornitza Stark Gene: smarce1 has been classified as Green List (High Evidence).
Mendeliome v0.12034 SMARCE1 Zornitza Stark Phenotypes for gene: SMARCE1 were changed from to Coffin-Siris syndrome 5, MIM# 616938
Mendeliome v0.12031 SMARCE1 Zornitza Stark reviewed gene: SMARCE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22426308, 23906836, 23929686, 32732226, 32436246, 32410215, 34205270; Phenotypes: Coffin-Siris syndrome 5, MIM# 616938; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12031 MAX Zornitza Stark Gene: max has been classified as Green List (High Evidence).
Mendeliome v0.12028 MAT1A Zornitza Stark Gene: mat1a has been classified as Green List (High Evidence).
Mendeliome v0.12028 MAT1A Zornitza Stark Phenotypes for gene: MAT1A were changed from to Hypermethioninemia, persistent, autosomal dominant, due to methionine adenosyltransferase I/III deficiency MIM#250850; Methionine adenosyltransferase deficiency, autosomal recessive MIM#250850; Disorders of the metabolism of sulphur amino acids
Mendeliome v0.12025 SNX14 Zornitza Stark Gene: snx14 has been classified as Green List (High Evidence).
Mendeliome v0.12025 SNX14 Zornitza Stark Phenotypes for gene: SNX14 were changed from to Spinocerebellar ataxia, autosomal recessive 20 (MIM#616354)
Mendeliome v0.12022 SNX14 Zornitza Stark reviewed gene: SNX14: Rating: GREEN; Mode of pathogenicity: None; Publications: 25439728, 25848753, 27913285; Phenotypes: Spinocerebellar ataxia, autosomal recessive 20 (MIM#616354); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12022 SNORD118 Zornitza Stark Gene: snord118 has been classified as Green List (High Evidence).
Mendeliome v0.12019 SNAP29 Zornitza Stark Gene: snap29 has been classified as Green List (High Evidence).
Mendeliome v0.12019 SNAP29 Zornitza Stark Phenotypes for gene: SNAP29 were changed from to Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome, MIM#609528
Mendeliome v0.12016 SNAP29 Zornitza Stark reviewed gene: SNAP29: Rating: GREEN; Mode of pathogenicity: None; Publications: 29051910, 21073448, 30793783; Phenotypes: Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome, MIM#609528; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12016 SNAP25 Zornitza Stark Gene: snap25 has been classified as Green List (High Evidence).
Mendeliome v0.12013 SNAI2 Zornitza Stark Gene: snai2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12010 SNAI2 Zornitza Stark Classified gene: SNAI2 as Amber List (moderate evidence)
Mendeliome v0.12010 SNAI2 Zornitza Stark Gene: snai2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.12009 SMS Zornitza Stark Gene: sms has been classified as Green List (High Evidence).
Mendeliome v0.12006 GRIN1 Zornitza Stark Phenotypes for gene: GRIN1 were changed from Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant, MIM# 614254; Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive, MIM# 617820 to Developmental and epileptic encephalopathy 101, MIM# 619814; Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant, MIM# 614254; Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive, MIM# 617820
Mendeliome v0.12005 GRIN1 Zornitza Stark edited their review of gene: GRIN1: Changed phenotypes: Developmental and epileptic encephalopathy 101, MIM# 619814, Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant, MIM# 614254, Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive, MIM# 617820
Mendeliome v0.12005 RPS10 Zornitza Stark Gene: rps10 has been classified as Green List (High Evidence).
Mendeliome v0.12002 ROBO3 Zornitza Stark Gene: robo3 has been classified as Green List (High Evidence).
Mendeliome v0.12002 ROBO3 Zornitza Stark Phenotypes for gene: ROBO3 were changed from to Gaze palsy, familial horizontal, with progressive scoliosis, 1 (MIM# 607313)
Mendeliome v0.11999 ROBO2 Zornitza Stark Gene: robo2 has been classified as Green List (High Evidence).
Mendeliome v0.11999 ROBO2 Zornitza Stark Phenotypes for gene: ROBO2 were changed from to Vesicoureteral reflux 2 - MIM#610878; CAKUT
Mendeliome v0.11996 ROBO2 Zornitza Stark reviewed gene: ROBO2: Rating: GREEN; Mode of pathogenicity: None; Publications: 18235093, 19350278, 24429398, 17357069, 26026792, 29194579, 34059960; Phenotypes: Vesicoureteral reflux 2 - MIM#610878, CAKUT; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11996 RNF216 Zornitza Stark Gene: rnf216 has been classified as Green List (High Evidence).
Mendeliome v0.11993 ATP2B2 Zornitza Stark Gene: atp2b2 has been classified as Green List (High Evidence).
Mendeliome v0.11993 ATP2B2 Zornitza Stark Phenotypes for gene: ATP2B2 were changed from progressive sensorineural deafness to Deafness, autosomal dominant 82, MIM# 619804; {Deafness, autosomal recessive 12, modifier of}, MIM# 601386
Mendeliome v0.11991 ATP2B2 Zornitza Stark edited their review of gene: ATP2B2: Changed phenotypes: Deafness, autosomal dominant 82, MIM# 619804, {Deafness, autosomal recessive 12, modifier of}, MIM# 601386
Mendeliome v0.11991 TFAP2B Zornitza Stark Gene: tfap2b has been classified as Green List (High Evidence).
Mendeliome v0.11990 TFAP2B Zornitza Stark changed review comment from: Well established association with syndromic and non-syndromic PDA.; to: Well established association with syndromic and non-syndromic PDA.

Four individuals reported in PMID: 31292255 (Correction in PMID: 31405973) as part of a craniosynostosis cohort: 2 de novo and 2 inherited. There is evidence for reduced penetrance as in one case the variant was inherited from an unaffected parent (affected parent for the other inherited variant).
Mendeliome v0.11990 TFAP2B Zornitza Stark edited their review of gene: TFAP2B: Changed publications: 31292255, 11505339, 15684060, 18752453, 21643846; Changed phenotypes: Char syndrome, MIM# 169100, Patent ductus arteriosus 2, MIM# 617035, Syndromic craniosynostosis
Mendeliome v0.11990 TFAP2B Zornitza Stark Phenotypes for gene: TFAP2B were changed from Char syndrome, MIM# 169100; Patent ductus arteriosus 2, MIM# 617035 to Char syndrome, MIM# 169100; Patent ductus arteriosus 2, MIM# 617035; Syndromic craniosynostosis
Mendeliome v0.11986 TERT Zornitza Stark Gene: tert has been classified as Green List (High Evidence).
Mendeliome v0.11986 TERT Zornitza Stark Phenotypes for gene: TERT were changed from to Dyskeratosis congenita, MIM# 613989; Pulmonary fibrosis and/or bone marrow failure, telomere-related, 1, MIM# 614742
Mendeliome v0.11983 TERT Zornitza Stark reviewed gene: TERT: Rating: GREEN; Mode of pathogenicity: None; Publications: 16247010, 15814878; Phenotypes: Dyskeratosis congenita, MIM# 613989, Pulmonary fibrosis and/or bone marrow failure, telomere-related, 1, MIM# 614742; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11983 TERC Zornitza Stark Gene: terc has been classified as Green List (High Evidence).
Mendeliome v0.11983 TERC Zornitza Stark Phenotypes for gene: TERC were changed from to Dyskeratosis congenita, autosomal dominant 1, MIM# 127550
Mendeliome v0.11980 TERC Zornitza Stark reviewed gene: TERC: Rating: GREEN; Mode of pathogenicity: None; Publications: 11574891; Phenotypes: Dyskeratosis congenita, autosomal dominant 1, MIM# 127550; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11980 TEK Zornitza Stark Gene: tek has been classified as Green List (High Evidence).
Mendeliome v0.11977 TEAD1 Zornitza Stark Gene: tead1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11975 TEAD1 Zornitza Stark changed review comment from: Sveinsson chorioretinal atrophy (SCRA) is characterized by bilateral, well-defined, tongue-shaped strips of atrophic retina and choroid that extend from the optic nerve into the peripheral ocular fundus. The lesions may be evident at birth and usually progress at a variable rate, sometimes leading to central visual loss. Separate small distinct circular atrophic lesions are observed in the peripheral ocular fundus in some patients. Congenital anterior polar cataracts are found in approximately 25% of affected individuals.

The vast majority of reported cases were of Icelandic origin but the characteristic clinical picture of SCRA is also described in patients of non-Icelandic descent. The variant reported in the Icelanding population is (c.1261T>C, p.Tyr421His), another variant at same position c.1261T>A, p.Tyr421Asn also reported in non-Icelandic family.

Functional data supports gene-disease association.; to: Sveinsson chorioretinal atrophy (SCRA) is characterized by bilateral, well-defined, tongue-shaped strips of atrophic retina and choroid that extend from the optic nerve into the peripheral ocular fundus. The lesions may be evident at birth and usually progress at a variable rate, sometimes leading to central visual loss. Separate small distinct circular atrophic lesions are observed in the peripheral ocular fundus in some patients. Congenital anterior polar cataracts are found in approximately 25% of affected individuals.

The vast majority of reported cases were of Icelandic origin but the characteristic clinical picture of SCRA is also described in patients of non-Icelandic descent. The variant reported in the Icelanding population is (c.1261T>C, p.Tyr421His), another variant at same position c.1261T>A, p.Tyr421Asn also reported in non-Icelandic family.

A de novo nonsense variant has also been reported in a case with Aicardi syndrome with infantile spasms, agenesis of the corpus callosum, and chorioretinal lacunae.
Mendeliome v0.11975 TEAD1 Zornitza Stark Classified gene: TEAD1 as Amber List (moderate evidence)
Mendeliome v0.11975 TEAD1 Zornitza Stark Gene: tead1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11973 TDP1 Zornitza Stark Phenotypes for gene: TDP1 were changed from to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1 , MIM# 607250
Mendeliome v0.11970 TDP1 Zornitza Stark Classified gene: TDP1 as Amber List (moderate evidence)
Mendeliome v0.11970 TDP1 Zornitza Stark Gene: tdp1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11969 TDP1 Zornitza Stark reviewed gene: TDP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 31182267, 12244316; Phenotypes: Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1 , MIM# 607250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11969 TCIRG1 Zornitza Stark Gene: tcirg1 has been classified as Green List (High Evidence).
Mendeliome v0.11969 TCIRG1 Zornitza Stark Phenotypes for gene: TCIRG1 were changed from to Osteopetrosis, autosomal recessive 1, MIM# 259700
Mendeliome v0.11966 TCIRG1 Zornitza Stark reviewed gene: TCIRG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34624559, 34210262, 30084437, 28816234; Phenotypes: Osteopetrosis, autosomal recessive 1, MIM# 259700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11966 TCF4 Zornitza Stark Gene: tcf4 has been classified as Green List (High Evidence).
Mendeliome v0.11963 TCAP Zornitza Stark Gene: tcap has been classified as Green List (High Evidence).
Mendeliome v0.11963 TCAP Zornitza Stark Phenotypes for gene: TCAP were changed from to Muscular dystrophy, limb-girdle, autosomal recessive 7, MIM# 601954
Mendeliome v0.11961 TCAP Zornitza Stark reviewed gene: TCAP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 7, MIM# 601954; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11961 TBX5 Zornitza Stark Gene: tbx5 has been classified as Green List (High Evidence).
Mendeliome v0.11958 TBX20 Zornitza Stark Gene: tbx20 has been classified as Green List (High Evidence).
Mendeliome v0.11955 TBL1XR1 Zornitza Stark Gene: tbl1xr1 has been classified as Green List (High Evidence).
Mendeliome v0.11952 TBCK Zornitza Stark Gene: tbck has been classified as Green List (High Evidence).
Mendeliome v0.11949 TBC1D23 Zornitza Stark Gene: tbc1d23 has been classified as Green List (High Evidence).
Mendeliome v0.11949 TBC1D23 Zornitza Stark Phenotypes for gene: TBC1D23 were changed from to Pontocerebellar hypoplasia, type 11, MIM# 617695
Mendeliome v0.11946 TBC1D1 Zornitza Stark Gene: tbc1d1 has been classified as Green List (High Evidence).
Mendeliome v0.11943 TAZ Zornitza Stark Gene: taz has been classified as Green List (High Evidence).
Mendeliome v0.11941 TAT Zornitza Stark Phenotypes for gene: TAT were changed from Tyrosinemia, type II, MIM# 276600 to Tyrosinaemia, type II, MIM# 276600
Mendeliome v0.11940 TAT Zornitza Stark Gene: tat has been classified as Green List (High Evidence).
Mendeliome v0.11940 TAT Zornitza Stark Phenotypes for gene: TAT were changed from to Tyrosinemia, type II, MIM# 276600
Mendeliome v0.11938 TAS2R38 Zornitza Stark Gene: tas2r38 has been classified as Red List (Low Evidence).
Mendeliome v0.11936 TAS2R38 Zornitza Stark Classified gene: TAS2R38 as Red List (low evidence)
Mendeliome v0.11936 TAS2R38 Zornitza Stark Gene: tas2r38 has been classified as Red List (Low Evidence).
Mendeliome v0.11935 TAS2R16 Zornitza Stark Gene: tas2r16 has been classified as Red List (Low Evidence).
Mendeliome v0.11935 TAS2R16 Zornitza Stark Phenotypes for gene: TAS2R16 were changed from to [Beta-glycopyranoside tasting], (3) {Alcohol dependence, susceptibility to} 617956
Mendeliome v0.11933 TAS2R16 Zornitza Stark Classified gene: TAS2R16 as Red List (low evidence)
Mendeliome v0.11933 TAS2R16 Zornitza Stark Gene: tas2r16 has been classified as Red List (Low Evidence).
Mendeliome v0.11932 TAS2R16 Zornitza Stark reviewed gene: TAS2R16: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: [Beta-glycopyranoside tasting], (3) {Alcohol dependence, susceptibility to} 617956; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11932 TANGO2 Zornitza Stark Gene: tango2 has been classified as Green List (High Evidence).
Mendeliome v0.11932 TANGO2 Zornitza Stark Phenotypes for gene: TANGO2 were changed from to Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, MIM# 616878
Mendeliome v0.11929 TANGO2 Zornitza Stark reviewed gene: TANGO2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26805782, 30245509; Phenotypes: Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, MIM# 616878; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11929 TACR3 Zornitza Stark Gene: tacr3 has been classified as Green List (High Evidence).
Mendeliome v0.11926 TAC3 Zornitza Stark Gene: tac3 has been classified as Green List (High Evidence).
Mendeliome v0.11923 T Zornitza Stark Gene: t has been classified as Red List (Low Evidence).
Mendeliome v0.11923 T Zornitza Stark Phenotypes for gene: T were changed from to Sacral agenesis with vertebral anomalies, MIM# 615709
Mendeliome v0.11920 T Zornitza Stark Classified gene: T as Red List (low evidence)
Mendeliome v0.11920 T Zornitza Stark Gene: t has been classified as Red List (Low Evidence).
Mendeliome v0.11919 T Zornitza Stark reviewed gene: T: Rating: RED; Mode of pathogenicity: None; Publications: 24253444, 28116192; Phenotypes: Sacral agenesis with vertebral anomalies 615709; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11911 LBR Alison Yeung Phenotypes for gene: LBR were changed from to Greenberg skeletal dysplasia, MIM# 215140
Mendeliome v0.11910 LBR Alison Yeung Gene: lbr has been classified as Green List (High Evidence).
Mendeliome v0.11908 LAT Alison Yeung Gene: lat has been classified as Green List (High Evidence).
Mendeliome v0.11903 L1CAM Zornitza Stark Phenotypes for gene: L1CAM were changed from Hydrocephalus due to aqueductal stenosis, MIM# 307000; MASA syndrome, MIM# 303350; L1 syndrome, MONDO:0017140 to Hydrocephalus due to aqueductal stenosis, MIM# 307000; MASA syndrome, MIM# 303350; L1 syndrome, MONDO:0017140; Corpus callosum, partial agenesis of, MIM# 304100
Mendeliome v0.11902 L1CAM Zornitza Stark reviewed gene: L1CAM: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hydrocephalus due to aqueductal stenosis, MIM# 307000, Corpus callosum, partial agenesis of, MIM# 304100; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.11900 NPRL3 Zornitza Stark Gene: nprl3 has been classified as Green List (High Evidence).
Mendeliome v0.11897 NPPC Zornitza Stark Gene: nppc has been classified as Red List (Low Evidence).
Mendeliome v0.11894 NPPC Zornitza Stark Classified gene: NPPC as Red List (low evidence)
Mendeliome v0.11894 NPPC Zornitza Stark Gene: nppc has been classified as Red List (Low Evidence).
Mendeliome v0.11893 NOTCH2 Zornitza Stark Gene: notch2 has been classified as Green List (High Evidence).
Mendeliome v0.11890 NOTCH1 Zornitza Stark Gene: notch1 has been classified as Green List (High Evidence).
Mendeliome v0.11887 NONO Zornitza Stark Gene: nono has been classified as Green List (High Evidence).
Mendeliome v0.11884 NOL3 Zornitza Stark Gene: nol3 has been classified as Red List (Low Evidence).
Mendeliome v0.11881 NOL3 Zornitza Stark Classified gene: NOL3 as Red List (low evidence)
Mendeliome v0.11881 NOL3 Zornitza Stark Gene: nol3 has been classified as Red List (Low Evidence).
Mendeliome v0.11880 NOG Zornitza Stark Gene: nog has been classified as Green List (High Evidence).
Mendeliome v0.11880 NOG Zornitza Stark Phenotypes for gene: NOG were changed from to Brachydactyly, type B2 - MIM#611377; Multiple synostoses syndrome 1 (MIM#186500); Stapes ankylosis with broad thumbs and toes (MIM#184460); Symphalangism, proximal, 1A (MIM#185800); Tarsal-carpal coalition syndrome (MIM#186570)
Mendeliome v0.11877 NNT Zornitza Stark Gene: nnt has been classified as Green List (High Evidence).
Mendeliome v0.11874 NLRP7 Zornitza Stark Gene: nlrp7 has been classified as Green List (High Evidence).
Mendeliome v0.11871 NLRP12 Zornitza Stark Gene: nlrp12 has been classified as Green List (High Evidence).
Mendeliome v0.11868 LAS1L Alison Yeung Gene: las1l has been classified as Green List (High Evidence).
Mendeliome v0.11864 LARGE1 Alison Yeung Gene: large1 has been classified as Green List (High Evidence).
Mendeliome v0.11864 LAMC3 Alison Yeung Gene: lamc3 has been classified as Green List (High Evidence).
Mendeliome v0.11864 LAMB2 Alison Yeung Gene: lamb2 has been classified as Green List (High Evidence).
Mendeliome v0.11864 LAMB2 Alison Yeung changed review comment from: Pierson syndrome (PIERS) is an autosomal recessive disorder comprising congenital nephrotic syndrome with diffuse mesangial sclerosis and distinct ocular abnormalities, including microcoria and hypoplasia of the ciliary and pupillary muscles, as well as other anomalies. Many patients die early, and those who survive tend to show neurodevelopmental delay and visual loss.

Nephrotic syndrome type 5 is an autosomal recessive disorder characterized by very early onset of progressive renal failure manifest as proteinuria with consecutive edema starting in utero or within the first 3 months of life. A subset of patients may develop mild ocular anomalies, such as myopia, nystagmus, and strabismus.

The two disorders are likely part of a spectrum. More than 5 unrelated families reported. ; to: Pierson syndrome (PIERS) is an autosomal recessive disorder comprising congenital nephrotic syndrome with diffuse mesangial sclerosis and distinct ocular abnormalities, including microcoria and hypoplasia of the ciliary and pupillary muscles, as well as other anomalies. Many patients die early, and those who survive tend to show neurodevelopmental delay and visual loss.

Nephrotic syndrome type 5 is an autosomal recessive disorder characterized by very early onset of progressive renal failure manifest as proteinuria with consecutive edema starting in utero or within the first 3 months of life. A subset of patients may develop mild ocular anomalies, such as myopia, nystagmus, and strabismus.

More than 5 unrelated families reported.
Mendeliome v0.11864 LAMB2 Alison Yeung changed review comment from: Pierson syndrome (PIERS) is an autosomal recessive disorder comprising congenital nephrotic syndrome with diffuse mesangial sclerosis and distinct ocular abnormalities, including microcoria and hypoplasia of the ciliary and pupillary muscles, as well as other anomalies. Many patients die early, and those who survive tend to show neurodevelopmental delay and visual loss.

Nephrotic syndrome type 5 is an autosomal recessive disorder characterized by very early onset of progressive renal failure manifest as proteinuria with consecutive edema starting in utero or within the first 3 months of life. A subset of patients may develop mild ocular anomalies, such as myopia, nystagmus, and strabismus.; to: Pierson syndrome (PIERS) is an autosomal recessive disorder comprising congenital nephrotic syndrome with diffuse mesangial sclerosis and distinct ocular abnormalities, including microcoria and hypoplasia of the ciliary and pupillary muscles, as well as other anomalies. Many patients die early, and those who survive tend to show neurodevelopmental delay and visual loss.

Nephrotic syndrome type 5 is an autosomal recessive disorder characterized by very early onset of progressive renal failure manifest as proteinuria with consecutive edema starting in utero or within the first 3 months of life. A subset of patients may develop mild ocular anomalies, such as myopia, nystagmus, and strabismus.

The two disorders are likely part of a spectrum. More than 5 unrelated families reported.
Mendeliome v0.11864 L1CAM Alison Yeung Gene: l1cam has been classified as Green List (High Evidence).
Mendeliome v0.11864 L1CAM Alison Yeung Phenotypes for gene: L1CAM were changed from to Hydrocephalus due to aqueductal stenosis, MIM# 307000; MASA syndrome, MIM# 303350; L1 syndrome, MONDO:0017140
Mendeliome v0.11863 L1CAM Alison Yeung reviewed gene: L1CAM: Rating: GREEN; Mode of pathogenicity: None; Publications: 11438988, 7920660, 8401593, 19565280; Phenotypes: Hydrocephalus due to aqueductal stenosis, MIM# 307000, MASA syndrome, MIM# 303350; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Mendeliome v0.11861 MYOM1 Zornitza Stark Classified gene: MYOM1 as Red List (low evidence)
Mendeliome v0.11861 MYOM1 Zornitza Stark Gene: myom1 has been classified as Red List (Low Evidence).
Mendeliome v0.11860 NOG Krithika Murali reviewed gene: NOG: Rating: GREEN; Mode of pathogenicity: None; Publications: 11846737, 18440889, 12089654, 10080184, 15066478, 22088931, 17381491; Phenotypes: Brachydactyly, type B2 - MIM#611377, Multiple synostoses syndrome 1 (MIM#186500), Stapes ankylosis with broad thumbs and toes (MIM#184460), Symphalangism, proximal, 1A (MIM#185800), Tarsal-carpal coalition syndrome (MIM#186570); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11860 STAG1 Zornitza Stark Gene: stag1 has been classified as Green List (High Evidence).
Mendeliome v0.11857 STAR Zornitza Stark Gene: star has been classified as Green List (High Evidence).
Mendeliome v0.11857 STAR Zornitza Stark Phenotypes for gene: STAR were changed from to Lipoid adrenal hyperplasia (MIM#201710)
Mendeliome v0.11854 STAR Zornitza Stark reviewed gene: STAR: Rating: GREEN; Mode of pathogenicity: None; Publications: 7892608, 8634702; Phenotypes: Lipoid adrenal hyperplasia (MIM#201710); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11854 STAT1 Zornitza Stark Gene: stat1 has been classified as Green List (High Evidence).
Mendeliome v0.11854 STAT1 Zornitza Stark Phenotypes for gene: STAT1 were changed from to Immunodeficiency 31A, mycobacteriosis, autosomal dominant, MIM# 614892; Immunodeficiency 31B, mycobacterial and viral infections, autosomal recessive, MIM# 613796; Immunodeficiency 31C, chronic mucocutaneous candidiasis, autosomal dominant, MIM# 614162
Mendeliome v0.11851 STAT1 Zornitza Stark reviewed gene: STAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 16934001, 22573496, 26513235, 12590259, 16585605, 20841510, 21714643, 21727188; Phenotypes: Immunodeficiency 31A, mycobacteriosis, autosomal dominant, MIM# 614892, Immunodeficiency 31B, mycobacterial and viral infections, autosomal recessive, MIM# 613796, Immunodeficiency 31C, chronic mucocutaneous candidiasis, autosomal dominant, MIM# 614162; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11851 STAT2 Zornitza Stark Gene: stat2 has been classified as Green List (High Evidence).
Mendeliome v0.11848 STS Zornitza Stark Gene: sts has been classified as Green List (High Evidence).
Mendeliome v0.11848 STS Zornitza Stark Phenotypes for gene: STS were changed from to Ichthyosis, X-linked 308100; Sterol metabolism disorder
Mendeliome v0.11846 STUB1 Zornitza Stark Gene: stub1 has been classified as Green List (High Evidence).
Mendeliome v0.11846 STUB1 Zornitza Stark Phenotypes for gene: STUB1 were changed from to Spinocerebellar ataxia, autosomal recessive 16, MIM# 615768; Spinocerebellar ataxia 48, MIM#618093
Mendeliome v0.11843 STUB1 Zornitza Stark edited their review of gene: STUB1: Changed publications: 25258038, 24742043, 32337344, 30381368, 31126790; Changed phenotypes: Spinocerebellar ataxia, autosomal recessive 16, MIM# 615768, Spinocerebellar ataxia 48, MIM#618093; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11843 STX11 Zornitza Stark Gene: stx11 has been classified as Green List (High Evidence).
Mendeliome v0.11843 STX11 Zornitza Stark Phenotypes for gene: STX11 were changed from to Haemophagocytic lymphohistiocytosis, familial, 4 , MIM#603552
Mendeliome v0.11840 STX11 Zornitza Stark edited their review of gene: STX11: Changed phenotypes: Haemophagocytic lymphohistiocytosis, familial, 4 , MIM#603552
Mendeliome v0.11840 STX11 Zornitza Stark reviewed gene: STX11: Rating: GREEN; Mode of pathogenicity: None; Publications: 15703195, 16278825, 16582076, 24459464; Phenotypes: Haemophagocytic lymphohistiocytosis, familial, 4 603552; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11840 NLRC4 Zornitza Stark Gene: nlrc4 has been classified as Green List (High Evidence).
Mendeliome v0.11836 NLGN3 Zornitza Stark Gene: nlgn3 has been classified as Green List (High Evidence).
Mendeliome v0.11834 NKX3-2 Zornitza Stark Gene: nkx3-2 has been classified as Green List (High Evidence).
Mendeliome v0.11834 NKX3-2 Zornitza Stark Phenotypes for gene: NKX3-2 were changed from to Spondylo-megaepiphyseal-metaphyseal dysplasia - MIM#613330
Mendeliome v0.11831 NIPAL4 Zornitza Stark Gene: nipal4 has been classified as Green List (High Evidence).
Mendeliome v0.11831 NIPAL4 Zornitza Stark Phenotypes for gene: NIPAL4 were changed from to Ichthyosis, congenital, autosomal recessive 6 - MIM#612281
Mendeliome v0.11828 NHS Zornitza Stark Gene: nhs has been classified as Green List (High Evidence).
Mendeliome v0.11825 NFKBIL1 Zornitza Stark Gene: nfkbil1 has been classified as Red List (Low Evidence).
Mendeliome v0.11824 NFKBIL1 Zornitza Stark Classified gene: NFKBIL1 as Red List (low evidence)
Mendeliome v0.11824 NFKBIL1 Zornitza Stark Gene: nfkbil1 has been classified as Red List (Low Evidence).
Mendeliome v0.11823 NFIA Zornitza Stark Gene: nfia has been classified as Green List (High Evidence).
Mendeliome v0.11819 NEXN Zornitza Stark Gene: nexn has been classified as Green List (High Evidence).
Mendeliome v0.11816 STX1B Zornitza Stark Gene: stx1b has been classified as Green List (High Evidence).
Mendeliome v0.11813 STX2 Zornitza Stark Gene: stx2 has been classified as Red List (Low Evidence).
Mendeliome v0.11813 STX2 Zornitza Stark Classified gene: STX2 as Red List (low evidence)
Mendeliome v0.11813 STX2 Zornitza Stark Gene: stx2 has been classified as Red List (Low Evidence).
Mendeliome v0.11812 STX4 Zornitza Stark Gene: stx4 has been classified as Red List (Low Evidence).
Mendeliome v0.11812 STX4 Zornitza Stark Classified gene: STX4 as Red List (low evidence)
Mendeliome v0.11812 STX4 Zornitza Stark Gene: stx4 has been classified as Red List (Low Evidence).
Mendeliome v0.11811 STXBP2 Zornitza Stark Gene: stxbp2 has been classified as Green List (High Evidence).
Mendeliome v0.11811 STXBP2 Zornitza Stark Phenotypes for gene: STXBP2 were changed from to Haemophagocytic lymphohistiocytosis, familial, 5, with or without microvillus inclusion disease 613101
Mendeliome v0.11808 STXBP2 Zornitza Stark reviewed gene: STXBP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 19804848; Phenotypes: Haemophagocytic lymphohistiocytosis, familial, 5, with or without microvillus inclusion disease 613101; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11808 SULT2B1 Zornitza Stark Gene: sult2b1 has been classified as Green List (High Evidence).
Mendeliome v0.11808 SULT2B1 Zornitza Stark Phenotypes for gene: SULT2B1 were changed from to Ichthyosis, congenital, autosomal recessive 14, MIM# 617571
Mendeliome v0.11805 SULT2B1 Zornitza Stark reviewed gene: SULT2B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28575648; Phenotypes: Ichthyosis, congenital, autosomal recessive 14, MIM# 617571; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11805 SUMF1 Zornitza Stark Gene: sumf1 has been classified as Green List (High Evidence).
Mendeliome v0.11802 SUMO4 Zornitza Stark Gene: sumo4 has been classified as Red List (Low Evidence).
Mendeliome v0.11799 SUMO4 Zornitza Stark Classified gene: SUMO4 as Red List (low evidence)
Mendeliome v0.11799 SUMO4 Zornitza Stark Gene: sumo4 has been classified as Red List (Low Evidence).
Mendeliome v0.11798 SURF1 Zornitza Stark Gene: surf1 has been classified as Green List (High Evidence).
Mendeliome v0.11795 SUZ12 Zornitza Stark Gene: suz12 has been classified as Green List (High Evidence).
Mendeliome v0.11792 NKX3-2 Krithika Murali reviewed gene: NKX3-2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20004766, 29704686; Phenotypes: Spondylo-megaepiphyseal-metaphyseal dysplasia - MIM#613330; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11792 NIPAL4 Krithika Murali reviewed gene: NIPAL4: Rating: GREEN; Mode of pathogenicity: None; Publications: 30578701; Phenotypes: Ichthyosis, congenital, autosomal recessive 6 - MIM#612281; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11792 NEK2 Zornitza Stark Gene: nek2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11789 NEK2 Zornitza Stark Classified gene: NEK2 as Amber List (moderate evidence)
Mendeliome v0.11789 NEK2 Zornitza Stark Gene: nek2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11788 SYCP3 Zornitza Stark Gene: sycp3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11785 SYCP3 Zornitza Stark Classified gene: SYCP3 as Amber List (moderate evidence)
Mendeliome v0.11785 SYCP3 Zornitza Stark Gene: sycp3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11784 SYNE4 Zornitza Stark Gene: syne4 has been classified as Green List (High Evidence).
Mendeliome v0.11784 SYNE4 Zornitza Stark Phenotypes for gene: SYNE4 were changed from to Deafness, autosomal recessive 76, MIM# 615540
Mendeliome v0.11781 SYNE4 Zornitza Stark reviewed gene: SYNE4: Rating: GREEN; Mode of pathogenicity: None; Publications: 23348741, 28958982; Phenotypes: Deafness, autosomal recessive 76, MIM# 615540; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11780 SYNGAP1 Zornitza Stark Gene: syngap1 has been classified as Green List (High Evidence).
Mendeliome v0.11777 SYNJ1 Zornitza Stark Gene: synj1 has been classified as Green List (High Evidence).
Mendeliome v0.11774 ADCY10 Elena Savva Gene: adcy10 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11774 SZT2 Zornitza Stark Gene: szt2 has been classified as Green List (High Evidence).
Mendeliome v0.11771 C2CD6 Zornitza Stark Gene: c2cd6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11771 C2CD6 Zornitza Stark Classified gene: C2CD6 as Amber List (moderate evidence)
Mendeliome v0.11771 C2CD6 Zornitza Stark Gene: c2cd6 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11770 C2CD6 Zornitza Stark gene: C2CD6 was added
gene: C2CD6 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: C2CD6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C2CD6 were set to 34919125; 34998468; 31985809
Phenotypes for gene: C2CD6 were set to Spermatogenic failure 68 , MIM# 619805
Review for gene: C2CD6 was set to AMBER
Added comment: Single individual and two mouse models.
Sources: Expert list
Mendeliome v0.11769 CCDC62 Zornitza Stark Gene: ccdc62 has been classified as Red List (Low Evidence).
Mendeliome v0.11769 CCDC62 Zornitza Stark gene: CCDC62 was added
gene: CCDC62 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CCDC62 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC62 were set to 31985809; 28339613
Phenotypes for gene: CCDC62 were set to Spermatogenic failure 67, MIM# 619803
Review for gene: CCDC62 was set to RED
Added comment: Single individual reported, supportive mouse model.
Sources: Expert list
Mendeliome v0.11768 TXNRD2 Zornitza Stark Gene: txnrd2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11765 TXNRD2 Zornitza Stark Classified gene: TXNRD2 as Amber List (moderate evidence)
Mendeliome v0.11765 TXNRD2 Zornitza Stark Gene: txnrd2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11764 TXNRD2 Zornitza Stark changed review comment from: Further cases reported in this large cohort of paediatric primary adrenal insufficiency.; to: Further cases reported in this large cohort of paediatric primary adrenal insufficiency.

Evidence for association with DCM is limited, considering pop frequency of variants reported.
Mendeliome v0.11764 ADCY10 Zornitza Stark Gene: adcy10 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11762 TALDO1 Zornitza Stark Gene: taldo1 has been classified as Green List (High Evidence).
Mendeliome v0.11759 USP9Y Zornitza Stark Gene: usp9y has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11756 USP9Y Zornitza Stark Classified gene: USP9Y as Amber List (moderate evidence)
Mendeliome v0.11756 USP9Y Zornitza Stark Gene: usp9y has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11754 ADAMTS10 Zornitza Stark changed review comment from: Weill-Marchesani syndrome is a rare connective tissue disorder characterized by short stature, brachydactyly, joint stiffness, eye anomalies, including microspherophakia, ectopia of the lenses, severe myopia, and glaucoma, and, occasionally, heart defects
Sources: Expert list; to: Weill-Marchesani syndrome is a rare connective tissue disorder characterized by short stature, brachydactyly, joint stiffness, eye anomalies, including microspherophakia, ectopia of the lenses, severe myopia, and glaucoma, and, occasionally, heart defects.

Multiple families reported.

Sources: Expert list
Mendeliome v0.11754 ADAMTS10 Zornitza Stark changed review comment from: Mild intellectual disability is described in around 10% of affected individuals.
Sources: Expert list; to: Weill-Marchesani syndrome is a rare connective tissue disorder characterized by short stature, brachydactyly, joint stiffness, eye anomalies, including microspherophakia, ectopia of the lenses, severe myopia, and glaucoma, and, occasionally, heart defects
Sources: Expert list
Mendeliome v0.11753 SARS2 Zornitza Stark Gene: sars2 has been classified as Green List (High Evidence).
Mendeliome v0.11753 SARS2 Zornitza Stark Phenotypes for gene: SARS2 were changed from to Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis, MIM#613845
Mendeliome v0.11750 SARS2 Zornitza Stark reviewed gene: SARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33751860; Phenotypes: Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis, MIM#613845; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11749 ACTN2 Zornitza Stark Classified gene: ACTN2 as Amber List (moderate evidence)
Mendeliome v0.11749 ACTN2 Zornitza Stark Gene: actn2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11748 USH2A Zornitza Stark Gene: ush2a has been classified as Green List (High Evidence).
Mendeliome v0.11745 NDUFS6 Zornitza Stark Gene: ndufs6 has been classified as Green List (High Evidence).
Mendeliome v0.11742 USH1G Zornitza Stark Gene: ush1g has been classified as Green List (High Evidence).
Mendeliome v0.11739 USH1C Zornitza Stark Gene: ush1c has been classified as Green List (High Evidence).
Mendeliome v0.11739 USH1C Zornitza Stark Phenotypes for gene: USH1C were changed from to Usher syndrome, type 1C, MIM# 276904; Deafness, autosomal recessive 18A, MIM# 602092
Mendeliome v0.11736 UROS Zornitza Stark Gene: uros has been classified as Green List (High Evidence).
Mendeliome v0.11733 NDUFS5 Zornitza Stark Gene: ndufs5 has been classified as Red List (Low Evidence).
Mendeliome v0.11733 NDUFS5 Zornitza Stark Classified gene: NDUFS5 as Red List (low evidence)
Mendeliome v0.11733 NDUFS5 Zornitza Stark Gene: ndufs5 has been classified as Red List (Low Evidence).
Mendeliome v0.11731 ADCY10 Elena Savva Classified gene: ADCY10 as Amber List (moderate evidence)
Mendeliome v0.11731 ADCY10 Elena Savva Gene: adcy10 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11730 ADAT3 Elena Savva Gene: adat3 has been classified as Green List (High Evidence).
Mendeliome v0.11730 ADAT3 Elena Savva Phenotypes for gene: ADAT3 were changed from to Mental retardation, autosomal recessive 36, MIM#615286
Mendeliome v0.11729 ADAMTS10 Elena Savva Phenotypes for gene: ADAMTS10 were changed from Weill-Marchesani syndrome 1, recessive, MIM#277600 to Weill-Marchesani syndrome 1, recessive, MIM#277600
Mendeliome v0.11728 ADAMTS10 Elena Savva Phenotypes for gene: ADAMTS10 were changed from to Weill-Marchesani syndrome 1, recessive, MIM#277600
Mendeliome v0.11727 ADAMTS10 Elena Savva Gene: adamts10 has been classified as Green List (High Evidence).
Mendeliome v0.11723 ADAM9 Elena Savva Gene: adam9 has been classified as Green List (High Evidence).
Mendeliome v0.11723 ACVRL1 Elena Savva Phenotypes for gene: ACVRL1 were changed from Telangiectasia, hereditary hemorrhagic, type 2 MIM#600376 to Telangiectasia, hereditary hemorrhagic, type 2 MIM#600376
Mendeliome v0.11723 ACVRL1 Elena Savva Phenotypes for gene: ACVRL1 were changed from Telangiectasia, hereditary hemorrhagic, type 2 MIM#600376 to Telangiectasia, hereditary hemorrhagic, type 2 MIM#600376
Mendeliome v0.11722 ACVRL1 Elena Savva Phenotypes for gene: ACVRL1 were changed from to Telangiectasia, hereditary hemorrhagic, type 2 MIM#600376
Mendeliome v0.11721 ACVRL1 Elena Savva Gene: acvrl1 has been classified as Green List (High Evidence).
Mendeliome v0.11720 ACVRL1 Elena Savva reviewed gene: ACVRL1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 16542389; Phenotypes: Telangiectasia, hereditary hemorrhagic, type 2 MIM#600376; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mendeliome v0.11719 SARS2 Samantha Ayres reviewed gene: SARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24034276, 21255763; Phenotypes: Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis, MIM#613845; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11718 ACTN2 Elena Savva Gene: actn2 has been classified as Green List (High Evidence).
Mendeliome v0.11717 ACADSB Elena Savva Gene: acadsb has been classified as Green List (High Evidence).
Mendeliome v0.11717 ACTG1 Elena Savva Gene: actg1 has been classified as Green List (High Evidence).
Mendeliome v0.11716 ACHE Elena Savva Gene: ache has been classified as Red List (Low Evidence).
Mendeliome v0.11716 ACP4 Elena Savva Phenotypes for gene: ACP4 were changed from Amelogenesis imperfecta, type IJ MIM#617297 to Amelogenesis imperfecta, type IJ MIM#617297
Mendeliome v0.11716 ACP4 Elena Savva Phenotypes for gene: ACP4 were changed from Amelogenesis imperfecta, type IJ MIM#617297 to Amelogenesis imperfecta, type IJ MIM#617297
Mendeliome v0.11715 ACP4 Elena Savva Phenotypes for gene: ACP4 were changed from to Amelogenesis imperfecta, type IJ MIM#617297
Mendeliome v0.11714 ACP4 Elena Savva Gene: acp4 has been classified as Green List (High Evidence).
Mendeliome v0.11712 ACHE Elena Savva Classified gene: ACHE as Red List (low evidence)
Mendeliome v0.11712 ACHE Elena Savva Gene: ache has been classified as Red List (Low Evidence).
Mendeliome v0.11708 WAS Zornitza Stark Gene: was has been classified as Green List (High Evidence).
Mendeliome v0.11705 UNC13D Zornitza Stark Phenotypes for gene: UNC13D were changed from to Haemophagocytic lymphohistiocytosis, familial, 3 MIM#608898
Mendeliome v0.11702 C8A Zornitza Stark Gene: c8a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11699 C8A Zornitza Stark Classified gene: C8A as Amber List (moderate evidence)
Mendeliome v0.11699 C8A Zornitza Stark Gene: c8a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11698 SAMHD1 Zornitza Stark Gene: samhd1 has been classified as Green List (High Evidence).
Mendeliome v0.11695 UNC119 Zornitza Stark Gene: unc119 has been classified as Green List (High Evidence).
Mendeliome v0.11692 UNC119 Zornitza Stark Classified gene: UNC119 as Green List (high evidence)
Mendeliome v0.11692 UNC119 Zornitza Stark Gene: unc119 has been classified as Green List (High Evidence).
Mendeliome v0.11691 UNC119 Zornitza Stark changed review comment from: Immunodeficiency 13: Single case reported with the missense Gly22Val. The allele frequency of this variant is >2% in the African/African American subpopulation in gnomAD v2.1, including 6 homozygotes. RED for this association.

Amber for association with cone-rod dystrophy.; to: Immunodeficiency 13: Single case reported with the missense Gly22Val. The allele frequency of this variant is >2% in the African/African American subpopulation in gnomAD v2.1, including 6 homozygotes. RED for this association.

Borderline Green for association with cone-rod dystrophy.
Mendeliome v0.11691 UNC119 Zornitza Stark Classified gene: UNC119 as Amber List (moderate evidence)
Mendeliome v0.11691 UNC119 Zornitza Stark Gene: unc119 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11690 SAMD9 Zornitza Stark Gene: samd9 has been classified as Green List (High Evidence).
Mendeliome v0.11690 SAMD9 Zornitza Stark Phenotypes for gene: SAMD9 were changed from to MIRAGE syndrome, MIM#617053; Tumoral calcinosis, familial, normophosphatemic, MIM#610455; Monosomy 7 myelodysplasia and leukemia syndrome 2, MIM# 619041
Mendeliome v0.11687 SAMD9 Zornitza Stark reviewed gene: SAMD9: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: MIRAGE syndrome, MIM#617053, Tumoral calcinosis, familial, normophosphatemic, MIM#610455, Monosomy 7 myelodysplasia and leukemia syndrome 2, MIM# 619041; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11687 UCP3 Zornitza Stark Gene: ucp3 has been classified as Red List (Low Evidence).
Mendeliome v0.11686 UCP3 Zornitza Stark Phenotypes for gene: UCP3 were changed from to {Obesity, severe, and type II diabetes}, MIM#601665
Mendeliome v0.11684 UCP3 Zornitza Stark Classified gene: UCP3 as Red List (low evidence)
Mendeliome v0.11684 UCP3 Zornitza Stark Gene: ucp3 has been classified as Red List (Low Evidence).
Mendeliome v0.11683 NDUFS3 Zornitza Stark Gene: ndufs3 has been classified as Green List (High Evidence).
Mendeliome v0.11680 USH2A Belinda Chong edited their review of gene: USH2A: Added comment: Well established gene-disease association - Usher syndrome, DEFINITIVE by ClinGen.

PMID 20507924: Screened the long isoform of USH2A in 80 patients with nonsyndromic autosomal recessive RP and identified at least 1 deleterious mutation in 19% of cases. The authors stated that their findings supported USH2A as the most common known cause of RP in the United States.

https://www.ncbi.nlm.nih.gov/books/NBK1341/, PMID 17296898, ClinVar
Reports of cosegregation of Usher Syndrome and Retinitis Pigmentosa; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11680 C4A Zornitza Stark Gene: c4a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11680 NDUFS2 Zornitza Stark Gene: ndufs2 has been classified as Green List (High Evidence).
Mendeliome v0.11675 C4A Ain Roesley Classified gene: C4A as Amber List (moderate evidence)
Mendeliome v0.11675 C4A Ain Roesley Gene: c4a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11674 C4A Ain Roesley changed review comment from: Associated with increased risk for systemic lupus erythematosus (SLE).
This is mostly involving haplotypes, gene copy number, gene conversions with/without C4B; to: Associated with increased risk for systemic lupus erythematosus (SLE).
This is mostly involving haplotypes, gene copy number, gene conversions with/without C4B

There are no LP/P SNV in clinvar

PMID: 32048120; 2019 Update of the IUIS Phenotypical Classification indicates that complete C4 deficiency requires both C4A+C4B and C4A alone leads to partial deficiency
Mendeliome v0.11674 USH1C Belinda Chong reviewed gene: USH1C: Rating: GREEN; Mode of pathogenicity: None; Publications: 31858762, 10973247, 10973248, 11239869, 21203349, 12107438; Phenotypes: Usher syndrome, type 1C, MIM# 276904, Deafness, autosomal recessive 18A, MIM# 602092, ?Non-syndromic hearing loss; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11674 C4B Ain Roesley Gene: c4b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11674 C4B Zornitza Stark Gene: c4b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11669 C4B Ain Roesley Classified gene: C4B as Amber List (moderate evidence)
Mendeliome v0.11669 C4B Ain Roesley Gene: c4b has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11668 C4B Ain Roesley changed review comment from: Associated with increased risk for systemic lupus erythematosus (SLE).
This is mostly involving haplotypes, gene copy number, gene conversions with/without C4A; to: Associated with increased risk for systemic lupus erythematosus (SLE).
This is mostly involving haplotypes, gene copy number, gene conversions with/without C4A

no LP/P SNVs in clinvar. (1 LP but evidence provided indicates that it was classified as a VUS)

PMID: 32048120;
2019 Update of the IUIS Phenotypical Classification indicates that complete C4 deficiency requires both C4A+C4B and C4A alone leads to partial deficiency
Mendeliome v0.11668 NDUFS1 Zornitza Stark Gene: ndufs1 has been classified as Green List (High Evidence).
Mendeliome v0.11665 UCP3 Belinda Chong changed review comment from: Inheritance: Autosomal dominant, autosomal recessive and multifactorial

PMID: 21544083
Identified four novel mutations in the UCP3 gene (V56M, A111V, V192I and Q252X) in 200 children with severe, early-onset obesity (body mass index-standard deviation score >2.5; onset: <4 years) living in Southern Italy. Indicated that protein UCP3 affects long-chain fatty acid metabolism and can prevent cytosolic triglyceride storage. Also suggested that telmisartan, which increases fatty acid oxidation in rat skeletal muscle, also improves UCP3 wt and mutant protein activity, including the dominant-negative UCP3 mutants (V56M & Q252X).

All variants are present in GnomAD there are 56 - V56M, 325 - A111V, 9 - V192I and 2 - A252X; to: Inheritance: Autosomal dominant, autosomal recessive and multifactorial

PMID: 21544083
Identified four novel mutations in the UCP3 gene (V56M, A111V, V192I and Q252X) in 200 children with severe, early-onset obesity (body mass index-standard deviation score >2.5; onset: <4 years) living in Southern Italy. Indicated that protein UCP3 affects long-chain fatty acid metabolism and can prevent cytosolic triglyceride storage. Also suggested that telmisartan, which increases fatty acid oxidation in rat skeletal muscle, also improves UCP3 wt and mutant protein activity, including the dominant-negative UCP3 mutants (V56M & Q252X). Single pathogenic variant in ClinVar

All variants are present in GnomAD there are 56 - V56M, 325 - A111V, 9 - V192I and 2 - A252X
Mendeliome v0.11665 UNC13D Belinda Chong reviewed gene: UNC13D: Rating: GREEN; Mode of pathogenicity: None; Publications: 14622600, 16825436, 17993578; Phenotypes: Hemophagocytic lymphohistiocytosis, familial, 3 MIM#608898; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.11665 C9 Ain Roesley Gene: c9 has been classified as Green List (High Evidence).
Mendeliome v0.11662 C8B Ain Roesley Gene: c8b has been classified as Green List (High Evidence).
Mendeliome v0.11659 C8A Ain Roesley changed review comment from: 6 unrelated (2 japanese and 4 africans) with 3 different variants between them (2 splice - 1 with aberrant splicing proven on cDNA and 1 nonsense)

PMID: 8098723; 3 families hom for a nonsense and 2 families 3rd het for the same nonsense and unknown 2nd allele

Amber because no other reports apart from these papers and comprehensive sequencing was not done even in the 2020 paper.; to: 6 unrelated (2 japanese and 4 africans) with 3 different variants between them (2 splice - 1 with aberrant splicing proven on cDNA and 1 nonsense)


Amber because no other reports apart from these papers and comprehensive sequencing was not done even in the 2020 paper.
Mendeliome v0.11659 SAMD9 Samantha Ayres reviewed gene: SAMD9: Rating: GREEN; Mode of pathogenicity: None; Publications: 33237688, 32619790, 16960814, 18094730; Phenotypes: MIRAGE syndrome, MIM#617053, Tumoral calcinosis, familial, normophosphatemic, MIM#610455, Monosomy 7 myelodysplasia and leukemia syndrome 2, MIM#619041; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11659 UCP3 Belinda Chong reviewed gene: UCP3: Rating: AMBER; Mode of pathogenicity: None; Publications: 10618503, 11238538, 21544083; Phenotypes: {Obesity, severe, and type II diabetes}; Mode of inheritance: Other
Mendeliome v0.11659 C7 Ain Roesley Gene: c7 has been classified as Green List (High Evidence).
Mendeliome v0.11652 C6 Ain Roesley Gene: c6 has been classified as Green List (High Evidence).
Mendeliome v0.11652 C5 Ain Roesley Gene: c5 has been classified as Green List (High Evidence).
Mendeliome v0.11649 C3 Ain Roesley Gene: c3 has been classified as Green List (High Evidence).
Mendeliome v0.11645 SMARCA4 Zornitza Stark Gene: smarca4 has been classified as Green List (High Evidence).
Mendeliome v0.11645 SMARCA4 Zornitza Stark Phenotypes for gene: SMARCA4 were changed from to Coffin-Siris syndrome 4, MIM# 614609
Mendeliome v0.11642 SMARCA4 Zornitza Stark reviewed gene: SMARCA4: Rating: GREEN; Mode of pathogenicity: None; Publications: 22426308; Phenotypes: Coffin-Siris syndrome 4, MIM# 614609; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11642 SMAD9 Zornitza Stark Gene: smad9 has been classified as Green List (High Evidence).
Mendeliome v0.11642 SMAD9 Zornitza Stark Phenotypes for gene: SMAD9 were changed from to Pulmonary hypertension, primary, 2 MIM#615342
Mendeliome v0.11639 SMAD9 Zornitza Stark reviewed gene: SMAD9: Rating: GREEN; Mode of pathogenicity: None; Publications: 29844917, 21920918, 19211612, 21898662; Phenotypes: Pulmonary hypertension, primary, 2 MIM#615342; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11639 SMAD7 Zornitza Stark Gene: smad7 has been classified as Red List (Low Evidence).
Mendeliome v0.11637 SMAD7 Zornitza Stark Classified gene: SMAD7 as Red List (low evidence)
Mendeliome v0.11637 SMAD7 Zornitza Stark Gene: smad7 has been classified as Red List (Low Evidence).
Mendeliome v0.11636 SMAD4 Zornitza Stark Gene: smad4 has been classified as Green List (High Evidence).
Mendeliome v0.11636 SMAD4 Zornitza Stark Phenotypes for gene: SMAD4 were changed from to Juvenile polyposis/hereditary haemorrhagic telangiectasia syndrome, MIM# 175050; Polyposis, juvenile intestinal, MIM# 174900; Myhre syndrome, MIM# 139210
Mendeliome v0.11633 SMAD4 Zornitza Stark reviewed gene: SMAD4: Rating: GREEN; Mode of pathogenicity: None; Publications: 30809044, 15235019, 16613914, 20101697, 22158539, 22243968; Phenotypes: Juvenile polyposis/hereditary haemorrhagic telangiectasia syndrome, MIM# 175050, Polyposis, juvenile intestinal, MIM# 174900, Myhre syndrome, MIM# 139210; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11633 SLITRK6 Zornitza Stark Gene: slitrk6 has been classified as Green List (High Evidence).
Mendeliome v0.11630 SLITRK1 Zornitza Stark Gene: slitrk1 has been classified as Red List (Low Evidence).
Mendeliome v0.11627 SLITRK1 Zornitza Stark Classified gene: SLITRK1 as Red List (low evidence)
Mendeliome v0.11627 SLITRK1 Zornitza Stark Gene: slitrk1 has been classified as Red List (Low Evidence).
Mendeliome v0.11626 SLCO1B3 Zornitza Stark Gene: slco1b3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11622 SLCO1B1 Zornitza Stark Classified gene: SLCO1B1 as Amber List (moderate evidence)
Mendeliome v0.11622 SLCO1B1 Zornitza Stark Gene: slco1b1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11620 SLCO1B3 Zornitza Stark Classified gene: SLCO1B3 as Amber List (moderate evidence)
Mendeliome v0.11620 SLCO1B3 Zornitza Stark Gene: slco1b3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11619 SLC9A9 Zornitza Stark Gene: slc9a9 has been classified as Red List (Low Evidence).
Mendeliome v0.11616 SLC9A9 Zornitza Stark Classified gene: SLC9A9 as Red List (low evidence)
Mendeliome v0.11616 SLC9A9 Zornitza Stark Gene: slc9a9 has been classified as Red List (Low Evidence).
Mendeliome v0.11615 SLC7A9 Zornitza Stark Gene: slc7a9 has been classified as Green List (High Evidence).
Mendeliome v0.11612 SLC6A9 Zornitza Stark Gene: slc6a9 has been classified as Green List (High Evidence).
Mendeliome v0.11609 SLC6A8 Zornitza Stark Gene: slc6a8 has been classified as Green List (High Evidence).
Mendeliome v0.11606 ENPP1 Zornitza Stark Phenotypes for gene: ENPP1 were changed from to Arterial calcification, generalized, of infancy, 1, MIM# 208000; Cole disease, MIM# 615522; Hypophosphatemic rickets, autosomal recessive, 2, MIM# 613312
Mendeliome v0.11603 ENPP1 Zornitza Stark reviewed gene: ENPP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24075184, 26617416, 28964717, 32598042, 35220637, 12881724, 15605415, 33005041, 20016754, 20137773, 20137772; Phenotypes: Arterial calcification, generalized, of infancy, 1, MIM# 208000, Cole disease, MIM# 615522, Hypophosphatemic rickets, autosomal recessive, 2, MIM# 613312; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11603 VMA21 Zornitza Stark Gene: vma21 has been classified as Green List (High Evidence).
Mendeliome v0.11603 VMA21 Zornitza Stark Phenotypes for gene: VMA21 were changed from to Myopathy, X-linked, with excessive autophagy, MIM# 310440
Mendeliome v0.11600 VMA21 Zornitza Stark reviewed gene: VMA21: Rating: GREEN; Mode of pathogenicity: None; Publications: 27916343, 25809233, 23315026; Phenotypes: Myopathy, X-linked, with excessive autophagy, MIM# 310440; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.11600 VPS33B Zornitza Stark Gene: vps33b has been classified as Green List (High Evidence).
Mendeliome v0.11600 VPS33B Zornitza Stark Phenotypes for gene: VPS33B were changed from to Arthrogryposis, renal dysfunction, and cholestasis 1 (MIM#208085)
Mendeliome v0.11597 VPS33B Zornitza Stark reviewed gene: VPS33B: Rating: GREEN; Mode of pathogenicity: None; Publications: 31240160, 31777725, 24415890, 15052268; Phenotypes: Arthrogryposis, renal dysfunction, and cholestasis 1 (MIM#208085); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11597 VPS35 Zornitza Stark Gene: vps35 has been classified as Green List (High Evidence).
Mendeliome v0.11594 VSX1 Zornitza Stark Gene: vsx1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11591 VSX1 Zornitza Stark Classified gene: VSX1 as Amber List (moderate evidence)
Mendeliome v0.11591 VSX1 Zornitza Stark Gene: vsx1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11590 VWF Zornitza Stark Gene: vwf has been classified as Green List (High Evidence).
Mendeliome v0.11588 VKORC1 Zornitza Stark Gene: vkorc1 has been classified as Green List (High Evidence).
Mendeliome v0.11588 VKORC1 Zornitza Stark Phenotypes for gene: VKORC1 were changed from to Vitamin K-dependent clotting factors, combined deficiency of, 2, MIM# 607473; Warfarin resistance, MIM# 122700
Mendeliome v0.11586 VIPAS39 Zornitza Stark Gene: vipas39 has been classified as Green List (High Evidence).
Mendeliome v0.11586 VIPAS39 Zornitza Stark Phenotypes for gene: VIPAS39 were changed from to Arthrogryposis, renal dysfunction, and cholestasis 2, MIM#613404
Mendeliome v0.11583 VIPAS39 Zornitza Stark reviewed gene: VIPAS39: Rating: GREEN; Mode of pathogenicity: None; Publications: 20190753, 35151346; Phenotypes: Arthrogryposis, renal dysfunction, and cholestasis 2, MIM#613404; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11583 VEGFA Zornitza Stark Gene: vegfa has been classified as Red List (Low Evidence).
Mendeliome v0.11582 VEGFA Zornitza Stark Classified gene: VEGFA as Red List (low evidence)
Mendeliome v0.11582 VEGFA Zornitza Stark Gene: vegfa has been classified as Red List (Low Evidence).
Mendeliome v0.11581 VDR Zornitza Stark Gene: vdr has been classified as Green List (High Evidence).
Mendeliome v0.11581 VDR Zornitza Stark Phenotypes for gene: VDR were changed from to Rickets, vitamin D-resistant, type IIA, MIM# 277440
Mendeliome v0.11578 VDR Zornitza Stark reviewed gene: VDR: Rating: GREEN; Mode of pathogenicity: None; Publications: 2849209, 9005998, 17970811; Phenotypes: Rickets, vitamin D-resistant, type IIA, MIM# 277440; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11578 VCL Zornitza Stark Gene: vcl has been classified as Green List (High Evidence).
Mendeliome v0.11575 VANGL2 Zornitza Stark Gene: vangl2 has been classified as Red List (Low Evidence).
Mendeliome v0.11572 VANGL2 Zornitza Stark Classified gene: VANGL2 as Red List (low evidence)
Mendeliome v0.11572 VANGL2 Zornitza Stark Gene: vangl2 has been classified as Red List (Low Evidence).
Mendeliome v0.11571 VANGL1 Zornitza Stark Gene: vangl1 has been classified as Red List (Low Evidence).
Mendeliome v0.11571 VANGL1 Zornitza Stark Phenotypes for gene: VANGL1 were changed from to Caudal regression syndrome, MIM# 600145; {Neural tube defects, susceptibility to} 182940
Mendeliome v0.11568 VANGL1 Zornitza Stark Classified gene: VANGL1 as Red List (low evidence)
Mendeliome v0.11568 VANGL1 Zornitza Stark Gene: vangl1 has been classified as Red List (Low Evidence).
Mendeliome v0.11567 VANGL1 Zornitza Stark reviewed gene: VANGL1: Rating: RED; Mode of pathogenicity: None; Publications: 17409324; Phenotypes: Caudal regression syndrome, MIM# 600145, {Neural tube defects, susceptibility to} 182940; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11567 VAMP1 Zornitza Stark Gene: vamp1 has been classified as Green List (High Evidence).
Mendeliome v0.11564 NDUFB8 Zornitza Stark Gene: ndufb8 has been classified as Green List (High Evidence).
Mendeliome v0.11561 NDUFAF7 Zornitza Stark Gene: ndufaf7 has been classified as Red List (Low Evidence).
Mendeliome v0.11558 NDUFAF7 Zornitza Stark Classified gene: NDUFAF7 as Red List (low evidence)
Mendeliome v0.11558 NDUFAF7 Zornitza Stark Gene: ndufaf7 has been classified as Red List (Low Evidence).
Mendeliome v0.11554 NDUFAF4 Zornitza Stark Gene: ndufaf4 has been classified as Green List (High Evidence).
Mendeliome v0.11551 EDARADD Bryony Thompson Gene: edaradd has been classified as Green List (High Evidence).
Mendeliome v0.11550 EDARADD Bryony Thompson reviewed gene: EDARADD: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301291, 34219261, 11780064, 26991760, 34573371, 20979233, 17354266, 26440664; Phenotypes: autosomal dominant hypohidrotic ectodermal dysplasia MONDO:0015884, autosomal recessive hypohidrotic ectodermal dysplasia MONDO:0016619; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.11550 EDAR Bryony Thompson Gene: edar has been classified as Green List (High Evidence).
Mendeliome v0.11550 EDAR Bryony Thompson Phenotypes for gene: EDAR were changed from to autosomal dominant hypohidrotic ectodermal dysplasia MONDO:0015884; autosomal recessive hypohidrotic ectodermal dysplasia MONDO:0016619
Mendeliome v0.11547 EDAR Bryony Thompson reviewed gene: EDAR: Rating: GREEN; Mode of pathogenicity: None; Publications: 10431241, 20301291, 16435307, 20979233, 23401279, 18384562; Phenotypes: autosomal dominant hypohidrotic ectodermal dysplasia MONDO:0015884, autosomal recessive hypohidrotic ectodermal dysplasia MONDO:0016619; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.11547 NDUFAF3 Zornitza Stark Gene: ndufaf3 has been classified as Green List (High Evidence).
Mendeliome v0.11544 NDUFA2 Zornitza Stark Gene: ndufa2 has been classified as Green List (High Evidence).
Mendeliome v0.11541 FRA10AC1 Ain Roesley Classified gene: FRA10AC1 as Green List (high evidence)
Mendeliome v0.11541 FRA10AC1 Ain Roesley Gene: fra10ac1 has been classified as Green List (High Evidence).
Mendeliome v0.11540 NDUFAF4 Krithika Murali edited their review of gene: NDUFAF4: Added comment: 3 unrelated families reported with patient-specific functional evidence provided for each.

PMID: 32949790 - report two siblings with facial dysmorphism and lactic acidosis diagnosed neonatally with subsequent fatal early encephalopathy with apneic episodes, irritability, central hypoventilation, liver involvement and hyperammonemia. Cerebral white matter anomalies reported in one patient and cardiomyopathy in the other. WES identified homozygous nonsense NDUFAF4 variants with absent NDUFAF4 expression in patient fibroblasts. OXPHOS assembly studies demonstrated almost undetectable levels of fully assembled complex I and complex I–containing supercomplexes and an abnormal accumulation of SCIII2IV1 supercomplexes. Morphologically, fibroblasts showed rounder mitochondria and a diminished degree of branching of the mitochondrial network.

PMID: 28853723 - report one patient born at 38 weeks after IOL for IUGR. Presented age 7 months with developmental regression, growth failure and central hypotonia. Brain MRI revealed diffuse bilateral signal alterations in the basal ganglia and thalami and an EEG showed generalized slowing with multifocal spikes consistent with an epileptogenic focus. Homozygous missense NDUFAF4 variants identified. Lentiviral complementation of patient fibroblasts with wild-type NDUFAF4 rescued complex I deficiency and assembly defect

PMID 18179882 - report multiple affected individuals from one family. Most presented soon after birth with severe metabolic acidosis and high plasma lactate levels. Patients who survived longer were repeatedly admitted because of exacerbation of the acidosis during intercurrent infections. One long-term survivor had profound ID.; Changed publications: 32949790, 28853723, 18179882
Mendeliome v0.11540 UBA5 Zornitza Stark Gene: uba5 has been classified as Green List (High Evidence).
Mendeliome v0.11540 UBA5 Zornitza Stark Phenotypes for gene: UBA5 were changed from to Spinocerebellar ataxia, autosomal recessive 24, MIM# 617133; Epileptic encephalopathy, early infantile, 44 617132; Hypomyelinating neuropathy
Mendeliome v0.11537 UBA5 Zornitza Stark changed review comment from: Bi-allelic variants in UBA5 cause a range of neurological phenotypes. Ataxia has been specifically described only in one sibling pair. Multiple individuals reported with a more severe EE/ID phenotype, and non-specific movement disorders.; to: Bi-allelic variants in UBA5 cause a range of neurological phenotypes. Ataxia has been specifically described only in one sibling pair. Multiple individuals reported with a more severe EE/ID phenotype, and non-specific movement disorders.

Also note these two reports of demyelinating peripheral neuropathy: 26872069 pair of sibs with mild ataxia, one with neuropathy; 32179706 five individuals from a consanguineous family presenting in infancy with severe fatal neuropathy. Some functional data. Due to early mortality, uncertain at present whether additional features would have developed.
Mendeliome v0.11537 UBA5 Zornitza Stark edited their review of gene: UBA5: Changed rating: GREEN; Changed publications: 26872069, 27545681, 27545674, 32179706, 26872069; Changed phenotypes: Spinocerebellar ataxia, autosomal recessive 24, MIM# 617133, Epileptic encephalopathy, early infantile, 44 617132, Hypomyelinating neuropathy
Mendeliome v0.11537 KANSL1 Zornitza Stark Gene: kansl1 has been classified as Green List (High Evidence).
Mendeliome v0.11537 IKBKG Zornitza Stark Gene: ikbkg has been classified as Green List (High Evidence).
Mendeliome v0.11537 IKBKG Zornitza Stark Phenotypes for gene: IKBKG were changed from to Ectodermal dysplasia and immunodeficiency 1, MIM# 300291; Immunodeficiency 33 , MIM#300636; Incontinentia pigmenti, MIM# 308300
Mendeliome v0.11535 IKBKG Zornitza Stark reviewed gene: IKBKG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ectodermal dysplasia and immunodeficiency 1, MIM# 300291, Immunodeficiency 33 , MIM#300636, Incontinentia pigmenti, MIM# 308300; 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 v0.11535 IKBKB Zornitza Stark Gene: ikbkb has been classified as Green List (High Evidence).
Mendeliome v0.11532 IL10RB Zornitza Stark Gene: il10rb has been classified as Green List (High Evidence).
Mendeliome v0.11532 IL10RB Zornitza Stark Phenotypes for gene: IL10RB were changed from to Inflammatory bowel disease 25, early onset, autosomal recessive, MIM# 612567
Mendeliome v0.11529 IL12B Zornitza Stark Gene: il12b has been classified as Green List (High Evidence).
Mendeliome v0.11529 IL12B Zornitza Stark Phenotypes for gene: IL12B were changed from to Immunodeficiency 29, mycobacteriosis, MIM# 614890
Mendeliome v0.11526 IL12B Zornitza Stark reviewed gene: IL12B: Rating: GREEN; Mode of pathogenicity: None; Publications: 9854038, 11753820, 34389021; Phenotypes: Immunodeficiency 29, mycobacteriosis, MIM# 614890; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11526 IL10RB Zornitza Stark reviewed gene: IL10RB: Rating: GREEN; Mode of pathogenicity: None; Publications: 19890111, 21519361, 35187668, 31096038; Phenotypes: Inflammatory bowel disease 25, early onset, autosomal recessive, MIM# 612567; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11526 IL10RA Zornitza Stark Gene: il10ra has been classified as Green List (High Evidence).
Mendeliome v0.11526 IL10RA Zornitza Stark Phenotypes for gene: IL10RA were changed from to Inflammatory bowel disease 28, early onset, autosomal recessive, MIM# 613148
Mendeliome v0.11523 IL10RA Zornitza Stark reviewed gene: IL10RA: Rating: GREEN; Mode of pathogenicity: None; Publications: 19890111, 21519361, 22476154; Phenotypes: Inflammatory bowel disease 28, early onset, autosomal recessive, MIM# 613148; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11523 IL10 Zornitza Stark Gene: il10 has been classified as Green List (High Evidence).
Mendeliome v0.11520 IGLL1 Zornitza Stark Gene: igll1 has been classified as Green List (High Evidence).
Mendeliome v0.11517 IGHMBP2 Zornitza Stark Gene: ighmbp2 has been classified as Green List (High Evidence).
Mendeliome v0.11514 CCDC134 Zornitza Stark Gene: ccdc134 has been classified as Green List (High Evidence).
Mendeliome v0.11514 CCDC134 Zornitza Stark Classified gene: CCDC134 as Green List (high evidence)
Mendeliome v0.11514 CCDC134 Zornitza Stark Gene: ccdc134 has been classified as Green List (High Evidence).
Mendeliome v0.11513 CCDC134 Zornitza Stark gene: CCDC134 was added
gene: CCDC134 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CCDC134 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC134 were set to 32181939; 34204301; 35019224
Phenotypes for gene: CCDC134 were set to Osteogenesis imperfecta, type XXII, MIM#619795
Review for gene: CCDC134 was set to GREEN
Added comment: Three unrelated families reported.
Sources: Expert list
Mendeliome v0.11512 RACGAP1 Zornitza Stark Gene: racgap1 has been classified as Red List (Low Evidence).
Mendeliome v0.11512 RACGAP1 Zornitza Stark gene: RACGAP1 was added
gene: RACGAP1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: RACGAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RACGAP1 were set to 34818416
Phenotypes for gene: RACGAP1 were set to Anaemia, congenital dyserythropoietic, type IIIb, autosomal recessive 619789
Review for gene: RACGAP1 was set to RED
Added comment: Single affected individual reported.
Sources: Expert Review
Mendeliome v0.11509 KIF23 Zornitza Stark Classified gene: KIF23 as Amber List (moderate evidence)
Mendeliome v0.11509 KIF23 Zornitza Stark Gene: kif23 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11508 IL12RB1 Zornitza Stark Gene: il12rb1 has been classified as Green List (High Evidence).
Mendeliome v0.11505 IL13 Zornitza Stark Gene: il13 has been classified as Red List (Low Evidence).
Mendeliome v0.11504 IL13 Zornitza Stark Classified gene: IL13 as Red List (low evidence)
Mendeliome v0.11504 IL13 Zornitza Stark Gene: il13 has been classified as Red List (Low Evidence).
Mendeliome v0.11503 NDUFAF2 Zornitza Stark Gene: ndufaf2 has been classified as Green List (High Evidence).
Mendeliome v0.11500 NDUFAF1 Zornitza Stark Gene: ndufaf1 has been classified as Green List (High Evidence).
Mendeliome v0.11497 NDUFA9 Zornitza Stark Gene: ndufa9 has been classified as Green List (High Evidence).
Mendeliome v0.11494 NDUFA7 Zornitza Stark Gene: ndufa7 has been classified as Red List (Low Evidence).
Mendeliome v0.11494 NDUFA7 Zornitza Stark Classified gene: NDUFA7 as Red List (low evidence)
Mendeliome v0.11494 NDUFA7 Zornitza Stark Gene: ndufa7 has been classified as Red List (Low Evidence).
Mendeliome v0.11493 TPTE2P5 Zornitza Stark Gene: tpte2p5 has been classified as Red List (Low Evidence).
Mendeliome v0.11493 TPTE2P5 Zornitza Stark Classified gene: TPTE2P5 as Red List (low evidence)
Mendeliome v0.11493 TPTE2P5 Zornitza Stark Gene: tpte2p5 has been classified as Red List (Low Evidence).
Mendeliome v0.11492 IL6 Zornitza Stark Gene: il6 has been classified as Red List (Low Evidence).
Mendeliome v0.11492 IL6 Zornitza Stark Phenotypes for gene: IL6 were changed from to {Crohn disease-associated growth failure} 266600; {Intracranial hemorrhage in brain cerebrovascular malformations, susceptibility to} 108010; {Rheumatoid arthritis, systemic juvenile} 604302; {Kaposi sarcoma, susceptibility to} 148000; {Type 1 diabetes mellitus} 222100; {Type 2 diabetes mellitus} 125853
Mendeliome v0.11491 IL6 Zornitza Stark Classified gene: IL6 as Red List (low evidence)
Mendeliome v0.11491 IL6 Zornitza Stark Gene: il6 has been classified as Red List (Low Evidence).
Mendeliome v0.11490 IL6 Zornitza Stark reviewed gene: IL6: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: {Crohn disease-associated growth failure} 266600, {Intracranial hemorrhage in brain cerebrovascular malformations, susceptibility to} 108010, {Rheumatoid arthritis, systemic juvenile} 604302, {Kaposi sarcoma, susceptibility to} 148000, {Type 1 diabetes mellitus} 222100, {Type 2 diabetes mellitus} 125853; Mode of inheritance: None
Mendeliome v0.11490 IL4 Zornitza Stark Gene: il4 has been classified as Red List (Low Evidence).
Mendeliome v0.11490 IL4 Zornitza Stark Classified gene: IL4 as Red List (low evidence)
Mendeliome v0.11490 IL4 Zornitza Stark Gene: il4 has been classified as Red List (Low Evidence).
Mendeliome v0.11489 IL36RN Zornitza Stark Gene: il36rn has been classified as Green List (High Evidence).
Mendeliome v0.11489 IL36RN Zornitza Stark Phenotypes for gene: IL36RN were changed from to Psoriasis 14, pustular, MIM# 614204
Mendeliome v0.11486 IL36RN Zornitza Stark reviewed gene: IL36RN: Rating: GREEN; Mode of pathogenicity: None; Publications: 21848462, 21839423, 22903787, 23648549; Phenotypes: Psoriasis 14, pustular, MIM# 614204; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11486 IL31RA Zornitza Stark Gene: il31ra has been classified as Red List (Low Evidence).
Mendeliome v0.11486 IL31RA Zornitza Stark Phenotypes for gene: IL31RA were changed from to Amyloidosis, primary localized cutaneous, 2, MIM# 613955
Mendeliome v0.11484 IL31RA Zornitza Stark Classified gene: IL31RA as Red List (low evidence)
Mendeliome v0.11484 IL31RA Zornitza Stark Gene: il31ra has been classified as Red List (Low Evidence).
Mendeliome v0.11483 IL31RA Zornitza Stark reviewed gene: IL31RA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Amyloidosis, primary localized cutaneous, 2, MIM# 613955; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11483 IL2RA Zornitza Stark Gene: il2ra has been classified as Green List (High Evidence).
Mendeliome v0.11480 IL1RN Zornitza Stark Gene: il1rn has been classified as Green List (High Evidence).
Mendeliome v0.11477 IREB2 Zornitza Stark Gene: ireb2 has been classified as Green List (High Evidence).
Mendeliome v0.11474 ISG15 Zornitza Stark Gene: isg15 has been classified as Green List (High Evidence).
Mendeliome v0.11471 ISCU Zornitza Stark Gene: iscu has been classified as Green List (High Evidence).
Mendeliome v0.11471 ISCU Zornitza Stark Phenotypes for gene: ISCU were changed from to Myopathy with lactic acidosis, hereditary, MIM# 255125
Mendeliome v0.11468 ISCU Zornitza Stark reviewed gene: ISCU: Rating: GREEN; Mode of pathogenicity: None; Publications: 29079705, 18304497, 18296749, 19567699; Phenotypes: Myopathy with lactic acidosis, hereditary, MIM# 255125; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11468 IRS1 Zornitza Stark Gene: irs1 has been classified as Red List (Low Evidence).
Mendeliome v0.11467 IRS1 Zornitza Stark Classified gene: IRS1 as Red List (low evidence)
Mendeliome v0.11467 IRS1 Zornitza Stark Gene: irs1 has been classified as Red List (Low Evidence).
Mendeliome v0.11466 IRF8 Zornitza Stark Gene: irf8 has been classified as Green List (High Evidence).
Mendeliome v0.11466 IRF8 Zornitza Stark Phenotypes for gene: IRF8 were changed from to Immunodeficiency 32A, mycobacteriosis, autosomal dominant, MIM# 614893; Immunodeficiency 32B, monocyte and dendritic cell deficiency, autosomal recessive, MIM# 226990
Mendeliome v0.11463 IRF8 Zornitza Stark reviewed gene: IRF8: Rating: GREEN; Mode of pathogenicity: None; Publications: 21524210, 27893462, 29128673, 28162909, 25122610; Phenotypes: Immunodeficiency 32A, mycobacteriosis, autosomal dominant, MIM# 614893, Immunodeficiency 32B, monocyte and dendritic cell deficiency, autosomal recessive, MIM# 226990; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11463 IRF5 Zornitza Stark Gene: irf5 has been classified as Red List (Low Evidence).
Mendeliome v0.11462 IRF5 Zornitza Stark Classified gene: IRF5 as Red List (low evidence)
Mendeliome v0.11462 IRF5 Zornitza Stark Gene: irf5 has been classified as Red List (Low Evidence).
Mendeliome v0.11461 IRF1 Zornitza Stark Gene: irf1 has been classified as Red List (Low Evidence).
Mendeliome v0.11461 IRF1 Zornitza Stark Classified gene: IRF1 as Red List (low evidence)
Mendeliome v0.11461 IRF1 Zornitza Stark Gene: irf1 has been classified as Red List (Low Evidence).
Mendeliome v0.11459 NDUFA10 Zornitza Stark Gene: ndufa10 has been classified as Green List (High Evidence).
Mendeliome v0.11456 NDST1 Zornitza Stark Gene: ndst1 has been classified as Green List (High Evidence).
Mendeliome v0.11456 NDST1 Zornitza Stark Phenotypes for gene: NDST1 were changed from to Mental retardation, autosomal recessive 46 - MIM#616116
Mendeliome v0.11453 NCR3 Zornitza Stark Gene: ncr3 has been classified as Red List (Low Evidence).
Mendeliome v0.11453 NCR3 Zornitza Stark Classified gene: NCR3 as Red List (low evidence)
Mendeliome v0.11453 NCR3 Zornitza Stark Gene: ncr3 has been classified as Red List (Low Evidence).
Mendeliome v0.11452 NCOA4 Zornitza Stark Gene: ncoa4 has been classified as Red List (Low Evidence).
Mendeliome v0.11452 NCOA4 Zornitza Stark Classified gene: NCOA4 as Red List (low evidence)
Mendeliome v0.11452 NCOA4 Zornitza Stark Gene: ncoa4 has been classified as Red List (Low Evidence).
Mendeliome v0.11451 NCF4 Zornitza Stark Gene: ncf4 has been classified as Green List (High Evidence).
Mendeliome v0.11451 NCF4 Zornitza Stark Phenotypes for gene: NCF4 were changed from to Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type III MIM#613960
Mendeliome v0.11448 NCF2 Zornitza Stark Gene: ncf2 has been classified as Green List (High Evidence).
Mendeliome v0.11448 NCF2 Zornitza Stark Phenotypes for gene: NCF2 were changed from to Chronic granulomatous disease 2, autosomal recessive, MIM# 233710
Mendeliome v0.11445 SALL4 Zornitza Stark Gene: sall4 has been classified as Green List (High Evidence).
Mendeliome v0.11442 TYROBP Zornitza Stark Gene: tyrobp has been classified as Green List (High Evidence).
Mendeliome v0.11442 TYROBP Zornitza Stark Phenotypes for gene: TYROBP were changed from to Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1, MIM# 221770
Mendeliome v0.11439 TYROBP Zornitza Stark reviewed gene: TYROBP: Rating: GREEN; Mode of pathogenicity: None; Publications: 10888890, 12370476, 27904822; Phenotypes: Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1, MIM# 221770; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11439 IRAK4 Zornitza Stark Gene: irak4 has been classified as Green List (High Evidence).
Mendeliome v0.11436 INSR Zornitza Stark Gene: insr has been classified as Green List (High Evidence).
Mendeliome v0.11433 INS Zornitza Stark Gene: ins has been classified as Green List (High Evidence).
Mendeliome v0.11430 INO80 Zornitza Stark Gene: ino80 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11427 INO80 Zornitza Stark Classified gene: INO80 as Amber List (moderate evidence)
Mendeliome v0.11427 INO80 Zornitza Stark Gene: ino80 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11426 IMPAD1 Zornitza Stark Gene: impad1 has been classified as Green List (High Evidence).
Mendeliome v0.11426 IMPAD1 Zornitza Stark Phenotypes for gene: IMPAD1 were changed from to Chondrodysplasia with joint dislocations, GPAPP type MIM#614078
Mendeliome v0.11423 IMPAD1 Zornitza Stark reviewed gene: IMPAD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22887726, 21549340; Phenotypes: Chondrodysplasia with joint dislocations, GPAPP type MIM#614078; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11423 ILF2 Zornitza Stark Gene: ilf2 has been classified as Red List (Low Evidence).
Mendeliome v0.11423 TYROBP Manny Jacobs reviewed gene: TYROBP: Rating: GREEN; Mode of pathogenicity: None; Publications: 27904822; Phenotypes: # 221770 POLYCYSTIC LIPOMEMBRANOUS OSTEODYSPLASIA WITH SCLEROSING LEUKOENCEPHALOPATHY 1; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11423 ILF2 Zornitza Stark Classified gene: ILF2 as Red List (low evidence)
Mendeliome v0.11423 ILF2 Zornitza Stark Gene: ilf2 has been classified as Red List (Low Evidence).
Mendeliome v0.11422 NDST1 Krithika Murali reviewed gene: NDST1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25125150, 21937992, 32878022, 28211985; Phenotypes: Mental retardation, autosomal recessive 46 - MIM#616116; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11422 NCF4 Krithika Murali reviewed gene: NCF4: Rating: GREEN; Mode of pathogenicity: None; Publications: 19692703, 16880254, 29969437; Phenotypes: Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type III MIM#613960; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11422 NCF2 Krithika Murali reviewed gene: NCF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 7795241, 10498624; Phenotypes: Chronic granulomatous disease 2, autosomal recessive, MIM# 233710; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11422 IFNGR2 Zornitza Stark Gene: ifngr2 has been classified as Green List (High Evidence).
Mendeliome v0.11422 IFNGR2 Zornitza Stark Phenotypes for gene: IFNGR2 were changed from to Immunodeficiency 28, mycobacteriosis, MIM# 614889
Mendeliome v0.11419 IFNGR2 Zornitza Stark reviewed gene: IFNGR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 15924140, 18625743, 31222290; Phenotypes: Immunodeficiency 28, mycobacteriosis, MIM# 614889; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11419 IFNGR1 Zornitza Stark Gene: ifngr1 has been classified as Green List (High Evidence).
Mendeliome v0.11419 IFNGR1 Zornitza Stark Phenotypes for gene: IFNGR1 were changed from to Immunodeficiency 27A, mycobacteriosis, AR, MIM# 209950; Immunodeficiency 27B, mycobacteriosis, AD, MIM# 615978
Mendeliome v0.11416 IFNGR1 Zornitza Stark reviewed gene: IFNGR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 7815885, 8960475, 9389728, 10811850, 10192386, 12244188, 15589309; Phenotypes: Immunodeficiency 27A, mycobacteriosis, AR, MIM# 209950, Immunodeficiency 27B, mycobacteriosis, AD, MIM# 615978; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11416 IFITM3 Zornitza Stark Gene: ifitm3 has been classified as Red List (Low Evidence).
Mendeliome v0.11415 IFITM3 Zornitza Stark Classified gene: IFITM3 as Red List (low evidence)
Mendeliome v0.11415 IFITM3 Zornitza Stark Gene: ifitm3 has been classified as Red List (Low Evidence).
Mendeliome v0.11414 IDH3B Zornitza Stark Gene: idh3b has been classified as Green List (High Evidence).
Mendeliome v0.11411 IDH2 Zornitza Stark Gene: idh2 has been classified as Green List (High Evidence).
Mendeliome v0.11408 ICOS Zornitza Stark Gene: icos has been classified as Green List (High Evidence).
Mendeliome v0.11405 ICAM4 Zornitza Stark Gene: icam4 has been classified as Red List (Low Evidence).
Mendeliome v0.11404 ICAM4 Zornitza Stark Classified gene: ICAM4 as Red List (low evidence)
Mendeliome v0.11404 ICAM4 Zornitza Stark Gene: icam4 has been classified as Red List (Low Evidence).
Mendeliome v0.11403 ACACA Zornitza Stark Gene: acaca has been classified as Red List (Low Evidence).
Mendeliome v0.11400 ACACA Zornitza Stark Classified gene: ACACA as Red List (low evidence)
Mendeliome v0.11400 ACACA Zornitza Stark Gene: acaca has been classified as Red List (Low Evidence).
Mendeliome v0.11399 ABL1 Zornitza Stark Gene: abl1 has been classified as Green List (High Evidence).
Mendeliome v0.11399 ABCG8 Zornitza Stark Gene: abcg8 has been classified as Green List (High Evidence).
Mendeliome v0.11399 ABCG8 Zornitza Stark Phenotypes for gene: ABCG8 were changed from to Sitosterolemia 1, MIM#210250
Mendeliome v0.11394 ACAD8 Elena Savva Gene: acad8 has been classified as Green List (High Evidence).
Mendeliome v0.11391 C2 Ain Roesley Gene: c2 has been classified as Green List (High Evidence).
Mendeliome v0.11388 ABCG8 Elena Savva reviewed gene: ABCG8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Sitosterolemia 1 MIM#210250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11387 C1S Ain Roesley Gene: c1s has been classified as Green List (High Evidence).
Mendeliome v0.11386 ABCC8 Elena Savva Gene: abcc8 has been classified as Green List (High Evidence).
Mendeliome v0.11386 ABCC8 Elena Savva Phenotypes for gene: ABCC8 were changed from to Diabetes mellitus, noninsulin-dependent MIM#125853; Diabetes mellitus, permanent neonatal 3, with or without neurologic features MIM#618857; Diabetes mellitus, transient neonatal 2 MIM#610374; Hyperinsulinemic hypoglycemia, familial, 1 MIM#256450; Hypoglycemia of infancy, leucine-sensitive MIM#240800
Mendeliome v0.11384 ABCC8 Elena Savva reviewed gene: ABCC8: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 21054355, 32027066, 32376986; Phenotypes: Diabetes mellitus, noninsulin-dependent MIM#125853, Diabetes mellitus, permanent neonatal 3, with or without neurologic features MIM#618857, Diabetes mellitus, transient neonatal 2 MIM#610374, Hyperinsulinemic hypoglycemia, familial, 1 MIM#256450, Hypoglycemia of infancy, leucine-sensitive MIM#240800; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11384 C1R Ain Roesley Gene: c1r has been classified as Green List (High Evidence).
Mendeliome v0.11382 ITCH Zornitza Stark Gene: itch has been classified as Green List (High Evidence).
Mendeliome v0.11379 C1QTNF5 Ain Roesley Gene: c1qtnf5 has been classified as Green List (High Evidence).
Mendeliome v0.11377 ITGA7 Zornitza Stark Gene: itga7 has been classified as Green List (High Evidence).
Mendeliome v0.11373 C1QC Ain Roesley Gene: c1qc has been classified as Green List (High Evidence).
Mendeliome v0.11372 ITPA Zornitza Stark Gene: itpa has been classified as Green List (High Evidence).
Mendeliome v0.11372 ITPA Zornitza Stark Phenotypes for gene: ITPA were changed from to Inosine triphosphatase deficiency MIM#613850; Developmental and epileptic encephalopathy 35 MIM#616647
Mendeliome v0.11369 IVD Zornitza Stark Gene: ivd has been classified as Green List (High Evidence).
Mendeliome v0.11365 C1QB Ain Roesley Gene: c1qb has been classified as Green List (High Evidence).
Mendeliome v0.11365 IYD Zornitza Stark Gene: iyd has been classified as Green List (High Evidence).
Mendeliome v0.11365 IYD Zornitza Stark Phenotypes for gene: IYD were changed from to Thyroid dyshormonogenesis 4, MIM# 274800
Mendeliome v0.11364 C12orf57 Ain Roesley Gene: c12orf57 has been classified as Green List (High Evidence).
Mendeliome v0.11364 C12orf4 Ain Roesley Gene: c12orf4 has been classified as Green List (High Evidence).
Mendeliome v0.11362 C1GALT1C1 Ain Roesley Gene: c1galt1c1 has been classified as Green List (High Evidence).
Mendeliome v0.11362 IYD Zornitza Stark changed review comment from: Four unrelated families reported.; to: Four unrelated families reported in 2008, limited reports since.
Mendeliome v0.11362 IYD Zornitza Stark reviewed gene: IYD: Rating: GREEN; Mode of pathogenicity: None; Publications: 18434651, 18434651; Phenotypes: Thyroid dyshormonogenesis 4, MIM# 274800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11358 C12orf4 Ain Roesley Phenotypes for gene: C12orf4 were changed from to Intellectual developmental disorder, autosomal recessive 66 MIM#618221
Mendeliome v0.11354 C12orf4 Ain Roesley reviewed gene: C12orf4: Rating: GREEN; Mode of pathogenicity: None; Publications: 34967075, 31334606, 27311568, 25558065, 28097321; Phenotypes: Intellectual developmental disorder, autosomal recessive 66 MIM#618221; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.11354 IARS2 Zornitza Stark Gene: iars2 has been classified as Green List (High Evidence).
Mendeliome v0.11354 IARS2 Zornitza Stark Phenotypes for gene: IARS2 were changed from to Cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia, MIM# 616007
Mendeliome v0.11351 IARS2 Zornitza Stark reviewed gene: IARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 28328135, 30419932, 25130867, 30041933; Phenotypes: Cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia, MIM# 616007; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11351 KAAG1 Zornitza Stark Gene: kaag1 has been classified as Red List (Low Evidence).
Mendeliome v0.11351 KAAG1 Zornitza Stark Classified gene: KAAG1 as Red List (low evidence)
Mendeliome v0.11351 KAAG1 Zornitza Stark Gene: kaag1 has been classified as Red List (Low Evidence).
Mendeliome v0.11350 KATNAL2 Zornitza Stark Gene: katnal2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11347 KATNAL2 Zornitza Stark Classified gene: KATNAL2 as Amber List (moderate evidence)
Mendeliome v0.11347 KATNAL2 Zornitza Stark Gene: katnal2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11346 KCNA1 Zornitza Stark Gene: kcna1 has been classified as Green List (High Evidence).
Mendeliome v0.11342 KCNA5 Zornitza Stark Gene: kcna5 has been classified as Green List (High Evidence).
Mendeliome v0.11339 KCND3 Zornitza Stark Gene: kcnd3 has been classified as Green List (High Evidence).
Mendeliome v0.11335 KCNE5 Zornitza Stark Gene: kcne5 has been classified as Red List (Low Evidence).
Mendeliome v0.11332 KCNE5 Zornitza Stark Classified gene: KCNE5 as Red List (low evidence)
Mendeliome v0.11332 KCNE5 Zornitza Stark Gene: kcne5 has been classified as Red List (Low Evidence).
Mendeliome v0.11331 KCNJ10 Zornitza Stark Gene: kcnj10 has been classified as Green List (High Evidence).
Mendeliome v0.11328 KCNK18 Zornitza Stark Gene: kcnk18 has been classified as Green List (High Evidence).
Mendeliome v0.11325 KCNK3 Zornitza Stark Gene: kcnk3 has been classified as Green List (High Evidence).
Mendeliome v0.11324 KCNK3 Zornitza Stark Phenotypes for gene: KCNK3 were changed from Pulmonary hypertension, primary, 4 MIM#615344 to Pulmonary hypertension, primary, 4 MIM#615344; Neurodevelopmental disorder, MONDO:0700092, KCNK3-related
Mendeliome v0.11323 KCNMA1 Zornitza Stark Gene: kcnma1 has been classified as Green List (High Evidence).
Mendeliome v0.11323 KCNMA1 Zornitza Stark Phenotypes for gene: KCNMA1 were changed from to Paroxysmal nonkinesigenic dyskinesia, 3, with or without generalized epilepsy, MIM# 609446; Cerebellar atrophy, developmental delay, and seizures, MIM# 617643; Liang-Wang syndrome, MIM# 618729
Mendeliome v0.11320 KCNMA1 Zornitza Stark reviewed gene: KCNMA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15937479, 26195193, 27567911, 29545233, 31427379, 31152168; Phenotypes: Paroxysmal nonkinesigenic dyskinesia, 3, with or without generalized epilepsy, MIM# 609446, Cerebellar atrophy, developmental delay, and seizures, MIM# 617643, Liang-Wang syndrome, MIM# 618729; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11320 NAT8L Zornitza Stark Gene: nat8l has been classified as Red List (Low Evidence).
Mendeliome v0.11320 KCNMB1 Zornitza Stark Gene: kcnmb1 has been classified as Red List (Low Evidence).
Mendeliome v0.11320 KCNMB1 Zornitza Stark Phenotypes for gene: KCNMB1 were changed from to {Hypertension, diastolic, resistance to} 608622
Mendeliome v0.11319 KCNMB1 Zornitza Stark Classified gene: KCNMB1 as Red List (low evidence)
Mendeliome v0.11319 KCNMB1 Zornitza Stark Gene: kcnmb1 has been classified as Red List (Low Evidence).
Mendeliome v0.11318 KCNMB1 Zornitza Stark reviewed gene: KCNMB1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Hypertension, diastolic, resistance to} 608622; Mode of inheritance: None
Mendeliome v0.11318 ECHS1 Zornitza Stark Gene: echs1 has been classified as Green List (High Evidence).
Mendeliome v0.11315 NAT8L Zornitza Stark Classified gene: NAT8L as Red List (low evidence)
Mendeliome v0.11315 NAT8L Zornitza Stark Gene: nat8l has been classified as Red List (Low Evidence).
Mendeliome v0.11314 NAT2 Zornitza Stark Gene: nat2 has been classified as Red List (Low Evidence).
Mendeliome v0.11311 NAT2 Zornitza Stark Classified gene: NAT2 as Red List (low evidence)
Mendeliome v0.11311 NAT2 Zornitza Stark Gene: nat2 has been classified as Red List (Low Evidence).
Mendeliome v0.11310 EDA Bryony Thompson Gene: eda has been classified as Green List (High Evidence).
Mendeliome v0.11310 EDA Bryony Thompson Phenotypes for gene: EDA were changed from to Ectodermal dysplasia 1, hypohidrotic, X-linked MIM#305100; Tooth agenesis, selective, X-linked 1 MIM#313500
Mendeliome v0.11307 EDA Bryony Thompson reviewed gene: EDA: Rating: GREEN; Mode of pathogenicity: None; Publications: 27144394, 8696334, 9507389, 9683615, 18657636; Phenotypes: Ectodermal dysplasia 1, hypohidrotic, X-linked MIM#305100, Tooth agenesis, selective, X-linked 1 MIM#313500; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.11303 ARHGAP35 Ain Roesley Classified gene: ARHGAP35 as Green List (high evidence)
Mendeliome v0.11303 ARHGAP35 Ain Roesley Gene: arhgap35 has been classified as Green List (High Evidence).
Mendeliome v0.11302 ARHGAP35 Ain Roesley Classified gene: ARHGAP35 as Green List (high evidence)
Mendeliome v0.11302 ARHGAP35 Ain Roesley Gene: arhgap35 has been classified as Green List (High Evidence).
Mendeliome v0.11301 KCNV2 Zornitza Stark Gene: kcnv2 has been classified as Green List (High Evidence).
Mendeliome v0.11298 KHDC3L Zornitza Stark Gene: khdc3l has been classified as Green List (High Evidence).
Mendeliome v0.11295 KIAA1109 Zornitza Stark changed review comment from: ALKKUCS is an autosomal recessive severe neurodevelopmental disorder characterized by arthrogryposis, brain abnormalities associated with cerebral parenchymal underdevelopment, and global developmental delay. Most affected individuals die in utero or soon after birth. Additional abnormalities may include hypotonia, dysmorphic facial features, and involvement of other organ systems, such as cardiac or renal. The few patients who survive have variable intellectual disability and may have seizures.; to: ALKKUCS is an autosomal recessive severe neurodevelopmental disorder characterized by arthrogryposis, brain abnormalities associated with cerebral parenchymal underdevelopment, and global developmental delay. Most affected individuals die in utero or soon after birth. Additional abnormalities may include hypotonia, dysmorphic facial features, and involvement of other organ systems, such as cardiac or renal. The few patients who survive have variable intellectual disability and may have seizures.

More than 10 families reported.
Mendeliome v0.11295 KIAA1109 Zornitza Stark Gene: kiaa1109 has been classified as Green List (High Evidence).
Mendeliome v0.11292 KIF1A Zornitza Stark Gene: kif1a has been classified as Green List (High Evidence).
Mendeliome v0.11289 KIF5A Zornitza Stark Gene: kif5a has been classified as Green List (High Evidence).
Mendeliome v0.11286 KIF5A Zornitza Stark edited their review of gene: KIF5A: Added comment: Neonatal intractable myoclonus is a severe neurologic disorder characterized by the onset of intractable myoclonic seizures soon after birth. Affected infants have intermittent apnea, abnormal eye movements, pallor of the optic nerve, and lack of developmental progress. Brain imaging shows a progressive leukoencephalopathy. At least 3 unrelated individuals with de novo LoF variants.

SPG10/CMT: variants are generally in the motor domain.; Changed publications: 30057544, 29892902, 28902413, 26403765, 25695920, 25008398, 27463701, 27414745; Changed phenotypes: Neuropathy, Spastic paraplegia 10, autosomal dominant, MIM# 604187, Myoclonus, intractable, neonatal, MIM# 617235
Mendeliome v0.11286 KIT Zornitza Stark Gene: kit has been classified as Green List (High Evidence).
Mendeliome v0.11286 KIT Zornitza Stark Phenotypes for gene: KIT were changed from to Piebaldism, MIM# 172800; Gastrointestinal stromal tumor, familial, MIM# 606764; Mastocytosis, cutaneous, MIM# 154800
Mendeliome v0.11284 KIT Zornitza Stark reviewed gene: KIT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Piebaldism, MIM# 172800, Gastrointestinal stromal tumor, familial, MIM# 606764, Mastocytosis, cutaneous, MIM# 154800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11284 KIZ Zornitza Stark Gene: kiz has been classified as Green List (High Evidence).
Mendeliome v0.11281 KLF11 Zornitza Stark Gene: klf11 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11278 KLF11 Zornitza Stark Classified gene: KLF11 as Amber List (moderate evidence)
Mendeliome v0.11278 KLF11 Zornitza Stark Gene: klf11 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11277 KLF6 Zornitza Stark Gene: klf6 has been classified as Red List (Low Evidence).
Mendeliome v0.11277 KLF6 Zornitza Stark Classified gene: KLF6 as Red List (low evidence)
Mendeliome v0.11277 KLF6 Zornitza Stark Gene: klf6 has been classified as Red List (Low Evidence).
Mendeliome v0.11276 KLHDC8B Zornitza Stark Gene: klhdc8b has been classified as Red List (Low Evidence).
Mendeliome v0.11275 KLHDC8B Zornitza Stark Classified gene: KLHDC8B as Red List (low evidence)
Mendeliome v0.11275 KLHDC8B Zornitza Stark Gene: klhdc8b has been classified as Red List (Low Evidence).
Mendeliome v0.11274 KLHL10 Zornitza Stark Gene: klhl10 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11271 KLHL10 Zornitza Stark Classified gene: KLHL10 as Amber List (moderate evidence)
Mendeliome v0.11271 KLHL10 Zornitza Stark Gene: klhl10 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11269 TLN1 Bryony Thompson Gene: tln1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11269 TLN1 Bryony Thompson Classified gene: TLN1 as Amber List (moderate evidence)
Mendeliome v0.11269 TLN1 Bryony Thompson Gene: tln1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11267 KLK1 Zornitza Stark Gene: klk1 has been classified as Red List (Low Evidence).
Mendeliome v0.11266 KLK1 Zornitza Stark Classified gene: KLK1 as Red List (low evidence)
Mendeliome v0.11266 KLK1 Zornitza Stark Gene: klk1 has been classified as Red List (Low Evidence).
Mendeliome v0.11265 KLKB1 Zornitza Stark Gene: klkb1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11262 KLKB1 Zornitza Stark Classified gene: KLKB1 as Amber List (moderate evidence)
Mendeliome v0.11262 KLKB1 Zornitza Stark Gene: klkb1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11261 KRT1 Zornitza Stark Gene: krt1 has been classified as Green List (High Evidence).
Mendeliome v0.11261 KRT1 Zornitza Stark Phenotypes for gene: KRT1 were changed from to Epidermolytic hyperkeratosis, MIM#113800; Ichthyosis, cyclic, with epidermolytic hyperkeratosis, MIM# 607602; Ichthyosis histrix, Curth-Macklin type, MIM# 146590; Palmoplantar keratoderma, epidermolytic, MIM# 144200; Palmoplantar keratoderma, nonepidermolytic, MIM# 600962
Mendeliome v0.11258 KRT1 Zornitza Stark reviewed gene: KRT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 7511022, 21271994, 11286630; Phenotypes: Epidermolytic hyperkeratosis, MIM#113800, Ichthyosis, cyclic, with epidermolytic hyperkeratosis, MIM# 607602, Ichthyosis histrix, Curth-Macklin type, MIM# 146590, Palmoplantar keratoderma, epidermolytic, MIM# 144200, Palmoplantar keratoderma, nonepidermolytic, MIM# 600962; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.11258 KRT12 Zornitza Stark Gene: krt12 has been classified as Green List (High Evidence).
Mendeliome v0.11255 TSR1 Bryony Thompson Gene: tsr1 has been classified as Red List (Low Evidence).
Mendeliome v0.11255 TSR1 Bryony Thompson gene: TSR1 was added
gene: TSR1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TSR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TSR1 were set to 31296288; 31296287
Phenotypes for gene: TSR1 were set to idiopathic spontaneous coronary artery dissection MONDO:0007385
Review for gene: TSR1 was set to RED
Added comment: A single case-control study with 85 SCAD cases and 296 non-SCAD controls from the Chinese Han population that underwent exome sequencing. TSR1 was the top hit in association analyses (p < 5.41 × 10-5 in both the optimal sequence kernel association and mixed effects score tests), with 5 variants identified in 8 SCAD cases.
Sources: Literature
Mendeliome v0.11254 TMEM151A Bryony Thompson Gene: tmem151a has been classified as Green List (High Evidence).
Mendeliome v0.11254 TMEM151A Bryony Thompson Classified gene: TMEM151A as Green List (high evidence)
Mendeliome v0.11254 TMEM151A Bryony Thompson Gene: tmem151a has been classified as Green List (High Evidence).
Mendeliome v0.11253 TMEM151A Bryony Thompson gene: TMEM151A was added
gene: TMEM151A was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TMEM151A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TMEM151A were set to 34820915; 34518509
Phenotypes for gene: TMEM151A were set to episodic kinesigenic dyskinesia MONDO:0044202
Review for gene: TMEM151A was set to GREEN
Added comment: PMID: 34820915 - 24 heterozygous TMEM151A variants detected in 29 PRRT2-negative patients from 25 families
PMID: 34518509 - TMEM151A variants identified in 3 AD families and 8 isolated PKD patients with incomplete penetrance identified in 3 of the isolated cases. Also, supporting mouse model and in vitro functional assays suggesting loss of function as the mechanism of disease.
Sources: Literature
Mendeliome v0.11252 KRT13 Zornitza Stark Gene: krt13 has been classified as Green List (High Evidence).
Mendeliome v0.11249 KRT16 Zornitza Stark Gene: krt16 has been classified as Green List (High Evidence).
Mendeliome v0.11246 KRT18 Zornitza Stark Gene: krt18 has been classified as Red List (Low Evidence).
Mendeliome v0.11246 KRT18 Zornitza Stark Phenotypes for gene: KRT18 were changed from to Cirrhosis, cryptogenic , MIM#215600
Mendeliome v0.11244 KRT18 Zornitza Stark Classified gene: KRT18 as Red List (low evidence)
Mendeliome v0.11244 KRT18 Zornitza Stark Gene: krt18 has been classified as Red List (Low Evidence).
Mendeliome v0.11243 KRT18 Zornitza Stark reviewed gene: KRT18: Rating: RED; Mode of pathogenicity: None; Publications: 9011570, 27689336, 20538000; Phenotypes: Cirrhosis, cryptogenic , MIM#215600; Mode of inheritance: None
Mendeliome v0.11243 KRT25 Zornitza Stark Gene: krt25 has been classified as Green List (High Evidence).
Mendeliome v0.11243 KRT25 Zornitza Stark Phenotypes for gene: KRT25 were changed from to Woolly hair, autosomal recessive 3 MIM#616760
Mendeliome v0.11240 KRT4 Zornitza Stark Gene: krt4 has been classified as Green List (High Evidence).
Mendeliome v0.11237 KRT74 Zornitza Stark Gene: krt74 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11237 KRT74 Zornitza Stark Phenotypes for gene: KRT74 were changed from to Ectodermal dysplasia 7, hair/nail type MIM#614929; Hypotrichosis 3 , MIM# 613981; Woolly hair, autosomal dominant, MIM# 194300
Mendeliome v0.11234 KRT74 Zornitza Stark Classified gene: KRT74 as Amber List (moderate evidence)
Mendeliome v0.11234 KRT74 Zornitza Stark Gene: krt74 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11233 KRT74 Zornitza Stark reviewed gene: KRT74: Rating: AMBER; Mode of pathogenicity: None; Publications: 24714551, 21188418, 20346438, 21188418; Phenotypes: Ectodermal dysplasia 7, hair/nail type MIM#614929, Hypotrichosis 3 , MIM# 613981, Woolly hair, autosomal dominant, MIM# 194300; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11233 KRT75 Zornitza Stark Gene: krt75 has been classified as Red List (Low Evidence).
Mendeliome v0.11232 KRT75 Zornitza Stark Classified gene: KRT75 as Red List (low evidence)
Mendeliome v0.11232 KRT75 Zornitza Stark Gene: krt75 has been classified as Red List (Low Evidence).
Mendeliome v0.11231 KRT81 Zornitza Stark Gene: krt81 has been classified as Green List (High Evidence).
Mendeliome v0.11228 NARS2 Zornitza Stark Gene: nars2 has been classified as Green List (High Evidence).
Mendeliome v0.11228 NARS2 Zornitza Stark Phenotypes for gene: NARS2 were changed from to Combined oxidative phosphorylation deficiency 24 - MIM#616239; Deafness, autosomal recessive 94 - MIM#618434
Mendeliome v0.11225 PNPLA3 Zornitza Stark Gene: pnpla3 has been classified as Red List (Low Evidence).
Mendeliome v0.11222 PNPLA3 Zornitza Stark Classified gene: PNPLA3 as Red List (low evidence)
Mendeliome v0.11222 PNPLA3 Zornitza Stark Gene: pnpla3 has been classified as Red List (Low Evidence).
Mendeliome v0.11221 NANS Zornitza Stark Gene: nans has been classified as Green List (High Evidence).
Mendeliome v0.11221 NANS Zornitza Stark Phenotypes for gene: NANS were changed from to Spondyloepimetaphyseal dysplasia, Camera-Genevieve type - MIM#610442
Mendeliome v0.11218 S1PR2 Zornitza Stark Gene: s1pr2 has been classified as Green List (High Evidence).
Mendeliome v0.11218 S1PR2 Zornitza Stark Phenotypes for gene: S1PR2 were changed from to Deafness, autosomal recessive 68, MIM# 610419
Mendeliome v0.11215 S1PR2 Zornitza Stark reviewed gene: S1PR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26805784, 29776397, 27383011; Phenotypes: Deafness, autosomal recessive 68, MIM# 610419; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11215 NALCN Zornitza Stark Gene: nalcn has been classified as Green List (High Evidence).
Mendeliome v0.11212 NAGS Zornitza Stark Gene: nags has been classified as Green List (High Evidence).
Mendeliome v0.11209 NACC1 Zornitza Stark Gene: nacc1 has been classified as Green List (High Evidence).
Mendeliome v0.11206 NAA15 Zornitza Stark Gene: naa15 has been classified as Green List (High Evidence).
Mendeliome v0.11203 NARS2 Krithika Murali reviewed gene: NARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25385316, 25807530, 30327238, 28077841; Phenotypes: Combined oxidative phosphorylation deficiency 24 - MIM#616239, ?Deafness, autosomal recessive 94 - MIM#618434; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11203 KRT83 Zornitza Stark Gene: krt83 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11203 KRT83 Zornitza Stark Phenotypes for gene: KRT83 were changed from to Erythrokeratodermia variabilis et progressiva 5, MIM# 617756; Monilethrix , MIM#158000
Mendeliome v0.11200 KRT83 Zornitza Stark Classified gene: KRT83 as Amber List (moderate evidence)
Mendeliome v0.11200 KRT83 Zornitza Stark Gene: krt83 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11199 KRT83 Zornitza Stark reviewed gene: KRT83: Rating: AMBER; Mode of pathogenicity: None; Publications: 27965375, 15744029, 25557232; Phenotypes: Erythrokeratodermia variabilis et progressiva 5, MIM# 617756, Monilethrix , MIM#158000; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11199 KRT10 Zornitza Stark Gene: krt10 has been classified as Green List (High Evidence).
Mendeliome v0.11199 KRT10 Zornitza Stark Phenotypes for gene: KRT10 were changed from to Epidermolytic hyperkeratosis, MIM#113800; Ichthyosis with confetti, MIM#609165; Ichthyosis, cyclic, with epidermolytic hyperkeratosis, MIM#607602
Mendeliome v0.11194 ERLEC1 Bryony Thompson Gene: erlec1 has been classified as Green List (High Evidence).
Mendeliome v0.11194 ERLEC1 Bryony Thompson Phenotypes for gene: ERLEC1 were changed from Class III malocclusion to autosomal dominant prognathism MONDO:0008312
Mendeliome v0.11193 ERBB4 Bryony Thompson Phenotypes for gene: ERBB4 were changed from Amyotrophic lateral sclerosis 19, MIM# MIM#615515; Intellectual disability to Amyotrophic lateral sclerosis 19, MIM# MIM#615515; Intellectual disability MONDO:0001071
Mendeliome v0.11192 NANS Krithika Murali reviewed gene: NANS: Rating: GREEN; Mode of pathogenicity: None; Publications: 8152878, 15726110, 8723082, 27213289, 7551156; Phenotypes: Spondyloepimetaphyseal dysplasia, Camera-Genevieve type - MIM#610442; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11190 IRX5 Zornitza Stark Classified gene: IRX5 as Green List (high evidence)
Mendeliome v0.11190 IRX5 Zornitza Stark Gene: irx5 has been classified as Green List (High Evidence).
Mendeliome v0.11189 IRX5 Zornitza Stark edited their review of gene: IRX5: Added comment: Third family with Hamamy syndrome and homozygous missense variant reported, p.Arg168His. Two cousins, >4 meioses, good segregation data.

4th family as part of large heterogenous cohort of consanguineous families also reported with homozygous frameshift (last exon), but limited phenotypic data.; Changed rating: GREEN; Changed publications: 22581230, 27453922, 34899143
Mendeliome v0.11189 EARS2 Bryony Thompson Gene: ears2 has been classified as Green List (High Evidence).
Mendeliome v0.11185 KRT8 Zornitza Stark Gene: krt8 has been classified as Red List (Low Evidence).
Mendeliome v0.11185 KRT8 Zornitza Stark Phenotypes for gene: KRT8 were changed from to Cirrhosis, cryptogenic, MIM# 215600
Mendeliome v0.11182 KRT8 Zornitza Stark Classified gene: KRT8 as Red List (low evidence)
Mendeliome v0.11182 KRT8 Zornitza Stark Gene: krt8 has been classified as Red List (Low Evidence).
Mendeliome v0.11181 KRT85 Zornitza Stark Gene: krt85 has been classified as Green List (High Evidence).
Mendeliome v0.11181 KRT85 Zornitza Stark Phenotypes for gene: KRT85 were changed from to Ectodermal dysplasia 4, hair/nail type MIM#602032
Mendeliome v0.11178 KRT86 Zornitza Stark Gene: krt86 has been classified as Green List (High Evidence).
Mendeliome v0.11175 KRT9 Zornitza Stark Gene: krt9 has been classified as Green List (High Evidence).
Mendeliome v0.11172 KY Zornitza Stark Gene: ky has been classified as Green List (High Evidence).
Mendeliome v0.11169 KYNU Zornitza Stark Gene: kynu has been classified as Green List (High Evidence).
Mendeliome v0.11169 KYNU Zornitza Stark Phenotypes for gene: KYNU were changed from to Hydroxykynureninuria MIM#236800; Vertebral, cardiac, renal, and limb defects syndrome 2 MIM#617661; Disorders of histidine, tryptophan or lysine metabolism
Mendeliome v0.11166 JAG1 Zornitza Stark Gene: jag1 has been classified as Green List (High Evidence).
Mendeliome v0.11163 JAG1 Zornitza Stark changed review comment from: Two unrelated families reported with CMT type 2. Affected individuals in both families exhibited severe vocal fold paresis, a rare feature of peripheral nerve disease that can be life-threatening. Studies of mutant protein posttranslational modification and localization indicated that the mutations (p.Ser577Arg, p.Ser650Pro) impair protein glycosylation and reduce JAG1 cell surface expression. Mice harboring heterozygous CMT2-associated mutations exhibited mild peripheral neuropathy, and homozygous expression resulted in embryonic lethality by midgestation. Pre-existing rat model.
Sources: Literature; to: Association with Alagille is very well established.

Two unrelated families reported with CMT type 2. Affected individuals in both families exhibited severe vocal fold paresis, a rare feature of peripheral nerve disease that can be life-threatening. Studies of mutant protein posttranslational modification and localization indicated that the mutations (p.Ser577Arg, p.Ser650Pro) impair protein glycosylation and reduce JAG1 cell surface expression. Mice harboring heterozygous CMT2-associated mutations exhibited mild peripheral neuropathy, and homozygous expression resulted in embryonic lethality by midgestation. Pre-existing rat model.
Sources: Literature
Mendeliome v0.11163 JUP Zornitza Stark Gene: jup has been classified as Green List (High Evidence).
Mendeliome v0.11163 JUP Zornitza Stark Phenotypes for gene: JUP were changed from to Arrhythmogenic right ventricular dysplasia 12, MIM# 611528; Naxos disease, MIM# 601214
Mendeliome v0.11160 JUP Zornitza Stark edited their review of gene: JUP: Changed phenotypes: Arrhythmogenic right ventricular dysplasia 12, MIM# 611528, Naxos disease, MIM# 601214
Mendeliome v0.11160 JUP Zornitza Stark reviewed gene: JUP: Rating: GREEN; Mode of pathogenicity: None; Publications: 2945574, 21668431, 2945574, 9610536, 18937352, 10902626, 15851108, 27170944, 11691526, 16893920, 29802319, 31275992, 25820315, 25820315, 25765472, 25705887, 25087486, 21668431, 20130592, 17924338, 20031617, 10902626, 20130592, 21320868, 32212272; Phenotypes: Arrhythmogenic right ventricular dysplasia 12, MIM# 611528; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11160 JPT1 Zornitza Stark Gene: jpt1 has been classified as Red List (Low Evidence).
Mendeliome v0.11160 JPT1 Zornitza Stark Classified gene: JPT1 as Red List (low evidence)
Mendeliome v0.11160 JPT1 Zornitza Stark Gene: jpt1 has been classified as Red List (Low Evidence).
Mendeliome v0.11159 JAK2 Zornitza Stark Gene: jak2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11156 JAK2 Zornitza Stark Classified gene: JAK2 as Amber List (moderate evidence)
Mendeliome v0.11156 JAK2 Zornitza Stark Gene: jak2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11155 ZNF644 Zornitza Stark Gene: znf644 has been classified as Green List (High Evidence).
Mendeliome v0.11152 ZNF513 Zornitza Stark Gene: znf513 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11149 ZNF513 Zornitza Stark Classified gene: ZNF513 as Amber List (moderate evidence)
Mendeliome v0.11149 ZNF513 Zornitza Stark Gene: znf513 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11148 ZNF408 Zornitza Stark Gene: znf408 has been classified as Green List (High Evidence).
Mendeliome v0.11145 ZNF335 Zornitza Stark Gene: znf335 has been classified as Green List (High Evidence).
Mendeliome v0.11145 ZNF335 Zornitza Stark Phenotypes for gene: ZNF335 were changed from to Microcephaly 10, primary, autosomal recessive (MIM#615095)
Mendeliome v0.11142 ZNF335 Zornitza Stark reviewed gene: ZNF335: Rating: GREEN; Mode of pathogenicity: None; Publications: 23178126, 27540107, 29652087; Phenotypes: Microcephaly 10, primary, autosomal recessive (MIM#615095); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11142 ZMYND11 Zornitza Stark Gene: zmynd11 has been classified as Green List (High Evidence).
Mendeliome v0.11139 ZFPM2 Zornitza Stark Gene: zfpm2 has been classified as Green List (High Evidence).
Mendeliome v0.11135 RPA1 Zornitza Stark Phenotypes for gene: RPA1 were changed from Bone marrow failure; T- and B-cell lymphopaenia; pulmonary fibrosis; skin manifestations; short telomeres to Pulmonary fibrosis and/or bone marrow failure, telomere-related, 6, MIM# 619767; Bone marrow failure; T- and B-cell lymphopaenia; pulmonary fibrosis; skin manifestations; short telomeres
Mendeliome v0.11134 RPA1 Zornitza Stark edited their review of gene: RPA1: Changed phenotypes: Pulmonary fibrosis and/or bone marrow failure, telomere-related, 6, MIM# 619767, Bone marrow failure, T- and B-cell lymphopaenia, pulmonary fibrosis, skin manifestations, short telomeres
Mendeliome v0.11134 OPCML Zornitza Stark Gene: opcml has been classified as Red List (Low Evidence).
Mendeliome v0.11133 OPCML Zornitza Stark Classified gene: OPCML as Red List (low evidence)
Mendeliome v0.11133 OPCML Zornitza Stark Gene: opcml has been classified as Red List (Low Evidence).
Mendeliome v0.11132 NFE2L1 Bryony Thompson Gene: nfe2l1 has been classified as Red List (Low Evidence).
Mendeliome v0.11132 NFE2L1 Bryony Thompson gene: NFE2L1 was added
gene: NFE2L1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NFE2L1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NFE2L1 were set to 35112409
Phenotypes for gene: NFE2L1 were set to Syndromic disease, MONDO:0002254
Review for gene: NFE2L1 was set to RED
Added comment: A single patient with developmental delay, hypotonia, hypospadias, bifid scrotum, and failure to thrive, with a heterozygous nonsense variant in the last exon. In vitro functional assays suggest a dominant-negative effect.
Sources: Literature
Mendeliome v0.11131 ZFP57 Zornitza Stark Gene: zfp57 has been classified as Green List (High Evidence).
Mendeliome v0.11131 ZFP57 Zornitza Stark Phenotypes for gene: ZFP57 were changed from to IUGR; Diabetes mellitus, transient neonatal 1 OMIM:601410; Multi Locus Imprinting Disturbance; diabetes mellitus, transient neonatal, 1, MONDO:0011073
Mendeliome v0.11128 ZFP57 Zornitza Stark reviewed gene: ZFP57: Rating: GREEN; Mode of pathogenicity: None; Publications: 18622393, 27075368, 23150280, 30315371, 31399135, 33053156; Phenotypes: IUGR, Diabetes mellitus, transient neonatal 1 OMIM:601410, Multi Locus Imprinting Disturbance, diabetes mellitus, transient neonatal, 1MONDO:0011073; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11128 XYLT2 Zornitza Stark Gene: xylt2 has been classified as Green List (High Evidence).
Mendeliome v0.11125 XRCC3 Zornitza Stark Gene: xrcc3 has been classified as Red List (Low Evidence).
Mendeliome v0.11125 XRCC3 Zornitza Stark Classified gene: XRCC3 as Red List (low evidence)
Mendeliome v0.11125 XRCC3 Zornitza Stark Gene: xrcc3 has been classified as Red List (Low Evidence).
Mendeliome v0.11124 XIAP Zornitza Stark Gene: xiap has been classified as Green List (High Evidence).
Mendeliome v0.11121 XG Zornitza Stark Gene: xg has been classified as Red List (Low Evidence).
Mendeliome v0.11121 XG Zornitza Stark Classified gene: XG as Red List (low evidence)
Mendeliome v0.11121 XG Zornitza Stark Gene: xg has been classified as Red List (Low Evidence).
Mendeliome v0.11115 OPDM4 Bryony Thompson Str: opdm4 has been classified as Green List (High Evidence).
Mendeliome v0.11115 OPDM4 Bryony Thompson Classified STR: OPDM4 as Green List (high evidence)
Mendeliome v0.11115 OPDM4 Bryony Thompson Str: opdm4 has been classified as Green List (High Evidence).
Mendeliome v0.11114 OPDM4 Bryony Thompson STR: OPDM4 was added
STR: OPDM4 was added to Mendeliome. Sources: Literature
Mode of inheritance for STR: OPDM4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: OPDM4 were set to 35148830
Phenotypes for STR: OPDM4 were set to Oculopharyngodistal myopathy MONDO:0025193
Review for STR: OPDM4 was set to GREEN
STR: OPDM4 was marked as clinically relevant
Added comment: 5'UTR repeat upstream of RILPL1. Analyses suggest that toxic RNA gain-of-function is the mechanism of disease for the repeat expansion. Distribution of CGG repeat units in RILPL1 ranged from 9 to 16 among 200 normal controls. The size of the CGG repeat ranged from 139 to 197 (169.91 ± 21.82) repeats in 11 unrelated individuals with OPDM. Segregation evidence from 1 family, with 2 affected individuals with the repeat expansion and 1 individual with essential tremor but not OPDM and 86 repeats (intermediate).
Sources: Literature
Mendeliome v0.11113 RECQL Alison Yeung Gene: recql has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11113 RECQL Alison Yeung Classified gene: RECQL as Amber List (moderate evidence)
Mendeliome v0.11113 RECQL Alison Yeung Gene: recql has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11112 HIST1H4E Alison Yeung Gene: hist1h4e has been classified as Green List (High Evidence).
Mendeliome v0.11112 HIST1H4E Alison Yeung Classified gene: HIST1H4E as Green List (high evidence)
Mendeliome v0.11112 HIST1H4E Alison Yeung Gene: hist1h4e has been classified as Green List (High Evidence).
Mendeliome v0.11111 HIST1H4D Zornitza Stark Gene: hist1h4d has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11111 HIST1H4D Zornitza Stark Classified gene: HIST1H4D as Amber List (moderate evidence)
Mendeliome v0.11111 HIST1H4D Zornitza Stark Gene: hist1h4d has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11110 RECQL Dean Phelan gene: RECQL was added
gene: RECQL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RECQL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RECQL were set to PMID: 35025765
Phenotypes for gene: RECQL were set to Photosensitivity; facial dysmorphism; xeropthalmia; skeletal abnormalities
Review for gene: RECQL was set to AMBER
Added comment: PMID: 35025765
- Homozygous missense variants identified in two seemingly unrelated families with a genome instability disorder. Both families had the same missense variant. Phenotype was progeroid facial features, skin photosensitivity, xeroderma, and slender elongated thumbs.
Sources: Literature
Mendeliome v0.11110 ZBTB11 Zornitza Stark Classified gene: ZBTB11 as Green List (high evidence)
Mendeliome v0.11110 ZBTB11 Zornitza Stark Gene: zbtb11 has been classified as Green List (High Evidence).
Mendeliome v0.11107 CPSF3 Alison Yeung Gene: cpsf3 has been classified as Green List (High Evidence).
Mendeliome v0.11107 AL117258.1 Zornitza Stark Gene: al117258.1 has been classified as Green List (High Evidence).
Mendeliome v0.11107 AL117258.1 Melanie Marty changed review comment from: Gene also known as CIROP

Homozygous or compound heterozygous CIROP variants identified in 12 families with congenital heart defects associated with heterotaxy.

Functional tests performed on Xenopus and zebrafish embryos showed that CIROP was essential for left side symmetry and is expressed in ciliated left–right organisers.
Sources: Literature; to: Gene also known as CIROP and LMLN2

Homozygous or compound heterozygous CIROP variants identified in 12 families with congenital heart defects associated with heterotaxy.

Functional tests performed on Xenopus and zebrafish embryos showed that CIROP was essential for left side symmetry and is expressed in ciliated left–right organisers.
Sources: Literature
Mendeliome v0.11105 CPSF3 Alison Yeung Classified gene: CPSF3 as Green List (high evidence)
Mendeliome v0.11105 CPSF3 Alison Yeung Gene: cpsf3 has been classified as Green List (High Evidence).
Mendeliome v0.11104 AL117258.1 Zornitza Stark Classified gene: AL117258.1 as Green List (high evidence)
Mendeliome v0.11104 AL117258.1 Zornitza Stark Gene: al117258.1 has been classified as Green List (High Evidence).
Mendeliome v0.11103 HIST1H4F Zornitza Stark Gene: hist1h4f has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11103 HIST1H4D Paul De Fazio gene: HIST1H4D was added
gene: HIST1H4D was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HIST1H4D was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: HIST1H4D were set to 35202563
Phenotypes for gene: HIST1H4D were set to Neurodevelopmental disorder, HIST1H4D-related MONDO:0700092
Review for gene: HIST1H4D was set to AMBER
gene: HIST1H4D was marked as current diagnostic
Added comment: Single individual described with a de novo missense variant Arg41His (Arg40 in H4 nomenclature). Apart from language delay and moderate ID, phenotypes included facial dysmorphisms and cochlear abnormalities and arhinencephaly on MRI. Hearing was normal. Birth length, OFC, weight were all reduced (-2 to -2.5SD).
A zebrafish model has developmental defects.
Sources: Literature
Mendeliome v0.11101 HIST1H4F Zornitza Stark Classified gene: HIST1H4F as Amber List (moderate evidence)
Mendeliome v0.11101 HIST1H4F Zornitza Stark Gene: hist1h4f has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11099 CPSF3 Belinda Chong gene: CPSF3 was added
gene: CPSF3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CPSF3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CPSF3 were set to 35121750
Phenotypes for gene: CPSF3 were set to Intellectual disability syndrome
Review for gene: CPSF3 was set to GREEN
Added comment: study of a deficit of observed homozygous carriers of missense variants, versus an expected number in a set of 153,054 chip-genotyped Icelanders, to identify potentially pathogenic genotypes

Six homozygous carriers of missense variants in CPSF3 show severe intellectual disability, seizures, microcephaly, and abnormal muscle tone.

- Four identified through Icelandic geneology (p.Gly468Glu), three carrier couples total of four children who had died prematurely. Tested archival samples for two of these children, and confirm a homozygous genotype.
- Two of Mexican descent (p.Ile354Thr), first-degree cousins
Sources: Literature
Mendeliome v0.11099 ZBTB11 Chern Lim reviewed gene: ZBTB11: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:35104841; Phenotypes: Intellectual developmental disorder, autosomal recessive 69 (MIM#618383), AR; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.11099 NRCAM Alison Yeung Classified gene: NRCAM as Green List (high evidence)
Mendeliome v0.11099 NRCAM Alison Yeung Gene: nrcam has been classified as Green List (High Evidence).
Mendeliome v0.11098 CRLS1 Zornitza Stark Gene: crls1 has been classified as Green List (High Evidence).
Mendeliome v0.11098 CRLS1 Zornitza Stark Classified gene: CRLS1 as Green List (high evidence)
Mendeliome v0.11098 CRLS1 Zornitza Stark Gene: crls1 has been classified as Green List (High Evidence).
Mendeliome v0.11097 AL117258.1 Melanie Marty gene: AL117258.1 was added
gene: AL117258.1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AL117258.1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AL117258.1 were set to 34903892
Phenotypes for gene: AL117258.1 were set to Heterotaxy, congenital heart defects
Review for gene: AL117258.1 was set to GREEN
Added comment: Gene also known as CIROP

Homozygous or compound heterozygous CIROP variants identified in 12 families with congenital heart defects associated with heterotaxy.

Functional tests performed on Xenopus and zebrafish embryos showed that CIROP was essential for left side symmetry and is expressed in ciliated left–right organisers.
Sources: Literature
Mendeliome v0.11097 NAV2 Alison Yeung Added comment: Comment when marking as ready: Single reported individual. Functional studies and mouse model supportive evidence.
Mendeliome v0.11097 NAV2 Alison Yeung Gene: nav2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11097 HIST1H4F Elena Savva gene: HIST1H4F was added
gene: HIST1H4F was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HIST1H4F was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: HIST1H4F were set to PMID: 35202563
Phenotypes for gene: HIST1H4F were set to Neurodevelopmental disorders
Review for gene: HIST1H4F was set to AMBER
Added comment: PMID: 35202563 - single de novo missense in a patient with neurodevelopmental features of intellectual disability and motor and/or gross developmental delay.
- zebrafish studies show a significant increase in all of mild dev delay, necrosis, defective organogenesis and pre-gastrulation failure
Sources: Literature
Mendeliome v0.11097 NAV2 Alison Yeung Classified gene: NAV2 as Amber List (moderate evidence)
Mendeliome v0.11097 NAV2 Alison Yeung Gene: nav2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11096 HIST1H4I Zornitza Stark Gene: hist1h4i has been classified as Green List (High Evidence).
Mendeliome v0.11095 NRCAM Ee Ming Wong gene: NRCAM was added
gene: NRCAM was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NRCAM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NRCAM were set to PMID: 35108495
Phenotypes for gene: NRCAM were set to neurodevelopmental disorder, MONDO:0700092
Penetrance for gene: NRCAM were set to unknown
Review for gene: NRCAM was set to GREEN
gene: NRCAM was marked as current diagnostic
Added comment: -Ten individuals from 8 families with developmental delay/intellectual disability, hypotonia, peripheral neuropathy, and/or spasticity.
- Affected individuals are biallelic for missense and/or LoF variants which are mainly in the fibronectin type III (Fn-III) domain
- Zebrafish mutants lacking the third Fn-III domain displayed significantly altered swimming behavior compared to wild-type larvae (p < 0.03) and a trend toward increased amounts of alpha-tubulin fibers in the dorsal telencephalon, demonstrating an alteration in white matter tracts and projections
Sources: Literature
Mendeliome v0.11094 HIST1H4I Zornitza Stark Classified gene: HIST1H4I as Green List (high evidence)
Mendeliome v0.11094 HIST1H4I Zornitza Stark Gene: hist1h4i has been classified as Green List (High Evidence).
Mendeliome v0.11093 ZBTB7A Zornitza Stark Gene: zbtb7a has been classified as Green List (High Evidence).
Mendeliome v0.11093 ZBTB7A Zornitza Stark Classified gene: ZBTB7A as Green List (high evidence)
Mendeliome v0.11093 ZBTB7A Zornitza Stark Gene: zbtb7a has been classified as Green List (High Evidence).
Mendeliome v0.11092 CRLS1 Michelle Torres gene: CRLS1 was added
gene: CRLS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CRLS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRLS1 were set to 35147173
Phenotypes for gene: CRLS1 were set to Mitochondrial disease MONDO:0044970 CRLS1-related
Added comment: - Three families (4 individuals) with cardiolipin deficiency.
- Two families (one consanguineous with 2 affected siblings) with homozygous the p.(Ile109Asn) had infantile progressive encephalopathy, bull’s eye maculopathy, auditory neuropathy, diabetes insipidus, autonomic instability, cardiac defects and early death.
- The fourth individual cHet p.(Ala172Asp) and p.(Leu217Phe) presented with chronic encephalopathy with neurodevelopmental regression, congenital nystagmus with decreased vision, sensorineural hearing loss, failure to thrive and acquired microcephaly.
- Functional studies on patient cells showed increased levels of the substrate of CRLS1 and impaired mitochondrial morphology and biogenesis
Sources: Literature
Mendeliome v0.11092 HIST1H4I Elena Savva gene: HIST1H4I was added
gene: HIST1H4I was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HIST1H4I was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: HIST1H4I were set to PMID: 35202563
Phenotypes for gene: HIST1H4I were set to Neurodevelopmental syndrome
Review for gene: HIST1H4I was set to GREEN
Added comment: PMID: 35202563
- 3 unrelated de novo patients, p.His75Arg was recurring and observed in 2/3 probands.
- Zebrafish study shows both variants resulted in a significant increases in developmental issues such as in mild dev delay, necrosis and defective organogenesis.
- All patients had intellectual disability and motor and/or gross developmental delay and dysmorphisms.
- 2/3 patients showed bilateral conductive hearing loss
Sources: Literature
Mendeliome v0.11092 NAV2 Dean Phelan gene: NAV2 was added
gene: NAV2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NAV2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAV2 were set to PMID:35218524
Phenotypes for gene: NAV2 were set to Developmental delay; cerebellar hypoplasia; cerebellar dysplasia
Review for gene: NAV2 was set to AMBER
Added comment: PMID:35218524
- Two compound heterozygous LOF variants identified in one female with developmental delay and a diagnosis of cerebellar hypoplasia and dysplasia. Functional studies showed cellular migration deficits. Hypomorphic mouse model revealed developmental anomalies including cerebellar hypoplasia and dysplasia, corpus callosum hypo-dysgenesis, and agenesis of the olfactory bulbs.
Sources: Literature
Mendeliome v0.11092 ZBTB7A Daniel Flanagan gene: ZBTB7A was added
gene: ZBTB7A was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ZBTB7A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZBTB7A were set to 34515416; 31645653
Phenotypes for gene: ZBTB7A were set to Macrocephaly, neurodevelopmental delay, lymphoid hyperplasia, and persistent fetal hemoglobin (MIM#619769)
Review for gene: ZBTB7A was set to GREEN
Added comment: PMID: 34515416. Monoallelic ZBTB7A variants identified in 12 individuals from 11 families, with macrocephaly (11/12), some degree of ID (12/12), autistic features (7/12) and hypertrophy of pharyngeal lymphoid tissue (12/12). Variants included LoF variants and missense, 8 variants were de novo.

PMID: 31645653. De novo ZBTB7A missense identified in a boy with macrocephaly, intellectual disability, and sleep apnea.
Sources: Expert list
Mendeliome v0.11092 TIAM1 Alison Yeung Gene: tiam1 has been classified as Green List (High Evidence).
Mendeliome v0.11092 TIAM1 Alison Yeung Classified gene: TIAM1 as Green List (high evidence)
Mendeliome v0.11092 TIAM1 Alison Yeung Gene: tiam1 has been classified as Green List (High Evidence).
Mendeliome v0.11090 EHD1 Zornitza Stark Gene: ehd1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11090 EHD1 Zornitza Stark Classified gene: EHD1 as Amber List (moderate evidence)
Mendeliome v0.11090 EHD1 Zornitza Stark Gene: ehd1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11089 EHD1 Zornitza Stark gene: EHD1 was added
gene: EHD1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EHD1 were set to 35149593
Phenotypes for gene: EHD1 were set to Inherited renal tubular disease, MONDO:0015962, EHD1-related
Review for gene: EHD1 was set to AMBER
Added comment: Six individuals (5-33 years) with proteinuria and a high-frequency hearing deficit reported with the homozygous missense variant c.1192C>T (p.R398W) in EHD1. Proteinuria (0.7-2.1 g/d) consisted predominantly of low molecular weight proteins, reflecting impaired renal proximal tubular endocytosis of filtered proteins. Ehd1 knockout and Ehd1R398W/R398W knockin mice also showed a high-frequency hearing deficit and impaired receptor-mediated endocytosis in proximal tubules, and a zebrafish model showed impaired ability to reabsorb low molecular weight dextran. Single founder variant but two animal models, hence Amber
Sources: Literature
Mendeliome v0.11088 IL6ST Zornitza Stark Phenotypes for gene: IL6ST were changed from Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523; Stuve-Wiedemann syndrome 2, MIM# 619751: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response; Hyper-IgE syndrome, autosomal dominant; Immunodeficiency 94 with autoinflammation and dysmorphic facies, MIM# 619750 to Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523; Stuve-Wiedemann syndrome 2, MIM# 619751: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response; Hyper-IgE recurrent infection syndrome 4A, autosomal dominant, MIM# 619752; Immunodeficiency 94 with autoinflammation and dysmorphic facies, MIM# 619750
Mendeliome v0.11087 IL6ST Zornitza Stark Phenotypes for gene: IL6ST were changed from Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523; Stuve-Wiedemann syndrome 2, MIM# 619751: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response; Hyper-IgE syndrome, autosomal dominant to Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523; Stuve-Wiedemann syndrome 2, MIM# 619751: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response; Hyper-IgE syndrome, autosomal dominant; Immunodeficiency 94 with autoinflammation and dysmorphic facies, MIM# 619750
Mendeliome v0.11086 IL6ST Zornitza Stark edited their review of gene: IL6ST: Changed phenotypes: Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523, Stuve-Wiedemann syndrome 2, MIM# 619751: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response, Hyper-IgE syndrome, autosomal dominant, Immunodeficiency 94 with autoinflammation and dysmorphic facies, MIM# 619750
Mendeliome v0.11086 PTCH1 Seb Lunke Gene: ptch1 has been classified as Green List (High Evidence).
Mendeliome v0.11083 RECQL4 Seb Lunke Gene: recql4 has been classified as Green List (High Evidence).
Mendeliome v0.11079 AP3D1 Zornitza Stark Classified gene: AP3D1 as Green List (high evidence)
Mendeliome v0.11079 AP3D1 Zornitza Stark Gene: ap3d1 has been classified as Green List (High Evidence).
Mendeliome v0.11077 PPP2R3C Zornitza Stark Gene: ppp2r3c has been classified as Green List (High Evidence).
Mendeliome v0.11077 PPP2R3C Zornitza Stark Classified gene: PPP2R3C as Green List (high evidence)
Mendeliome v0.11077 PPP2R3C Zornitza Stark Gene: ppp2r3c has been classified as Green List (High Evidence).
Mendeliome v0.11076 PPP2R3C Zornitza Stark gene: PPP2R3C was added
gene: PPP2R3C was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PPP2R3C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPP2R3C were set to 30893644; 34714774; 34750818
Phenotypes for gene: PPP2R3C were set to Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy, OMIM # 618419
Review for gene: PPP2R3C was set to GREEN
Added comment: Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy (GDRM) is characterized by 46,XY complete gonadal dysgenesis in association with extragonadal anomalies, low birth weight, typical facial gestalt, rod and cone dystrophy, sensorineural hearing loss, omphalocele, anal atresia, renal agenesis, skeletal abnormalities, dry and scaly skin, severe myopathy, and neuromotor delay. 11 unrelated families with syndromic complete gonadal dysgenesis. 9 families had 46,XY females with complete gonadal dysgenesis, but 2 families had 46,XX patients with hypergonadotropic hypogonadism, nonvisualized gonads, primary amenorrhea, and absence of secondary sexual characteristics. Variants segregated with disease in each family and were not found in ethnically matched controls or in public variant databases. The heterozygous fathers exhibited morphologic abnormalities of spermatozoa and reduced fertility.
Sources: Literature
Mendeliome v0.11075 CDX2 Zornitza Stark Phenotypes for gene: CDX2 were changed from Persistent cloaca to Genetic multiple congenital anomalies/dysmorphic syndrome, MONDO:0043005; Congenital abnormalities of anus, renal and urogenital system, vertebrae and/or the limbs
Mendeliome v0.11074 CHKA Zornitza Stark Gene: chka has been classified as Green List (High Evidence).
Mendeliome v0.11073 CHKA Zornitza Stark Classified gene: CHKA as Green List (high evidence)
Mendeliome v0.11073 CHKA Zornitza Stark Gene: chka has been classified as Green List (High Evidence).
Mendeliome v0.11072 CDX2 Chirag Patel Classified gene: CDX2 as Green List (high evidence)
Mendeliome v0.11072 CDX2 Chirag Patel Gene: cdx2 has been classified as Green List (High Evidence).
Mendeliome v0.11071 CDX2 Chirag Patel edited their review of gene: CDX2: Added comment: 9 families, with heterozygous variants identified with WES, presenting with congenital abnormalities affecting the development of the anus, the renal and urogenital system, the vertebrae and/or the limbs in varying sequences and severity (incl. sirenomelia and persistent cloaca). A recurrent pathogenic missense variant in the HOX domain of the protein p.(Arg237His) was found in 3 unrelated families. In the mouse cdx2 is essential for anteroposterior patterning of embryonal axis and morphogenesis of cloacal structures. Cdx2 heterozygous conditional mutant mice show a variable phenotype (including imperforate anus, sirenomelia, posterior vertebral truncations, and bladder anomalies).; Changed rating: GREEN; Changed publications: PMID: 29177441, 34671974; Changed phenotypes: Congenital abnormalities of anus, renal and urogenital system, vertebrae and/or the limbs; Set current diagnostic: yes
Mendeliome v0.11071 CHKA Konstantinos Varvagiannis gene: CHKA was added
gene: CHKA was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CHKA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHKA were set to 35202461
Phenotypes for gene: CHKA were set to Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature
Penetrance for gene: CHKA were set to Complete
Review for gene: CHKA was set to GREEN
Added comment: Klöckner (2022 - PMID: 35202461) describe the phenotype of 6 individuals (from 5 unrelated families) harboring biallelic CHKA variants.

Shared features incl. abnormal muscle tone(6/6 - hypertonia or hypotonia, 3/6 each), DD/ID (6/6,severe in 4, severe/profound in 2), epilepsy (6/6 - onset: infancy - 3y2m | epileptic spasms or GS at onset), microcephaly (6/6), movement disorders (3/6 - incl. dyskinesia, rigidity, choreoatetotic movements). 2/5 individuals exhibited MRI abnormalities, notably hypomyelination. Short stature was observed in 4/6.

Eventual previous genetic testing was not discussed.

Exome sequencing (quattro ES for 2 sibs, trio ES for 1 individual, singleton for 3 probands) revealed biallelic CHKA variants in all affected individuals. Sanger sequencing was performed for confirmation and segregation studies.

Other variants (in suppl.) were not deemed to be causative for the neurodevelopmental phenotype.

3 different missense, 1 start-loss and 1 truncating variant were identified, namely (NM_0012772.2):
- c.421C>T/p.(Arg141Trp) [3 hmz subjects from 2 consanguineous families],
- c.580C>T/p.Pro194Ser [1 hmz individual born to consanguineous parents],
- c.2T>C/p.(Met1?) [1 hmz individual born to related parents],
- c.14dup/p.(Cys6Leufs*19) in trans with c.1021T>C/p.(Phe341Leu) in 1 individual.

CHKA encodes choline kinase alpha, an enzyme catalyzing the first step of phospholipid synthesis in the Kennedy pathway. The pathway is involved in de novo synthesis of glycerophospholipids, phosphatidylcholine and phosphatidylethanolamine being the most abundant in eukaryotic membranes.

CHKA with its paralog (CHKB) phosphorylates either choline or ethanolamine to phosphocholine or phosphoethanolamine respectively with conversion of ATP to ADP.

As the authors comment, biallelic pathogenic variants in CHKB cause a NDD with muscular dystrophy, hypotonia, ID, microcephaly and structural mitochondrial anomalies (MIM 602541). [Prominent mitochondrial patterning was observed in a single muscle biopsy available from an individual with biallelic CHKA variants].

Other disorders of the Kennedy pathway (due to biallelic PCYT2, SELENOI, PCYT1A variants) present with overlapping features incl. variable DD/ID (no-severe), microcephaly, seizures, visual impairment etc.

CHKA variants were either absent or observed once in gnomAD, affected highly conserved AAs with multiple in silico predictions in favor of a deleterious effect.

In silico modeling suggests structural effects for several of the missense variants (Arg141Trp, Pro194Ser presumably affect ADP binding, Phe341 lying close to the binding site of phosphocholine).

Each of the missense variants was expressed in yeast cells and W. Blot suggested expression at the expected molecular weight at comparative levels. The 3 aforementioned variants exhibited reduced catalytic activity (20%, 15%, 50% respectively).

NMD is thought to underly the deleterious effect of the frameshift one (not studied).

The start-loss variant is expected to result in significantly impaired expression and protein function as eventual utilization of the next possible start codon - occurring at position 123 - would remove 26% of the protein.

Chka(-/-) is embryonically lethal in mice, suggesting that complete loss is not compatible with life. Reduction of choline kinase activity by 30% in heterozygous mice did not appear to result in behavioral abnormalities although this was not studied in detail (PMID cited: 18029352). Finally, screening of 1566 mouse lines identified 198 genes whose disruption yields neuroanatomical phenotypes, Chka(+/-) mice being among these (PMID cited: 31371714).

There is no associated phenotype in OMIM, Gene2Phenotype or SysID.

Overall this gene can be considered for inclusion in the ID and epilepsy panes with green or amber rating (>3 individuals, >3 variants, variant studies, overlapping phenotype of disorders belonging to the same pathway, etc). Consider also inclusion in the microcephaly panel (where available this seemed to be of postnatal onset).
Sources: Literature
Mendeliome v0.11070 SOST Seb Lunke Gene: sost has been classified as Green List (High Evidence).
Mendeliome v0.11070 SOST Seb Lunke Phenotypes for gene: SOST were changed from to Sclerosteosis 1, OMIM#269500; Craniodiaphyseal dysplasia, OMIM#122860
Mendeliome v0.11067 SOST Seb Lunke reviewed gene: SOST: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301406, 35160258, 21221996, 17853455; Phenotypes: Sclerosteosis 1, OMIM#269500, Craniodiaphyseal dysplasia, OMIM#122860; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.11066 PTDSS1 Zornitza Stark Gene: ptdss1 has been classified as Green List (High Evidence).
Mendeliome v0.11063 SLC22A4 Zornitza Stark Gene: slc22a4 has been classified as Red List (Low Evidence).
Mendeliome v0.11061 SLC22A4 Zornitza Stark Classified gene: SLC22A4 as Red List (low evidence)
Mendeliome v0.11061 SLC22A4 Zornitza Stark Gene: slc22a4 has been classified as Red List (Low Evidence).
Mendeliome v0.11059 HSF2BP Zornitza Stark Classified gene: HSF2BP as Green List (high evidence)
Mendeliome v0.11059 HSF2BP Zornitza Stark Gene: hsf2bp has been classified as Green List (High Evidence).
Mendeliome v0.11056 TBC1D24 Zornitza Stark Gene: tbc1d24 has been classified as Green List (High Evidence).
Mendeliome v0.11056 TBC1D24 Zornitza Stark Phenotypes for gene: TBC1D24 were changed from to Deafness, autosomal dominant 65 MIM#616044; Deafness, autosomal recessive 86 MIM#614617; Developmental and epileptic encephalopathy 16 MIM#615338; DOORS syndrome MIM#220500; Epilepsy, rolandic, with proxysmal exercise-induce dystonia and writer's cramp MIM#608105; Myoclonic epilepsy, infantile, familial MIM#605021
Mendeliome v0.11053 SUCLG1 Zornitza Stark Gene: suclg1 has been classified as Green List (High Evidence).
Mendeliome v0.11050 RUNX2 Zornitza Stark Gene: runx2 has been classified as Green List (High Evidence).
Mendeliome v0.11050 RUNX2 Zornitza Stark Phenotypes for gene: RUNX2 were changed from to Cleidocranial dysplasia MIM#119600; Cleidocranial dysplasia, forme fruste, dental anomalies only MIM#119600; Cleidocranial dysplasia, forme fruste, with brachydactyly MIM#119600; Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly MIM#156510
Mendeliome v0.11047 RRM2B Zornitza Stark Gene: rrm2b has been classified as Green List (High Evidence).
Mendeliome v0.11044 RNASET2 Zornitza Stark Gene: rnaset2 has been classified as Green List (High Evidence).
Mendeliome v0.11041 C17orf53 Zornitza Stark Gene: c17orf53 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11041 C17orf53 Zornitza Stark Classified gene: C17orf53 as Amber List (moderate evidence)
Mendeliome v0.11041 C17orf53 Zornitza Stark Gene: c17orf53 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11037 TFAM Zornitza Stark Classified gene: TFAM as Green List (high evidence)
Mendeliome v0.11037 TFAM Zornitza Stark Gene: tfam has been classified as Green List (High Evidence).
Mendeliome v0.11036 TFAM Zornitza Stark edited their review of gene: TFAM: Added comment: PMID: 32399598. Homozygous missense variant predicted pathogenic in patient presenting with Perrault syndrome and intellectual disability

PMID: 34647195. Same homozygous missense variant in two sisters with premature ovarian insufficiency +/- seizures and their brother with seizures + intellectual disability. Patient fibroblasts have mtDNA depletion

PMID: 34647195. Zebrafish model with in-frame deletion has ovarian dysgenesis and mtDNA depletion; Changed rating: GREEN; Changed publications: 27448789, 29021295, 9500544, 32399598, 34647195, 34647195; Changed phenotypes: Mitochondrial DNA depletion syndrome 15 (hepatocerebral type) MIM#617156, Perrault syndrome
Mendeliome v0.11036 SPATA16 Zornitza Stark Gene: spata16 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11033 SPATA16 Zornitza Stark Classified gene: SPATA16 as Amber List (moderate evidence)
Mendeliome v0.11033 SPATA16 Zornitza Stark Gene: spata16 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11032 TNFRSF10B Zornitza Stark Gene: tnfrsf10b has been classified as Red List (Low Evidence).
Mendeliome v0.11029 TNFRSF10B Zornitza Stark Classified gene: TNFRSF10B as Red List (low evidence)
Mendeliome v0.11029 TNFRSF10B Zornitza Stark Gene: tnfrsf10b has been classified as Red List (Low Evidence).
Mendeliome v0.11028 MAPK8IP1 Zornitza Stark Gene: mapk8ip1 has been classified as Red List (Low Evidence).
Mendeliome v0.11025 MAPK8IP1 Zornitza Stark Classified gene: MAPK8IP1 as Red List (low evidence)
Mendeliome v0.11025 MAPK8IP1 Zornitza Stark Gene: mapk8ip1 has been classified as Red List (Low Evidence).
Mendeliome v0.11024 SMIM1 Zornitza Stark Gene: smim1 has been classified as Red List (Low Evidence).
Mendeliome v0.11023 SMIM1 Zornitza Stark Classified gene: SMIM1 as Red List (low evidence)
Mendeliome v0.11023 SMIM1 Zornitza Stark Gene: smim1 has been classified as Red List (Low Evidence).
Mendeliome v0.11022 ACKR1 Zornitza Stark Gene: ackr1 has been classified as Red List (Low Evidence).
Mendeliome v0.11021 ACKR1 Zornitza Stark Classified gene: ACKR1 as Red List (low evidence)
Mendeliome v0.11021 ACKR1 Zornitza Stark Gene: ackr1 has been classified as Red List (Low Evidence).
Mendeliome v0.11020 OGG1 Zornitza Stark Gene: ogg1 has been classified as Red List (Low Evidence).
Mendeliome v0.11017 OGG1 Zornitza Stark Classified gene: OGG1 as Red List (low evidence)
Mendeliome v0.11017 OGG1 Zornitza Stark Gene: ogg1 has been classified as Red List (Low Evidence).
Mendeliome v0.11016 B3GALNT1 Zornitza Stark Gene: b3galnt1 has been classified as Red List (Low Evidence).
Mendeliome v0.11016 B3GALNT1 Zornitza Stark Phenotypes for gene: B3GALNT1 were changed from to Blood group, globoside system MIM#615021
Mendeliome v0.11015 B3GALNT1 Zornitza Stark Classified gene: B3GALNT1 as Red List (low evidence)
Mendeliome v0.11015 B3GALNT1 Zornitza Stark Gene: b3galnt1 has been classified as Red List (Low Evidence).
Mendeliome v0.11014 SERPINA7 Zornitza Stark Gene: serpina7 has been classified as Green List (High Evidence).
Mendeliome v0.11011 TBC1D24 Ain Roesley reviewed gene: TBC1D24: Rating: GREEN; Mode of pathogenicity: None; Publications: 25719194; Phenotypes: Deafness, autosomal dominant 65 MIM#616044, Deafness, autosomal recessive 86 MIM#614617, Developmental and epileptic encephalopathy 16 MIM#615338, DOORS syndrome MIM#220500, Epilepsy, rolandic, with proxysmal exercise-induce dystonia and writer's cramp MIM#608105, Myoclonic epilepsy, infantile, familial MIM#605021; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.11011 RUNX2 Ain Roesley reviewed gene: RUNX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301686; Phenotypes: Cleidocranial dysplasia MIM#119600, Cleidocranial dysplasia, forme fruste, dental anomalies only MIM#119600, Cleidocranial dysplasia, forme fruste, with brachydactyly MIM#119600, Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly MIM#156510; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.11011 DLC1 Bryony Thompson Gene: dlc1 has been classified as Green List (High Evidence).
Mendeliome v0.11011 DLC1 Bryony Thompson Classified gene: DLC1 as Green List (high evidence)
Mendeliome v0.11011 DLC1 Bryony Thompson Gene: dlc1 has been classified as Green List (High Evidence).
Mendeliome v0.11009 IL6ST Zornitza Stark Phenotypes for gene: IL6ST were changed from Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523; Stuve-Wiedemann-like syndrome: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response; Hyper-IgE syndrome, autosomal dominant to Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523; Stuve-Wiedemann syndrome 2, MIM# 619751: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response; Hyper-IgE syndrome, autosomal dominant
Mendeliome v0.11008 IL6ST Zornitza Stark edited their review of gene: IL6ST: Changed phenotypes: Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523, Stuve-Wiedemann syndrome 2, MIM# 619751: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response, Hyper-IgE syndrome, autosomal dominant
Mendeliome v0.11008 WARS2 Zornitza Stark Gene: wars2 has been classified as Green List (High Evidence).
Mendeliome v0.11008 WARS2 Zornitza Stark Phenotypes for gene: WARS2 were changed from to Parkinsonism-dystonia 3, childhood-onset, MIM# 619738; Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures, MIM# 617710
Mendeliome v0.11005 WARS2 Zornitza Stark reviewed gene: WARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29120065, 31970218, 34890876, 28236339, 28650581, 28905505, 30920170; Phenotypes: Parkinsonism-dystonia 3, childhood-onset, MIM# 619738, Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures, MIM# 617710; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11005 NHLH2 Zornitza Stark Gene: nhlh2 has been classified as Red List (Low Evidence).
Mendeliome v0.11005 NHLH2 Zornitza Stark gene: NHLH2 was added
gene: NHLH2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: NHLH2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NHLH2 were set to 35066646
Phenotypes for gene: NHLH2 were set to Hypogonadotropic hypogonadism 27 without anosmia , MIM# 619755
Review for gene: NHLH2 was set to RED
Added comment: Single individual reported homozygous for a missense variant in this gene. Two other individuals heterozygous for missense variants identified as part of this cohort; however, had alternative diagnoses.
Sources: Literature
Mendeliome v0.11004 B3GALNT1 Paul De Fazio reviewed gene: B3GALNT1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Blood group, globoside system MIM#615021; Mode of inheritance: Unknown; Current diagnostic: yes
Mendeliome v0.11003 NDUFA11 Zornitza Stark Gene: ndufa11 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.11000 NDUFA11 Zornitza Stark Classified gene: NDUFA11 as Amber List (moderate evidence)
Mendeliome v0.11000 NDUFA11 Zornitza Stark Gene: ndufa11 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10999 TBK1 Chern Lim reviewed gene: TBK1: Rating: RED; Mode of pathogenicity: None; Publications: 25803835, 26581300; Phenotypes: Frontotemporal dementia and/or amyotrophic lateral sclerosis 4 (MIM#616439), AD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.10999 RIN2 Zornitza Stark Gene: rin2 has been classified as Green List (High Evidence).
Mendeliome v0.10999 RIN2 Zornitza Stark Phenotypes for gene: RIN2 were changed from to Macrocephaly, alopecia, cutis laxa, and scoliosis, MIM#613075
Mendeliome v0.10996 RIN2 Zornitza Stark reviewed gene: RIN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 19631308, 20424861, 20954239, 24449201, 30769224; Phenotypes: Macrocephaly, alopecia, cutis laxa, and scoliosis, MIM#613075; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10996 DLD Zornitza Stark Gene: dld has been classified as Green List (High Evidence).
Mendeliome v0.10991 TBX15 Zornitza Stark Gene: tbx15 has been classified as Green List (High Evidence).
Mendeliome v0.10991 TBX15 Zornitza Stark Phenotypes for gene: TBX15 were changed from to Cousin syndrome, MIM# 260660
Mendeliome v0.10988 TBX15 Zornitza Stark reviewed gene: TBX15: Rating: GREEN; Mode of pathogenicity: None; Publications: 19068278, 24039145; Phenotypes: Cousin syndrome, MIM# 260660; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10988 TBX18 Zornitza Stark Gene: tbx18 has been classified as Green List (High Evidence).
Mendeliome v0.10985 TBX4 Zornitza Stark Phenotypes for gene: TBX4 were changed from Posterior amelia with pelvis and pulmonary hypoplasia; small patella syndrome to Amelia, posterior, with pelvic and pulmonary hypoplasia syndrome, MIM# 601360; Ischiocoxopodopatellar syndrome with or without pulmonary arterial hypertension, MIM# 147891
Mendeliome v0.10983 TGDS Zornitza Stark Gene: tgds has been classified as Green List (High Evidence).
Mendeliome v0.10980 THOC6 Zornitza Stark Gene: thoc6 has been classified as Green List (High Evidence).
Mendeliome v0.10977 DRC1 Zornitza Stark Phenotypes for gene: DRC1 were changed from Ciliary dyskinesia, primary, 21, MIM# 615294 to Ciliary dyskinesia, primary, 21, MIM# 615294; Male infertility
Mendeliome v0.10975 DRC1 Zornitza Stark edited their review of gene: DRC1: Added comment: PMID 34169321: two individuals reported with homozygous variants and morphological abnormalities of sperm/male infertility.; Changed publications: 31960620, 34169321; Changed phenotypes: Ciliary dyskinesia, primary, 21, MIM# 615294, Male infertility
Mendeliome v0.10974 HOXB6 Zornitza Stark Classified gene: HOXB6 as Red List (low evidence)
Mendeliome v0.10974 HOXB6 Zornitza Stark Gene: hoxb6 has been classified as Red List (Low Evidence).
Mendeliome v0.10973 FUZ Zornitza Stark Gene: fuz has been classified as Red List (Low Evidence).
Mendeliome v0.10973 FUZ Zornitza Stark Classified gene: FUZ as Red List (low evidence)
Mendeliome v0.10973 FUZ Zornitza Stark Gene: fuz has been classified as Red List (Low Evidence).
Mendeliome v0.10972 FTSJ1 Zornitza Stark Gene: ftsj1 has been classified as Green List (High Evidence).
Mendeliome v0.10969 FLAD1 Zornitza Stark Gene: flad1 has been classified as Green List (High Evidence).
Mendeliome v0.10966 FGF17 Zornitza Stark Gene: fgf17 has been classified as Green List (High Evidence).
Mendeliome v0.10963 SYP Zornitza Stark Gene: syp has been classified as Green List (High Evidence).
Mendeliome v0.10959 ZFYVE26 Zornitza Stark Gene: zfyve26 has been classified as Green List (High Evidence).
Mendeliome v0.10959 ZFYVE26 Zornitza Stark Phenotypes for gene: ZFYVE26 were changed from to Spastic paraplegia 15, autosomal recessive MIM#270700
Mendeliome v0.10956 ZDHHC9 Zornitza Stark Gene: zdhhc9 has been classified as Green List (High Evidence).
Mendeliome v0.10953 FUZ Ain Roesley gene: FUZ was added
gene: FUZ was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FUZ was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FUZ were set to 21840926
Phenotypes for gene: FUZ were set to {Neural tube defects, susceptibility to} MIM#182940
Penetrance for gene: FUZ were set to unknown
Review for gene: FUZ was set to RED
gene: FUZ was marked as current diagnostic
Added comment: Spina bifida cohort. Negative for VANGL1 and VANGL2, only FUZ was sequenced.
Variants identified in 5 individuals.
Arg404Gln (39 hets in gnomAD) and Asp354Tyr (6 hets in gnomAD). These variants are listed as risk factor in ClinVar
Pro39Ser (absent in gnomAD) was de novo by parental sanger and showed reduced cell mobility on scratch assays.

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

Finally, hom KO mouse models were done to prove neural tube defects
Sources: Literature
Mendeliome v0.10953 ZFYVE26 Ain Roesley reviewed gene: ZFYVE26: Rating: GREEN; Mode of pathogenicity: None; Publications: 34057829; Phenotypes: Spastic paraplegia 15, autosomal recessive MIM#270700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10951 BAG5 Zornitza Stark Gene: bag5 has been classified as Green List (High Evidence).
Mendeliome v0.10951 BAG5 Zornitza Stark Classified gene: BAG5 as Green List (high evidence)
Mendeliome v0.10951 BAG5 Zornitza Stark Gene: bag5 has been classified as Green List (High Evidence).
Mendeliome v0.10950 BAG5 Zornitza Stark gene: BAG5 was added
gene: BAG5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BAG5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BAG5 were set to 35044787
Phenotypes for gene: BAG5 were set to Cardiomyopathy, dilated, 2F, MIM# 619747
Review for gene: BAG5 was set to GREEN
Added comment: 5 individuals from four unrelated families reported. All had early-onset disease, with the diagnosis being made in the second decade of life in 4 patients (families 1, 3, and 4) and at age 34 in 1 (family 2). Refractory ventricular arrhythmias (tachycardia or fibrillation), severely reduced left ventricular ejection fractions, elevated left ventricular diastolic dimensions, and elevated brain natriuretic peptide (BNP) levels reported. All developed severe heart failure requiring placement of a left ventricular assist device for circulatory support, and at least 1 underwent cardiac transplantation.
Sources: Literature
Mendeliome v0.10949 BCO1 Zornitza Stark Gene: bco1 has been classified as Red List (Low Evidence).
Mendeliome v0.10949 BCO1 Zornitza Stark Classified gene: BCO1 as Red List (low evidence)
Mendeliome v0.10949 BCO1 Zornitza Stark Gene: bco1 has been classified as Red List (Low Evidence).
Mendeliome v0.10948 PRKCH Zornitza Stark Gene: prkch has been classified as Red List (Low Evidence).
Mendeliome v0.10948 PRKCH Zornitza Stark Classified gene: PRKCH as Red List (low evidence)
Mendeliome v0.10948 PRKCH Zornitza Stark Gene: prkch has been classified as Red List (Low Evidence).
Mendeliome v0.10947 ALDH2 Zornitza Stark Gene: aldh2 has been classified as Red List (Low Evidence).
Mendeliome v0.10946 ALDH2 Zornitza Stark Classified gene: ALDH2 as Red List (low evidence)
Mendeliome v0.10946 ALDH2 Zornitza Stark Gene: aldh2 has been classified as Red List (Low Evidence).
Mendeliome v0.10945 ABHD16A Zornitza Stark Gene: abhd16a has been classified as Green List (High Evidence).
Mendeliome v0.10945 ABHD16A Zornitza Stark Phenotypes for gene: ABHD16A were changed from Spastic paraplegia; Intellectual Disability; Callosome to Spastic paraplegia 86, autosomal recessive, MIM# 619735; Intellectual Disability; Corpus callosum abnormalities
Mendeliome v0.10944 ABHD16A Zornitza Stark reviewed gene: ABHD16A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 86, autosomal recessive, MIM# 619735; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10944 GSPT2 Zornitza Stark Gene: gspt2 has been classified as Red List (Low Evidence).
Mendeliome v0.10943 SUMO1 Zornitza Stark Gene: sumo1 has been classified as Red List (Low Evidence).
Mendeliome v0.10941 SUMO1 Zornitza Stark Classified gene: SUMO1 as Red List (low evidence)
Mendeliome v0.10941 SUMO1 Zornitza Stark Gene: sumo1 has been classified as Red List (Low Evidence).
Mendeliome v0.10940 THUMPD1 Zornitza Stark Gene: thumpd1 has been classified as Green List (High Evidence).
Mendeliome v0.10939 THUMPD1 Zornitza Stark Classified gene: THUMPD1 as Green List (high evidence)
Mendeliome v0.10939 THUMPD1 Zornitza Stark Gene: thumpd1 has been classified as Green List (High Evidence).
Mendeliome v0.10938 THUMPD1 Chern Lim changed review comment from: Broly, M. et al. (2022), AJHG:
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other; to: Broly, M. et al. (2022), AJHG:
- 13 individuals from 8 families, biallelic loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other
Mendeliome v0.10938 THUMPD1 Chern Lim changed review comment from: Broly, M. et al. (2022):
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other; to: Broly, M. et al. (2022), AJHG:
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other
Mendeliome v0.10938 THUMPD1 Chern Lim changed review comment from: Broly, M. et al. (2022) manuscript accepted in AJHG:
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other; to: Broly, M. et al. (2022):
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other
Mendeliome v0.10938 THUMPD1 Chern Lim gene: THUMPD1 was added
gene: THUMPD1 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: THUMPD1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: THUMPD1 were set to Syndromic form of intellectual disability associated with developmental delay, behavioral abnormalities, hearing loss and facial dysmorphism, AR
Review for gene: THUMPD1 was set to GREEN
gene: THUMPD1 was marked as current diagnostic
Added comment: Broly, M. et al. (2022) manuscript accepted in AJHG:
- 13 individuals from 8 families, loss of function variants (PTVs, one missense, one single AA del).
- Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism and ophthalmological abnormalities.
Sources: Other
Mendeliome v0.10938 RAB39B Zornitza Stark Gene: rab39b has been classified as Green List (High Evidence).
Mendeliome v0.10935 PTCHD1 Zornitza Stark Gene: ptchd1 has been classified as Green List (High Evidence).
Mendeliome v0.10932 PPP3CA Zornitza Stark Gene: ppp3ca has been classified as Green List (High Evidence).
Mendeliome v0.10932 PPP3CA Zornitza Stark Phenotypes for gene: PPP3CA were changed from to Developmental and epileptic encephalopathy 91, MIM#617711; Arthrogryposis, cleft palate, craniosynostosis and impaired intellectual development, MIM#618265
Mendeliome v0.10929 PLP1 Zornitza Stark Gene: plp1 has been classified as Green List (High Evidence).
Mendeliome v0.10926 LDB3 Zornitza Stark Gene: ldb3 has been classified as Green List (High Evidence).
Mendeliome v0.10923 PPP3CA Chern Lim changed review comment from: PMID: 29432562:
- Overexpression studies using yeast showed missense variants in the autoinhibitory domain resulted in gain of function, missense variants in the catalytic domain resulted in loss of function (however dom-neg has not been ruled out).
- Loss-of-function and gain-of-function mutations of PPP3CA lead to early onset epileptic encephalopathy and multiple congenital abnormalities, respectively.

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

PMID: 32593294:
- Reported a patient with PTV in the C-term predicted to escape NMD, clinical features consistent with MIM#617711.
- 15 variants have been reported. Summarised that missense variants in catalytic domain and those upstream of autoinhibitory domain, PTVs in C-term predicted to escape NMD: LoF, MIM#617711; missense in autoinhibitory domain: GoF, MIM#618265.
Mendeliome v0.10923 PPP3CA Chern Lim reviewed gene: PPP3CA: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 29432562, 32593294; Phenotypes: Developmental and epileptic encephalopathy 91, MIM#617711, Arthrogryposis, cleft palate, craniosynostosis and impaired intellectual development, MIM#618265; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.10922 HYAL2 Zornitza Stark Classified gene: HYAL2 as Green List (high evidence)
Mendeliome v0.10922 HYAL2 Zornitza Stark Gene: hyal2 has been classified as Green List (High Evidence).
Mendeliome v0.10921 PAX5 Zornitza Stark Gene: pax5 has been classified as Green List (High Evidence).
Mendeliome v0.10920 COL25A1 Bryony Thompson Phenotypes for gene: COL25A1 were changed from Fibrosis of extraocular muscles, congenital, 5, MIM# 616219 to Fibrosis of extraocular muscles, congenital, 5, MIM# 616219; arthrogryposis multiplex congenita MONDO:0015168
Mendeliome v0.10918 COL25A1 Bryony Thompson reviewed gene: COL25A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35077597, 26437029; Phenotypes: arthrogryposis multiplex congenita MONDO:0015168; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10918 RPL8 Bryony Thompson Gene: rpl8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10918 RPL8 Bryony Thompson Classified gene: RPL8 as Amber List (moderate evidence)
Mendeliome v0.10918 RPL8 Bryony Thompson Gene: rpl8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10917 ABCB4 Zornitza Stark Phenotypes for gene: ABCB4 were changed from Cholestasis, progressive familial intrahepatic 3 MIM#602347; disorder of bile acid metabolism to Cholestasis, progressive familial intrahepatic 3 MIM#602347; disorder of bile acid metabolism; Gallbladder disease 1 (MIM#600803)
Mendeliome v0.10913 ABCB4 Lucy Spencer reviewed gene: ABCB4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 18482588, 28924228, 32376413; Phenotypes: Cholestasis, intrahepatic, of pregnancy, 3 (MIM#614972), Gallbladder disease 1 (MIM#600803); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.10909 EEF1B2 Bryony Thompson Classified gene: EEF1B2 as Green List (high evidence)
Mendeliome v0.10909 EEF1B2 Bryony Thompson Gene: eef1b2 has been classified as Green List (High Evidence).
Mendeliome v0.10908 ARR3 Bryony Thompson Gene: arr3 has been classified as Green List (High Evidence).
Mendeliome v0.10908 ARR3 Bryony Thompson Classified gene: ARR3 as Green List (high evidence)
Mendeliome v0.10908 ARR3 Bryony Thompson Gene: arr3 has been classified as Green List (High Evidence).
Mendeliome v0.10907 ARR3 Bryony Thompson gene: ARR3 was added
gene: ARR3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARR3 was set to Other
Publications for gene: ARR3 were set to 27829781; 35001458
Phenotypes for gene: ARR3 were set to Myopia 26, X-linked, female-limited MIM#301010
Review for gene: ARR3 was set to GREEN
Added comment: At least 6 multi-generational families with female-limited early-onset high myopia. Only female carriers are affected and hemizygous males are unaffected. Authors hypothesise the mode of inheritance might be explained by metabolic interference due to X-inactivation.
Sources: Literature
Mendeliome v0.10906 SLC26A8 Bryony Thompson Gene: slc26a8 has been classified as Green List (High Evidence).
Mendeliome v0.10903 PYROXD2 Zornitza Stark Gene: pyroxd2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10903 PYROXD2 Zornitza Stark Classified gene: PYROXD2 as Amber List (moderate evidence)
Mendeliome v0.10903 PYROXD2 Zornitza Stark Gene: pyroxd2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10902 PYROXD2 Zornitza Stark gene: PYROXD2 was added
gene: PYROXD2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PYROXD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PYROXD2 were set to 35055180
Phenotypes for gene: PYROXD2 were set to Mitochondrial disease, MONDO:0044970
Review for gene: PYROXD2 was set to AMBER
Added comment: Single individual reported, functional data.
Sources: Literature
Mendeliome v0.10900 OBSCN Zornitza Stark Phenotypes for gene: OBSCN were changed from Hypertrophic cardiomyopathy to Rhabdomyolysis MONDO:0005290, OBSCN-related
Mendeliome v0.10897 OBSCN Zornitza Stark Classified gene: OBSCN as Green List (high evidence)
Mendeliome v0.10897 OBSCN Zornitza Stark Gene: obscn has been classified as Green List (High Evidence).
Mendeliome v0.10896 HAND2 Zornitza Stark Gene: hand2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10893 HAND2 Zornitza Stark Classified gene: HAND2 as Amber List (moderate evidence)
Mendeliome v0.10893 HAND2 Zornitza Stark Gene: hand2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10892 POP1 Zornitza Stark Gene: pop1 has been classified as Green List (High Evidence).
Mendeliome v0.10892 POP1 Zornitza Stark Phenotypes for gene: POP1 were changed from to Anauxetic dysplasia 2, OMIM:617396; Anauxetic dysplasia 2, MONDO:0054561
Mendeliome v0.10889 POP1 Zornitza Stark reviewed gene: POP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21455487, 27380734, 28067412; Phenotypes: Anauxetic dysplasia 2, OMIM:617396, Anauxetic dysplasia 2, MONDO:0054561; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10888 MVD Zornitza Stark Phenotypes for gene: MVD were changed from Porokeratosis 7, multiple types, MIM# 614714 to Porokeratosis 7, multiple types, MIM# 614714; Nonsyndromic genetic hearing loss MONDO:0019497, MVD-related, AR
Mendeliome v0.10886 PLCD1 Zornitza Stark Gene: plcd1 has been classified as Green List (High Evidence).
Mendeliome v0.10883 AKAP10 Zornitza Stark Gene: akap10 has been classified as Red List (Low Evidence).
Mendeliome v0.10881 AKAP10 Zornitza Stark Classified gene: AKAP10 as Red List (low evidence)
Mendeliome v0.10881 AKAP10 Zornitza Stark Gene: akap10 has been classified as Red List (Low Evidence).
Mendeliome v0.10880 HMCN1 Zornitza Stark Gene: hmcn1 has been classified as Red List (Low Evidence).
Mendeliome v0.10877 HMCN1 Zornitza Stark Classified gene: HMCN1 as Red List (low evidence)
Mendeliome v0.10877 HMCN1 Zornitza Stark Gene: hmcn1 has been classified as Red List (Low Evidence).
Mendeliome v0.10876 CCND1 Zornitza Stark Gene: ccnd1 has been classified as Red List (Low Evidence).
Mendeliome v0.10874 CCND1 Zornitza Stark Classified gene: CCND1 as Red List (low evidence)
Mendeliome v0.10874 CCND1 Zornitza Stark Gene: ccnd1 has been classified as Red List (Low Evidence).
Mendeliome v0.10873 PADI4 Zornitza Stark Gene: padi4 has been classified as Red List (Low Evidence).
Mendeliome v0.10871 PADI4 Zornitza Stark Classified gene: PADI4 as Red List (low evidence)
Mendeliome v0.10871 PADI4 Zornitza Stark Gene: padi4 has been classified as Red List (Low Evidence).
Mendeliome v0.10869 PDSS2 Zornitza Stark Gene: pdss2 has been classified as Green List (High Evidence).
Mendeliome v0.10866 PDHX Zornitza Stark Gene: pdhx has been classified as Green List (High Evidence).
Mendeliome v0.10863 NDUFS8 Zornitza Stark Gene: ndufs8 has been classified as Green List (High Evidence).
Mendeliome v0.10860 NDUFV1 Zornitza Stark Gene: ndufv1 has been classified as Green List (High Evidence).
Mendeliome v0.10857 FZR1 Alison Yeung Gene: fzr1 has been classified as Green List (High Evidence).
Mendeliome v0.10857 FZR1 Alison Yeung Classified gene: FZR1 as Green List (high evidence)
Mendeliome v0.10857 FZR1 Alison Yeung Gene: fzr1 has been classified as Green List (High Evidence).
Mendeliome v0.10856 COL4A6 Zornitza Stark Classified gene: COL4A6 as Green List (high evidence)
Mendeliome v0.10856 COL4A6 Zornitza Stark Gene: col4a6 has been classified as Green List (High Evidence).
Mendeliome v0.10855 SEZ6 Alison Yeung Gene: sez6 has been classified as Red List (Low Evidence).
Mendeliome v0.10855 SEZ6 Alison Yeung Classified gene: SEZ6 as Red List (low evidence)
Mendeliome v0.10855 SEZ6 Alison Yeung Gene: sez6 has been classified as Red List (Low Evidence).
Mendeliome v0.10854 ADAMTS1 Zornitza Stark Gene: adamts1 has been classified as Red List (Low Evidence).
Mendeliome v0.10854 ADAMTS1 Zornitza Stark Classified gene: ADAMTS1 as Red List (low evidence)
Mendeliome v0.10854 ADAMTS1 Zornitza Stark Gene: adamts1 has been classified as Red List (Low Evidence).
Mendeliome v0.10850 ATP5O Alison Yeung Gene: atp5o has been classified as Red List (Low Evidence).
Mendeliome v0.10850 ATP5O Alison Yeung Classified gene: ATP5O as Red List (low evidence)
Mendeliome v0.10850 ATP5O Alison Yeung Gene: atp5o has been classified as Red List (Low Evidence).
Mendeliome v0.10849 SEZ6 Paul De Fazio gene: SEZ6 was added
gene: SEZ6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SEZ6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SEZ6 were set to 34135477
Phenotypes for gene: SEZ6 were set to Nonsyndromic genetic hearing loss MONDO:0019497, SEZ6-related
Review for gene: SEZ6 was set to RED
gene: SEZ6 was marked as current diagnostic
Added comment: Homozygous missense variant p.(Val698Ile) identified in 4 affected individuals from a single consanguineous Pakistani family by WES. 5 other genotyped unaffected individuals were heterozygous or homozygous wild-type. Variant is in gnomad (36 hets, 0 hom).

RNA expression studies show the gene is expressed in the mouse inner ear, but no functional studies were performed on the variant (in silico analysis only).
Sources: Literature
Mendeliome v0.10848 ATP5E Zornitza Stark Classified gene: ATP5E as Green List (high evidence)
Mendeliome v0.10848 ATP5E Zornitza Stark Gene: atp5e has been classified as Green List (High Evidence).
Mendeliome v0.10847 OBSCN Ee Ming Wong reviewed gene: OBSCN: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34957489; Phenotypes: Rhabdomyolysis MONDO:0005290, OBSCN-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10846 ADAMTS1 Paul De Fazio gene: ADAMTS1 was added
gene: ADAMTS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ADAMTS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTS1 were set to 34135477
Phenotypes for gene: ADAMTS1 were set to Nonsyndromic genetic hearing loss MONDO:0019497, ADAMTS1-related
Review for gene: ADAMTS1 was set to RED
gene: ADAMTS1 was marked as current diagnostic
Added comment: Homozygous missense variant p.(Ser135Ala) identified in 3 affected siblings from a single consanguineous Pakistani family by WES. A fourth unaffected sibling was homozygous wild type. Variant is in gnomad (26 hets, 1 hom).

RNA expression studies show the gene is expressed in the mouse inner ear, but no functional studies were performed on the variant (in silico analysis only).
Sources: Literature
Mendeliome v0.10846 RBL2 Alison Yeung Classified gene: RBL2 as Green List (high evidence)
Mendeliome v0.10846 RBL2 Alison Yeung Gene: rbl2 has been classified as Green List (High Evidence).
Mendeliome v0.10844 ATP5O Ain Roesley gene: ATP5O was added
gene: ATP5O was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATP5O was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP5O were set to 34954817
Phenotypes for gene: ATP5O were set to mitochondrial disease, ATP5F1E-related MONDO:0044970
Penetrance for gene: ATP5O were set to Complete
Review for gene: ATP5O was set to RED
gene: ATP5O was marked as current diagnostic
Added comment: Now known as ATP5PO (HGNC)

1 compound het individual with dev delay, muscular hypotonia, ID, dystonia, seizures and neurologic regression
Sources: Literature
Mendeliome v0.10844 BAP1 Anna Ritchie changed review comment from: 11 de novo germline heterozygous missense BAP1 variants associated with a rare syndromic neurodevelopmental disorder. Functional analysis showed that most of the variants cannot rescue the consequences of BAP1 inactivation, suggesting a loss-of-function mechanism. All affected individuals harboring a de novo BAP1 variant had DD or ID (11/11) characterized notably by speech (11/ 11) and motor delay (6/11). Most of them had hypotonia (7/11), seizures (6/11), and abnormal behavior (8/10), including autism spectrum disorder, attention deficit hyperactivity disorder, and hypersensitivity. Almost all individuals showed dysmorphic facial features (10/11), and more than half (6/11) had skeletal mal- formations (involving the hands [4/11], feet [3/11], or spine [2/11],). Most of the individuals had growth failure (9/11), including four individuals with a very short stature.
Sources: Literature; to: 11 de novo germline heterozygous missense BAP1 variants associated with a rare syndromic neurodevelopmental disorder. Functional analysis showed that most of the variants cannot rescue the consequences of BAP1 inactivation, suggesting a loss-of-function mechanism. All affected individuals harboring a de novo BAP1 variant had DD or ID (11/11) characterized notably by speech (11/ 11) and motor delay (6/11). Most of them had hypotonia (7/11), seizures (6/11), and abnormal behavior (8/10), including autism spectrum disorder, attention deficit hyperactivity disorder, and hypersensitivity. Almost all individuals showed dysmorphic facial features (10/11), and more than half (6/11) had skeletal malformations (involving the hands [4/11], feet [3/11], or spine [2/11]). Most of the individuals had growth failure (9/11), including four individuals with a very short stature.
Sources: Literature
Mendeliome v0.10844 BAP1 Anna Ritchie changed review comment from: 11 de novo germline heterozygous missense BAP1 variants associated with a rare syndromic neurodevelopmental disorder. Functional analysis showed that most of the variants cannot rescue the consequences of BAP1 inactivation, suggesting a loss-of-function mechanism. Patients phenotypes also included developmental delay, speech and motor delay, seizures, hypotonia, abnormal behaviour, autism, attention deficit hyperactivity disorder, and hypersensitivity.
Sources: Literature; to: 11 de novo germline heterozygous missense BAP1 variants associated with a rare syndromic neurodevelopmental disorder. Functional analysis showed that most of the variants cannot rescue the consequences of BAP1 inactivation, suggesting a loss-of-function mechanism. All affected individuals harboring a de novo BAP1 variant had DD or ID (11/11) characterized notably by speech (11/ 11) and motor delay (6/11). Most of them had hypotonia (7/11), seizures (6/11), and abnormal behavior (8/10), including autism spectrum disorder, attention deficit hyperactivity disorder, and hypersensitivity. Almost all individuals showed dysmorphic facial features (10/11), and more than half (6/11) had skeletal mal- formations (involving the hands [4/11], feet [3/11], or spine [2/11],). Most of the individuals had growth failure (9/11), including four individuals with a very short stature.
Sources: Literature
Mendeliome v0.10844 TMEM53 Zornitza Stark Gene: tmem53 has been classified as Green List (High Evidence).
Mendeliome v0.10844 TMEM53 Zornitza Stark Classified gene: TMEM53 as Green List (high evidence)
Mendeliome v0.10844 TMEM53 Zornitza Stark Gene: tmem53 has been classified as Green List (High Evidence).
Mendeliome v0.10843 TMEM53 Zornitza Stark Phenotypes for gene: TMEM53 were changed from Sclerosing bone disorder, macrocephaly, impaired vision, short stature to Primary bone dysplasia MONDO:0018230, TMEM53-related; Sclerosing bone disorder, macrocephaly, impaired vision, short stature
Mendeliome v0.10842 MAN2C1 Alison Yeung Gene: man2c1 has been classified as Green List (High Evidence).
Mendeliome v0.10841 MAN2C1 Alison Yeung Classified gene: MAN2C1 as Green List (high evidence)
Mendeliome v0.10841 MAN2C1 Alison Yeung Gene: man2c1 has been classified as Green List (High Evidence).
Mendeliome v0.10840 SLC38A3 Zornitza Stark Gene: slc38a3 has been classified as Green List (High Evidence).
Mendeliome v0.10839 SLC38A3 Zornitza Stark Classified gene: SLC38A3 as Green List (high evidence)
Mendeliome v0.10839 SLC38A3 Zornitza Stark Gene: slc38a3 has been classified as Green List (High Evidence).
Mendeliome v0.10838 BAP1 Anna Ritchie gene: BAP1 was added
gene: BAP1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BAP1 were set to PMID: 35051358
Phenotypes for gene: BAP1 were set to syndromic intellectual disability MONDO:0000508
Penetrance for gene: BAP1 were set to unknown
Review for gene: BAP1 was set to GREEN
Added comment: 11 de novo germline heterozygous missense BAP1 variants associated with a rare syndromic neurodevelopmental disorder. Functional analysis showed that most of the variants cannot rescue the consequences of BAP1 inactivation, suggesting a loss-of-function mechanism. Patients phenotypes also included developmental delay, speech and motor delay, seizures, hypotonia, abnormal behaviour, autism, attention deficit hyperactivity disorder, and hypersensitivity.
Sources: Literature
Mendeliome v0.10838 ARSK Zornitza Stark Gene: arsk has been classified as Green List (High Evidence).
Mendeliome v0.10838 ARSK Zornitza Stark Phenotypes for gene: ARSK were changed from Mucopolysaccharidosis to Mucopolysaccharidosis MONDO:0019249, ARSK-related
Mendeliome v0.10837 ARSK Zornitza Stark Classified gene: ARSK as Green List (high evidence)
Mendeliome v0.10837 ARSK Zornitza Stark Gene: arsk has been classified as Green List (High Evidence).
Mendeliome v0.10836 TMEM53 Lucy Spencer gene: TMEM53 was added
gene: TMEM53 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TMEM53 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM53 were set to PMID: 33824347
Phenotypes for gene: TMEM53 were set to Sclerosing bone disorder, macrocephaly, impaired vision, short stature
Review for gene: TMEM53 was set to GREEN
Added comment: PMID: 33824347- Previously unknown type of sclerosing bone disorder in 4 independent families, bi-allelic LOF variants in TMEM53. 5 individuals from 4 families, all have proportional or short limbed stature, not identifiable at birth. Head deformities (macrocephaly, dolichocephaly, prominent forehead), epicanthic folds, thick vermilion of upper and lower lips. Vision diminished after early childhood due to optic nerve compression.

3 of 4 families confirmed consanguineous, and all affected members from all 4 families have homozygous variants inherited from heterozygous parents. 3 families have the same splicing variant proven to cause exon 2 skipping and an NMD frameshift by RT-PCR. The other family has a an NMD frameshift variant. So 4 families but only 2 variants.
Sources: Literature
Mendeliome v0.10835 MAN2C1 Michelle Torres gene: MAN2C1 was added
gene: MAN2C1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MAN2C1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAN2C1 were set to 35045343
Phenotypes for gene: MAN2C1 were set to neurodevelopmental disorder MONDO:0700092 MAN2C1-related
Review for gene: MAN2C1 was set to GREEN
Added comment: Six individuals from four different families, including two fetuses, exhibiting dysmorphic facial features, congenital anomalies such as tongue hamartoma, variable degrees of intellectual disability, and brain anomalies including polymicrogyria, interhemispheric cysts, hypothalamic hamartoma, callosal anomalies, and hypoplasia of brainstem and cerebellar vermis. Variants include PTC and missense.
Sources: Literature
Mendeliome v0.10835 ARSK Paul De Fazio gene: ARSK was added
gene: ARSK was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARSK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARSK were set to 34916232; 32856704
Phenotypes for gene: ARSK were set to Mucopolysaccharidosis
Review for gene: ARSK was set to GREEN
gene: ARSK was marked as current diagnostic
Added comment: 4 individuals from 2 unrelated consanguineous families (Turkish and Indian) reported with a homozygous missense and an NMD-predicted nonsense variant. Affected individuals had features of mucopolysaccharidosis such as short stature, coarse facial features and dysostosis multiplex. Urinary GAG excretion was normal by conventional methods, but LC-MS/MS in 2 individuals revealed an increase in specific dermatan sulfate-derived disaccharides. Functional studies showed reduced protein levels and reduced enzyme activity for the nonsense and missense variant respectively.

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

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

Variable ID, possibly related to variant type with LoF variants associated with more severe ID. All individuals had microcephaly, hypoplasia or agenesis of the corpus callosum, growth retardation, and craniofacial dysmorphism.; Changed rating: GREEN; Changed publications: 15203205, 34694367; Changed phenotypes: Neurodevelopmental disorder, MONDO:0700092, FRA10AC1-related; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10835 NDUFS7 Zornitza Stark Gene: ndufs7 has been classified as Green List (High Evidence).
Mendeliome v0.10832 NDUFA1 Zornitza Stark Gene: ndufa1 has been classified as Green List (High Evidence).
Mendeliome v0.10829 MYO5A Zornitza Stark Gene: myo5a has been classified as Green List (High Evidence).
Mendeliome v0.10826 LRPPRC Zornitza Stark Gene: lrpprc has been classified as Green List (High Evidence).
Mendeliome v0.10823 PLCB1 Zornitza Stark Gene: plcb1 has been classified as Green List (High Evidence).
Mendeliome v0.10820 PLAA Zornitza Stark Gene: plaa has been classified as Green List (High Evidence).
Mendeliome v0.10820 PLAA Zornitza Stark Phenotypes for gene: PLAA were changed from to Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, MIM# 617527
Mendeliome v0.10817 PLAA Zornitza Stark reviewed gene: PLAA: Rating: GREEN; Mode of pathogenicity: None; Publications: 28007986, 28413018, 31322726; Phenotypes: Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, MIM# 617527; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10817 PGAP1 Zornitza Stark Gene: pgap1 has been classified as Green List (High Evidence).
Mendeliome v0.10813 NAA20 Zornitza Stark Phenotypes for gene: NAA20 were changed from Intellectual disability; Microcephaly; Neurodevelopmental disorder MONDO:0700092 to Intellectual developmental disorder, autosomal recessive 73, MIM# 619717
Mendeliome v0.10812 NAA20 Zornitza Stark edited their review of gene: NAA20: Changed phenotypes: Intellectual developmental disorder, autosomal recessive 73, MIM# 619717
Mendeliome v0.10812 LEMD3 Ain Roesley reviewed gene: LEMD3: Rating: GREEN; Mode of pathogenicity: None; Publications: 34098227, 33598273, 32519343, 32151766, 32151766; Phenotypes: Buschke-Ollendorff syndrome MIM#166700, Osteopoikilosis with or without melorheostosis MIM#166700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.10812 MGP Zornitza Stark Gene: mgp has been classified as Green List (High Evidence).
Mendeliome v0.10808 ABCC9 Zornitza Stark Phenotypes for gene: ABCC9 were changed from Hypertrichotic osteochondrodysplasia, MIM# 239850; Cantu syndrome; mild ID, similar facies, myopathy, cerebral white matter hyperintensities; cardiac systolic dysfunction to Hypertrichotic osteochondrodysplasia, MIM# 239850; Cantu syndrome; Intellectual disability and myopathy syndrome, MIM# 619719
Mendeliome v0.10806 ABCC9 Zornitza Stark edited their review of gene: ABCC9: Changed phenotypes: Hypertrichotic osteochondrodysplasia, MIM# 239850, Cantu syndrome, Intellectual disability and myopathy syndrome, MIM# 619719
Mendeliome v0.10806 ACP5 Zornitza Stark Phenotypes for gene: ACP5 were changed from to Spondyloenchondrodysplasia with immune dysregulation, OMIM# 607944
Mendeliome v0.10800 PIK3R5 Zornitza Stark Gene: pik3r5 has been classified as Red List (Low Evidence).
Mendeliome v0.10797 PIK3R5 Zornitza Stark Classified gene: PIK3R5 as Red List (low evidence)
Mendeliome v0.10797 PIK3R5 Zornitza Stark Gene: pik3r5 has been classified as Red List (Low Evidence).
Mendeliome v0.10796 KIF26B Zornitza Stark Gene: kif26b has been classified as Red List (Low Evidence).
Mendeliome v0.10796 KIF26B Zornitza Stark gene: KIF26B was added
gene: KIF26B was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: KIF26B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF26B were set to 30151950
Phenotypes for gene: KIF26B were set to Progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis
Review for gene: KIF26B was set to RED
Added comment: 1 report only of infant with progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis secondary to the involvement of anterior horn cells and ventral (motor) nerves. Whole exome sequencing on the trio identified a de novo KIF26B missense variant (p.Gly546Ser). Functional analysis of the variant protein in cultured cells revealed a reduction in the KIF26B protein's ability to promote cell adhesion, a defect that potentially contributes to its pathogenicity.
Sources: Expert Review
Mendeliome v0.10795 ACP5 Alison Yeung Gene: acp5 has been classified as Green List (High Evidence).
Mendeliome v0.10795 ACP5 Alison Yeung reviewed gene: ACP5: Rating: GREEN; Mode of pathogenicity: None; Publications: 26854080, 26951490, 21217755, 26789720, 2363422, 21217752; Phenotypes: spondyloenchondrodysplasia with immune dysregulation, OMIM# 607944; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10795 ACP2 Alison Yeung Gene: acp2 has been classified as Red List (Low Evidence).
Mendeliome v0.10795 ACP2 Alison Yeung Classified gene: ACP2 as Red List (low evidence)
Mendeliome v0.10795 ACP2 Alison Yeung Gene: acp2 has been classified as Red List (Low Evidence).
Mendeliome v0.10794 CHP1 Zornitza Stark Gene: chp1 has been classified as Green List (High Evidence).
Mendeliome v0.10794 CHP1 Zornitza Stark Classified gene: CHP1 as Green List (high evidence)
Mendeliome v0.10794 CHP1 Zornitza Stark Gene: chp1 has been classified as Green List (High Evidence).
Mendeliome v0.10793 CHP1 Zornitza Stark gene: CHP1 was added
gene: CHP1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: CHP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHP1 were set to 29379881; 32787936
Phenotypes for gene: CHP1 were set to Spastic ataxia 9, autosomal recessive, MIM #618438
Review for gene: CHP1 was set to GREEN
Added comment: 2 different consanguineous families with 2 affected siblings with ataxia (1 paediatric onset, 1 adult onset). 3 of the patients had cerebellar atrophy. WES identified homozygous variants in CHP1 gene in both families (K19del and Arg91Cys), which segregated with the disorder in the family.

Decreased CHP1 protein on IHC of cerebellar tissue in family with Arg91Cys variant. In vitro functional expression studies in HEK293 cells showed that the K19del mutation resulted in decreased protein expression, with normal levels of transcript, suggesting defects in protein stability. The mutant protein formed massive protein aggregates in transfected neuronal cell bodies and neurite-like projections, whereas the wildtype protein showed a more uniform distribution. The mutant protein altered CHP1 association into functional complexes and impaired membrane localization of the Na+/H+ transporter NHE1. The findings indicated that the CHP1 mutation likely causes ataxia in an NHE1-dependent manner, resembling the mechanism observed in the Chp1 vacillator mutant mouse.
Sources: Expert Review
Mendeliome v0.10792 PI4KA Zornitza Stark Phenotypes for gene: PI4KA were changed from Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, MIM# 616531; Neurodevelopmental syndrome with hypomyelinating leukodystrophy; Spastic paraplegia 84, autosomal recessive, MIM# 619621 to Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, MIM# 616531; Neurodevelopmental syndrome with hypomyelinating leukodystrophy; Spastic paraplegia 84, autosomal recessive, MIM# 619621; Gastrointestinal defects and immunodeficiency syndrome 2, MIM# 619708
Mendeliome v0.10791 PI4KA Zornitza Stark edited their review of gene: PI4KA: Changed phenotypes: Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, MIM# 616531, Neurodevelopmental syndrome with hypomyelinating leukodystrophy, Spastic paraplegia 84, autosomal recessive, MIM# 619621, Gastrointestinal defects and immunodeficiency syndrome 2, MIM# 619708
Mendeliome v0.10790 TCF12 Zornitza Stark Phenotypes for gene: TCF12 were changed from Craniosynostosis 3, MIM# 615314; Kallman syndrome to Craniosynostosis 3, MIM# 615314; Hypogonadotropic hypogonadism 26 with or without anosmia, MIM# 619718; Kallman syndrome
Mendeliome v0.10789 TCF12 Zornitza Stark edited their review of gene: TCF12: Changed phenotypes: Craniosynostosis 3, MIM# 615314, Hypogonadotropic hypogonadism 26 with or without anosmia, MIM# 619718, Kallman syndrome
Mendeliome v0.10788 CYS1 Zornitza Stark Gene: cys1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10788 CYS1 Zornitza Stark Classified gene: CYS1 as Amber List (moderate evidence)
Mendeliome v0.10788 CYS1 Zornitza Stark Gene: cys1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10787 CYS1 Zornitza Stark gene: CYS1 was added
gene: CYS1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CYS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYS1 were set to 34521872
Phenotypes for gene: CYS1 were set to Polycystic kidney disease, MONDO:0020642
Review for gene: CYS1 was set to AMBER
Added comment: Single family reported. However, extensive experimental data, including mouse model.
Sources: Literature
Mendeliome v0.10786 KIF1B Zornitza Stark Classified gene: KIF1B as Red List (low evidence)
Mendeliome v0.10786 KIF1B Zornitza Stark Gene: kif1b has been classified as Red List (Low Evidence).
Mendeliome v0.10785 CAMK2G Zornitza Stark Gene: camk2g has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10785 CAMK2G Zornitza Stark Classified gene: CAMK2G as Amber List (moderate evidence)
Mendeliome v0.10785 CAMK2G Zornitza Stark Gene: camk2g has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10783 CSNK2B Zornitza Stark Gene: csnk2b has been classified as Green List (High Evidence).
Mendeliome v0.10780 NCAPD3 Zornitza Stark Gene: ncapd3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10780 NCAPD3 Zornitza Stark Phenotypes for gene: NCAPD3 were changed from to Microcephaly 22, primary, autosomal recessive, MIM# 617984
Mendeliome v0.10777 NCAPD3 Zornitza Stark Classified gene: NCAPD3 as Amber List (moderate evidence)
Mendeliome v0.10777 NCAPD3 Zornitza Stark Gene: ncapd3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10776 NCAPD3 Zornitza Stark reviewed gene: NCAPD3: Rating: AMBER; Mode of pathogenicity: None; Publications: 27737959; Phenotypes: Microcephaly 22, primary, autosomal recessive, MIM# 617984; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10776 CYP2C8 Zornitza Stark Gene: cyp2c8 has been classified as Red List (Low Evidence).
Mendeliome v0.10775 CYP2C8 Zornitza Stark Classified gene: CYP2C8 as Red List (low evidence)
Mendeliome v0.10775 CYP2C8 Zornitza Stark Gene: cyp2c8 has been classified as Red List (Low Evidence).
Mendeliome v0.10774 HPGD Zornitza Stark Gene: hpgd has been classified as Green List (High Evidence).
Mendeliome v0.10774 HPGD Zornitza Stark Phenotypes for gene: HPGD were changed from to Hypertrophic osteoarthropathy, primary, autosomal recessive 1 MIM#259100; Cranioosteoarthropathy MIM#259100
Mendeliome v0.10771 GLMN Zornitza Stark Gene: glmn has been classified as Green List (High Evidence).
Mendeliome v0.10768 GDI1 Zornitza Stark Gene: gdi1 has been classified as Green List (High Evidence).
Mendeliome v0.10764 NECTIN1 Zornitza Stark Gene: nectin1 has been classified as Green List (High Evidence).
Mendeliome v0.10764 NECTIN1 Zornitza Stark Phenotypes for gene: NECTIN1 were changed from to Cleft lip/palate-ectodermal dysplasia syndrome MIM#225060; Zlotogora-Ogur syndrome
Mendeliome v0.10761 AGR2 Zornitza Stark Gene: agr2 has been classified as Green List (High Evidence).
Mendeliome v0.10761 AGR2 Zornitza Stark Classified gene: AGR2 as Green List (high evidence)
Mendeliome v0.10761 AGR2 Zornitza Stark Gene: agr2 has been classified as Green List (High Evidence).
Mendeliome v0.10760 AGR2 Zornitza Stark gene: AGR2 was added
gene: AGR2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: AGR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGR2 were set to 34952832
Phenotypes for gene: AGR2 were set to CF-like disorder
Review for gene: AGR2 was set to GREEN
Added comment: 13 patients from 9 families with a CF-like phenotype consisting of recurrent lower respiratory infections (13/13), failure to thrive (13/13) and chronic diarrhoea (8/13), with high morbidity and mortality. All patients had biallelic variants in AGR2, (1) two splice-site variants, (2) gene deletion and (3) three missense variants.
Sources: Literature
Mendeliome v0.10759 HPGD Ain Roesley reviewed gene: HPGD: Rating: GREEN; Mode of pathogenicity: None; Publications: 20406614, 32282352, 31878983, 29282707; Phenotypes: Hypertrophic osteoarthropathy, primary, autosomal recessive 1 MIM#259100, Cranioosteoarthropathy MIM#259100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10759 IKZF2 Zornitza Stark Gene: ikzf2 has been classified as Green List (High Evidence).
Mendeliome v0.10759 IKZF2 Zornitza Stark Classified gene: IKZF2 as Green List (high evidence)
Mendeliome v0.10759 IKZF2 Zornitza Stark Gene: ikzf2 has been classified as Green List (High Evidence).
Mendeliome v0.10758 IKZF2 Zornitza Stark gene: IKZF2 was added
gene: IKZF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IKZF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IKZF2 were set to 34920454
Phenotypes for gene: IKZF2 were set to Immune dysregulation
Review for gene: IKZF2 was set to GREEN
Added comment: Six individuals with systemic lupus erythematosus, immune thrombocytopenia or EBV-associated haemophagocytic lymphohistiocytosis reported with variants in this gene. Patients exhibited hypogammaglobulinaemia, decreased number of T-follicular helper and NK-cells.
Sources: Literature
Mendeliome v0.10757 RHBDF2 Zornitza Stark Gene: rhbdf2 has been classified as Green List (High Evidence).
Mendeliome v0.10757 RHBDF2 Zornitza Stark Phenotypes for gene: RHBDF2 were changed from to Tylosis with esophageal cancer, MIM# 148500; Immune dysregulation
Mendeliome v0.10754 RHBDF2 Zornitza Stark reviewed gene: RHBDF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22265016, 22638770, 34937930; Phenotypes: Tylosis with esophageal cancer, MIM# 148500, Immune dysregulation; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.10751 ANGPT2 Zornitza Stark edited their review of gene: ANGPT2: Added comment: Bi-allelic disease PMID 34876502: single family reported with four fetuses with hydrops fetalis homozygous for ANGPT2 NM_001147.2:c.557A>G. The consanguineous parents and surviving sibblings (a girl and a boy), were heterozygous for this variant. This variant is predicted to create a cryptic exonic splice site, resulting in a r.557_566del and nonsense-mediated mRNA decay. This prediction was supported by the lack of a transcript from this allele in the parents.; Changed publications: 32908006, 34876502; Changed phenotypes: Lymphatic malformation-10, MIM#619369, Primary lymphoedema, Hydrops; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.10751 BET1 Zornitza Stark Gene: bet1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10751 BET1 Zornitza Stark Classified gene: BET1 as Amber List (moderate evidence)
Mendeliome v0.10751 BET1 Zornitza Stark Gene: bet1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10749 NECTIN1 Ain Roesley reviewed gene: NECTIN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25913853, 10932188; Phenotypes: Cleft lip/palate-ectodermal dysplasia syndrome MIM#225060, Zlotogora-Ogur syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10749 PAX8 Zornitza Stark Gene: pax8 has been classified as Green List (High Evidence).
Mendeliome v0.10749 PAX8 Zornitza Stark Phenotypes for gene: PAX8 were changed from to Hypothyroidism, congenital, due to thyroid dysgenesis or hypoplasia, MIM# 218700; Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS)
Mendeliome v0.10746 PAX8 Zornitza Stark reviewed gene: PAX8: Rating: GREEN; Mode of pathogenicity: None; Publications: 33434492, 9590296, 11232006, 15356023, 15718293; Phenotypes: Hypothyroidism, congenital, due to thyroid dysgenesis or hypoplasia, MIM# 218700, Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10746 PAPSS2 Zornitza Stark Gene: papss2 has been classified as Green List (High Evidence).
Mendeliome v0.10742 UQCRC2 Zornitza Stark Classified gene: UQCRC2 as Green List (high evidence)
Mendeliome v0.10742 UQCRC2 Zornitza Stark Gene: uqcrc2 has been classified as Green List (High Evidence).
Mendeliome v0.10739 FMN2 Zornitza Stark Gene: fmn2 has been classified as Green List (High Evidence).
Mendeliome v0.10739 FMN2 Zornitza Stark Phenotypes for gene: FMN2 were changed from to Intellectual developmental disorder, autosomal recessive 47, MIM#616193
Mendeliome v0.10736 FMN2 Zornitza Stark reviewed gene: FMN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25480035, 32162566, 24161494; Phenotypes: Intellectual developmental disorder, autosomal recessive 47, MIM#616193; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10736 HAND1 Zornitza Stark Gene: hand1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10736 HAND1 Zornitza Stark Classified gene: HAND1 as Amber List (moderate evidence)
Mendeliome v0.10736 HAND1 Zornitza Stark Gene: hand1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10732 ILK Zornitza Stark Gene: ilk has been classified as Red List (Low Evidence).
Mendeliome v0.10729 ILK Zornitza Stark Classified gene: ILK as Red List (low evidence)
Mendeliome v0.10729 ILK Zornitza Stark Gene: ilk has been classified as Red List (Low Evidence).
Mendeliome v0.10728 ZIC4 Zornitza Stark Gene: zic4 has been classified as Red List (Low Evidence).
Mendeliome v0.10727 ZIC4 Zornitza Stark Classified gene: ZIC4 as Red List (low evidence)
Mendeliome v0.10727 ZIC4 Zornitza Stark Gene: zic4 has been classified as Red List (Low Evidence).
Mendeliome v0.10726 FKBP10 Zornitza Stark Gene: fkbp10 has been classified as Green List (High Evidence).
Mendeliome v0.10726 FKBP10 Zornitza Stark Phenotypes for gene: FKBP10 were changed from to Bruck syndrome 1, MONDO:0009806; Osteogenesis imperfecta, type XI, OMIM:610968; Osteogenesis imperfecta type 11, MONDO:0012592; Bruck syndrome 1, OMIM:259450
Mendeliome v0.10723 FKBP10 Zornitza Stark reviewed gene: FKBP10: Rating: GREEN; Mode of pathogenicity: None; Publications: 20696291, 20362275, 20839288, 21567934, 21567934, 23712425, 22718341; Phenotypes: Bruck syndrome 1, MONDO:0009806, Osteogenesis imperfecta, type XI, OMIM:610968, Osteogenesis imperfecta type 11, MONDO:0012592, Bruck syndrome 1, OMIM:259450; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10723 FAM46A Zornitza Stark Gene: fam46a has been classified as Green List (High Evidence).
Mendeliome v0.10723 FAM46A Zornitza Stark Phenotypes for gene: FAM46A were changed from to Osteogenesis imperfecta, type XVIII MIM#617952
Mendeliome v0.10720 DYNC1I1 Zornitza Stark Gene: dync1i1 has been classified as Green List (High Evidence).
Mendeliome v0.10720 DYNC1I1 Zornitza Stark Classified gene: DYNC1I1 as Green List (high evidence)
Mendeliome v0.10720 DYNC1I1 Zornitza Stark Gene: dync1i1 has been classified as Green List (High Evidence).
Mendeliome v0.10719 GATA5 Zornitza Stark Gene: gata5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10716 GATA5 Zornitza Stark Classified gene: GATA5 as Amber List (moderate evidence)
Mendeliome v0.10716 GATA5 Zornitza Stark Gene: gata5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10715 MYPN Zornitza Stark Gene: mypn has been classified as Green List (High Evidence).
Mendeliome v0.10715 MYPN Zornitza Stark Phenotypes for gene: MYPN were changed from to Nemaline myopathy 11, autosomal recessive MIM#617336 AR; cardiomyopathy MIM#615248 AD
Mendeliome v0.10712 MYL9 Zornitza Stark Classified gene: MYL9 as Green List (high evidence)
Mendeliome v0.10712 MYL9 Zornitza Stark Gene: myl9 has been classified as Green List (High Evidence).
Mendeliome v0.10711 MSTO1 Zornitza Stark Gene: msto1 has been classified as Green List (High Evidence).
Mendeliome v0.10708 MDH2 Zornitza Stark Gene: mdh2 has been classified as Green List (High Evidence).
Mendeliome v0.10705 FOXH1 Zornitza Stark Gene: foxh1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10702 FOXH1 Zornitza Stark Classified gene: FOXH1 as Amber List (moderate evidence)
Mendeliome v0.10702 FOXH1 Zornitza Stark Gene: foxh1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10701 MBOAT7 Zornitza Stark Gene: mboat7 has been classified as Green List (High Evidence).
Mendeliome v0.10698 SIN3A Zornitza Stark Marked gene: SIN3A as ready
Mendeliome v0.10698 SIN3A Zornitza Stark Gene: sin3a has been classified as Green List (High Evidence).
Mendeliome v0.10698 SIN3A Zornitza Stark Phenotypes for gene: SIN3A were changed from to Witteveen-Kolk syndrome, OMIM # 613406
Mendeliome v0.10697 SIN3A Zornitza Stark Publications for gene: SIN3A were set to
Mendeliome v0.10696 SIN3A Zornitza Stark Mode of inheritance for gene: SIN3A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10695 SIN3A Zornitza Stark reviewed gene: SIN3A: Rating: GREEN; Mode of pathogenicity: None; Publications: 27399968; Phenotypes: Witteveen-Kolk syndrome, OMIM # 613406; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10695 SYN1 Zornitza Stark Gene: syn1 has been classified as Green List (High Evidence).
Mendeliome v0.10692 DCC Zornitza Stark Gene: dcc has been classified as Green List (High Evidence).
Mendeliome v0.10692 DCC Zornitza Stark Phenotypes for gene: DCC were changed from to Mirror movements 1 and/or agenesis of the corpus callosum, OMIM #157600; Gaze palsy, familial horizontal, with progressive scoliosis, 2,OMIM # 617542
Mendeliome v0.10689 DCC Zornitza Stark reviewed gene: DCC: Rating: GREEN; Mode of pathogenicity: None; Publications: 20431009, 31697046, 21242494, 28250454, 28250456; Phenotypes: Mirror movements 1 and/or agenesis of the corpus callosum, OMIM #157600, Gaze palsy, familial horizontal, with progressive scoliosis, 2,OMIM # 617542; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.10689 SNX10 Zornitza Stark Gene: snx10 has been classified as Green List (High Evidence).
Mendeliome v0.10689 SNX10 Zornitza Stark Phenotypes for gene: SNX10 were changed from to Osteopetrosis, autosomal recessive 8, MIM# 615085
Mendeliome v0.10686 SNX10 Zornitza Stark reviewed gene: SNX10: Rating: GREEN; Mode of pathogenicity: None; Publications: 22499339, 23123320, 33678645, 32278070, 30977576, 30898715; Phenotypes: Osteopetrosis, autosomal recessive 8, MIM# 615085; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10686 MEOX1 Zornitza Stark Gene: meox1 has been classified as Green List (High Evidence).
Mendeliome v0.10686 MEOX1 Zornitza Stark Phenotypes for gene: MEOX1 were changed from to Klippel-Feil syndrome 2, OMIM:214300; Klippel-Feil syndrome 2, autosomal recessive, MONDO:0008958
Mendeliome v0.10683 MEOX1 Zornitza Stark reviewed gene: MEOX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24073994, 23290072; Phenotypes: Klippel-Feil syndrome 2, OMIM:214300, Klippel-Feil syndrome 2, autosomal recessive, MONDO:0008958; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10683 OTUD6B Zornitza Stark Gene: otud6b has been classified as Green List (High Evidence).
Mendeliome v0.10680 OTUD6B Zornitza Stark changed review comment from: IDDFSDA is a severe multisystem disorder characterized by global developmental delay, microcephaly, absent speech, hypotonia, growth retardation with prenatal onset, feeding difficulties, structural brain abnormalities, congenital malformations including congenital heart disease, and musculoskeletal features. In 2017, 12 patients from 6 unrelated families with IDDFSDA identified with 4 homozygous mutations in the OTUD6B gene (WES and Sanger, and segregated with the disorder in the families). Other cases reported since. Suitable for fetal anomalies panel.; to: IDDFSDA is a severe multisystem disorder characterized by global developmental delay, microcephaly, absent speech, hypotonia, growth retardation with prenatal onset, feeding difficulties, structural brain abnormalities, congenital malformations including congenital heart disease, and musculoskeletal features. In 2017, 12 patients from 6 unrelated families with IDDFSDA identified with 4 homozygous mutations in the OTUD6B gene (WES and Sanger, and segregated with the disorder in the families). Other cases reported since.
Mendeliome v0.10680 SERPINH1 Zornitza Stark Gene: serpinh1 has been classified as Green List (High Evidence).
Mendeliome v0.10680 SERPINH1 Zornitza Stark Phenotypes for gene: SERPINH1 were changed from to Osteogenesis imperfecta, type X, MIM# 613848; Osteogenesis imperfecta type 10, MONDO:0013459
Mendeliome v0.10677 SERPINH1 Zornitza Stark reviewed gene: SERPINH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20188343, 25510505, 31179625, 29520608; Phenotypes: Osteogenesis imperfecta, type X, MIM# 613848, Osteogenesis imperfecta type 10, MONDO:0013459; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10677 SERPINF1 Zornitza Stark Gene: serpinf1 has been classified as Green List (High Evidence).
Mendeliome v0.10677 SERPINF1 Zornitza Stark Phenotypes for gene: SERPINF1 were changed from to Osteogenesis imperfecta, type VI, MIM# 613982
Mendeliome v0.10674 SERPINF1 Zornitza Stark reviewed gene: SERPINF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21353196, 23054245; Phenotypes: Osteogenesis imperfecta, type VI, MIM# 613982; Mode of inheritance: None
Mendeliome v0.10674 PITX1 Zornitza Stark Gene: pitx1 has been classified as Green List (High Evidence).
Mendeliome v0.10674 PITX1 Zornitza Stark Phenotypes for gene: PITX1 were changed from to Brachydactyly-elbow wrist dysplasia syndrome, MONDO:0008520; Clubfoot, MONDO:0007342; Liebenberg syndrome, OMIM:186550; Clubfoot, congenital, with or without deficiency of long bones and/or mirror-image polydactyly, OMIM:119800
Mendeliome v0.10671 PITX1 Zornitza Stark reviewed gene: PITX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21775501, 22258522, 18950742; Phenotypes: Brachydactyly-elbow wrist dysplasia syndrome, MONDO:0008520, Clubfoot, MONDO:0007342, Liebenberg syndrome, OMIM:186550, Clubfoot, congenital, with or without deficiency of long bones and/or mirror-image polydactyly, OMIM:119800; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10671 ICAM1 Zornitza Stark Gene: icam1 has been classified as Red List (Low Evidence).
Mendeliome v0.10671 ICAM1 Zornitza Stark Classified gene: ICAM1 as Red List (low evidence)
Mendeliome v0.10671 ICAM1 Zornitza Stark Gene: icam1 has been classified as Red List (Low Evidence).
Mendeliome v0.10670 IRAK3 Zornitza Stark Gene: irak3 has been classified as Red List (Low Evidence).
Mendeliome v0.10670 IRAK3 Zornitza Stark Classified gene: IRAK3 as Red List (low evidence)
Mendeliome v0.10670 IRAK3 Zornitza Stark Gene: irak3 has been classified as Red List (Low Evidence).
Mendeliome v0.10669 CAPN10 Zornitza Stark Gene: capn10 has been classified as Red List (Low Evidence).
Mendeliome v0.10667 CAPN10 Zornitza Stark Classified gene: CAPN10 as Red List (low evidence)
Mendeliome v0.10667 CAPN10 Zornitza Stark Gene: capn10 has been classified as Red List (Low Evidence).
Mendeliome v0.10666 SPARC Zornitza Stark Gene: sparc has been classified as Green List (High Evidence).
Mendeliome v0.10666 SPARC Zornitza Stark Phenotypes for gene: SPARC were changed from to Osteogenesis imperfecta, type XVII, MIM# 616507
Mendeliome v0.10663 SPARC Zornitza Stark reviewed gene: SPARC: Rating: GREEN; Mode of pathogenicity: None; Publications: 26027498, 34462290; Phenotypes: Osteogenesis imperfecta, type XVII, MIM# 616507; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10663 WNT7A Seb Lunke Gene: wnt7a has been classified as Green List (High Evidence).
Mendeliome v0.10660 XYLT1 Seb Lunke Gene: xylt1 has been classified as Green List (High Evidence).
Mendeliome v0.10659 ZIC1 Seb Lunke Phenotypes for gene: ZIC1 were changed from to Structural brain anomalies with impaired intellectual development and craniosynostosis, OMIM#618736
Mendeliome v0.10658 ZIC1 Seb Lunke Gene: zic1 has been classified as Green List (High Evidence).
Mendeliome v0.10656 ZIC1 Seb Lunke reviewed gene: ZIC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26340333, 30391508; Phenotypes: Structural brain anomalies with impaired intellectual development and craniosynostosis, OMIM#618736; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10656 STRADA Zornitza Stark Gene: strada has been classified as Green List (High Evidence).
Mendeliome v0.10652 YAP1 Zornitza Stark Gene: yap1 has been classified as Green List (High Evidence).
Mendeliome v0.10649 WDR73 Zornitza Stark Gene: wdr73 has been classified as Green List (High Evidence).
Mendeliome v0.10646 USP18 Zornitza Stark Gene: usp18 has been classified as Green List (High Evidence).
Mendeliome v0.10643 FAM46A Belinda Chong reviewed gene: FAM46A: Rating: GREEN; Mode of pathogenicity: None; Publications: 29358272; Phenotypes: Osteogenesis imperfecta, type XVIII MIM#617952; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10643 TBX22 Zornitza Stark Gene: tbx22 has been classified as Green List (High Evidence).
Mendeliome v0.10643 TBX22 Zornitza Stark Phenotypes for gene: TBX22 were changed from to Cleft palate with ankyloglossia, MIM# 303400; Abruzzo-Erickson syndrome, MIM# 302905
Mendeliome v0.10640 TBX22 Zornitza Stark reviewed gene: TBX22: Rating: GREEN; Mode of pathogenicity: None; Publications: 11559848, 12374769, 14729838, 17868388, 22784330, 22784330; Phenotypes: Cleft palate with ankyloglossia, MIM# 303400, Abruzzo-Erickson syndrome, MIM# 302905; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.10640 MYPN Ain Roesley reviewed gene: MYPN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Nemaline myopathy 11, autosomal recessive MIM#617336 AR, cardiomyopathy MIM#615248 AD; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10640 MYL9 Ain Roesley edited their review of gene: MYL9: Added comment: PMID:32621347;
3rd family with non-consanguineous parents and 3 TOPs. 2 were genotyped and found to be hom for the same deletion of exon 4 as reported by PMID: 29453416

Possibly 4th proband in PMID: 33264186 but specifics including genotype were lacking and overlapping institute/hospital as PMID: 33031641; Changed publications: 32621347, 33264186
Mendeliome v0.10640 MYL9 Ain Roesley reviewed gene: MYL9: Rating: GREEN; Mode of pathogenicity: None; Publications: 33264186; Phenotypes: Megacystis-microcolon-intestinal hypoperistalsis syndrome, MIM#619365; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10638 ANAPC7 Zornitza Stark Gene: anapc7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10638 ANAPC7 Zornitza Stark Classified gene: ANAPC7 as Amber List (moderate evidence)
Mendeliome v0.10638 ANAPC7 Zornitza Stark Gene: anapc7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10637 ANAPC7 Zornitza Stark gene: ANAPC7 was added
gene: ANAPC7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ANAPC7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ANAPC7 were set to 34942119
Phenotypes for gene: ANAPC7 were set to Ferguson-Bonni neurodevelopmental syndrome, MIM# 619699
Review for gene: ANAPC7 was set to AMBER
Added comment: 11 individuals of Amish heritage reported homozygous for an intragenic deletion. Clinical features included ID, hypotonia, deafness in 5, relatively small head size (but microcephaly only in 1), and occasional congenital anomalies.

Supportive mouse model.

Amber rating in light of this being a founder variant.
Sources: Literature
Mendeliome v0.10636 DLX5 Zornitza Stark Gene: dlx5 has been classified as Green List (High Evidence).
Mendeliome v0.10633 DLX5 Zornitza Stark changed review comment from: A homozygous missense mutation (Q178P) was identified in 2 affected sisters from a consanguineous Yemeni family with split-hand/foot malformation and hearing loss, who had no detectable chromosomal aberration, Shamseldin et al. (2012).

A heterozygosity missense mutation (Q186H) was identified in a 31-year-old Chinese woman with SHFM, Wang et al. (2014).
A heterozygosity nonsense mutationIn (E39X) was identified in the probands from 2 unrelated Polish families with isolated SHFM, Sowinska-Seidler et al. (2014).

Animal model evidence - mouse; to: A homozygous missense mutation (Q178P) was identified in 2 affected sisters from a consanguineous Yemeni family with split-hand/foot malformation and hearing loss, who had no detectable chromosomal aberration, Shamseldin et al. (2012).

A heterozygosity missense mutation (Q186H) was identified in a 31-year-old Chinese woman with SHFM, Wang et al. (2014).
A heterozygosity nonsense mutationIn (E39X) was identified in the probands from 2 unrelated Polish families with isolated SHFM, Sowinska-Seidler et al. (2014).

Animal model evidence - mouse

Green for mono-allelic, Amber for bi-allelic.
Mendeliome v0.10632 GUCY2C Zornitza Stark Gene: gucy2c has been classified as Green List (High Evidence).
Mendeliome v0.10629 GPC3 Zornitza Stark Gene: gpc3 has been classified as Green List (High Evidence).
Mendeliome v0.10629 GPC3 Zornitza Stark Phenotypes for gene: GPC3 were changed from to Simpson-Golabi-Behmel syndrome, type 1, MIM# 312870
Mendeliome v0.10627 GPC3 Zornitza Stark reviewed gene: GPC3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Simpson-Golabi-Behmel syndrome, type 1, MIM# 312870; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.10627 PDCD10 Zornitza Stark Gene: pdcd10 has been classified as Green List (High Evidence).
Mendeliome v0.10624 LGI4 Zornitza Stark Gene: lgi4 has been classified as Green List (High Evidence).
Mendeliome v0.10624 LGI4 Zornitza Stark Phenotypes for gene: LGI4 were changed from to Arthrogryposis multiplex congenita, neurogenic, with myelin defect, MIM#617468
Mendeliome v0.10621 LGI4 Zornitza Stark reviewed gene: LGI4: Rating: GREEN; Mode of pathogenicity: None; Publications: 28318499, 34288120; Phenotypes: Arthrogryposis multiplex congenita, neurogenic, with myelin defect, MIM#617468; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10621 LFNG Zornitza Stark Gene: lfng has been classified as Green List (High Evidence).
Mendeliome v0.10621 LFNG Zornitza Stark Phenotypes for gene: LFNG were changed from to Spondylocostal dysostosis 3, autosomal recessive, MIM# 609813
Mendeliome v0.10618 LFNG Zornitza Stark reviewed gene: LFNG: Rating: GREEN; Mode of pathogenicity: None; Publications: 9690472, 16385447, 30531807, 9690473; Phenotypes: Spondylocostal dysostosis 3, autosomal recessive, MIM# 609813; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10618 SLC39A7 Zornitza Stark Phenotypes for gene: SLC39A7 were changed from Antibody deficiency; early onset infections; blistering dermatosis; failure to thrive; thrombocytopaenia to Agammaglobulinaemia 9, autosomal recessive, MIM# 619693; Antibody deficiency; early onset infections; blistering dermatosis; failure to thrive; thrombocytopaenia
Mendeliome v0.10617 SLC39A7 Zornitza Stark edited their review of gene: SLC39A7: Changed phenotypes: Agammaglobulinemia 9, autosomal recessive, MIM# 619693, Antibody deficiency, early onset infections, blistering dermatosis, failure to thrive, thrombocytopaenia
Mendeliome v0.10617 RNF220 Zornitza Stark Phenotypes for gene: RNF220 were changed from Leukodystrophy; CNS hypomyelination; Ataxia; Intellectual disability; Sensorineural hearing impairment; Elevated hepatic transaminases; Hepatic fibrosis; Dilated cardiomyopathy; Spastic paraplegia; Dysarthria; Abnormality of the corpus callosum to Leukodystrophy, hypomyelinating, 23, with ataxia, deafness, liver dysfunction, and dilated cardiomyopathy, MIM# 619688; Leukodystrophy; CNS hypomyelination; Ataxia; Intellectual disability; Sensorineural hearing impairment; Elevated hepatic transaminases; Hepatic fibrosis; Dilated cardiomyopathy; Spastic paraplegia; Dysarthria; Abnormality of the corpus callosum
Mendeliome v0.10616 RNF220 Zornitza Stark edited their review of gene: RNF220: Changed phenotypes: Leukodystrophy, hypomyelinating, 23, with ataxia, deafness, liver dysfunction, and dilated cardiomyopathy, MIM# 619688, Leukodystrophy, CNS hypomyelination, Ataxia, Intellectual disability, Sensorineural hearing impairment, Elevated hepatic transaminases, Hepatic fibrosis, Dilated cardiomyopathy, Spastic paraplegia, Dysarthria, Abnormality of the corpus callosum
Mendeliome v0.10616 SLC33A1 Zornitza Stark Gene: slc33a1 has been classified as Green List (High Evidence).
Mendeliome v0.10613 ITPKC Zornitza Stark Gene: itpkc has been classified as Red List (Low Evidence).
Mendeliome v0.10612 ITPKC Zornitza Stark Classified gene: ITPKC as Red List (low evidence)
Mendeliome v0.10612 ITPKC Zornitza Stark Gene: itpkc has been classified as Red List (Low Evidence).
Mendeliome v0.10611 MAMLD1 Zornitza Stark Gene: mamld1 has been classified as Green List (High Evidence).
Mendeliome v0.10608 INPP5K Zornitza Stark Gene: inpp5k has been classified as Green List (High Evidence).
Mendeliome v0.10605 IGFBP7 Zornitza Stark Gene: igfbp7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10605 IGFBP7 Zornitza Stark Phenotypes for gene: IGFBP7 were changed from to Retinal arterial macroaneurysm with supravalvular pulmonic stenosis MIM#614224
Mendeliome v0.10602 IGFBP7 Zornitza Stark Classified gene: IGFBP7 as Amber List (moderate evidence)
Mendeliome v0.10602 IGFBP7 Zornitza Stark Gene: igfbp7 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10601 IGFBP7 Zornitza Stark reviewed gene: IGFBP7: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Retinal arterial macroaneurysm with supravalvular pulmonic stenosis MIM#614224; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10600 KISS1R Zornitza Stark Gene: kiss1r has been classified as Green List (High Evidence).
Mendeliome v0.10597 IDH1 Zornitza Stark Gene: idh1 has been classified as Green List (High Evidence).
Mendeliome v0.10593 HNRNPH2 Zornitza Stark Gene: hnrnph2 has been classified as Green List (High Evidence).
Mendeliome v0.10590 KCNT1 Zornitza Stark Gene: kcnt1 has been classified as Green List (High Evidence).
Mendeliome v0.10587 ITPKC Ain Roesley changed review comment from: Currently no mendelian gene-disease assocation. Best known for polymorphisms associated with Kawasaki disease susceptibility.

KO mouse models looking at protein expression and effect on multiciliary beating frequency and spermatozoa, no significant defects in both; to: Currently no mendelian gene-disease association. Best known for polymorphisms associated with Kawasaki disease susceptibility.

KO mouse models looking at tissue protein expression and effect on multiciliary beating frequency and spermatozoa, no significant defects in both
Mendeliome v0.10586 PRKAR1B Zornitza Stark Phenotypes for gene: PRKAR1B were changed from Global developmental delay; Intellectual disability; Autism; Attention deficit hyperactivity disorder; Aggressive behavior; Abnormality of movement; Upslanted palpebral fissure to Marbach-Schaaf neurodevelopmental syndrome MIM#619680; Global developmental delay; Intellectual disability; Autism; Attention deficit hyperactivity disorder; Aggressive behavior; Abnormality of movement; Upslanted palpebral fissure
Mendeliome v0.10577 TLR8 Zornitza Stark edited their review of gene: TLR8: Added comment: PMID 34981838: Monozygotic male twins, hemizygous for the G572V (maternally inherited), who suffer from severe autoimmune haemolytic anemia (AIHA) worsening with infections, and autoinflammation presenting as fevers, enteritis, arthritis and CNS vasculitis. Functional showed variant causes impaired stability of the TLR8 protein, cross-reactivity to TLR7 ligands and reduced ability of TLR8 to attenuate TLR7 signaling.; Changed publications: 33512449, 34981838; Changed phenotypes: Immunodeficiency, bone marrow failure, Autoinflammatory syndrome MONDO:0019751
Mendeliome v0.10577 MARS Zornitza Stark Phenotypes for gene: MARS were changed from Interstitial lung and liver disease, MIM#615486; Charcot-Marie-Tooth disease, axonal, type 2U, MIM# 616280; Trichothiodystrophy, MONDO:0018053 to Interstitial lung and liver disease, MIM#615486; Charcot-Marie-Tooth disease, axonal, type 2U, MIM# 616280; Trichothiodystrophy 9, nonphotosensitive, MIM# 619692
Mendeliome v0.10576 AARS Zornitza Stark Phenotypes for gene: AARS were changed from Epileptic encephalopathy, early infantile, 29, MIM# 616339; Charcot-Marie-Tooth disease, axonal, type 2N, MIM# 613287; trichothiodystrophy, MONDO:0018053; Leukoencephalopathy, hereditary diffuse, with spheroids 2, MIM# 619661 to Epileptic encephalopathy, early infantile, 29, MIM# 616339; Charcot-Marie-Tooth disease, axonal, type 2N, MIM# 613287; Spastic paraplegia 85, autosomal recessive, MIM# 619686; Ataxia, sensory, 1, autosomal dominant, MIM# 608984; Leukoencephalopathy, hereditary diffuse, with spheroids 2, MIM# 619661
Mendeliome v0.10575 RNF170 Zornitza Stark Gene: rnf170 has been classified as Green List (High Evidence).
Mendeliome v0.10575 RNF170 Zornitza Stark Phenotypes for gene: RNF170 were changed from to Spastic paraplegia 85, autosomal recessive, MIM# 619686; Ataxia, sensory, 1, autosomal dominant, MIM# 608984
Mendeliome v0.10573 RNF170 Zornitza Stark reviewed gene: RNF170: Rating: GREEN; Mode of pathogenicity: None; Publications: 31636353, 21115467, 32943585; Phenotypes: Spastic paraplegia 85, autosomal recessive, MIM# 619686, Ataxia, sensory, 1, autosomal dominant, MIM# 608984; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.10573 IGFBP7 Ain Roesley reviewed gene: IGFBP7: Rating: RED; Mode of pathogenicity: None; Publications: 34519236, 31730227, 32429784; Phenotypes: Retinal arterial macroaneurysm with supravalvular pulmonic stenosis MIM#614224; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10573 VPS50 Zornitza Stark Phenotypes for gene: VPS50 were changed from Neonatal cholestatic liver disease; Failure to thrive; Profound global developmental delay; Postnatal microcephaly; Seizures; Abnormality of the corpus callosum to Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis , MIM#619685; Neonatal cholestatic liver disease; Failure to thrive; Profound global developmental delay; Postnatal microcephaly; Seizures; Abnormality of the corpus callosum
Mendeliome v0.10572 VPS50 Zornitza Stark edited their review of gene: VPS50: Changed phenotypes: Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis , MIM#619685, Neonatal cholestatic liver disease, Failure to thrive, Profound global developmental delay, Postnatal microcephaly, Seizures, Abnormality of the corpus callosum
Mendeliome v0.10570 AARS Zornitza Stark edited their review of gene: AARS: Added comment: PMID 31775912: single multigenerational family with leukoencephalopathy segregating AARS1 variant.; Changed publications: 28493438, 25817015, 20045102, 22009580, 22206013, 30373780, 26032230, 31775912; Changed phenotypes: Epileptic encephalopathy, early infantile, 29, MIM# 616339, Charcot-Marie-Tooth disease, axonal, type 2N, MIM# 613287, Leukoencephalopathy, hereditary diffuse, with spheroids 2, MIM# 619661
Mendeliome v0.10570 CRACR2A Zornitza Stark Added comment: Comment when marking as ready: Single individual.
Mendeliome v0.10570 CRACR2A Zornitza Stark Gene: cracr2a has been classified as Red List (Low Evidence).
Mendeliome v0.10567 PRDM13 Zornitza Stark Phenotypes for gene: PRDM13 were changed from Retinal dystrophy; Chorioretinal atrophy, progressive bifocal, MIM# 600790 to Retinal dystrophy; Chorioretinal atrophy, progressive bifocal, MIM# 600790; intellectual disability, MONDO:0001071, PRDM13-associated; ataxia with cerebellar hypoplasia, MONDO:0016054, PRDM13-associated; congenital hypogonadotropic hypogonadism, MONDO:0015770
Mendeliome v0.10564 PRDM13 Zornitza Stark Added comment: Comment when marking as ready: Bi-allelic variants: Recessive disease causing ID and DSD described in three reportedly unrelated families (2 consanguineous), but all are from Malta, and all share the same 13bp deletion spanning an exon-intron boundary. Mouse KO is embryonically lethal, and tissue specific KO failed to replicate many of the patients phenotypes, other than hypoplasia of the cerebellar vermis and hemispheres at P21.
Mendeliome v0.10564 PRDM13 Zornitza Stark Gene: prdm13 has been classified as Green List (High Evidence).
Mendeliome v0.10563 ATP5A1 Naomi Baker edited their review of gene: ATP5A1: Added comment: PMID: 34954817 reports three individuals with de novo monoallelic missense variants. One of these is the recurrent p.(Arg207His) variant while the other two variants are different substitutions. The three patients presented with a variable phenotypes: (1) a 14-year-old girl who presented during the first few months of life with developmental delay, failure-to-thrive, and lactic acidosis. She recovered and had no persistent neurologic phenotype; (2) a 17-year-old boy with psychomotor delay, intellectual disability, ataxia, spastic paraparesis, and dystonia; (3) a 12-year-old girl with psychomotor retardation, spastic tetraparesis, generalized dystonia, absent speech, swallowing problems, and increased blood lactate concentrations. Enzymatic investigations of muscle tissue from patient 1 showed a decrease in ATPase activity.; Changed publications: PMID: 34954817
Mendeliome v0.10563 ATP5G3 Seb Lunke Gene: atp5g3 has been classified as Green List (High Evidence).
Mendeliome v0.10562 ATP5G3 Seb Lunke Classified gene: ATP5G3 as Green List (high evidence)
Mendeliome v0.10562 ATP5G3 Seb Lunke Gene: atp5g3 has been classified as Green List (High Evidence).
Mendeliome v0.10561 ATP5G3 Naomi Baker edited their review of gene: ATP5G3: Added comment: Note that HGNC approved gene name is ATP5MC3.

PMID: 34636445 reports a missense variant identified in a large single-family pedigree with dystonia and spastic paraplegia. The variant was identified via exome sequencing of the proband and a distant cousin, focussing on variants within the previously determined linkage region. The identical missense variant was also identified in a patient with childhood onset dystonic syndrome and was shown to be de novo. Functional studies of fibroblast cell lines from affected father (HSP) and proband of large family demonstrated decreased complex V function. A drosophila model containing the missense variant had reduced mobility and reduced complex V activity.

PMID: 34954817 reports de novo monoallelic missense variants in three individuals, however one of these individuals was reported in above paper. The other two patients were: (1) a-15-year-old girl with milestone delay, pyramidal signs, and generalized dystonia with prominent upper-body involvement, and (2) a 6-year-old boy with delayed psychomotor development, lower-extremity spasticity, and elevated blood lactate levels; Changed rating: GREEN; Changed publications: PMID: 34636445, 34954817
Mendeliome v0.10561 PRDM13 Seb Lunke reviewed gene: PRDM13: Rating: AMBER; Mode of pathogenicity: None; Publications: 34730112; Phenotypes: intellectual disability, MONDO:0001071, PRDM13-associated, ataxia with cerebellar hypoplasia, MONDO:MONDO:0016054. PRDM13-associated, congenital hypogonadotropic hypogonadism, MONDO:0015770 Edit; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10561 CCND2 Alison Yeung Gene: ccnd2 has been classified as Green List (High Evidence).
Mendeliome v0.10559 IFT140 Alison Yeung Phenotypes for gene: IFT140 were changed from Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920; MONDO:0009964; Retinitis pigmentosa 80, MIM# 617781 to Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920; MONDO:0009964; Retinitis pigmentosa 80, MIM# 617781; Cystic Kidney Disease, MONDO: 0002473
Mendeliome v0.10558 PPIA Seb Lunke Gene: ppia has been classified as Red List (Low Evidence).
Mendeliome v0.10558 ATP5G3 Naomi Baker gene: ATP5G3 was added
gene: ATP5G3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATP5G3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP5G3 were set to PMID: 34636445
Phenotypes for gene: ATP5G3 were set to Dystonia, early-onset, and/or spastic paraplegia, MIM#619681
Review for gene: ATP5G3 was set to AMBER
Added comment: Note that new gene name is ATP5MC3.

Paper reports the same missense variant identified in a large single-family pedigree with dystonia and spastic paraplegia, and also de novo in a patient with childhood onset dystonic syndrome. Drosophila model with missense variant also studied. Functional studies of fibroblast cells lines from affected father and proband demonstrated decreased complex V function.
Sources: Literature
Mendeliome v0.10558 RPL10L Alison Yeung Gene: rpl10l has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10558 PPIA Seb Lunke Classified gene: PPIA as Red List (low evidence)
Mendeliome v0.10558 PPIA Seb Lunke Gene: ppia has been classified as Red List (Low Evidence).
Mendeliome v0.10558 RPL10L Alison Yeung Classified gene: RPL10L as Amber List (moderate evidence)
Mendeliome v0.10558 RPL10L Alison Yeung Added comment: Comment on list classification: heterozygous variants in three unrelated patients presenting with azoospermia. Given the common phenotype, need a few more cases to convert to green list.
Mendeliome v0.10558 RPL10L Alison Yeung Gene: rpl10l has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10557 DNHD1 Seb Lunke Gene: dnhd1 has been classified as Green List (High Evidence).
Mendeliome v0.10557 DNHD1 Seb Lunke Classified gene: DNHD1 as Green List (high evidence)
Mendeliome v0.10557 DNHD1 Seb Lunke Gene: dnhd1 has been classified as Green List (High Evidence).
Mendeliome v0.10556 NAA10 Ain Roesley edited their review of gene: NAA10: Added comment: For Ogden association:
lethal X-linked. 9 males from 3 families with recurrent Ser37Pro
All presenting the distinctive and recognizable phenotype, which includes mostly postnatal growth retardation, global severe developmental delay, characteristic craniofacial features, and structural cardiac anomalies and/or arrhythmias

For non-lethal syndromic ID:
reported in 10 males and (mostly de novo) in 37 females
variants causing this are missense located along the protein and 1 truncating

For syndromic microopththamia: variants are in the UTR; Changed mode of inheritance: Other
Mendeliome v0.10556 SLC35F1 Seb Lunke Gene: slc35f1 has been classified as Red List (Low Evidence).
Mendeliome v0.10555 SLC35F1 Seb Lunke Classified gene: SLC35F1 as Red List (low evidence)
Mendeliome v0.10555 SLC35F1 Seb Lunke Gene: slc35f1 has been classified as Red List (Low Evidence).
Mendeliome v0.10554 MYH1 Seb Lunke Gene: myh1 has been classified as Red List (Low Evidence).
Mendeliome v0.10554 CRACR2A Alison Yeung Gene: cracr2a has been classified as Red List (Low Evidence).
Mendeliome v0.10554 PPIA Naomi Baker gene: PPIA was added
gene: PPIA was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PPIA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPIA were set to PMID: 34972208
Phenotypes for gene: PPIA were set to amyotrophic lateral sclerosis, MONDO:0004976
Review for gene: PPIA was set to RED
Added comment: Paper characterizes a knockout mouse model that recapitulates key features of ALS-FTD. Also identified a heterozygous missense variant in one patient with sporadic amyotrophic lateral sclerosis. Functional studies of the missense variant suggest loss-of-function.
Sources: Literature
Mendeliome v0.10554 MYH1 Seb Lunke Phenotypes for gene: MYH1 were changed from recurrent rhabdomyolysis to rhabdomyolysis, MONDO:0005290
Mendeliome v0.10554 CRACR2A Alison Yeung Classified gene: CRACR2A as Red List (low evidence)
Mendeliome v0.10554 CRACR2A Alison Yeung Gene: cracr2a has been classified as Red List (Low Evidence).
Mendeliome v0.10553 DNHD1 Daniel Flanagan gene: DNHD1 was added
gene: DNHD1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DNHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNHD1 were set to 34932939
Phenotypes for gene: DNHD1 were set to Male infertility due to sperm motility disorder (MONDO:0018395)
Review for gene: DNHD1 was set to GREEN
Added comment: Biallelic DNHD1 variants identified in 8 unrelated probands with asthenoteratozoospermia, reduced sperm motility and abnormal sperm morphology. DNHD1 knockout mice were infertile and had significantly reduced sperm concentration and motility rates, consistent with human individuals.
Sources: Literature
Mendeliome v0.10553 MYH1 Seb Lunke Classified gene: MYH1 as Red List (low evidence)
Mendeliome v0.10553 MYH1 Seb Lunke Gene: myh1 has been classified as Red List (Low Evidence).
Mendeliome v0.10552 PI4KA Paul De Fazio reviewed gene: PI4KA: Rating: GREEN; Mode of pathogenicity: None; Publications: 34415310; Phenotypes: Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis MIM#616531, Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis MONDO:0014679; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10552 IFT140 Alison Yeung reviewed gene: IFT140: Rating: GREEN; Mode of pathogenicity: None; Publications: 34890546, 22503633, 23418020, 28288023, 28724397, 26216056, 26968735; Phenotypes: Short-rib thoracic dysplasia 9 with or without polydactyly, MIM# 266920, Retinitis pigmentosa 80, MIM# 617781, Cystic Kidney Disease, MONDO# 0002473; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.10552 MYH1 Ain Roesley gene: MYH1 was added
gene: MYH1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MYH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYH1 were set to 33755318
Phenotypes for gene: MYH1 were set to recurrent rhabdomyolysis
Penetrance for gene: MYH1 were set to unknown
Review for gene: MYH1 was set to RED
gene: MYH1 was marked as current diagnostic
Added comment: 18 yr old male from a consaguineous family.
WES was performed and a homozygous c.1295A>C:p.K432T was found. Only 1 het in gnomad v2 and v3.
no protein functional work was done
Sources: Literature
Mendeliome v0.10551 PAK2 Zornitza Stark Gene: pak2 has been classified as Red List (Low Evidence).
Mendeliome v0.10551 PAK2 Zornitza Stark Classified gene: PAK2 as Red List (low evidence)
Mendeliome v0.10551 PAK2 Zornitza Stark Gene: pak2 has been classified as Red List (Low Evidence).
Mendeliome v0.10550 PAK2 Arina Puzriakova gene: PAK2 was added
gene: PAK2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PAK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PAK2 were set to 33693784
Phenotypes for gene: PAK2 were set to Knobloch 2 syndrome
Review for gene: PAK2 was set to RED
Added comment: Antonarakis et al., 2021 (PMID: 33693784) reported two affected siblings from a non-consanguineous New Zealand family. Both had retinal detachment and interstitial parenchymal pulmonary changes on chest X-rays, but only one child had additional significant features such as cataract, posterior encephalocele, severe DD/ID with ASD, and epilepsy. WES revealed a heterozygous PAK2 variant (c.1303 G>A, p.Glu435Lys) in both individuals that apparently occurred de novo indicating parental germ-line mosaicism; however, mosaicism could not be detected by deep sequencing of blood parental DNA. Functional studies showed that the variant, located in the kinase domain, results in a partial loss of the kinase activity.
Sources: Literature
Mendeliome v0.10549 TBX2 Zornitza Stark Gene: tbx2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10546 TBX2 Zornitza Stark Classified gene: TBX2 as Amber List (moderate evidence)
Mendeliome v0.10546 TBX2 Zornitza Stark Gene: tbx2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10545 SLC27A4 Zornitza Stark Gene: slc27a4 has been classified as Green List (High Evidence).
Mendeliome v0.10545 SLC27A4 Zornitza Stark Phenotypes for gene: SLC27A4 were changed from to Ichthyosis prematurity syndrome, MIM#608649
Mendeliome v0.10542 TBX2 Krithika Murali changed review comment from: Liu et al. (2018) reported 4 affected individuals from 2 unrelated families with congenital cardiac defects (ASD, PDA, double outlet right ventricle, pulmonary stenosis), skeletal abnormalities (camptodactyly, congenital fusion thoracic spine, hemivertebrae ).Thymus aplasia/hypoplasia, cleft palate also noted. Other associated features include - facial dysmorphisms, variable developmental delay, and endocrine system disorders (e.g. autoimmune hypothyroidism, hypoparathyroidism).

PMID23727221 and PMID30223900 - TBX2 gene and TBX2 gene promoter sequencing in congenital heart disease cohorts versus controls - not enough supportive evidence for variant pathogenicity, including no segregation data. Variants prevalent in population databases also included as likely pathogenic.

PMID 20635360 - de novo dup 17q23.2 encompassing TBX2 gene in boy with cognitive impairment, multiple congenital defects and prenatal onset growth restriction. Part of BCAS3 gene (associated with autosomal recessive Hengel-Maroofian-Schols syndrome) also included in duplication. No supportive evidence of TBX2 gene function impairment in the patient provided.; to: Liu et al. (2018) reported 4 affected individuals from 2 unrelated families with congenital cardiac defects (ASD, PDA, double outlet right ventricle, pulmonary stenosis), skeletal abnormalities (camptodactyly, congenital fusion thoracic spine, hemivertebrae ).Thymus aplasia/hypoplasia, cleft palate also noted. Other associated features include - facial dysmorphisms, variable developmental delay, and endocrine system disorders (e.g. autoimmune hypothyroidism, hypoparathyroidism).

PMID23727221 and PMID30223900 - TBX2 gene and TBX2 gene promoter sequencing in congenital heart disease cohorts versus controls - not enough supportive evidence for variant pathogenicity, including no segregation data. Variants prevalent in population databases also included as potentially disease causing.

PMID 20635360 - de novo dup 17q23.2 encompassing TBX2 gene in boy with cognitive impairment, multiple congenital defects and prenatal onset growth restriction. Part of BCAS3 gene (associated with autosomal recessive Hengel-Maroofian-Schols syndrome) also included in duplication. No supportive evidence of TBX2 gene function impairment in the patient provided.
Mendeliome v0.10542 SLC27A4 Seb Lunke reviewed gene: SLC27A4: Rating: GREEN; Mode of pathogenicity: None; Publications: 21856041, 19631310, 31168818; Phenotypes: Ichthyosis prematurity syndrome, MIM#608649; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10542 SMAD6 Zornitza Stark Gene: smad6 has been classified as Green List (High Evidence).
Mendeliome v0.10542 SMAD6 Zornitza Stark Phenotypes for gene: SMAD6 were changed from to {Radioulnar synostosis, nonsyndromic} 179300; {Craniosynostosis 7, susceptibility to} 617439; Aortic valve disease 2 MIM# 614823
Mendeliome v0.10539 SMAD6 Zornitza Stark edited their review of gene: SMAD6: Changed phenotypes: {Radioulnar synostosis, nonsyndromic} 179300, {Craniosynostosis 7, susceptibility to} 617439, Aortic valve disease 2 MIM# 614823
Mendeliome v0.10539 SMAD6 Zornitza Stark reviewed gene: SMAD6: Rating: GREEN; Mode of pathogenicity: None; Publications: 31138930, 32499606, 27606499, 22275001, 28659821, 30963242, 30848080, 30796334; Phenotypes: {Radioulnar synostosis, nonsyndromic} 179300, {Craniosynostosis 7, susceptibility to} 617439; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10539 SLC26A2 Seb Lunke Gene: slc26a2 has been classified as Green List (High Evidence).
Mendeliome v0.10539 SLC26A2 Seb Lunke Phenotypes for gene: SLC26A2 were changed from to Achondrogenesis 1B, MIM#600972; Atelosteogenesis, type II, MIM#256050; Diastrophic dysplasia, MIM#222600; Epiphyseal dysplasia, multiple, 4, MIM#226900
Mendeliome v0.10536 SLC26A2 Seb Lunke reviewed gene: SLC26A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301483, 20301689; Phenotypes: Achondrogenesis 1B, MIM#600972, Atelosteogenesis, type II, MIM#256050, Diastrophic dysplasia, MIM#222600, Epiphyseal dysplasia, multiple, 4, MIM#226900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10536 TUBB4A Zornitza Stark Gene: tubb4a has been classified as Green List (High Evidence).
Mendeliome v0.10536 TUBB4A Zornitza Stark Phenotypes for gene: TUBB4A were changed from to Dystonia 4, torsion, autosomal dominant, OMIM #128101; Leukodystrophy, hypomyelinating, 6, OMIM # 612438
Mendeliome v0.10533 TUBB4A Zornitza Stark reviewed gene: TUBB4A: Rating: GREEN; Mode of pathogenicity: None; Publications: 24850488, 23582646, 23424103, 23595291, 33084096, 32943487; Phenotypes: Dystonia 4, torsion, autosomal dominant, OMIM #128101, Leukodystrophy, hypomyelinating, 6, OMIM # 612438; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10533 TWIST1 Zornitza Stark Gene: twist1 has been classified as Green List (High Evidence).
Mendeliome v0.10533 TWIST1 Zornitza Stark Phenotypes for gene: TWIST1 were changed from to Craniosynostosis 1, MIM# 123100; Saethre-Chotzen syndrome with or without eyelid anomalies, MIM# 101400; Sweeny-Cox syndrome, MIM# 617746; Robinow-Sorauf syndrome, MIM# 180750
Mendeliome v0.10530 TWIST1 Zornitza Stark reviewed gene: TWIST1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17343269, 9585583, 12116251, 31299755, 30040876; Phenotypes: Craniosynostosis 1, MIM# 123100, Saethre-Chotzen syndrome with or without eyelid anomalies, MIM# 101400, Sweeny-Cox syndrome, MIM# 617746, Robinow-Sorauf syndrome, MIM# 180750; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10530 SLC25A24 Seb Lunke Gene: slc25a24 has been classified as Green List (High Evidence).
Mendeliome v0.10523 MBNL1 Zornitza Stark Gene: mbnl1 has been classified as Red List (Low Evidence).
Mendeliome v0.10523 MBNL1 Zornitza Stark Classified gene: MBNL1 as Red List (low evidence)
Mendeliome v0.10523 MBNL1 Zornitza Stark Gene: mbnl1 has been classified as Red List (Low Evidence).
Mendeliome v0.10522 PDK3 Zornitza Stark Gene: pdk3 has been classified as Green List (High Evidence).
Mendeliome v0.10519 PRDM9 Zornitza Stark Gene: prdm9 has been classified as Green List (High Evidence).
Mendeliome v0.10519 PRDM9 Zornitza Stark Classified gene: PRDM9 as Green List (high evidence)
Mendeliome v0.10519 PRDM9 Zornitza Stark Gene: prdm9 has been classified as Green List (High Evidence).
Mendeliome v0.10518 PRDM9 Zornitza Stark gene: PRDM9 was added
gene: PRDM9 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRDM9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRDM9 were set to 34257419
Phenotypes for gene: PRDM9 were set to Inherited primary ovarian failure MONDO:0019852
Review for gene: PRDM9 was set to GREEN
Added comment: The primordial follicle pool is determined by the meiosis process, which is initiated by programmed DNA double strand breaks (DSB) and homologous recombination. PRDM9 is a meiosis-specific histone H3 methyltransferase and a major determinant of meiotic recombination hotspots in mammals. 3 pathogenic heterozygous variants in PRDM9 identified in 4 patients with POI. Functional studies showed the variants in PRDM9 impaired its methyltransferase activity. Prdm9+/- mice were subfertile, and showed increased percentage of germ cells at abnormal pachytene stage with decreased number of PRDM9-dependent DSBs and insufficient recombination.
Sources: Literature
Mendeliome v0.10517 DZIP1L Zornitza Stark Gene: dzip1l has been classified as Green List (High Evidence).
Mendeliome v0.10514 PPA2 Zornitza Stark Gene: ppa2 has been classified as Green List (High Evidence).
Mendeliome v0.10511 NAA20 Zornitza Stark Gene: naa20 has been classified as Green List (High Evidence).
Mendeliome v0.10511 NAA20 Zornitza Stark Classified gene: NAA20 as Green List (high evidence)
Mendeliome v0.10511 NAA20 Zornitza Stark Gene: naa20 has been classified as Green List (High Evidence).
Mendeliome v0.10509 PLA2G7 Zornitza Stark Gene: pla2g7 has been classified as Red List (Low Evidence).
Mendeliome v0.10506 PLA2G7 Zornitza Stark Classified gene: PLA2G7 as Red List (low evidence)
Mendeliome v0.10506 PLA2G7 Zornitza Stark Gene: pla2g7 has been classified as Red List (Low Evidence).
Mendeliome v0.10505 RAB23 Zornitza Stark Gene: rab23 has been classified as Green List (High Evidence).
Mendeliome v0.10502 DSG1 Zornitza Stark Gene: dsg1 has been classified as Green List (High Evidence).
Mendeliome v0.10502 DSG1 Zornitza Stark Phenotypes for gene: DSG1 were changed from to Erythroderma, congenital, with palmoplantar keratoderma, hypotrichosis, and hyper IgE, AR (MIM#615508); Keratosis palmoplantaris striata I, AD (MIM# 148700)
Mendeliome v0.10499 DPF2 Zornitza Stark Gene: dpf2 has been classified as Green List (High Evidence).
Mendeliome v0.10499 DPF2 Zornitza Stark Phenotypes for gene: DPF2 were changed from to Coffin-Siris syndrome 7, MIM#618027
Mendeliome v0.10496 DNAJC19 Zornitza Stark Gene: dnajc19 has been classified as Green List (High Evidence).
Mendeliome v0.10493 DSG1 Belinda Chong reviewed gene: DSG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19558595, 29315490, 31192455, 23974871, 29229434, 33666035; Phenotypes: Erythroderma, congenital, with palmoplantar keratoderma, hypotrichosis, and hyper IgE, AR (MIM#615508), Keratosis palmoplantaris striata I, AD (MIM# 148700); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10493 KCNC1 Zornitza Stark Gene: kcnc1 has been classified as Green List (High Evidence).
Mendeliome v0.10493 KCNC1 Zornitza Stark Phenotypes for gene: KCNC1 were changed from to Epilepsy, progressive myoclonic 7 (MIM#616187); Intellectual disability; Movement disorders
Mendeliome v0.10491 KCNC1 Zornitza Stark changed review comment from: Additional individuals reported with different variants, causing a broad range of neurological phenotypes including ID and movement disorders.; to: Additional individuals reported with different variants, causing a broad range of neurological phenotypes including ID and movement disorders.

Likely reflects different mechanisms (LoF vs GoF).
Mendeliome v0.10489 JAK3 Zornitza Stark Gene: jak3 has been classified as Green List (High Evidence).
Mendeliome v0.10489 JAK3 Zornitza Stark Phenotypes for gene: JAK3 were changed from to SCID, autosomal recessive, T-negative/B-positive type MIM# 600802
Mendeliome v0.10486 GBE1 Zornitza Stark Gene: gbe1 has been classified as Green List (High Evidence).
Mendeliome v0.10483 KCNC1 Daniel Flanagan reviewed gene: KCNC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25401298; Phenotypes: Epilepsy, progressive myoclonic 7 (MIM#616187); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10483 DPF2 Belinda Chong reviewed gene: DPF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29429572, 31706665; Phenotypes: Coffin-Siris syndrome 7 MIM#618027; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.10483 FREM1 Zornitza Stark Gene: frem1 has been classified as Green List (High Evidence).
Mendeliome v0.10480 FRAS1 Zornitza Stark Gene: fras1 has been classified as Green List (High Evidence).
Mendeliome v0.10477 SGPL1 Seb Lunke Gene: sgpl1 has been classified as Green List (High Evidence).
Mendeliome v0.10475 SGPL1 Seb Lunke reviewed gene: SGPL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33074640; Phenotypes: Sphingosine Phosphate Lyase Insufficiency Syndrome, Nephrotic syndrome, type 14, MIM#617575; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10475 FOXP3 Zornitza Stark Gene: foxp3 has been classified as Green List (High Evidence).
Mendeliome v0.10472 MMP3 Zornitza Stark Gene: mmp3 has been classified as Red List (Low Evidence).
Mendeliome v0.10470 MMP3 Zornitza Stark Classified gene: MMP3 as Red List (low evidence)
Mendeliome v0.10470 MMP3 Zornitza Stark Gene: mmp3 has been classified as Red List (Low Evidence).
Mendeliome v0.10469 LRAT Zornitza Stark Gene: lrat has been classified as Green List (High Evidence).
Mendeliome v0.10469 LRAT Zornitza Stark Phenotypes for gene: LRAT were changed from to Leber congenital amaurosis 14 MIM#613341; Retinal dystrophy, early-onset severe MIM#613341; Retinitis pigmentosa, juvenile MIM#613341
Mendeliome v0.10466 LRAT Zornitza Stark reviewed gene: LRAT: Rating: GREEN; Mode of pathogenicity: None; Publications: 11381255, 18055821, 22570351, 17011878, 29973277, 24625443, 22559933, 31448181; Phenotypes: Leber congenital amaurosis 14 MIM#613341, Retinal dystrophy, early-onset severe MIM#613341, Retinitis pigmentosa, juvenile MIM#613341; Mode of inheritance: None
Mendeliome v0.10466 GRM1 Zornitza Stark Gene: grm1 has been classified as Green List (High Evidence).
Mendeliome v0.10466 GRM1 Zornitza Stark Phenotypes for gene: GRM1 were changed from to Spinocerebellar ataxia 44 MIM#617691; Spinocerebellar ataxia, autosomal recessive 13 MIM#614831
Mendeliome v0.10461 GPX4 Zornitza Stark Gene: gpx4 has been classified as Green List (High Evidence).
Mendeliome v0.10461 GPX4 Zornitza Stark Phenotypes for gene: GPX4 were changed from to Spondylometaphyseal dysplasia, Sedaghatian type MIM#250220
Mendeliome v0.10458 SLC12A6 Zornitza Stark Phenotypes for gene: SLC12A6 were changed from Andermann syndrome; Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum; Intermediate CMT to Andermann syndrome; Agenesis of the corpus callosum with peripheral neuropathy, MIM#21800; Intermediate CMT
Mendeliome v0.10457 SLC12A6 Zornitza Stark edited their review of gene: SLC12A6: Changed phenotypes: Andermann syndrome, Agenesis of the corpus callosum with peripheral neuropathy, MIM#21800, Intermediate CMT
Mendeliome v0.10457 GPKOW Zornitza Stark Gene: gpkow has been classified as Red List (Low Evidence).
Mendeliome v0.10457 GPKOW Zornitza Stark Classified gene: GPKOW as Red List (low evidence)
Mendeliome v0.10457 GPKOW Zornitza Stark Gene: gpkow has been classified as Red List (Low Evidence).
Mendeliome v0.10456 GNA11 Zornitza Stark Gene: gna11 has been classified as Green List (High Evidence).
Mendeliome v0.10452 FOXC2 Zornitza Stark Gene: foxc2 has been classified as Green List (High Evidence).
Mendeliome v0.10452 FOXC2 Zornitza Stark Phenotypes for gene: FOXC2 were changed from to Lymphoedema-distichiasis syndrome, MIM# 153400
Mendeliome v0.10449 FOXC2 Zornitza Stark reviewed gene: FOXC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 11078474, 11694548, 11371511; Phenotypes: Lymphoedema-distichiasis syndrome, MIM# 153400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10449 GRM1 Ain Roesley reviewed gene: GRM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22901947, 26308914, 31319223; Phenotypes: Spinocerebellar ataxia 44 MIM#617691, Spinocerebellar ataxia, autosomal recessive 13 MIM#614831; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10449 GRHL2 Ain Roesley reviewed gene: GRHL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27612988, 19415813; Phenotypes: Ectodermal dysplasia/short stature syndrome MIM#616029; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10448 GPX4 Ain Roesley reviewed gene: GPX4: Rating: GREEN; Mode of pathogenicity: None; Publications: 24706940, 32827718; Phenotypes: Spondylometaphyseal dysplasia, Sedaghatian type MIM#250220; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10448 GPKOW Ain Roesley gene: GPKOW was added
gene: GPKOW was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: GPKOW was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: GPKOW were set to 28612833
Phenotypes for gene: GPKOW were set to male-lethal microcephaly with intrauterine growth restriction
Penetrance for gene: GPKOW were set to unknown
Review for gene: GPKOW was set to RED
gene: GPKOW was marked as current diagnostic
Added comment: - multi-generational family with 5 deceased males (only 1 genotyped)
- X-exome sequencing identified NM_015698.4:c.331+5G>A, which segregated through the obligate carriers
- RNA from female carriers confirmed splicing defects, which leads to NMD

no additional reports since
Sources: Literature
Mendeliome v0.10448 HOXC13 Zornitza Stark Gene: hoxc13 has been classified as Green List (High Evidence).
Mendeliome v0.10448 HOXC13 Zornitza Stark Phenotypes for gene: HOXC13 were changed from to Ectodermal dysplasia 9, hair/nail type MIM#614931
Mendeliome v0.10445 FZD6 Zornitza Stark Gene: fzd6 has been classified as Green List (High Evidence).
Mendeliome v0.10442 SIX5 Zornitza Stark Tag disputed tag was added to gene: SIX5.
Mendeliome v0.10442 SIX5 Zornitza Stark Publications for gene: SIX5 were set to 17357085; 33624842; 20301554; 24730701; 22447252
Mendeliome v0.10441 SIX5 Zornitza Stark Classified gene: SIX5 as Amber List (moderate evidence)
Mendeliome v0.10441 SIX5 Zornitza Stark Gene: six5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10440 SIX5 Zornitza Stark changed review comment from: Multiple families reported.; to: Multiple families reported. However, association between SIX5 variants and BOR is DISPUTED by ClinGen: Association has been reported in at least 6 probands in 2 publications (17357085, 24429398), however the reported variants are high in frequency in population databases, have no evidence of pathogenicity, and/or an alternate cause of disease has later been reported (21280147). This gene-disease association is supported by protein interaction and biochemical function studies (14704431, 17357085, 11950062). While EYA1 and SIX1 gene inactivation in mice leads to ear and kidney abnormalities, two independent SIX5 mouse models have cataracts and no ear or kidney abnormalities (10802667, 10802668). In summary, there is convincing evidence disputing the association between SIX5 and autosomal dominant branchio-oto-renal syndrome.
Mendeliome v0.10440 SIX5 Zornitza Stark edited their review of gene: SIX5: Changed rating: AMBER; Changed publications: 17357085, 33624842, 20301554, 24730701, 22447252, 21280147, 14704431, 11950062, 10802667, 10802668
Mendeliome v0.10440 SIX5 Zornitza Stark Marked gene: SIX5 as ready
Mendeliome v0.10440 SIX5 Zornitza Stark Gene: six5 has been classified as Green List (High Evidence).
Mendeliome v0.10440 SIX5 Zornitza Stark Phenotypes for gene: SIX5 were changed from Branchiootorenal syndrome 2, MIM# 610896 to Branchiootorenal syndrome 2, MIM# 610896
Mendeliome v0.10439 SIX5 Zornitza Stark Phenotypes for gene: SIX5 were changed from to Branchiootorenal syndrome 2, MIM# 610896
Mendeliome v0.10438 SIX5 Zornitza Stark Publications for gene: SIX5 were set to
Mendeliome v0.10437 SIX5 Zornitza Stark Mode of inheritance for gene: SIX5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10436 SIX5 Zornitza Stark reviewed gene: SIX5: Rating: GREEN; Mode of pathogenicity: None; Publications: 17357085, 33624842, 20301554, 24730701, 22447252; Phenotypes: Branchiootorenal syndrome 2, MIM# 610896; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10436 SKI Seb Lunke Gene: ski has been classified as Green List (High Evidence).
Mendeliome v0.10433 SKI Seb Lunke changed review comment from: Well established gene disease association with craniosynostosis, skeletal, and cardiovascular anomalies, high-arched palate, micrognathia. Inguinal or umbilical hernia also described. Most common skeletal manifestations are arachnodactyly, pectus deformity, camptodactyly, scoliosis.

LoF not fully established on only missense described so far. Some functional work suggest potential GoF for TGF beta signalling, but not conclusive. Not enough evidence so far to go against LoF.; to: Well established gene disease association with craniosynostosis, skeletal, and cardiovascular anomalies, high-arched palate, micrognathia. Inguinal or umbilical hernia also described. Most common skeletal manifestations are arachnodactyly, pectus deformity, camptodactyly, scoliosis.

LoF not fully established as only missense described so far. Some functional work suggest potential GoF for TGF beta signalling, but not conclusive. Not enough evidence so far to go against LoF.
Mendeliome v0.10433 SKI Seb Lunke commented on gene: SKI: Well established gene disease association with craniosynostosis, skeletal, and cardiovascular anomalies, high-arched palate, micrognathia. Inguinal or umbilical hernia also described. Most common skeletal manifestations are arachnodactyly, pectus deformity, camptodactyly, scoliosis.

LoF not fully established on only missense described so far. Some functional work suggest potential GoF for TGF beta signalling, but not conclusive. Not enough evidence so far to go against LoF.
Mendeliome v0.10433 KEL Zornitza Stark Gene: kel has been classified as Red List (Low Evidence).
Mendeliome v0.10432 KEL Zornitza Stark Classified gene: KEL as Red List (low evidence)
Mendeliome v0.10432 KEL Zornitza Stark Gene: kel has been classified as Red List (Low Evidence).
Mendeliome v0.10431 COX15 Zornitza Stark Gene: cox15 has been classified as Green List (High Evidence).
Mendeliome v0.10428 TECRL Zornitza Stark Gene: tecrl has been classified as Green List (High Evidence).
Mendeliome v0.10428 TECRL Zornitza Stark Classified gene: TECRL as Green List (high evidence)
Mendeliome v0.10428 TECRL Zornitza Stark Gene: tecrl has been classified as Green List (High Evidence).
Mendeliome v0.10427 TECRL Zornitza Stark gene: TECRL was added
gene: TECRL was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: TECRL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TECRL were set to 17666061; 27861123; 30790670; 33367594
Phenotypes for gene: TECRL were set to Ventricular tachycardia, catecholaminergic polymorphic, 3, MIM# 614021
Review for gene: TECRL was set to GREEN
Added comment: DEFINITIVE by ClinGen
Homozygous or cpd heterozygous pathogenic variants in TECRL have been identified in patients with CPVT in at least 3 families in the literature with functional evidence.
- 17666061 one consanguineous family with 4 affected relatives (siblings or 1stcousins)
- 27861123 consanguineous family with 8 affected relatives (siblings or 1stcousins)
- 30790670 reported in a single family with one child with features of CPVT
-A multi-centre review published in 2020 provided an update on these cases and described two additional CPVT cases (homozygous p.Tyr197Ter nonsense variant and homozygous exon 2 deletion) and a family with three children with sudden cardiac death, where one was homozygous for the c.331+1G>A splice donor variant, PMID 33367594
Sources: Expert Review
Mendeliome v0.10426 CCDC115 Zornitza Stark Gene: ccdc115 has been classified as Green List (High Evidence).
Mendeliome v0.10423 C2orf71 Zornitza Stark Gene: c2orf71 has been classified as Green List (High Evidence).
Mendeliome v0.10420 SH3PXD2B Zornitza Stark Gene: sh3pxd2b has been classified as Green List (High Evidence).
Mendeliome v0.10417 SETBP1 Zornitza Stark Gene: setbp1 has been classified as Green List (High Evidence).
Mendeliome v0.10415 SETBP1 Zornitza Stark changed review comment from: GoF variants cause Schinzel-Giedion syndrome, whereas LoF variants cause SETBP1-haploinsufficiency syndrome, over 40 individuals reviewed in PMID 34807554.; to: GoF variants cause Schinzel-Giedion syndrome, a severe multi-system disorder characterized by recognizable facial characteristics, severe-profound intellectual disability, intractable epilepsy, cortical visual impairment, deafness, and congenital anomalies such as cardiac defects, urogenital defects, and bone abnormalities. Causative pathogenic variants are clustered within a 12-base pair hot spot region in exon 4.

LoF variants cause SETBP1-haploinsufficiency syndrome, characterized by hypotonia and mild motor developmental delay; intellectual abilities ranging from normal to severe disability; speech and language disorder; behavioral problems (most commonly attention/concentration deficits and hyperactivity, impulsivity), and refractive errors and strabismus. Over 40 individuals reviewed in PMID 34807554.
Mendeliome v0.10414 SCN4A Zornitza Stark Gene: scn4a has been classified as Green List (High Evidence).
Mendeliome v0.10414 SCN4A Zornitza Stark Phenotypes for gene: SCN4A were changed from to Hyperkalemic periodic paralysis, type 2, MIM# 170500; Hypokalemic periodic paralysis, type 2, MIM# 613345; Myasthenic syndrome, congenital, 16, MIM# 614198; Myotonia congenita, atypical, acetazolamide-responsive , MIM#608390; Paramyotonia congenita , MIM#168300
Mendeliome v0.10411 SCN4A Zornitza Stark reviewed gene: SCN4A: Rating: GREEN; Mode of pathogenicity: None; Publications: 34671263; Phenotypes: Hyperkalemic periodic paralysis, type 2, MIM# 170500, Hypokalemic periodic paralysis, type 2, MIM# 613345, Myasthenic syndrome, congenital, 16, MIM# 614198, Myotonia congenita, atypical, acetazolamide-responsive , MIM#608390, Paramyotonia congenita , MIM#168300; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.10410 TRAP1 Zornitza Stark Gene: trap1 has been classified as Green List (High Evidence).
Mendeliome v0.10407 BRWD3 Zornitza Stark Gene: brwd3 has been classified as Green List (High Evidence).
Mendeliome v0.10404 ING1 Seb Lunke Gene: ing1 has been classified as Red List (Low Evidence).
Mendeliome v0.10404 ING1 Seb Lunke Classified gene: ING1 as Red List (low evidence)
Mendeliome v0.10404 ING1 Seb Lunke Added comment: Comment on list classification: Cancer association only
Mendeliome v0.10404 ING1 Seb Lunke Gene: ing1 has been classified as Red List (Low Evidence).
Mendeliome v0.10403 BCKDHB Zornitza Stark Gene: bckdhb has been classified as Green List (High Evidence).
Mendeliome v0.10400 BCKDHA Zornitza Stark Gene: bckdha has been classified as Green List (High Evidence).
Mendeliome v0.10397 FSCN2 Seb Lunke Gene: fscn2 has been classified as Red List (Low Evidence).
Mendeliome v0.10394 FSCN2 Seb Lunke Classified gene: FSCN2 as Red List (low evidence)
Mendeliome v0.10394 FSCN2 Seb Lunke Gene: fscn2 has been classified as Red List (Low Evidence).
Mendeliome v0.10394 FSCN2 Seb Lunke Classified gene: FSCN2 as Red List (low evidence)
Mendeliome v0.10394 FSCN2 Seb Lunke Gene: fscn2 has been classified as Red List (Low Evidence).
Mendeliome v0.10392 AUH Zornitza Stark Gene: auh has been classified as Green List (High Evidence).
Mendeliome v0.10389 ATP8B1 Zornitza Stark edited their review of gene: ATP8B1: Changed phenotypes: Cholestasis, progressive familial intrahepatic 1, MIM# 211600, Cholestasis, benign recurrent intrahepatic, MIM# 243300, Cholestasis, intrahepatic, of pregnancy, 1, MIM# 147480
Mendeliome v0.10389 ATP8B1 Zornitza Stark Gene: atp8b1 has been classified as Green List (High Evidence).
Mendeliome v0.10389 ATP8B1 Zornitza Stark changed review comment from: Well established gene-disease association, early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver failure.

Spectrum of severity, with missense variants causing milder/benign disease. Mono-allelic variants linked to cholestasis of pregnancy.; to: Spectrum of severity, with missense variants causing milder/benign disease. Mono-allelic variants linked to cholestasis of pregnancy.
Mendeliome v0.10389 ATP8B1 Zornitza Stark changed review comment from: Well established gene-disease association, early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver failure.

Spectrum of severity. Mono-allelic variants linked to cholestasis of pregnancy.; to: Well established gene-disease association, early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver failure.

Spectrum of severity, with missense variants causing milder/benign disease. Mono-allelic variants linked to cholestasis of pregnancy.
Mendeliome v0.10389 ATP8B1 Zornitza Stark changed review comment from: Well established gene-disease association, early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver failure.; to: Well established gene-disease association, early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver failure.

Spectrum of severity. Mono-allelic variants linked to cholestasis of pregnancy.
Mendeliome v0.10388 ATP8B1 Zornitza Stark Phenotypes for gene: ATP8B1 were changed from Cholestasis, progressive familial intrahepatic 1, MIM# 211600; Cholestasis, benign recurrent intrahepatic, MIM# 243300 to Cholestasis, progressive familial intrahepatic 1, MIM# 211600; Cholestasis, benign recurrent intrahepatic, MIM# 243300; Cholestasis, intrahepatic, of pregnancy, 1, MIM# 147480
Mendeliome v0.10386 ATP8B1 Zornitza Stark Phenotypes for gene: ATP8B1 were changed from to Cholestasis, progressive familial intrahepatic 1, MIM# 211600; Cholestasis, benign recurrent intrahepatic, MIM# 243300
Mendeliome v0.10384 ATP8B1 Zornitza Stark reviewed gene: ATP8B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15239083; Phenotypes: Cholestasis, progressive familial intrahepatic 1, MIM# 211600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10384 RNF213 Zornitza Stark Gene: rnf213 has been classified as Green List (High Evidence).
Mendeliome v0.10382 DRD5 Zornitza Stark Gene: drd5 has been classified as Red List (Low Evidence).
Mendeliome v0.10382 DRD5 Zornitza Stark Classified gene: DRD5 as Red List (low evidence)
Mendeliome v0.10382 DRD5 Zornitza Stark Gene: drd5 has been classified as Red List (Low Evidence).
Mendeliome v0.10381 AXIN1 Zornitza Stark Gene: axin1 has been classified as Red List (Low Evidence).
Mendeliome v0.10379 AXIN1 Zornitza Stark Classified gene: AXIN1 as Red List (low evidence)
Mendeliome v0.10379 AXIN1 Zornitza Stark Gene: axin1 has been classified as Red List (Low Evidence).
Mendeliome v0.10378 ASL Zornitza Stark Gene: asl has been classified as Green List (High Evidence).
Mendeliome v0.10375 ARG1 Zornitza Stark Gene: arg1 has been classified as Green List (High Evidence).
Mendeliome v0.10372 TWIST2 Zornitza Stark Gene: twist2 has been classified as Green List (High Evidence).
Mendeliome v0.10372 TWIST2 Zornitza Stark Phenotypes for gene: TWIST2 were changed from to Ablepharon-macrostomia syndrome, MIM# 200110; Barber-Say syndrome, MIM# 209885; Focal facial dermal dysplasia 3, Setleis type, MIM# 227260
Mendeliome v0.10369 TWIST2 Zornitza Stark reviewed gene: TWIST2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26119818, 20691403, 21931173, 26119818; Phenotypes: Ablepharon-macrostomia syndrome, MIM# 200110, Barber-Say syndrome, MIM# 209885, Focal facial dermal dysplasia 3, Setleis type, MIM# 227260; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.10369 APTX Zornitza Stark Gene: aptx has been classified as Green List (High Evidence).
Mendeliome v0.10366 ALDH4A1 Zornitza Stark Gene: aldh4a1 has been classified as Green List (High Evidence).
Mendeliome v0.10363 VLDLR Zornitza Stark Gene: vldlr has been classified as Green List (High Evidence).
Mendeliome v0.10363 VLDLR Zornitza Stark Phenotypes for gene: VLDLR were changed from to Cerebellar hypoplasia and mental retardation with or without quadrupedal locomotion 1, MIM# 224050
Mendeliome v0.10360 VLDLR Zornitza Stark reviewed gene: VLDLR: Rating: GREEN; Mode of pathogenicity: None; Publications: 16080122, 18326629, 10380922; Phenotypes: Cerebellar hypoplasia and mental retardation with or without quadrupedal locomotion 1, MIM# 224050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10360 CSTF2 Zornitza Stark Gene: cstf2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10360 CSTF2 Zornitza Stark Classified gene: CSTF2 as Amber List (moderate evidence)
Mendeliome v0.10360 CSTF2 Zornitza Stark Gene: cstf2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10359 CSTF2 Zornitza Stark gene: CSTF2 was added
gene: CSTF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: CSTF2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: CSTF2 were set to 32816001
Phenotypes for gene: CSTF2 were set to Intellectual disability
Review for gene: CSTF2 was set to AMBER
Added comment: Four individuals from a single family, spanning two generations, segregating a missense variant. Functional data, including a mouse model and a gene reporter assay.
Sources: Literature
Mendeliome v0.10358 ALAD Zornitza Stark Gene: alad has been classified as Green List (High Evidence).
Mendeliome v0.10355 HMGCR Zornitza Stark Phenotypes for gene: HMGCR were changed from to [Low density lipoprotein cholesterol level QTL 3]
Mendeliome v0.10354 HMGCR Zornitza Stark Gene: hmgcr has been classified as Red List (Low Evidence).
Mendeliome v0.10353 HMGCR Zornitza Stark Classified gene: HMGCR as Red List (low evidence)
Mendeliome v0.10353 HMGCR Zornitza Stark Gene: hmgcr has been classified as Red List (Low Evidence).
Mendeliome v0.10352 FLVCR2 Zornitza Stark Gene: flvcr2 has been classified as Green List (High Evidence).
Mendeliome v0.10349 FLT4 Zornitza Stark Gene: flt4 has been classified as Green List (High Evidence).
Mendeliome v0.10341 FBLN5 Zornitza Stark Gene: fbln5 has been classified as Green List (High Evidence).
Mendeliome v0.10341 FBLN5 Zornitza Stark Phenotypes for gene: FBLN5 were changed from to Cutis laxa, autosomal recessive, type IA, MIM#219100; Neuropathy, hereditary, with or without age-related macular degeneration (MIM#608895)
Mendeliome v0.10338 FBLN5 Zornitza Stark changed review comment from: Cutis laxa: >3 families reported with bi-allelic variants and functional data including mouse model. Single individual reported in 2003 with mono-allelic disease (large intragenic duplication).

Neuropathy +/- macular degeneration:
PMID: 32757322
- 38 individuals from 19 families
- all missense, R373C, D329V and R331H
- some carriers were subjectively healthy although pes cavus, diminished or absent deep tendon reflexesor NCV studies indicate peripheral neuropathy

PMID: 31945625
- 1 family with 2 affecteds, R373C
- 1 obligate carrier presented no symptoms

PMID: 28332470
- 3 affecteds in 1 family with R373C; to: Cutis laxa: >3 families reported with bi-allelic variants and functional data including mouse model. Single individual reported in 2003 with mono-allelic disease (large intragenic duplication).
Mendeliome v0.10338 FBLN5 Zornitza Stark reviewed gene: FBLN5: Rating: GREEN; Mode of pathogenicity: None; Publications: 12618961, 3232707, 22829427, 11805835, 32757322, 31945625, 23328402, 28332470; Phenotypes: Cutis laxa, autosomal recessive, type IA, MIM#219100, Neuropathy, hereditary, with or without age-related macular degeneration (MIM#608895); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.10334 KCNJ8 Zornitza Stark Classified gene: KCNJ8 as Green List (high evidence)
Mendeliome v0.10334 KCNJ8 Zornitza Stark Gene: kcnj8 has been classified as Green List (High Evidence).
Mendeliome v0.10333 CITED2 Zornitza Stark Gene: cited2 has been classified as Green List (High Evidence).
Mendeliome v0.10330 VPS53 Zornitza Stark reviewed gene: VPS53: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pontocerebellar hypoplasia, type 2E, OMIM #615851; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10330 VPS53 Zornitza Stark Phenotypes for gene: VPS53 were changed from to Pontocerebellar hypoplasia, type 2E, OMIM #615851
Mendeliome v0.10327 NKX2-6 Zornitza Stark Gene: nkx2-6 has been classified as Green List (High Evidence).
Mendeliome v0.10327 NKX2-6 Zornitza Stark Phenotypes for gene: NKX2-6 were changed from to Conotruncal heart malformations - MIM#217095; Persistent truncus arteriosus - MIM#217095
Mendeliome v0.10324 WNT10B Zornitza Stark Phenotypes for gene: WNT10B were changed from to Split-hand/foot malformation 6, OMIM #601906; Tooth agenesis, selective, 8, OMIM #617073
Mendeliome v0.10321 YY1 Zornitza Stark Gene: yy1 has been classified as Green List (High Evidence).
Mendeliome v0.10318 NKX2-6 Krithika Murali reviewed gene: NKX2-6: Rating: GREEN; Mode of pathogenicity: None; Publications: 24421281, 15649947, 32198970, 25380965, 25319568; Phenotypes: Conotruncal heart malformations - MIM#217095, Persistent truncus arteriosus - MIM#217095; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10318 GM2A Zornitza Stark Gene: gm2a has been classified as Green List (High Evidence).
Mendeliome v0.10318 GM2A Zornitza Stark Phenotypes for gene: GM2A were changed from to GM2-gangliosidosis, AB variant MIM#272750
Mendeliome v0.10314 GFRA1 Zornitza Stark Classified gene: GFRA1 as Green List (high evidence)
Mendeliome v0.10314 GFRA1 Zornitza Stark Gene: gfra1 has been classified as Green List (High Evidence).
Mendeliome v0.10313 VPS53 Alison Yeung Gene: vps53 has been classified as Green List (High Evidence).
Mendeliome v0.10313 VPS53 Alison Yeung reviewed gene: VPS53: Rating: GREEN; Mode of pathogenicity: None; Publications: 24577744, 12920088; Phenotypes: Pontocerebellar hypoplasia, type 2E, OMIM #615851; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10313 GLI1 Zornitza Stark Gene: gli1 has been classified as Green List (High Evidence).
Mendeliome v0.10313 GLI1 Zornitza Stark Classified gene: GLI1 as Green List (high evidence)
Mendeliome v0.10313 GLI1 Zornitza Stark Gene: gli1 has been classified as Green List (High Evidence).
Mendeliome v0.10312 WNT10B Alison Yeung Gene: wnt10b has been classified as Green List (High Evidence).
Mendeliome v0.10312 WNT10B Alison Yeung reviewed gene: WNT10B: Rating: GREEN; Mode of pathogenicity: None; Publications: 20635353, 24211389, 27321946; Phenotypes: Split-hand/foot malformation 6, OMIM #601906, Tooth agenesis, selective, 8, OMIM #617073; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.10312 GM2A Ain Roesley reviewed gene: GM2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 28417072, 28192816, 27402091, 33819415; Phenotypes: GM2-gangliosidosis, AB variant MIM#272750; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10312 GFRA1 Ain Roesley reviewed gene: GFRA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34737117; Phenotypes: renal agenesis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10312 ADAMTS2 Zornitza Stark Gene: adamts2 has been classified as Green List (High Evidence).
Mendeliome v0.10309 AIPL1 Zornitza Stark Phenotypes for gene: AIPL1 were changed from Leber congenital amaurosis 4, 604393 Cone-rod dystrophy, 604393 Retinitis pigmentosa, juvenile, 604393 to Leber congenital amaurosis 4, 604393; Cone-rod dystrophy, 604393; Retinitis pigmentosa, juvenile, 604393
Mendeliome v0.10308 AIPL1 Zornitza Stark edited their review of gene: AIPL1: Changed phenotypes: Leber congenital amaurosis 4, 604393, Cone-rod dystrophy, 604393, Retinitis pigmentosa, juvenile, 604393
Mendeliome v0.10308 AGA Zornitza Stark changed review comment from: 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.; to: 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 ID. Multiple families and mouse model.
Mendeliome v0.10308 ACAT1 Zornitza Stark Gene: acat1 has been classified as Green List (High Evidence).
Mendeliome v0.10306 ACADS Zornitza Stark Gene: acads has been classified as Green List (High Evidence).
Mendeliome v0.10303 ACADM Zornitza Stark Gene: acadm has been classified as Green List (High Evidence).
Mendeliome v0.10301 CYP26B1 Zornitza Stark Gene: cyp26b1 has been classified as Green List (High Evidence).
Mendeliome v0.10301 CYP26B1 Zornitza Stark Phenotypes for gene: CYP26B1 were changed from to Craniosynostosis with radiohumeral fusions and other skeletal and craniofacial anomalies, MIM# 614416
Mendeliome v0.10298 CYP26B1 Zornitza Stark reviewed gene: CYP26B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27410456, 22019272; Phenotypes: Craniosynostosis with radiohumeral fusions and other skeletal and craniofacial anomalies, MIM# 614416; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10298 CTU2 Zornitza Stark Gene: ctu2 has been classified as Green List (High Evidence).
Mendeliome v0.10298 CTU2 Zornitza Stark Phenotypes for gene: CTU2 were changed from to Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome, MIM#618142
Mendeliome v0.10295 CTU2 Zornitza Stark reviewed gene: CTU2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27480277, 26633546, 31301155; Phenotypes: Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome, MIM#618142; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10295 CTDP1 Zornitza Stark Gene: ctdp1 has been classified as Green List (High Evidence).
Mendeliome v0.10292 CRELD1 Zornitza Stark Classified gene: CRELD1 as Amber List (moderate evidence)
Mendeliome v0.10292 CRELD1 Zornitza Stark Gene: creld1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10291 HHAT Zornitza Stark Classified gene: HHAT as Green List (high evidence)
Mendeliome v0.10291 HHAT Zornitza Stark Gene: hhat has been classified as Green List (High Evidence).
Mendeliome v0.10290 SPIDR Zornitza Stark Gene: spidr has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10290 SPIDR Zornitza Stark Phenotypes for gene: SPIDR were changed from Primary ovarian insufficiency to Ovarian dysgenesis 9, MIM# 619665
Mendeliome v0.10289 SPIDR Zornitza Stark reviewed gene: SPIDR: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Ovarian dysgenesis 9, MIM# 619665; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10289 KIF12 Zornitza Stark Phenotypes for gene: KIF12 were changed from Cholestasis; High Gamma-Glutamyltransferase (GGT) to Cholestasis, progressive familial intrahepatic, 8, MIM# 619662
Mendeliome v0.10288 KIF12 Zornitza Stark edited their review of gene: KIF12: Changed phenotypes: Cholestasis, progressive familial intrahepatic, 8, MIM# 619662
Mendeliome v0.10287 TNR Zornitza Stark Phenotypes for gene: TNR were changed from Spastic para- or tetraparesis; Axial muscular hypotonia; Intellectual disability; Transient opisthotonus to Neurodevelopmental disorder, nonprogressive, with spasticity and transient opisthotonus, MIM# 619653; Spastic para- or tetraparesis; Axial muscular hypotonia; Intellectual disability; Transient opisthotonus
Mendeliome v0.10286 TNR Zornitza Stark edited their review of gene: TNR: Changed phenotypes: Neurodevelopmental disorder, nonprogressive, with spasticity and transient opisthotonus, MIM# 619653, Spastic para- or tetraparesis, Axial muscular hypotonia, Intellectual disability, Transient opisthotonus
Mendeliome v0.10286 CTSB Zornitza Stark Gene: ctsb has been classified as Red List (Low Evidence).
Mendeliome v0.10283 CTSB Zornitza Stark Classified gene: CTSB as Red List (low evidence)
Mendeliome v0.10283 CTSB Zornitza Stark Gene: ctsb has been classified as Red List (Low Evidence).
Mendeliome v0.10280 MSR1 Zornitza Stark Gene: msr1 has been classified as Red List (Low Evidence).
Mendeliome v0.10277 MSR1 Zornitza Stark Classified gene: MSR1 as Red List (low evidence)
Mendeliome v0.10277 MSR1 Zornitza Stark Gene: msr1 has been classified as Red List (Low Evidence).
Mendeliome v0.10276 CPAMD8 Zornitza Stark Gene: cpamd8 has been classified as Green List (High Evidence).
Mendeliome v0.10276 CPAMD8 Zornitza Stark Phenotypes for gene: CPAMD8 were changed from to Anterior segment dysgenesis 8, MIM# 617319
Mendeliome v0.10273 CPAMD8 Zornitza Stark reviewed gene: CPAMD8: Rating: GREEN; Mode of pathogenicity: None; Publications: 32274568; Phenotypes: Anterior segment dysgenesis 8, MIM# 617319; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10272 USP53 Zornitza Stark changed review comment from: Another 7 unrelated families with cholestasis reported. Jaundice began at age <7 months. Cholestasis was transient, with documented resolution of hyperbilirubinaemia in all (oldest patient aged 5 years). One individual had deafness.; to: Another 11 unrelated families with cholestasis reported. Jaundice began at age <7 months. Cholestasis was transient, with documented resolution of hyperbilirubinaemia in all (oldest patient aged 15 years). Childhood-onset deafness reported in two families.
Mendeliome v0.10272 USP53 Zornitza Stark Phenotypes for gene: USP53 were changed from Cholestasis; deafness to Cholestasis, progressive familial intrahepatic, 7, with or without hearing loss, MIM# 619658
Mendeliome v0.10271 USP53 Zornitza Stark edited their review of gene: USP53: Changed phenotypes: Cholestasis, progressive familial intrahepatic, 7, with or without hearing loss 619658
Mendeliome v0.10271 HOXB1 Zornitza Stark Gene: hoxb1 has been classified as Green List (High Evidence).
Mendeliome v0.10270 HOXB1 Zornitza Stark Phenotypes for gene: HOXB1 were changed from to Facial paresis, hereditary congenital, 3, MIM# 614744; MONDO:0013880
Mendeliome v0.10268 HOXB1 Zornitza Stark reviewed gene: HOXB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22770981, 26007620, 27144914; Phenotypes: Facial paresis, hereditary congenital, 3, MIM# 614744; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10268 COLEC10 Zornitza Stark Gene: colec10 has been classified as Green List (High Evidence).
Mendeliome v0.10265 COL4A3BP Zornitza Stark Gene: col4a3bp has been classified as Green List (High Evidence).
Mendeliome v0.10261 MIB1 Zornitza Stark Classified gene: MIB1 as Amber List (moderate evidence)
Mendeliome v0.10261 MIB1 Zornitza Stark Gene: mib1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10260 ZBTB20 Zornitza Stark Gene: zbtb20 has been classified as Green List (High Evidence).
Mendeliome v0.10257 MIB1 Chern Lim changed review comment from: Luxan 2013 (PMID: 23314057):
- V943F, seg with LVNC in 1 fam, (gnomADv2: 43 hets).
- R530X, seg with LVNC in 1 fam, (gv2: 13 hets).

Li 2018 (PMID: 30322850):
- in 4 CHD patients: p.Q237H (gv2v3 absent), p.W271G (gv2v3 absent), p.S520R (v2 5 hets) and p.T312Kfs*55 (NMD-pred, absent but many comparables in gnomAD).
- HEK293T cells transfection studies showed: T312Kfs*55 and W271G strongly impaired MIB1 function on substrate ubiquitination, while Q237H and S520R had slight or no obvious changes. Interaction between MIB1 and JAG1 is severely interrupted by p.T312Kfs*55 and p.W271G, but not really in the other 2 missense.
- Overexpression of wt or mutant in zebrafish all resulted in dysmorphic pheno, therefore not informative.

DCM-association = none by Clingen (9/4/2020), ref Luxan 2013 and other pprs, and mentioned gnomAD had too many LoF variants.

De Ligt 2012 (PMID: 23033978): de novo R174H (gnomADv2: 7 hets), indvl with severe ID who also has a de novo R47* in WAC (an AD ID gene with LoF established, variant is P in ClinVar), no other pt-specific pheno provided.

Kaplanis 2021 (PMID: 33057194): Developmental disorders paper.
- 2 missense variants, de novo: 18-19383967-G-A (p.Glu491Lys, gv2 1 het, gv3 absent, GeneDx), 18-19378124-C-T (Thr391Ile, gv2v3 absent, DDD, de novo, no mention of heart pheno).
- Of 6 PTVs, 4 had at least 10 hets each in gnomADv2.; to: Luxan 2013 (PMID: 23314057):
- V943F, seg with LVNC in 1 fam, (gnomADv2: 43 hets).
- R530X, seg with LVNC in 1 fam, (gv2: 13 hets).

Li 2018 (PMID: 30322850):
- in 4 CHD patients: p.Q237H (gv2v3 absent), p.W271G (gv2v3 absent), p.S520R (v2 5 hets) and p.T312Kfs*55 (NMD-pred, absent but many comparables in gnomAD).
- HEK293T cells transfection studies showed: T312Kfs*55 and W271G strongly impaired MIB1 function on substrate ubiquitination, while Q237H and S520R had slight or no obvious changes. Interaction between MIB1 and JAG1 is severely interrupted by p.T312Kfs*55 and p.W271G, but not really in the other 2 missense.
- Overexpression of wt or mutant in zebrafish all resulted in dysmorphic pheno, therefore not informative.

DCM-association = none by Clingen (9/4/2020), ref Luxan 2013 and other pprs, and mentioned gnomAD had too many LoF variants.

De Ligt 2012 (PMID: 23033978): de novo R174H (gnomADv2: 7 hets), indvl with severe ID who also has a de novo R47* in WAC (an AD ID gene with LoF established, variant is P in ClinVar), no other pt-specific pheno provided.

Kaplanis 2021 (PMID: 33057194): Developmental disorders paper.
- 2 missense variants, de novo: 18-19383967-G-A (p.Glu491Lys, gv2 1 het, gv3 absent), 18-19378124-C-T (Thr391Ile, gv2v3 absent, DDD, de novo, no mention of heart pheno).
- Of 6 PTVs, 4 had at least 10 hets each in gnomADv2.
Mendeliome v0.10257 ABO Zornitza Stark Gene: abo has been classified as Red List (Low Evidence).
Mendeliome v0.10256 ABO Zornitza Stark Classified gene: ABO as Red List (low evidence)
Mendeliome v0.10256 ABO Zornitza Stark Gene: abo has been classified as Red List (Low Evidence).
Mendeliome v0.10255 TLR1 Zornitza Stark Gene: tlr1 has been classified as Red List (Low Evidence).
Mendeliome v0.10254 TLR1 Zornitza Stark Classified gene: TLR1 as Red List (low evidence)
Mendeliome v0.10254 TLR1 Zornitza Stark Gene: tlr1 has been classified as Red List (Low Evidence).
Mendeliome v0.10251 REL Zornitza Stark Classified gene: REL as Amber List (moderate evidence)
Mendeliome v0.10251 REL Zornitza Stark Gene: rel has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10250 REL Zornitza Stark changed review comment from: Second unrelated individual reported, homozygous splice site variant.

Immunodeficiency-92 (IMD92) is an autosomal recessive primary immunodeficiency characterized by the onset of recurrent infections in infancy or early childhood. Infectious agents are broad, including bacterial, viral, fungal, and parasitic, including Cryptosporidium and Mycobacteria. Patient lymphocytes show defects in both T- and B-cell proliferation, cytokine secretion, and overall function, and there is also evidence of dysfunction of NK, certain antigen-presenting cells, and myeloid subsets.; to: Second unrelated individual reported, with a different homozygous splice site variant.

Immunodeficiency-92 (IMD92) is an autosomal recessive primary immunodeficiency characterized by the onset of recurrent infections in infancy or early childhood. Infectious agents are broad, including bacterial, viral, fungal, and parasitic, including Cryptosporidium and Mycobacteria. Patient lymphocytes show defects in both T- and B-cell proliferation, cytokine secretion, and overall function, and there is also evidence of dysfunction of NK, certain antigen-presenting cells, and myeloid subsets.
Mendeliome v0.10250 REL Zornitza Stark edited their review of gene: REL: Added comment: Second unrelated individual reported, homozygous splice site variant.

Immunodeficiency-92 (IMD92) is an autosomal recessive primary immunodeficiency characterized by the onset of recurrent infections in infancy or early childhood. Infectious agents are broad, including bacterial, viral, fungal, and parasitic, including Cryptosporidium and Mycobacteria. Patient lymphocytes show defects in both T- and B-cell proliferation, cytokine secretion, and overall function, and there is also evidence of dysfunction of NK, certain antigen-presenting cells, and myeloid subsets.; Changed rating: AMBER; Changed publications: 31103457, 34623332; Changed phenotypes: Immunodeficiency 92, MIM# 619652, Combined immunodeficiency, T cells: normal, decreased memory CD4, poor proliferation, B cells: low, mostly naive, few switched memory B cells, impaired proliferation, Recurrent infections with bacteria, mycobacteria, salmonella and opportunistic organisms, Defective innate immunity
Mendeliome v0.10249 SLC26A5 Zornitza Stark Classified gene: SLC26A5 as Amber List (moderate evidence)
Mendeliome v0.10249 SLC26A5 Zornitza Stark Gene: slc26a5 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10248 SLC26A5 Zornitza Stark commented on gene: SLC26A5: Another publication identified, plus another individual with bi-allelic variants reported by a diagnostic laboratory. This gene-disease association is supported by mouse models, biochemical function studies and expression studies (12239568, 10821263, 11423665, 12719379, 18466744, 27091614, 17998209). Classified as LIMITED by ClinGen in 2017.
Mendeliome v0.10248 SEMA7A Zornitza Stark Gene: sema7a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10248 SEMA7A Zornitza Stark Phenotypes for gene: SEMA7A were changed from to Decreased bone mineral density; Kallmann syndrome; progressive familial intrahepatic cholestasis
Mendeliome v0.10245 SEMA7A Zornitza Stark Classified gene: SEMA7A as Amber List (moderate evidence)
Mendeliome v0.10245 SEMA7A Zornitza Stark Gene: sema7a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10244 SEMA7A Paul De Fazio changed review comment from: Koh et al 2006 (PMID:16372136) identified an association between common polymorphisms and decreased bone mineral density in 560 postmenopausal Korean women.

Zhao et al 2020 (PMID:31650878) identified a heterozygous splice variant at -3 (absent from gnomad) in a young woman with Kallman syndrome. It was inherited from her father, who had retarded pubertal development but a normal sense of smell.

Pan et al 2021 (PMID:34585848) identified a homozygous missense variant (gnomad: 107 hets 0 homs) in a child with progressive familial intrahepatic cholestasis. Mouse knock-ins recapitulated the patient phenotype.

Low evidence for association with disease.; to: Koh et al 2006 (PMID:16372136) identified an association between common polymorphisms and decreased bone mineral density in 560 postmenopausal Korean women.

Zhao et al 2020 (PMID:31650878) identified a heterozygous splice variant at -3 (absent from gnomad) in a young woman with Kallman syndrome. It was inherited from her father, who had retarded pubertal development but a normal sense of smell.

Pan et al 2021 (PMID:34585848) identified a homozygous missense variant (gnomad: 107 hets 0 homs) in a child with progressive familial intrahepatic cholestasis. Homozygous mice recapitulated the patient phenotype.

Rated amber due to 1 patient and mouse model in PMID:34585848.
Mendeliome v0.10244 SEMA7A Paul De Fazio changed review comment from: There is no conclusive evidence of association with monogenic disease for this gene.

Koh et al 2006 (PMID:16372136) identified an association between common polymorphisms and decreased bone mineral density in 560 postmenopausal Korean women.

Zhao et al 2020 (PMID:31650878) identified a heterozygous splice variant at -3 (absent from gnomad) in a young woman with Kallman syndrome. It was inherited from her father, who had retarded pubertal development but a normal sense of smell.

Pan et al 2021 (PMID:34585848) identified a homozygous missense variant (gnomad: 107 hets 0 homs) in a child with progressive familial intrahepatic cholestasis. Mouse knock-ins recapitulated the patient phenotype.; to: Koh et al 2006 (PMID:16372136) identified an association between common polymorphisms and decreased bone mineral density in 560 postmenopausal Korean women.

Zhao et al 2020 (PMID:31650878) identified a heterozygous splice variant at -3 (absent from gnomad) in a young woman with Kallman syndrome. It was inherited from her father, who had retarded pubertal development but a normal sense of smell.

Pan et al 2021 (PMID:34585848) identified a homozygous missense variant (gnomad: 107 hets 0 homs) in a child with progressive familial intrahepatic cholestasis. Mouse knock-ins recapitulated the patient phenotype.

Low evidence for association with disease.
Mendeliome v0.10244 SEMA7A Paul De Fazio reviewed gene: SEMA7A: Rating: RED; Mode of pathogenicity: None; Publications: 16372136, 31650878, 34585848; Phenotypes: Decreased bone mineral density, Kallmann syndrome, progressive familial intrahepatic cholestasis; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10244 CLMP Zornitza Stark Gene: clmp has been classified as Green List (High Evidence).
Mendeliome v0.10241 ERF Zornitza Stark Gene: erf has been classified as Green List (High Evidence).
Mendeliome v0.10241 ERF Zornitza Stark Phenotypes for gene: ERF were changed from to Craniosynostosis 4, MIM# 600775; Chitayat syndrome, MIM# 617180
Mendeliome v0.10238 ERF Zornitza Stark edited their review of gene: ERF: Changed phenotypes: Craniosynostosis 4, MIM# 600775, Chitayat syndrome, MIM# 617180
Mendeliome v0.10238 ERF Zornitza Stark reviewed gene: ERF: Rating: GREEN; Mode of pathogenicity: None; Publications: 23354439, 26097063, 32370745, 30758909, 27738187; Phenotypes: Craniosynostosis 4, MIM# 600775; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10238 EOGT Zornitza Stark Gene: eogt has been classified as Green List (High Evidence).
Mendeliome v0.10235 ADSL Zornitza Stark Gene: adsl has been classified as Green List (High Evidence).
Mendeliome v0.10232 KCND2 Zornitza Stark Gene: kcnd2 has been classified as Green List (High Evidence).
Mendeliome v0.10231 KCND2 Zornitza Stark Classified gene: KCND2 as Green List (high evidence)
Mendeliome v0.10231 KCND2 Zornitza Stark Gene: kcnd2 has been classified as Green List (High Evidence).
Mendeliome v0.10230 EYA1 Zornitza Stark Gene: eya1 has been classified as Green List (High Evidence).
Mendeliome v0.10227 FBXL4 Zornitza Stark Gene: fbxl4 has been classified as Green List (High Evidence).
Mendeliome v0.10224 GALE Zornitza Stark Gene: gale has been classified as Green List (High Evidence).
Mendeliome v0.10224 GALK1 Zornitza Stark Gene: galk1 has been classified as Green List (High Evidence).
Mendeliome v0.10223 FOXRED1 Zornitza Stark Gene: foxred1 has been classified as Green List (High Evidence).
Mendeliome v0.10219 FREM2 Zornitza Stark Gene: frem2 has been classified as Green List (High Evidence).
Mendeliome v0.10212 GATA4 Zornitza Stark Gene: gata4 has been classified as Green List (High Evidence).
Mendeliome v0.10208 COMT Zornitza Stark Gene: comt has been classified as Red List (Low Evidence).
Mendeliome v0.10208 COMT Zornitza Stark Classified gene: COMT as Red List (low evidence)
Mendeliome v0.10208 COMT Zornitza Stark Gene: comt has been classified as Red List (Low Evidence).
Mendeliome v0.10207 FAT4 Ain Roesley reviewed gene: FAT4: Rating: GREEN; Mode of pathogenicity: None; Publications: 29681106; Phenotypes: Hennekam lymphangiectasia-lymphedema syndrome 2 MIM#616006, Van Maldergem syndrome 2 MIM#615546; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10206 ZNFX1 Zornitza Stark Phenotypes for gene: ZNFX1 were changed from Multisystem inflammation; susceptibility to viral infections; monocytosis; susceptibility to mycobacterial infection to Immunodeficiency 91 and hyperinflammation, MIM# 619644
Mendeliome v0.10204 KCND2 Eleanor Williams gene: KCND2 was added
gene: KCND2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KCND2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KCND2 were set to 24501278; 16934482; 29581270; 34245260
Phenotypes for gene: KCND2 were set to global developmental delay, HP:0001263; seizure, HP:0001250
Mode of pathogenicity for gene: KCND2 was set to Other
Review for gene: KCND2 was set to GREEN
Added comment: 6 new unrelated cases with developmental delay reported in PMID: 34245260 (Zhang et al 2021), 3 of whom had seizures. All had heterozygous missense variants of KCND2 in sites known to be critical for channel gating (E323K, P403A, two individuals, V404L, two individuals and V404M). Functional studies suggest that these missense changes cause both a partial loss-of-function (LOF) and gain-of-function (GOF). The V404 change appears to increase epileptic seizure susceptibility with the 3 patients with a V404 change showing this phenotype.

PMID:24501278 - Lee et al, 2014 - reports pair of monozygotic twin boys with infantile onset severe refractory epilepsy and autism. A de novo heterozygous missense variant was identified by WES - V404M.

PMID: 29581270 - Lin et al, 2018 - performed functional work that shows V404M enhances inactivation of channels that have not yet opened and dramatically impairs the inactivation of channels that have opened.

PMID:16934482 - Singh et al, 2006 - reports a patient with cognative impairment who also went on to have seizures starting from age 13 with a 5 bp deletion in KCND2 leading to premature stop codon. The proband's asymptomatic father also shared this variant.
Sources: Literature
Mendeliome v0.10204 EIF2B2 Zornitza Stark Gene: eif2b2 has been classified as Green List (High Evidence).
Mendeliome v0.10201 CHRNB2 Zornitza Stark Gene: chrnb2 has been classified as Green List (High Evidence).
Mendeliome v0.10198 CHRNB1 Zornitza Stark Gene: chrnb1 has been classified as Green List (High Evidence).
Mendeliome v0.10194 CHRNA3 Zornitza Stark changed review comment from: Five individuals from three unrelated families.; to: Five individuals from three unrelated families.

Onset is in utero or early childhood.

Affected individuals have impaired neuronal bladder and ureteral innervation causing coordination defects that result in secondary structural defects of the renal system, including hydronephrosis, vesicoureteral reflux (VUR), and small kidneys, that may result in chronic kidney disease as well as recurrent urinary tract infections (UTIs). Surgical treatment of VUR is not effective. Most individuals also have additional autonomic features, most commonly impaired pupillary reflex and sometimes orthostatic hypotension.
Mendeliome v0.10194 CHD8 Zornitza Stark Gene: chd8 has been classified as Green List (High Evidence).
Mendeliome v0.10191 CCDC22 Zornitza Stark Gene: ccdc22 has been classified as Green List (High Evidence).
Mendeliome v0.10187 RNF212 Zornitza Stark Gene: rnf212 has been classified as Red List (Low Evidence).
Mendeliome v0.10185 RNF212 Zornitza Stark Classified gene: RNF212 as Red List (low evidence)
Mendeliome v0.10185 RNF212 Zornitza Stark Gene: rnf212 has been classified as Red List (Low Evidence).
Mendeliome v0.10184 ADCY5 Zornitza Stark Phenotypes for gene: ADCY5 were changed from Dyskinesia, familial, with facial myokymia, MIM# 606703; MONDO:0011707 to Dyskinesia, familial, with facial myokymia, MIM# 606703; MONDO:0011707; Hyperkinetic movement disorder with dyskinesia, myoclonus, chorea, and dystonia-2 (HYDMCD2), MIM#619647; Neurodevelopmental disorder with hyperkinetic movements and dyskinesia (NEDHYD), MIM#619651
Mendeliome v0.10181 ADCY5 Zornitza Stark edited their review of gene: ADCY5: Added comment: Neurodevelopmental disorder with hyperkinetic movements and dyskinesia (NEDHYD) is an autosomal recessive complex neurologic disorder characterized by severe global developmental delay with axial hypotonia, impaired intellectual development, poor overall growth, and abnormal involuntary hyperkinetic movements, including dystonia, myoclonus, spasticity, and orofacial dyskinesia. It is the most severe manifestation of ADCY5-related dyskinetic disorders. Five individuals from 2 families reported.

Autosomal recessive hyperkinetic movement disorder with dyskinesia, myoclonus, chorea, and dystonia-2 (HYDMCD2) is characterized by the onset of abnormal involuntary movements, mainly affecting the limbs and causing walking difficulties, in the first decade. The severity is variable; some patients have orofacial dyskinesia, resulting in speech difficulties, or develop neuropsychiatric features, including anxiety and social withdrawal. Cardiomyopathy has rarely been described and may be a manifestation of the disorder. Eight individuals from 2 families reported.; Changed publications: 22782511, 24700542, 33051786, 32647899, 33704598, 34631954, 28971144, 30975617; Changed phenotypes: Dyskinesia, familial, with facial myokymia, MIM# 606703, MONDO:0011707, Hyperkinetic movement disorder with dyskinesia, myoclonus, chorea, and dystonia-2 (HYDMCD2), MIM#619647, Neurodevelopmental disorder with hyperkinetic movements and dyskinesia (NEDHYD), MIM#619651; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.10181 CANT1 Zornitza Stark Gene: cant1 has been classified as Green List (High Evidence).
Mendeliome v0.10181 CANT1 Zornitza Stark Phenotypes for gene: CANT1 were changed from to Desbuquois dysplasia 1 MIM#251450; Epiphyseal dysplasia, multiple, 7, MIM# 617719
Mendeliome v0.10177 CANT1 Zornitza Stark reviewed gene: CANT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19853239, 21037275, 28742282; Phenotypes: Desbuquois dysplasia 1 MIM#251450, Epiphyseal dysplasia, multiple, 7, MIM# 617719; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10177 CAMK2A Zornitza Stark Gene: camk2a has been classified as Green List (High Evidence).
Mendeliome v0.10177 CAMK2A Zornitza Stark Phenotypes for gene: CAMK2A were changed from to Mental retardation, autosomal recessive 63 MIM#618095; Mental retardation, autosomal dominant 53 MIM#617798
Mendeliome v0.10174 CAMK2A Zornitza Stark reviewed gene: CAMK2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 32600977, 29784083, 29560374; Phenotypes: Mental retardation, autosomal recessive 63 MIM#618095, Mental retardation, autosomal dominant 53 MIM#617798; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.10174 AGRP Zornitza Stark Gene: agrp has been classified as Red List (Low Evidence).
Mendeliome v0.10174 AGRP Zornitza Stark Phenotypes for gene: AGRP were changed from to {Leanness, inherited} 601665; {Obesity, late-onset} 601665
Mendeliome v0.10173 AGRP Zornitza Stark Classified gene: AGRP as Red List (low evidence)
Mendeliome v0.10173 AGRP Zornitza Stark Gene: agrp has been classified as Red List (Low Evidence).
Mendeliome v0.10172 AGRP Zornitza Stark reviewed gene: AGRP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Leanness, inherited} 601665, {Obesity, late-onset} 601665; Mode of inheritance: None
Mendeliome v0.10172 C1QBP Zornitza Stark Gene: c1qbp has been classified as Green List (High Evidence).
Mendeliome v0.10169 BOLA3 Zornitza Stark Gene: bola3 has been classified as Green List (High Evidence).
Mendeliome v0.10166 B9D2 Zornitza Stark Gene: b9d2 has been classified as Green List (High Evidence).
Mendeliome v0.10162 EBP Zornitza Stark Gene: ebp has been classified as Green List (High Evidence).
Mendeliome v0.10162 EBP Zornitza Stark Phenotypes for gene: EBP were changed from to Chondrodysplasia punctata, X-linked dominant MIM#302960; Conradi-Hunermann syndrome; MEND syndrome, MIM#300960
Mendeliome v0.10159 EBP Zornitza Stark reviewed gene: EBP: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Chondrodysplasia punctata, X-linked dominant MIM#302960, Conradi-Hunermann syndrome, MEND syndrome, MIM#300960; 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 v0.10159 DYM Zornitza Stark Gene: dym has been classified as Green List (High Evidence).
Mendeliome v0.10159 DYM Zornitza Stark Phenotypes for gene: DYM were changed from to Smith-McCort dysplasia , MM#607326; Dyggve-Melchior-Clausen disease, MIM#223800
Mendeliome v0.10156 DYM Zornitza Stark reviewed gene: DYM: Rating: GREEN; Mode of pathogenicity: None; Publications: 12491225, 12554689, 16470731, 19005420; Phenotypes: Smith-McCort dysplasia , MM#607326, Dyggve-Melchior-Clausen disease, MIM#223800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10156 DOCK6 Zornitza Stark Gene: dock6 has been classified as Green List (High Evidence).
Mendeliome v0.10152 DNAH9 Zornitza Stark Gene: dnah9 has been classified as Green List (High Evidence).
Mendeliome v0.10152 DNAH9 Zornitza Stark Phenotypes for gene: DNAH9 were changed from to Ciliary dyskinesia, primary, 40, MIM# 618300
Mendeliome v0.10149 DNAH9 Zornitza Stark reviewed gene: DNAH9: Rating: GREEN; Mode of pathogenicity: None; Publications: 30471717, 30471718; Phenotypes: Ciliary dyskinesia, primary, 40, MIM# 618300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10149 NEK10 Zornitza Stark Phenotypes for gene: NEK10 were changed from Primary ciliary dyskinesia; bronchiectasis to Ciliary dyskinesia, primary, 44, MIM# 618781
Mendeliome v0.10148 NEK10 Zornitza Stark edited their review of gene: NEK10: Changed phenotypes: Ciliary dyskinesia, primary, 44, MIM# 618781
Mendeliome v0.10148 NFIX Zornitza Stark Gene: nfix has been classified as Green List (High Evidence).
Mendeliome v0.10145 GFM1 Zornitza Stark Gene: gfm1 has been classified as Green List (High Evidence).
Mendeliome v0.10142 GJA3 Zornitza Stark Gene: gja3 has been classified as Green List (High Evidence).
Mendeliome v0.10139 NECTIN4 Zornitza Stark Gene: nectin4 has been classified as Green List (High Evidence).
Mendeliome v0.10139 NECTIN4 Zornitza Stark Phenotypes for gene: NECTIN4 were changed from to Ectodermal dysplasia-syndactyly syndrome 1 (MIM#613573)
Mendeliome v0.10136 NECTIN4 Zornitza Stark reviewed gene: NECTIN4: Rating: GREEN; Mode of pathogenicity: None; Publications: 24577405, 20691405, 25529316; Phenotypes: Ectodermal dysplasia-syndactyly syndrome 1 (MIM#613573); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10136 GJC2 Zornitza Stark Gene: gjc2 has been classified as Green List (High Evidence).
Mendeliome v0.10136 GJC2 Zornitza Stark Phenotypes for gene: GJC2 were changed from to Spastic paraplegia 44, autosomal recessive MIM#613206; Leukodystrophy, hypomyelinating, 2 MIM#608804; Lymphatic malformation 3 MIM#613480
Mendeliome v0.10133 EPHB4 Zornitza Stark Gene: ephb4 has been classified as Green List (High Evidence).
Mendeliome v0.10130 WNT4 Zornitza Stark Gene: wnt4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10130 WNT4 Zornitza Stark Phenotypes for gene: WNT4 were changed from to Mullerian aplasia and hyperandrogenism (MIM#158330); SERKAL syndrome, OMIM #611812
Mendeliome v0.10127 WNT4 Zornitza Stark Classified gene: WNT4 as Amber List (moderate evidence)
Mendeliome v0.10127 WNT4 Zornitza Stark Gene: wnt4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10126 WNT4 Zornitza Stark reviewed gene: WNT4: Rating: AMBER; Mode of pathogenicity: None; Publications: 22503279, 21377155, 16959810, 18179883, 15317892, 18182450; Phenotypes: Mullerian aplasia and hyperandrogenism (MIM#158330), SERKAL syndrome, OMIM #611812; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.10126 WWOX Zornitza Stark Gene: wwox has been classified as Green List (High Evidence).
Mendeliome v0.10126 WWOX Zornitza Stark Phenotypes for gene: WWOX were changed from to Spinocerebellar ataxia, autosomal recessive 12, MIM# 614322; Developmental and epileptic encephalopathy 28, MIM# 616211
Mendeliome v0.10123 WWOX Zornitza Stark reviewed gene: WWOX: Rating: GREEN; Mode of pathogenicity: None; Publications: 24456803, 25411445, 32051108, 32037574, 24369382, 34831305, 33916893; Phenotypes: Spinocerebellar ataxia, autosomal recessive 12, MIM# 614322, Developmental and epileptic encephalopathy 28, MIM# 616211; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10123 ZNF750 Zornitza Stark Gene: znf750 has been classified as Red List (Low Evidence).
Mendeliome v0.10123 ZNF750 Zornitza Stark Phenotypes for gene: ZNF750 were changed from to Seborrhea-like dermatitis with psoriasiform elements, MIM# 610227
Mendeliome v0.10120 ZNF750 Zornitza Stark Classified gene: ZNF750 as Red List (low evidence)
Mendeliome v0.10120 ZNF750 Zornitza Stark Gene: znf750 has been classified as Red List (Low Evidence).
Mendeliome v0.10119 ZNF750 Zornitza Stark reviewed gene: ZNF750: Rating: RED; Mode of pathogenicity: None; Publications: 22185198, 16751772, 22936986; Phenotypes: Seborrhea-like dermatitis with psoriasiform elements, MIM# 610227; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10119 GLB1 Zornitza Stark Gene: glb1 has been classified as Green List (High Evidence).
Mendeliome v0.10119 GLB1 Zornitza Stark Phenotypes for gene: GLB1 were changed from to GM1-gangliosidosis, type I MIM#230500; GM1-gangliosidosis, type II MIM# 230600; GM1-gangliosidosis, type III MIM#230650; Mucopolysaccharidosis type IVB (Morquio) MIM#253010
Mendeliome v0.10116 LACC1 Bryony Thompson Gene: lacc1 has been classified as Green List (High Evidence).
Mendeliome v0.10116 LACC1 Bryony Thompson Classified gene: LACC1 as Green List (high evidence)
Mendeliome v0.10116 LACC1 Bryony Thompson Gene: lacc1 has been classified as Green List (High Evidence).
Mendeliome v0.10114 TRIM27 Zornitza Stark Gene: trim27 has been classified as Red List (Low Evidence).
Mendeliome v0.10113 TRIM27 Zornitza Stark Classified gene: TRIM27 as Red List (low evidence)
Mendeliome v0.10113 TRIM27 Zornitza Stark Gene: trim27 has been classified as Red List (Low Evidence).
Mendeliome v0.10112 CR1 Zornitza Stark Gene: cr1 has been classified as Red List (Low Evidence).
Mendeliome v0.10112 CR1 Zornitza Stark Classified gene: CR1 as Red List (low evidence)
Mendeliome v0.10112 CR1 Zornitza Stark Gene: cr1 has been classified as Red List (Low Evidence).
Mendeliome v0.10111 ASTL Zornitza Stark Gene: astl has been classified as Red List (Low Evidence).
Mendeliome v0.10111 ASTL Zornitza Stark gene: ASTL was added
gene: ASTL was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: ASTL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASTL were set to 34704130
Phenotypes for gene: ASTL were set to Oocyte maturation defect 11, MIM# 619643
Review for gene: ASTL was set to RED
Added comment: Oocyte maturation defect-11 (OOMD11) is characterized by reduced or absent fertility and poor embryonic outcomes with assisted reproductive technology. Single family with two affected siblings reported.
Sources: Expert list
Mendeliome v0.10110 TERB2 Zornitza Stark Gene: terb2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10110 TERB2 Zornitza Stark Classified gene: TERB2 as Amber List (moderate evidence)
Mendeliome v0.10110 TERB2 Zornitza Stark Gene: terb2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10109 TERB2 Zornitza Stark gene: TERB2 was added
gene: TERB2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: TERB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TERB2 were set to 33211200
Phenotypes for gene: TERB2 were set to Spermatogenic failure 59, MIM# 619645
Review for gene: TERB2 was set to AMBER
Added comment: One family with three affected siblings; mouse model.
Sources: Literature
Mendeliome v0.10108 SPIDR Bryony Thompson Classified gene: SPIDR as Amber List (moderate evidence)
Mendeliome v0.10108 SPIDR Bryony Thompson Gene: spidr has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10105 REC8 Bryony Thompson Gene: rec8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10105 REC8 Bryony Thompson Classified gene: REC8 as Amber List (moderate evidence)
Mendeliome v0.10105 REC8 Bryony Thompson Gene: rec8 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10104 ATP6V1B2 Zornitza Stark Gene: atp6v1b2 has been classified as Green List (High Evidence).
Mendeliome v0.10103 REC8 Bryony Thompson gene: REC8 was added
gene: REC8 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: REC8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: REC8 were set to 34794894; 15515002; 34707299
Phenotypes for gene: REC8 were set to Primary ovarian insufficiency
Review for gene: REC8 was set to AMBER
Added comment: PMID: 34707299 - a French POI case with compound het predicted loss of function variants
PMID: 15515002 - Rec8-/- female mice demonstrated ovarian dysgenesis and lack of ovarian follicles at reproductive maturity.
PMID: 27603904 - 2 sisters with POI segregating a missense in REC8 inherited from the unaffected mother (p.Gln154Arg) and a missense in GDF9 inherited from the father. Possible digenic inheritance.
Sources: Literature
Mendeliome v0.10101 GDF6 Ain Roesley reviewed gene: GDF6: Rating: GREEN; Mode of pathogenicity: None; Publications: 30733656, 29130651, 26643732, 19129173, 23307924, 32737436; Phenotypes: Klippel-Feil syndrome 1, autosomal dominantMIM#118100, Leber congenital amaurosis 17 (MIM#615360), Microphthalmia, isolated 4 (MIM#613094), Multiple synostoses syndrome 4 (MIM#617898); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10101 MSH5 Bryony Thompson Classified gene: MSH5 as Green List (high evidence)
Mendeliome v0.10101 MSH5 Bryony Thompson Gene: msh5 has been classified as Green List (High Evidence).
Mendeliome v0.10100 MSH5 Bryony Thompson changed review comment from: 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; to: 4 unrelated male azoospermia cases with 3 different homozygous frameshift/missense variants. 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 v0.10100 MSH5 Bryony Thompson changed review comment from: 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; to: 4 unrelated male azoospermia cases with 3 different homozygous frameshift/missense variants. 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 v0.10100 MSH4 Bryony Thompson Gene: msh4 has been classified as Green List (High Evidence).
Mendeliome v0.10100 MSH4 Bryony Thompson Classified gene: MSH4 as Green List (high evidence)
Mendeliome v0.10100 MSH4 Bryony Thompson Gene: msh4 has been classified as Green List (High Evidence).
Mendeliome v0.10099 ASXL2 Zornitza Stark Gene: asxl2 has been classified as Green List (High Evidence).
Mendeliome v0.10096 MSH4 Bryony Thompson gene: MSH4 was added
gene: MSH4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MSH4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MSH4 were set to 34794894; 10809667; 12478991; 28541421; 32741963; 33437391; 34755185; 33448284
Phenotypes for gene: MSH4 were set to Primary ovarian insufficiency; azoospermia
Review for gene: MSH4 was set to GREEN
Added comment: PMID: 34755185 - 2 siblings, 1 with non-obstructive azoospermia and 1 with POI, both homozygous for a stopgain variant. 1 male with non-obstructive azoospermia and biallelic variants.
PMID: 33448284 - 2 sisters with POI and 3 brothers with azoospermia in a consanguineous family with a homozygous missense variant (p.Ser754Leu)
PMID: 33437391 - 1 case with non-obstructive azoospermia with a homozygous stopgain variant
PMID: 32741963 - 2 unrelated cases with spermatogenic arrest with homozygous missense variants (p.Pro638Leu; p. Ser754Leu)
PMID: 28541421 - 2 sisters with POI and homozygous for a splice site variant
PMID: 10809667 - Msh4-/- male mice are infertile and Msh4-/- female mice lacked most oocytes in the ovaries.
Sources: Literature
Mendeliome v0.10095 ASPH Zornitza Stark Gene: asph has been classified as Green List (High Evidence).
Mendeliome v0.10095 ASPH Zornitza Stark Phenotypes for gene: ASPH were changed from to Traboulsi syndrome , MIM#601552
Mendeliome v0.10092 ASPH Zornitza Stark reviewed gene: ASPH: Rating: GREEN; Mode of pathogenicity: None; Publications: 24768550, 30194805, 34018898; Phenotypes: Traboulsi syndrome , MIM#601552; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10092 ARHGAP29 Zornitza Stark Gene: arhgap29 has been classified as Green List (High Evidence).
Mendeliome v0.10089 GJC2 Ain Roesley reviewed gene: GJC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 19056803, 31431325, 25059390, 20537300, 21266381; Phenotypes: Spastic paraplegia 44, autosomal recessive MIM#613206, Leukodystrophy, hypomyelinating, 2 MIM#608804, Lymphatic malformation 3 MIM#613480; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10089 MEIOB Bryony Thompson Classified gene: MEIOB as Green List (high evidence)
Mendeliome v0.10089 MEIOB Bryony Thompson Gene: meiob has been classified as Green List (High Evidence).
Mendeliome v0.10088 MEIOB Bryony Thompson gene: MEIOB was added
gene: MEIOB was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MEIOB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MEIOB were set to 34794894; 24068956; 31000419; 28206990
Phenotypes for gene: MEIOB were set to Spermatogenic failure 22 MIM#617706; primary ovarian insufficiency
Review for gene: MEIOB was set to GREEN
Added comment: At least 6 cases in 3 families, plus a mouse model for spermatogenic failure. A single family and a mouse model for POI.
PMID: 28206990 - 4 infertile brothers with a homozygous missense variant.
PMID: 32741963 - 2 unrelated males with complete spermatocytic arrest and homozygous truncating variants.
PMID: 24068956 - infertile male and female null mouse model.
PMID: 31000419 - Single family with a homozygous splicing variant in 2 sisters with POI.
Sources: Literature
Mendeliome v0.10087 GLB1 Ain Roesley reviewed gene: GLB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24156116; Phenotypes: GM1-gangliosidosis, type I MIM#230500, GM1-gangliosidosis, type II MIM# 230600, GM1-gangliosidosis, type III MIM#230650, Mucopolysaccharidosis type IVB (Morquio) MIM#253010; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.10087 HELQ Bryony Thompson Gene: helq has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10087 HELQ Bryony Thompson commented on gene: HELQ: A single POI heterozygous for a frameshift variant (c.3095delA;p.Tyr1032Serfs*4), and a null mouse model (both homozygous and heterozygous) with subfertility and germ cell attrition.
Mendeliome v0.10087 HELQ Bryony Thompson Classified gene: HELQ as Amber List (moderate evidence)
Mendeliome v0.10087 HELQ Bryony Thompson Gene: helq has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10085 AP3B2 Zornitza Stark Gene: ap3b2 has been classified as Green List (High Evidence).
Mendeliome v0.10082 ANTXR2 Zornitza Stark Gene: antxr2 has been classified as Green List (High Evidence).
Mendeliome v0.10082 ANTXR2 Zornitza Stark Phenotypes for gene: ANTXR2 were changed from to Hyaline fibromatosis syndrome, MIM# 228600; MONDO:0009229
Mendeliome v0.10079 ANTXR2 Zornitza Stark reviewed gene: ANTXR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 12973667, 14508707; Phenotypes: Hyaline fibromatosis syndrome, MIM# 228600, MONDO:0009229; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10079 SLC29A3 Zornitza Stark Gene: slc29a3 has been classified as Green List (High Evidence).
Mendeliome v0.10079 SLC29A3 Zornitza Stark Phenotypes for gene: SLC29A3 were changed from to Histiocytosis-lymphadenopathy plus syndrome, MIM# 602782
Mendeliome v0.10076 SLC29A3 Zornitza Stark reviewed gene: SLC29A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 18940313, 19336477, 22238637; Phenotypes: Histiocytosis-lymphadenopathy plus syndrome, MIM# 602782; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10074 TBC1D32 Zornitza Stark Classified gene: TBC1D32 as Green List (high evidence)
Mendeliome v0.10074 TBC1D32 Zornitza Stark Gene: tbc1d32 has been classified as Green List (High Evidence).
Mendeliome v0.10073 BLOC1S1 Zornitza Stark Gene: bloc1s1 has been classified as Green List (High Evidence).
Mendeliome v0.10073 BLOC1S1 Zornitza Stark Classified gene: BLOC1S1 as Green List (high evidence)
Mendeliome v0.10073 BLOC1S1 Zornitza Stark Gene: bloc1s1 has been classified as Green List (High Evidence).
Mendeliome v0.10071 CLCN7 Zornitza Stark Gene: clcn7 has been classified as Green List (High Evidence).
Mendeliome v0.10071 CLCN7 Zornitza Stark Phenotypes for gene: CLCN7 were changed from to Hypopigmentation, organomegaly, and delayed myelination and development, MIM# 618541; Osteopetrosis, autosomal recessive 4, MIM# 611490
Mendeliome v0.10068 CLCN7 Zornitza Stark reviewed gene: CLCN7: Rating: GREEN; Mode of pathogenicity: None; Publications: 31155284; Phenotypes: Hypopigmentation, organomegaly, and delayed myelination and development, MIM# 618541, Osteopetrosis, autosomal recessive 4, MIM# 611490; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.10068 TMEM260 Zornitza Stark Classified gene: TMEM260 as Green List (high evidence)
Mendeliome v0.10068 TMEM260 Zornitza Stark Gene: tmem260 has been classified as Green List (High Evidence).
Mendeliome v0.10067 SNIP1 Zornitza Stark Classified gene: SNIP1 as Amber List (moderate evidence)
Mendeliome v0.10067 SNIP1 Zornitza Stark Gene: snip1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10066 SNIP1 Zornitza Stark edited their review of gene: SNIP1: Added comment: A single (founder) variant NM_024700.4:c.1097A>G, p.(Glu366Gly) has been reported in over 30 cases of Psychomotor retardation, epilepsy, and craniofacial dysmorphism OMIM:614501 in the Amish community (PMIDs: 22279524; 34570759). Cases are homozygous for this variant and unaffected members of the families are heterozygous or wt. Overexpression of the equivalent mouse variant in mouse inner medullary collecting duct cells, resulted in a more aggregated appearance in the nucleus compared to wildtype. The variant protein maybe unstable as Western blots showed reduced levels of the variant protein (PMID: 22279524). Whole transcriptomic analysis of patient blood was performed in PMID: 34570759. This revealed 11 upregulated and 32 downregulated genes, of which 24 had previously been associated with neurological disease.; Changed rating: AMBER; Changed publications: 22279524, 34570759
Mendeliome v0.10066 TAF4 Zornitza Stark Gene: taf4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10066 TAF4 Zornitza Stark Classified gene: TAF4 as Amber List (moderate evidence)
Mendeliome v0.10066 TAF4 Zornitza Stark Gene: taf4 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10063 RAB11A Zornitza Stark Classified gene: RAB11A as Green List (high evidence)
Mendeliome v0.10063 RAB11A Zornitza Stark Gene: rab11a has been classified as Green List (High Evidence).
Mendeliome v0.10062 PLK1 Zornitza Stark Gene: plk1 has been classified as Green List (High Evidence).
Mendeliome v0.10062 PLK1 Zornitza Stark Classified gene: PLK1 as Green List (high evidence)
Mendeliome v0.10062 PLK1 Zornitza Stark Gene: plk1 has been classified as Green List (High Evidence).
Mendeliome v0.10059 RAP1GDS1 Zornitza Stark Classified gene: RAP1GDS1 as Green List (high evidence)
Mendeliome v0.10059 RAP1GDS1 Zornitza Stark Gene: rap1gds1 has been classified as Green List (High Evidence).
Mendeliome v0.10058 PRRX1 Zornitza Stark Gene: prrx1 has been classified as Green List (High Evidence).
Mendeliome v0.10055 MMP15 Zornitza Stark Gene: mmp15 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10055 MMP15 Zornitza Stark Classified gene: MMP15 as Amber List (moderate evidence)
Mendeliome v0.10055 MMP15 Zornitza Stark Gene: mmp15 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10054 MMP15 Zornitza Stark gene: MMP15 was added
gene: MMP15 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MMP15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMP15 were set to 33875846
Phenotypes for gene: MMP15 were set to Cholestasis; Congenital heart disease
Review for gene: MMP15 was set to AMBER
Added comment: Three individuals from two families with bi-allelic variants and very similar phenotype including rare combination of symtoms (Alagille-like) cholestasis with hepatomegaly and congenital heart disease.
Sources: Literature
Mendeliome v0.10053 RPA1 Zornitza Stark Gene: rpa1 has been classified as Green List (High Evidence).
Mendeliome v0.10053 RPA1 Zornitza Stark Classified gene: RPA1 as Green List (high evidence)
Mendeliome v0.10053 RPA1 Zornitza Stark Gene: rpa1 has been classified as Green List (High Evidence).
Mendeliome v0.10052 RPA1 Zornitza Stark gene: RPA1 was added
gene: RPA1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RPA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPA1 were set to 34767620
Phenotypes for gene: RPA1 were set to Bone marrow failure; T- and B-cell lymphopaenia; pulmonary fibrosis; skin manifestations; short telomeres
Mode of pathogenicity for gene: RPA1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: RPA1 was set to GREEN
Added comment: 4 individuals with gain of function variants with bone marrow failure, myelodysplastic syndrome, T- and B-cell lymphopaenia, pulmonary fibrosis, or skin manifestations reported.
Sources: Literature
Mendeliome v0.10051 AXIN2 Zornitza Stark Gene: axin2 has been classified as Green List (High Evidence).
Mendeliome v0.10048 ATP9A Zornitza Stark Gene: atp9a has been classified as Green List (High Evidence).
Mendeliome v0.10047 ATP9A Zornitza Stark Classified gene: ATP9A as Green List (high evidence)
Mendeliome v0.10047 ATP9A Zornitza Stark Gene: atp9a has been classified as Green List (High Evidence).
Mendeliome v0.10046 ECM1 Zornitza Stark Gene: ecm1 has been classified as Green List (High Evidence).
Mendeliome v0.10044 ECM1 Zornitza Stark changed review comment from: PMID: 11929856 - Hamada et al 2002 - looked at 6 different unrelated consanguineous families (from Saudi Arabia, Kuwait, Pakistan, The Netherlands, UK, and a group of South African families with a probable common ancestor) with a clinical diagnosis of Lipoid proteinosis (LP)/Urbach–Wiethe disease. They performed a genome-wide linkage analysis and identified a region and then looked at the expression of candidate genes in fibroblasts from patients compared to controls. ECM1 was found to have lower expression levels. 6 homozygous deletion variants were identified in the patients. In one family they established that the parents were heterozygous for the variant.

PMID: 28720532 - Afifi et al 2017 - studied 12 patients from 10 unrelated consanguineous Egyptian families with a clinical diagnosis of lipoid proteinosis. The patients reported progressive hoarseness of voice and easily damaged skin by minor trauma or friction. Homozygous ECM1 variants were detected in affected members in all families: 1 family had a missense variant, 5 families had splice site variants and 4 families had indels predicted to cause frameshifts. Parents were found to be heterozygous for the variants.

PMID: 33159951 - Zhu et al 2021 - a novel homozygous three-nucleotide duplication (c.506_508dupCTG) in ECM in two siblings affected with LP from a consanguineous Chinese family.; to: Lipoid proteinosis of Urbach and Wiethe is a rare autosomal recessive disorder typified by generalized thickening of skin, mucosae, and certain viscera. Classic features include beaded eyelid papules and laryngeal infiltration leading to hoarseness. The disorder is clinically heterogeneous, with affected individuals displaying differing degrees of skin scarring and infiltration, variable signs of hoarseness and respiratory distress, and in some cases neurologic abnormalities such as temporal lobe epilepsy. Histologically, there is widespread deposition of hyaline (glycoprotein) material and disruption/reduplication of basement membrane

PMID: 11929856 - Hamada et al 2002 - looked at 6 different unrelated consanguineous families (from Saudi Arabia, Kuwait, Pakistan, The Netherlands, UK, and a group of South African families with a probable common ancestor) with a clinical diagnosis of Lipoid proteinosis (LP)/Urbach–Wiethe disease. They performed a genome-wide linkage analysis and identified a region and then looked at the expression of candidate genes in fibroblasts from patients compared to controls. ECM1 was found to have lower expression levels. 6 homozygous deletion variants were identified in the patients. In one family they established that the parents were heterozygous for the variant.

PMID: 28720532 - Afifi et al 2017 - studied 12 patients from 10 unrelated consanguineous Egyptian families with a clinical diagnosis of lipoid proteinosis. The patients reported progressive hoarseness of voice and easily damaged skin by minor trauma or friction. Homozygous ECM1 variants were detected in affected members in all families: 1 family had a missense variant, 5 families had splice site variants and 4 families had indels predicted to cause frameshifts. Parents were found to be heterozygous for the variants.

PMID: 33159951 - Zhu et al 2021 - a novel homozygous three-nucleotide duplication (c.506_508dupCTG) in ECM in two siblings affected with LP from a consanguineous Chinese family.
Mendeliome v0.10041 SMPX Zornitza Stark edited their review of gene: SMPX: Added comment: PMID 33974137: Four different missense variants were identified in ten patients from nine families in five different countries. Haplotype analysis of patients with similar ancestry revealed two different founder mutations in Southern Europe and France, indicating that the prevalence in these populations may be higher. Clinical features: adult-onset, usually distal more than proximal limb muscle weakness, slowly progressing over decades with preserved walking. Lower limb muscle imaging showed a characteristic pattern of muscle involvement and fatty degeneration. Histopathological and electron microscopic analysis of patient muscle biopsies revealed myopathic findings with rimmed vacuoles and the presence of sarcoplasmic inclusions, some with amyloid-like characteristics. In silico predictions and subsequent cell culture studies showed that the missense mutations increase aggregation propensity of the SMPX protein. In cell culture studies, overexpressed SMPX localized to stress granules and slowed down their clearance.; Changed publications: 21549342, 21549336, 21893181, 22911656, 28542515, 33974137; Changed phenotypes: Deafness, X-linked 4, MIM# 300066, Distal myopathy, adult-onset
Mendeliome v0.10041 PIEZO1 Zornitza Stark Phenotypes for gene: PIEZO1 were changed from Lymphatic malformation 6, 616843; Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema, 194380 to Lymphatic malformation 6, 616843; Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema, 194380; Erythrocytosis
Mendeliome v0.10039 PIEZO1 Zornitza Stark reviewed gene: PIEZO1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 33181827; Phenotypes: Erythrocytosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.10039 CNKSR2 Zornitza Stark Gene: cnksr2 has been classified as Green List (High Evidence).
Mendeliome v0.10036 FGF5 Zornitza Stark Gene: fgf5 has been classified as Green List (High Evidence).
Mendeliome v0.10036 FGF5 Zornitza Stark Classified gene: FGF5 as Green List (high evidence)
Mendeliome v0.10036 FGF5 Zornitza Stark Gene: fgf5 has been classified as Green List (High Evidence).
Mendeliome v0.10035 FGF5 Zornitza Stark gene: FGF5 was added
gene: FGF5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FGF5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FGF5 were set to 24989505
Phenotypes for gene: FGF5 were set to Hypertrichosis
Review for gene: FGF5 was set to GREEN
Added comment: Two families reported, aware of additional unpublished case.
Sources: Literature
Mendeliome v0.10034 ANK3 Zornitza Stark Phenotypes for gene: ANK3 were changed from Mental retardation, autosomal recessive, 37, MIM# 615493 to Mental retardation, autosomal recessive, 37 615493; Intellectual disability, autosomal dominant
Mendeliome v0.10032 ANK3 Zornitza Stark Classified gene: ANK3 as Green List (high evidence)
Mendeliome v0.10032 ANK3 Zornitza Stark Gene: ank3 has been classified as Green List (High Evidence).
Mendeliome v0.10031 ANK3 Zornitza Stark edited their review of gene: ANK3: Added comment: PMID 34218362: four unrelated novel, and two previously published patients with heterozygos ANK3 LoF variants are reported/summarized.; Changed rating: GREEN; Changed publications: 23390136, 28687526, 34218362; Changed phenotypes: Mental retardation, autosomal recessive, 37 615493, Intellectual disability, autosomal dominant
Mendeliome v0.10031 HIBADH Zornitza Stark Gene: hibadh has been classified as Red List (Low Evidence).
Mendeliome v0.10031 HIBADH Zornitza Stark gene: HIBADH was added
gene: HIBADH was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: HIBADH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HIBADH were set to 34176136
Phenotypes for gene: HIBADH were set to Organic aciduria
Review for gene: HIBADH was set to RED
Added comment: Single family reported with two siblings presenting with 3-Hydroxyisobutyric aciduria. Male sib with neurodevelopmental symptoms, female sibling asymptomatic. No functional studies
Sources: Literature
Mendeliome v0.10027 LAMB1 Zornitza Stark edited their review of gene: LAMB1: Added comment: Association between mono-allelic variants and adult-onset leukoencephalopathy:

LAMB1 variants found in 5 families with cerebral small vessel disease. 4 are truncating frameshifts (and 2 of the families have the same frameshift), 1 is a canonical splice. All families had adult onset of symptoms ranging from 20-63yo. All have white matter hypersignals. ‘These variants are associated with a novel phenotype characterized by the association of a hippocampal type episodic memory defect and a diffuse vascular leukoencephalopathy.’; Changed publications: 23472759, 25925986, 29888467, 25925986, 32548278, 34606115; Changed phenotypes: Lissencephaly 5, MIM# 615191, Cystic leukoencephalopathy, Adult-onset leukoencephalopathy; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.10027 OGDHL Alison Yeung Gene: ogdhl has been classified as Green List (High Evidence).
Mendeliome v0.10027 OGDHL Alison Yeung Classified gene: OGDHL as Green List (high evidence)
Mendeliome v0.10027 OGDHL Alison Yeung Gene: ogdhl has been classified as Green List (High Evidence).
Mendeliome v0.10026 SLIRP Zornitza Stark Gene: slirp has been classified as Red List (Low Evidence).
Mendeliome v0.10026 SLIRP Zornitza Stark Classified gene: SLIRP as Red List (low evidence)
Mendeliome v0.10026 SLIRP Zornitza Stark Gene: slirp has been classified as Red List (Low Evidence).
Mendeliome v0.10025 FOXR1 Zornitza Stark Gene: foxr1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10025 FOXR1 Zornitza Stark Classified gene: FOXR1 as Amber List (moderate evidence)
Mendeliome v0.10025 FOXR1 Zornitza Stark Gene: foxr1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10024 TAB2 Zornitza Stark Gene: tab2 has been classified as Green List (High Evidence).
Mendeliome v0.10021 FAAH2 Zornitza Stark Gene: faah2 has been classified as Red List (Low Evidence).
Mendeliome v0.10020 FAAH2 Zornitza Stark Classified gene: FAAH2 as Red List (low evidence)
Mendeliome v0.10020 FAAH2 Zornitza Stark Gene: faah2 has been classified as Red List (Low Evidence).
Mendeliome v0.10019 FOXR1 Paul De Fazio changed review comment from: 1 patient described with a de novo missense variant. Phenotypes include: postnatal microcephaly, progressive brain atrophy, skeletal abnormalities, brain abnormalities, ophthalmic abnormalities, neuromuscular abnornmalities, and dysmorphic features.

In vitro functional evidence is supportive of pathogenicity (variant causes protein instability and abnormal nuclear aggregation).

A mouse knockout has comparable phenotypes, and a severe survival deficit.

Rated amber (1 patient, functional evidence, mouse model).
Sources: Literature; to: 1 patient described with a de novo missense variant. Phenotypes include: postnatal microcephaly, progressive brain atrophy, skeletal abnormalities, brain abnormalities, ophthalmic abnormalities, neuromuscular abnormalities, and dysmorphic features. A variant in ATP1A3 was considered to have contributed to the final phenotype.

In vitro functional evidence is supportive of pathogenicity (variant causes protein instability and abnormal nuclear aggregation).

A mouse knockout has comparable phenotypes, and a severe survival deficit.

Rated amber (1 patient, functional evidence, mouse model).
Sources: Literature
Mendeliome v0.10019 SLIRP Belinda Chong gene: SLIRP was added
gene: SLIRP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SLIRP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLIRP were set to 34426662
Phenotypes for gene: SLIRP were set to Mitochondrial encephalomyopathy with complex I and IV deficiency
Review for gene: SLIRP was set to RED
Added comment: Single Dutch non-consanguineous patient having mitochondrial encephalomyopathy with complex I and complex IV deficiency, whole exome sequencing revealed two compound heterozygous variants (NM_031210.5:c.248_252del; NP_112487.1:p.(Ile83Argfs*10) and NC_000014.8:g.78177003 A > G; NM_031210.5:c.98-178 A > G) in SLIRP. Report SLIRP variants as a novel cause of mitochondrial encephalomyopathy with OXPHOS deficiency
Sources: Literature
Mendeliome v0.10019 OGDH Zornitza Stark Gene: ogdh has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10019 OGDH Zornitza Stark Classified gene: OGDH as Amber List (moderate evidence)
Mendeliome v0.10019 OGDH Zornitza Stark Gene: ogdh has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10018 OGDH Zornitza Stark gene: OGDH was added
gene: OGDH was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: OGDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OGDH were set to 32383294
Phenotypes for gene: OGDH were set to Developmental delay; ataxia; seizure; raised lactate
Review for gene: OGDH was set to AMBER
Added comment: Two siblings reported with homozygous missense variant in this gene and global developmental delay, elevated lactate, ataxia and seizure. Fibroblast analysis and modeling of the mutation in Drosophila were used to evaluate pathogenicity of the variant. Note previous report of an individual with developmental delay, hypotonia, and movement disorders and metabolic decompensation and biochemical evidence of OGDH deficiency but genetic testing not done.
Sources: Literature
Mendeliome v0.10017 FOXR1 Paul De Fazio gene: FOXR1 was added
gene: FOXR1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FOXR1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FOXR1 were set to 34723967
Phenotypes for gene: FOXR1 were set to Postnatal microcephaly, progressive brain atrophy and global developmental delay
Review for gene: FOXR1 was set to AMBER
gene: FOXR1 was marked as current diagnostic
Added comment: 1 patient described with a de novo missense variant. Phenotypes include: postnatal microcephaly, progressive brain atrophy, skeletal abnormalities, brain abnormalities, ophthalmic abnormalities, neuromuscular abnornmalities, and dysmorphic features.

In vitro functional evidence is supportive of pathogenicity (variant causes protein instability and abnormal nuclear aggregation).

A mouse knockout has comparable phenotypes, and a severe survival deficit.

Rated amber (1 patient, functional evidence, mouse model).
Sources: Literature
Mendeliome v0.10017 FAAH2 Ain Roesley changed review comment from: PMID: 34645488;
- 1x nonsense variant inherited from normal mother
- proband presented with a classical Zellweger syndrome phenotype including global developmental delay, seizure disorder, severe hypotonia, failure to thrive, adrenal insufficiency and elevated very long-chain fatty acids and liver enzymes
- this variant has 2 hemizygotes in gnomAD

PMID: 25885783;
- 1x missense inherited from normal mother and absent in normal brother
- presented with autistic features, anxiety, pseudoseizures, ataxia, supranuclear gaze palsy, and isolated learning disabilities
- biochemical studies on patient fibroblasts confirmed a defect in FAAH2 activity resulting in altered levels of endocannabinoid metabolites.
- BUT this variant has 30 hemizygotes in gnomoad
Sources: Literature; to: PMID: 34645488;
- 1x nonsense variant inherited from normal mother
- proband presented with a classical Zellweger syndrome phenotype including global developmental delay, seizure disorder, severe hypotonia, failure to thrive, adrenal insufficiency and elevated very long-chain fatty acids and liver enzymes
- this variant has 2 hemizygotes in gnomAD

PMID: 25885783;
- 1x missense inherited from normal mother and absent in normal brother
- presented with autistic features, anxiety, pseudoseizures, ataxia, supranuclear gaze palsy, and isolated learning disabilities
- biochemical studies on patient fibroblasts confirmed a defect in FAAH2 activity resulting in altered levels of endocannabinoid metabolites.
- BUT this variant has 30 hemizygotes in gnomAD
Sources: Literature
Mendeliome v0.10017 FAAH2 Ain Roesley gene: FAAH2 was added
gene: FAAH2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: FAAH2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: FAAH2 were set to PMID: 34645488
Penetrance for gene: FAAH2 were set to unknown
Review for gene: FAAH2 was set to RED
gene: FAAH2 was marked as current diagnostic
Added comment: PMID: 34645488;
- 1x nonsense variant inherited from normal mother
- proband presented with a classical Zellweger syndrome phenotype including global developmental delay, seizure disorder, severe hypotonia, failure to thrive, adrenal insufficiency and elevated very long-chain fatty acids and liver enzymes
- this variant has 2 hemizygotes in gnomAD

PMID: 25885783;
- 1x missense inherited from normal mother and absent in normal brother
- presented with autistic features, anxiety, pseudoseizures, ataxia, supranuclear gaze palsy, and isolated learning disabilities
- biochemical studies on patient fibroblasts confirmed a defect in FAAH2 activity resulting in altered levels of endocannabinoid metabolites.
- BUT this variant has 30 hemizygotes in gnomoad
Sources: Literature
Mendeliome v0.10017 NT5E Zornitza Stark Gene: nt5e has been classified as Green List (High Evidence).
Mendeliome v0.10014 ARPC4 Bryony Thompson Gene: arpc4 has been classified as Green List (High Evidence).
Mendeliome v0.10014 ARPC4 Bryony Thompson Classified gene: ARPC4 as Green List (high evidence)
Mendeliome v0.10014 ARPC4 Bryony Thompson Gene: arpc4 has been classified as Green List (High Evidence).
Mendeliome v0.10013 ARPC4 Bryony Thompson gene: ARPC4 was added
gene: ARPC4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ARPC4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARPC4 were set to DOI:https://doi.org/10.1016/j.xhgg.2021.100072
Phenotypes for gene: ARPC4 were set to Microcephaly; mild motor delays; significant speech impairment
Review for gene: ARPC4 was set to GREEN
Added comment: 7 affected individuals from 6 families (gonadal mosaicism was confirmed in the mother of the 2 affected siblings) with a recurrent missense variant (NM_005718.4:c.472C>T; p.R158C). The variant was associated with a decreased amount of F-actin in cells from two affected individuals.
Sources: Literature
Mendeliome v0.10012 TNFRSF11A Zornitza Stark Gene: tnfrsf11a has been classified as Green List (High Evidence).
Mendeliome v0.10012 TNFRSF11A Zornitza Stark Phenotypes for gene: TNFRSF11A were changed from to Osteopetrosis, autosomal recessive 7 - MIM# 612301
Mendeliome v0.10009 TNFRSF11A Zornitza Stark reviewed gene: TNFRSF11A: Rating: GREEN; Mode of pathogenicity: None; Publications: 18606301, 32048120; Phenotypes: Osteopetrosis, autosomal recessive 7 - MIM# 612301; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.10009 RNF125 Zornitza Stark Gene: rnf125 has been classified as Green List (High Evidence).
Mendeliome v0.10006 ERMAP Zornitza Stark Gene: ermap has been classified as Red List (Low Evidence).
Mendeliome v0.10005 ERMAP Zornitza Stark Classified gene: ERMAP as Red List (low evidence)
Mendeliome v0.10005 ERMAP Zornitza Stark Gene: ermap has been classified as Red List (Low Evidence).
Mendeliome v0.10004 UNC93B1 Zornitza Stark Gene: unc93b1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10001 UNC93B1 Zornitza Stark Classified gene: UNC93B1 as Amber List (moderate evidence)
Mendeliome v0.10001 UNC93B1 Zornitza Stark Gene: unc93b1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.10000 UNC93B1 Zornitza Stark Classified gene: UNC93B1 as Red List (low evidence)
Mendeliome v0.10000 UNC93B1 Zornitza Stark Gene: unc93b1 has been classified as Red List (Low Evidence).
Mendeliome v0.9999 PLS3 Zornitza Stark Gene: pls3 has been classified as Green List (High Evidence).
Mendeliome v0.9999 PLS3 Zornitza Stark Phenotypes for gene: PLS3 were changed from to Bone mineral density QTL18, osteoporosis - MIM#300910
Mendeliome v0.9996 PLS3 Zornitza Stark reviewed gene: PLS3: Rating: GREEN; Mode of pathogenicity: None; Publications: 32655496, 25209159, 29736964, 29884797, 28777485, 24088043; Phenotypes: Bone mineral density QTL18, osteoporosis - MIM#300910; 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 v0.9996 MMP9 Zornitza Stark Gene: mmp9 has been classified as Green List (High Evidence).
Mendeliome v0.9996 MMP9 Zornitza Stark Phenotypes for gene: MMP9 were changed from to Metaphyseal anadysplasia 2, MIM# 613073
Mendeliome v0.9993 MMP9 Zornitza Stark reviewed gene: MMP9: Rating: GREEN; Mode of pathogenicity: None; Publications: 19615667, 28342220, 34407464; Phenotypes: Metaphyseal anadysplasia 2, MIM# 613073; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9993 EDN3 Zornitza Stark Gene: edn3 has been classified as Green List (High Evidence).
Mendeliome v0.9990 DLL3 Zornitza Stark Gene: dll3 has been classified as Green List (High Evidence).
Mendeliome v0.9990 DLL3 Zornitza Stark Phenotypes for gene: DLL3 were changed from to Spondylocostal dysostosis 1, autosomal recessive, MIM# 277300
Mendeliome v0.9987 DLL3 Zornitza Stark reviewed gene: DLL3: Rating: GREEN; Mode of pathogenicity: None; Publications: 10742114, 12746394; Phenotypes: Spondylocostal dysostosis 1, autosomal recessive, MIM# 277300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9984 CARD10 Zornitza Stark Gene: card10 has been classified as Red List (Low Evidence).
Mendeliome v0.9984 CARD10 Zornitza Stark gene: CARD10 was added
gene: CARD10 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: CARD10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CARD10 were set to 32238915
Phenotypes for gene: CARD10 were set to Immunodeficiency 89 and autoimmunity, MIM# 619632
Review for gene: CARD10 was set to RED
Added comment: A pair of siblings reported with adult onset of recurrent infections, allergies, microcytic anaemia, and Crohn disease. Homozygous missense variant.
Sources: Expert list
Mendeliome v0.9983 TBX21 Zornitza Stark Gene: tbx21 has been classified as Red List (Low Evidence).
Mendeliome v0.9980 TBX21 Zornitza Stark Classified gene: TBX21 as Red List (low evidence)
Mendeliome v0.9980 TBX21 Zornitza Stark Gene: tbx21 has been classified as Red List (Low Evidence).
Mendeliome v0.9979 SMAD2 Melanie Marty changed review comment from: 9 individuals from 5 families with wide spectrum of autosomal dominant aortic and arterial aneurysmal disease combined with connective tissue disease similar to Marfan syndrome and Loeys-Dietz syndrome.; to: 10 individuals from 5 families with wide spectrum of autosomal dominant aortic and arterial aneurysmal disease combined with connective tissue disease similar to Marfan syndrome and Loeys-Dietz syndrome.
Mendeliome v0.9979 DHCR24 Zornitza Stark Gene: dhcr24 has been classified as Green List (High Evidence).
Mendeliome v0.9979 DHCR24 Zornitza Stark Phenotypes for gene: DHCR24 were changed from to Desmosterolosis MIM#602398; Disorders of the metabolism of sterols
Mendeliome v0.9976 DHCR24 Zornitza Stark reviewed gene: DHCR24: Rating: GREEN; Mode of pathogenicity: None; Publications: 33524375, 21671375, 12457401, 29175559, 21559050, 29175559; Phenotypes: Desmosterolosis, MIM# 602398; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9976 EMD Zornitza Stark Gene: emd has been classified as Green List (High Evidence).
Mendeliome v0.9973 MTPAP Zornitza Stark Gene: mtpap has been classified as Green List (High Evidence).
Mendeliome v0.9973 MTPAP Zornitza Stark Phenotypes for gene: MTPAP were changed from to Spastic ataxia 4, autosomal recessive 613672; Lethal encephalopathy
Mendeliome v0.9970 MTPAP Zornitza Stark reviewed gene: MTPAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 20970105, 25008111, 26319014, 31779033; Phenotypes: Spastic ataxia 4, autosomal recessive 613672, Lethal encephalopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9970 GTPBP3 Zornitza Stark Gene: gtpbp3 has been classified as Green List (High Evidence).
Mendeliome v0.9967 GRIP1 Zornitza Stark Gene: grip1 has been classified as Green List (High Evidence).
Mendeliome v0.9964 GRHL3 Zornitza Stark Gene: grhl3 has been classified as Green List (High Evidence).
Mendeliome v0.9961 GNPTAB Zornitza Stark Gene: gnptab has been classified as Green List (High Evidence).
Mendeliome v0.9961 GNPTAB Zornitza Stark Phenotypes for gene: GNPTAB were changed from to Mucolipidosis II alpha/beta, MIM# 252500; MONDO:0009650; Mucolipidosis III alpha/beta, MIM# 252600; MONDO:0018931
Mendeliome v0.9958 GNPTAB Zornitza Stark reviewed gene: GNPTAB: Rating: GREEN; Mode of pathogenicity: None; Publications: 16465621; Phenotypes: Mucolipidosis II alpha/beta, MIM# 252500, MONDO:0009650, Mucolipidosis III alpha/beta, MIM# 252600, MONDO:0018931; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9958 AMMECR1 Zornitza Stark Gene: ammecr1 has been classified as Green List (High Evidence).
Mendeliome v0.9958 AMMECR1 Zornitza Stark Phenotypes for gene: AMMECR1 were changed from to Midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis, MIM# 300990
Mendeliome v0.9955 AMMECR1 Zornitza Stark reviewed gene: AMMECR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27811305, 28089922, 29193635; Phenotypes: Midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis, MIM# 300990; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.9955 AMACR Zornitza Stark Gene: amacr has been classified as Green List (High Evidence).
Mendeliome v0.9955 AMACR Zornitza Stark Phenotypes for gene: AMACR were changed from to Bile acid synthesis defect, congenital, 4, MIM# 214950; Alpha-methylacyl-CoA racemase deficiency, MIM# 614307
Mendeliome v0.9952 AMACR Zornitza Stark reviewed gene: AMACR: Rating: GREEN; Mode of pathogenicity: None; Publications: 31951345, 24735479, 12512044, 10655068, 34267495, 33047465; Phenotypes: Bile acid synthesis defect, congenital, 4, MIM# 214950, Alpha-methylacyl-CoA racemase deficiency, MIM# 614307; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9952 GNPTAB Ain Roesley reviewed gene: GNPTAB: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301728; Phenotypes: Mucolipidosis II alpha/beta MIM#252500, Mucolipidosis III alpha/beta MIM#252600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.9951 DMC1 Bryony Thompson Gene: dmc1 has been classified as Green List (High Evidence).
Mendeliome v0.9951 DMC1 Bryony Thompson Classified gene: DMC1 as Green List (high evidence)
Mendeliome v0.9951 DMC1 Bryony Thompson Gene: dmc1 has been classified as Green List (High Evidence).
Mendeliome v0.9950 DMC1 Bryony Thompson gene: DMC1 was added
gene: DMC1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DMC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DMC1 were set to 34794894; 29331980; 9660954; 9660953; 18166824
Phenotypes for gene: DMC1 were set to Primary ovarian insufficiency; non-obstructive azoospermia
Review for gene: DMC1 was set to GREEN
Added comment: PMID: 34515795 - a homozygous frameshift (p. Glu10Asnfs*31) cosegregated with non-obstructive azoospermia in 1 brother and diminished ovarian reserve (not primary ovarian insufficiency) in 2 sisters in a non-consanguineous family. Further homozygous knockout mice study demonstrated total failure of follicle development and spermatogenesis in male mice.
PMID: 29331980 - a homozygous missense (p.Asp36Asn) cosegregated with non-obstructive azoospermia and POI phenotypes in a single family.
PMID: 18166824 - a POI case identified with a homozygous missense (p.Met200Val, 185 homozygotes in gnomAD v2.1), which is too common for a recessive Mendelian disease
PMID: 9660954, 9660953 - both male and female knockout mice are sterile
Sources: Literature
Mendeliome v0.9949 CPEB1 Bryony Thompson Gene: cpeb1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9949 CPEB1 Bryony Thompson Classified gene: CPEB1 as Amber List (moderate evidence)
Mendeliome v0.9949 CPEB1 Bryony Thompson Gene: cpeb1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9947 CD44 Zornitza Stark Gene: cd44 has been classified as Red List (Low Evidence).
Mendeliome v0.9946 CD44 Zornitza Stark Classified gene: CD44 as Red List (low evidence)
Mendeliome v0.9946 CD44 Zornitza Stark Gene: cd44 has been classified as Red List (Low Evidence).
Mendeliome v0.9944 BCAM Zornitza Stark Gene: bcam has been classified as Red List (Low Evidence).
Mendeliome v0.9944 BCAM Zornitza Stark Classified gene: BCAM as Red List (low evidence)
Mendeliome v0.9944 BCAM Zornitza Stark Gene: bcam has been classified as Red List (Low Evidence).
Mendeliome v0.9943 DDR2 Zornitza Stark Gene: ddr2 has been classified as Green List (High Evidence).
Mendeliome v0.9943 DDR2 Zornitza Stark Phenotypes for gene: DDR2 were changed from to Spondylometaepiphyseal dysplasia, short limb-hand type, MIM#271665; Warburg-Cinotti syndrome, MIM# 618175
Mendeliome v0.9940 DDR2 Zornitza Stark reviewed gene: DDR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 19110212, 20223752, 30449416; Phenotypes: Spondylometaepiphyseal dysplasia, short limb-hand type, MIM#271665, Warburg-Cinotti syndrome, MIM# 618175; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.9940 PRKG2 Zornitza Stark Phenotypes for gene: PRKG2 were changed from Acromesomelic dysplasia to Acromesomelic dysplasia 4, MIM# 619636; Spondylometaphyseal dysplasia, Pagnamenta type, MIM# 619638
Mendeliome v0.9939 PRKG2 Zornitza Stark edited their review of gene: PRKG2: Changed phenotypes: Acromesomelic dysplasia 4, MIM# 619636, Spondylometaphyseal dysplasia, Pagnamenta type, MIM# 619638
Mendeliome v0.9939 MSX2 Zornitza Stark Gene: msx2 has been classified as Green List (High Evidence).
Mendeliome v0.9939 MSX2 Zornitza Stark Phenotypes for gene: MSX2 were changed from to Craniosynostosis 2 (MIM#604757); Parietal foramina 1 (MIM#168500); Parietal foramina with cleidocranial dysplasia (MIM#168550)
Mendeliome v0.9936 AKT2 Zornitza Stark Gene: akt2 has been classified as Green List (High Evidence).
Mendeliome v0.9936 BNC1 Bryony Thompson Gene: bnc1 has been classified as Green List (High Evidence).
Mendeliome v0.9933 BNC1 Bryony Thompson Classified gene: BNC1 as Green List (high evidence)
Mendeliome v0.9933 BNC1 Bryony Thompson Gene: bnc1 has been classified as Green List (High Evidence).
Mendeliome v0.9931 ACVR1 Zornitza Stark Phenotypes for gene: ACVR1 were changed from Fibrodysplasia ossificans progressiva, MIM# 135100 to Fibrodysplasia ossificans progressiva, MIM# 135100; Congenital heart disease
Mendeliome v0.9929 ACVR1 Zornitza Stark changed review comment from: Fibrodysplasia ossificans progressiva is a rare autosomal dominant disease with complete penetrance involving progressive ossification of skeletal muscle, fascia, tendons, and ligaments. FOP has a prevalence of approximately 1 in 2 million worldwide, and shows no geographic, ethnic, racial, or gender preference. Individuals with FOP appear normal at birth except for great toe abnormalities: the great toes are short, deviated, and monophalangic. Ossification occurs progressively over the course of a lifetime in an inevitable and unpredictable episodic manner.

Multiple unrelated families reported. The R206H variant is recurrent.; to: Fibrodysplasia ossificans progressiva is a rare autosomal dominant disease with complete penetrance involving progressive ossification of skeletal muscle, fascia, tendons, and ligaments. FOP has a prevalence of approximately 1 in 2 million worldwide, and shows no geographic, ethnic, racial, or gender preference. Individuals with FOP appear normal at birth except for great toe abnormalities: the great toes are short, deviated, and monophalangic. Ossification occurs progressively over the course of a lifetime in an inevitable and unpredictable episodic manner.

Multiple unrelated families reported. The R206H variant is recurrent.

Note variants in this gene are also associated with congenital heart disease, PMID 29089047.
Mendeliome v0.9929 ACVR1 Zornitza Stark edited their review of gene: ACVR1: Changed publications: 16642017, 29089047; Changed phenotypes: Fibrodysplasia ossificans progressiva, MIM# 135100, Congenital heart disease
Mendeliome v0.9929 MSX2 Daniel Flanagan reviewed gene: MSX2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23949913, 27884935, 23918290, 2359311, 22948472, 19533795, 10742103, 14571277; Phenotypes: Craniosynostosis 2 (MIM#604757), Parietal foramina 1 (MIM#168500), Parietal foramina with cleidocranial dysplasia (MIM#168550); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9929 ACVR1 Zornitza Stark Gene: acvr1 has been classified as Green List (High Evidence).
Mendeliome v0.9929 ACVR1 Zornitza Stark Phenotypes for gene: ACVR1 were changed from to Fibrodysplasia ossificans progressiva, MIM# 135100
Mendeliome v0.9926 ACVR1 Zornitza Stark reviewed gene: ACVR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 16642017; Phenotypes: Fibrodysplasia ossificans progressiva, MIM# 135100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9926 MOCS2 Zornitza Stark Gene: mocs2 has been classified as Green List (High Evidence).
Mendeliome v0.9923 ANKRD31 Bryony Thompson Gene: ankrd31 has been classified as Green List (High Evidence).
Mendeliome v0.9923 ANKRD31 Bryony Thompson Classified gene: ANKRD31 as Green List (high evidence)
Mendeliome v0.9923 ANKRD31 Bryony Thompson Gene: ankrd31 has been classified as Green List (High Evidence).
Mendeliome v0.9921 ACO2 Zornitza Stark Gene: aco2 has been classified as Green List (High Evidence).
Mendeliome v0.9918 DAZL Bryony Thompson Gene: dazl has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9918 DAZL Bryony Thompson Classified gene: DAZL as Amber List (moderate evidence)
Mendeliome v0.9918 DAZL Bryony Thompson Gene: dazl has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9917 DAZL Bryony Thompson gene: DAZL was added
gene: DAZL was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: DAZL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DAZL were set to 34794894; 33095795; 16884537; 9288969
Phenotypes for gene: DAZL were set to Primary ovarian insufficiency
Review for gene: DAZL was set to AMBER
Added comment: PMID: 33095795 - Single POI case with heterozygous stopgain (c.640C>T:p.Q214*).
PMID: 16884537 - 4 heterozygous unrelated early menopause/POI cases with heterozygous missense (all rare in gnomAD v2.1, except p.Asn10His which has 14 hets)
PMID: 9288969 - supporting knockout mouse model
Sources: Literature
Mendeliome v0.9915 CYP17A1 Zornitza Stark Gene: cyp17a1 has been classified as Green List (High Evidence).
Mendeliome v0.9912 CYP11B1 Zornitza Stark Gene: cyp11b1 has been classified as Green List (High Evidence).
Mendeliome v0.9912 CYP11B1 Zornitza Stark Phenotypes for gene: CYP11B1 were changed from to Adrenal hyperplasia, congenital, due to 11-beta-hydroxylase deficiency, MIM# 202010; Aldosteronism, glucocorticoid-remediable, MIM# 103900
Mendeliome v0.9909 CYP11B1 Zornitza Stark reviewed gene: CYP11B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 8768848, 1731223, 29703198; Phenotypes: Adrenal hyperplasia, congenital, due to 11-beta-hydroxylase deficiency, MIM# 202010, Aldosteronism, glucocorticoid-remediable, MIM# 103900; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.9909 CYP11A1 Zornitza Stark Gene: cyp11a1 has been classified as Green List (High Evidence).
Mendeliome v0.9906 CWC27 Zornitza Stark Gene: cwc27 has been classified as Green List (High Evidence).
Mendeliome v0.9903 PPIB Zornitza Stark Gene: ppib has been classified as Green List (High Evidence).
Mendeliome v0.9903 PPIB Zornitza Stark Phenotypes for gene: PPIB were changed from to Osteogenesis imperfecta, type IX, MIM# 259440
Mendeliome v0.9900 PPIB Zornitza Stark reviewed gene: PPIB: Rating: GREEN; Mode of pathogenicity: None; Publications: 19781681, 32392875; Phenotypes: Osteogenesis imperfecta, type IX, MIM# 259440; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9900 POLR3H Bryony Thompson Gene: polr3h has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9900 POLR3H Bryony Thompson Classified gene: POLR3H as Amber List (moderate evidence)
Mendeliome v0.9900 POLR3H Bryony Thompson Gene: polr3h has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9898 POLR2C Bryony Thompson Gene: polr2c has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9898 POLR2C Bryony Thompson Classified gene: POLR2C as Amber List (moderate evidence)
Mendeliome v0.9898 POLR2C Bryony Thompson Gene: polr2c has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9897 POLR2C Bryony Thompson gene: POLR2C was added
gene: POLR2C was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: POLR2C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLR2C were set to 34794894; 29367954
Phenotypes for gene: POLR2C were set to Primary ovarian insufficiency
Review for gene: POLR2C was set to AMBER
Added comment: One family with POI segregating a nonsense variant (p.Lys152Ter) and a case with sporadic POI with a splice region variant (c.206-3C>T). Knockdown of the gene in an embryonic carcinoma cell line resulted in decreased protein production and impaired cell proliferation.
Two missense in premature ovarian failure cases submitted to ClinVar by Shandong Provincial Hospital Affiliated to Shandong University (SCV001877131.1, SCV001877153.1).
Sources: Literature
Mendeliome v0.9896 ELAC2 Zornitza Stark Gene: elac2 has been classified as Green List (High Evidence).
Mendeliome v0.9893 KHDRBS1 Bryony Thompson Gene: khdrbs1 has been classified as Green List (High Evidence).
Mendeliome v0.9893 KHDRBS1 Bryony Thompson Classified gene: KHDRBS1 as Green List (high evidence)
Mendeliome v0.9893 KHDRBS1 Bryony Thompson Gene: khdrbs1 has been classified as Green List (High Evidence).
Mendeliome v0.9891 CUL4B Zornitza Stark Gene: cul4b has been classified as Green List (High Evidence).
Mendeliome v0.9888 CTSK Zornitza Stark Gene: ctsk has been classified as Green List (High Evidence).
Mendeliome v0.9888 CTSK Zornitza Stark Phenotypes for gene: CTSK were changed from to Pycnodysostosis, MIM# 265800
Mendeliome v0.9886 CTSK Zornitza Stark reviewed gene: CTSK: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Pycnodysostosis, MIM# 265800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9886 CTCF Zornitza Stark Gene: ctcf has been classified as Green List (High Evidence).
Mendeliome v0.9883 CSNK2A1 Zornitza Stark Gene: csnk2a1 has been classified as Green List (High Evidence).
Mendeliome v0.9880 CRYGD Zornitza Stark Gene: crygd has been classified as Green List (High Evidence).
Mendeliome v0.9877 CRYGC Zornitza Stark Gene: crygc has been classified as Green List (High Evidence).
Mendeliome v0.9874 CRYBB3 Zornitza Stark Gene: crybb3 has been classified as Green List (High Evidence).
Mendeliome v0.9871 CRYBB2 Zornitza Stark Gene: crybb2 has been classified as Green List (High Evidence).
Mendeliome v0.9868 CRYBB1 Zornitza Stark Gene: crybb1 has been classified as Green List (High Evidence).
Mendeliome v0.9865 TNFAIP3 Zornitza Stark Gene: tnfaip3 has been classified as Green List (High Evidence).
Mendeliome v0.9862 SFTPA1 Zornitza Stark Phenotypes for gene: SFTPA1 were changed from Idiopathic pulmonary fibrosis to Idiopathic pulmonary fibrosis; Interstitial lung disease 1, MIM# 619611
Mendeliome v0.9861 SFTPA1 Zornitza Stark edited their review of gene: SFTPA1: Changed phenotypes: Idiopathic pulmonary fibrosis, Interstitial lung disease 1, MIM# 619611
Mendeliome v0.9861 PI4KA Zornitza Stark Phenotypes for gene: PI4KA were changed from Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, MIM# 616531; Neurodevelopmental syndrome with hypomyelinating leukodystrophy to Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, MIM# 616531; Neurodevelopmental syndrome with hypomyelinating leukodystrophy; Spastic paraplegia 84, autosomal recessive, MIM# 619621
Mendeliome v0.9860 PI4KA Zornitza Stark edited their review of gene: PI4KA: Changed phenotypes: Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis, MIM# 616531, Neurodevelopmental syndrome with hypomyelinating leukodystrophy, Spastic paraplegia 84, autosomal recessive, MIM# 619621
Mendeliome v0.9860 UCP2 Zornitza Stark Gene: ucp2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9860 UCP2 Zornitza Stark Phenotypes for gene: UCP2 were changed from to {Obesity, susceptibility to, BMIQ4} 607447; Hyperinsulinism
Mendeliome v0.9857 UCP2 Zornitza Stark Classified gene: UCP2 as Amber List (moderate evidence)
Mendeliome v0.9857 UCP2 Zornitza Stark Gene: ucp2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9856 UCP2 Zornitza Stark reviewed gene: UCP2: Rating: AMBER; Mode of pathogenicity: None; Publications: 19065272, 11381268; Phenotypes: {Obesity, susceptibility to, BMIQ4} 607447, Hyperinsulinism; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9856 CRYBA4 Zornitza Stark Gene: cryba4 has been classified as Green List (High Evidence).
Mendeliome v0.9853 CRYBA1 Zornitza Stark Gene: cryba1 has been classified as Green List (High Evidence).
Mendeliome v0.9850 CRYAA Zornitza Stark Gene: cryaa has been classified as Green List (High Evidence).
Mendeliome v0.9847 CALU Zornitza Stark Gene: calu has been classified as Red List (Low Evidence).
Mendeliome v0.9847 CALU Zornitza Stark Classified gene: CALU as Red List (low evidence)
Mendeliome v0.9847 CALU Zornitza Stark Gene: calu has been classified as Red List (Low Evidence).
Mendeliome v0.9846 EDNRA Zornitza Stark Gene: ednra has been classified as Green List (High Evidence).
Mendeliome v0.9846 EDNRA Zornitza Stark Phenotypes for gene: EDNRA were changed from to Mandibulofacial dysostosis with alopecia, MIM# 616367
Mendeliome v0.9843 EDNRA Zornitza Stark reviewed gene: EDNRA: Rating: GREEN; Mode of pathogenicity: None; Publications: 25772936, 27671791; Phenotypes: Mandibulofacial dysostosis with alopecia, MIM# 616367; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9843 DVL3 Zornitza Stark Gene: dvl3 has been classified as Green List (High Evidence).
Mendeliome v0.9840 IRF6 Zornitza Stark Gene: irf6 has been classified as Green List (High Evidence).
Mendeliome v0.9838 IRF6 Zornitza Stark Gene: irf6 has been classified as Green List (High Evidence).
Mendeliome v0.9835 MATN3 Zornitza Stark Gene: matn3 has been classified as Green List (High Evidence).
Mendeliome v0.9835 MATN3 Zornitza Stark Phenotypes for gene: MATN3 were changed from to Spondyloepimetaphyseal dysplasia, Borochowitz-Cormier-Daire type (MIM#608728); Epiphyseal dysplasia, multiple, 5 (MIM#607078)
Mendeliome v0.9832 INPPL1 Zornitza Stark Gene: inppl1 has been classified as Green List (High Evidence).
Mendeliome v0.9832 INPPL1 Zornitza Stark Phenotypes for gene: INPPL1 were changed from to Opsismodysplasia MIM#258480
Mendeliome v0.9829 MAF Zornitza Stark Gene: maf has been classified as Green List (High Evidence).
Mendeliome v0.9826 LRP4 Zornitza Stark Gene: lrp4 has been classified as Green List (High Evidence).
Mendeliome v0.9826 LRP4 Zornitza Stark Phenotypes for gene: LRP4 were changed from to Cenani-Lenz syndactyly syndrome (MIM#212780); Myasthenic syndrome, congenital, 17, MIM# 616304; Sclerosteosis 2, MIM# 614305; Syndactyly
Mendeliome v0.9824 LRP4 Zornitza Stark reviewed gene: LRP4: Rating: GREEN; Mode of pathogenicity: None; Publications: 24234652, 26052878, 24200689, 21471202, 32286743, 28477420, 26751728, 29524275; Phenotypes: Myasthenic syndrome, congenital, 17, MIM# 616304, Sclerosteosis 2, MIM# 614305, Syndactyly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9823 MLC1 Zornitza Stark Gene: mlc1 has been classified as Green List (High Evidence).
Mendeliome v0.9820 MMP13 Zornitza Stark Gene: mmp13 has been classified as Green List (High Evidence).
Mendeliome v0.9820 MMP13 Zornitza Stark Phenotypes for gene: MMP13 were changed from to Metaphyseal anadysplasia 1 (MIM#602111); Metaphyseal dysplasia, Spahr type (MIM#250400); ?Spondyloepimetaphyseal dysplasia, Missouri type (MIM#602111)
Mendeliome v0.9818 MBTPS2 Zornitza Stark Gene: mbtps2 has been classified as Green List (High Evidence).
Mendeliome v0.9818 MBTPS2 Zornitza Stark Phenotypes for gene: MBTPS2 were changed from to Osteogenesis imperfecta, type XIX, (MIM301014); IFAP syndrome with or without BRESHECK syndrome (MIM#308205); Keratosis follicularis spinulosa decalvans, X-linked (MIM#308800); Olmsted syndrome, X-linked (MIM#300918)
Mendeliome v0.9815 IHH Zornitza Stark Gene: ihh has been classified as Green List (High Evidence).
Mendeliome v0.9814 IHH Zornitza Stark Phenotypes for gene: IHH were changed from to Acrocapitofemoral dysplasia MIM#607778; Brachydactyly, type A1 MIM#112500
Mendeliome v0.9810 KCTD1 Zornitza Stark Gene: kctd1 has been classified as Green List (High Evidence).
Mendeliome v0.9807 KCNJ2 Zornitza Stark Gene: kcnj2 has been classified as Green List (High Evidence).
Mendeliome v0.9804 MID1 Zornitza Stark Gene: mid1 has been classified as Green List (High Evidence).
Mendeliome v0.9801 KAT6A Zornitza Stark Gene: kat6a has been classified as Green List (High Evidence).
Mendeliome v0.9800 MESP2 Zornitza Stark Gene: mesp2 has been classified as Green List (High Evidence).
Mendeliome v0.9800 MESP2 Zornitza Stark Phenotypes for gene: MESP2 were changed from to Spondylocostal dysostosis 2, autosomal recessive (MIM#608681)
Mendeliome v0.9795 ZNF365 Zornitza Stark Gene: znf365 has been classified as Red List (Low Evidence).
Mendeliome v0.9795 ZNF365 Zornitza Stark Classified gene: ZNF365 as Red List (low evidence)
Mendeliome v0.9795 ZNF365 Zornitza Stark Gene: znf365 has been classified as Red List (Low Evidence).
Mendeliome v0.9794 CRLF1 Zornitza Stark Gene: crlf1 has been classified as Green List (High Evidence).
Mendeliome v0.9791 CPT2 Zornitza Stark Gene: cpt2 has been classified as Green List (High Evidence).
Mendeliome v0.9788 COX7B Zornitza Stark Gene: cox7b has been classified as Green List (High Evidence).
Mendeliome v0.9785 MATN3 Daniel Flanagan reviewed gene: MATN3: Rating: GREEN; Mode of pathogenicity: None; Publications: 31724101, 32025536, 11968079, 14729835; Phenotypes: Spondyloepimetaphyseal dysplasia, Borochowitz-Cormier-Daire type (MIM#608728), Epiphyseal dysplasia, multiple, 5 (MIM#607078); Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.9785 INPPL1 Ain Roesley reviewed gene: INPPL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23273567, 34529350, 34094554; Phenotypes: Opsismodysplasia MIM#258480; Mode of inheritance: None; Current diagnostic: yes
Mendeliome v0.9785 COQ4 Zornitza Stark Gene: coq4 has been classified as Green List (High Evidence).
Mendeliome v0.9782 COLEC11 Zornitza Stark Gene: colec11 has been classified as Green List (High Evidence).
Mendeliome v0.9779 MBTPS2 Daniel Flanagan reviewed gene: MBTPS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27380894, 19361614, 21426410; Phenotypes: Osteogenesis imperfecta, type XIX, (MIM301014), IFAP syndrome with or without BRESHECK syndrome (MIM#308205), Keratosis follicularis spinulosa decalvans, X-linked (MIM#308800), ?Olmsted syndrome, X-linked (MIM#300918); 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 v0.9779 MMP13 Daniel Flanagan reviewed gene: MMP13: Rating: GREEN; Mode of pathogenicity: Other; Publications: 19615667, 24781753, 24648384; Phenotypes: Metaphyseal anadysplasia 1 (MIM#602111), Metaphyseal dysplasia, Spahr type (MIM#250400), ?Spondyloepimetaphyseal dysplasia, Missouri type (MIM#602111); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.9779 IHH Ain Roesley reviewed gene: IHH: Rating: GREEN; Mode of pathogenicity: None; Publications: 34530144, 12632327, 32311039, 29155992; Phenotypes: Acrocapitofemoral dysplasia MIM#607778, Brachydactyly, type A1 MIM#112500; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.9779 MESP2 Daniel Flanagan reviewed gene: MESP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 18485326; Phenotypes: Spondylocostal dysostosis 2, autosomal recessive (MIM#608681); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9779 COG1 Zornitza Stark Gene: cog1 has been classified as Green List (High Evidence).
Mendeliome v0.9776 NEBL Bryony Thompson Classified gene: NEBL as Amber List (moderate evidence)
Mendeliome v0.9776 NEBL Bryony Thompson Added comment: Comment on list classification: Limited gene-disease vailidity, Classification - 09/25/2020 by ClinGen Dilated Cardiomyopathy GCEP. Evidence Summary: NEBL was evaluated for autosomal dominant dilated cardiomyopathy (DCM). Human genetic evidence supporting this gene-disease relationship includes case-level data. Arimura and colleagues (2000, PMID: 11140941) analyzed 83 DCM patients and 311 healthy controls, identifying 4 missense variants of unknown significance (VUSs) in 4 DCM cases. High minor allele frequencies (MAFs) and lack of segregation excluded these variants as evidence. Purevjav and colleagues (2010, PMID: 20951326) investigated a total of 260 DCM patients and 300 unrelated ethnic matched controls by direct DNA sequencing. Authors identified 4 missense VUSs. One of these variants (Q128R) was downgraded in level of evidence due to the lack of segregation. The other 3 variants were not scored because of their MAF. Perrot and colleagues (2016, PMID: 27186169) investigated a total of 389 patients with DCM, HCM, or LVNC, 320 Caucasian sex-matched controls and 192 Caucasian sex-matched blood donors and identified 3 missense VUSs in 4 families. One of these variants was also carried by healthy relatives and therefore was excluded, however this may be explained by reduced penetrance. The 2 other variants lacked segregation as well and therefore were also excluded. In addition, this gene-disease association is supported by animal models. Mastronotaro and colleagues (2015, PMID: 25987543) created a NEBL knockout mice that exhibited normal cardiac function up to 9 months of age but after 2 weeks of transaortic constriction (TAC), these mice showed Z-line widening since the age of 5 months and upregulation of cardiac stress genes (basal and after TAC) However, absence of clinical DCM features in KO-NEBL mice as well as Western Blot analysis which contradicted previous findings by showing a similar protein expression between knockout and wild-type mice, excluding it as evidence. Purevjav and colleagues (2010, PMID: 20951326) generated a transgenic mouse overexpressing WT or mutant NEBL under the control of the α-MyHC promoter (4 variants were tested). Mice overexpressing p.K60N or p.Q128R variants died within 1 year because of severe heart enlargement and heart failure. Mice overexpressing p.G202R or p.A592E were born and developed normally but after 6 months displayed reduced stress tolerance, cardiac enlargement due to left ventricle dilation, myocyte disarray, and interstitial cell infiltration. In summary, there is limited evidence to support this gene-disease relationship. More evidence is needed to support the relationship of NEBL and autosomal dominant DCM. This classification was approved by the ClinGen Dilated Cardiomyopathy Working Group on October 11, 2019 (SOP Version 7). Gene Clinical Validity Standard Operating Procedures (SOP) - SOP7
Mendeliome v0.9776 NEBL Bryony Thompson Gene: nebl has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9775 SPATA5L1 Zornitza Stark Phenotypes for gene: SPATA5L1 were changed from Intellectual disability; spastic-dystonic cerebral palsy; epilepsy; hearing loss to Neurodevelopmental disorder with hearing loss and spasticity, MIM# 619616; Deafness, autosomal recessive 119, MIM# 619615
Mendeliome v0.9774 SPATA5L1 Zornitza Stark edited their review of gene: SPATA5L1: Added comment: Note some of the affected individuals had isolated deafness, hence two OMIM phenotypes have been associated with this gene. All were of Ashkenazi Jewish origin, and had the p.Ile466Met founder variant, either hmz or compound het with another variant.; Changed publications: 34626583; Changed phenotypes: Neurodevelopmental disorder with hearing loss and spasticity, MIM# 619616, Deafness, autosomal recessive 119, MIM# 619615
Mendeliome v0.9774 MEIS2 Zornitza Stark Gene: meis2 has been classified as Green List (High Evidence).
Mendeliome v0.9771 LAMA4 Zornitza Stark Gene: lama4 has been classified as Red List (Low Evidence).
Mendeliome v0.9768 LAMA4 Zornitza Stark Classified gene: LAMA4 as Red List (low evidence)
Mendeliome v0.9768 LAMA4 Zornitza Stark Gene: lama4 has been classified as Red List (Low Evidence).
Mendeliome v0.9766 DSTYK Zornitza Stark Classified gene: DSTYK as Amber List (moderate evidence)
Mendeliome v0.9766 DSTYK Zornitza Stark Gene: dstyk has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9765 ATP1A2 Zornitza Stark Phenotypes for gene: ATP1A2 were changed from Alternating hemiplegia of childhood 1, MIM#104290; Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies, MIM# 619602; Developmental and epileptic encephalopathy, polymicrogyria to Alternating hemiplegia of childhood 1, MIM#104290; Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies, MIM# 619602; Developmental and epileptic encephalopathy 98, MIM# 619605
Mendeliome v0.9764 ATP1A2 Zornitza Stark edited their review of gene: ATP1A2: Changed phenotypes: Alternating hemiplegia of childhood 1, MIM#104290, Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies, MIM# 619602, Developmental and epileptic encephalopathy 98, MIM# 619605
Mendeliome v0.9764 ATP1A2 Zornitza Stark Phenotypes for gene: ATP1A2 were changed from Alternating hemiplegia of childhood 1, MIM#104290; Hydrops fetalis, microcephaly, arthrogryposis, extensive cortical malformations; Developmental and epileptic encephalopathy, polymicrogyria to Alternating hemiplegia of childhood 1, MIM#104290; Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies, MIM# 619602; Developmental and epileptic encephalopathy, polymicrogyria
Mendeliome v0.9763 ATP1A2 Zornitza Stark edited their review of gene: ATP1A2: Changed phenotypes: Alternating hemiplegia of childhood 1, MIM#104290, Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies, MIM# 619602, Developmental and epileptic encephalopathy, polymicrogyria
Mendeliome v0.9762 PRKG2 Zornitza Stark reviewed gene: PRKG2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34782440; Phenotypes: Acromesomelic dysplasia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9762 CNTNAP2 Zornitza Stark Gene: cntnap2 has been classified as Green List (High Evidence).
Mendeliome v0.9762 CNTNAP2 Zornitza Stark Phenotypes for gene: CNTNAP2 were changed from to Cortical dysplasia-focal epilepsy syndrome, MIM# 610042
Mendeliome v0.9759 CNTNAP2 Zornitza Stark reviewed gene: CNTNAP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 16571880, 19896112, 27439707; Phenotypes: Cortical dysplasia-focal epilepsy syndrome, MIM# 610042; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9759 CKAP2L Zornitza Stark Gene: ckap2l has been classified as Green List (High Evidence).
Mendeliome v0.9756 P3H1 Zornitza Stark Gene: p3h1 has been classified as Green List (High Evidence).
Mendeliome v0.9756 P3H1 Zornitza Stark Phenotypes for gene: P3H1 were changed from to Osteogenesis imperfecta, type VIII, MIM# 610915
Mendeliome v0.9753 P3H1 Dean Phelan reviewed gene: P3H1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 17277775, 19088120, 27864101, 33737016; Phenotypes: Osteogenesis imperfecta; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9753 CHST3 Zornitza Stark Gene: chst3 has been classified as Green List (High Evidence).
Mendeliome v0.9753 CHST3 Zornitza Stark Phenotypes for gene: CHST3 were changed from to Spondyloepiphyseal dysplasia with congenital joint dislocations, MIM# 143095
Mendeliome v0.9750 CHST3 Zornitza Stark reviewed gene: CHST3: Rating: GREEN; Mode of pathogenicity: None; Publications: 18513679; Phenotypes: Spondyloepiphyseal dysplasia with congenital joint dislocations, MIM# 143095; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9750 IL1RAPL1 Zornitza Stark Gene: il1rapl1 has been classified as Green List (High Evidence).
Mendeliome v0.9747 IFITM5 Zornitza Stark Gene: ifitm5 has been classified as Green List (High Evidence).
Mendeliome v0.9747 IFITM5 Zornitza Stark Phenotypes for gene: IFITM5 were changed from to Osteogenesis imperfecta, type V MIM#610967
Mendeliome v0.9743 CHRND Zornitza Stark Gene: chrnd has been classified as Green List (High Evidence).
Mendeliome v0.9740 CHRNA1 Zornitza Stark Gene: chrna1 has been classified as Green List (High Evidence).
Mendeliome v0.9737 IMPAD1 Ain Roesley reviewed gene: IMPAD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22887726, 21549340; Phenotypes: Chondrodysplasia with joint dislocations, GPAPP type MIM#614078; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.9737 MAFB Zornitza Stark Gene: mafb has been classified as Green List (High Evidence).
Mendeliome v0.9737 MAFB Zornitza Stark Phenotypes for gene: MAFB were changed from to Multicentric carpotarsal osteolysis syndrome (MIM#166300); Duane retraction syndrome 3, MIM# 617041
Mendeliome v0.9735 IFITM5 Ain Roesley edited their review of gene: IFITM5: Added comment: Comment on mode of pathogenicity: LoF not established, alternative neomorph/GoF postulated but not yet conclusively proven; Changed mode of pathogenicity: Other
Mendeliome v0.9734 ASIP Zornitza Stark Marked gene: ASIP as ready
Mendeliome v0.9734 ASIP Zornitza Stark Gene: asip has been classified as Red List (Low Evidence).
Mendeliome v0.9734 ASIP Zornitza Stark Classified gene: ASIP as Red List (low evidence)
Mendeliome v0.9734 ASIP Zornitza Stark Gene: asip has been classified as Red List (Low Evidence).
Mendeliome v0.9733 MAFB Daniel Flanagan reviewed gene: MAFB: Rating: GREEN; Mode of pathogenicity: None; Publications: 23956186, 30208859; Phenotypes: Multicentric carpotarsal osteolysis syndrome (MIM#166300); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9733 IFITM5 Ain Roesley reviewed gene: IFITM5: Rating: GREEN; Mode of pathogenicity: None; Publications: 22863190, 22863195, 32383316, 24519609; Phenotypes: Osteogenesis imperfecta, type V MIM#610967; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Mendeliome v0.9733 CHKB Zornitza Stark Gene: chkb has been classified as Green List (High Evidence).
Mendeliome v0.9730 CHAMP1 Zornitza Stark Gene: champ1 has been classified as Green List (High Evidence).
Mendeliome v0.9727 CFTR Zornitza Stark Gene: cftr has been classified as Green List (High Evidence).
Mendeliome v0.9727 CFTR Zornitza Stark Phenotypes for gene: CFTR were changed from to Cystic fibrosis, MIM# 219700; Congenital bilateral absence of vas deferens, MIM# 277180
Mendeliome v0.9725 CFTR Zornitza Stark reviewed gene: CFTR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cystic fibrosis, MIM# 219700, Congenital bilateral absence of vas deferens, MIM# 277180; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9725 ASIP Ain Roesley reviewed gene: ASIP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None; Current diagnostic: yes
Mendeliome v0.9725 ETV6 Zornitza Stark Gene: etv6 has been classified as Green List (High Evidence).
Mendeliome v0.9722 BSG Zornitza Stark Gene: bsg has been classified as Red List (Low Evidence).
Mendeliome v0.9721 BSG Zornitza Stark Classified gene: BSG as Red List (low evidence)
Mendeliome v0.9721 BSG Zornitza Stark Gene: bsg has been classified as Red List (Low Evidence).
Mendeliome v0.9720 TPCN2 Zornitza Stark Gene: tpcn2 has been classified as Red List (Low Evidence).
Mendeliome v0.9718 TPCN2 Zornitza Stark Classified gene: TPCN2 as Red List (low evidence)
Mendeliome v0.9718 TPCN2 Zornitza Stark Gene: tpcn2 has been classified as Red List (Low Evidence).
Mendeliome v0.9717 MYO9B Zornitza Stark Gene: myo9b has been classified as Red List (Low Evidence).
Mendeliome v0.9715 MYO9B Zornitza Stark Classified gene: MYO9B as Red List (low evidence)
Mendeliome v0.9715 MYO9B Zornitza Stark Gene: myo9b has been classified as Red List (Low Evidence).
Mendeliome v0.9714 HKDC1 Zornitza Stark Gene: hkdc1 has been classified as Red List (Low Evidence).
Mendeliome v0.9713 CENPJ Zornitza Stark Gene: cenpj has been classified as Green List (High Evidence).
Mendeliome v0.9713 CENPJ Zornitza Stark Phenotypes for gene: CENPJ were changed from to Microcephaly 6, primary, autosomal recessive, MIM# 608393, MONDO:0012029; Seckel syndrome 4, MIM# 613676, MONDO:0013358
Mendeliome v0.9710 CENPJ Zornitza Stark reviewed gene: CENPJ: Rating: GREEN; Mode of pathogenicity: None; Publications: 20522431, 23166506, 15793586, 20978018, 22775483, 32677750, 32549991; Phenotypes: Microcephaly 6, primary, autosomal recessive, MIM# 608393, MONDO:0012029, Seckel syndrome 4, MIM# 613676, MONDO:0013358; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9710 CDON Zornitza Stark Gene: cdon has been classified as Green List (High Evidence).
Mendeliome v0.9707 CDON Zornitza Stark changed review comment from: >5 unrelated families reported, however note some of the variants are present at a very low frequentcy in gnomad (1-4) and some are inherited. Mouse model.; to: >5 unrelated families reported, however note some of the variants are present at a very low frequentcy in gnomad (1-4) and some are inherited. Mouse model.

Note single report of bi-allelic variants in association with coloboma: PMID 32729136
Mendeliome v0.9707 CDH3 Zornitza Stark Gene: cdh3 has been classified as Green List (High Evidence).
Mendeliome v0.9707 CDH3 Zornitza Stark Phenotypes for gene: CDH3 were changed from to Ectodermal dysplasia, ectrodactyly, and macular dystrophy, MIM# 225280; Hypotrichosis, congenital, with juvenile macular dystrophy, MIM# 601553
Mendeliome v0.9704 CDH3 Zornitza Stark reviewed gene: CDH3: Rating: GREEN; Mode of pathogenicity: None; Publications: 11544476, 15805154, 28061825, 22140374; Phenotypes: Ectodermal dysplasia, ectrodactyly, and macular dystrophy, MIM# 225280, Hypotrichosis, congenital, with juvenile macular dystrophy, MIM# 601553; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9704 MICAL1 Zornitza Stark Gene: mical1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9704 EFHC1 Bryony Thompson Classified gene: EFHC1 as Red List (low evidence)
Mendeliome v0.9704 EFHC1 Bryony Thompson Added comment: Comment on list classification: ClinGen Epilepsy GCEP gene-disease association curation: Disputed - We have disregarded the very limited functional evidence in light of the complete lack of genetic evidence connecting EFHC1 and epilepsy. In summary, there is convincing evidence disputing the association between EFHC1 and epilepsy. All variants in EFHC1 associated with epilepsy have contradictory evidence for disease association (too common in ExAC/gnomAD, with minor allele frequencies (MAF) of 2.857e-5 to 0.05973). More evidence is needed to either support or refute the role EFHC1 plays in this disease. Classification - 07/27/2018, reviewed Sept 2021
Mendeliome v0.9704 EFHC1 Bryony Thompson Gene: efhc1 has been classified as Red List (Low Evidence).
Mendeliome v0.9703 MICAL1 Bryony Thompson Classified gene: MICAL1 as Amber List (moderate evidence)
Mendeliome v0.9703 MICAL1 Bryony Thompson Gene: mical1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9702 MICAL1 Bryony Thompson gene: MICAL1 was added
gene: MICAL1 was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: MICAL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MICAL1 were set to 29394500; 21638339
Phenotypes for gene: MICAL1 were set to Autosomal dominant epilepsy with auditory features (ADEAF)
Review for gene: MICAL1 was set to AMBER
Added comment: Two families with supporting in vitro functional assays. Assessment of expression pattern of Mical-1 in the temporal neocortex of patients with intractable temporal epilepsy and pilocarpine-induced rat model, suggests Mical-1 may associate with inner pathophysiological modulation in epilepsy.
Sources: Expert list
Mendeliome v0.9701 CPA6 Bryony Thompson Classified gene: CPA6 as Red List (low evidence)
Mendeliome v0.9701 CPA6 Bryony Thompson Added comment: Comment on list classification: ClinGen Epilepsy GCEP has reviewed both inheritances for gene-disease associations with epilepsy: AR disease is Disputed - There is contradictory case level and experimental data regarding any association between CPA6 and autosomal recessive epilepsy. Classification - 07/29/2021 AD disease is Refuted- There is very limited evidence supporting a gene-disease association. Many of the reported pathogenic variants have been subsequently identified as having a high minor allele frequency in population databases. Classification - 07/29/2021
Mendeliome v0.9701 CPA6 Bryony Thompson Gene: cpa6 has been classified as Red List (Low Evidence).
Mendeliome v0.9699 CNTN2 Bryony Thompson Classified gene: CNTN2 as Amber List (moderate evidence)
Mendeliome v0.9699 CNTN2 Bryony Thompson Gene: cntn2 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9697 ADSSL1 Zornitza Stark Gene: adssl1 has been classified as Green List (High Evidence).
Mendeliome v0.9694 BRAT1 Zornitza Stark Gene: brat1 has been classified as Green List (High Evidence).
Mendeliome v0.9690 CFAP45 Zornitza Stark Phenotypes for gene: CFAP45 were changed from Situs inversus; asthenospermia to Heterotaxy, visceral, 11, autosomal, with male infertility, MIM#619608
Mendeliome v0.9688 BMPR1B Zornitza Stark Gene: bmpr1b has been classified as Green List (High Evidence).
Mendeliome v0.9688 BMPR1B Zornitza Stark Phenotypes for gene: BMPR1B were changed from to Acromesomelic dysplasia, Demirhan type, MIM# 609441; Brachydactyly, type A1, D, MIM# 616849; Brachydactyly, type A2, MIM# 112600
Mendeliome v0.9685 BMPR1B Zornitza Stark reviewed gene: BMPR1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 15805157, 24129431, 26105076, 25758993, 14523231, 14523231; Phenotypes: Acromesomelic dysplasia, Demirhan type, MIM# 609441, Brachydactyly, type A1, D, MIM# 616849, Brachydactyly, type A2, MIM# 112600; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.9685 BMPER Zornitza Stark Gene: bmper has been classified as Green List (High Evidence).
Mendeliome v0.9685 BMPER Zornitza Stark Phenotypes for gene: BMPER were changed from to Diaphanospondylodysostosis, MIM#608022
Mendeliome v0.9682 BMPER Zornitza Stark commented on gene: BMPER: Perinatal lethal skeletal dysplasia.

The primary skeletal characteristics include small chest, abnormal vertebral segmentation, and posterior rib gaps containing incompletely differentiated mesenchymal tissue. Consistent craniofacial features include ocular hypertelorism, epicanthal folds, depressed nasal bridge with short nose, and low-set ears. The most commonly described extraskeletal finding is nephroblastomatosis with cystic kidneys, but other visceral findings have been described in some cases.

At least 5 unrelated families reported.
Mendeliome v0.9682 BMP4 Zornitza Stark Gene: bmp4 has been classified as Green List (High Evidence).
Mendeliome v0.9679 BMP2 Zornitza Stark Gene: bmp2 has been classified as Green List (High Evidence).
Mendeliome v0.9676 BMP1 Zornitza Stark Gene: bmp1 has been classified as Green List (High Evidence).
Mendeliome v0.9676 BMP1 Zornitza Stark Phenotypes for gene: BMP1 were changed from to Osteogenesis imperfecta, type XIII , MIM#614856
Mendeliome v0.9673 BMP1 Zornitza Stark reviewed gene: BMP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25402547, 22052668, 22482805, 25214535; Phenotypes: Osteogenesis imperfecta, type XIII , MIM#614856; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9673 BIN1 Zornitza Stark Gene: bin1 has been classified as Green List (High Evidence).
Mendeliome v0.9670 BHLHA9 Zornitza Stark Gene: bhlha9 has been classified as Green List (High Evidence).
Mendeliome v0.9667 DLL4 Zornitza Stark Gene: dll4 has been classified as Green List (High Evidence).
Mendeliome v0.9664 BFSP2 Zornitza Stark Gene: bfsp2 has been classified as Green List (High Evidence).
Mendeliome v0.9661 HR Zornitza Stark Gene: hr has been classified as Green List (High Evidence).
Mendeliome v0.9661 HR Zornitza Stark Phenotypes for gene: HR were changed from to Alopecia universalis MIM#203655; Atrichia with papular lesions MIM#209500
Mendeliome v0.9659 HPSE2 Zornitza Stark Gene: hpse2 has been classified as Green List (High Evidence).
Mendeliome v0.9655 HNRNPK Zornitza Stark Gene: hnrnpk has been classified as Green List (High Evidence).
Mendeliome v0.9652 HES7 Zornitza Stark Gene: hes7 has been classified as Green List (High Evidence).
Mendeliome v0.9652 HES7 Zornitza Stark Phenotypes for gene: HES7 were changed from to Spondylocostal dysostosis 4, autosomal recessive MIM#613686
Mendeliome v0.9649 DIS3L2 Zornitza Stark Gene: dis3l2 has been classified as Green List (High Evidence).
Mendeliome v0.9646 DDX3X Zornitza Stark Gene: ddx3x has been classified as Green List (High Evidence).
Mendeliome v0.9643 SIK3 Zornitza Stark Marked gene: SIK3 as ready
Mendeliome v0.9643 SIK3 Zornitza Stark Gene: sik3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9643 SIK3 Zornitza Stark Phenotypes for gene: SIK3 were changed from ?Spondyloepimetaphyseal dysplasia, Krakow type - #618162 to Spondyloepimetaphyseal dysplasia, Krakow type - #618162
Mendeliome v0.9642 SIK3 Zornitza Stark Classified gene: SIK3 as Amber List (moderate evidence)
Mendeliome v0.9642 SIK3 Zornitza Stark Gene: sik3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9641 HSD17B3 Zornitza Stark Gene: hsd17b3 has been classified as Green List (High Evidence).
Mendeliome v0.9638 HR Ain Roesley reviewed gene: HR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Alopecia universalis MIM#203655, Atrichia with papular lesions MIM#209500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.9638 HES7 Ain Roesley reviewed gene: HES7: Rating: ; Mode of pathogenicity: None; Publications: 29459493, 23897666, 18775957, 20087400; Phenotypes: Spondylocostal dysostosis 4, autosomal recessive MIM#613686; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v0.9638 MYH10 Zornitza Stark Gene: myh10 has been classified as Green List (High Evidence).
Mendeliome v0.9638 MYH10 Zornitza Stark Classified gene: MYH10 as Green List (high evidence)
Mendeliome v0.9638 MYH10 Zornitza Stark Gene: myh10 has been classified as Green List (High Evidence).
Mendeliome v0.9637 C9orf3 Zornitza Stark Gene: c9orf3 has been classified as Green List (High Evidence).
Mendeliome v0.9637 C9orf3 Zornitza Stark Classified gene: C9orf3 as Green List (high evidence)
Mendeliome v0.9637 C9orf3 Zornitza Stark Gene: c9orf3 has been classified as Green List (High Evidence).
Mendeliome v0.9636 C9orf3 Zornitza Stark gene: C9orf3 was added
gene: C9orf3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: C9orf3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C9orf3 were set to 34596301
Phenotypes for gene: C9orf3 were set to Dystonia 31, MIM# 619565
Review for gene: C9orf3 was set to GREEN
Added comment: Dystonia-31 (DYT31) is an autosomal recessive progressive neurologic disorder characterized by involuntary muscle twisting movements and postural abnormalities affecting the upper and lower limbs, neck, face, and trunk. Some patients may have orofacial dyskinesia resulting in articulation and swallowing difficulties. The age at onset ranges from childhood to young adulthood. There are usually no additional neurologic symptoms, although late-onset parkinsonism was reported in 1 family.

5 individuals from 4 unrelated families reported.

HGNC approved name is AOPEP.
Sources: Literature
Mendeliome v0.9634 ASXL1 Zornitza Stark Gene: asxl1 has been classified as Green List (High Evidence).
Mendeliome v0.9631 ASNS Zornitza Stark Gene: asns has been classified as Green List (High Evidence).
Mendeliome v0.9628 SIK3 Krithika Murali gene: SIK3 was added
gene: SIK3 was added to Mendeliome. Sources: Expert list,Literature
Mode of inheritance for gene: SIK3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SIK3 were set to 30232230; 22318228
Phenotypes for gene: SIK3 were set to ?Spondyloepimetaphyseal dysplasia, Krakow type - #618162
Review for gene: SIK3 was set to AMBER
Added comment: Biallelic SIK3 variants reported in 2 siblings from a consanguineous family with an uncharacterised skeletal dysplasia. Radiographic features included widened/flared metaphyses with irregular ossifications, motheaten long bones, fragmentation of the proximal metacarpals, rounded vertebral bodies, and a distinctive transverse gap seen in the tibias.

In addition to the skeletal phenotype, the siblings manifested significant developmental delay with brain MRI abnormalities, a severe unclassified immunodeficiency, and normal parathyroid hormone concentration with mild hypercalcemia.

One sibling had a more severe phenotype, particularly immunodeficiency, and died of Epstein-Barr virus induced small muscle cancer at 10 years of age.

Mouse models support impaired chondrocyte development with skeletal dysplasia phenotye.
Sources: Expert list, Literature
Mendeliome v0.9628 ANTXR1 Zornitza Stark Gene: antxr1 has been classified as Green List (High Evidence).
Mendeliome v0.9625 ANOS1 Zornitza Stark Gene: anos1 has been classified as Green List (High Evidence).
Mendeliome v0.9622 LTBP4 Zornitza Stark Gene: ltbp4 has been classified as Green List (High Evidence).
Mendeliome v0.9622 LTBP4 Zornitza Stark Phenotypes for gene: LTBP4 were changed from to Cutis laxa, autosomal recessive, type IC, MIM# 613177
Mendeliome v0.9619 LTBP4 Zornitza Stark reviewed gene: LTBP4: Rating: GREEN; Mode of pathogenicity: None; Publications: 22829427, 19836010, 28684544; Phenotypes: Cutis laxa, autosomal recessive, type IC, MIM# 613177; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9619 EFEMP2 Zornitza Stark Gene: efemp2 has been classified as Green List (High Evidence).
Mendeliome v0.9619 EFEMP2 Zornitza Stark Phenotypes for gene: EFEMP2 were changed from to Autosomal recessive cutis laxa type 1B (ARCL1B), MIM# 614437
Mendeliome v0.9616 EFEMP2 Zornitza Stark reviewed gene: EFEMP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30140196, 23532871, 31548410, 19664000; Phenotypes: Autosomal recessive cutis laxa type 1B (ARCL1B), MIM# 614437; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9616 MYH10 Krithika Murali gene: MYH10 was added
gene: MYH10 was added to Mendeliome. Sources: Expert list,Literature
Mode of inheritance for gene: MYH10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYH10 were set to 24825879; 24901346; 25356899; 22495309; 25003005
Phenotypes for gene: MYH10 were set to Microcephaly; Intellectual Disability
Review for gene: MYH10 was set to GREEN
Added comment: De novo variants were identified in 5 unrelated individuals with moderate-severe ID and developmental delay.

Other reported phenotypic features include microcephaly (4/5), IUGR/failure to thrive (4/5), cerebral atrophy (3/5), hydrocephalus (2/5), congenital bilateral hip dysplasia (2/5), cerebellar atrophy (1/5), congenital diaphragmatic hernia (1/5), cranial nerve palsy (1/5), nystagmus (1/5), dysplastic kidney (1/5).

Defects in heart development, body wall closure and other birth defects noted in mouse models.
Sources: Expert list, Literature
Mendeliome v0.9616 CSF2RB Zornitza Stark Gene: csf2rb has been classified as Green List (High Evidence).
Mendeliome v0.9613 CSF2RA Zornitza Stark Gene: csf2ra has been classified as Green List (High Evidence).
Mendeliome v0.9608 RNPC3 Zornitza Stark Classified gene: RNPC3 as Green List (high evidence)
Mendeliome v0.9608 RNPC3 Zornitza Stark Gene: rnpc3 has been classified as Green List (High Evidence).
Mendeliome v0.9607 COG6 Zornitza Stark changed review comment from: More than 5 unrelated families reported. Key features include growth retardation, developmental delay, microcephaly, liver and gastrointestinal disease, joint contractures and episodic fever. Ectodermal signs such as hypohidrosis/hyperthermia, hyperkeratosis and tooth anomalies are prominent. Note Shaheen syndrome, MIM#615328 is an allelic disorder, with overlapping clinical features, but normal transferring isoforms recorded creating confusion about whether it represents a distinct entity.; to: More than 5 unrelated families reported. Key features include growth retardation, developmental delay, microcephaly, liver and gastrointestinal disease, joint contractures and episodic fever. Ectodermal signs such as hypohidrosis/hyperthermia, hyperkeratosis and tooth anomalies are prominent. Note Shaheen syndrome, MIM#615328 is an allelic disorder, with overlapping clinical features, but normal transferrin isoforms recorded creating confusion about whether it represents a distinct entity.
Mendeliome v0.9605 OTUD7A Zornitza Stark Classified gene: OTUD7A as Amber List (moderate evidence)
Mendeliome v0.9605 OTUD7A Zornitza Stark Gene: otud7a has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9604 GNAQ Zornitza Stark Gene: gnaq has been classified as Green List (High Evidence).
Mendeliome v0.9604 GNAQ Zornitza Stark Phenotypes for gene: GNAQ were changed from to Sturge-Weber syndrome, somatic, mosaic 185300; Capillary malformations, congenital, 1, somatic, mosaic 163000; Phacomatosis pigmentovascularis
Mendeliome v0.9600 GNAQ Zornitza Stark reviewed gene: GNAQ: Rating: GREEN; Mode of pathogenicity: Other; Publications: 30920161; Phenotypes: Sturge-Weber syndrome, somatic, mosaic 185300, Capillary malformations, congenital, 1, somatic, mosaic 163000, Phacomatosis pigmentovascularis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9600 AKR1C2 Zornitza Stark Gene: akr1c2 has been classified as Red List (Low Evidence).
Mendeliome v0.9600 AKR1C2 Zornitza Stark Phenotypes for gene: AKR1C2 were changed from to 46XY sex reversal 8, MIM# 614279; Obesity
Mendeliome v0.9597 AKR1C2 Zornitza Stark Classified gene: AKR1C2 as Red List (low evidence)
Mendeliome v0.9597 AKR1C2 Zornitza Stark Gene: akr1c2 has been classified as Red List (Low Evidence).
Mendeliome v0.9596 AKR1C2 Zornitza Stark reviewed gene: AKR1C2: Rating: RED; Mode of pathogenicity: None; Publications: 21802064, 25322899, 33675863; Phenotypes: 46XY sex reversal 8, MIM# 614279, Obesity; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9596 AMER1 Zornitza Stark Gene: amer1 has been classified as Green List (High Evidence).
Mendeliome v0.9596 AMER1 Zornitza Stark Phenotypes for gene: AMER1 were changed from to Osteopathia striata with cranial sclerosis, MIM# 300373
Mendeliome v0.9593 AMER1 Zornitza Stark reviewed gene: AMER1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20209645, 19079258; Phenotypes: Osteopathia striata with cranial sclerosis, MIM# 300373; 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 v0.9593 ALG1 Zornitza Stark Gene: alg1 has been classified as Green List (High Evidence).
Mendeliome v0.9590 NUP85 Eleanor Williams reviewed gene: NUP85: Rating: ; Mode of pathogenicity: None; Publications: 34170319; Phenotypes: intellectual disability, Primary autosomal recessive microcephaly and Seckel syndrome spectrum disorders (MCPH–SCKS); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9590 TUB Zornitza Stark Gene: tub has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9590 TUB Zornitza Stark Phenotypes for gene: TUB were changed from to Retinal dystrophy and obesity, MIM# 616188
Mendeliome v0.9587 TUB Zornitza Stark Classified gene: TUB as Amber List (moderate evidence)
Mendeliome v0.9587 TUB Zornitza Stark Gene: tub has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9586 TUB Zornitza Stark reviewed gene: TUB: Rating: AMBER; Mode of pathogenicity: None; Publications: 24375934, 28852204; Phenotypes: Retinal dystrophy and obesity, MIM# 616188; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9586 KSR2 Zornitza Stark Gene: ksr2 has been classified as Red List (Low Evidence).
Mendeliome v0.9586 KSR2 Zornitza Stark gene: KSR2 was added
gene: KSR2 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: KSR2 was set to Other
Publications for gene: KSR2 were set to 29273807; 24209692
Phenotypes for gene: KSR2 were set to Obesity
Review for gene: KSR2 was set to RED
Added comment: PMID: 24209692 Targeted deletion of Ksr2 leads to obesity in mice, suggesting a role in energy homeostasis. PMID: 29273807 GWAS identified KSR2 (13 genes studied) implicated in extreme obesity.
Sources: Expert Review
Mendeliome v0.9585 SIM1 Zornitza Stark Phenotypes for gene: SIM1 were changed from to congenital obesity; Prader-Willi-like syndrome
Mendeliome v0.9584 SIM1 Zornitza Stark Publications for gene: SIM1 were set to
Mendeliome v0.9583 SIM1 Zornitza Stark Mode of inheritance for gene: SIM1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9582 SIM1 Zornitza Stark Classified gene: SIM1 as Green List (high evidence)
Mendeliome v0.9582 SIM1 Zornitza Stark Gene: sim1 has been classified as Green List (High Evidence).
Mendeliome v0.9581 SIM1 Zornitza Stark edited their review of gene: SIM1: Added comment: At least 20 probands with reduced penetrance reported.

PMID:33434169;
1x missense inherited from normal mother

PMID:30926952;
2x unrelated - 1 missense 1 splice. Family history noted

PMID:23778136;
4 children with clinical features of PWL syndrome, including severe obesity - all missense
1x inherited from normal father

PMID:23778139;
at least 13 families with segregation and reduced penetrance evidence - all missense
In vitro luciferase done to show LoF

NOTE:
Individuals with Prader-Willi-like phenotype may have 6q16.2del instead, which encompasses SIM1; Changed rating: GREEN; Changed publications: 33434169, 30926952, 23778136, 23778139; Changed phenotypes: congenital obesity, Prader-Willi-like syndrome; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9581 POMC Zornitza Stark Gene: pomc has been classified as Green List (High Evidence).
Mendeliome v0.9581 POMC Zornitza Stark Phenotypes for gene: POMC were changed from to Obesity, adrenal insufficiency, and red hair due to POMC deficiency MIM#609734
Mendeliome v0.9579 MLIP Zornitza Stark Gene: mlip has been classified as Green List (High Evidence).
Mendeliome v0.9579 MLIP Zornitza Stark Phenotypes for gene: MLIP were changed from 34581780 to MLIP-related myopathy with rhabdomyolysis
Mendeliome v0.9577 MLIP Zornitza Stark Classified gene: MLIP as Green List (high evidence)
Mendeliome v0.9577 MLIP Zornitza Stark Gene: mlip has been classified as Green List (High Evidence).
Mendeliome v0.9575 MLIP Michelle Torres edited their review of gene: MLIP: Changed publications: 34581780; Changed phenotypes: MLIP-related myopathy with rhabdomyolysis
Mendeliome v0.9575 CACNA1A Zornitza Stark Gene: cacna1a has been classified as Green List (High Evidence).
Mendeliome v0.9572 KIAA0391 Zornitza Stark Gene: kiaa0391 has been classified as Green List (High Evidence).
Mendeliome v0.9571 KIAA0391 Zornitza Stark Classified gene: KIAA0391 as Green List (high evidence)
Mendeliome v0.9571 KIAA0391 Zornitza Stark Gene: kiaa0391 has been classified as Green List (High Evidence).
Mendeliome v0.9570 STT3A Zornitza Stark Gene: stt3a has been classified as Green List (High Evidence).
Mendeliome v0.9569 KIAA0391 Lucy Spencer changed review comment from: Four unrelated families with multisystem disease associated with bi-allelic variants in PRORP. Affected individuals presented with variable phenotypes comprising sensorineural hearing loss, primary ovarian insufficiency, developmental delay, and brain white matter changes.

-1 consanguineous family with homozygous missense in 3 affected sisters, het parents unaffected. Siblings had profound bilateral SNHL in infancy. In teens developed primary amenorrhea/Perrault syndrome, and hypergonadotropic hypogonadism.
-1 unrelated male with compound het missense, each inherited from an unaffected parent. Hearing loss noted at 3, diagnosed at 5.
-1 unrelated male compound het for a missense and a frameshift. appendicular hypertonia in infancy, mild dysmorphism. Severe global dev delay at 20 months. Normal hearing at 18 months, but at 3 years had bilateral SNHL.
-an affected mother and her 2 affected children (son and daughter), homozygous for a missense. Father is heterozygous and unaffected. Son has psychotic disorder, autistic traits. Sister had intrauterine growth retardation, global developmental delay, and seizures in the first years of life. Mother presented with retrobulbar optic neuritis and tonic pupil at 39 years of age, then with asthenia, myalgias, memory loss, and frequent headaches.

All variants are in p.400s.
Sources: Literature; to: Four unrelated families with multisystem disease associated with bi-allelic variants in PRORP. Affected individuals presented with variable phenotypes comprising sensorineural hearing loss, primary ovarian insufficiency, developmental delay, and brain white matter changes.

-1 consanguineous family with homozygous missense in 3 affected sisters, het parents unaffected. Siblings had profound bilateral SNHL in infancy. In teens developed primary amenorrhea/Perrault syndrome, and hypergonadotropic hypogonadism.
-1 unrelated male with compound het missense, each inherited from an unaffected parent. Hearing loss noted at 3, diagnosed at 5.
-1 unrelated male compound het for a missense and a frameshift. appendicular hypertonia in infancy, mild dysmorphism. Severe global dev delay at 20 months. Normal hearing at 18 months, but at 3 years had bilateral SNHL.
-an affected mother and her 2 affected children (son and daughter), homozygous for a missense. Father is heterozygous and unaffected. Son has psychotic disorder, autistic traits. Sister had intrauterine growth retardation, global developmental delay, and seizures in the first years of life. Mother presented with retrobulbar optic neuritis and tonic pupil at 39 years of age, then with asthenia, myalgias, memory loss, and frequent headaches.

All variants are in p.400s.
Sources: Literature
Mendeliome v0.9567 KIAA0391 Lucy Spencer gene: KIAA0391 was added
gene: KIAA0391 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KIAA0391 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA0391 were set to PMID: 34715011
Added comment: Four unrelated families with multisystem disease associated with bi-allelic variants in PRORP. Affected individuals presented with variable phenotypes comprising sensorineural hearing loss, primary ovarian insufficiency, developmental delay, and brain white matter changes.

-1 consanguineous family with homozygous missense in 3 affected sisters, het parents unaffected. Siblings had profound bilateral SNHL in infancy. In teens developed primary amenorrhea/Perrault syndrome, and hypergonadotropic hypogonadism.
-1 unrelated male with compound het missense, each inherited from an unaffected parent. Hearing loss noted at 3, diagnosed at 5.
-1 unrelated male compound het for a missense and a frameshift. appendicular hypertonia in infancy, mild dysmorphism. Severe global dev delay at 20 months. Normal hearing at 18 months, but at 3 years had bilateral SNHL.
-an affected mother and her 2 affected children (son and daughter), homozygous for a missense. Father is heterozygous and unaffected. Son has psychotic disorder, autistic traits. Sister had intrauterine growth retardation, global developmental delay, and seizures in the first years of life. Mother presented with retrobulbar optic neuritis and tonic pupil at 39 years of age, then with asthenia, myalgias, memory loss, and frequent headaches.

All variants are in p.400s.
Sources: Literature
Mendeliome v0.9567 SPATA5L1 Zornitza Stark Gene: spata5l1 has been classified as Green List (High Evidence).
Mendeliome v0.9567 SPATA5L1 Zornitza Stark Classified gene: SPATA5L1 as Green List (high evidence)
Mendeliome v0.9567 SPATA5L1 Zornitza Stark Gene: spata5l1 has been classified as Green List (High Evidence).
Mendeliome v0.9566 MLIP Michelle Torres gene: MLIP was added
gene: MLIP was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MLIP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MLIP were set to 34581780
Review for gene: MLIP was set to GREEN
Added comment: PMID: 34581780: 7 individuals with 6 families with truncating (one splice that also resulted in a frameshift variant) biallelic variants (used NM_1281746).

In 3 patients patients’ skeletal muscle, these variants were shown to cause reduction overall RNA expression levels of the predominant MLIP isoform.

Patients presented with a consistent phenotype characterized by mild muscle weakness, exercise-induced muscle pain, variable susceptibility to episodes of rhabdomyolysis, and persistent basal elevated serum creatine kinase levels.
Sources: Literature
Mendeliome v0.9566 SPRED2 Zornitza Stark Gene: spred2 has been classified as Green List (High Evidence).
Mendeliome v0.9566 SPRED2 Zornitza Stark Classified gene: SPRED2 as Green List (high evidence)
Mendeliome v0.9566 SPRED2 Zornitza Stark Gene: spred2 has been classified as Green List (High Evidence).
Mendeliome v0.9565 KPNA3 Zornitza Stark Gene: kpna3 has been classified as Green List (High Evidence).
Mendeliome v0.9564 KPNA3 Zornitza Stark Classified gene: KPNA3 as Green List (high evidence)
Mendeliome v0.9564 KPNA3 Zornitza Stark Gene: kpna3 has been classified as Green List (High Evidence).
Mendeliome v0.9563 SPRED2 Dean Phelan gene: SPRED2 was added
gene: SPRED2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SPRED2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPRED2 were set to PMID: 34626534
Phenotypes for gene: SPRED2 were set to developmental delay; intellectual disability; cardiac defects; short stature; skeletal anomalies; a typical facial gestalt
Review for gene: SPRED2 was set to GREEN
Added comment: PMID: 34626534
Homozygosity for three different variants c.187C>T (p.Arg63∗), c.299T>C (p.Leu100Pro), and c.1142_1143delTT (p.Leu381Hisfs∗95) were identified in four subjects from three families. All variants severely affected protein stability, causing accelerated degradation, and variably perturbed SPRED2 functional behaviour. The clinical phenotype of the four affected individuals included developmental delay, intellectual disability, cardiac defects, short stature, skeletal anomalies, and a typical facial gestalt as major features, without the occurrence of the distinctive skin signs characterizing Legius syndrome.
Sources: Literature
Mendeliome v0.9562 POMC Zornitza Stark reviewed gene: POMC: Rating: GREEN; Mode of pathogenicity: None; Publications: 33666293; Phenotypes: Obesity, adrenal insufficiency, and red hair due to POMC deficiency MIM#609734; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9562 PHF6 Zornitza Stark Gene: phf6 has been classified as Green List (High Evidence).
Mendeliome v0.9559 PCSK1 Zornitza Stark Gene: pcsk1 has been classified as Green List (High Evidence).
Mendeliome v0.9559 PCSK1 Zornitza Stark Phenotypes for gene: PCSK1 were changed from to Obesity with impaired prohormone processing MIM#600955
Mendeliome v0.9556 PCSK1 Zornitza Stark reviewed gene: PCSK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30383237; Phenotypes: Obesity with impaired prohormone processing MIM#600955; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9556 SLC4A3 Zornitza Stark Gene: slc4a3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9556 SLC4A3 Zornitza Stark Classified gene: SLC4A3 as Amber List (moderate evidence)
Mendeliome v0.9556 SLC4A3 Zornitza Stark Gene: slc4a3 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9555 EHBP1L1 Zornitza Stark Gene: ehbp1l1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9555 EHBP1L1 Zornitza Stark Classified gene: EHBP1L1 as Amber List (moderate evidence)
Mendeliome v0.9555 EHBP1L1 Zornitza Stark Gene: ehbp1l1 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9539 GNPNAT1 Zornitza Stark Phenotypes for gene: GNPNAT1 were changed from Rhizomelic skeletal dysplasia to Rhizomelic dysplasia, Ain-Naz type, MIM#619598
Mendeliome v0.9538 GNPNAT1 Zornitza Stark reviewed gene: GNPNAT1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Rhizomelic dysplasia, Ain-Naz type, MIM#619598; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9538 CDH1 Krithika Murali gene: CDH1 was added
gene: CDH1 was added to Mendeliome. Sources: Expert list,Literature
Mode of inheritance for gene: CDH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CDH1 were set to Blepharocheilodontic syndrome 1- MIM#119580; Cleft lip and palate
Review for gene: CDH1 was set to GREEN
Added comment: Well-established gene-disease association with blepharocheilodontic syndrome (BDC) and orofacial clefting.

Gene also associated with cancer predisposition - diffuse gastric cancer (juvenile onset reported) and lobular breast cancer.
Sources: Expert list, Literature
Mendeliome v0.9538 GRIK2 Zornitza Stark Phenotypes for gene: GRIK2 were changed from Mental retardation, autosomal recessive, 6 MIM# 611092; Nonsyndromic neurodevelopmental disorder, autosomal dominant to Mental retardation, autosomal recessive, 6 MIM# 611092; Neurodevelopmental disorder with impaired language and ataxia and with or without seizures, MIM# 619580
Mendeliome v0.9537 CACNA1C Krithika Murali gene: CACNA1C was added
gene: CACNA1C was added to Mendeliome. Sources: Expert list,Literature
Mode of inheritance for gene: CACNA1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CACNA1C were set to Timothy syndrome - MIM# 601005; Neurodevelopmental abnormalities and epilepsy, no OMIM#; Long QT syndrome 8- MIM#618447
Review for gene: CACNA1C was set to GREEN
Added comment: Well-established gene-disease association with Timothy Syndrome

Rodan et al. (2021) reported 25 individuals from 22 families with heterozygous truncating and missense variants in CACNA1C. The individuals presented with developmental delays, intellectual disability, autism, hypotonia, ataxia, and epilepsy BUT absence of classic features of Timothy syndrome or long QT syndrome.
Sources: Expert list, Literature
Mendeliome v0.9537 BGN Krithika Murali gene: BGN was added
gene: BGN was added to Mendeliome. Sources: Expert list,Literature
Mode of inheritance for gene: BGN was set to Other
Publications for gene: BGN were set to 27236923; 27632686
Phenotypes for gene: BGN were set to Meester-Loeys syndrome - #300989; Spondyloepimetaphyseal dysplasia, X-linked - #300106
Review for gene: BGN was set to GREEN
Added comment: Well-established gene-disease associated with X-linked spondyloepimetaphyseal dysplasia (SEMD) and Meester-Loeys syndrome (connective tissue disorder with phenotypic features including aortic dissection, aortic aneurysym, dysmorphism, joint hypermobility and mild skeletal dysplasia - with juvenile-onset reported in males)

SEMD - X-linked recessive inheritance
Meester-Loeys syndrome - hemizygous males, monoallelic mutations may cause disease in females (may be less severe, later onset than males)
Sources: Expert list, Literature
Mendeliome v0.9537 ATP13A2 Krithika Murali gene: ATP13A2 was added
gene: ATP13A2 was added to Mendeliome. Sources: Expert list,Literature
Mode of inheritance for gene: ATP13A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP13A2 were set to 1694263
Phenotypes for gene: ATP13A2 were set to Kufor-Rakeb syndrome - MIM#606693
Review for gene: ATP13A2 was set to GREEN
Added comment: Well-established gene-disease association with Kufor-Rakeb syndrome, a form of autosomal recessive hereditary parkinsonism and dementia showing juvenile onset, as well as neuronal ceroid lipofucinosis (NCL) features in some families. Also associated with adult-onset hereditary spastic paraparesis.
Sources: Expert list, Literature
Mendeliome v0.9537 CEP19 Zornitza Stark Gene: cep19 has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9537 CEP19 Zornitza Stark Phenotypes for gene: CEP19 were changed from Morbid obesity and spermatogenic failure MIM#615703 to Morbid obesity and spermatogenic failure MIM#615703; Bardet-Biedl syndorme
Mendeliome v0.9536 MUC5B Zornitza Stark Gene: muc5b has been classified as Red List (Low Evidence).
Mendeliome v0.9536 MUC5B Zornitza Stark Phenotypes for gene: MUC5B were changed from to {Pulmonary fibrosis, idiopathic, susceptibility to}, MIM# 178500
Mendeliome v0.9533 MUC5B Zornitza Stark Classified gene: MUC5B as Red List (low evidence)
Mendeliome v0.9533 MUC5B Zornitza Stark Gene: muc5b has been classified as Red List (Low Evidence).
Mendeliome v0.9532 MUC5B Zornitza Stark reviewed gene: MUC5B: Rating: RED; Mode of pathogenicity: None; Publications: 21506741, 21506748; Phenotypes: {Pulmonary fibrosis, idiopathic, susceptibility to}, MIM# 178500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9532 AHDC1 Zornitza Stark Gene: ahdc1 has been classified as Green List (High Evidence).
Mendeliome v0.9529 AGTR1 Zornitza Stark Gene: agtr1 has been classified as Green List (High Evidence).
Mendeliome v0.9529 AGTR1 Zornitza Stark Phenotypes for gene: AGTR1 were changed from to Renal tubular dysgenesis, MIM# 267430
Mendeliome v0.9526 AGTR1 Zornitza Stark reviewed gene: AGTR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 16116425; Phenotypes: Renal tubular dysgenesis, MIM# 267430; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9526 AGT Zornitza Stark Gene: agt has been classified as Green List (High Evidence).
Mendeliome v0.9526 AGT Zornitza Stark Phenotypes for gene: AGT were changed from to Renal tubular dysgenesis, MIM# 267430
Mendeliome v0.9523 AGT Zornitza Stark reviewed gene: AGT: Rating: GREEN; Mode of pathogenicity: None; Publications: 16116425, 34234805, 33163725; Phenotypes: Renal tubular dysgenesis, MIM# 267430; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9522 ADAMTS17 Zornitza Stark Gene: adamts17 has been classified as Green List (High Evidence).
Mendeliome v0.9522 ADAMTS17 Zornitza Stark Phenotypes for gene: ADAMTS17 were changed from to Weill-Marchesani 4 syndrome, recessive, MIM# 613195
Mendeliome v0.9519 ADAMTS17 Zornitza Stark reviewed gene: ADAMTS17: Rating: GREEN; Mode of pathogenicity: None; Publications: 19836009, 22486325, 24940034, 30712880; Phenotypes: Weill-Marchesani 4 syndrome, recessive, MIM# 613195; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9519 ACY1 Zornitza Stark Gene: acy1 has been classified as Green List (High Evidence).
Mendeliome v0.9516 ACE Zornitza Stark Gene: ace has been classified as Green List (High Evidence).
Mendeliome v0.9516 ACE Zornitza Stark Phenotypes for gene: ACE were changed from to Renal tubular dysgenesis, MIM# 267430
Mendeliome v0.9513 ACE Zornitza Stark reviewed gene: ACE: Rating: GREEN; Mode of pathogenicity: None; Publications: 16116425, 22095942; Phenotypes: Renal tubular dysgenesis, MIM# 267430; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9513 ACADVL Zornitza Stark Gene: acadvl has been classified as Green List (High Evidence).
Mendeliome v0.9510 FAN1 Zornitza Stark Gene: fan1 has been classified as Green List (High Evidence).
Mendeliome v0.9507 MANBA Zornitza Stark Phenotypes for gene: MANBA were changed from Mannosidosis, beta, MIM# 248510; MONDO:0009562 to Mannosidosis, beta, MIM# 248510; MONDO:0009562; Nystagmus, autosomal dominant
Mendeliome v0.9504 MANBA Zornitza Stark edited their review of gene: MANBA: Added comment: Two mono-allelic variants reported in association with isolated nystagmus. Note bi-allelic variants cause a lysosomal storage disorder.; Changed publications: 30552791, 25741867; Changed phenotypes: Mannosidosis, beta, MIM# 248510, MONDO:0009562, Nystagmus, autosomal dominant; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.9504 AHR Zornitza Stark reviewed gene: AHR: Rating: AMBER; Mode of pathogenicity: None; Publications: 31009037, 33193710; Phenotypes: Foveal hypoplasia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9502 ETHE1 Zornitza Stark commented on gene: ETHE1: Severe metabolic disorder characterized by neurodevelopmental delay and regression, prominent pyramidal and extrapyramidal signs, recurrent petechiae, orthostatic acrocyanosis, and chronic diarrhoea. Brain MRI shows necrotic lesions in deep gray matter structures.
Mendeliome v0.9502 ETHE1 Zornitza Stark Gene: ethe1 has been classified as Green List (High Evidence).
Mendeliome v0.9499 RHO Zornitza Stark Gene: rho has been classified as Green List (High Evidence).
Mendeliome v0.9499 RHO Zornitza Stark Phenotypes for gene: RHO were changed from to Night blindness, congenital stationary, autosomal dominant 1, MIM# 610445; Retinitis pigmentosa 4, autosomal dominant or recessive, MIM# 613731
Mendeliome v0.9496 RHO Zornitza Stark reviewed gene: RHO: Rating: GREEN; Mode of pathogenicity: None; Publications: 18487375, 27812022, 31213501, 1303237; Phenotypes: Night blindness, congenital stationary, autosomal dominant 1, MIM# 610445, Retinitis pigmentosa 4, autosomal dominant or recessive, MIM# 613731; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.9496 RDH12 Zornitza Stark Gene: rdh12 has been classified as Green List (High Evidence).
Mendeliome v0.9496 RDH12 Zornitza Stark Phenotypes for gene: RDH12 were changed from to Leber congenital amaurosis 13, MIM# 612712; Retinitis pigmentosa, autosomal dominant
Mendeliome v0.9493 RDH12 Zornitza Stark reviewed gene: RDH12: Rating: GREEN; Mode of pathogenicity: None; Publications: 16269441, 15322982, 15258582, 31505163; Phenotypes: Leber congenital amaurosis 13, MIM# 612712, Retinitis pigmentosa, autosomal dominant; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.9493 RD3 Zornitza Stark Gene: rd3 has been classified as Green List (High Evidence).
Mendeliome v0.9493 RD3 Zornitza Stark Phenotypes for gene: RD3 were changed from to Leber congenital amaurosis 12, MIM#610612
Mendeliome v0.9490 RD3 Zornitza Stark reviewed gene: RD3: Rating: GREEN; Mode of pathogenicity: None; Publications: 23308101, 22531706, 17186464; Phenotypes: Leber congenital amaurosis 12, MIM#610612; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9489 EXOSC5 Zornitza Stark Phenotypes for gene: EXOSC5 were changed from Short stature; Motor developmental delays; Cerebellar hypoplasia; Ataxia to Cerebellar ataxia, brain abnormalities, and cardiac conduction defects, MIM# 619576; Short stature; Motor developmental delays; Cerebellar hypoplasia; Ataxia
Mendeliome v0.9488 PRPH2 Zornitza Stark edited their review of gene: PRPH2: Changed phenotypes: Leber congenital amaurosis 18, MIM#608133, Macular dystrophy, vitelliform, 3, MIM#608161, Retinitis pigmentosa 7 and digenic form, MIM#608133, Choroidal dystrophy, central areolar 2, MIM#613105, Macular dystrophy, patterned, 1, MIM#169150 Retinitis punctata albescens, MIM#136880
Mendeliome v0.9488 PRPH2 Zornitza Stark Gene: prph2 has been classified as Green List (High Evidence).
Mendeliome v0.9488 PRPH2 Zornitza Stark Phenotypes for gene: PRPH2 were changed from Leber congenital amaurosis 18, MIM#608133; Macular dystrophy, vitelliform, 3, MIM#608161; Retinitis pigmentosa 7 and digenic form, MIM#608133 to Leber congenital amaurosis 18, MIM#608133; Macular dystrophy, vitelliform, 3, MIM#608161; Retinitis pigmentosa 7 and digenic form, MIM#608133; Choroidal dystrophy, central areolar 2, MIM#613105; Macular dystrophy, patterned, 1, MIM#169150; Retinitis punctata albescens, MIM#136880
Mendeliome v0.9487 PRPH2 Zornitza Stark Phenotypes for gene: PRPH2 were changed from to Leber congenital amaurosis 18, MIM#608133; Macular dystrophy, vitelliform, 3, MIM#608161; Retinitis pigmentosa 7 and digenic form, MIM#608133
Mendeliome v0.9484 PRPH2 Zornitza Stark reviewed gene: PRPH2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32660024; Phenotypes: Leber congenital amaurosis 18, MIM#608133 Macular dystrophy, vitelliform, 3, MIM#608161 Retinitis pigmentosa 7 and digenic form, MIM#608133 Choroidal dystrophy, central areolar 2, MIM#613105 Macular dystrophy, patterned, 1, MIM#169150 Retinitis punctata albescens, MIM#136880; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.9484 XBP1 Zornitza Stark Gene: xbp1 has been classified as Red List (Low Evidence).
Mendeliome v0.9483 XBP1 Zornitza Stark Classified gene: XBP1 as Red List (low evidence)
Mendeliome v0.9483 XBP1 Zornitza Stark Gene: xbp1 has been classified as Red List (Low Evidence).
Mendeliome v0.9481 BCL9L Zornitza Stark Gene: bcl9l has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9480 BCL9L Zornitza Stark Classified gene: BCL9L as Amber List (moderate evidence)
Mendeliome v0.9480 BCL9L Zornitza Stark Gene: bcl9l has been classified as Amber List (Moderate Evidence).
Mendeliome v0.9479 IMPDH1 Zornitza Stark Gene: impdh1 has been classified as Green List (High Evidence).
Mendeliome v0.9479 IMPDH1 Zornitza Stark Phenotypes for gene: IMPDH1 were changed from to Leber congenital amaurosis 11 (MIM# 613837); Retinitis pigmentosa 10 (MIM# 180105)
Mendeliome v0.9476 IMPDH1 Zornitza Stark reviewed gene: IMPDH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 16384941; Phenotypes: Leber congenital amaurosis 11 (MIM# 613837), Retinitis pigmentosa 10 (MIM# 180105); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.9476 KCNJ13 Zornitza Stark Gene: kcnj13 has been classified as Green List (High Evidence).
Mendeliome v0.9476 KCNJ13 Zornitza Stark Phenotypes for gene: KCNJ13 were changed from to Leber congenital amaurosis 16 MIM#614186; Snowflake vitreoretinal degeneration, MIM# 193230
Mendeliome v0.9473 KCNJ13 Zornitza Stark changed review comment from: LCA and bi-allelic variants: at least 4 individuals reported. Green.

Single family reported with snowflake vitreoretinal degeneration and mono-allelic variant, supportive functional data. Amber/Red.; to: Variants in KCNJ13 are associated with two retinal disorders; Leber congenital amaurosis (LCA) and snowflake vitreoretinal degeneration (SVD), though individuals with bi-allelic variants and LCA with subsequent fibrovascular proliferation described (PMID 31647904).

LCA and bi-allelic variants: at least 4 individuals reported. Green.

Single family reported with snowflake vitreoretinal degeneration and mono-allelic variant, supportive functional data. Amber/Red.
Mendeliome v0.9473 KCNJ13 Zornitza Stark reviewed gene: KCNJ13: Rating: GREEN; Mode of pathogenicity: None; Publications: 27203561, 25475713, 21763485, 18179896, 23255580, 31647904; Phenotypes: Leber congenital amaurosis 16 MIM#614186, Snowflake vitreoretinal degeneration, MIM# 193230; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v0.9473 LRIT3 Zornitza Stark Gene: lrit3 has been classified as Green List (High Evidence).
Mendeliome v0.9473 LRIT3 Zornitza Stark Phenotypes for gene: LRIT3 were changed from to Night blindness, congenital stationary (complete), 1F, autosomal recessive, MIM# 615058
Mendeliome v0.9470 LRIT3 Zornitza Stark reviewed gene: LRIT3: Rating: GREEN; Mode of pathogenicity: None; Publications: 23246293, 24598786, 31578364, 27428514; Phenotypes: Night blindness, congenital stationary (complete), 1F, autosomal recessive, MIM# 615058; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9470 NYX Zornitza Stark Gene: nyx has been classified as Green List (High Evidence).
Mendeliome v0.9467 GRM6 Zornitza Stark Gene: grm6 has been classified as Green List (High Evidence).
Mendeliome v0.9467 GRM6 Zornitza Stark Phenotypes for gene: GRM6 were changed from to Night blindness, congenital stationary (complete), 1B, autosomal recessive 257270
Mendeliome v0.9464 GRM6 Zornitza Stark reviewed gene: GRM6: Rating: GREEN; Mode of pathogenicity: None; Publications: 22008250; Phenotypes: Night blindness, congenital stationary (complete), 1B, autosomal recessive 257270; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9464 GRK1 Zornitza Stark Gene: grk1 has been classified as Green List (High Evidence).
Mendeliome v0.9461 GPR179 Zornitza Stark Gene: gpr179 has been classified as Green List (High Evidence).
Mendeliome v0.9461 GPR179 Zornitza Stark Phenotypes for gene: GPR179 were changed from to Night blindness, congenital stationary (complete), 1E, autosomal recessive (MIM#614565)
Mendeliome v0.9458 GPR179 Zornitza Stark reviewed gene: GPR179: Rating: GREEN; Mode of pathogenicity: None; Publications: 22325361; Phenotypes: Night blindness, congenital stationary (complete), 1E, autosomal recessive (MIM#614565); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9458 GNAT2 Zornitza Stark Gene: gnat2 has been classified as Green List (High Evidence).
Mendeliome v0.9458 GNAT2 Zornitza Stark Phenotypes for gene: GNAT2 were changed from to Achromatopsia 4, MIM#613856
Mendeliome v0.9455 GNAT2 Zornitza Stark reviewed gene: GNAT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32203983, 17251445; Phenotypes: Achromatopsia 4 MIM#613856; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9453 DEF6 Zornitza Stark Classified gene: DEF6 as Green List (high evidence)
Mendeliome v0.9453 DEF6 Zornitza Stark Gene: def6 has been classified as Green List (High Evidence).
Mendeliome v0.9452 DEF6 Zornitza Stark edited their review of gene: DEF6: Added comment: Additional family reported with 4 affected siblings.; Changed rating: GREEN; Changed publications: 31308374, 32562707; Changed phenotypes: Immunodeficiency 87 and autoimmunity, MIM# 619573, Systemic autoimmunity
Mendeliome v0.9452 CABP4 Zornitza Stark Gene: cabp4 has been classified as Green List (High Evidence).
Mendeliome v0.9452 CABP4 Zornitza Stark Phenotypes for gene: CABP4 were changed from to Cone-rod synaptic disorder, congenital nonprogressive, MIM# 610427
Mendeliome v0.9449 CABP4 Zornitza Stark reviewed gene: CABP4: Rating: GREEN; Mode of pathogenicity: None; Publications: 16960802, 19074807, 20157620; Phenotypes: Cone-rod synaptic disorder, congenital nonprogressive, MIM# 610427; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9449 ATF6 Zornitza Stark Gene: atf6 has been classified as Green List (High Evidence).
Mendeliome v0.9449 ATF6 Zornitza Stark Phenotypes for gene: ATF6 were changed from to Achromatopsia 7, MIM#616517
Mendeliome v0.9446 ATF6 Zornitza Stark reviewed gene: ATF6: Rating: GREEN; Mode of pathogenicity: None; Publications: 26063662, 26029869; Phenotypes: Achromatopsia 7, MIM#616517; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.9446 AIPL1 Zornitza Stark Gene: aipl1 has been classified as Green List (High Evidence).
Mendeliome v0.9446 AIPL1 Zornitza Stark Phenotypes for gene: AIPL1 were changed from to Leber congenital amaurosis 4, 604393 Cone-rod dystrophy, 604393 Retinitis pigmentosa, juvenile, 604393
Mendeliome v0.9443 AIPL1 Zornitza Stark reviewed gene: AIPL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 10615133; Phenotypes: Leber congenital amaurosis 4, 604393 Cone-rod dystrophy, 604393 Retinitis pigmentosa, juvenile, 604393; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mendeliome v0.9443 GNAS-AS1 Zornitza Stark Gene: gnas-as1 has been classified as Red List (Low Evidence).
Mendeliome v0.9440 GNAS-AS1 Zornitza Stark Classified gene: GNAS-AS1 as Red List (low evidence)
Mendeliome v0.9440 GNAS-AS1 Zornitza Stark Gene: gnas-as1 has been classified as Red List (Low Evidence).
Mendeliome v0.9437 SFTPC Zornitza Stark Gene: sftpc has been classified as Green List (High Evidence).
Mendeliome v0.9434 SFTPB Zornitza Stark Gene: sftpb has been classified as Green List (High Evidence).