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Intellectual disability v5.366 AGPAT3 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, only one family was reported so far with AGPAT3 biallelic variants and intellectual disability. In addition, functional evidence is also available, Hence, this gene should be rated amber.
Intellectual disability v5.366 AGPAT3 Achchuthan Shanmugasundram Gene: agpat3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.365 AGPAT3 Achchuthan Shanmugasundram Phenotypes for gene: AGPAT3 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.365 AGPAT3 Achchuthan Shanmugasundram Phenotypes for gene: AGPAT3 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.365 AGPAT3 Achchuthan Shanmugasundram Phenotypes for gene: AGPAT3 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.364 AGPAT3 Achchuthan Shanmugasundram Phenotypes for gene: AGPAT3 were changed from Neurodevelopmental disorder (MONDO#0700092), AGPAT3-related to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.363 AGPAT3 Achchuthan Shanmugasundram edited their review of gene: AGPAT3: Changed phenotypes to: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071
Intellectual disability v5.363 AGPAT3 Achchuthan Shanmugasundram reviewed gene: AGPAT3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v4.50 VWA8 Arina Puzriakova Tag watchlist tag was added to gene: VWA8.
Retinal disorders v4.50 VWA8 Arina Puzriakova Classified gene: VWA8 as Amber List (moderate evidence)
Retinal disorders v4.50 VWA8 Arina Puzriakova Added comment: Comment on list classification: New gene added by Hannah Knight. A single family (PMID: 37012052) with 11 individuals all presenting initial symptoms of visual defects which later progressed to macular changes, including macular degeneration and dystrophy. Two variants (c.3070G>A;c.4558C>T (p.Gly1024Arg; p.Arg1520Ter)) on the same allele of the VWA8 gene were found to segregate with disease. Expression studies showed reduced protein expression. Zebrafish knockdown model displayed a similar phenotype to that of humans.

Although there is only one family reported to date, multi-generational segregation with disease and concordant phenotype in a knockdown zebrafish model supports pathogenicity and therefore rating Amber with a 'watchlist' tag.
Retinal disorders v4.50 VWA8 Arina Puzriakova Gene: vwa8 has been classified as Amber List (Moderate Evidence).
Retinal disorders v4.49 VWA8 Arina Puzriakova Phenotypes for gene: VWA8 were changed from ?Retinitis pigmentosa 97 to ?Retinitis pigmentosa 97, OMIM:620422
Cytopenia - NOT Fanconi anaemia v3.21 DUT Arina Puzriakova Tag Q4_23_NHS_review was removed from gene: DUT.
Monogenic diabetes v2.54 DUT Arina Puzriakova Tag Q4_23_NHS_review was removed from gene: DUT.
Monogenic diabetes v2.54 DUT Arina Puzriakova Entity copied from Primary immunodeficiency or monogenic inflammatory bowel disease v4.133
Monogenic diabetes v2.54 DUT Arina Puzriakova gene: DUT was added
gene: DUT was added to Monogenic diabetes. Sources: Expert Review Amber,Literature
Q4_23_promote_green, Q4_23_NHS_review tags were added to gene: DUT.
Mode of inheritance for gene: DUT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DUT were set to 28073829; 35611808; 35931051
Phenotypes for gene: DUT were set to Bone marrow failure and diabetes mellitus syndrome, OMIM:620044
Cytopenia - NOT Fanconi anaemia v3.21 DUT Arina Puzriakova Entity copied from Primary immunodeficiency or monogenic inflammatory bowel disease v4.133
Cytopenia - NOT Fanconi anaemia v3.21 DUT Arina Puzriakova gene: DUT was added
gene: DUT was added to Cytopenia - NOT Fanconi anaemia. Sources: Expert Review Amber,Literature
Q4_23_promote_green, Q4_23_NHS_review tags were added to gene: DUT.
Mode of inheritance for gene: DUT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DUT were set to 28073829; 35611808; 35931051
Phenotypes for gene: DUT were set to Bone marrow failure and diabetes mellitus syndrome, OMIM:620044
Primary immunodeficiency or monogenic inflammatory bowel disease v4.133 DUT Arina Puzriakova Publications for gene: DUT were set to
Primary immunodeficiency or monogenic inflammatory bowel disease v4.132 DUT Arina Puzriakova Tag Q4_23_promote_green tag was added to gene: DUT.
Tag Q4_23_NHS_review tag was added to gene: DUT.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.132 DUT Arina Puzriakova Classified gene: DUT as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.132 DUT Arina Puzriakova Added comment: Comment on list classification: New gene added by Hannah Knight. Homozygous variants identified in at least 10 individuals from 6 unrelated families (French, Egyptian, two Libyan, Sudanese and Scottish) with bone marrow failure and diabetes. DUT silencing in human and rat pancreatic β-cells results in apoptosis via the intrinsic cell death pathway.

Overall there is sufficient evidence to promote this gene to Green at the next GMS panel update.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.132 DUT Arina Puzriakova Gene: dut has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.131 DUT Arina Puzriakova Phenotypes for gene: DUT were changed from Bone marrow failure and diabetes mellitus syndrome to Bone marrow failure and diabetes mellitus syndrome, OMIM:620044
Intellectual disability v5.363 SLC12A6 Arina Puzriakova Phenotypes for gene: SLC12A6 were changed from Agenesis of the corpus callosum with peripheral neuropathy, 218000 -3; AGENESIS OF THE CORPUS CALLOSUM WITH PERIPHERAL NEUROPATHY (ACCPN) to Agenesis of the corpus callosum with peripheral neuropathy, OMIM:218000
Hereditary neuropathy v1.473 SLC12A6 Arina Puzriakova Phenotypes for gene: SLC12A6 were changed from Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum; Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum to Charcot-Marie-Tooth disease, axonal, type 2II, OMIM:620068; Agenesis of the corpus callosum with peripheral neuropathy, OMIM:218000
Fetal anomalies v3.123 SLC12A6 Arina Puzriakova Phenotypes for gene: SLC12A6 were changed from AGENESIS OF THE CORPUS CALLOSUM WITH PERIPHERAL NEUROPATHY to Charcot-Marie-Tooth disease, axonal, type 2II, OMIM:620068; Agenesis of the corpus callosum with peripheral neuropathy, OMIM:218000
Hereditary neuropathy or pain disorder v3.69 SLC12A6 Arina Puzriakova Phenotypes for gene: SLC12A6 were changed from Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum to Charcot-Marie-Tooth disease, axonal, type 2II, OMIM:620068; Agenesis of the corpus callosum with peripheral neuropathy, OMIM:218000
Hereditary neuropathy or pain disorder v3.68 SLC12A6 Arina Puzriakova commented on gene: SLC12A6
Hereditary neuropathy or pain disorder v3.68 SLC12A6 Arina Puzriakova Publications for gene: SLC12A6 were set to 12368912; 31439721; 27485015; 16606917; 17893295; 21628467
Hereditary neuropathy or pain disorder v3.67 SLC12A6 Arina Puzriakova Tag Q4_23_promote_green tag was added to gene: SLC12A6.
Tag Q4_23_NHS_review tag was added to gene: SLC12A6.
Intellectual disability v5.362 C20orf24 Arina Puzriakova commented on gene: C20orf24: Added new-gene-name tag, new approved HGNC gene symbol for C20orf24 is RAB5IF
Intellectual disability v5.362 C20orf24 Arina Puzriakova Classified gene: C20orf24 as Red List (low evidence)
Intellectual disability v5.362 C20orf24 Arina Puzriakova Added comment: Comment on list classification: New gene added by Hannah Knight. Biallelic LoF variant identified in a patient with craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome. Authors suggested possible low penetrance due to two relatives with heterozygous variant and cleft lip and/or palate (PMID: 35614220).

Rating Red as only a single family reported to date. In OMIM the relationship between the phenotype and gene is provisional.
Intellectual disability v5.362 C20orf24 Arina Puzriakova Gene: c20orf24 has been classified as Red List (Low Evidence).
Intellectual disability v5.361 C20orf24 Arina Puzriakova Phenotypes for gene: C20orf24 were changed from ?Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome 2 to ?Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome 2, OMIM:616994
Intellectual disability v5.360 C20orf24 Arina Puzriakova Tag new-gene-name tag was added to gene: C20orf24.
Intellectual disability v5.360 MTF1 Sarah Leigh changed review comment from: Comment on publications: PMID: 23033978 reports MTF1: NM_005955.2 c.333del p.(Thr112Hisfs*26) as a de novo variant in a patient with severe ID, who also carries a maternally inherited TRPC5 NM_012471.2 c.1999C>A p.(Pro667Thr) variant (tables S3 & S10).; to: Comment on publications: PMID: 23033978 reports MTF1: NM_005955.2 c.333del p.(Thr112Hisfs*26) as a de novo variant in a patient with severe ID, who also carries a maternally inherited TRPC5 NM_012471.2 c.1999C>A p.(Pro667Thr) variant (tables S3, S9 & S10).
Intellectual disability v5.360 TRPC5 Sarah Leigh Added comment: Comment on publications: PMID: 23033978 reports MTF1: NM_005955.2 c.333del p.(Thr112Hisfs*26) as a de novo variant in a patient with severe ID, who also carries a maternally inherited TRPC5 NM_012471.2 c.1999C>A p.(Pro667Thr) variant (tables S3, S9 & S10).
Intellectual disability v5.360 TRPC5 Sarah Leigh Publications for gene: TRPC5 were set to 36323681
Intellectual disability v5.359 MTF1 Sarah Leigh Added comment: Comment on publications: PMID: 23033978 reports MTF1: NM_005955.2 c.333del p.(Thr112Hisfs*26) as a de novo variant in a patient with severe ID, who also carries a maternally inherited TRPC5 NM_012471.2 c.1999C>A p.(Pro667Thr) variant (tables S3 & S10).
Intellectual disability v5.359 MTF1 Sarah Leigh Publications for gene: MTF1 were set to 26350204; 28901405; 18341605; 23033978
Intellectual disability v5.358 MTF1 Sarah Leigh Publications for gene: MTF1 were set to 26350204; 28901405; 18341605
Intellectual disability v5.357 TRPC5 Sarah Leigh Entity copied from DDG2P v3.79
Intellectual disability v5.357 TRPC5 Sarah Leigh gene: TRPC5 was added
gene: TRPC5 was added to Intellectual disability - microarray and sequencing. Sources: DD-Gene2Phenotype,Expert Review Red
Mode of inheritance for gene: TRPC5 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: TRPC5 were set to 36323681
Phenotypes for gene: TRPC5 were set to TRPC5-related neurodevelopmental disorder
Intellectual disability v5.356 CDK16 Sarah Leigh Classified gene: CDK16 as Amber List (moderate evidence)
Intellectual disability v5.356 CDK16 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v5.356 CDK16 Sarah Leigh Gene: cdk16 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.355 CDK16 Sarah Leigh Tag Q4_23_promote_green tag was added to gene: CDK16.
Tag Q4_23_NHS_review tag was added to gene: CDK16.
Intellectual disability v5.355 CDK16 Sarah Leigh Added comment: Comment on phenotypes: Intellectual disability, MONDO:0001071 is the phenotype listed for CDK16 in Gene2Phen (2nd January 2024)
Intellectual disability v5.355 CDK16 Sarah Leigh Phenotypes for gene: CDK16 were changed from to Intellectual disability, MONDO:0001071
Intellectual disability v5.354 CDK16 Sarah Leigh edited their review of gene: CDK16: Added comment: To date, CDK16 variants have not been associated with a phenotype in OMIM, but have a limited association with intellectual disability (ID) in Gen2Phen. Four CDK16 variants have been associated with a spectrum of phenotypic features, including ID (n= 3), autism spectrum disorder (n= 3), seizures (n= 2) and spacity (n= 2)(PMID:36323681, 31981491, 25644381).; Changed rating: GREEN
Intellectual disability v5.354 CDK16 Sarah Leigh Publications for gene: CDK16 were set to 26350204; 25644381
Likely inborn error of metabolism v4.88 LDHD Sarah Leigh edited their review of gene: LDHD: Added comment: LDHD variants have been associated with D-lactic aciduria with susceptibility to gout (OMIM:245450), but not with a phenotype in Gen2Phen. At least seven LDHD variants have been reported in seven unrelated cases (PMID: 30931947;31638601;34258137;37021930).; Changed rating: GREEN
Likely inborn error of metabolism v4.88 LDHD Sarah Leigh Phenotypes for gene: LDHD were changed from D-lactic aciduria with susceptibility to gout, OMIM:245450 to D-lactic aciduria with susceptibility to gout, OMIM:245450; lactic aciduria due to D-lactic acid, MONDO:0009505
Likely inborn error of metabolism v4.87 LDHD Sarah Leigh Classified gene: LDHD as Amber List (moderate evidence)
Likely inborn error of metabolism v4.87 LDHD Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Likely inborn error of metabolism v4.87 LDHD Sarah Leigh Gene: ldhd has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v4.86 LDHD Sarah Leigh Publications for gene: LDHD were set to 30931947; 31638601
Likely inborn error of metabolism v4.85 LDHD Sarah Leigh Phenotypes for gene: LDHD were changed from D-lactic aciduria with susceptibility to gout to D-lactic aciduria with susceptibility to gout, OMIM:245450
Likely inborn error of metabolism v4.84 LDHD Sarah Leigh Classified gene: LDHD as Amber List (moderate evidence)
Likely inborn error of metabolism v4.84 LDHD Sarah Leigh Gene: ldhd has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v4.84 LDHD Sarah Leigh Classified gene: LDHD as Amber List (moderate evidence)
Likely inborn error of metabolism v4.84 LDHD Sarah Leigh Gene: ldhd has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.353 ACACA Sarah Leigh Tag Q4_23_NHS_review was removed from gene: ACACA.
Intellectual disability v5.353 ACACA Sarah Leigh Entity copied from Likely inborn error of metabolism - targeted testing not possible v4.83
Intellectual disability v5.353 ACACA Sarah Leigh gene: ACACA was added
gene: ACACA was added to Intellectual disability - microarray and sequencing. Sources: Expert Review Amber,Literature
Q4_23_promote_green, Q4_23_NHS_review tags were added to gene: ACACA.
Mode of inheritance for gene: ACACA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACACA were set to 6114432; 34552920; 36709796
Phenotypes for gene: ACACA were set to Acetyl-CoA carboxylase deficiency, OMIM: 613933
Likely inborn error of metabolism v4.83 ACACA Sarah Leigh Publications for gene: ACACA were updated from 6114432; 16103361; 34552920; 36709796 to 6114432; 34552920; 36709796
Likely inborn error of metabolism v4.82 ACACA Sarah Leigh Publications for gene: ACACA were set to 6114432; 34552920; 36709796
Likely inborn error of metabolism v4.81 ACACA Sarah Leigh Tag Q4_23_promote_green tag was added to gene: ACACA.
Tag Q4_23_NHS_review tag was added to gene: ACACA.
Likely inborn error of metabolism v4.81 ACACA Sarah Leigh reviewed gene: ACACA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Primary immunodeficiency or monogenic inflammatory bowel disease v4.130 LYN Achchuthan Shanmugasundram Classified gene: LYN as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.130 LYN Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (four unrelated cases and functional studies) for the promotion of this gene to green rating in the next GMS review.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.130 LYN Achchuthan Shanmugasundram Gene: lyn has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.129 LYN Achchuthan Shanmugasundram Phenotypes for gene: LYN were changed from Autoinflammatory; Neutrophilic vasculitis; Liver fibrosis; Chronic urticaria; Atopic dermatitis; Fever to Autoinflammatory disease, systemic, with vasculitis, OMIM:620376
Primary immunodeficiency or monogenic inflammatory bowel disease v4.128 LYN Achchuthan Shanmugasundram Publications for gene: LYN were set to 36122175
Primary immunodeficiency or monogenic inflammatory bowel disease v4.127 LYN Achchuthan Shanmugasundram Mode of pathogenicity for gene: LYN was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Primary immunodeficiency or monogenic inflammatory bowel disease v4.126 LYN Achchuthan Shanmugasundram Mode of inheritance for gene: LYN was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v4.125 LYN Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: LYN.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.125 LYN Achchuthan Shanmugasundram changed review comment from: As reviewed by Boaz Palterer, there are four unrelated patients reported with systemic autoinflammatory disorder (SAID) and identified with de novo LYN variants. Of these one patient was reported in PMID:36122175 and three unrelated boys were reported in PMID:36932076. The patient data was also supported by functional evidence, which suggested gain of function mechanism for variants.

This gene was associated with relevant phenotypes in OMIM (MIM #620376), but not yet in Gene2Phenotype.; to: As reviewed by Boaz Palterer, there are four unrelated patients reported with systemic autoinflammatory disorder (SAID) and identified with de novo LYN variants. Of these one patient was reported in PMID:36122175 and three unrelated boys were reported in PMID:36932076. The patient data was also supported by functional evidence, which suggested gain of function mechanism for LYN variants.

This gene was associated with relevant phenotypes in OMIM (MIM #620376), but not yet in Gene2Phenotype.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.125 LYN Achchuthan Shanmugasundram changed review comment from: As reviewed by Boaz Palterer, there are four unrelated patients reported with systemic autoinflammatory disorder (SAID) and identified with de novo LYN variants. Of these one patient was reported in PMID:36122175 and three unrelated boys were reported in PMID:36932076. The patient data was also supported by functional evidence which suggested gain of function mechanism for variants.

This gene was associated with relevant phenotypes in OMIM (MIM #620376), but not yet in Gene2Phenotype.; to: As reviewed by Boaz Palterer, there are four unrelated patients reported with systemic autoinflammatory disorder (SAID) and identified with de novo LYN variants. Of these one patient was reported in PMID:36122175 and three unrelated boys were reported in PMID:36932076. The patient data was also supported by functional evidence, which suggested gain of function mechanism for variants.

This gene was associated with relevant phenotypes in OMIM (MIM #620376), but not yet in Gene2Phenotype.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.125 LYN Achchuthan Shanmugasundram reviewed gene: LYN: 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: 36122175, 36932076; Phenotypes: Autoinflammatory disease, systemic, with vasculitis, OMIM:620376; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Likely inborn error of metabolism v4.81 ACACA Sarah Leigh Publications for gene: ACACA were set to 34552920; 36709796
Likely inborn error of metabolism v4.80 ACACA Sarah Leigh Publications for gene: ACACA were set to 34552920; 36709796
Likely inborn error of metabolism v4.80 ACACA Sarah Leigh Publications for gene: ACACA were set to 34552920
Likely inborn error of metabolism v4.79 ACACA Sarah Leigh Phenotypes for gene: ACACA were changed from Acetyl-CoA carboxylase deficiency to Acetyl-CoA carboxylase deficiency, OMIM: 613933
Likely inborn error of metabolism v4.78 ACACA Sarah Leigh Classified gene: ACACA as Amber List (moderate evidence)
Likely inborn error of metabolism v4.78 ACACA Sarah Leigh Gene: acaca has been classified as Amber List (Moderate Evidence).
Cystic kidney disease v4.24 NEK8 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: NEK8.
Cystic kidney disease v4.24 NEK8 Achchuthan Shanmugasundram Classified gene: NEK8 as Amber List (moderate evidence)
Cystic kidney disease v4.24 NEK8 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available in support of the association of monoallelic NEK8 variants with polycystic kidney disease. Hence, this gene can be promoted to green rating in the next GMS review.
Cystic kidney disease v4.24 NEK8 Achchuthan Shanmugasundram Gene: nek8 has been classified as Amber List (Moderate Evidence).
Cystic kidney disease v4.23 NEK8 Achchuthan Shanmugasundram Mode of inheritance for gene: NEK8 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cystic kidney disease v4.22 NEK8 Achchuthan Shanmugasundram edited their review of gene: NEK8: Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Cystic kidney disease v4.22 NEK8 Achchuthan Shanmugasundram changed review comment from: PMID:37598857 reported the identification of monoallelic NEK8 variants in 12 different families reported with autosomal dominant polycystic kidney disease (ADPKD). Of these, de novo missense variant p.Arg45Trp was found in 10 families and missense variants p.Ile150Met and p.Lys157Gln were found in one family each. Patient fibroblasts show normal ciliogenesis and normal localisation and expression of NEK8.

PMID:18199800 reported one patient with biallelic NEK8 variant (p.His425Tyr) and with nephronophthisis. Nephronophthisis is an autosomal recessive kidney disease that leads to kidney cyst formation and progressive renal failure.

Although nephronophthisis 9 (MIM #613824) caused by biallelic variants is reported in both OMIM and Gene2Phenotype, cystic kidney disease caused by monoallelic variants are not yet reported in these resources.; to: PMID:37598857 reported the identification of monoallelic NEK8 variants in 12 different families reported with autosomal dominant polycystic kidney disease (ADPKD). Of these, de novo missense variant p.Arg45Trp was found in 10 families and missense variants p.Ile150Met and p.Lys157Gln were found in one family each. Patient fibroblasts show normal ciliogenesis and normal localisation and expression of NEK8. Carriers of AR-NEK8 disease do not show renal manifestations, as variants are LOF and these variants are suspected of dominant negative effect.

PMID:18199800 reported one patient with biallelic NEK8 variant (p.His425Tyr) and with nephronophthisis. Nephronophthisis is an autosomal recessive kidney disease that leads to kidney cyst formation and progressive renal failure.

Although nephronophthisis 9 (MIM #613824) caused by biallelic variants is reported in both OMIM and Gene2Phenotype, cystic kidney disease caused by monoallelic variants are not yet reported in these resources.
Cystic kidney disease v4.22 NEK8 Achchuthan Shanmugasundram Mode of pathogenicity for gene: NEK8 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Cystic kidney disease v4.21 NEK8 Achchuthan Shanmugasundram Publications for gene: NEK8 were set to
Cystic kidney disease v4.20 NEK8 Achchuthan Shanmugasundram Phenotypes for gene: NEK8 were changed from Ciliopathy genes associated with cystic kidney disease to polycystic kidney disease, MONDO:0020642; ?Nephronophthisis 9, OMIM:613824
Cystic kidney disease v4.19 NEK8 Achchuthan Shanmugasundram changed review comment from: PMID:37598857 reported the identification of monoallelic NEK8 variants in 12 different families reported with autosomal dominant polycystic kidney disease (ADPKD). Of these, de novo missense variant p.Arg45Trp was found in 10 families and missense variants p.Ile150Met and p.Lys157Gln were found in one family each. Patient fibroblasts show normal ciliogenesis and normal localisation and expression of NEK8.; to: PMID:37598857 reported the identification of monoallelic NEK8 variants in 12 different families reported with autosomal dominant polycystic kidney disease (ADPKD). Of these, de novo missense variant p.Arg45Trp was found in 10 families and missense variants p.Ile150Met and p.Lys157Gln were found in one family each. Patient fibroblasts show normal ciliogenesis and normal localisation and expression of NEK8.

PMID:18199800 reported one patient with biallelic NEK8 variant (p.His425Tyr) and with nephronophthisis. Nephronophthisis is an autosomal recessive kidney disease that leads to kidney cyst formation and progressive renal failure.

Although nephronophthisis 9 (MIM #613824) caused by biallelic variants is reported in both OMIM and Gene2Phenotype, cystic kidney disease caused by monoallelic variants are not yet reported in these resources.
Cystic kidney disease v4.19 NEK8 Achchuthan Shanmugasundram edited their review of gene: NEK8: Changed publications to: 18199800, 37598857; Changed phenotypes to: polycystic kidney disease, MONDO:0020642, ?Nephronophthisis 9, OMIM:613824
Cystic kidney disease v4.19 NEK8 Achchuthan Shanmugasundram reviewed gene: NEK8: Rating: GREEN; Mode of pathogenicity: None; Publications: 37598857; Phenotypes: polycystic kidney disease, MONDO:0020642; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - narrow panel v4.43 ASL Eleanor Williams changed review comment from: Argininosuccinic aciduria (ASA) is caused by homozygous mutation in the gene encoding argininosuccinate lyase (ASL). Onset is typically in the neonatal period or in late infancy.

The association of biallelic variants in ASL and the phenotype of Argininosuccinic aciduria is well established. e.g.

PMID: 12384776 - Linnebank et al 2002 - homozygous/compound het variants in ASL in 27 unrelated individuals of different ancestries. No phenotype information is given. They also found a complete homologue of this gene on chr 22 which is predicted to encode an immunoglobulin-lambda-like mRNA.

PMID: 17326097 - Trevisson et al 2007 - report homozygous/compound het variants in ASL in 12 Italian patients with ASA. Ataxia is not mentioned as a phenotypic feature.

PMID: 29326055 - AlTassan et al 2018 - a retrospective review of 54 Saudi Arabian patients with ASA from January 2000 to December 2015. 35 patients (63%) had genetic data available all with variants in the ASL gene; c.1060C > T; p.(Gln354*) in 26 patients; c.556C > T; p.(Arg186Trp) in 7 patients, c.602+1G > T in one patient and 1062+5G > C in one patient. Ataxia is not mentioned as a phenotypic feature.

More recent retrospectives show that ataxia is reported in approx. 10% of individuals. 2 confirmed cases with ataxia and ASL variants are reported.

PMID: 38044746 - Gurung et al 2023 - conducted a UK national multicentre retrospective study assessing the movement disorder phenotype in ASA patients from July 2015 to June 2022. 60 patients were studied with a median age of 12.7 years (range: 6 months to 53 years). 17 (28%) individuals had ASA with neurodegenerative-related symptoms, movement disorder, hypotonia/fatigue and abnormal behaviour. Of these 7 were reported to show ataxia and 4 of these individuals presented with ataxia by age 11 or less. Homozygous or compound het ASL variants were recorded in 25/60 paitents including 2 out of 7 patients with ataxia. Genotype data was not available for other patients.

PMID: 28251416 - Baruteau et al 2017 - conducted a retrospective and prospective analysis of patients in the UK with ASA from March 2013 - December 2015. Ataxia was reported in 9 out of 52 patients studied.

(PMID: 36994644 - Elkhateeb et al 2023 - characterise the incidence of epilepsy in patients with ASA. ); to: Argininosuccinic aciduria (ASA) is caused by homozygous mutation in the gene encoding argininosuccinate lyase (ASL). Onset is typically in the neonatal period or in late infancy.

The association of biallelic variants in ASL and the phenotype of Argininosuccinic aciduria is well established. e.g.

PMID: 12384776 - Linnebank et al 2002 - homozygous/compound het variants in ASL in 27 unrelated individuals of different ancestries. No phenotype information is given. They also found a complete homologue of this gene on chr 22 which is predicted to encode an immunoglobulin-lambda-like mRNA.

PMID: 17326097 - Trevisson et al 2007 - report homozygous/compound het variants in ASL in 12 Italian patients with ASA. Ataxia is not mentioned as a phenotypic feature.

PMID: 29326055 - AlTassan et al 2018 - a retrospective review of 54 Saudi Arabian patients with ASA from January 2000 to December 2015. 35 patients (63%) had genetic data available all with variants in the ASL gene; c.1060C > T; p.(Gln354*) in 26 patients; c.556C > T; p.(Arg186Trp) in 7 patients, c.602+1G > T in one patient and 1062+5G > C in one patient. Ataxia is not mentioned as a phenotypic feature.

More recent retrospectives show that ataxia is reported in approx. 10% of individuals with Argininosuccinic aciduria. 2 cases with ataxia and ASL variant identified are reported.

PMID: 38044746 - Gurung et al 2023 - conducted a UK national multicentre retrospective study assessing the movement disorder phenotype in ASA patients from July 2015 to June 2022. 60 patients were studied with a median age of 12.7 years (range: 6 months to 53 years). 17 (28%) individuals had ASA with neurodegenerative-related symptoms, movement disorder, hypotonia/fatigue and abnormal behaviour. Of these 7 were reported to show ataxia and 4 of these individuals presented with ataxia by age 11 or less. Homozygous or compound het ASL variants were recorded in 25/60 paitents including 2 out of 7 patients with ataxia. Genotype data was not available for other patients.

PMID: 28251416 - Baruteau et al 2017 - conducted a retrospective and prospective analysis of patients in the UK with ASA from March 2013 - December 2015. Ataxia was reported in 9 out of 52 patients studied.

(PMID: 36994644 - Elkhateeb et al 2023 - characterise the incidence of epilepsy in patients with ASA. )
Retinal disorders v4.48 TTC21B Nour Elkhateeb reviewed gene: TTC21B: Rating: GREEN; Mode of pathogenicity: None; Publications: 21068128, 33599192; Phenotypes: Retinal dystrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.43 ASL Eleanor Williams commented on gene: ASL
Skeletal dysplasia v4.32 UBA2 Eleanor Williams Tag Q4_23_promote_green tag was added to gene: UBA2.
Tag Q4_23_NHS_review tag was added to gene: UBA2.
Skeletal dysplasia v4.32 UBA2 Eleanor Williams commented on gene: UBA2: As reviewer notes there are now additional cases reported with variants in UBA2 and skeletal defects including:

PMID: 34040189 - Schnur et al 2021 - report 16 individuals from 7 families who have variable phenotypes including Aplasia cutis congenita and skeletal defects. Ectrodyctly is present in some individuals from 4/7 families and other skeletal phenotypes such as hip abnormalities, plagiocephaly, Wormian bones, syndactyly, kyphoscoliosis, Variants were heterozygous rare variants not found in GnomAD and consist of frameshift, nonsense and missense variants.
Intellectual disability v5.352 DLG2 Achchuthan Shanmugasundram Tag epigenetics was removed from gene: DLG2.
Intellectual disability v5.352 DIP2B Achchuthan Shanmugasundram Tag epigenetics was removed from gene: DIP2B.
Familial prostate cancer v1.3 BRCA2 Achchuthan Shanmugasundram Tag stratified-medicine was removed from gene: BRCA2.
Familial prostate cancer v1.3 BRCA1 Achchuthan Shanmugasundram Tag stratified-medicine was removed from gene: BRCA1.
Early onset or syndromic epilepsy v4.135 ALPL Achchuthan Shanmugasundram Tag drug-indication was removed from gene: ALPL.
Parkinson Disease and Complex Parkinsonism v1.120 HTT_CAG Achchuthan Shanmugasundram Tag anticipation was removed from STR: HTT_CAG.
Intellectual disability v5.352 GABRQ Achchuthan Shanmugasundram Phenotypes for gene: GABRQ were changed from ASD; schizophrenia; migraine to autism spectrum disorder, MONDO:0005258; schizophrenia, MONDO:0005090; migraine disorder, MONDO:0005277
Intellectual disability v5.351 GABRQ Achchuthan Shanmugasundram Tag Schizophrenia was removed from gene: GABRQ.
Adult onset leukodystrophy v3.23 RNASET2 Achchuthan Shanmugasundram Tag Q4_21_expert_review was removed from gene: RNASET2.
Tag Q4_21_rating was removed from gene: RNASET2.
Adult onset leukodystrophy v3.23 POLR1C Achchuthan Shanmugasundram Tag Q4_21_expert_review was removed from gene: POLR1C.
Tag Q4_21_rating was removed from gene: POLR1C.
Hydrocephalus v4.3 MYMK Achchuthan Shanmugasundram Tag Q4_21_expert_review was removed from gene: MYMK.
Tag Q4_21_rating was removed from gene: MYMK.
Tag Q4_21_phenotype was removed from gene: MYMK.
Adult onset leukodystrophy v3.23 MARS Achchuthan Shanmugasundram Tag Q4_21_expert_review was removed from gene: MARS.
Tag Q4_21_rating was removed from gene: MARS.
Tag Q4_21_phenotype was removed from gene: MARS.
Hydrocephalus v4.3 HYLS1 Achchuthan Shanmugasundram Tag Q4_21_expert_review was removed from gene: HYLS1.
Tag Q4_21_rating was removed from gene: HYLS1.
Congenital hyperinsulinism v3.4 GPC3 Achchuthan Shanmugasundram Tag Q4_21_expert_review was removed from gene: GPC3.
Tag Q4_21_rating was removed from gene: GPC3.
Tag Q4_21_phenotype was removed from gene: GPC3.
Adult onset dystonia, chorea or related movement disorder v3.18 GBA Achchuthan Shanmugasundram Tag Q4_21_expert_review was removed from gene: GBA.
Tag Q4_21_rating was removed from gene: GBA.
Severe microcephaly v4.48 DPP6 Achchuthan Shanmugasundram Tag Q4_21_expert_review was removed from gene: DPP6.
Tag Q4_21_rating was removed from gene: DPP6.
Adult onset leukodystrophy v3.23 COL4A2 Achchuthan Shanmugasundram Tag Q4_21_expert_review was removed from gene: COL4A2.
Tag Q4_21_rating was removed from gene: COL4A2.
Tag Q4_21_phenotype was removed from gene: COL4A2.
Congenital hyperinsulinism v3.4 AKT2 Achchuthan Shanmugasundram Tag Q4_21_expert_review was removed from gene: AKT2.
Tag Q4_21_rating was removed from gene: AKT2.
Tag Q4_21_phenotype was removed from gene: AKT2.
Adult onset leukodystrophy v3.23 AARS Achchuthan Shanmugasundram Tag Q4_21_expert_review was removed from gene: AARS.
Tag Q4_21_rating was removed from gene: AARS.
Cerebral vascular malformations v3.8 SETD5 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: SETD5.
Tag Q3_22_expert_review was removed from gene: SETD5.
Neonatal diabetes v4.4 ONECUT1 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: ONECUT1.
Tag Q3_22_NHS_review was removed from gene: ONECUT1.
Tag Q3_22_expert_review was removed from gene: ONECUT1.
Cerebral vascular malformations v3.8 CNOT3 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: CNOT3.
Tag Q3_22_expert_review was removed from gene: CNOT3.
Neonatal diabetes v4.4 CNOT1 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: CNOT1.
Tag Q3_22_NHS_review was removed from gene: CNOT1.
Tag Q3_22_expert_review was removed from gene: CNOT1.
Cerebral vascular malformations v3.8 CHD4 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: CHD4.
Tag Q3_22_expert_review was removed from gene: CHD4.
Fetal anomalies v3.122 MED12 Achchuthan Shanmugasundram Tag Q3_21_MOI was removed from gene: MED12.
Tag Q3_21_expert_review was removed from gene: MED12.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.125 DCLRE1B Achchuthan Shanmugasundram Tag Q3_21_rating was removed from gene: DCLRE1B.
Tag Q3_21_expert_review was removed from gene: DCLRE1B.
Childhood onset dystonia, chorea or related movement disorder v3.56 AFG3L2 Achchuthan Shanmugasundram Tag Q2_21_rating was removed from gene: AFG3L2.
Tag Q2_21_phenotype was removed from gene: AFG3L2.
Fetal anomalies v3.122 KIDINS220 Achchuthan Shanmugasundram Tag Q2_21_rating was removed from gene: KIDINS220.
Tag Q2_21_expert_review was removed from gene: KIDINS220.
Tag Q2_21_MOI was removed from gene: KIDINS220.
Fetal anomalies v3.122 LIFR Achchuthan Shanmugasundram Tag Q2_22_MOI was removed from gene: LIFR.
Tag Q2_22_expert_review was removed from gene: LIFR.
Intellectual disability v5.351 FAR1 Achchuthan Shanmugasundram Tag Q2_21_expert_review was removed from gene: FAR1.
Tag Q2_21_MOI was removed from gene: FAR1.
Hydrocephalus v4.3 ERF Achchuthan Shanmugasundram Tag Q2_21_rating was removed from gene: ERF.
Tag Q2_21_expert_review was removed from gene: ERF.
Holoprosencephaly - NOT chromosomal v4.4 DISP1 Achchuthan Shanmugasundram Tag Q2_21_rating was removed from gene: DISP1.
Tag Q2_21_expert_review was removed from gene: DISP1.
Monogenic hearing loss v4.25 COL9A3 Achchuthan Shanmugasundram Tag Q2_21_rating was removed from gene: COL9A3.
Tag Q2_21_phenotype was removed from gene: COL9A3.
Tag Q2_21_expert_review was removed from gene: COL9A3.
Hereditary neuropathy or pain disorder v3.67 SLC12A6 Achchuthan Shanmugasundram Tag Q1_22_rating was removed from gene: SLC12A6.
Monogenic hearing loss v4.25 FOXI1 Achchuthan Shanmugasundram Tag Q1_22_expert_review was removed from gene: FOXI1.
Tag Q1_22_MOI was removed from gene: FOXI1.
Congenital myopathy v4.34 TNNT1 Achchuthan Shanmugasundram Publications for gene: TNNT1 were set to 26296490; 25430424; 32994279
Congenital myopathy v4.33 SELENON Achchuthan Shanmugasundram edited their review of gene: SELENON: Changed phenotypes to: Muscular dystrophy, rigid spine, 1, OMIM:602771
Congenital muscular dystrophy v4.20 DAG1 Achchuthan Shanmugasundram Publications for gene: DAG1 were set to 26380289; 24052401; 25934851; 22810924
Congenital muscular dystrophy v4.19 EMD Achchuthan Shanmugasundram Tag Q2_21_expert_review was removed from gene: EMD.
Tag Q2_23_expert_review tag was added to gene: EMD.
Congenital muscular dystrophy v4.19 COL4A1 Eleanor Williams Tag Q3_23_NHS_review tag was added to gene: COL4A1.
Congenital myopathy v4.33 LETM1 Eleanor Williams Tag Q3_23_NHS_review tag was added to gene: LETM1.
Congenital muscular dystrophy v4.19 POGLUT1 Eleanor Williams Tag Q4_22_NHS_review tag was added to gene: POGLUT1.
Congenital muscular dystrophy v4.19 EMD Eleanor Williams commented on gene: EMD
Congenital muscular dystrophy v4.19 EMD Eleanor Williams Tag Q2_21_expert_review tag was added to gene: EMD.
Possible mitochondrial disorder - nuclear genes v3.68 ATP5E Eleanor Williams Tag Q4_23_promote_green tag was added to gene: ATP5E.
Tag Q4_23_expert_review tag was added to gene: ATP5E.
Familial tumours of the nervous system v2.1 Achchuthan Shanmugasundram Panel version 2.0 has been signed off on 2023-12-20
Familial tumours of the nervous system v2.0 Achchuthan Shanmugasundram promoted panel to version 2.0
Hereditary isolated diabetes insipidus v2.1 Achchuthan Shanmugasundram Panel version 2.0 has been signed off on 2023-12-20
Hereditary isolated diabetes insipidus v2.0 Achchuthan Shanmugasundram promoted panel to version 2.0
Hereditary diffuse gastric cancer v2.1 Achchuthan Shanmugasundram Panel version 2.0 has been signed off on 2023-12-20
Hereditary diffuse gastric cancer v2.0 Achchuthan Shanmugasundram promoted panel to version 2.0
Hereditary diffuse gastric cancer v1.10 Eleanor Williams List of related panels changed from R215; CDH1-related cancer syndrome to CDH1-related cancer syndrome; R215
Hereditary isolated diabetes insipidus v1.9 Eleanor Williams List of related panels changed from R440; Neuropophyseal diabetes insipidus to Neuropophyseal diabetes insipidus; R440
Hereditary isolated diabetes insipidus v1.7 Achchuthan Shanmugasundram Panel name changed from Neuropophyseal diabetes insipidus to Hereditary isolated diabetes insipidus
List of related panels changed from R440 to R440; Neuropophyseal diabetes insipidus
Hereditary diffuse gastric cancer v1.6 Achchuthan Shanmugasundram Panel name changed from CDH1-related cancer syndrome to Hereditary diffuse gastric cancer
List of related panels changed from R215 to R215; CDH1-related cancer syndrome
Structural eye disease v3.72 SLC25A24 Achchuthan Shanmugasundram Classified gene: SLC25A24 as Amber List (moderate evidence)
Structural eye disease v3.72 SLC25A24 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.
Structural eye disease v3.72 SLC25A24 Achchuthan Shanmugasundram Gene: slc25a24 has been classified as Amber List (Moderate Evidence).
Structural eye disease v3.71 SLC25A24 Achchuthan Shanmugasundram Publications for gene: SLC25A24 were set to 29903433; 29100093; 29100094
Structural eye disease v3.70 SLC25A24 Achchuthan Shanmugasundram Mode of inheritance for gene: SLC25A24 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v3.69 SLC25A24 Achchuthan Shanmugasundram Tag Q4_23_NHS_review tag was added to gene: SLC25A24.
Structural eye disease v3.69 SLC25A24 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: SLC25A24.
Structural eye disease v3.69 SLC25A24 Achchuthan Shanmugasundram changed review comment from: There are six unrelated cases reported in total, of which five cases had c.650G>A (p.Arg217His) variant and one patient had c.649C>T (p.Arg217Cys).; to: There are six unrelated cases reported in total, of which five cases had c.650G>A (p.Arg217His) variant and one patient had c.649C>T (p.Arg217Cys). Both these variants are on the same amino acid. However, these cases were from people of multiple descent/ geographic locations. Experiments from patient-derived fibroblasts demonstrated that SLC25A24 variants lead to mitochondrial dysfunction with increased sensitivity to oxidative stress.
Structural eye disease v3.69 SLC25A24 Achchuthan Shanmugasundram changed review comment from: There are six unrelated cases reported in total, of which five cases had c.650G>A (p.Arg217His) variant and one patient had c.649C>T p.Arg217Cys; to: There are six unrelated cases reported in total, of which five cases had c.650G>A (p.Arg217His) variant and one patient had c.649C>T (p.Arg217Cys).
Structural eye disease v3.69 SLC25A24 Achchuthan Shanmugasundram reviewed gene: SLC25A24: Rating: GREEN; Mode of pathogenicity: None; Publications: 29100093, 31775791; Phenotypes: Fontaine progeroid syndrome, OMIM:612289; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v3.69 KIF11 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: KIF11.
Tag Q4_23_NHS_review tag was added to gene: KIF11.
Structural eye disease v3.69 KIF11 Achchuthan Shanmugasundram Classified gene: KIF11 as Amber List (moderate evidence)
Structural eye disease v3.69 KIF11 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Hannah Knight, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.
Structural eye disease v3.69 KIF11 Achchuthan Shanmugasundram Gene: kif11 has been classified as Amber List (Moderate Evidence).
Structural eye disease v3.68 KIF11 Achchuthan Shanmugasundram Phenotypes for gene: KIF11 were changed from Chorioretinopathy, Lymphedema or Mental Retardation, MCLMR, 152950 to Microcephaly with or without chorioretinopathy, lymphedema, or impaired intellectual development, OMIM:152950
Structural eye disease v3.67 KIF11 Achchuthan Shanmugasundram Publications for gene: KIF11 were set to 27212378
Structural eye disease v3.66 KIF11 Achchuthan Shanmugasundram Mode of inheritance for gene: KIF11 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v3.65 KIF11 Achchuthan Shanmugasundram reviewed gene: KIF11: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Microcephaly with or without chorioretinopathy, lymphedema, or impaired intellectual development, OMIM:152950; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Childhood solid tumours v4.9 CDKN2A Terri McVeigh gene: CDKN2A was added
gene: CDKN2A was added to Childhood solid tumours. Sources: Expert Review,Literature
Mode of inheritance for gene: CDKN2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDKN2A were set to 24451801; 30207590
Phenotypes for gene: CDKN2A were set to cutaneous melanoma; pancreatic cancer; astrocytomas
Penetrance for gene: CDKN2A were set to Incomplete
Review for gene: CDKN2A was set to GREEN
Added comment: Discussed at UKCGG/cancer leads meeting 06/07/2023 - agreed reasonable to include on panel
Sources: Expert Review, Literature
Childhood solid tumours v4.9 BAP1 Terri McVeigh gene: BAP1 was added
gene: BAP1 was added to Childhood solid tumours. Sources: Expert Review
Mode of inheritance for gene: BAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BAP1 were set to 23552620; 30517737; 31382694; https://doi.org/10.1016/j.ejcped.2023.100023; 29981911
Phenotypes for gene: BAP1 were set to uveal melanoma; mesothelioma; cholangiocarcioma; cutaneous melanoma; renal cell carcinoma; meningioma
Penetrance for gene: BAP1 were set to Incomplete
Review for gene: BAP1 was set to GREEN
Added comment: Discussed at UKCGG/cancer leads meeting 06/07/2023 - agreed reasonable to include on panel
Sources: Expert Review
Structural eye disease v3.65 KIAA0586 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.; to: Comment on list classification: As reviewed by Hannah Knight, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Structural eye disease v3.65 KIAA0586 Achchuthan Shanmugasundram Classified gene: KIAA0586 as Amber List (moderate evidence)
Structural eye disease v3.65 KIAA0586 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Structural eye disease v3.65 KIAA0586 Achchuthan Shanmugasundram Gene: kiaa0586 has been classified as Amber List (Moderate Evidence).
Structural eye disease v3.64 KIAA0586 Achchuthan Shanmugasundram Phenotypes for gene: KIAA0586 were changed from to Joubert syndrome 23, OMIM:616490; Short-rib thoracic dysplasia 14 with polydactyly, OMIM:616546
Structural eye disease v3.63 KIAA0586 Achchuthan Shanmugasundram Publications for gene: KIAA0586 were set to 30055837
Structural eye disease v3.62 KIAA0586 Achchuthan Shanmugasundram Mode of inheritance for gene: KIAA0586 was changed from to BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v3.61 KIAA0586 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: KIAA0586.
Tag Q4_23_NHS_review tag was added to gene: KIAA0586.
Structural eye disease v3.61 KIAA0586 Achchuthan Shanmugasundram reviewed gene: KIAA0586: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Joubert syndrome 23, OMIM:616490, Short-rib thoracic dysplasia 14 with polydactyly, OMIM:616546; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v3.61 CRYBB2 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: CRYBB2.
Tag Q4_23_NHS_review tag was added to gene: CRYBB2.
Structural eye disease v3.61 CRYBB2 Achchuthan Shanmugasundram Classified gene: CRYBB2 as Amber List (moderate evidence)
Structural eye disease v3.61 CRYBB2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Hannah Knight, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.
Structural eye disease v3.61 CRYBB2 Achchuthan Shanmugasundram Gene: crybb2 has been classified as Amber List (Moderate Evidence).
Structural eye disease v3.60 CRYBB2 Achchuthan Shanmugasundram Publications for gene: CRYBB2 were set to 29386872
Structural eye disease v3.59 CRYBB2 Achchuthan Shanmugasundram Phenotypes for gene: CRYBB2 were changed from Cataract 3, multiple types, 601547 to Cataract 3, multiple types, OMIM:601547
Structural eye disease v3.58 CRYBB2 Achchuthan Shanmugasundram reviewed gene: CRYBB2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal disorders v4.48 MVK Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: MVK.
Tag Q4_23_NHS_review tag was added to gene: MVK.
Retinal disorders v4.48 MVK Achchuthan Shanmugasundram Classified gene: MVK as Amber List (moderate evidence)
Retinal disorders v4.48 MVK Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Siying Lin, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.
Retinal disorders v4.48 MVK Achchuthan Shanmugasundram Gene: mvk has been classified as Amber List (Moderate Evidence).
Retinal disorders v4.47 MVK Achchuthan Shanmugasundram Phenotypes for gene: MVK were changed from Hyper-IgD syndrome, OMIM:260920; Mevalonic aciduria, OMIM:610377 to Hyper-IgD syndrome, OMIM:260920; Mevalonic aciduria, OMIM:610377; retinitis pigmentosa, MONDO:0019200
Retinal disorders v4.46 MVK Achchuthan Shanmugasundram edited their review of gene: MVK: Changed phenotypes to: retinitis pigmentosa, MONDO:0019200
Retinal disorders v4.46 MVK Achchuthan Shanmugasundram Publications for gene: MVK were set to 24084495
Retinal disorders v4.45 MVK Achchuthan Shanmugasundram reviewed gene: MVK: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v4.28 RETREG1 Gavin Ryan gene: RETREG1 was added
gene: RETREG1 was added to Childhood onset hereditary spastic paraplegia. Sources: NHS GMS
Mode of inheritance for gene: RETREG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RETREG1 were set to 24327336
Penetrance for gene: RETREG1 were set to unknown
Review for gene: RETREG1 was set to GREEN
Added comment: Aydinlar et al identified individuals with hereditary neuropathy caused by variant in this gene who also had spasticity. Further, LoF homozygous variant in this gene identified via Diagnostic Discovery in 100K and GMS WGS patient with features of Progressive spasticity, facial hypotonia, dysarthria, and fatiguable weakness.
Sources: NHS GMS
Intellectual disability v5.351 MYH10 Achchuthan Shanmugasundram Classified gene: MYH10 as Amber List (moderate evidence)
Intellectual disability v5.351 MYH10 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.
Intellectual disability v5.351 MYH10 Achchuthan Shanmugasundram Gene: myh10 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.350 MYH10 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: MYH10.
Intellectual disability v5.350 MYH10 Achchuthan Shanmugasundram Phenotypes for gene: MYH10 were changed from Neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071; MYH10-related Multiple congenital anomalies to Neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071; MYH10-related Multiple congenital anomalies
Intellectual disability v5.350 MYH10 Achchuthan Shanmugasundram Phenotypes for gene: MYH10 were changed from MYH10-related Multiple congenital anomalies, Intellectual disability to Neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071; MYH10-related Multiple congenital anomalies
Intellectual disability v5.349 MYH10 Achchuthan Shanmugasundram Publications for gene: MYH10 were set to 25356899; 25003005
Intellectual disability v5.348 MYH10 Achchuthan Shanmugasundram Mode of inheritance for gene: MYH10 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.347 MYH10 Achchuthan Shanmugasundram reviewed gene: MYH10: Rating: GREEN; Mode of pathogenicity: None; Publications: 35980381; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ichthyosis and erythrokeratoderma v3.19 ABHD5 Tom Cullup gene: ABHD5 was added
gene: ABHD5 was added to Ichthyosis and erythrokeratoderma. Sources: Expert list
Mode of inheritance for gene: ABHD5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABHD5 were set to PubMed: 11590543
Phenotypes for gene: ABHD5 were set to Chanarin-Dorfman syndrome
Penetrance for gene: ABHD5 were set to Complete
Review for gene: ABHD5 was set to GREEN
Added comment: Green gene on multiple panels including PPK. Request from Dr G Petrof, GOSH, to add this gene to ichthyosis, as this is part of presenting phenotype in Chanarin-Dorfman syndrome.
Sources: Expert list
Skeletal dysplasia v4.32 PSMC3 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: PSMC3.
Skeletal dysplasia v4.32 PSMC3 Achchuthan Shanmugasundram Classified gene: PSMC3 as Amber List (moderate evidence)
Skeletal dysplasia v4.32 PSMC3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of monoallelic PSMC3 variants with skeletal malformations and hence this gene can be promoted to green rating in the next GMS review.
Skeletal dysplasia v4.32 PSMC3 Achchuthan Shanmugasundram Gene: psmc3 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v4.31 PSMC3 Achchuthan Shanmugasundram changed review comment from: 23 individuals with neurodevelopmental disorder were identified with 15 different de novo missense variants. Skeletal malformations were observed in 11/15 (73%) cases (scoliosis, acetabular dysplasia, brachymetatarsy)
Sources: Literature; to: 23 individuals with neurodevelopmental disorder were identified with 15 different de novo missense variants. Skeletal malformations were observed in 11/15 (73%) cases (scoliosis, acetabular dysplasia, brachymetatarsy).

Monoallelic variants in PSMC3 are not yet associated with any relevant phenotypes in OMIM or in Gene2Phenotype.
Sources: Literature
Skeletal dysplasia v4.31 PSMC3 Achchuthan Shanmugasundram gene: PSMC3 was added
gene: PSMC3 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: PSMC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSMC3 were set to 37256937
Phenotypes for gene: PSMC3 were set to neurodevelopmental disorder, MONDO:0700092; scoliosis, MONDO:0005392; Acetabular dysplasia, HP:0008807; brachymetatarsy
Review for gene: PSMC3 was set to GREEN
Added comment: 23 individuals with neurodevelopmental disorder were identified with 15 different de novo missense variants. Skeletal malformations were observed in 11/15 (73%) cases (scoliosis, acetabular dysplasia, brachymetatarsy)
Sources: Literature
Hereditary neuropathy or pain disorder v3.67 PSMC3 Achchuthan Shanmugasundram Classified gene: PSMC3 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v3.67 PSMC3 Achchuthan Shanmugasundram Gene: psmc3 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v3.66 PSMC3 Achchuthan Shanmugasundram gene: PSMC3 was added
gene: PSMC3 was added to Hereditary neuropathy or pain disorder. Sources: Literature
Mode of inheritance for gene: PSMC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMC3 were set to 32500975
Phenotypes for gene: PSMC3 were set to ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354
Review for gene: PSMC3 was set to AMBER
Added comment: Three individuals from a single extended consanguineous Turkish pedigree was reported with early-onset and rapidly progressive deafness, early-onset cataract, severe developmental delay, severely impaired intellectual development, subcutaneous calcifications and peripheral neuropathy. They were identified with homozygous variant in PSMC3 gene (c.1127 + 337A>G). Functional studies in patient fibroblast cells suggested that the patient PSMC3 variant is responsible for proteasome failure affecting protein homeostasis under stress conditions. This is also supported by evidence from zebrafish models, where PSMC3 knockout has reproduced the human phenotype with inner ear development anomalies as well as cataracts.
Sources: Literature
Severe microcephaly v4.48 PSMC3 Achchuthan Shanmugasundram Classified gene: PSMC3 as Amber List (moderate evidence)
Severe microcephaly v4.48 PSMC3 Achchuthan Shanmugasundram Gene: psmc3 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v4.47 PSMC3 Achchuthan Shanmugasundram changed review comment from: 23 individuals with neurodevelopmental disorder were identified with 15 different de novo missense variants. Microcephaly was reported in in 6/17 (35%) cases, of which severe macrocephaly was in 2/16 (13%) cases.
Sources: Literature; to: 23 individuals with neurodevelopmental disorder were identified with 15 different de novo missense variants. Microcephaly was reported in in 6/17 (35%) cases, of which severe macrocephaly was in 2/16 (13%) cases.
Sources: Literature
Severe microcephaly v4.47 PSMC3 Achchuthan Shanmugasundram gene: PSMC3 was added
gene: PSMC3 was added to Severe microcephaly. Sources: Literature
Mode of inheritance for gene: PSMC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSMC3 were set to 37256937
Phenotypes for gene: PSMC3 were set to neurodevelopmental disorder, MONDO:0700092; microcephaly, MONDO:0001149
Review for gene: PSMC3 was set to AMBER
Added comment: 23 individuals with neurodevelopmental disorder were identified with 15 different de novo missense variants. Microcephaly was reported in in 6/17 (35%) cases, of which severe macrocephaly was in 2/16 (13%) cases.
Sources: Literature
Monogenic hearing loss v4.25 PSMC3 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence available for the association of monoallelic variants in this gene with hearing loss and hence this gene can be promoted to green rating in the next GMS review.; to: Comment on list classification: This gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.347 PSMC3 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence available for the association of monoallelic variants in this gene with hearing loss and hence this gene can be promoted to green rating in the next GMS review.; to: Comment on list classification: This gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.347 PSMC3 Achchuthan Shanmugasundram changed review comment from: Comment on mode of inheritance: There is sufficient evidence for the association of monoallelic variants from this gene with intellectual disability. However, there is only one family reported with biallelic variants. Hence, the MOI is set as "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted".; to: Comment on mode of inheritance: There is sufficient evidence available for the association of monoallelic variants from this gene with intellectual disability. However, there is only one family reported with biallelic variants. Hence, the MOI is set as "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted".
Intellectual disability v5.347 PSMC3 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence available for the association of monoallelic variants in this gene with hearing loss and hence this gene can be promoted to green rating in the next GMS review.; to: Comment on list classification: There is sufficient evidence available for the association of monoallelic variants in this gene with hearing loss and hence this gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.347 PSMC3 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: This gene can be promoted to green rating at the next GMS review.; to: Comment on list classification: There is sufficient evidence available for the association of monoallelic variants in this gene with hearing loss and hence this gene can be promoted to green rating in the next GMS review.
Monogenic hearing loss v4.25 PSMC3 Achchuthan Shanmugasundram Classified gene: PSMC3 as Amber List (moderate evidence)
Monogenic hearing loss v4.25 PSMC3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of monoallelic variants in this gene with hearing loss and hence this gene can be promoted to green rating in the next GMS review.
Monogenic hearing loss v4.25 PSMC3 Achchuthan Shanmugasundram Gene: psmc3 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.24 PSMC3 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence for the association of monoallelic variants from this gene with hearing loss. However, there is only one family reported with biallelic variants. Hence, the MOI is set as "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted".
Monogenic hearing loss v4.24 PSMC3 Achchuthan Shanmugasundram Mode of inheritance for gene: PSMC3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic hearing loss v4.23 PSMC3 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: PSMC3.
Monogenic hearing loss v4.23 PSMC3 Achchuthan Shanmugasundram gene: PSMC3 was added
gene: PSMC3 was added to Monogenic hearing loss. Sources: Literature
Mode of inheritance for gene: PSMC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSMC3 were set to 32500975; 37256937
Phenotypes for gene: PSMC3 were set to ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092; autosomal dominant nonsyndromic hearing loss, MONDO:0019587
Review for gene: PSMC3 was set to GREEN
Added comment: PMID:32500975 - Three individuals from a single extended consanguineous Turkish pedigree was reported with early-onset and rapidly progressive deafness, early-onset cataract, severe developmental delay, severely impaired intellectual development, subcutaneous calcifications and peripheral neuropathy. They were identified with homozygous variant in PSMC3 gene (c.1127 + 337A>G). Functional studies in patient fibroblast cells suggested that the patient PSMC3 variant is responsible for proteasome failure affecting protein homeostasis under stress conditions. This is also supported by evidence from zebrafish models, where PSMC3 knockout has reproduced the human phenotype with inner ear development anomalies as well as cataracts.

PMID:37256937 - 23 individuals with neurodevelopmental disorder were identified with 15 different de novo missense variants. Apart from one child (patient 2), all others had developmental delay characterised by speech delay (19/19) alone or with intellectual disability (16/18) and motor delay (15/19). 9/19 patients had hearing loss, of which two were labelled as sensorineural and one was labelled as conductive. In addition, structural modeling as well as proteomic and transcriptomic analyses of T cells derived from patients with PSMC3 variants implicated the PSMC3 variants in proteasome dysfunction through disruption of substrate translocation, induction of proteotoxic stress, and alterations in proteins controlling developmental and innate immune program.

The phenotype caused by recessive PSMC3 variants has been reported in OMIM (MIM #619354), but not in Gene2Phenotype. However, the phenotype caused by dominant variants has not yet been reported in either resources.
Sources: Literature
Intellectual disability v5.347 PSMC3 Achchuthan Shanmugasundram changed review comment from: PMID:32500975 - Three individuals from a single extended consanguineous Turkish pedigree was reported with early-onset and rapidly progressive deafness, early-onset cataract, severe developmental delay, severely impaired intellectual development, subcutaneous calcifications and peripheral neuropathy. There were identified with homozygous variant in PSMC3 gene (c.1127 + 337A>G). Functional studies in patient fibroblast cells suggested that the patient PSMC3 variant is responsible for proteasome failure affecting protein homeostasis under stress conditions. This is also supported by evidence from zebrafish models, where PSMC3 knockout has reproduced the human phenotype with inner ear development anomalies as well as cataracts.

PMID:37256937 - 23 individuals with neurodevelopmental disorder were identified with 15 different de novo missense variants. Apart from one child (patient 2), all others had developmental delay characterised by speech delay (19/19) alone or with intellectual disability (16/18) and motor delay (15/19). In addition, structural modeling as well as proteomic and transcriptomic analyses of T cells derived from patients with PSMC3 variants implicated the PSMC3 variants in proteasome dysfunction through disruption of substrate translocation, induction of proteotoxic stress, and alterations in proteins controlling developmental and innate immune program.

The phenotype caused by recessive PSMC3 variants has been reported in OMIM (MIM #619354), but not in Gene2Phenotype. However, the phenotype caused by dominant variants has not yet been reported in either resources.; to: PMID:32500975 - Three individuals from a single extended consanguineous Turkish pedigree was reported with early-onset and rapidly progressive deafness, early-onset cataract, severe developmental delay, severely impaired intellectual development, subcutaneous calcifications and peripheral neuropathy. They were identified with homozygous variant in PSMC3 gene (c.1127 + 337A>G). Functional studies in patient fibroblast cells suggested that the patient PSMC3 variant is responsible for proteasome failure affecting protein homeostasis under stress conditions. This is also supported by evidence from zebrafish models, where PSMC3 knockout has reproduced the human phenotype with inner ear development anomalies as well as cataracts.

PMID:37256937 - 23 individuals with neurodevelopmental disorder were identified with 15 different de novo missense variants. Apart from one child (patient 2), all others had developmental delay characterised by speech delay (19/19) alone or with intellectual disability (16/18) and motor delay (15/19). In addition, structural modeling as well as proteomic and transcriptomic analyses of T cells derived from patients with PSMC3 variants implicated the PSMC3 variants in proteasome dysfunction through disruption of substrate translocation, induction of proteotoxic stress, and alterations in proteins controlling developmental and innate immune program.

The phenotype caused by recessive PSMC3 variants has been reported in OMIM (MIM #619354), but not in Gene2Phenotype. However, the phenotype caused by dominant variants has not yet been reported in either resources.
Intellectual disability v5.347 PSMC3 Achchuthan Shanmugasundram changed review comment from: PMID:32500975 - Three individuals from a single extended consanguineous Turkish pedigree was reported with early-onset and rapidly progressive deafness, early-onset cataract, severe developmental delay, severely impaired intellectual development, subcutaneous calcifications and peripheral neuropathy. There were identified with homozygous variant in PSMC3 gene (c.1127 + 337A>G). Functional studies in patient fibroblast cells suggested that the patient PSMC3 variant is responsible for proteasome failure affecting protein homeostasis under stress conditions. This is also supported by evidence from zebrafish models, where PSMC3 knockout has reproduced the human phenotype with inner ear development anomalies as well as cataracts.

PMID:37256937 - 23 individuals with neurodevelopmental disorder was identified with 15 different de novo missense variants. Apart from one child (patient 2), all others had developmental delay characterised by speech delay (19/19) alone or with intellectual disability (16/18) and motor delay (15/19). In addition, structural modeling as well as proteomic and transcriptomic analyses of T cells derived from patients with PSMC3 variants implicated the PSMC3 variants in proteasome dysfunction through disruption of substrate translocation, induction of proteotoxic stress, and alterations in proteins controlling developmental and innate immune program.

The phenotype caused by recessive PSMC3 variants has been reported in OMIM (MIM #619354), but not in Gene2Phenotype. However, the phenotype caused by dominant variants has not yet been reported in either resources.; to: PMID:32500975 - Three individuals from a single extended consanguineous Turkish pedigree was reported with early-onset and rapidly progressive deafness, early-onset cataract, severe developmental delay, severely impaired intellectual development, subcutaneous calcifications and peripheral neuropathy. There were identified with homozygous variant in PSMC3 gene (c.1127 + 337A>G). Functional studies in patient fibroblast cells suggested that the patient PSMC3 variant is responsible for proteasome failure affecting protein homeostasis under stress conditions. This is also supported by evidence from zebrafish models, where PSMC3 knockout has reproduced the human phenotype with inner ear development anomalies as well as cataracts.

PMID:37256937 - 23 individuals with neurodevelopmental disorder were identified with 15 different de novo missense variants. Apart from one child (patient 2), all others had developmental delay characterised by speech delay (19/19) alone or with intellectual disability (16/18) and motor delay (15/19). In addition, structural modeling as well as proteomic and transcriptomic analyses of T cells derived from patients with PSMC3 variants implicated the PSMC3 variants in proteasome dysfunction through disruption of substrate translocation, induction of proteotoxic stress, and alterations in proteins controlling developmental and innate immune program.

The phenotype caused by recessive PSMC3 variants has been reported in OMIM (MIM #619354), but not in Gene2Phenotype. However, the phenotype caused by dominant variants has not yet been reported in either resources.
Ataxia and cerebellar anomalies - narrow panel v4.43 THG1L Achchuthan Shanmugasundram Classified gene: THG1L as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v4.43 THG1L Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Ataxia and cerebellar anomalies - narrow panel v4.43 THG1L Achchuthan Shanmugasundram Gene: thg1l has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v4.42 THG1L Achchuthan Shanmugasundram Phenotypes for gene: THG1L were changed from Spinocerebellar ataxia, autosomal recessive 28, OMIM:618800; Spinocerebellar ataxia, autosomal recessive 28, MONDO:0032923 to Spinocerebellar ataxia, autosomal recessive 28, OMIM:618800, MONDO:0032923
Ataxia and cerebellar anomalies - narrow panel v4.41 THG1L Achchuthan Shanmugasundram Publications for gene: THG1L were set to 27307223; 30214071; 31168944
Ataxia and cerebellar anomalies - narrow panel v4.40 THG1L Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: THG1L.
Tag Q4_23_NHS_review tag was added to gene: THG1L.
Ataxia and cerebellar anomalies - narrow panel v4.40 THG1L Achchuthan Shanmugasundram reviewed gene: THG1L: Rating: GREEN; Mode of pathogenicity: None; Publications: 27307223, 30214071, 31168944, 33682303, 37670026; Phenotypes: Spinocerebellar ataxia, autosomal recessive 28, OMIM:618800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Malformations of cortical development v4.19 COL4A1 Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has been associated with relevant phenotypes in both OMIM and Gene2Phenotype (Porencephaly 1 with 'definitive' rating in the DD panel).
Malformations of cortical development v4.19 COL4A1 Achchuthan Shanmugasundram Phenotypes for gene: COL4A1 were changed from Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps, OMIM:611773; Brain small vessel disease with or without ocular anomalies, OMIM:175780; Microangiopathy and leukoencephalopathy, pontine, autosomal dominant, OMIM:618564; {Hemorrhage, intracerebral, susceptibility to}, OMIM:614519 to Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps, OMIM:611773; Brain small vessel disease with or without ocular anomalies, OMIM:175780; Microangiopathy and leukoencephalopathy, pontine, autosomal dominant, OMIM:618564; {Hemorrhage, intracerebral, susceptibility to}, OMIM:614519
Malformations of cortical development v4.18 COL4A1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Nour Elkhateeb, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.; to: Comment on list classification: As reviewed by Nour Elkhateeb, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Malformations of cortical development v4.18 COL4A2 Achchuthan Shanmugasundram Classified gene: COL4A2 as Amber List (moderate evidence)
Malformations of cortical development v4.18 COL4A2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Nour Elkhateeb, there is sufficient evidence for the promotion of this gene to green rating in the next GMS review.
Malformations of cortical development v4.18 COL4A2 Achchuthan Shanmugasundram Gene: col4a2 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v4.17 COL4A2 Achchuthan Shanmugasundram changed review comment from: There are at least three unrelated cases of porencephaly reported with monoallelic variants in COL4A2.

This gene has also been associated with relevant phenotypes in both OMIM and Gene2Phenotype (with 'moderate' rating in the DD panel).; to: There are at least three unrelated cases of porencephaly reported with monoallelic variants in COL4A2.

This gene has also been associated with relevant phenotypes in both OMIM and Gene2Phenotype (Porencephaly 2 with 'moderate' rating in the DD panel).
Malformations of cortical development v4.17 COL4A2 Achchuthan Shanmugasundram Phenotypes for gene: COL4A2 were changed from Malformations of cortical development; Schizencephaly; porencephaly; polymicrogyria; focal cortical dysplasia; nodular heterotopia to Brain small vessel disease 2, OMIM:614483; {Hemorrhage, intracerebral, susceptibility to}, OMIM:614519
Malformations of cortical development v4.16 COL4A2 Achchuthan Shanmugasundram Mode of inheritance for gene: COL4A2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Malformations of cortical development v4.15 COL4A2 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: COL4A2.
Tag Q4_23_NHS_review tag was added to gene: COL4A2.
Malformations of cortical development v4.15 COL4A2 Achchuthan Shanmugasundram reviewed gene: COL4A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Brain small vessel disease 2, OMIM:614483, {Hemorrhage, intracerebral, susceptibility to}, OMIM:614519; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Malformations of cortical development v4.15 COL4A1 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: COL4A1.
Tag Q4_23_NHS_review tag was added to gene: COL4A1.
Malformations of cortical development v4.15 COL4A1 Achchuthan Shanmugasundram Classified gene: COL4A1 as Amber List (moderate evidence)
Malformations of cortical development v4.15 COL4A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Nour Elkhateeb, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Malformations of cortical development v4.15 COL4A1 Achchuthan Shanmugasundram Gene: col4a1 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v4.14 COL4A1 Achchuthan Shanmugasundram Mode of inheritance for gene: COL4A1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Malformations of cortical development v4.13 COL4A1 Achchuthan Shanmugasundram Phenotypes for gene: COL4A1 were changed from Malformations of cortical development; Schizencephaly; porencephaly; polymicrogyria; focal cortical dysplasia; nodular heterotopia to Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps, OMIM:611773; Brain small vessel disease with or without ocular anomalies, OMIM:175780; Microangiopathy and leukoencephalopathy, pontine, autosomal dominant, OMIM:618564; {Hemorrhage, intracerebral, susceptibility to}, OMIM:614519
Malformations of cortical development v4.12 COL4A1 Achchuthan Shanmugasundram reviewed gene: COL4A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps, OMIM:611773, Brain small vessel disease with or without ocular anomalies, OMIM:175780, Microangiopathy and leukoencephalopathy, pontine, autosomal dominant, OMIM:618564, {Hemorrhage, intracerebral, susceptibility to}, OMIM:614519; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Inherited polyposis and early onset colorectal cancer - germline testing v2.10 GREM1 Arina Puzriakova edited their review of gene: GREM1: Changed publications to: 25992589, 26947005, 28242209, 27984123, 9024286, 10092300, 12696020, 18084292, 21128281, 22561515, 24586997, 26493165, 29804199, 25419707
Inherited polyposis and early onset colorectal cancer - germline testing v2.10 GREM1 Arina Puzriakova Tag currently-ngs-unreportable was removed from gene: GREM1.
Tag gene-duplication was removed from gene: GREM1.
Inherited polyposis and early onset colorectal cancer - germline testing v2.10 GREM1 Arina Puzriakova changed review comment from: Comment on list classification: Following review by the specialist service group, it has been agreed that this gene should be rated as Green at the next GMS panel update.

Upregulation of GREM1 expression in colorectal mucosa has been linked to hereditary mixed polyposis syndrome.
Most described patients are carriers of the Ashkenazi founder variant, a 40-kb upstream duplication that spans the 3' end of the neighbouring SCG5 gene. However, there are other duplications of different sizes that have been associated with disease (and some don’t incorporate the 3’ end of SCG5).

There is currently no evidence of small variants or a whole gene duplication of GREM1 causing a similar phenotype.

There is sufficient evidence to support a definitive gene-disease relationship but the providing GLH need to account for the upstream sequence location and size of reported variants in their primer design (as R211 (v2.10) is currently a purely wet-lab/non-WGS test).; to: Comment on list classification: Following review by the specialist service group, it has been agreed that this gene should be rated as Green at the next GMS panel update.

Upregulation of GREM1 expression in colorectal mucosa has been linked to hereditary mixed polyposis syndrome.
Most described patients are carriers of the Ashkenazi founder variant, a 40-kb upstream duplication that spans the 3' end of the neighbouring SCG5 gene. However, there are other duplications of different sizes that have been associated with disease (and some don’t incorporate the 3’ end of SCG5).

There is currently no evidence of small variants or a whole gene duplication of GREM1 causing a similar phenotype.

There is sufficient evidence to support a definitive gene-disease relationship but the providing GLH need to account for the upstream sequence location and size of reported variants in their primer design (as R211 v2.10 is currently a purely wet-lab/non-WGS test).
Inherited polyposis and early onset colorectal cancer - germline testing v2.10 GREM1 Arina Puzriakova changed review comment from: Comment on list classification: Following review by the specialist service group, it has been agreed that this gene should be rated as Green at the next GMS panel update.

Upregulation of GREM1 expression in colorectal mucosa has been linked to hereditary mixed polyposis syndrome. This is caused by a 40-kb upstream duplication that spans the 3' end of the neighbouring SCG5 gene. There is currently no evidence of small variants or a whole gene duplication of GREM1 (without SCG5 involvement) causing a similar phenotype.

There is sufficient evidence to support a definitive gene-disease relationship but the providing GLH will have to account for the upstream sequence location and size of reported variants in their primer design (as R211 is currently a purely wet-lab/non-WGS test).

The SCG5-GREM1 duplication would not be detected by the NGS pipeline and this should be considered if this clinical indication ever moves to WGS in the future.; to: Comment on list classification: Following review by the specialist service group, it has been agreed that this gene should be rated as Green at the next GMS panel update.

Upregulation of GREM1 expression in colorectal mucosa has been linked to hereditary mixed polyposis syndrome.
Most described patients are carriers of the Ashkenazi founder variant, a 40-kb upstream duplication that spans the 3' end of the neighbouring SCG5 gene. However, there are other duplications of different sizes that have been associated with disease (and some don’t incorporate the 3’ end of SCG5).

There is currently no evidence of small variants or a whole gene duplication of GREM1 causing a similar phenotype.

There is sufficient evidence to support a definitive gene-disease relationship but the providing GLH need to account for the upstream sequence location and size of reported variants in their primer design (as R211 (v2.10) is currently a purely wet-lab/non-WGS test).
Mitochondrial disorders v4.127 SLC25A36 Achchuthan Shanmugasundram Classified gene: SLC25A36 as Amber List (moderate evidence)
Mitochondrial disorders v4.127 SLC25A36 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Hannah Knight, there is sufficient evidence available for the association of this gene with green rating in the next GMS review.
Mitochondrial disorders v4.127 SLC25A36 Achchuthan Shanmugasundram Gene: slc25a36 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v4.126 SLC25A36 Achchuthan Shanmugasundram Phenotypes for gene: SLC25A36 were changed from Hyperinsulinemic hypoglycemia, familial, 8 to Hyperinsulinemic hypoglycemia, familial, 8, OMIM:620211
Mitochondrial disorders v4.125 SLC25A36 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: SLC25A36.
Tag Q4_23_NHS_review tag was added to gene: SLC25A36.
Mitochondrial disorders v4.125 SLC25A36 Achchuthan Shanmugasundram reviewed gene: SLC25A36: Rating: GREEN; Mode of pathogenicity: None; Publications: 34576089, 34971397, 36695547; Phenotypes: Hyperinsulinemic hypoglycemia, familial, 8, OMIM:620211; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v4.45 MVK Siying Lin reviewed gene: MVK: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35916082; Phenotypes: Retinal dystrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v4.125 PCK2 Achchuthan Shanmugasundram Classified gene: PCK2 as Amber List (moderate evidence)
Mitochondrial disorders v4.125 PCK2 Achchuthan Shanmugasundram Gene: pck2 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v4.124 PCK2 Achchuthan Shanmugasundram Phenotypes for gene: PCK2 were changed from PEPCK deficiency, mitochondrial, OMIM:261650; Abnormal gait; peripheral neuropathy to PEPCK deficiency, mitochondrial, OMIM:261650; Abnormal gait; peripheral neuropathy
Mitochondrial disorders v4.124 PCK2 Achchuthan Shanmugasundram Phenotypes for gene: PCK2 were changed from Abnormal gait; peripheral neuropathy to PEPCK deficiency, mitochondrial, OMIM:261650; Abnormal gait; peripheral neuropathy
Mitochondrial disorders v4.123 PCK2 Achchuthan Shanmugasundram reviewed gene: PCK2: Rating: AMBER; Mode of pathogenicity: None; Publications: 36845668; Phenotypes: PEPCK deficiency, mitochondrial, OMIM:261650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v4.123 MRPS28 Achchuthan Shanmugasundram Classified gene: MRPS28 as Red List (low evidence)
Mitochondrial disorders v4.123 MRPS28 Achchuthan Shanmugasundram Gene: mrps28 has been classified as Red List (Low Evidence).
Mitochondrial disorders v4.122 MRPS28 Achchuthan Shanmugasundram Phenotypes for gene: MRPS28 were changed from ?Combined oxidative phosphorylation deficiency 47 to ?Combined oxidative phosphorylation deficiency 47, OMIM:618958
Mitochondrial disorders v4.121 MRPS28 Achchuthan Shanmugasundram changed review comment from: PMID:30566640 reported a single patient with intrauterine growth retardation, craniofacial dysmorphism and developmental delay and identified with a seemingly homozygous missense variant c.356A>G/ p.Lys119Arg. The variant was present in the mother in a heterozygous state, but not in the father who likely carried a large deletion spanning exon 2 and parts of introns 1 and 2 that could account for the apparent homozygosity of the patient.; to: PMID:30566640 reported a single patient with intrauterine growth retardation, craniofacial dysmorphism and developmental delay and identified with biallelic MRPS28 variants.
Mitochondrial disorders v4.121 MRPS28 Achchuthan Shanmugasundram reviewed gene: MRPS28: Rating: RED; Mode of pathogenicity: None; Publications: 30566640; Phenotypes: ?Combined oxidative phosphorylation deficiency 47, OMIM:618958; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v4.121 MRPS25 Achchuthan Shanmugasundram Classified gene: MRPS25 as Red List (low evidence)
Mitochondrial disorders v4.121 MRPS25 Achchuthan Shanmugasundram Gene: mrps25 has been classified as Red List (Low Evidence).
Mitochondrial disorders v4.120 MRPS25 Achchuthan Shanmugasundram Phenotypes for gene: MRPS25 were changed from ?Combined oxidative phosphorylation deficiency 50 to ?Combined oxidative phosphorylation deficiency 50, OMIM:619025
Mitochondrial disorders v4.119 MRPS25 Achchuthan Shanmugasundram reviewed gene: MRPS25: Rating: RED; Mode of pathogenicity: None; Publications: 31039582; Phenotypes: ?Combined oxidative phosphorylation deficiency 50, OMIM:619025; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v4.119 MIEF2 Achchuthan Shanmugasundram Phenotypes for gene: MIEF2 were changed from ?Combined oxidative phosphorylation deficiency 49 to ?Combined oxidative phosphorylation deficiency 49, OMIM:619024
Mitochondrial disorders v4.118 MIEF2 Achchuthan Shanmugasundram Classified gene: MIEF2 as Red List (low evidence)
Mitochondrial disorders v4.118 MIEF2 Achchuthan Shanmugasundram Gene: mief2 has been classified as Red List (Low Evidence).
Mitochondrial disorders v4.117 MIEF2 Achchuthan Shanmugasundram reviewed gene: MIEF2: Rating: RED; Mode of pathogenicity: None; Publications: 29361167; Phenotypes: ?Combined oxidative phosphorylation deficiency 49, OMIM:619024; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v4.117 TEFM Achchuthan Shanmugasundram Deleted their comment
Mitochondrial disorders v4.117 TEFM Achchuthan Shanmugasundram Classified gene: TEFM as Amber List (moderate evidence)
Mitochondrial disorders v4.117 TEFM Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Hannah Knight, there is sufficient evidence available (five unrelated families) for the association of this gene with green rating in the next GMS review.
Mitochondrial disorders v4.117 TEFM Achchuthan Shanmugasundram Gene: tefm has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v4.117 TEFM Achchuthan Shanmugasundram Classified gene: TEFM as Amber List (moderate evidence)
Mitochondrial disorders v4.117 TEFM Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Hannah Knight, there is sufficient evidence available (five unrelated families) for the association of this gene with green rating in the next GMS review.
Mitochondrial disorders v4.117 TEFM Achchuthan Shanmugasundram Gene: tefm has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v4.116 TEFM Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: TEFM.
Tag Q4_23_NHS_review tag was added to gene: TEFM.
Mitochondrial disorders v4.116 TEFM Achchuthan Shanmugasundram reviewed gene: TEFM: Rating: GREEN; Mode of pathogenicity: None; Publications: 36823193; Phenotypes: Combined oxidative phosphorylation deficiency 58, OMIM:620451; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.347 TEFM Achchuthan Shanmugasundram Classified gene: TEFM as Amber List (moderate evidence)
Intellectual disability v5.347 TEFM Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Intellectual disability v5.347 TEFM Achchuthan Shanmugasundram Gene: tefm has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.346 TEFM Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: TEFM.
Intellectual disability v5.346 TEFM Achchuthan Shanmugasundram reviewed gene: TEFM: Rating: GREEN; Mode of pathogenicity: None; Publications: 36823193; Phenotypes: Combined oxidative phosphorylation deficiency 58, OMIM:620451; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v4.135 TEFM Achchuthan Shanmugasundram Classified gene: TEFM as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.135 TEFM Achchuthan Shanmugasundram Gene: tefm has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.134 TEFM Achchuthan Shanmugasundram changed review comment from: Three patients from two unrelated families with biallelic TEFM variants had seizures.; to: PMID:36823193 reported seven individuals from five unrelated families presenting with mitochondrial respiratory chain deficiency and they were identified with biallelic TEFM variants. Three of these patients from two unrelated families had seizures.
Early onset or syndromic epilepsy v4.134 TEFM Achchuthan Shanmugasundram reviewed gene: TEFM: Rating: AMBER; Mode of pathogenicity: None; Publications: 36823193; Phenotypes: Combined oxidative phosphorylation deficiency 58, OMIM:620451; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Inherited polyposis and early onset colorectal cancer - germline testing v2.10 GREM1 Arina Puzriakova Publications for gene: GREM1 were set to
Early onset or syndromic epilepsy v4.134 TEFM Achchuthan Shanmugasundram Entity copied from Mitochondrial disorders v4.116
Early onset or syndromic epilepsy v4.134 TEFM Achchuthan Shanmugasundram gene: TEFM was added
gene: TEFM was added to Early onset or syndromic epilepsy. Sources: Literature
Mode of inheritance for gene: TEFM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TEFM were set to 36823193
Phenotypes for gene: TEFM were set to Combined oxidative phosphorylation deficiency 58, OMIM:620451
Intellectual disability v5.346 TEFM Achchuthan Shanmugasundram Entity copied from Mitochondrial disorders v4.116
Intellectual disability v5.346 TEFM Achchuthan Shanmugasundram gene: TEFM was added
gene: TEFM was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: TEFM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TEFM were set to 36823193
Phenotypes for gene: TEFM were set to Combined oxidative phosphorylation deficiency 58, OMIM:620451
Mitochondrial disorders v4.116 TEFM Achchuthan Shanmugasundram Phenotypes for gene: TEFM were changed from Combined oxidative phosphorylation deficiency 58 to Combined oxidative phosphorylation deficiency 58, OMIM:620451
Inherited polyposis and early onset colorectal cancer - germline testing v2.9 GREM1 Arina Puzriakova edited their review of gene: GREM1: Changed rating: GREEN
Rhabdomyolysis and metabolic muscle disorders v3.46 TAMM41 Achchuthan Shanmugasundram Classified gene: TAMM41 as Amber List (moderate evidence)
Rhabdomyolysis and metabolic muscle disorders v3.46 TAMM41 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (two unrelated cases and functional studies) for the promotion of this gene to green rating in the next GMS review.
Rhabdomyolysis and metabolic muscle disorders v3.46 TAMM41 Achchuthan Shanmugasundram Gene: tamm41 has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and metabolic muscle disorders v3.45 TAMM41 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: TAMM41.
Rhabdomyolysis and metabolic muscle disorders v3.45 TAMM41 Achchuthan Shanmugasundram gene: TAMM41 was added
gene: TAMM41 was added to Rhabdomyolysis and metabolic muscle disorders. Sources: Literature
Mode of inheritance for gene: TAMM41 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAMM41 were set to 35321494
Phenotypes for gene: TAMM41 were set to Combined oxidative phosphorylation deficiency 56, OMIM:620139
Review for gene: TAMM41 was set to GREEN
Added comment: PMID:35321494 reported three unrelated individuals with mitochondrial disease that share clinical features, including lethargy at birth, hypotonia, developmental delay, myopathy, and ptosis. Two of these three individuals were reported with myopathy (proximal and distal in one and proximal in other). They were identified with compound heterozygous variants in TAMM41 gene. In addition, 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.
Sources: Literature
Mitochondrial disorders v4.115 TAMM41 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: TAMM41.
Tag Q4_23_NHS_review tag was added to gene: TAMM41.
Mitochondrial disorders v4.115 TAMM41 Achchuthan Shanmugasundram Classified gene: TAMM41 as Amber List (moderate evidence)
Mitochondrial disorders v4.115 TAMM41 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Hannah Knight, there is sufficient evidence available (three unrelated cases and functional studies) for the promotion of this gene to green rating in the next GMS review.
Mitochondrial disorders v4.115 TAMM41 Achchuthan Shanmugasundram Gene: tamm41 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v4.114 TAMM41 Achchuthan Shanmugasundram Phenotypes for gene: TAMM41 were changed from Combined oxidative phosphorylation deficiency 56 to Combined oxidative phosphorylation deficiency 56, OMIM:620139
Mitochondrial disorders v4.113 TAMM41 Achchuthan Shanmugasundram reviewed gene: TAMM41: Rating: GREEN; Mode of pathogenicity: None; Publications: 35321494; Phenotypes: Combined oxidative phosphorylation deficiency 56, OMIM:620139; Mode of inheritance: None
Respiratory ciliopathies including non-CF bronchiectasis v3.9 SPEF2 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: SPEF2.
Tag Q4_23_NHS_review tag was added to gene: SPEF2.
Respiratory ciliopathies including non-CF bronchiectasis v3.9 SPEF2 Achchuthan Shanmugasundram Classified gene: SPEF2 as Amber List (moderate evidence)
Respiratory ciliopathies including non-CF bronchiectasis v3.9 SPEF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Steven Cowman, there is sufficient evidence available for this gene to be promoted to green rating in the next GMS update.
Respiratory ciliopathies including non-CF bronchiectasis v3.9 SPEF2 Achchuthan Shanmugasundram Gene: spef2 has been classified as Amber List (Moderate Evidence).
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.27 ABHD5 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: ABHD5.
Tag Q4_23_NHS_review tag was added to gene: ABHD5.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.27 ABHD5 Achchuthan Shanmugasundram changed review comment from: As reviewed by Oliver Watkinson, Chanarin-Dorfman is a neutral lipid storage disorder and myopathy(generally tends to be slowly progressive muscle weakness) is part of the phenotype in 59% of reported cases (PMID:33455044). I agree with him that it should be included as part of R381 - Other rare neuromuscular disorders super panel (465). ; to: As reviewed by Oliver Watkinson, Chanarin-Dorfman is a neutral lipid storage disorder and myopathy(generally tends to be slowly progressive muscle weakness) is part of the phenotype in 59% of reported cases (PMID:33455044). I agree with him that it should be included as part of R381 - Other rare neuromuscular disorders super panel (465).

This gene should therefore be added with green rating in this panel and also in panel 66 (as myopathy is caused by enzyme deficiency/ metabolic disorder).
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.27 ABHD5 Achchuthan Shanmugasundram Classified gene: ABHD5 as Amber List (moderate evidence)
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.27 ABHD5 Achchuthan Shanmugasundram Gene: abhd5 has been classified as Amber List (Moderate Evidence).
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.26 ABHD5 Achchuthan Shanmugasundram Phenotypes for gene: ABHD5 were changed from OMIM 604780 (Chanarin-Dorfman syndrome) to Chanarin-Dorfman syndrome, OMIM:275630
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.25 ABHD5 Achchuthan Shanmugasundram changed review comment from: As reviewed by Oliver Watkinson, Chanarin-Dorfman is a neutral lipid storage disorder and myopathy(generally tends to be slowly progressive muscle weakness) is part of the phenotype in 59% of reported cases (PMID:33455044). I agree with him that it should be included as part of R381 - Other rare neuromuscular disorders super panel (465). However, this gene should be included as part of Rhabdomyolysis and metabolic muscle disorders panel (66) rather than this panel. This is because I cannot see any evidence of limb-girdle muscular dystrophy/ weakness and the myopathy caused was due to enzyme deficiency/ metabolic disorder.; to: As reviewed by Oliver Watkinson, Chanarin-Dorfman is a neutral lipid storage disorder and myopathy(generally tends to be slowly progressive muscle weakness) is part of the phenotype in 59% of reported cases (PMID:33455044). I agree with him that it should be included as part of R381 - Other rare neuromuscular disorders super panel (465).
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.25 ABHD5 Achchuthan Shanmugasundram edited their review of gene: ABHD5: Changed rating: GREEN
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.25 ABHD5 Achchuthan Shanmugasundram changed review comment from: As reviewed by Oliver Watkinson, Chanarin-Dorfman is a neutral lipid storage disorder and myopathy(generally tends to be slowly progressive muscle weakness) is part of the phenotype in 59% of reported cases (PMID:33455044). I agree with him that it should be included as part of R381 - Other rare neuromuscular disorders super panel (465). However, this gene should be included as part of Rhabdomyolysis and metabolic muscle disorders panel (66) rather than this panel. This is because I cannot see any evidence of limb-girdle dystrophy/ weakness and the myopathy caused was due to metabolic disorder.; to: As reviewed by Oliver Watkinson, Chanarin-Dorfman is a neutral lipid storage disorder and myopathy(generally tends to be slowly progressive muscle weakness) is part of the phenotype in 59% of reported cases (PMID:33455044). I agree with him that it should be included as part of R381 - Other rare neuromuscular disorders super panel (465). However, this gene should be included as part of Rhabdomyolysis and metabolic muscle disorders panel (66) rather than this panel. This is because I cannot see any evidence of limb-girdle muscular dystrophy/ weakness and the myopathy caused was due to enzyme deficiency/ metabolic disorder.
Inherited polyposis and early onset colorectal cancer - germline testing v2.9 GREM1 Arina Puzriakova Classified gene: GREM1 as Amber List (moderate evidence)
Inherited polyposis and early onset colorectal cancer - germline testing v2.9 GREM1 Arina Puzriakova Added comment: Comment on list classification: Following review by the specialist service group, it has been agreed that this gene should be rated as Green at the next GMS panel update.

Upregulation of GREM1 expression in colorectal mucosa has been linked to hereditary mixed polyposis syndrome. This is caused by a 40-kb upstream duplication that spans the 3' end of the neighbouring SCG5 gene. There is currently no evidence of small variants or a whole gene duplication of GREM1 (without SCG5 involvement) causing a similar phenotype.

There is sufficient evidence to support a definitive gene-disease relationship but the providing GLH will have to account for the upstream sequence location and size of reported variants in their primer design (as R211 is currently a purely wet-lab/non-WGS test).

The SCG5-GREM1 duplication would not be detected by the NGS pipeline and this should be considered if this clinical indication ever moves to WGS in the future.
Inherited polyposis and early onset colorectal cancer - germline testing v2.9 GREM1 Arina Puzriakova Gene: grem1 has been classified as Amber List (Moderate Evidence).
Inherited polyposis and early onset colorectal cancer - germline testing v2.8 GREM1 Arina Puzriakova Tag regulatory-region tag was added to gene: GREM1.
Inherited polyposis and early onset colorectal cancer - germline testing v2.8 GREM1 Arina Puzriakova Tag regulatory-region was removed from gene: GREM1.
Tag Q4_23_promote_green tag was added to gene: GREM1.
Tag Q4_23_NHS_review tag was added to gene: GREM1.
Inherited polyposis and early onset colorectal cancer - germline testing v2.8 GREM1 Arina Puzriakova Tag currently-ngs-unreportable tag was added to gene: GREM1.
Tag gene-duplication tag was added to gene: GREM1.
Tag regulatory-region tag was added to gene: GREM1.
Respiratory ciliopathies including non-CF bronchiectasis v3.8 NME5 Achchuthan Shanmugasundram Classified gene: NME5 as Amber List (moderate evidence)
Respiratory ciliopathies including non-CF bronchiectasis v3.8 NME5 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (two unrelated cases and zebrafish model) for the promotion of this gene to green rating in the next GMS update.
Respiratory ciliopathies including non-CF bronchiectasis v3.8 NME5 Achchuthan Shanmugasundram Gene: nme5 has been classified as Amber List (Moderate Evidence).
Respiratory ciliopathies including non-CF bronchiectasis v3.7 NME5 Achchuthan Shanmugasundram Phenotypes for gene: NME5 were changed from Primary ciliary dyskinesia to Ciliary dyskinesia, primary, 48, without situs inversus, OMIM:620032
Respiratory ciliopathies including non-CF bronchiectasis v3.6 NME5 Achchuthan Shanmugasundram Publications for gene: NME5 were set to 32185794; 31479451
Respiratory ciliopathies including non-CF bronchiectasis v3.5 NME5 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: NME5.
Tag Q4_23_NHS_review tag was added to gene: NME5.
Respiratory ciliopathies including non-CF bronchiectasis v3.5 NME5 Achchuthan Shanmugasundram changed review comment from: Two unrelated cases were reported with biallelic NME5 variants. One patient was homozygous for p.Trp191Ter variant, while other was compound heterozygous with the same variant and p.Tyr160PhefsTer11. In addition, morpholino knockdown of nme5 in zebrafish embryos resulted in motile cilia defects with phenotypes compatible with ciliopathy.; to: Two unrelated cases were reported with biallelic NME5 variants. One patient was homozygous for p.Trp191Ter variant, while other was compound heterozygous with the same variant and p.Tyr160PhefsTer11. In addition, morpholino knockdown of nme5 in zebrafish embryos resulted in motile cilia defects with phenotypes compatible with ciliopathy.

This gene has been associated with relevant phenotypes in both OMIM (MIM #620032) and Gene2Phenotype (with 'definitive' rating in the DD panel).
Respiratory ciliopathies including non-CF bronchiectasis v3.5 NME5 Achchuthan Shanmugasundram reviewed gene: NME5: Rating: GREEN; Mode of pathogenicity: None; Publications: 32185794, 37957793; Phenotypes: Ciliary dyskinesia, primary, 48, without situs inversus, OMIM:620032; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Respiratory ciliopathies including non-CF bronchiectasis v3.5 FOXJ1 Achchuthan Shanmugasundram Classified gene: FOXJ1 as Amber List (moderate evidence)
Respiratory ciliopathies including non-CF bronchiectasis v3.5 FOXJ1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Steven Cowman, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Respiratory ciliopathies including non-CF bronchiectasis v3.5 FOXJ1 Achchuthan Shanmugasundram Gene: foxj1 has been classified as Amber List (Moderate Evidence).
Respiratory ciliopathies including non-CF bronchiectasis v3.4 FOXJ1 Achchuthan Shanmugasundram Publications for gene: FOXJ1 were set to 31630787
Respiratory ciliopathies including non-CF bronchiectasis v3.3 FOXJ1 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: FOXJ1.
Tag Q4_23_NHS_review tag was added to gene: FOXJ1.
Respiratory ciliopathies including non-CF bronchiectasis v3.3 FOXJ1 Achchuthan Shanmugasundram reviewed gene: FOXJ1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rhabdomyolysis and metabolic muscle disorders v3.44 ABHD5 Achchuthan Shanmugasundram changed review comment from: Chanarin-Dorfman is a neutral lipid storage disorder. Myopathy, identified through raised CK levels and muscle biopsy, was a commonly observed finding in 59% (86/147) cases with ABHD5 deficiency. The myopathy tends to generally be a slowly progressive muscle weakness and rarely culminates in cardiomyopathy.

This gene has been associated with relevant phenotypes in both OMIM (MIM #275630) and Gene2Phenotype (with 'definitive' rating in the DD panel), and muscle weakness has been recorded as one of the features in both resources.

As the myopathy was caused by metabolic deficiency, this gene should be added to this panel.
Sources: Literature; to: Chanarin-Dorfman is a neutral lipid storage disorder. Myopathy, identified through raised CK levels and muscle biopsy, was a commonly observed finding in 59% (86/147) cases with ABHD5 deficiency. The myopathy tends to generally be a slowly progressive muscle weakness and rarely culminates in cardiomyopathy.

This gene has been associated with relevant phenotypes in both OMIM (MIM #275630) and Gene2Phenotype (with 'definitive' rating in the DD panel), and muscle weakness has been recorded as one of the features in both resources.

As myopathy is caused by metabolic deficiency, this gene should be added to this panel.
Sources: Literature
Rhabdomyolysis and metabolic muscle disorders v3.44 ABHD5 Achchuthan Shanmugasundram changed review comment from: Chanarin-Dorfman is a neutral lipid storage disorder. Myopathy, identified through raised CK levels and muscle biopsy, was a commonly observed finding in 59% (86/147) cases with ABHD5 deficiency. The myopathy tends to generally be a slowly progressive muscle weakness and rarely culminates in cardiomyopathy.

This gene has been associated with relevant phenotypes in both OMIM (MIM #275630) and Gene2Phenotype (with 'definitive' rating in the DD panel), and muscle weakness has been recorded as one of the features in both resources.
Sources: Literature; to: Chanarin-Dorfman is a neutral lipid storage disorder. Myopathy, identified through raised CK levels and muscle biopsy, was a commonly observed finding in 59% (86/147) cases with ABHD5 deficiency. The myopathy tends to generally be a slowly progressive muscle weakness and rarely culminates in cardiomyopathy.

This gene has been associated with relevant phenotypes in both OMIM (MIM #275630) and Gene2Phenotype (with 'definitive' rating in the DD panel), and muscle weakness has been recorded as one of the features in both resources.

As the myopathy was caused by metabolic deficiency, this gene should be added to this panel.
Sources: Literature
Rhabdomyolysis and metabolic muscle disorders v3.44 ABHD5 Achchuthan Shanmugasundram Classified gene: ABHD5 as Amber List (moderate evidence)
Rhabdomyolysis and metabolic muscle disorders v3.44 ABHD5 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in this panel in the next GMS review.
Rhabdomyolysis and metabolic muscle disorders v3.44 ABHD5 Achchuthan Shanmugasundram Gene: abhd5 has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and metabolic muscle disorders v3.43 ABHD5 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: ABHD5.
Rhabdomyolysis and metabolic muscle disorders v3.43 ABHD5 Achchuthan Shanmugasundram gene: ABHD5 was added
gene: ABHD5 was added to Rhabdomyolysis and metabolic muscle disorders. Sources: Literature
Mode of inheritance for gene: ABHD5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABHD5 were set to 33455044
Phenotypes for gene: ABHD5 were set to Chanarin-Dorfman syndrome, OMIM:275630
Review for gene: ABHD5 was set to GREEN
Added comment: Chanarin-Dorfman is a neutral lipid storage disorder. Myopathy, identified through raised CK levels and muscle biopsy, was a commonly observed finding in 59% (86/147) cases with ABHD5 deficiency. The myopathy tends to generally be a slowly progressive muscle weakness and rarely culminates in cardiomyopathy.

This gene has been associated with relevant phenotypes in both OMIM (MIM #275630) and Gene2Phenotype (with 'definitive' rating in the DD panel), and muscle weakness has been recorded as one of the features in both resources.
Sources: Literature
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.25 ABHD5 Achchuthan Shanmugasundram edited their review of gene: ABHD5: Added comment: As reviewed by Oliver Watkinson, Chanarin-Dorfman is a neutral lipid storage disorder and myopathy(generally tends to be slowly progressive muscle weakness) is part of the phenotype in 59% of reported cases (PMID:33455044). I agree with him that it should be included as part of R381 - Other rare neuromuscular disorders super panel (465). However, this gene should be included as part of Rhabdomyolysis and metabolic muscle disorders panel (66) rather than this panel. This is because I cannot see any evidence of limb-girdle dystrophy/ weakness and the myopathy caused was due to metabolic disorder.; Changed publications to: 33455044; Changed phenotypes to: Chanarin-Dorfman syndrome, OMIM:275630
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.25 ABHD5 Achchuthan Shanmugasundram reviewed gene: ABHD5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Chanarin-Dorfman syndrome, OMIM<; Mode of inheritance: None
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.25 PNPLA2 Achchuthan Shanmugasundram Phenotypes for gene: PNPLA2 were changed from Neutral lipid storage disease with myopathy 610717 to Neutral lipid storage disease with myopathy, OMIM:610717
Rhabdomyolysis and metabolic muscle disorders v3.42 PNPLA2 Achchuthan Shanmugasundram Classified gene: PNPLA2 as Amber List (moderate evidence)
Rhabdomyolysis and metabolic muscle disorders v3.42 PNPLA2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are sufficient number of cases associating biallelic PNPLA2 variants to muscle and upper and lower limb weakness and dystrophy of shoulder girdle. Hence, this gene can be promoted to GREEN in this panel at the next GMS update.

This gene has also been associated with phenotypes in both OMIM (MIM #610717) and Gene2Phenotype (with 'strong' rating in DD panel).
Rhabdomyolysis and metabolic muscle disorders v3.42 PNPLA2 Achchuthan Shanmugasundram Gene: pnpla2 has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and metabolic muscle disorders v3.41 PNPLA2 Achchuthan Shanmugasundram Deleted their comment
Rhabdomyolysis and metabolic muscle disorders v3.41 PNPLA2 Achchuthan Shanmugasundram Phenotypes for gene: PNPLA2 were changed from Neutral lipid storage disease with myopathy 610717 to Neutral lipid storage disease with myopathy, OMIM:610717
Rhabdomyolysis and metabolic muscle disorders v3.40 PNPLA2 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: PNPLA2.
Tag Q4_23_promote_green tag was added to gene: PNPLA2.
Rhabdomyolysis and metabolic muscle disorders v3.40 PNPLA2 Achchuthan Shanmugasundram Entity copied from Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.24
Rhabdomyolysis and metabolic muscle disorders v3.40 PNPLA2 Achchuthan Shanmugasundram gene: PNPLA2 was added
gene: PNPLA2 was added to Rhabdomyolysis and metabolic muscle disorders. Sources: Expert list,Expert Review Amber
Q2_23_promote_green tags were added to gene: PNPLA2.
Mode of inheritance for gene: PNPLA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNPLA2 were set to 18952067; 21544567; 25956450; 32269696
Phenotypes for gene: PNPLA2 were set to Neutral lipid storage disease with myopathy 610717
Congenital muscular dystrophy v4.19 GOLGA2 Achchuthan Shanmugasundram Phenotypes for gene: GOLGA2 were changed from Secondary dystroglycanopathy; Developmental delay with hypotonia, myopathy, and brain abnormalities to Developmental delay with hypotonia, myopathy, and brain abnormalities, OMIM:620240
Congenital muscular dystrophy v4.18 GOLGA2 Achchuthan Shanmugasundram edited their review of gene: GOLGA2: Changed phenotypes to: Developmental delay with hypotonia, myopathy, and brain abnormalities, OMIM:620240
Congenital muscular dystrophy v4.18 GOLGA2 Achchuthan Shanmugasundram Classified gene: GOLGA2 as Amber List (moderate evidence)
Congenital muscular dystrophy v4.18 GOLGA2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Hannah Knight, there are three unrelated cases and zebrafish model in support of the disease association. Hence, this gene can be promoted to green rating in the next GMS review.
Congenital muscular dystrophy v4.18 GOLGA2 Achchuthan Shanmugasundram Gene: golga2 has been classified as Amber List (Moderate Evidence).
Congenital muscular dystrophy v4.17 GOLGA2 Achchuthan Shanmugasundram Phenotypes for gene: GOLGA2 were changed from Secondary dystroglycanopathy to Secondary dystroglycanopathy; Developmental delay with hypotonia, myopathy, and brain abnormalities
Congenital muscular dystrophy v4.16 GOLGA2 Achchuthan Shanmugasundram Publications for gene: GOLGA2 were set to 26742501; 30237576
Congenital muscular dystrophy v4.15 GOLGA2 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: GOLGA2.
Tag Q4_23_NHS_review tag was added to gene: GOLGA2.
Congenital muscular dystrophy v4.15 GOLGA2 Achchuthan Shanmugasundram reviewed gene: GOLGA2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dilated and arrhythmogenic cardiomyopathy v2.20 FKRP Achchuthan Shanmugasundram Classified gene: FKRP as Amber List (moderate evidence)
Dilated and arrhythmogenic cardiomyopathy v2.20 FKRP Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be considered for promotion to green rating in this panel in the next GMS review.
Dilated and arrhythmogenic cardiomyopathy v2.20 FKRP Achchuthan Shanmugasundram Gene: fkrp has been classified as Amber List (Moderate Evidence).
Dilated and arrhythmogenic cardiomyopathy v2.19 FKRP Achchuthan Shanmugasundram Phenotypes for gene: FKRP were changed from to Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 5, OMIM:607155
Dilated and arrhythmogenic cardiomyopathy v2.18 FKRP Achchuthan Shanmugasundram Publications for gene: FKRP were set to
Dilated and arrhythmogenic cardiomyopathy v2.17 FKRP Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: FKRP.
Tag Q4_23_NHS_review tag was added to gene: FKRP.
Dilated and arrhythmogenic cardiomyopathy v2.17 FKRP Achchuthan Shanmugasundram changed review comment from: PMID:32914449 reviewed 56 patients with limb-girdle muscular dystrophy and biallelic FKRP variants, of which 45% of patients had dilated cardiomyopathy as part of the phenotype with a median age of 54 years for patients homozygous for the common founder c.826C>A, compared to 18 years of age for other variants.

Dilated cardiomyopathy was also reported as part of the LGMD phenotype in both OMIM (MIM #607155) and Gene2Phenotype.; to: As reviewed by Oliver Watkinson, the limb-girdle muscular dystrophy phenotype caused by biallelic FKRP variants includes dilated cardiomyopathy as part of the phenotype.

PMID:32914449 reviewed 56 patients with limb-girdle muscular dystrophy and biallelic FKRP variants, of which 45% of patients had dilated cardiomyopathy as part of the phenotype with a median age of 54 years for patients homozygous for the common founder c.826C>A, compared to 18 years of age for other variants.

There were also a number of cases reported with dilated cardiomyopathy being the presenting condition and preceding overt skeletal muscle disease as noted by Oliver Watkinson including the recent case that he has seen in hospital.

Dilated cardiomyopathy was also reported as part of the LGMD phenotype in both OMIM (MIM #607155) and Gene2Phenotype.
Dilated and arrhythmogenic cardiomyopathy v2.17 FKRP Achchuthan Shanmugasundram reviewed gene: FKRP: Rating: GREEN; Mode of pathogenicity: None; Publications: 32914449; Phenotypes: Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 5, OMIM:607155; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v4.46 KMT2B Arina Puzriakova Tag Q3_23_promote_green was removed from gene: KMT2B.
Tag Q4_23_promote_green tag was added to gene: KMT2B.
Intellectual disability v5.345 KMT2B Arina Puzriakova Tag Q3_23_promote_green was removed from gene: KMT2B.
Tag Q4_23_promote_green tag was added to gene: KMT2B.
Retinal disorders v4.45 RPE65 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: RPE65.
Tag Q4_23_MOI tag was added to gene: RPE65.
Retinal disorders v4.45 RPE65 Arina Puzriakova Tag Q3_23_MOI was removed from gene: RPE65.
Tag Q4_23_promote_green tag was added to gene: RPE65.
Ataxia and cerebellar anomalies - narrow panel v4.40 ASL Nour Elkhateeb gene: ASL was added
gene: ASL was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: ASL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASL were set to 38044746; 36994644; 28251416
Phenotypes for gene: ASL were set to Ataxia
Added comment: Ataxia has been reported in multiple individuals with argininosuccinic aciduria (PMID 38044746, 36994644, 28251416).
Sources: Literature
Childhood onset dystonia, chorea or related movement disorder v3.56 ASL Nour Elkhateeb reviewed gene: ASL: Rating: GREEN; Mode of pathogenicity: None; Publications: 38044746, 36994644, 28251416; Phenotypes: Movement disorder, tremor, dystonia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v4.45 RPE65 Arina Puzriakova Phenotypes for gene: RPE65 were changed from Leber congenital amaurosis 2; Retinitis pigmentosa 20; Leber Congenital Amaurosis; Leber congenital amaurosis 2, 204100; Eye Disorders; Retinitis Pigmentosa, Recessive; Retinitis pigmentosa to Leber congenital amaurosis 2, OMIM:204100 (AR); Retinitis pigmentosa 20, OMIM:613794 (AR); Retinitis pigmentosa 87 with choroidal involvement, OMIM:618697 (AD)
Retinal disorders v4.44 RPE65 Arina Puzriakova Publications for gene: RPE65 were set to
Retinal disorders v4.43 RPE65 Arina Puzriakova Tag Q3_23_MOI tag was added to gene: RPE65.
Retinal disorders v4.43 RPE65 Arina Puzriakova Added comment: Comment on mode of inheritance: Biallelic variants cause retinitis pigmentosa and leber congenital amaurosis. Heterozygous variants have also been found in at least 4 unrelated families with choroid/retinal atrophy that mimics certain aspects of choroideremia (PMIDs: 21654732; 27307694; 29947567).

This supports a change in MOI from biallelic to both mono- and biallelic at the next GMS panel update.
Retinal disorders v4.43 RPE65 Arina Puzriakova Mode of inheritance for gene: RPE65 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v3.56 KMT2B Arina Puzriakova Phenotypes for gene: KMT2B were changed from Dystonia 28, childhood-onset 617284; early-onset dystonia to Dystonia 28, childhood-onset, OMIM:617284; Complex early-onset dystonia
Fetal anomalies v3.122 KMT2B Arina Puzriakova Phenotypes for gene: KMT2B were changed from Complex early-onset dystonia to Dystonia 28, childhood-onset, OMIM:617284; Complex early-onset dystonia
Adult onset neurodegenerative disorder v4.42 KMT2B Arina Puzriakova Phenotypes for gene: KMT2B were changed from early-onset dystonia to Dystonia 28, childhood-onset, OMIM:617284; early-onset dystonia
Structural basal ganglia disorders v1.39 KMT2B Arina Puzriakova Phenotypes for gene: KMT2B were changed from Dystonia 28, childhood-onset 617284 to Dystonia 28, childhood-onset, OMIM:617284; early-onset dystonia
Early onset dystonia v1.147 KMT2B Arina Puzriakova Phenotypes for gene: KMT2B were changed from early-onset dystonia to Dystonia 28, childhood-onset, OMIM:617284; early-onset dystonia
Severe microcephaly v4.46 KMT2B Arina Puzriakova changed review comment from: At least 80 patients have been reported with either KMT2B intragenic variants or chromosomal microdeletions. Clinical presentation most commonly comprises early-onset dystonia, but there were also reports of atypical patterns of dystonia evolution and a subgroup of patients with a neurodevelopmental disorder in the absence of dystonia.

Microcephaly of relevant severity to this panel has been reported in a sufficient number of cases to warrant inclusion on this panel with a Green rating.
Sources: Literature; to: At least 80 patients have been reported with either KMT2B intragenic variants or chromosomal microdeletions. Clinical presentation most commonly comprises early-onset dystonia, but there were also reports of atypical patterns of dystonia evolution and a subgroup of patients with a neurodevelopmental disorder in the absence of dystonia.

Microcephaly of relevant severity to this panel has been reported in a sufficient number of cases to warrant inclusion on this panel with a Green rating at the next GMS panel update.
Sources: Literature
Severe microcephaly v4.46 KMT2B Arina Puzriakova Classified gene: KMT2B as Amber List (moderate evidence)
Severe microcephaly v4.46 KMT2B Arina Puzriakova Gene: kmt2b has been classified as Amber List (Moderate Evidence).
Severe microcephaly v4.45 KMT2B Arina Puzriakova gene: KMT2B was added
gene: KMT2B was added to Severe microcephaly. Sources: Literature
Q3_23_promote_green tags were added to gene: KMT2B.
Mode of inheritance for gene: KMT2B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KMT2B were set to 27839873; 27839873; 33150406
Phenotypes for gene: KMT2B were set to Dystonia 28, childhood-onset, OMIM:617284; Intellectual developmental disorder, autosomal dominant 68, OMIM:619934
Review for gene: KMT2B was set to GREEN
Added comment: At least 80 patients have been reported with either KMT2B intragenic variants or chromosomal microdeletions. Clinical presentation most commonly comprises early-onset dystonia, but there were also reports of atypical patterns of dystonia evolution and a subgroup of patients with a neurodevelopmental disorder in the absence of dystonia.

Microcephaly of relevant severity to this panel has been reported in a sufficient number of cases to warrant inclusion on this panel with a Green rating.
Sources: Literature
Intellectual disability v5.345 KMT2B Arina Puzriakova Classified gene: KMT2B as Amber List (moderate evidence)
Intellectual disability v5.345 KMT2B Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update. Inclusion on this panel would also ensure this gene is included on the Paediatric disorders super panel which is appropriate for the phenotype.
Intellectual disability v5.345 KMT2B Arina Puzriakova Gene: kmt2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.344 KMT2B Arina Puzriakova Phenotypes for gene: KMT2B were changed from Dystonia 28, childhood-onset, 617284 to Dystonia 28, childhood-onset, OMIM:617284; Intellectual developmental disorder, autosomal dominant 68, OMIM:619934
Intellectual disability v5.343 KMT2B Arina Puzriakova Publications for gene: KMT2B were set to 25529582; 27839873; 27992417; 29276005; 25405613; 29289525; 29697234; 31216378
Intellectual disability v5.342 KMT2B Arina Puzriakova Tag watchlist was removed from gene: KMT2B.
Tag Q3_23_promote_green tag was added to gene: KMT2B.
Intellectual disability v5.342 KMT2B Arina Puzriakova reviewed gene: KMT2B: Rating: ; Mode of pathogenicity: None; Publications: 33150406; Phenotypes: ; Mode of inheritance: None
Severe microcephaly v4.44 NSD2 Sarah Leigh changed review comment from: Microcephaly is well recognized as a feature associated with pathogenic NSD2 variants. Of the published reports of microcephaly 50% (7/14) can be regarded as being severe, with a occipitofrontal circumference (OFC) below -3.0 standard deviations below the mean for age (PMID: 33941880 (including a review of previously published reports S4 table, PMID: 33276791).; to: Microcephaly is well recognized as a feature associated with pathogenic NSD2 variants. PMID: 33941880 reports three NSD2 variants in three unrelated cases of Rauch-Steindl syndrome (OMIM:619695), who have severe microcephaly (Occipitofrontal circumference (OFC) below >3.0 SD). Similarly, PMID: 33276791 reports a case with
OFC of 44 cm (<−3SD). Further cases are examined in the supplementary table 4 in PMID: 33941880
Severe microcephaly v4.44 NSD2 Sarah Leigh Classified gene: NSD2 as Amber List (moderate evidence)
Severe microcephaly v4.44 NSD2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be green on this panel.
Severe microcephaly v4.44 NSD2 Sarah Leigh Gene: nsd2 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v4.43 NSD2 Sarah Leigh Tag Q4_23_promote_green tag was added to gene: NSD2.
Severe microcephaly v4.43 NSD2 Sarah Leigh reviewed gene: NSD2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v5.342 NSD2 Sarah Leigh Phenotypes for gene: NSD2 were changed from Intrauterine growth retardation; Growth delay; Microcephaly; Muscular hypotonia; Neurodevelopmental delay; Intellectual disability; No OMIM number to Rauch-Steindl syndrome, OMIM:619695; Rauch-Steindl syndrome, MONDO:0859219
DDG2P v3.79 NSD2 Sarah Leigh Phenotypes for gene: NSD2 were changed from NSD2-related developmental disorder (monoallelic) to Rauch-Steindl syndrome, OMIM:619695; Rauch-Steindl syndrome, MONDO:0859219
Laterality disorders and isomerism v3.8 NSD2 Sarah Leigh Phenotypes for gene: NSD2 were changed from to Rauch-Steindl syndrome, OMIM:619695; Rauch-Steindl syndrome, MONDO:0859219
Severe microcephaly v4.43 NSD2 Sarah Leigh Phenotypes for gene: NSD2 were changed from microcephaly, MONDO:0001149 to Rauch-Steindl syndrome, OMIM:619695; Rauch-Steindl syndrome, MONDO:0859219
Severe microcephaly v4.42 NSD2 Sarah Leigh Publications for gene: NSD2 were set to 30345613; 31171569; 29760529; 29892088
Intellectual disability v5.341 C20orf24 Hannah Knight gene: C20orf24 was added
gene: C20orf24 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: C20orf24 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C20orf24 were set to 35614220
Phenotypes for gene: C20orf24 were set to ?Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome 2
Added comment: HGNC Approved Gene Symbol: RAB5IF
PMID: 35614220 (2022) identified a homozygous nonsense variant (p.W25X) in a Turkish boy previously reported by PMID: 24194475 to have bilateral cleft lip, complete cleft palate, moderate to severe intellectual delay and dysmorphic features. FHx of cleft lip/cleft palate as well in relatives who were heterozygous for the reported variant
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v4.125 DUT Hannah Knight gene: DUT was added
gene: DUT was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: DUT was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DUT were set to Bone marrow failure and diabetes mellitus syndrome
Review for gene: DUT was set to AMBER
Added comment: PMID: 28073829 (2017) - two unrelated consanguineous families with diabetes and bone marrow aplasia, both homozygous for p.Y142C
PMID: 35611808 (2022) - another family, two affected children with thrombocytopenia, macrocytosis, with or without anemia, followed by non-autoimmune diabetes. Same homozygous missense variant identified as before
PMID: 35931051 (2022) - identified probands who came from two independent families, had bi-allelic DUT variants, and presented with severe pancytopenia and mucocutaneous skin features. Information in supplementary materials. One patient homozygous for p.Tyr142Cys and the other compound het for p.Arg173Trp and p.Tyr227Cys
Sources: Literature
Mitochondrial disorders v4.113 PCK2 Hannah Knight gene: PCK2 was added
gene: PCK2 was added to Mitochondrial disorders. Sources: Literature
Mode of inheritance for gene: PCK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCK2 were set to 36845668
Phenotypes for gene: PCK2 were set to Abnormal gait; peripheral neuropathy
Review for gene: PCK2 was set to AMBER
Added comment: PMID: 36845668 (2023) identified three patients in two families with a common phenotype and likely pathogenic variants in PCK2:
A 3-year-old girl with ataxia and weakness, who was found to be compound heterozygous for p.Ser23Ter and p.Pro170Leu
Two siblings with abnormal gait and weakness who were found to both be homozygous for p.Arg193Ter. Unaffected sibling did not carry the variant
Sources: Literature
Likely inborn error of metabolism v4.77 LDHD Hannah Knight gene: LDHD was added
gene: LDHD was added to Likely inborn error of metabolism - targeted testing not possible. Sources: Literature
Mode of inheritance for gene: LDHD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LDHD were set to 30931947; 31638601
Phenotypes for gene: LDHD were set to D-lactic aciduria with susceptibility to gout
Review for gene: LDHD was set to AMBER
Added comment: PMID: 30931947 (2019) reported two unrelated patients with homozygous missense variants in LDHD (p.Thr463Met and p.Trp374Cys)
PMID: 31638601 (2019) reported a 4-generation consanguineous Bedouin-Israeli family with autosomal recessive hyperuricemia. A homozygous missense variant in LDHD was identified (p.R370W)
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v4.125 IFNGR2 Arina Puzriakova Publications for gene: IFNGR2 were set to 9616207; 15924140; 18625743; 30264912
Primary immunodeficiency or monogenic inflammatory bowel disease v4.124 IFNGR2 Arina Puzriakova Phenotypes for gene: IFNGR2 were changed from Immunodeficiency 28, Mycobacteriosis, 614889; Defects with susceptibility to mycobacterial infection (MSMD); Susceptibility to mycobacteria and Salmonella; Defects in Intrinsic and Innate Immunity to Immunodeficiency 28, mycobacteriosis, OMIM:614889
Mitochondrial disorders v4.113 SLC25A36 Hannah Knight gene: SLC25A36 was added
gene: SLC25A36 was added to Mitochondrial disorders. Sources: Literature
Mode of inheritance for gene: SLC25A36 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A36 were set to 34576089; 34971397; 36695547
Phenotypes for gene: SLC25A36 were set to Hyperinsulinemic hypoglycemia, familial, 8
Review for gene: SLC25A36 was set to GREEN
Added comment: More than three cases reported in past three years
PMID: 34576089 (2021) - first case, a 12-year-old patient with hypothyroidism, hyperinsulinism, hyperammonemia, chronical obstipation, short stature, along with language and general developmental delay. Homozygous frameshift variant identified c.803dupT, p.Ser269llefs*35
PMID: 34971397 (2022) - two siblings with homozygous splice site variant
PMID: 36695547 (2023) - four individuals of two Bedouin Israeli related families - same homozygous splice site variant identified
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v4.40 THG1L Hannah Knight reviewed gene: THG1L: Rating: AMBER; Mode of pathogenicity: None; Publications: 33682303, 33682303; Phenotypes: Spinocerebellar ataxia, autosomal recessive 28; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v4.77 ACACA Hannah Knight gene: ACACA was added
gene: ACACA was added to Likely inborn error of metabolism - targeted testing not possible. Sources: Literature
Mode of inheritance for gene: ACACA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACACA were set to 34552920
Phenotypes for gene: ACACA were set to Acetyl-CoA carboxylase deficiency
Review for gene: ACACA was set to AMBER
Added comment: PMID: 34552920 (2021) reported a baby who presented in her first two years of life with global developmental delay, microcephaly, hypotonia, and dysmorphic facial features. Two VUS's in ACACA were identified, and a decreased level of ACC1 and ACC1 enzyme activity was detected in patient-derived lymphocytes. In vitro studies revealed a disruption of lipid homeostasis in patient-derived lymphocytes, further inducing the deficit of cell motility capacity and that the deficiency could be partly attenuated by palmitate.
Sources: Literature
Mitochondrial disorders v4.113 MRPS28 Hannah Knight gene: MRPS28 was added
gene: MRPS28 was added to Mitochondrial disorders. Sources: Literature
Mode of inheritance for gene: MRPS28 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MRPS28 were set to 30566640
Phenotypes for gene: MRPS28 were set to ?Combined oxidative phosphorylation deficiency 47
Review for gene: MRPS28 was set to AMBER
Added comment: PMID: 30566640 (2019) reported a 30-year-old man with a multisystemic mitochondrial disorder and compound heterozygous variants in the MRPS28 gene. Patient fibroblasts showed decreased MRPS28 protein levels compared to controls. There were variable deficiencies of complexes I, III, IV, and V activities and complex assembly associated with decreased mitochondrial respiration activity in vitro. Additional studies of patient fibroblasts showed impaired assembly of the small mitoribosomal subunit (bS1m, encoded by MRPS28), decreased levels of 12S rRNA, and impaired mitochondrial translation. These defects could be rescued by expression of wildtype MRPS28
Sources: Literature
Mitochondrial disorders v4.113 MRPS25 Hannah Knight gene: MRPS25 was added
gene: MRPS25 was added to Mitochondrial disorders. Sources: Literature
Mode of inheritance for gene: MRPS25 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MRPS25 were set to 31039582
Phenotypes for gene: MRPS25 were set to ?Combined oxidative phosphorylation deficiency 50
Review for gene: MRPS25 was set to AMBER
Added comment: PMID: 31039582 (2019) reported a 25-year-old man, born of unrelated parents, with a mitochondrial encephalomyopathy and a homozygous missense variant in the MRPS25 gene (P72L). Patient fibroblasts showed decreased protein levels of MRPS25, about one-tenth of controls. Levels of other polypeptides of the 28S ribosomal subunit were also decreased, suggesting that the mutation adversely affected assembly or stability of the 28S subunit. Further in vitro studies of patient fibroblasts showed impaired mitochondrial translation and decreased protein levels of respiratory chain complexes I, III, and IV. Expression of wildtype MRPS25 in patient fibroblasts resulted in partial restoration of OXPHOS protein levels. The findings suggested that MRPS25 is required for mitochondrial protein synthesis, and that this defect causes decreased levels of mitochondrial respiratory chain subunits and impaired mitochondrial translation.
Sources: Literature
Mitochondrial disorders v4.113 MIEF2 Hannah Knight gene: MIEF2 was added
gene: MIEF2 was added to Mitochondrial disorders. Sources: Literature
Mode of inheritance for gene: MIEF2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MIEF2 were set to 29361167
Phenotypes for gene: MIEF2 were set to ?Combined oxidative phosphorylation deficiency 49
Review for gene: MIEF2 was set to AMBER
Added comment: PMID: 29361167 (2018) reported a 15-year-old boy, born of consanguineous Jewish parents, with combined oxidative phosphorylation deficiency-49 and a homozygous nonsense variant in the MIEF2 gene (Q92X). Patient skeletal muscle and fibroblasts showed a combined decrease in mitochondrial respiratory chain enzymes, particularly complexes I and IV, elongated mitochondria with abnormal cristae, decreased mitochondrial fission, and increased fusion events. The cellular phenotype could be rescued by expression of wildtype MIEF2. The findings were consistent with a defect in mitochondrial dynamics
Sources: Literature
Mitochondrial disorders v4.113 TAMM41 Hannah Knight gene: TAMM41 was added
gene: TAMM41 was added to Mitochondrial disorders. Sources: Literature
Mode of inheritance for gene: TAMM41 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAMM41 were set to 35321494
Phenotypes for gene: TAMM41 were set to Combined oxidative phosphorylation deficiency 56
Review for gene: TAMM41 was set to GREEN
Added comment: PMID: 35321494 (2022) report three unrelated individuals with mitochondrial disease and compound heterozygous variants in this gene + functional studies
Sources: Literature
Mitochondrial disorders v4.113 TEFM Hannah Knight gene: TEFM was added
gene: TEFM was added to Mitochondrial disorders. Sources: Literature
Mode of inheritance for gene: TEFM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TEFM were set to 36823193
Phenotypes for gene: TEFM were set to Combined oxidative phosphorylation deficiency 58
Review for gene: TEFM was set to GREEN
Added comment: PMID: 36823193 (2023) report seven TEFM variants (four missense, two frameshift and one in-frame 2-amino acid deletion) in seven individuals from five unrelated families who present with mitochondrial respiratory chain deficiency and a wide range of infantile or childhood-onset neurological and neuromuscular symptoms, due to abnormal mitochondrial transcription. Zebrafish model as well
Sources: Literature
Iron metabolism disorders - NOT common HFE mutations v2.3 STAB1 Edoardo Monfrini gene: STAB1 was added
gene: STAB1 was added to Iron metabolism disorders - NOT common HFE mutations. Sources: Literature
Mode of inheritance for gene: STAB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STAB1 were set to 37490907
Phenotypes for gene: STAB1 were set to Hyperferritinemia without iron overload
Penetrance for gene: STAB1 were set to Complete
Review for gene: STAB1 was set to GREEN
Added comment: Sources: Literature
Malformations of cortical development v4.12 COL4A2 Nour Elkhateeb edited their review of gene: COL4A2: Changed rating: GREEN
Paediatric or syndromic cardiomyopathy v3.43 RRAGC Achchuthan Shanmugasundram Phenotypes for gene: RRAGC were changed from Dilated cardiomyopathy, hepatopathy and brain abnormalities to Long-Olsen syndrome, OMIM:620609
Paediatric or syndromic cardiomyopathy v3.42 RRAGC Achchuthan Shanmugasundram reviewed gene: RRAGC: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Long-Olsen syndrome, OMIM:620609; Mode of inheritance: None
Paediatric or syndromic cardiomyopathy v3.42 RRAGC Achchuthan Shanmugasundram Tag gene-checked was removed from gene: RRAGC.
Early onset or syndromic epilepsy v4.133 ASL Nour Elkhateeb changed review comment from: Epilepsy is reported as a common phenotype in individuals with argininosuccinic aciduria (ASA) with incidence between 42%-60% (PMID 36994644, 21744316, 28251416). The epilepsy phenotype occurs early in the natural history of ASA. The epilepsy phenotype is severe, with a significant cohort of patients presenting with pharmacoresistant seizures, and with status epilepticus. Epilepsy onset preceded ASA diagnosis in several reported patients (PMID: 36994644).
Sources: Literature, ClinGen; to: Epilepsy is reported as a common phenotype in individuals with argininosuccinic aciduria (ASA) with incidence between 42%-60% (PMID 36994644, 21744316, 28251416). The epilepsy phenotype occurs early in the natural history of ASA, with a median between at 2-5.5 years (PMID 36994644, 21744316, 28251416). The epilepsy phenotype is severe, with a significant cohort of patients presenting with pharmacoresistant seizures, and with status epilepticus. Epilepsy onset preceded ASA diagnosis in several reported patients (PMID: 36994644).
Sources: Literature, ClinGen
Early onset or syndromic epilepsy v4.133 ASL Nour Elkhateeb changed review comment from: Epilepsy is reported as a common phenotype in individuals with argininosuccinic aciduria (ASA) with incidence between 42%-60%. The epilepsy phenotype occurs early in the natural history of ASA. The epilepsy phenotype is severe, with a significant cohort of patients presenting with pharmacoresistant seizures, and with status epilepticus. Epilepsy onset preceded ASA diagnosis in several reported patients.
Sources: Literature, ClinGen; to: Epilepsy is reported as a common phenotype in individuals with argininosuccinic aciduria (ASA) with incidence between 42%-60% (PMID 36994644, 21744316, 28251416). The epilepsy phenotype occurs early in the natural history of ASA. The epilepsy phenotype is severe, with a significant cohort of patients presenting with pharmacoresistant seizures, and with status epilepticus. Epilepsy onset preceded ASA diagnosis in several reported patients (PMID: 36994644).
Sources: Literature, ClinGen
Early onset or syndromic epilepsy v4.133 ASL Nour Elkhateeb gene: ASL was added
gene: ASL was added to Early onset or syndromic epilepsy. Sources: Literature,ClinGen
Mode of inheritance for gene: ASL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASL were set to 36994644; 21744316; 28251416
Phenotypes for gene: ASL were set to Seizure; Neurodevelopmental delay; Intellectual disability; Autism; Abnormality of movement; Ataxia; Hepatomegaly; Elevated hepatic transaminase; Renal tubular dysfunction; Abnormal hair morphology
Penetrance for gene: ASL were set to Complete
Review for gene: ASL was set to GREEN
Added comment: Epilepsy is reported as a common phenotype in individuals with argininosuccinic aciduria (ASA) with incidence between 42%-60%. The epilepsy phenotype occurs early in the natural history of ASA. The epilepsy phenotype is severe, with a significant cohort of patients presenting with pharmacoresistant seizures, and with status epilepticus. Epilepsy onset preceded ASA diagnosis in several reported patients.
Sources: Literature, ClinGen
COVID-19 research v1.140 IKBKB Arina Puzriakova Phenotypes for gene: IKBKB were changed from Immunodeficiency 15, 615592; Immunodeficiencies affecting cellular and humoral immunity; Combined immunodeficiency; Recurrent bacterial, viral, fungal infections, opportunistic infections to Immunodeficiency 15A, OMIM:618204 (AD); Immunodeficiency 15B, OMIM:615592 (AR); Combined immunodeficiency; Recurrent bacterial, viral, fungal infections, opportunistic infections; Immunodeficiencies affecting cellular and humoral immunity
COVID-19 research v1.139 IKBKB Arina Puzriakova Added comment: Comment on mode of inheritance: Updated from 'biallelic' to 'both mono- and biallelic' as both inheritance patterns are associated with a relevant phenotype of primary immunodeficiency, but AR disease is more severe with earlier onset.
COVID-19 research v1.139 IKBKB Arina Puzriakova Mode of inheritance for gene: IKBKB was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Congenital hypothyroidism v2.18 IYD Arina Puzriakova Added comment: Comment on publications: Previous phenotypes - PMID:18434651 (Moreno et al., 2008): 2 missense mutations and a 3bp deletion were identified in 4 patients with hypothryoidism from 3 unrelated families;PMID:22535972 (Burniat et al., 2012) identified a homozygous IYD mutation in a child born to first-cousins. A 4.5-yr-old unaffected sister was found homozygous for the mutation;24629858 (Review);18765512
Congenital hypothyroidism v2.18 IYD Arina Puzriakova Publications for gene: IYD were set to PMID:18434651 (Moreno et al., 2008): 2 missense mutations and a 3bp deletion were identified in 4 patients with hypothryoidism from 3 unrelated families; PMID:22535972 (Burniat et al., 2012) identified a homozygous IYD mutation in a child born to first-cousins. A 4.5-yr-old unaffected sister was found homozygous for the mutation; 24629858 (Review); 18765512
Congenital hypothyroidism v2.17 IYD Arina Puzriakova Phenotypes for gene: IYD were changed from Congenital hypothyroidism; Thyroid dyshormonogenesis 4, 274800; goitre; childhood/adolescent onset hypothyroidism; normal iodide organification; raised urinary MIT and DIT to Thyroid dyshormonogenesis 4, OMIM:274800
Hypogonadotropic hypogonadism v1.40 NSMF Arina Puzriakova changed review comment from: Comment on mode of inheritance: Updated from biallelic to monoallelic as only heterozygous variants in this gene have been reported in association with IHH, even though this only partially explains the phenotype in some cases due to possible oligogenic variants in other genes such as FGFR1 and HS6ST1.; to: Comment on mode of inheritance: Updated from biallelic to monoallelic as only heterozygous variants in this gene have been reported in association with IHH, even though this only partially explains the phenotype in some cases due to oligogenic variants in other genes such as FGFR1 and HS6ST1.
Hypogonadotropic hypogonadism v1.40 NSMF Arina Puzriakova changed review comment from: Comment on mode of inheritance: Updated from biallelic to monoallelic as only heterozygous variants in this gene have been reported in association with IHH, even though this is only partially explains the phenotype due to possible oligogenic variants in other genes such as FGFR1 and HS6ST1.; to: Comment on mode of inheritance: Updated from biallelic to monoallelic as only heterozygous variants in this gene have been reported in association with IHH, even though this only partially explains the phenotype in some cases due to possible oligogenic variants in other genes such as FGFR1 and HS6ST1.
Hypogonadotropic hypogonadism v1.40 NSMF Arina Puzriakova Classified gene: NSMF as Red List (low evidence)
Hypogonadotropic hypogonadism v1.40 NSMF Arina Puzriakova Added comment: Comment on list classification: Downgrading from Green to Red to align with the classification on the GMS equivalent panel (https://panelapp.genomicsengland.co.uk/panels/650/gene/NSMF/).

Review by Zornitza Stark (Australian Genomics) - 18 Jul 2020
"Rare variants reported in individuals with IHH; however, variants in other IHH genes also present, and at least one of the variants has a very high population frequency in gnomad (intronic 8-bp deletion ending 14 bp before exon 10 (1159-14_-22del), present in 258 individuals)."

Review by Ivone Leong (Genomics England Curator) - 24 Mar 2021
"This gene is associated with a phenotype in OMIM but not in Gene2Phenotype. PMID:27803842 describes a murine Nsmf knockout model that shows that Nsmf does not have a role in the migration of GnRH-positive neurons during early development.
Given the available evidence, this gene should be demoted to Red status."
Hypogonadotropic hypogonadism v1.40 NSMF Arina Puzriakova Gene: nsmf has been classified as Red List (Low Evidence).
Hypogonadotropic hypogonadism v1.39 NSMF Arina Puzriakova Publications for gene: NSMF were set to 15362570; 17235395; 21300340
Hypogonadotropic hypogonadism v1.38 NSMF Arina Puzriakova Phenotypes for gene: NSMF were changed from Hypogonadotropic hypogonadism 9 with or without anosmia, 614838; Endocrine Disorders including conditions such as hypogonadotropic hypogonadism (with or without anosmia): Sequencing Panel (Emory) to Hypogonadotropic hypogonadism 9 with or without anosmia, OMIM:614838
Hypogonadotropic hypogonadism v1.37 NSMF Arina Puzriakova Added comment: Comment on mode of inheritance: Updated from biallelic to monoallelic as only heterozygous variants in this gene have been reported in association with IHH, even though this is only partially explains the phenotype due to possible oligogenic variants in other genes such as FGFR1 and HS6ST1.
Hypogonadotropic hypogonadism v1.37 NSMF Arina Puzriakova Mode of inheritance for gene: NSMF was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypogonadotropic hypogonadism (GMS) v3.14 NSMF Arina Puzriakova Added comment: Comment on mode of inheritance: Updated from biallelic to monoallelic as only heterozygous variants in this gene have been reported in association with IHH, even though this is only partially explains the phenotype due to possible oligogenic variants in other genes such as FGFR1 and HS6ST1.
Hypogonadotropic hypogonadism (GMS) v3.14 NSMF Arina Puzriakova Mode of inheritance for gene: NSMF was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v3.121 NSMF Arina Puzriakova Mode of pathogenicity for gene: NSMF was changed from to Other
Fetal anomalies v3.120 NSMF Arina Puzriakova Phenotypes for gene: NSMF were changed from Hypogonadotropic hypogonadism 9 with or without anosmia 614838 to Hypogonadotropic hypogonadism 9 with or without anosmia, OMIM:614838
Autoinflammatory disorders v1.11 UBA1 Arina Puzriakova Publications for gene: UBA1 were set to 33108101; 33690815; 34048852; 34077651; 34196684
Autoinflammatory disorders v1.10 UBA1 Arina Puzriakova Tag to_be_confirmed_NHSE was removed from gene: UBA1.
Autoinflammatory disorders v1.10 UBA1 Arina Puzriakova Classified gene: UBA1 as Green List (high evidence)
Autoinflammatory disorders v1.10 UBA1 Arina Puzriakova Added comment: Comment on list classification: Following further discussions with the GMS specialist group, it was agreed that the coverage of this test does include somatic variant detection. Therefore, the rating of this gene has been updated to green and the mode of inheritance set to "Other" following NHS Genomic Medicine Service approval.
Autoinflammatory disorders v1.10 UBA1 Arina Puzriakova Gene: uba1 has been classified as Green List (High Evidence).
Autoinflammatory disorders v1.9 UBA1 Arina Puzriakova Mode of pathogenicity for gene: UBA1 was changed from to Other
Early onset or syndromic epilepsy v4.133 CLCN2 Sarah Leigh commented on gene: CLCN2: The association between CLCN2 and epilepsy has been refuted by ClinGen Epilepsy Expert Panel on the meeting date March 15, 2022 (https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_ba2a1616-b3d7-4762-a546-c838333db683-2022-03-15T040000.000Z)
Early onset or syndromic epilepsy v4.133 MAGI2 Sarah Leigh commented on gene: MAGI2: Sarah Leigh commented on gene: MAGI2: Clingen refuted association with epilepsy https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_7d622b88-9c77-47f8-93b1-808517da0cff-2023-10-17T190000.000Z?page=1&size=25&search=
Malformations of cortical development v4.12 CASP2 Achchuthan Shanmugasundram Classified gene: CASP2 as Amber List (moderate evidence)
Malformations of cortical development v4.12 CASP2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is sufficient evidence available (three unrelated families) for the association of biallelic CASP2 variants with lissencephaly. Hence, this gene can be promoted to green rating in the next GMS update.
Malformations of cortical development v4.12 CASP2 Achchuthan Shanmugasundram Gene: casp2 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v4.11 CASP2 Achchuthan Shanmugasundram Phenotypes for gene: CASP2 were changed from neurodevelopmental disorder MONDO:0700092, CASP2-related to neurodevelopmental disorder, MONDO:0700092; hereditary cerebral malformation, MONDO:0957008
Malformations of cortical development v4.10 CASP2 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: CASP2.
Malformations of cortical development v4.10 CASP2 Achchuthan Shanmugasundram reviewed gene: CASP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 37880421; Phenotypes: neurodevelopmental disorder, MONDO:0700092, hereditary cerebral malformation, MONDO:0957008; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.341 CASP2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.341 CASP2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.341 CASP2 Achchuthan Shanmugasundram Classified gene: CASP2 as Amber List (moderate evidence)
Intellectual disability v5.341 CASP2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Dmitrijs Rots, there are at least three unrelated families reported with biallelic CASP2 variants and intellectual disability/ global developmental delay. Hence, this gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.341 CASP2 Achchuthan Shanmugasundram Gene: casp2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.341 CASP2 Achchuthan Shanmugasundram Classified gene: CASP2 as Amber List (moderate evidence)
Intellectual disability v5.341 CASP2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Dmitrijs Rots, there are at least three unrelated families reported with biallelic CASP2 variants and intellectual disability/ global developmental delay. Hence, this gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.341 CASP2 Achchuthan Shanmugasundram Gene: casp2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.341 CASP2 Achchuthan Shanmugasundram Classified gene: CASP2 as Amber List (moderate evidence)
Intellectual disability v5.341 CASP2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Dmitrijs Rots, there are at least three unrelated families reported with biallelic CASP2 variants and intellectual disability/ global developmental delay. Hence, this gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.341 CASP2 Achchuthan Shanmugasundram Gene: casp2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.340 CASP2 Achchuthan Shanmugasundram Phenotypes for gene: CASP2 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.340 CASP2 Achchuthan Shanmugasundram Phenotypes for gene: CASP2 were changed from Autosomal recessive mental retardation to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.339 CASP2 Achchuthan Shanmugasundram Publications for gene: CASP2 were set to 26350204; 24896178; 21937992
Intellectual disability v5.338 CASP2 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: CASP2.
Intellectual disability v5.338 CASP2 Achchuthan Shanmugasundram reviewed gene: CASP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 37880421; Phenotypes: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v4.133 MAGI2 Sarah Leigh Deleted their comment
Early onset or syndromic epilepsy v4.133 CACNB4 Sarah Leigh Tag refuted tag was added to gene: CACNB4.
Early onset or syndromic epilepsy v4.133 CACNB4 Sarah Leigh Tag Q4_23_demote_red tag was added to gene: CACNB4.
Early onset or syndromic epilepsy v4.133 CACNB4 Sarah Leigh edited their review of gene: CACNB4: Added comment: The gene disease association between CACNB4 and epilepsy has been refuted by ClinGen Epilepsy Gene Curation Expert Panel on July 5, 2022 (SOP Version 9)(https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_d2fad131-8e91-4874-9394-8b86d6d62abb-2022-07-05T160000.000Z?page=1&size=25&search= ); Changed rating: RED
Early onset or syndromic epilepsy v4.133 MAGI2 Sarah Leigh Tag disputed was removed from gene: MAGI2.
Tag refuted tag was added to gene: MAGI2.
Early onset or syndromic epilepsy v4.133 MAGI2 Sarah Leigh commented on gene: MAGI2: Clingen refuted association with epilepsy https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_7d622b88-9c77-47f8-93b1-808517da0cff-2023-10-17T190000.000Z?page=1&size=25&search=
Structural eye disease v3.58 KIF11 Hannah Knight reviewed gene: KIF11: Rating: GREEN; Mode of pathogenicity: None; Publications: 24281367; Phenotypes: Microcephaly with or without chorioretinopathy, lymphedema, or impaired intellectual development; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v3.58 KIAA0586 Hannah Knight reviewed gene: KIAA0586: Rating: GREEN; Mode of pathogenicity: None; Publications: 30055837, 36580738, 28125082; Phenotypes: Joubert syndrome 23; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v3.58 CRYBB2 Hannah Knight reviewed gene: CRYBB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29386872, 25489230, 21402992, 2240043, 9158139; Phenotypes: Cataract 3, multiple types; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v3.58 SLC25A24 Hannah Knight reviewed gene: SLC25A24: Rating: AMBER; Mode of pathogenicity: None; Publications: 31775791; Phenotypes: Fontaine progeroid syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mitochondrial disorders v4.113 ATP5B Sarah Leigh commented on gene: ATP5B: In the opinion of Helen Brittain (Clinical Fellow, Genomics England) is "There is a lack of clarity over the penetrance, plus also the phenotypes are somewhat disparate (the twins had DD with episodic hyperthermia, whereas the other cases presented with dystonia). A gene:disease association cannot be made at this time".
Mitochondrial disorder with complex V deficiency v2.12 ATP5B Sarah Leigh commented on gene: ATP5B: In the opinion of Helen Brittain (Clinical Fellow, Genomics England) is "There is a lack of clarity over the penetrance, plus also the phenotypes are somewhat disparate (the twins had DD with episodic hyperthermia, whereas the other cases presented with dystonia). A gene:disease association cannot be made at this time".
Likely inborn error of metabolism v4.77 ATP5B Sarah Leigh commented on gene: ATP5B: In the opinion of Helen Brittain (Clinical Fellow, Genomics England) is "There is a lack of clarity over the penetrance, plus also the phenotypes are somewhat disparate (the twins had DD with episodic hyperthermia, whereas the other cases presented with dystonia). A gene:disease association cannot be made at this time".
Possible mitochondrial disorder - nuclear genes v3.68 ATP5B Sarah Leigh commented on gene: ATP5B: In the opinion of Helen Brittain (Clinical Fellow, Genomics England) is "There is a lack of clarity over the penetrance, plus also the phenotypes are somewhat disparate (the twins had DD with episodic hyperthermia, whereas the other cases presented with dystonia). A gene:disease association cannot be made at this time".
Early onset or syndromic epilepsy v4.133 ZBTB47 Sarah Leigh changed review comment from: Asked the opinion of Helen Brittain (Genomics England, Clinical Fellow), regarding the recommended rating of ZBTB47.; to: The opinion of Helen Brittain (Genomics England, Clinical Fellow), was that ZBTB47 should be green on the Intellectual disability and Early onset or syndromic epilepsy panels.
Intellectual disability v5.338 ZBTB47 Sarah Leigh commented on gene: ZBTB47: The opinion of Helen Brittain (Genomics England, Clinical Fellow), was that ZBTB47 should be green on the Intellectual disability and Early onset or syndromic epilepsy panels.
Early onset or syndromic epilepsy v4.133 ZBTB47 Sarah Leigh edited their review of gene: ZBTB47: Added comment: ZBTB47 variants have not been associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 37743782 reports five unrelated patients with de novo missense variants in ZBTB47 (c.2039A>G, p.(Glu680Gly) in one patient and c.1429G>A, p.(Glu477Lys) in four others), with a phenotype that included developmental delay, intellectual disability, seizures, hypotonia, gait abnormalities, and variable movement abnormalities.; Changed rating: GREEN
Intellectual disability v5.338 ZBTB47 Sarah Leigh edited their review of gene: ZBTB47: Added comment: ZBTB47 variants have not been associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 37743782 reports five unrelated patients with de novo missense variants in ZBTB47 (c.2039A>G, p.(Glu680Gly) in one patient and c.1429G>A, p.(Glu477Lys) in four others), with a phenotype that included developmental delay, intellectual disability, seizures, hypotonia, gait abnormalities, and variable movement abnormalities.; Changed rating: GREEN
Early onset or syndromic epilepsy v4.133 ZBTB47 Sarah Leigh Phenotypes for gene: ZBTB47 were changed from Neurodevelopmental disorder, MONDO; 0700092 to Neurodevelopmental disorder, MONDO:0700092
Early onset or syndromic epilepsy v4.132 ZBTB47 Sarah Leigh Phenotypes for gene: ZBTB47 were changed from Neurodevelopmental disorder (MONDO#0700092), ZBTB47-related to Neurodevelopmental disorder, MONDO; 0700092
Intellectual disability v5.338 ZBTB47 Sarah Leigh Phenotypes for gene: ZBTB47 were changed from Neurodevelopmental disorder (MONDO#0700092), ZBTB47-related to Neurodevelopmental disorder, MONDO; 0700092
Intellectual disability v5.337 ZBTB47 Sarah Leigh Tag Q4_23_promote_green tag was added to gene: ZBTB47.
Early onset or syndromic epilepsy v4.131 ZBTB47 Sarah Leigh Tag Q4_23_promote_green tag was added to gene: ZBTB47.
Early onset or syndromic epilepsy v4.131 ZBTB47 Sarah Leigh Entity copied from Intellectual disability - microarray and sequencing v5.337
Early onset or syndromic epilepsy v4.131 ZBTB47 Sarah Leigh gene: ZBTB47 was added
gene: ZBTB47 was added to Early onset or syndromic epilepsy. Sources: Literature,Expert Review Amber
Mode of inheritance for gene: ZBTB47 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZBTB47 were set to 37743782
Phenotypes for gene: ZBTB47 were set to Neurodevelopmental disorder (MONDO#0700092), ZBTB47-related
Early onset or syndromic epilepsy v4.130 MAST4 Sarah Leigh Entity copied from Intellectual disability - microarray and sequencing v5.337
Early onset or syndromic epilepsy v4.130 MAST4 Sarah Leigh gene: MAST4 was added
gene: MAST4 was added to Early onset or syndromic epilepsy. Sources: Literature,Expert Review Amber
Q4_23_promote_green tags were added to gene: MAST4.
Mode of inheritance for gene: MAST4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAST4 were set to 36910266; 33057194
Phenotypes for gene: MAST4 were set to neurodevelopmental disorder MONDO:0700092, MAST4-related
Respiratory ciliopathies including non-CF bronchiectasis v3.3 FOXJ1 Steven Cowman reviewed gene: FOXJ1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31630787, 37469238, 37813609; Phenotypes: Motile ciliopathy, situs inversus, hydrocephalus; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Respiratory ciliopathies including non-CF bronchiectasis v3.3 NME5 Steven Cowman reviewed gene: NME5: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 37957793; Phenotypes: Primary ciliary dyskinesia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Respiratory ciliopathies including non-CF bronchiectasis v3.3 SPEF2 Steven Cowman reviewed gene: SPEF2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31942643, 31942643, 31545650; Phenotypes: Primary ciliary dyskinesia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Respiratory ciliopathies including non-CF bronchiectasis v3.3 SPEF2 Steven Cowman Deleted their review
Respiratory ciliopathies including non-CF bronchiectasis v3.3 SPEF2 Steven Cowman reviewed gene: SPEF2: Rating: ; Mode of pathogenicity: None; Publications: PMID: 31942643; Phenotypes: ; Mode of inheritance: None
COVID-19 research v1.138 IL21R Arina Puzriakova Phenotypes for gene: IL21R were changed from Combined immunodeficiency; Atypical Severe Combined Immunodeficiency (Atypical SCID); Immunodeficiency 56, 615207; Immunodeficiencies affecting cellular and humoral immunity; Omenn syndrome; Immunodeficiency, primary, autosomal recessive, IL21R-related; IL-21R deficiency; Severe combined immunodeficiency (SCID); Recurrent infections, Pneumocystis jiroveci, Cryptosporidium infections and liver disease to Immunodeficiency 56, OMIM:615207; Atypical Severe Combined Immunodeficiency (Atypical SCID); Combined immunodeficiency; Omenn syndrome; Recurrent infections, Pneumocystis jiroveci, Cryptosporidium infections and liver disease; Immunodeficiencies affecting cellular and humoral immunity
Primary immunodeficiency or monogenic inflammatory bowel disease v4.123 IL21R Arina Puzriakova Phenotypes for gene: IL21R were changed from Immunodeficiency 56, 615207; Immunodeficiency, primary, autosomal recessive, IL21R-related; Atypical Severe Combined Immunodeficiency (Atypical SCID); Combined immunodeficiency; Omenn syndrome; Severe combined immunodeficiency (SCID); IL-21R deficiency; Recurrent infections, Pneumocystis jiroveci, Cryptosporidium infections and liver disease; Immunodeficiencies affecting cellular and humoral immunity to Immunodeficiency 56, OMIM:615207
Retinal disorders v4.42 NRL Arina Puzriakova Phenotypes for gene: NRL were changed from Retinal degeneration, autosomal recessive, clumped pigment type (AR); Retinitis pigmentosa 27 (AD); Eye Disorders; Retinitis Pigmentosa, Dominant; Retinitis pigmentosa; Retinitis pigmentosa 27, 613750 to Retinal degeneration, autosomal recessive, clumped pigment type (AR); Retinitis pigmentosa 27, OMIM:613750
Structural eye disease v3.58 NRL Arina Puzriakova Phenotypes for gene: NRL were changed from Retinitis pigmentosa 27, 613750; Eye Disorders to Retinitis pigmentosa 27, OMIM:613750
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.24 ABHD5 Oliver Watkinson gene: ABHD5 was added
gene: ABHD5 was added to Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies. Sources: Literature
Mode of inheritance for gene: ABHD5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABHD5 were set to 33455044
Phenotypes for gene: ABHD5 were set to OMIM 604780 (Chanarin-Dorfman syndrome)
Penetrance for gene: ABHD5 were set to Complete
Review for gene: ABHD5 was set to GREEN
Added comment: Chanarin-Dorfman is a neutral lipid storage disorder. The review here summarises the world literature to date, with a good paragraph about myopathy towards the end of the discussion. The phenotype is quite variable, and can include multiple organ systems, but overall 59% of patients have high CK and muscle weakness. Skeletal muscle biopsy findings of lipid storage in this disorder are well described. Thus, this gene probably ought to be part of R381, and this seems like the best sub-panel to put it in, given that PNPLA2, a similar disorder, is also on this panel.
Sources: Literature
Cytopenia - NOT Fanconi anaemia v3.20 TUBA8 Hannah Knight gene: TUBA8 was added
gene: TUBA8 was added to Cytopenia - NOT Fanconi anaemia. Sources: Literature
Mode of inheritance for gene: TUBA8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBA8 were set to 34704371
Phenotypes for gene: TUBA8 were set to Macrothrombocytopenia, isolated, 2, autosomal dominant
Review for gene: TUBA8 was set to AMBER
Added comment: PMID: 34704371 (2022) identified rare variants in this gene in patients with macrothrombocytopenia. Associated with a phenotype on OMIM
Sources: Literature
Cytopenia - NOT Fanconi anaemia v3.20 TUBA4A Hannah Knight gene: TUBA4A was added
gene: TUBA4A was added to Cytopenia - NOT Fanconi anaemia. Sources: Literature
Mode of inheritance for gene: TUBA4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBA4A were set to 30760556
Phenotypes for gene: TUBA4A were set to Thrombocytopenia
Review for gene: TUBA4A was set to RED
Added comment: Linked to thrombocytopenia (PMID: 30760556, 2019) - only one patient reported
Sources: Literature
Early onset or syndromic epilepsy v4.129 PIGM Sarah Leigh Tag Q4_23_NHS_review was removed from gene: PIGM.
Early onset or syndromic epilepsy v4.129 PIGM Sarah Leigh changed review comment from: A single PIGM variant (NM_145167.2(PIGM):c.-270C>G)(rs587776528) has been associated with Glycosylphosphatidylinositol deficiency, (OMIM:610293) and as limited Gen2Phen gene for the same condition.
To date, this variant has only been reported in people of Arab or Turkish descent. Microsatellite- and SNP-based haplotypes encompassing PIGM reported in PMID:19168132, suggested that a founder effect in the two families (one Arab and one Turkish) was unlikely. However, subsequent occurrences of the variant in two additional unrelated Arab families (PMID: 31445883) might suggest that this variant is confined within the Middle Eastern populations.
Functional studies have shown that this variant reduces transcription of PIGM and blocks mannosylation of glycosylphosphatidylinositol anchor (PMID: 16767100).; to: A single PIGM variant (NM_145167.2(PIGM):c.-270C>G)(rs587776528) has been associated with Glycosylphosphatidylinositol deficiency, (OMIM:610293) and as limited Gen2Phen gene for the same condition.
To date, this variant has only been reported in people of Arab or Turkish descent. Microsatellite- and SNP-based haplotypes encompassing PIGM reported in PMID:19168132, suggested that a founder effect in the two families (one Arab and one Turkish) was unlikely. However, subsequent occurrences of the variant in two additional unrelated Arab families (PMID: 31445883) might suggest that this variant is confined within the Middle Eastern populations.
Functional studies have shown that this variant reduces transcription of PIGM and blocks mannosylation of glycosylphosphatidylinositol anchor (PMID: 16767100).
Absence seizures were apparent in 5/7 individuals from 5/6 families with OMIM:610293 biallelic for rs587776528 (table 1, PMID: 31445883).
Early onset or syndromic epilepsy v4.129 PIGM Sarah Leigh Entity copied from Likely inborn error of metabolism - targeted testing not possible v4.77
Early onset or syndromic epilepsy v4.129 PIGM Sarah Leigh gene: PIGM was added
gene: PIGM was added to Early onset or syndromic epilepsy. Sources: NHS GMS,Expert Review Amber,London North GLH
promoter, non-coding-known-pathogenic, Q4_23_promote_green, Q4_23_NHS_review tags were added to gene: PIGM.
Mode of inheritance for gene: PIGM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGM were set to 27604308; 16767100; 25293775; 17442906; 31445883
Phenotypes for gene: PIGM were set to Glycosylphosphatidylinositol deficiency, OMIM:610293
Undiagnosed metabolic disorders v1.607 PIGM Sarah Leigh Tag non-coding-known-pathogenic tag was added to gene: PIGM.
Likely inborn error of metabolism v4.77 PIGM Sarah Leigh Tag promoter tag was added to gene: PIGM.
Congenital disorders of glycosylation v4.13 PIGM Sarah Leigh Tag non-coding-known-pathogenic tag was added to gene: PIGM.
Tag Q4_23_promote_green tag was added to gene: PIGM.
Congenital disorders of glycosylation v4.13 PIGM Sarah Leigh changed review comment from: A single PIGM variant (NM_145167.2(PIGM):c.-270C>G) has been associated with Glycosylphosphatidylinositol deficiency, (OMIM:610293) and as limited Gen2Phen gene for the same condition.
To date, this variant has only been reported in people of Arab or Turkish descent. Microsatellite- and SNP-based haplotypes encompassing PIGM reported in PMID:19168132, suggested that a founder effect in the two families (one Arab and one Turkish) was unlikely. However, subsequent occurrences of the variant in two additional unrelated Arab families (PMID: 31445883) might suggest that this variant is confined within the Middle Eastern populations.
Functional studies have shown that this variant reduces transcription of PIGM and blocks mannosylation of glycosylphosphatidylinositol anchor (PMID: 16767100).; to: A single PIGM variant (NM_145167.2(PIGM):c.-270C>G)(rs587776528) has been associated with Glycosylphosphatidylinositol deficiency, (OMIM:610293) and as limited Gen2Phen gene for the same condition.
To date, this variant has only been reported in people of Arab or Turkish descent. Microsatellite- and SNP-based haplotypes encompassing PIGM reported in PMID:19168132, suggested that a founder effect in the two families (one Arab and one Turkish) was unlikely. However, subsequent occurrences of the variant in two additional unrelated Arab families (PMID: 31445883) might suggest that this variant is confined within the Middle Eastern populations.
Functional studies have shown that this variant reduces transcription of PIGM and blocks mannosylation of glycosylphosphatidylinositol anchor (PMID: 16767100).
Likely inborn error of metabolism v4.77 PIGM Sarah Leigh edited their review of gene: PIGM: Added comment: A single PIGM variant (NM_145167.2(PIGM):c.-270C>G)(rs587776528) has been associated with Glycosylphosphatidylinositol deficiency, (OMIM:610293) and as limited Gen2Phen gene for the same condition.
To date, this variant has only been reported in people of Arab or Turkish descent. Microsatellite- and SNP-based haplotypes encompassing PIGM reported in PMID:19168132, suggested that a founder effect in the two families (one Arab and one Turkish) was unlikely. However, subsequent occurrences of the variant in two additional unrelated Arab families (PMID: 31445883) might suggest that this variant is confined within the Middle Eastern populations.
Functional studies have shown that this variant reduces transcription of PIGM and blocks mannosylation of glycosylphosphatidylinositol anchor (PMID: 16767100).; Changed rating: GREEN
Undiagnosed metabolic disorders v1.607 PIGM Sarah Leigh changed review comment from: A single PIGM variant (NM_145167.2(PIGM):c.-270C>G) has been associated with Glycosylphosphatidylinositol deficiency, (OMIM:610293) and as limited Gen2Phen gene for the same condition.
To date, this variant has only been reported in people of Arab or Turkish descent. Microsatellite- and SNP-based haplotypes encompassing PIGM reported in PMID:19168132, suggested that a founder effect in the two families (one Arab and one Turkish) was unlikely. However, subsequent occurrences of the variant in two additional unrelated Arab families (PMID: 31445883) might suggest that this variant is confined within the Middle Eastern populations.
Functional studies have shown that this variant reduces transcription of PIGM and blocks mannosylation of glycosylphosphatidylinositol anchor (PMID: 16767100).; to: A single PIGM variant (NM_145167.2(PIGM):c.-270C>G)(rs587776528) has been associated with Glycosylphosphatidylinositol deficiency, (OMIM:610293) and as limited Gen2Phen gene for the same condition.
To date, this variant has only been reported in people of Arab or Turkish descent. Microsatellite- and SNP-based haplotypes encompassing PIGM reported in PMID:19168132, suggested that a founder effect in the two families (one Arab and one Turkish) was unlikely. However, subsequent occurrences of the variant in two additional unrelated Arab families (PMID: 31445883) might suggest that this variant is confined within the Middle Eastern populations.
Functional studies have shown that this variant reduces transcription of PIGM and blocks mannosylation of glycosylphosphatidylinositol anchor (PMID: 16767100).
Likely inborn error of metabolism v4.77 PIGM Sarah Leigh Tag non-coding-known-pathogenic tag was added to gene: PIGM.
Tag Q4_23_promote_green tag was added to gene: PIGM.
Tag Q4_23_NHS_review tag was added to gene: PIGM.
Undiagnosed metabolic disorders v1.607 PIGM Sarah Leigh Classified gene: PIGM as Green List (high evidence)
Undiagnosed metabolic disorders v1.607 PIGM Sarah Leigh Gene: pigm has been classified as Green List (High Evidence).
Congenital disorders of glycosylation v4.13 PIGM Sarah Leigh Classified gene: PIGM as Amber List (moderate evidence)
Congenital disorders of glycosylation v4.13 PIGM Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Congenital disorders of glycosylation v4.13 PIGM Sarah Leigh Gene: pigm has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v4.77 PIGM Sarah Leigh Classified gene: PIGM as Amber List (moderate evidence)
Likely inborn error of metabolism v4.77 PIGM Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Likely inborn error of metabolism v4.77 PIGM Sarah Leigh Gene: pigm has been classified as Amber List (Moderate Evidence).
Congenital disorders of glycosylation v4.12 PIGM Sarah Leigh edited their review of gene: PIGM: Added comment: A single PIGM variant (NM_145167.2(PIGM):c.-270C>G) has been associated with Glycosylphosphatidylinositol deficiency, (OMIM:610293) and as limited Gen2Phen gene for the same condition.
To date, this variant has only been reported in people of Arab or Turkish descent. Microsatellite- and SNP-based haplotypes encompassing PIGM reported in PMID:19168132, suggested that a founder effect in the two families (one Arab and one Turkish) was unlikely. However, subsequent occurrences of the variant in two additional unrelated Arab families (PMID: 31445883) might suggest that this variant is confined within the Middle Eastern populations.
Functional studies have shown that this variant reduces transcription of PIGM and blocks mannosylation of glycosylphosphatidylinositol anchor (PMID: 16767100).; Changed rating: GREEN
Undiagnosed metabolic disorders v1.606 PIGM Sarah Leigh edited their review of gene: PIGM: Added comment: A single PIGM variant (NM_145167.2(PIGM):c.-270C>G) has been associated with Glycosylphosphatidylinositol deficiency, (OMIM:610293) and as limited Gen2Phen gene for the same condition.
To date, this variant has only been reported in people of Arab or Turkish descent. Microsatellite- and SNP-based haplotypes encompassing PIGM reported in PMID:19168132, suggested that a founder effect in the two families (one Arab and one Turkish) was unlikely. However, subsequent occurrences of the variant in two additional unrelated Arab families (PMID: 31445883) might suggest that this variant is confined within the Middle Eastern populations.
Functional studies have shown that this variant reduces transcription of PIGM and blocks mannosylation of glycosylphosphatidylinositol anchor (PMID: 16767100).; Changed rating: GREEN
Congenital disorders of glycosylation v4.12 PIGM Sarah Leigh Publications for gene: PIGM were set to 27604308; 16767100; 25293775
Undiagnosed metabolic disorders v1.606 PIGM Sarah Leigh Publications for gene: PIGM were set to 27604308; 16767100; 25293775; 17442906
Congenital disorders of glycosylation v4.11 PIGM Sarah Leigh Added comment: Comment on phenotypes: Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency;Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation
Congenital disorders of glycosylation v4.11 PIGM Sarah Leigh Phenotypes for gene: PIGM were changed from Glycosylphosphatidylinositol deficiency, 610293; Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency; Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation to Glycosylphosphatidylinositol deficiency, OMIM:610293
Undiagnosed metabolic disorders v1.605 PIGM Sarah Leigh Phenotypes for gene: PIGM were changed from Glycosylphosphatidylinositol deficiency 610293 to Glycosylphosphatidylinositol deficiency, OMIM:610293
Likely inborn error of metabolism v4.76 PIGM Sarah Leigh Phenotypes for gene: PIGM were changed from Glycosylphosphatidylinositol deficiency 610293 to Glycosylphosphatidylinositol deficiency, OMIM:610293
Likely inborn error of metabolism v4.75 PIGM Sarah Leigh Publications for gene: PIGM were set to 27604308; 16767100; 25293775; 17442906
Ataxia and cerebellar anomalies - narrow panel v4.40 DLG4 Dmitrijs Rots gene: DLG4 was added
gene: DLG4 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: DLG4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DLG4 were set to PMID: 33597769
Phenotypes for gene: DLG4 were set to Intellectual developmental disorder, autosomal dominant 62
Penetrance for gene: DLG4 were set to Complete
Review for gene: DLG4 was set to GREEN
Added comment: PMID: 33597769 described a large cohort with DLG4-synaptopathy, where at least 19 individuals are with movement disorders, and 9 are with ataxia.
Sources: Literature
Adult onset neurodegenerative disorder v4.41 DAO Ivone Leong Tag refuted tag was added to gene: DAO.
Adult onset neurodegenerative disorder v4.41 DAO Ivone Leong Classified gene: DAO as Red List (low evidence)
Adult onset neurodegenerative disorder v4.41 DAO Ivone Leong Added comment: Comment on list classification: This gene has been demoted from Amber to Red. This gene has been refuted by ClinGen ALS spectrum disorders (https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_35ac00ac-3279-4c7e-89b6-8a75e3cae414-2022-04-12T103808.867Z?page=1&size=25&search=) (4/12/2022)
Adult onset neurodegenerative disorder v4.41 DAO Ivone Leong Gene: dao has been classified as Red List (Low Evidence).
Adult onset neurodegenerative disorder v4.40 DAO Ivone Leong Publications for gene: DAO were set to 29194436; 20368421
Rhabdomyolysis and metabolic muscle disorders v3.39 HADHB Dmitrijs Rots reviewed gene: HADHB: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35403730; Phenotypes: episodic myopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v4.113 HADHB Dmitrijs Rots reviewed gene: HADHB: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35403730; Phenotypes: episodic myopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v4.113 HADHB Dmitrijs Rots Deleted their review
Mitochondrial disorders v4.113 HADHB Dmitrijs Rots reviewed gene: HADHB: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 35403730; Phenotypes: episodic myopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.337 CASP2 Dmitrijs Rots reviewed gene: CASP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 37880421; Phenotypes: neurodevelopmental disorder with lissencephaly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dilated and arrhythmogenic cardiomyopathy v2.17 FKRP Oliver Watkinson reviewed gene: FKRP: Rating: GREEN; Mode of pathogenicity: None; Publications: 32914449, 19705481, 18060779, 15833432; Phenotypes: Dilated cardiomyopathy, Limb girdle muscular dystrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v3.57 GDF3 Sarah Leigh Tag Q4_23_demote_amber tag was added to gene: GDF3.
Tag Q4_23_expert_review tag was added to gene: GDF3.
Structural eye disease v3.57 GDF3 Sarah Leigh changed review comment from: A total of GDF3 variants have been reported in PMID: 19864492, 24281366 & 29260090 in patients with ocular phenotypes. It has been noted, that some of the variants have been found in gnomAD v4.0.0 at a high frequency and in unaffected relatives of the patients. A summary of the allele frequencies and other information is presented below.
NM_020634.3(GDF3):c.796C>T (p.Arg266Cys)
• rs140926412
• https://gnomad.broadinstitute.org/variant/12-7690177-G-A?dataset=gnomad_r4
• gnomAD v4.0.0 exomes & genomes: 4046/1614130 = allele frequency of 0.002507 which could be considered as scoring BS1 depending on the frequency of the disease
• PMID: 19864492; 29260090
NM_020634.3(GDF3):c.584G>A (p.Arg195Gln)
• rs146973734
• https://gnomad.broadinstitute.org/variant/12-7690389-C-T?dataset=gnomad_r4
• gnomAD v4.0.0 exomes & genomes: 239/1614062 = allele frequency 0.0001481 which could be considered as scoring PM2 depending on the frequency of the disease
• PMID: 19864492 one patient with Unilateral microphthalmia
NM_020634.3(GDF3):c.820C>T (p.Arg274Trp)
• rs387906946
• https://gnomad.broadinstitute.org/variant/12-7690153-G-A?dataset=gnomad_r4
• gnomAD v4.0.0 exomes & genomes: 156/1614148 = allele frequency 0.00009665 which could be considered as scoring PM2 depending on the frequency of the disease
• PMID: 19864492 one patient with Unilateral microphthalmia and coloboma
NM_020634.3(GDF3):c.914T>C (p.Leu305Pro)
• rs387906945
• https://gnomad.broadinstitute.org/variant/12-7690059-A-G?dataset=gnomad_r4
• gnomAD v4.0.0 exomes & genomes: 349/1614130 = allele frequency 0.0002162 which could be considered slightly too frequent to score PM2 depending on the frequency of the disease
• PMID: 19864492 three cases:
o 1 patient (2.1) with Unilateral microphthalmia and incomplete penetrance.
o 1 patient (2.2) unaffected father of 2.1
o 1 patient with Bilateral iris coloboma
NM_020634.3(GDF3):c.974C>T (p.Pro325Leu)
• rs566697767
• https://gnomad.broadinstitute.org/variant/12-7689999-G-A?dataset=gnomad_r4
• gnomAD v4.0.0 exomes & genomes: 77/1613890 = allele frequency 0.00004771 which could be considered as scoring PM2 depending on the frequency of the disease
• PMID: 24281366
o 1 patient 11 with microphthalmia and coloboma, also compound heterozygote for two missense mutations in CYP1B1, c.1103G>A, p.(Arg368His), and c.685G>A, p.(Glu229Lys), which is associated with ocular phenotypes (OMIM: 231300 & OMIM: 617315) and is Green on Structural eye disease panel
o 1 patient unaffected father of the patient above

As a result of this analysis, it seems unlikely that c.796C>T (p.Arg266Cys) is disease causing, due to its high frequency in gnomAD v4.0.0. The contribution of c.974C>T (p.Pro325Leu) to the disease is unknown, as it has only been seen in a patient who was also compound heterozygous for CYP1B1 variants. Plus, c.974C>T (p.Pro325Leu) was also seen in the unaffected father of the patient, as was c.914T>C (p.Leu305Pro); leading to the assertion that the effects of GDF3 variants of is subject to reduced penetrance. The variants c.584G>A (p.Arg195Gln) and c.820C>T (p.Arg274Trp) were found at low frequency in gnomAD v4.0.0. and there were no reports of unaffected carriers of these variants in the cited publications.; to: A total of five GDF3 variants have been reported in PMID: 19864492, 24281366 & 29260090 in patients with ocular phenotypes. It has been noted, that some of the variants have been found in gnomAD v4.0.0 at a high frequency and in unaffected relatives of the patients. A summary of the allele frequencies and other information is presented below.
NM_020634.3(GDF3):c.796C>T (p.Arg266Cys)
• rs140926412
• https://gnomad.broadinstitute.org/variant/12-7690177-G-A?dataset=gnomad_r4
• gnomAD v4.0.0 exomes & genomes: 4046/1614130 = allele frequency of 0.002507 which could be considered as scoring BS1 depending on the frequency of the disease
• PMID: 19864492; 29260090
NM_020634.3(GDF3):c.584G>A (p.Arg195Gln)
• rs146973734
• https://gnomad.broadinstitute.org/variant/12-7690389-C-T?dataset=gnomad_r4
• gnomAD v4.0.0 exomes & genomes: 239/1614062 = allele frequency 0.0001481 which could be considered as scoring PM2 depending on the frequency of the disease
• PMID: 19864492 one patient with Unilateral microphthalmia
NM_020634.3(GDF3):c.820C>T (p.Arg274Trp)
• rs387906946
• https://gnomad.broadinstitute.org/variant/12-7690153-G-A?dataset=gnomad_r4
• gnomAD v4.0.0 exomes & genomes: 156/1614148 = allele frequency 0.00009665 which could be considered as scoring PM2 depending on the frequency of the disease
• PMID: 19864492 one patient with Unilateral microphthalmia and coloboma
NM_020634.3(GDF3):c.914T>C (p.Leu305Pro)
• rs387906945
• https://gnomad.broadinstitute.org/variant/12-7690059-A-G?dataset=gnomad_r4
• gnomAD v4.0.0 exomes & genomes: 349/1614130 = allele frequency 0.0002162 which could be considered slightly too frequent to score PM2 depending on the frequency of the disease
• PMID: 19864492 three cases:
o 1 patient (2.1) with Unilateral microphthalmia and incomplete penetrance.
o 1 patient (2.2) unaffected father of 2.1
o 1 patient with Bilateral iris coloboma
NM_020634.3(GDF3):c.974C>T (p.Pro325Leu)
• rs566697767
• https://gnomad.broadinstitute.org/variant/12-7689999-G-A?dataset=gnomad_r4
• gnomAD v4.0.0 exomes & genomes: 77/1613890 = allele frequency 0.00004771 which could be considered as scoring PM2 depending on the frequency of the disease
• PMID: 24281366
o 1 patient 11 with microphthalmia and coloboma, also compound heterozygote for two missense mutations in CYP1B1, c.1103G>A, p.(Arg368His), and c.685G>A, p.(Glu229Lys), which is associated with ocular phenotypes (OMIM: 231300 & OMIM: 617315) and is Green on Structural eye disease panel
o 1 patient unaffected father of the patient above

As a result of this analysis, it seems unlikely that c.796C>T (p.Arg266Cys) is disease causing, due to its high frequency in gnomAD v4.0.0. The contribution of c.974C>T (p.Pro325Leu) to the disease is unknown, as it has only been seen in a patient who was also compound heterozygous for CYP1B1 variants. Plus, c.974C>T (p.Pro325Leu) was also seen in the unaffected father of the patient, as was c.914T>C (p.Leu305Pro); leading to the assertion that the effects of GDF3 variants of is subject to reduced penetrance. The variants c.584G>A (p.Arg195Gln) and c.820C>T (p.Arg274Trp) were found at low frequency in gnomAD v4.0.0. and there were no reports of unaffected carriers of these variants in the cited publications.
Structural eye disease v3.57 GDF3 Sarah Leigh changed review comment from: A total of GDF3 variants have been reported in PMID: 19864492, 24281366 & 29260090 in patients with ocular phenotypes. It has been noted, that some of the variants have been found in gnomAD v4.0.0 at a high frequency and in unaffected relatives of the patients. A summary of the allele frequencies and other information is presented below.
NM_020634.3(GDF3):c.796C>T (p.Arg266Cys)
• rs140926412
• https://gnomad.broadinstitute.org/variant/12-7690177-G-A?dataset=gnomad_r4
• gnomAD v4.0.0 exomes & genomes: 4046/1614130 = allele frequency of 0.002507 which could be considered as scoring BS1 depending on the frequency of the disease
• PMID: 19864492; 29260090
NM_020634.3(GDF3):c.584G>A (p.Arg195Gln)
• rs146973734
• https://gnomad.broadinstitute.org/variant/12-7690389-C-T?dataset=gnomad_r4
• gnomAD v4.0.0 exomes & genomes: 239/1614062 = allele frequency 0.0001481 which could be considered as scoring PM2 depending on the frequency of the disease
• PMID: 19864492 one patient with Unilateral microphthalmia
NM_020634.3(GDF3):c.820C>T (p.Arg274Trp)
• rs387906946
• https://gnomad.broadinstitute.org/variant/12-7690153-G-A?dataset=gnomad_r4
• gnomAD v4.0.0 exomes & genomes: 156/1614148 = allele frequency 0.00009665 which could be considered as scoring PM2 depending on the frequency of the disease
• PMID: 19864492 one patient with Unilateral microphthalmia and coloboma
NM_020634.3(GDF3):c.914T>C (p.Leu305Pro)
• rs387906945
• https://gnomad.broadinstitute.org/variant/12-7690059-A-G?dataset=gnomad_r4
• gnomAD v4.0.0 exomes & genomes: 349/1614130 = allele frequency 0.0002162 which could be considered slightly too frequent to score PM2 depending on the frequency of the disease
• PMID: 19864492 three cases:
o 1 patient (2.1) with Unilateral microphthalmia and incomplete penetrance.
o 1 patient (2.2) unaffected father of 2.1
o 1 patient with Bilateral iris coloboma
NM_020634.3(GDF3):c.974C>T (p.Pro325Leu)
• rs566697767
• https://gnomad.broadinstitute.org/variant/12-7689999-G-A?dataset=gnomad_r4
• gnomAD v4.0.0 exomes & genomes: 77/1613890 = allele frequency 0.00004771 which could be considered as scoring PM2 depending on the frequency of the disease
• PMID: 24281366
o 1 patient 11 with microphthalmia and coloboma, also compound heterozygote for two missense mutations in CYP1B1, c.1103G>A, p.(Arg368His), and c.685G>A, p.(Glu229Lys), which is associated with ocular phenotypes (OMIM: 231300 & OMIM: 617315) and is Green on Structural eye disease panel
o 1 patient unaffected father of the patient above

As a result of this analysis, it seems unlikely that c.796C>T (p.Arg266Cys) is disease causing, due to its high frequency in gnomAD v4.0.0. The contribution of c.974C>T (p.Pro325Leu) to the disease is unknown, as it has only been seen in a patient who was also compound heterozygous for CYP1B1 variants. Plus, c.974C>T (p.Pro325Leu) was also seen in the unaffected father of the patient, as was c.914T>C (p.Leu305Pro), leading to the assertion the effects of GDF3 variants of is subject to reduced penetrance. The variants c.584G>A (p.Arg195Gln) and c.820C>T (p.Arg274Trp) were found at low frequency in gnomAD v4.0.0. and there were no reports of unaffected carriers in these publications.; to: A total of GDF3 variants have been reported in PMID: 19864492, 24281366 & 29260090 in patients with ocular phenotypes. It has been noted, that some of the variants have been found in gnomAD v4.0.0 at a high frequency and in unaffected relatives of the patients. A summary of the allele frequencies and other information is presented below.
NM_020634.3(GDF3):c.796C>T (p.Arg266Cys)
• rs140926412
• https://gnomad.broadinstitute.org/variant/12-7690177-G-A?dataset=gnomad_r4
• gnomAD v4.0.0 exomes & genomes: 4046/1614130 = allele frequency of 0.002507 which could be considered as scoring BS1 depending on the frequency of the disease
• PMID: 19864492; 29260090
NM_020634.3(GDF3):c.584G>A (p.Arg195Gln)
• rs146973734
• https://gnomad.broadinstitute.org/variant/12-7690389-C-T?dataset=gnomad_r4
• gnomAD v4.0.0 exomes & genomes: 239/1614062 = allele frequency 0.0001481 which could be considered as scoring PM2 depending on the frequency of the disease
• PMID: 19864492 one patient with Unilateral microphthalmia
NM_020634.3(GDF3):c.820C>T (p.Arg274Trp)
• rs387906946
• https://gnomad.broadinstitute.org/variant/12-7690153-G-A?dataset=gnomad_r4
• gnomAD v4.0.0 exomes & genomes: 156/1614148 = allele frequency 0.00009665 which could be considered as scoring PM2 depending on the frequency of the disease
• PMID: 19864492 one patient with Unilateral microphthalmia and coloboma
NM_020634.3(GDF3):c.914T>C (p.Leu305Pro)
• rs387906945
• https://gnomad.broadinstitute.org/variant/12-7690059-A-G?dataset=gnomad_r4
• gnomAD v4.0.0 exomes & genomes: 349/1614130 = allele frequency 0.0002162 which could be considered slightly too frequent to score PM2 depending on the frequency of the disease
• PMID: 19864492 three cases:
o 1 patient (2.1) with Unilateral microphthalmia and incomplete penetrance.
o 1 patient (2.2) unaffected father of 2.1
o 1 patient with Bilateral iris coloboma
NM_020634.3(GDF3):c.974C>T (p.Pro325Leu)
• rs566697767
• https://gnomad.broadinstitute.org/variant/12-7689999-G-A?dataset=gnomad_r4
• gnomAD v4.0.0 exomes & genomes: 77/1613890 = allele frequency 0.00004771 which could be considered as scoring PM2 depending on the frequency of the disease
• PMID: 24281366
o 1 patient 11 with microphthalmia and coloboma, also compound heterozygote for two missense mutations in CYP1B1, c.1103G>A, p.(Arg368His), and c.685G>A, p.(Glu229Lys), which is associated with ocular phenotypes (OMIM: 231300 & OMIM: 617315) and is Green on Structural eye disease panel
o 1 patient unaffected father of the patient above

As a result of this analysis, it seems unlikely that c.796C>T (p.Arg266Cys) is disease causing, due to its high frequency in gnomAD v4.0.0. The contribution of c.974C>T (p.Pro325Leu) to the disease is unknown, as it has only been seen in a patient who was also compound heterozygous for CYP1B1 variants. Plus, c.974C>T (p.Pro325Leu) was also seen in the unaffected father of the patient, as was c.914T>C (p.Leu305Pro); leading to the assertion that the effects of GDF3 variants of is subject to reduced penetrance. The variants c.584G>A (p.Arg195Gln) and c.820C>T (p.Arg274Trp) were found at low frequency in gnomAD v4.0.0. and there were no reports of unaffected carriers of these variants in the cited publications.
Structural eye disease v3.57 GDF3 Sarah Leigh Deleted their comment
Structural eye disease v3.57 GDF3 Sarah Leigh edited their review of gene: GDF3: Added comment: A total of GDF3 variants have been reported in PMID: 19864492, 24281366 & 29260090 in patients with ocular phenotypes. It has been noted, that some of the variants have been found in gnomAD v4.0.0 at a high frequency and in unaffected relatives of the patients. A summary of the allele frequencies and other information is presented below.
NM_020634.3(GDF3):c.796C>T (p.Arg266Cys)
• rs140926412
• https://gnomad.broadinstitute.org/variant/12-7690177-G-A?dataset=gnomad_r4
• gnomAD v4.0.0 exomes & genomes: 4046/1614130 = allele frequency of 0.002507 which could be considered as scoring BS1 depending on the frequency of the disease
• PMID: 19864492; 29260090
NM_020634.3(GDF3):c.584G>A (p.Arg195Gln)
• rs146973734
• https://gnomad.broadinstitute.org/variant/12-7690389-C-T?dataset=gnomad_r4
• gnomAD v4.0.0 exomes & genomes: 239/1614062 = allele frequency 0.0001481 which could be considered as scoring PM2 depending on the frequency of the disease
• PMID: 19864492 one patient with Unilateral microphthalmia
NM_020634.3(GDF3):c.820C>T (p.Arg274Trp)
• rs387906946
• https://gnomad.broadinstitute.org/variant/12-7690153-G-A?dataset=gnomad_r4
• gnomAD v4.0.0 exomes & genomes: 156/1614148 = allele frequency 0.00009665 which could be considered as scoring PM2 depending on the frequency of the disease
• PMID: 19864492 one patient with Unilateral microphthalmia and coloboma
NM_020634.3(GDF3):c.914T>C (p.Leu305Pro)
• rs387906945
• https://gnomad.broadinstitute.org/variant/12-7690059-A-G?dataset=gnomad_r4
• gnomAD v4.0.0 exomes & genomes: 349/1614130 = allele frequency 0.0002162 which could be considered slightly too frequent to score PM2 depending on the frequency of the disease
• PMID: 19864492 three cases:
o 1 patient (2.1) with Unilateral microphthalmia and incomplete penetrance.
o 1 patient (2.2) unaffected father of 2.1
o 1 patient with Bilateral iris coloboma
NM_020634.3(GDF3):c.974C>T (p.Pro325Leu)
• rs566697767
• https://gnomad.broadinstitute.org/variant/12-7689999-G-A?dataset=gnomad_r4
• gnomAD v4.0.0 exomes & genomes: 77/1613890 = allele frequency 0.00004771 which could be considered as scoring PM2 depending on the frequency of the disease
• PMID: 24281366
o 1 patient 11 with microphthalmia and coloboma, also compound heterozygote for two missense mutations in CYP1B1, c.1103G>A, p.(Arg368His), and c.685G>A, p.(Glu229Lys), which is associated with ocular phenotypes (OMIM: 231300 & OMIM: 617315) and is Green on Structural eye disease panel
o 1 patient unaffected father of the patient above

As a result of this analysis, it seems unlikely that c.796C>T (p.Arg266Cys) is disease causing, due to its high frequency in gnomAD v4.0.0. The contribution of c.974C>T (p.Pro325Leu) to the disease is unknown, as it has only been seen in a patient who was also compound heterozygous for CYP1B1 variants. Plus, c.974C>T (p.Pro325Leu) was also seen in the unaffected father of the patient, as was c.914T>C (p.Leu305Pro), leading to the assertion the effects of GDF3 variants of is subject to reduced penetrance. The variants c.584G>A (p.Arg195Gln) and c.820C>T (p.Arg274Trp) were found at low frequency in gnomAD v4.0.0. and there were no reports of unaffected carriers in these publications.; Changed rating: AMBER
Hereditary neuropathy or pain disorder v3.65 SARS Achchuthan Shanmugasundram Classified gene: SARS as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v3.65 SARS Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of SARS1 gene in this panel in the next GMS review.
Hereditary neuropathy or pain disorder v3.65 SARS Achchuthan Shanmugasundram Gene: sars has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v3.64 SARS Achchuthan Shanmugasundram Phenotypes for gene: SARS were changed from CMTi to hereditary peripheral neuropathy, MONDO:0020127
Hereditary neuropathy or pain disorder v3.63 SARS Achchuthan Shanmugasundram Publications for gene: SARS were set to 37706277,36088542
Hereditary neuropathy or pain disorder v3.62 SARS Achchuthan Shanmugasundram Tag new-gene-name tag was added to gene: SARS.
Tag Q4_23_promote_green tag was added to gene: SARS.
Tag Q4_23_NHS_review tag was added to gene: SARS.
Hereditary neuropathy or pain disorder v3.62 SARS Achchuthan Shanmugasundram commented on gene: SARS: Added new-gene-name tag, new approved HGNC gene symbol for SARS is SARS1.
Hereditary neuropathy or pain disorder v3.62 SARS Achchuthan Shanmugasundram changed review comment from: PMID:36088542 - Two different heterozygous missense variants within the aminoacylation domain of SARS1 gene was identified in 16 affected individuals from three unrelated families with Charcot-Marie-Tooth (CMT) disease. The mutant SerRS proteins exhibited reduced aminoacylation activity and abnormal SerRS dimerization, which suggests the impairment of total protein synthesis and induction of eIF2α phosphorylation.

PMID:37706277 - A female patient with demyelinating CMT was identified with a heterozygous variant in SARS1 gene.


Biallelic variants in this gene have already been associated with relevant phenotypes in both OMIM (MIM #617709) and Gene2Phenotype, while monoallelic variants are associated with phenotype only in Gene2Phenotype (with 'limited' rating in the DD panel).; to: PMID:36088542 - Two different heterozygous missense variants within the aminoacylation domain of SARS1 gene was identified in 16 affected individuals from three unrelated families with Charcot-Marie-Tooth (CMT) disease. The mutant SerRS proteins exhibited reduced aminoacylation activity and abnormal SerRS dimerization, which suggests the impairment of total protein synthesis and induction of eIF2α phosphorylation.

PMID:37706277 - A female patient with demyelinating CMT was identified with a heterozygous variant in SARS1 gene.

Biallelic variants in this gene have already been associated with relevant phenotypes in both OMIM (MIM #617709) and Gene2Phenotype, while monoallelic variants are associated with phenotype only in Gene2Phenotype (with 'limited' rating in the DD panel).
Hereditary neuropathy or pain disorder v3.62 SARS Achchuthan Shanmugasundram reviewed gene: SARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 36088542, 37706277; Phenotypes: hereditary peripheral neuropathy, MONDO:0020127; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v3.57 GDF3 Sarah Leigh Publications for gene: GDF3 were set to 19864492; 29260090
Retinal disorders v4.41 VWA8 Hannah Knight gene: VWA8 was added
gene: VWA8 was added to Retinal disorders. Sources: Literature
Mode of inheritance for gene: VWA8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VWA8 were set to 37012052
Phenotypes for gene: VWA8 were set to ?Retinitis pigmentosa 97
Review for gene: VWA8 was set to AMBER
Added comment: PMID: 37012052 (2023) identified VWA8 as a novel cause of adRP in a four generation family with 11 affected family members.
6 of the affected members appear to have been tested and confirmed to carry the variant, while 5 unaffected members appear to have been confirmed NOT to
Sources: Literature
Congenital muscular dystrophy v4.15 GOLGA2 Hannah Knight reviewed gene: GOLGA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34424553; Phenotypes: Developmental delay with hypotonia, myopathy, and brain abnormalities; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v4.74 PIGM Hannah Knight reviewed gene: PIGM: Rating: GREEN; Mode of pathogenicity: None; Publications: 31445883; Phenotypes: Glycosylphosphatidylinositol deficiency 610293; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.24 POPDC3 Hannah Knight reviewed gene: POPDC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 35075722, 35842834, 37104941; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 26; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Possible mitochondrial disorder - nuclear genes v3.68 HSPA9 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: HSPA9.
Tag Q4_23_NHS_review tag was added to gene: HSPA9.
Possible mitochondrial disorder - nuclear genes v3.68 HSPA9 Achchuthan Shanmugasundram Classified gene: HSPA9 as Amber List (moderate evidence)
Possible mitochondrial disorder - nuclear genes v3.68 HSPA9 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of biallelic variants in HSPA9 gene to Even-plus syndrome. Hence, this gene should be promoted to green rating in the next GMS review.
Possible mitochondrial disorder - nuclear genes v3.68 HSPA9 Achchuthan Shanmugasundram Gene: hspa9 has been classified as Amber List (Moderate Evidence).
Possible mitochondrial disorder - nuclear genes v3.67 HSPA9 Achchuthan Shanmugasundram Mode of inheritance for gene: HSPA9 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Possible mitochondrial disorder - nuclear genes v3.66 HSPA9 Achchuthan Shanmugasundram Publications for gene: HSPA9 were set to 26598328; 32869452; 35779070; 36052765
Possible mitochondrial disorder - nuclear genes v3.65 HSPA9 Achchuthan Shanmugasundram changed review comment from: As reviewed by Hannah Knight, there are more than three unrelated cases identified with biallelic HSPA9 variants and reported with Even-plus syndrome (MIM #616854).

However, there are only two unrelated families identified with monoallelic HSPA9 variants and reported with sideroblastic anemia-4 (PMID:26491070).; to: As reviewed by Hannah Knight, there are more than three unrelated cases identified with biallelic HSPA9 variants and reported with Even-plus syndrome (MIM #616854).

However, there are only two unrelated families identified with monoallelic HSPA9 variants and reported with sideroblastic anemia-4 (MIM #182170) (PMID:26491070).
Possible mitochondrial disorder - nuclear genes v3.65 HSPA9 Achchuthan Shanmugasundram reviewed gene: HSPA9: Rating: GREEN; Mode of pathogenicity: None; Publications: 26491070, 26598328, 32869452, 35779070, 36052765; Phenotypes: Even-plus syndrome, OMIM:616854, Anemia, sideroblastic, 4, OMIM:182170; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Possible mitochondrial disorder - nuclear genes v3.65 HSPA9 Achchuthan Shanmugasundram Deleted their review
Likely inborn error of metabolism v4.74 HSPA9 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.; to: Comment on list classification: As reviewed by Hannah Knight, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.
Corneal dystrophy v3.9 LTBP2 Arina Puzriakova Classified gene: LTBP2 as Amber List (moderate evidence)
Corneal dystrophy v3.9 LTBP2 Arina Puzriakova Added comment: Comment on list classification: This gene could be promoted to Green at the next GMS panel update.
Corneal dystrophy v3.9 LTBP2 Arina Puzriakova Gene: ltbp2 has been classified as Amber List (Moderate Evidence).
Corneal dystrophy v3.8 LTBP2 Arina Puzriakova gene: LTBP2 was added
gene: LTBP2 was added to Corneal dystrophy. Sources: Literature
Q4_23_promote_green tags were added to gene: LTBP2.
Mode of inheritance for gene: LTBP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LTBP2 were set to 19656777; 19361779; 21081970; 20179738; 22539340; 20617341; 22025892
Phenotypes for gene: LTBP2 were set to Microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma, OMIM:251750; Glaucoma 3, primary congenital, D, OMIM:613086; Weill-Marchesani syndrome 3, recessive, OMIM:614819
Review for gene: LTBP2 was set to GREEN
Added comment: Variants in this gene are typically associated with ocular abnormalities, including microspherophakia, megalocornea, ectopia lentis and glaucoma. At least three unrelated individual cases have been associated with megalocornea. This gene was rated as green on the Corneal abnormalities 100K panel and is associated with a relevant phenotype in OMIM and Gene2Phenotype.
Sources: Literature
Intellectual disability v5.337 CLEC16A Dmitrijs Rots gene: CLEC16A was added
gene: CLEC16A was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: CLEC16A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLEC16A were set to PMID: 36538041
Phenotypes for gene: CLEC16A were set to severe neurodevelopmental disorder including microcephaly, brain atrophy, corpus callosum dysgenesis, and growth retardation
Penetrance for gene: CLEC16A were set to Complete
Review for gene: CLEC16A was set to GREEN
Added comment: Two independent cases reported PMID: 36538041with biallelic variants and functional evidence. Sufficient for the green rating.
Sources: Literature
Ehlers Danlos syndrome with a likely monogenic cause v3.9 LTBP2 Arina Puzriakova Publications for gene: LTBP2 were set to PMID: 20179738; PMID: 20617341
Monogenic diabetes v2.53 SMPD4 Dmitrijs Rots gene: SMPD4 was added
gene: SMPD4 was added to Monogenic diabetes. Sources: Literature
Mode of inheritance for gene: SMPD4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMPD4 were set to PMID: 36732302
Phenotypes for gene: SMPD4 were set to NDD, microcephaly and diabetes
Penetrance for gene: SMPD4 were set to Complete
Review for gene: SMPD4 was set to AMBER
Added comment: PMID: 36732302 reported three independent families with multiple affected individuals with biallelic SMPD4 variants with severe NDD and insulin-dependent diabetes. Given the syndromic presentation - not sure about the relevancy for the panel.
Sources: Literature
Ehlers Danlos syndrome with a likely monogenic cause v3.8 LTBP2 Arina Puzriakova Phenotypes for gene: LTBP2 were changed from Inreased arm-span-to-height ratio; Decreased upper-to-lower body ratio; Lens dislocation; Pectus excavatum; Myopia to Microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma, OMIM:251750; Glaucoma 3, primary congenital, D, OMIM:613086; Weill-Marchesani syndrome 3, recessive, OMIM:614819
Ehlers Danlos syndrome with a likely monogenic cause v3.7 LTBP2 Arina Puzriakova Tag Q4_23_promote_green tag was added to gene: LTBP2.
Ehlers Danlos syndrome with a likely monogenic cause v3.7 LTBP2 Arina Puzriakova Classified gene: LTBP2 as Amber List (moderate evidence)
Ehlers Danlos syndrome with a likely monogenic cause v3.7 LTBP2 Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Andžela Lazdāne. Variants are typically associated with ocular abnormalities, and in a subset of cases (>3) marfanoid features may be observed. Marfan syndrome is an important differential diagnosis for this panel and therefore this gene could be promoted to Green at the next GMS review.
Ehlers Danlos syndrome with a likely monogenic cause v3.7 LTBP2 Arina Puzriakova Gene: ltbp2 has been classified as Amber List (Moderate Evidence).
Possible mitochondrial disorder - nuclear genes v3.65 HSPA9 Achchuthan Shanmugasundram Publications for gene: HSPA9 were set to
Possible mitochondrial disorder - nuclear genes v3.64 HSPA9 Achchuthan Shanmugasundram Phenotypes for gene: HSPA9 were changed from Even-plus syndrome, 616854; Anemia, sideroblastic, 4, 182170; Also Parkinson disease association? to Even-plus syndrome, OMIM:616854; Anemia, sideroblastic, 4, OMIM:182170
Possible mitochondrial disorder - nuclear genes v3.63 HSPA9 Achchuthan Shanmugasundram reviewed gene: HSPA9: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Even-plus syndrome, OMIM:616854; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v4.74 HSPA9 Achchuthan Shanmugasundram Classified gene: HSPA9 as Amber List (moderate evidence)
Likely inborn error of metabolism v4.74 HSPA9 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.
Likely inborn error of metabolism v4.74 HSPA9 Achchuthan Shanmugasundram Gene: hspa9 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v4.73 HSPA9 Achchuthan Shanmugasundram Phenotypes for gene: HSPA9 were changed from Even-plus syndrome, OMIM:616854 to Even-plus syndrome, OMIM:616854
Likely inborn error of metabolism v4.72 HSPA9 Achchuthan Shanmugasundram Phenotypes for gene: HSPA9 were changed from Even-plus syndrome 616854 to Even-plus syndrome, OMIM:616854
Likely inborn error of metabolism v4.71 HSPA9 Achchuthan Shanmugasundram Publications for gene: HSPA9 were set to 26598328; 32869452; 35779070; 36052765
Likely inborn error of metabolism v4.71 HSPA9 Achchuthan Shanmugasundram Publications for gene: HSPA9 were set to 26598328; 32869452; 35779070; 36052765
Likely inborn error of metabolism v4.70 HSPA9 Achchuthan Shanmugasundram Publications for gene: HSPA9 were set to PMID: 26598328
Likely inborn error of metabolism v4.69 HSPA9 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: HSPA9.
Tag Q4_23_NHS_review tag was added to gene: HSPA9.
Likely inborn error of metabolism v4.69 HSPA9 Achchuthan Shanmugasundram reviewed gene: HSPA9: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Even-plus syndrome, OMIM:616854; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cytopenia - NOT Fanconi anaemia v3.20 SRPRA Achchuthan Shanmugasundram Classified gene: SRPRA as Amber List (moderate evidence)
Cytopenia - NOT Fanconi anaemia v3.20 SRPRA Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Hannah Knight, there is one case and functional studies (including zebrafish model) available in support of the association of this gene with severe congenital neutropenia. Hence, this gene can be rated amber with current evidence.
Cytopenia - NOT Fanconi anaemia v3.20 SRPRA Achchuthan Shanmugasundram Gene: srpra has been classified as Amber List (Moderate Evidence).
Cytopenia - NOT Fanconi anaemia v3.19 SRPRA Achchuthan Shanmugasundram Phenotypes for gene: SRPRA were changed from Severe congenital neutropenia to severe congenital neutropenia, MONDO:0018542
Cytopenia - NOT Fanconi anaemia v3.18 SRPRA Achchuthan Shanmugasundram reviewed gene: SRPRA: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: severe congenital neutropenia, MONDO:0018542; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cytopenia - NOT Fanconi anaemia v3.18 SRP19 Achchuthan Shanmugasundram Classified gene: SRP19 as Amber List (moderate evidence)
Cytopenia - NOT Fanconi anaemia v3.18 SRP19 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Hannah Knight, there are two related families with severe congenital neutropenia and functional studies in support of this association. Hence, this gene can be rated amber with current evidence.
Cytopenia - NOT Fanconi anaemia v3.18 SRP19 Achchuthan Shanmugasundram Gene: srp19 has been classified as Amber List (Moderate Evidence).
Cytopenia - NOT Fanconi anaemia v3.17 SRP19 Achchuthan Shanmugasundram Phenotypes for gene: SRP19 were changed from Severe congenital neutropenia to severe congenital neutropenia, MONDO:0018542
Cytopenia - NOT Fanconi anaemia v3.16 SRP19 Achchuthan Shanmugasundram reviewed gene: SRP19: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: severe congenital neutropenia, MONDO:0018542; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cytopenia - NOT Fanconi anaemia v3.16 SEC61A1 Achchuthan Shanmugasundram Publications for gene: SEC61A1 were set to 32325141; 27392076
Cytopenia - NOT Fanconi anaemia v3.15 SEC61A1 Achchuthan Shanmugasundram Phenotypes for gene: SEC61A1 were changed from Severe congenital neutropenia; Tubulointerstitial kidney disease, autosomal dominant, 5 to severe congenital neutropenia, MONDO:0018542; Tubulointerstitial kidney disease, autosomal dominant, 5, OMIM:617056
Cytopenia - NOT Fanconi anaemia v3.14 SEC61A1 Achchuthan Shanmugasundram Classified gene: SEC61A1 as Amber List (moderate evidence)
Cytopenia - NOT Fanconi anaemia v3.14 SEC61A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Hannah Knight, there are two unrelated cases reported with neutropenia. Hence, this gene can be rated amber with the current evidence.
Cytopenia - NOT Fanconi anaemia v3.14 SEC61A1 Achchuthan Shanmugasundram Gene: sec61a1 has been classified as Amber List (Moderate Evidence).
Cytopenia - NOT Fanconi anaemia v3.13 SEC61A1 Achchuthan Shanmugasundram reviewed gene: SEC61A1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: severe congenital neutropenia, MONDO:0018542, Tubulointerstitial kidney disease, autosomal dominant, 5, OMIM:617056; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypogonadotropic hypogonadism (GMS) v3.13 PROP1 Achchuthan Shanmugasundram Phenotypes for gene: PROP1 were changed from Combined Pituitary Hormone deficiency (OMIM 262600) to Pituitary hormone deficiency, combined, 2, OMIM:262600
Hypogonadotropic hypogonadism (GMS) v3.12 PROP1 Achchuthan Shanmugasundram Publications for gene: PROP1 were set to
Hypogonadotropic hypogonadism (GMS) v3.11 PROP1 Achchuthan Shanmugasundram Classified gene: PROP1 as Amber List (moderate evidence)
Hypogonadotropic hypogonadism (GMS) v3.11 PROP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.
Hypogonadotropic hypogonadism (GMS) v3.11 PROP1 Achchuthan Shanmugasundram Gene: prop1 has been classified as Amber List (Moderate Evidence).
Hypogonadotropic hypogonadism (GMS) v3.10 PROP1 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: PROP1.
Hypogonadotropic hypogonadism (GMS) v3.10 PROP1 Achchuthan Shanmugasundram reviewed gene: PROP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11549703, 15941866; Phenotypes: Pituitary hormone deficiency, combined, 2, OMIM:262600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.337 VCP Achchuthan Shanmugasundram Phenotypes for gene: VCP were changed from Neurodevelopmental disorder (MONDO: 0700092) to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.336 VCP Achchuthan Shanmugasundram edited their review of gene: VCP: Changed phenotypes to: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071
Intellectual disability v5.336 VCP Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: VCP.
Intellectual disability v5.336 VCP Achchuthan Shanmugasundram Classified gene: VCP as Amber List (moderate evidence)
Intellectual disability v5.336 VCP Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is sufficient evidence available for adding this gene with green rating in the next GMS update.
Intellectual disability v5.336 VCP Achchuthan Shanmugasundram Gene: vcp has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.335 VCP Achchuthan Shanmugasundram reviewed gene: VCP: Rating: GREEN; Mode of pathogenicity: None; Publications: 37883978; Phenotypes: Intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v3.62 SLC12A6 Christopher Record reviewed gene: SLC12A6: Rating: GREEN; Mode of pathogenicity: None; Publications: 27485015, 36542484, 35733399, 31439721, 33323309; Phenotypes: CMT1, CMT2, CMTi, dHMN; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v3.62 SARS Christopher Record gene: SARS was added
gene: SARS was added to Hereditary neuropathy or pain disorder. Sources: Expert Review
Mode of inheritance for gene: SARS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SARS were set to 37706277,36088542
Phenotypes for gene: SARS were set to CMTi
Penetrance for gene: SARS were set to Complete
Review for gene: SARS was set to GREEN
Added comment: Dominant or de novo dominant plausibly causing CMT in four unrelated families. Another amino-acyl tRNA synthetase causing CMT
Sources: Expert Review
Hypogonadotropic hypogonadism (GMS) v3.10 CUL4B Achchuthan Shanmugasundram Classified gene: CUL4B as Amber List (moderate evidence)
Hypogonadotropic hypogonadism (GMS) v3.10 CUL4B Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Hypogonadotropic hypogonadism (GMS) v3.10 CUL4B Achchuthan Shanmugasundram Gene: cul4b has been classified as Amber List (Moderate Evidence).
Hypogonadotropic hypogonadism (GMS) v3.9 CUL4B Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: CUL4B.
Hypogonadotropic hypogonadism (GMS) v3.9 CUL4B Achchuthan Shanmugasundram reviewed gene: CUL4B: Rating: GREEN; Mode of pathogenicity: None; Publications: 25385192; Phenotypes: Intellectual developmental disorder, X-linked syndromic, Cabezas type, OMIM:300354; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Congenital adrenal hypoplasia v3.9 KDM1A Lauma Freimane edited their review of gene: KDM1A: Changed publications to: 34906447, 34655521
Haematological malignancies cancer susceptibility v4.4 POT1 Lauma Freimane reviewed gene: POT1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Haematological malignancies cancer susceptibility v4.4 POT1 Lauma Freimane gene: POT1 was added
gene: POT1 was added to Haematological malignancies cancer susceptibility. Sources: Expert Review
Mode of inheritance for gene: POT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POT1 were set to PMID: 36467798; 30213928
Phenotypes for gene: POT1 were set to Multiple myeloma
Penetrance for gene: POT1 were set to unknown
gene: POT1 was marked as current diagnostic
Congenital adrenal hypoplasia v3.9 KDM1A Lauma Freimane gene: KDM1A was added
gene: KDM1A was added to Congenital adrenal hypoplasia. Sources: Expert Review
Mode of inheritance for gene: KDM1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KDM1A were set to 34906447
Phenotypes for gene: KDM1A were set to Food-dependent Cushing syndrome (FDCS)
Review for gene: KDM1A was set to GREEN
gene: KDM1A was marked as current diagnostic
Added comment: KDM1A inactivation explains about 90% of food-dependent Cushing syndrome observed in patients with primary bilateral macronodular adrenal hyperplasia (PBMAH) (PMID: 34906447).
Sources: Expert Review
Haematological malignancies cancer susceptibility v4.4 KDM1A Lauma Freimane gene: KDM1A was added
gene: KDM1A was added to Haematological malignancies cancer susceptibility. Sources: Expert list
Mode of inheritance for gene: KDM1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KDM1A were set to 29559475
Phenotypes for gene: KDM1A were set to Multiple myeloma
Review for gene: KDM1A was set to GREEN
gene: KDM1A was marked as current diagnostic
Added comment: KDM1A is the first autosomal dominant MM germline predisposition gene, providing new insights into its mechanistic roles as a tumor suppressor during post-germinal center B cell differentiation (PMID: 29559475).
Sources: Expert list
Cytopenia - NOT Fanconi anaemia v3.13 TCIRG1 Achchuthan Shanmugasundram Tag watchlist tag was added to gene: TCIRG1.
Cytopenia - NOT Fanconi anaemia v3.13 TCIRG1 Achchuthan Shanmugasundram Classified gene: TCIRG1 as Amber List (moderate evidence)
Cytopenia - NOT Fanconi anaemia v3.13 TCIRG1 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are three cases reported so far, only two of these cases were reported in peer-reviewed publications. Hence, this gene is currently rated amber. In addition, watchlist tag has been added.
Cytopenia - NOT Fanconi anaemia v3.13 TCIRG1 Achchuthan Shanmugasundram Gene: tcirg1 has been classified as Amber List (Moderate Evidence).
Cytopenia - NOT Fanconi anaemia v3.12 TCIRG1 Achchuthan Shanmugasundram Phenotypes for gene: TCIRG1 were changed from Congenital neutropenia to severe congenital neutropenia, MONDO:0018542
Cytopenia - NOT Fanconi anaemia v3.11 TCIRG1 Achchuthan Shanmugasundram Publications for gene: TCIRG1 were set to 24753205
Cytopenia - NOT Fanconi anaemia v3.10 TCIRG1 Achchuthan Shanmugasundram reviewed gene: TCIRG1: Rating: AMBER; Mode of pathogenicity: None; Publications: 24753205, 35573728; Phenotypes: severe congenital neutropenia, MONDO:0018542; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypertrophic cardiomyopathy v4.6 TULP3 Achchuthan Shanmugasundram Tag Q2_23_NHS_review tag was added to gene: TULP3.
Structural eye disease v3.56 GDF3 Sarah Leigh Deleted their comment
Structural eye disease v3.56 GDF3 Sarah Leigh Tag Q4_23_promote_green was removed from gene: GDF3.
Tag Q4_23_NHS_review was removed from gene: GDF3.
Mitochondrial disorders v4.113 ATP5B Sarah Leigh Classified gene: ATP5B as Amber List (moderate evidence)
Mitochondrial disorders v4.113 ATP5B Sarah Leigh Gene: atp5b has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v4.69 ATP5B Sarah Leigh Classified gene: ATP5B as Amber List (moderate evidence)
Likely inborn error of metabolism v4.69 ATP5B Sarah Leigh Gene: atp5b has been classified as Amber List (Moderate Evidence).
Possible mitochondrial disorder - nuclear genes v3.63 ATP5B Sarah Leigh reviewed gene: ATP5B: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Likely inborn error of metabolism v4.68 ATP5B Sarah Leigh reviewed gene: ATP5B: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mitochondrial disorders v4.112 ATP5B Sarah Leigh reviewed gene: ATP5B: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mitochondrial disorder with complex V deficiency v2.12 ATP5B Sarah Leigh reviewed gene: ATP5B: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Mitochondrial disorder with complex V deficiency v2.12 ATP5B Sarah Leigh Penetrance for gene ATP5B was set from to None
Mitochondrial disorders v4.112 ATP5B Sarah Leigh Penetrance for gene ATP5B was set from to Complete
Likely inborn error of metabolism v4.68 ATP5B Sarah Leigh Penetrance for gene ATP5B was set from to None
Possible mitochondrial disorder - nuclear genes v3.63 ATP5B Sarah Leigh Penetrance for gene ATP5B was set from to None
Likely inborn error of metabolism v4.67 ATP5B Sarah Leigh Mode of inheritance for gene: ATP5B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Possible mitochondrial disorder - nuclear genes v3.62 ATP5B Sarah Leigh Mode of inheritance for gene: ATP5B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mitochondrial disorders v4.111 ATP5B Sarah Leigh Mode of inheritance for gene: ATP5B was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mitochondrial disorder with complex V deficiency v2.11 ATP5B Sarah Leigh Mode of inheritance for gene: ATP5B was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Likely inborn error of metabolism v4.66 ATP5B Sarah Leigh Phenotypes for gene: ATP5B were changed from No OMIM phenotype to ?Hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation 2, OMIM: 620085
Possible mitochondrial disorder - nuclear genes v3.61 ATP5B Sarah Leigh Phenotypes for gene: ATP5B were changed from No OMIM phenotype to ?Hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation 2, OMIM: 620085
Mitochondrial disorders v4.110 ATP5B Sarah Leigh Phenotypes for gene: ATP5B were changed from No OMIM phenotype to ?Hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation 2, OMIM: 620085
Mitochondrial disorder with complex V deficiency v2.10 ATP5B Sarah Leigh Phenotypes for gene: ATP5B were changed from No OMIM phenotype to ?Hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation 2, OMIM: 620085
Mitochondrial disorders v4.109 ATP5B Sarah Leigh Publications for gene: ATP5B were set to
Mitochondrial disorder with complex V deficiency v2.9 ATP5B Sarah Leigh Publications for gene: ATP5B were set to
Likely inborn error of metabolism v4.65 ATP5B Sarah Leigh Publications for gene: ATP5B were set to
Possible mitochondrial disorder - nuclear genes v3.60 ATP5B Sarah Leigh Publications for gene: ATP5B were set to
Early onset or syndromic epilepsy v4.128 PTCD3 Sarah Leigh Entity copied from Likely inborn error of metabolism - targeted testing not possible v4.64
Early onset or syndromic epilepsy v4.128 PTCD3 Sarah Leigh gene: PTCD3 was added
gene: PTCD3 was added to Early onset or syndromic epilepsy. Sources: Expert list,Expert Review Amber
Q4_23_promote_green tags were added to gene: PTCD3.
Mode of inheritance for gene: PTCD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTCD3 were set to 30607703; 30706245; 36450274
Phenotypes for gene: PTCD3 were set to ?Combined oxidative phosphorylation deficiency 51, OMIM:619057; combined oxidative phosphorylation deficiency 51, MONDO:0033631
Likely inborn error of metabolism v4.64 PTCD3 Sarah Leigh Tag Q4_23_promote_green tag was added to gene: PTCD3.
Mitochondrial disorders v4.108 PTCD3 Sarah Leigh Tag Q4_23_promote_green tag was added to gene: PTCD3.
Mitochondrial disorders v4.108 PTCD3 Sarah Leigh edited their review of gene: PTCD3: Added comment: PTCD3 variants are associated with ?Combined oxidative phosphorylation deficiency 51 (OMIM:619057), but not associated with phenotype in Gen2Phen. At least six variants have been reported in three unrelated cases, with OMIM:619057 (PMID: 30607703; 36450274). Functional studies also support the involvement of PTCD3 variants in this condition (PMID: 30607703; 36450274).; Changed rating: GREEN
Likely inborn error of metabolism v4.64 PTCD3 Sarah Leigh edited their review of gene: PTCD3: Added comment: PTCD3 variants are associated with ?Combined oxidative phosphorylation deficiency 51 (OMIM:619057), but not associated with phenotype in Gen2Phen. At least six variants have been reported in three unrelated cases, with OMIM:619057 (PMID: 30607703; 36450274). Functional studies also support the involvement of PTCD3 variants in this condition (PMID: 30607703; 36450274).; Changed rating: GREEN
Mitochondrial disorders v4.108 PTCD3 Sarah Leigh Phenotypes for gene: PTCD3 were changed from ?Combined oxidative phosphorylation deficiency 51, OMIM:619057 to ?Combined oxidative phosphorylation deficiency 51, OMIM:619057; combined oxidative phosphorylation deficiency 51, MONDO:0033631
Likely inborn error of metabolism v4.64 PTCD3 Sarah Leigh Phenotypes for gene: PTCD3 were changed from ?Combined oxidative phosphorylation deficiency 51, OMIM:619057 to ?Combined oxidative phosphorylation deficiency 51, OMIM:619057; combined oxidative phosphorylation deficiency 51, MONDO:0033631
Possible mitochondrial disorder - nuclear genes v3.59 PTCD3 Sarah Leigh Phenotypes for gene: PTCD3 were changed from ?Combined oxidative phosphorylation deficiency 51, OMIM:619057 to ?Combined oxidative phosphorylation deficiency 51, OMIM:619057; combined oxidative phosphorylation deficiency 51, MONDO:0033631
Possible mitochondrial disorder - nuclear genes v3.58 PTCD3 Sarah Leigh Tag Q4_23_promote_green tag was added to gene: PTCD3.
Tag Q4_23_NHS_review tag was added to gene: PTCD3.
Possible mitochondrial disorder - nuclear genes v3.58 PTCD3 Sarah Leigh edited their review of gene: PTCD3: Added comment: PTCD3 variants are associated with ?Combined oxidative phosphorylation deficiency 51 (OMIM:619057), but not associated with phenotype in Gen2Phen. At least six variants have been reported in three unrelated cases, with OMIM:619057 (PMID: 30607703; 36450274). Functional studies also support the involvement of PTCD3 variants in this condition (PMID: 30607703; 36450274).; Changed rating: GREEN
Likely inborn error of metabolism v4.63 PTCD3 Sarah Leigh Classified gene: PTCD3 as Amber List (moderate evidence)
Likely inborn error of metabolism v4.63 PTCD3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Likely inborn error of metabolism v4.63 PTCD3 Sarah Leigh Gene: ptcd3 has been classified as Amber List (Moderate Evidence).
Possible mitochondrial disorder - nuclear genes v3.58 PTCD3 Sarah Leigh Classified gene: PTCD3 as Amber List (moderate evidence)
Possible mitochondrial disorder - nuclear genes v3.58 PTCD3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Possible mitochondrial disorder - nuclear genes v3.58 PTCD3 Sarah Leigh Gene: ptcd3 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v4.107 PTCD3 Sarah Leigh Classified gene: PTCD3 as Amber List (moderate evidence)
Mitochondrial disorders v4.107 PTCD3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Mitochondrial disorders v4.107 PTCD3 Sarah Leigh Gene: ptcd3 has been classified as Amber List (Moderate Evidence).
Retinal disorders v4.41 CFAP20 Ivone Leong Tag Q4_23_promote_green tag was added to gene: CFAP20.
Retinal disorders v4.41 CFAP20 Ivone Leong Classified gene: CFAP20 as Amber List (moderate evidence)
Retinal disorders v4.41 CFAP20 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. This gene has been given an Amber rating; however, this gene should be promoted to Green at the next GMS review.
Retinal disorders v4.41 CFAP20 Ivone Leong Gene: cfap20 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v4.106 PTCD3 Sarah Leigh Phenotypes for gene: PTCD3 were changed from No OMIM phenotype to ?Combined oxidative phosphorylation deficiency 51, OMIM:619057
Likely inborn error of metabolism v4.62 PTCD3 Sarah Leigh Phenotypes for gene: PTCD3 were changed from low birth weight, mental retardation, and optic atrophy to ?Combined oxidative phosphorylation deficiency 51, OMIM:619057
Possible mitochondrial disorder - nuclear genes v3.57 PTCD3 Sarah Leigh Phenotypes for gene: PTCD3 were changed from No OMIM phenotype to ?Combined oxidative phosphorylation deficiency 51, OMIM:619057
Mitochondrial disorders v4.105 PTCD3 Sarah Leigh Publications for gene: PTCD3 were set to 30607703
Likely inborn error of metabolism v4.61 PTCD3 Sarah Leigh Publications for gene: PTCD3 were set to 30607703; 30706245
Possible mitochondrial disorder - nuclear genes v3.56 PTCD3 Sarah Leigh Publications for gene: PTCD3 were set to 30607703; 36450274
Possible mitochondrial disorder - nuclear genes v3.55 PTCD3 Sarah Leigh Publications for gene: PTCD3 were set to 30607703
Likely inborn error of metabolism v4.60 MRM2 Sarah Leigh Publications for gene: MRM2 were set to 28973171
Mitochondrial disorders v4.104 MRM2 Sarah Leigh Publications for gene: MRM2 were set to 28973171
Hereditary neuropathy v1.472 VRK1 Dmitrijs Rots reviewed gene: VRK1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37257665; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v4.22 PTPRQ Arina Puzriakova Phenotypes for gene: PTPRQ were changed from Deafness, autosomal recessive 84A, 613391; Deafness,autosomalrecessive84A,613391 to Deafness, autosomal dominant 73, OMIM:617663; Deafness, autosomal recessive 84A, OMIM:613391
Monogenic hearing loss v4.21 PTPRQ Arina Puzriakova Added comment: Comment on publications: Previous publications listed: "PMID: 20346435 report a homozygous variant resulting in Tyr497Ter in 2 Dutch siblings with AR nonsyndromic hearing loss, and not found in matched controls. A homozygous variant resulting in Arg457Gly identified in 2 Moroccan siblings with AR nonsyndromic hearing loss, was also not found in matched controls."
Monogenic hearing loss v4.21 PTPRQ Arina Puzriakova Publications for gene: PTPRQ were set to PMID: 20346435 report a homozygous variant resulting in Tyr497Ter in 2 Dutch siblings with AR nonsyndromic hearing loss, and not found in matched controls. A homozygous variant resulting in Arg457Gly identified in 2 Moroccan siblings with AR nonsyndromic hearing loss, was also not found in matched controls.
Retinal disorders v4.40 RCBTB1 Arina Puzriakova Phenotypes for gene: RCBTB1 were changed from familial exudative vitreoretinopathy; Coats disease; Retinal dystrophy with or without extraocular anomalies, 617175 to Familial exudative vitreoretinopathy; Coats disease; Retinal dystrophy with or without extraocular anomalies, OMIM:617175
Retinal disorders v4.39 RP1L1 Arina Puzriakova Phenotypes for gene: RP1L1 were changed from Occult Macular Dystrophy; Occult macular dystrophy, 613587 to Occult macular dystrophy, OMIM:613587 (AD); Retinitis pigmentosa 88, OMIM:618826 (AR)
Likely inborn error of metabolism v4.59 MRM2 Sarah Leigh Tag Q4_23_promote_green tag was added to gene: MRM2.
Mitochondrial disorders v4.103 MRM2 Sarah Leigh Tag Q4_23_promote_green tag was added to gene: MRM2.
Possible mitochondrial disorder - nuclear genes v3.54 MRM2 Sarah Leigh Tag Q4_23_promote_green tag was added to gene: MRM2.
Tag Q4_23_NHS_review tag was added to gene: MRM2.
Palmoplantar keratodermas v3.17 SASH1 Arina Puzriakova Mode of inheritance for gene: SASH1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v4.59 MRM2 Sarah Leigh edited their review of gene: MRM2: Added comment: MRM2 variants have been associated with ?Mitochondrial DNA depletion syndrome 17 (OMIM:618567), but not associated with phenotype in Gen2Phen. To date three biallelic MRM2 variants have been reported three unrelated cases (PMID: 28973171;36002240), supportive yeast functional studies have also been presented (PMID: 36002240).; Changed rating: GREEN
Mitochondrial disorders v4.103 MRM2 Sarah Leigh edited their review of gene: MRM2: Added comment: MRM2 variants have been associated with ?Mitochondrial DNA depletion syndrome 17 (OMIM:618567), but not associated with phenotype in Gen2Phen. To date three biallelic MRM2 variants have been reported three unrelated cases (PMID: 28973171;36002240), supportive yeast functional studies have also been presented (PMID: 36002240).; Changed rating: GREEN
Intellectual disability v5.335 DPP6 Ivone Leong commented on gene: DPP6
Palmoplantar keratodermas v3.16 SASH1 Arina Puzriakova Phenotypes for gene: SASH1 were changed from Dyschromatosis (het); Pigmentation defects, palmoplantar keratoderma, spinocellular carcinoma (homo) to ?Cancer, alopecia, pigment dyscrasia, onychodystrophy, and keratoderma, OMIM:618373
Possible mitochondrial disorder - nuclear genes v3.54 MRM2 Sarah Leigh edited their review of gene: MRM2: Added comment: MRM2 variants have been associated with ?Mitochondrial DNA depletion syndrome 17 (OMIM:618567), but not associated with phenotype in Gen2Phen. To date three biallelic MRM2 variants have been reported three unrelated cases (PMID: 28973171;36002240), supportive yeast functional studies have also been presented (PMID: 36002240).; Changed rating: GREEN
Ichthyosis and erythrokeratoderma v3.19 SASH1 Arina Puzriakova Phenotypes for gene: SASH1 were changed from Pigmentation defects, palmoplantar keratoderma and skin carcinoma to ?Cancer, alopecia, pigment dyscrasia, onychodystrophy, and keratoderma, OMIM:618373
Palmoplantar keratoderma and erythrokeratodermas v1.29 SASH1 Arina Puzriakova Phenotypes for gene: SASH1 were changed from Pigmentation defects, palmoplantar keratoderma and skin carcinoma to ?Cancer, alopecia, pigment dyscrasia, onychodystrophy, and keratoderma, OMIM:618373
Intellectual disability v5.335 DPP6 Ivone Leong Tag Q4_23_demote_red tag was added to gene: DPP6.
Tag Q4_23_NHS_review tag was added to gene: DPP6.
Tag Q4_23_expert_review tag was added to gene: DPP6.
Pigmentary skin disorders v3.5 SASH1 Arina Puzriakova Phenotypes for gene: SASH1 were changed from Pigmentation defects, palmoplantar keratoderma, spinocellular carcinoma (homo); DYSCHROMATOSIS UNIVERSALIS HEREDITARIA 1; DUH1; Dyschromatosis (het) to Dyschromatosis universalis hereditaria 1, OMIM:127500 (AD); ?Cancer, alopecia, pigment dyscrasia, onychodystrophy, and keratoderma, OMIM:618373 (AR)
Pigmentary skin disorders v3.4 SASH1 Arina Puzriakova Tag watchlist_moi tag was added to gene: SASH1.
Likely inborn error of metabolism v4.59 MRM2 Sarah Leigh Classified gene: MRM2 as Amber List (moderate evidence)
Likely inborn error of metabolism v4.59 MRM2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Likely inborn error of metabolism v4.59 MRM2 Sarah Leigh Gene: mrm2 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v4.103 MRM2 Sarah Leigh Classified gene: MRM2 as Amber List (moderate evidence)
Mitochondrial disorders v4.103 MRM2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Mitochondrial disorders v4.103 MRM2 Sarah Leigh Gene: mrm2 has been classified as Amber List (Moderate Evidence).
Possible mitochondrial disorder - nuclear genes v3.54 MRM2 Sarah Leigh Classified gene: MRM2 as Amber List (moderate evidence)
Possible mitochondrial disorder - nuclear genes v3.54 MRM2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Possible mitochondrial disorder - nuclear genes v3.54 MRM2 Sarah Leigh Gene: mrm2 has been classified as Amber List (Moderate Evidence).
Congenital fibrosis of the extraocular muscles v1.16 MYF5 Ivone Leong Tag watchlist was removed from gene: MYF5.
Tag Q4_23_promote_green tag was added to gene: MYF5.
Tag Q4_23_NHS_review tag was added to gene: MYF5.
Congenital fibrosis of the extraocular muscles v1.16 MYF5 Ivone Leong commented on gene: MYF5: There is now enough evidence for this gene to be promoted to Green status. This gene should be promoted to Green at the next GMS review.
Possible mitochondrial disorder - nuclear genes v3.53 MRM2 Sarah Leigh Publications for gene: MRM2 were set to 28973171
Congenital fibrosis of the extraocular muscles v1.16 MYF5 Ivone Leong Publications for gene: MYF5 were set to 29887215
Bleeding and platelet disorders v3.7 BLOC1S5 Ivone Leong Tag Q4_23_promote_green tag was added to gene: BLOC1S5.
Tag Q4_23_NHS_review tag was added to gene: BLOC1S5.
Bleeding and platelet disorders v3.7 BLOC1S5 Ivone Leong commented on gene: BLOC1S5
Bleeding and platelet disorders v3.7 BLOC1S5 Ivone Leong Phenotypes for gene: BLOC1S5 were changed from Hermansky–Pudlak syndrome to Hermansky–Pudlak syndrome 11, OMIM:619172; Hermansky-Pudlak syndrome 11, MONDO:0030903
Bleeding and platelet disorders v3.6 BLOC1S5 Ivone Leong Publications for gene: BLOC1S5 were set to 32565547
Possible mitochondrial disorder - nuclear genes v3.52 ATP5E Sarah Leigh Publications for gene: ATP5E were set to 20566710; 25954304
Likely inborn error of metabolism v4.58 SEC23B Arina Puzriakova Tag Q4_23_MOI tag was added to gene: SEC23B.
Intellectual disability v5.335 SEC23B Arina Puzriakova Phenotypes for gene: SEC23B were changed from Dyserythropoietic anemia, congenital, type II, 224100 to Dyserythropoietic anemia, congenital, type II, OMIM:224100
Fetal anomalies v3.119 SEC23B Arina Puzriakova Phenotypes for gene: SEC23B were changed from ANEMIA, DYSERYTHROPOIETIC CONGENITAL, TYPE II to Dyserythropoietic anemia, congenital, type II, OMIM:224100
Rare anaemia v3.4 SEC23B Arina Puzriakova Phenotypes for gene: SEC23B were changed from 224100 ANEMIA, DYSERYTHROPOIETIC CONGENITAL, TYPE II; Congenital Dyserythropoietic Anemia; 224100 Congenital dyserythropoietic anaemia type 2; ANEMIA, DYSERYTHROPOIETIC CONGENITAL, TYPE II; Anemia, dyserythropoieticcongenital, type II, 224100; Congenital dyserythropoietic anemia type II to Dyserythropoietic anemia, congenital, type II, OMIM:224100
Likely inborn error of metabolism v4.58 SEC23B Arina Puzriakova Phenotypes for gene: SEC23B were changed from Dyserythropoietic anemia, congenital, type II 224100; COPII component SEC23B (Disorders of multiple glycosylation and other glycosylation pathways, V-ATPase deficiencies) to Dyserythropoietic anemia, congenital, type II, OMIM:224100; COPII component SEC23B (Disorders of multiple glycosylation and other glycosylation pathways, V-ATPase deficiencies)
Cytopenias and congenital anaemias v1.112 SEC23B Arina Puzriakova Phenotypes for gene: SEC23B were changed from Congenital dyserythropoietic anemia type II; Congenital Dyserythropoietic Anemia; Anemia, dyserythropoieticcongenital, type II, 224100; ANEMIA, DYSERYTHROPOIETIC CONGENITAL, TYPE II to Dyserythropoietic anemia, congenital, type II, OMIM:224100
Undiagnosed metabolic disorders v1.604 SEC23B Arina Puzriakova Phenotypes for gene: SEC23B were changed from COPII component SEC23B (Disorders of multiple glycosylation and other glycosylation pathways, V-ATPase deficiencies); Dyserythropoietic anemia, congenital, type II 224100 to Dyserythropoietic anemia, congenital, type II, OMIM:224100; COPII component SEC23B (Disorders of multiple glycosylation and other glycosylation pathways, V-ATPase deficiencies)
Congenital disorders of glycosylation v4.10 SEC23B Arina Puzriakova Phenotypes for gene: SEC23B were changed from Dyserythropoietic anemia, congenital, type II 224100; COPII component SEC23B (Disorders of multiple glycosylation and other glycosylation pathways, V-ATPase deficiencies) to Dyserythropoietic anemia, congenital, type II, OMIM:224100; COPII component SEC23B (Disorders of multiple glycosylation and other glycosylation pathways, V-ATPase deficiencies)
Inherited non-medullary thyroid cancer v1.7 SEC23B Arina Puzriakova Classified gene: SEC23B as Red List (low evidence)
Inherited non-medullary thyroid cancer v1.7 SEC23B Arina Puzriakova Added comment: Comment on list classification: There is limited evidence linking this gene with Cowden syndrome (monoallelic variants). Only one family has been reported to date (PMID:26522472). The other variant identified in 2 unrelated women discussed in previous reviews, has since been reclassified as a VUS.

This gene:disease association is provisional in OMIM, 'limited' disease confidence category in G2P and is not listed in ClinGen (whereas CDAII is).

On this basis, downgrading the rating of this gene from Green to Red.
Inherited non-medullary thyroid cancer v1.7 SEC23B Arina Puzriakova Gene: sec23b has been classified as Red List (Low Evidence).
Likely inborn error of metabolism v4.57 SEC23B Arina Puzriakova Added comment: Comment on mode of inheritance: There is limited evidence linking this gene with Cowden syndrome (monoallelic variants). Only one family has been reported to date (PMID:26522472). This gene:disease association is provisional in OMIM, 'limited' disease confidence category in G2P and is not listed in ClinGen (whereas CDAII is). Biallelic phenotype remains relevant to this panel (PMID: 35163229).

On this basis, the MOI should be updated from 'Both mono- and biallelic' to 'Biallelic' only at the next GMS panel update.
Likely inborn error of metabolism v4.57 SEC23B Arina Puzriakova Mode of inheritance for gene: SEC23B was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital disorders of glycosylation v4.9 SEC23B Arina Puzriakova Tag Q4_23_MOI tag was added to gene: SEC23B.
Undiagnosed metabolic disorders v1.603 SEC23B Arina Puzriakova Added comment: Comment on mode of inheritance: There is limited evidence linking this gene with Cowden syndrome (monoallelic variants). Only one family has been reported to date (PMID:26522472). This gene:disease association is provisional in OMIM, 'limited' disease confidence category in G2P and is not listed in ClinGen (whereas CDAII is). Biallelic phenotype remains relevant to this panel (PMID: 35163229).

On this basis, updating the MOI from 'Both mono- and biallelic' to 'Biallelic' only.
Undiagnosed metabolic disorders v1.603 SEC23B Arina Puzriakova Mode of inheritance for gene: SEC23B was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Congenital disorders of glycosylation v4.9 SEC23B Arina Puzriakova Added comment: Comment on mode of inheritance: There is limited evidence linking this gene with Cowden syndrome (monoallelic variants). Only one family has been reported to date (PMID:26522472). This gene:disease association is provisional in OMIM, 'limited' disease confidence category in G2P and is not listed in ClinGen (whereas CDAII is). Biallelic phenotype remains relevant to this panel (PMID: 35163229).

On this basis, the MOI should be updated from 'Both mono- and biallelic' to 'Biallelic' only at the next GMS panel update.
Congenital disorders of glycosylation v4.9 SEC23B Arina Puzriakova Mode of inheritance for gene: SEC23B was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Likely inborn error of metabolism v4.56 SEC23B Arina Puzriakova Publications for gene: SEC23B were set to 22208203
Undiagnosed metabolic disorders v1.602 SEC23B Arina Puzriakova Publications for gene: SEC23B were set to 27604308
Congenital disorders of glycosylation v4.8 SEC23B Arina Puzriakova Publications for gene: SEC23B were set to 22208203
Inherited non-medullary thyroid cancer v1.6 SEC23B Arina Puzriakova Phenotypes for gene: SEC23B were changed from Cowden syndrome 7 616858 to Cowden syndrome 7, OMIM:616858
Intellectual disability v5.334 RAP1B Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.334 RAP1B Achchuthan Shanmugasundram Classified gene: RAP1B as Amber List (moderate evidence)
Intellectual disability v5.334 RAP1B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Intellectual disability v5.334 RAP1B Achchuthan Shanmugasundram Gene: rap1b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.334 RAP1B Achchuthan Shanmugasundram Classified gene: RAP1B as Amber List (moderate evidence)
Intellectual disability v5.334 RAP1B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Intellectual disability v5.334 RAP1B Achchuthan Shanmugasundram Gene: rap1b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.333 RAP1B Achchuthan Shanmugasundram Publications for gene: RAP1B were set to 32627184; 26280580
Autoinflammatory disorders v1.8 SEC23B Arina Puzriakova Phenotypes for gene: SEC23B were changed from Dyserythropoietic anemia, congenital, type II to Dyserythropoietic anemia, congenital, type II, OMIM:224100
Intellectual disability v5.332 RAP1B Achchuthan Shanmugasundram Tag watchlist was removed from gene: RAP1B.
Tag Q4_23_promote_green tag was added to gene: RAP1B.
Autoinflammatory disorders v1.7 SEC23B Arina Puzriakova changed review comment from: Comment on list classification: New gene added to this panel by Lauma Freimane (Children's Clinical University Hospital). Biallelic variants are associated with congenital dyserythropoietic anemia (CDA) type II with multiple unrelated cases reported. These defective erythroblasts cannot develop into functional mature red blood cells. The resulting shortage of healthy red blood cells leads to the characteristic signs and symptoms of anemia, as well as complications including an enlarged liver and spleen (hepatosplenomegaly) and an abnormal buildup of iron that can damage the body's organs. Could not find evidence of an autoinflammatory component of this disorder and therefore rating as red on this panel.; to: Comment on list classification: New gene added to this panel by Lauma Freimane (Children's Clinical University Hospital). Biallelic variants are associated with congenital dyserythropoietic anemia (CDA) type II with multiple unrelated cases reported. These defective erythroblasts cannot develop into functional mature red blood cells. The resulting shortage of healthy red blood cells leads to the characteristic signs and symptoms of anemia, as well as complications including an enlarged liver and spleen (hepatosplenomegaly) and an abnormal buildup of iron that can damage the body's organs. Could not find strong evidence of an autoinflammatory component of this disorder and therefore rating as red on this panel.
Intellectual disability v5.332 RAP1B Achchuthan Shanmugasundram changed review comment from: PMID:35451551 - New patient reported with mild intellectual disability, bicuspid aortic valve, dilation of aortic root and ascending aorta, hearing loss, and long‐standing thrombocytopenia with lymphopenia. A novel, missense RAP1B variant (p.Ala59Gly) has been identified in this patient. This variant is on the neighbouring amino acid to one of the previously reported variants (p.Gly60Arg). This variant is confirmed de novo and not in gnomAD; to: PMID:35451551 - New patient reported with mild intellectual disability, bicuspid aortic valve, dilation of aortic root and ascending aorta, hearing loss, and long‐standing thrombocytopenia with lymphopenia. A novel, missense RAP1B variant (p.Ala59Gly) has been identified in this patient. This variant is on the neighbouring amino acid to one of the previously reported variants (p.Gly60Arg). This variant is confirmed de novo and not in gnomAD.

This gene has been associated with relevant phenotype in Gene2Phenotype database (with 'limited' rating in the DD panel), but not yet been associated with phenotypes in OMIM.
Intellectual disability v5.332 RAP1B Achchuthan Shanmugasundram reviewed gene: RAP1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 35451551; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autoinflammatory disorders v1.7 SEC23B Arina Puzriakova Classified gene: SEC23B as Red List (low evidence)
Autoinflammatory disorders v1.7 SEC23B Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Lauma Freimane (Children's Clinical University Hospital). Biallelic variants are associated with congenital dyserythropoietic anemia (CDA) type II with multiple unrelated cases reported. These defective erythroblasts cannot develop into functional mature red blood cells. The resulting shortage of healthy red blood cells leads to the characteristic signs and symptoms of anemia, as well as complications including an enlarged liver and spleen (hepatosplenomegaly) and an abnormal buildup of iron that can damage the body's organs. Could not find evidence of an autoinflammatory component of this disorder and therefore rating as red on this panel.
Autoinflammatory disorders v1.7 SEC23B Arina Puzriakova Gene: sec23b has been classified as Red List (Low Evidence).
Autoinflammatory disorders v1.6 PRF1 Arina Puzriakova Publications for gene: PRF1 were set to 32098966
Autoinflammatory disorders v1.5 PRF1 Arina Puzriakova Classified gene: PRF1 as Amber List (moderate evidence)
Autoinflammatory disorders v1.5 PRF1 Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Lauma Freimane (Children's Clinical University Hospital). Biallelic variants are associated with
Hemophagocytic Lymphohistiocytosis (HLH) with multiple unrelated cases reported. This is a hyperinflammatory disorder which leads to to impaired function of cytotoxic T cells and NK cells, consistent with a defect in cellular cytotoxicity. Acquired HLH can be caused by autoinflammatory and autoimmune diseases; however, familial HLH caused by biallelic variants in this gene do not necessarily cause autoinflammation.

For this reason, rating this gene:disease association as amber on this panel. Cases should be picked up via the 'R15 Primary immunodeficiency or monogenic inflammatory bowel disease' panel, where it is already green.
Autoinflammatory disorders v1.5 PRF1 Arina Puzriakova Gene: prf1 has been classified as Amber List (Moderate Evidence).
Cytopenia - NOT Fanconi anaemia v3.10 RAP1B Achchuthan Shanmugasundram Tag watchlist was removed from gene: RAP1B.
Tag Q4_23_promote_green tag was added to gene: RAP1B.
Tag Q4_23_NHS_review tag was added to gene: RAP1B.
Cytopenia - NOT Fanconi anaemia v3.10 RAP1B Achchuthan Shanmugasundram Classified gene: RAP1B as Amber List (moderate evidence)
Cytopenia - NOT Fanconi anaemia v3.10 RAP1B Achchuthan Shanmugasundram Added comment: Comment on list classification: There are three unrelated cases with cytopenia and hence this gene can be promoted to green rating in the next GMS review.

This gene has been associated with relevant phenotype in Gene2Phenotype database (with 'limited' rating in the DD panel), but not yet been associated with phenotypes in OMIM.
Cytopenia - NOT Fanconi anaemia v3.10 RAP1B Achchuthan Shanmugasundram Gene: rap1b has been classified as Amber List (Moderate Evidence).
Cytopenia - NOT Fanconi anaemia v3.9 RAP1B Achchuthan Shanmugasundram Publications for gene: RAP1B were set to 32627184; 26280580
Cytopenia - NOT Fanconi anaemia v3.8 RAP1B Achchuthan Shanmugasundram Mode of inheritance for gene: RAP1B was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cytopenia - NOT Fanconi anaemia v3.7 RAP1B Achchuthan Shanmugasundram reviewed gene: RAP1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 32627184, 35451551; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Haemophagocytic syndrome with absent perforin expression v1.2 PRF1 Arina Puzriakova Phenotypes for gene: PRF1 were changed from to Hemophagocytic lymphohistiocytosis, familial, 2, OMIM:603553
Autoinflammatory disorders v1.4 PRF1 Arina Puzriakova Phenotypes for gene: PRF1 were changed from Familial hemophagocytic lymphohistiocytosis-2 (FHL2) (OMIM: 603553) to Hemophagocytic lymphohistiocytosis, familial, 2, OMIM:603553
Primary immunodeficiency or monogenic inflammatory bowel disease v4.122 PRF1 Arina Puzriakova Phenotypes for gene: PRF1 were changed from Hemophagocytic lymphohistiocytosis, familial 2, 603553; FHL2; Familial hemophagocytic lymphohistiocytosis syndromes (FHLH); HPLH2; HLH2; Fever, HSM, Hemophagocytic lymphohistiocytosis (HLH), cytopenias; Diseases of Immune Dysregulation to Hemophagocytic lymphohistiocytosis, familial, 2, OMIM:603553
Fetal anomalies v3.118 ESAM Achchuthan Shanmugasundram Phenotypes for gene: ESAM were changed from intracranial hemorrhage; cerebral anomalies to Neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity, OMIM:620371
Fetal anomalies v3.117 ESAM Achchuthan Shanmugasundram Publications for gene: ESAM were set to PMID: 36996813
Fetal anomalies v3.116 ESAM Achchuthan Shanmugasundram Classified gene: ESAM as Amber List (moderate evidence)
Fetal anomalies v3.116 ESAM Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Julia Baptista, PMID:36996813 reported foetal intracranial hemorrhage in four foetuses from three unrelated families. Hence, there is sufficient evidence for this gene to be promoted to green rating in this panel in the next GMS review.
Fetal anomalies v3.116 ESAM Achchuthan Shanmugasundram Gene: esam has been classified as Amber List (Moderate Evidence).
Fetal anomalies v3.115 ESAM Achchuthan Shanmugasundram Tag Q4_23_expert_review tag was added to gene: ESAM.
Fetal anomalies v3.115 ESAM Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: ESAM.
Fetal anomalies v3.115 ESAM Achchuthan Shanmugasundram reviewed gene: ESAM: Rating: GREEN; Mode of pathogenicity: None; Publications: 36996813; Phenotypes: Neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity, OMIM:620371; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ectodermal dysplasia v3.22 KRT83 Arina Puzriakova Tag watchlist tag was added to gene: KRT83.
Ectodermal dysplasia v3.22 KRT83 Arina Puzriakova Classified gene: KRT83 as Amber List (moderate evidence)
Ectodermal dysplasia v3.22 KRT83 Arina Puzriakova Added comment: Comment on list classification: KRT81 is associated with two relevant phenotypes in OMIM (MIM# 158000) and G2P with a 'definitive' disease confidence classification for monilethrix. Monoallelic variant have been linked to monilethrix in two families (PMID: 15744029; 25557232) while biallelic variants were found in one family with EKVP5 (PMID: 27965375).

Overall no additional evidence has been published since the last review and therefore going to maintain the amber rating for now, but adding a 'watchlist' tag to monitor for additional evidence that may lead to future upgrade to green.

Other keratin genes, like KRT81 and KRT86 have been added as amber with the recommendation of being made green at the next review.
Ectodermal dysplasia v3.22 KRT83 Arina Puzriakova Gene: krt83 has been classified as Amber List (Moderate Evidence).
Ectodermal dysplasia v3.21 KRT86 Arina Puzriakova Publications for gene: KRT86 were set to 10469314; 10594761; 10504448; 12653715; 10878478; 25557232
Ectodermal dysplasia v3.20 KRT81 Arina Puzriakova Tag Q4_23_promote_green tag was added to gene: KRT81.
Tag Q4_23_NHS_review tag was added to gene: KRT81.
Ectodermal dysplasia v3.20 KRT81 Arina Puzriakova Publications for gene: KRT81 were set to
Inherited phaeochromocytoma and paraganglioma excluding NF1 v2.6 DLST Ivone Leong Tag Q4_23_demote_red tag was added to gene: DLST.
Ectodermal dysplasia v3.19 KRT81 Arina Puzriakova Classified gene: KRT81 as Amber List (moderate evidence)
Ectodermal dysplasia v3.19 KRT81 Arina Puzriakova Added comment: Comment on list classification: KRT81 is associated with a relevant phenotype in OMIM (MIM# 158000) and G2P with a 'definitive' disease confidence classification. Monoallelic variant have been linked to monilethrix. In addition to the two families previously discussed (PMID: 9665406; 9402962), there are an additional three unrelated cases reported in the literature (PMID: 10504448; 14714571; 25557232), particularly for recurrent variants at p.Glu413. KRT81 variants have been found in unaffected family members, suggesting reduced penetrance.
Overall there are sufficient cases to support an association with monilethrix, and therefore this gene can be promoted to Green at the next GMS panel update.
Ectodermal dysplasia v3.19 KRT81 Arina Puzriakova Gene: krt81 has been classified as Amber List (Moderate Evidence).
Inherited phaeochromocytoma and paraganglioma excluding NF1 v2.6 MDH2 Ivone Leong Tag Q4_23_demote_red tag was added to gene: MDH2.
Inherited phaeochromocytoma and paraganglioma excluding NF1 v2.6 SLC25A11 Ivone Leong Tag Q4_23_demote_red tag was added to gene: SLC25A11.
Inherited phaeochromocytoma and paraganglioma excluding NF1 v2.6 DLST Ivone Leong commented on gene: DLST: This gene has been tagged for additional expert review due to conflicting reviews. The gene rating will remain Green pending the results of the expert review.
Inherited phaeochromocytoma and paraganglioma excluding NF1 v2.6 DLST Ivone Leong Tag Q4_23_NHS_review tag was added to gene: DLST.
Tag Q4_23_expert_review tag was added to gene: DLST.
Inherited phaeochromocytoma and paraganglioma excluding NF1 v2.6 MDH2 Ivone Leong Tag Q4_23_NHS_review tag was added to gene: MDH2.
Tag Q4_23_expert_review tag was added to gene: MDH2.
Inherited phaeochromocytoma and paraganglioma excluding NF1 v2.6 MDH2 Ivone Leong commented on gene: MDH2: This gene has been tagged for additional expert review due to conflicting reviews. The gene rating will remain Green pending the results of the expert review.
Inherited phaeochromocytoma and paraganglioma excluding NF1 v2.6 SLC25A11 Ivone Leong commented on gene: SLC25A11: This gene has been tagged for additional expert review due to conflicting reviews. The gene rating will remain Green pending the results of the expert review.
Inherited phaeochromocytoma and paraganglioma excluding NF1 v2.6 SLC25A11 Ivone Leong Tag Q4_23_NHS_review tag was added to gene: SLC25A11.
Tag Q4_23_expert_review tag was added to gene: SLC25A11.
Inherited phaeochromocytoma and paraganglioma excluding NF1 v2.6 DLST Ivone Leong Phenotypes for gene: DLST were changed from Paragangliomas 7, OMIM:618475 to Paragangliomas 7, OMIM:618475; Paragangliomas 7, MONDO:0032771
Inherited phaeochromocytoma and paraganglioma excluding NF1 v2.5 MDH2 Ivone Leong Phenotypes for gene: MDH2 were changed from PPGL to PPGL; pheochromocytoma-paraganglioma, MONDO:0035540
Inherited phaeochromocytoma and paraganglioma excluding NF1 v2.4 SLC25A11 Ivone Leong Phenotypes for gene: SLC25A11 were changed from Paragangliomas 6, OMIM:618464 to Paragangliomas 6, OMIM:618464; Paragangliomas 6, MONDO:0032767
Optic neuropathy v4.16 MCAT Ivone Leong Phenotypes for gene: MCAT were changed from progressive autosomal recessive optic neuropathy to progressive autosomal recessive optic neuropathy; Hereditary optic neuropathy, MONDO:0020249
Optic neuropathy v4.15 MCAT Ivone Leong Publications for gene: MCAT were set to 31915829
Optic neuropathy v4.14 MCAT Ivone Leong Classified gene: MCAT as Amber List (moderate evidence)
Optic neuropathy v4.14 MCAT Ivone Leong Added comment: Comment on list classification: Promoted from Red to Amber, based on new evidence of a second case (PMID:33918393).
Optic neuropathy v4.14 MCAT Ivone Leong Gene: mcat has been classified as Amber List (Moderate Evidence).
Ectodermal dysplasia v3.18 KRT86 Arina Puzriakova Publications for gene: KRT86 were set to PMID: 10469314; 10594761; 10504448; 12653715
Ectodermal dysplasia v3.17 KRT86 Arina Puzriakova Classified gene: KRT86 as Amber List (moderate evidence)
Ectodermal dysplasia v3.17 KRT86 Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Ronnie Wright (NWGLH). KRT86 is associated with a relevant phenotype in OMIM (MIM# 158000) and G2P with a 'definitive' disease confidence classification. Monoallelic variant have been linked to monilethrix and multiple (>3) families have been reported in the literature. Overall there is enough evidence to promote this gene to Green at the next GMS panel update.
Ectodermal dysplasia v3.17 KRT86 Arina Puzriakova Gene: krt86 has been classified as Amber List (Moderate Evidence).
Ectodermal dysplasia v3.16 KRT86 Arina Puzriakova Tag Q4_23_promote_green tag was added to gene: KRT86.
Tag Q4_23_NHS_review tag was added to gene: KRT86.
Ectodermal dysplasia v3.16 KRT83 Arina Puzriakova Phenotypes for gene: KRT83 were changed from to Monilethrix, OMIM:158000
Ectodermal dysplasia v3.15 KRT81 Arina Puzriakova Phenotypes for gene: KRT81 were changed from to Monilethrix, OMIM:158000
Ectodermal dysplasia v3.14 KRT86 Arina Puzriakova Phenotypes for gene: KRT86 were changed from Monilethrix to Monilethrix, OMIM:158000
Thoracic aortic aneurysm or dissection (GMS) v3.7 PMEPA1 Ivone Leong Phenotypes for gene: PMEPA1 were changed from thoracic aortic aneurysm; tall stature; dolichocephaly; abnormal axial skeletal morphology; pes planus to thoracic aortic aneurysm, MONDO:0005396; tall stature; dolichocephaly; abnormal axial skeletal morphology; pes planus; Loeys-Dietz syndrome, MONDO:0018954
Thoracic aortic aneurysm or dissection (GMS) v3.6 PMEPA1 Ivone Leong Tag Q4_23_promote_green tag was added to gene: PMEPA1.
Tag Q4_23_NHS_review tag was added to gene: PMEPA1.
Thoracic aortic aneurysm or dissection (GMS) v3.6 PMEPA1 Ivone Leong Classified gene: PMEPA1 as Amber List (moderate evidence)
Thoracic aortic aneurysm or dissection (GMS) v3.6 PMEPA1 Ivone Leong Added comment: Comment on list classification: New gene submitted by Andrew Mumford (University of Bristol). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. PMID: 36928819 describes 8 families with truncating variants affecting the same polycytosine area in this gene. In the 100KGP cohort, three families of European ancestry with FTAAD have the same variant. This same variant was identified independently in 3 families of Japanese ancestry in a separate Japanese patient group. A second variant in the same polycycstine stretch was identified in a different FTAAD case enrolled in the 100KGP pilot programme. A third variant (5 bp deletion in the same stretch which caused a frameshift mutation) was identified in a family in Belgium.

"All pedigrees exhibited dominant inheritance of aortic aneurysm disease with incomplete penetrance and skeletal features including pectus deformity, scoliosis and arachnodactyly with complete penetrance". The authors found four HPO terms related to the musculoskeletal system were significantly enriched, which suggested the phenotypic characteristics of the syndromic aortopathy Loeys–Dietz syndrome.

Based on the above evidence this gene has been given an Amber gene rating and should be promoted to Green at the next GMS review.
Thoracic aortic aneurysm or dissection (GMS) v3.6 PMEPA1 Ivone Leong Gene: pmepa1 has been classified as Amber List (Moderate Evidence).
Thoracic aortic aneurysm or dissection (GMS) v3.5 PMEPA1 Ivone Leong Publications for gene: PMEPA1 were set to PMID:36928819
Primary lymphoedema v3.9 ERG Ivone Leong Phenotypes for gene: ERG were changed from primary lymphoedema to primary lymphoedema, MONDO:0019175
Primary lymphoedema v3.8 ERG Ivone Leong Tag Q4_23_promote_green tag was added to gene: ERG.
Tag Q4_23_NHS_review tag was added to gene: ERG.
Primary lymphoedema v3.8 ERG Ivone Leong Classified gene: ERG as Amber List (moderate evidence)
Primary lymphoedema v3.8 ERG Ivone Leong Added comment: Comment on list classification: New gene submitted by Andrew Mumford (University of Bristol). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. PMID: 36928819 describes 3 families with frameshift variants (2 nonsense-mediated decay variants and 1 protein truncating variant). There is also a fourth family with a protein truncating variant; however, there are other clinical features and lymphoedema was only identified during chart review. Over expression of mutant cDNA caused mislocalisation of ERG in the cytoplasm, preventing it from binding to DNA and functioning as a transcription factor.

Based on the above evidence this gene has been given an Amber gene rating and should be promoted to Green at the next GMS review.
Primary lymphoedema v3.8 ERG Ivone Leong Gene: erg has been classified as Amber List (Moderate Evidence).
Primary lymphoedema v3.7 ERG Ivone Leong Publications for gene: ERG were set to
Intellectual disability v5.332 DPP6 Gavin Ryan reviewed gene: DPP6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v3.56 GDF3 Zornitza Stark changed review comment from: p.Arg266Cys is present in >4,000 individuals in gnomad v4, casting serious doubts about pathogenicity.; to: p.Arg266Cys is present in >4,000 individuals in gnomad v4, casting serious doubts about pathogenicity.

p.Arg195Gln is present in 239 individuals which is also very high even for 'variable penetrance'.

p.Arg274Trp is present in 156.

p.Leu305Pro in 349. Also classified 'benign' in ClinVar.

p.Pro325Leu in 77.
Structural eye disease v3.56 GDF3 Zornitza Stark reviewed gene: GDF3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Malformations of cortical development v4.10 CASP2 Zornitza Stark gene: CASP2 was added
gene: CASP2 was added to Malformations of cortical development. Sources: Literature
Mode of inheritance for gene: CASP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CASP2 were set to 37880421
Phenotypes for gene: CASP2 were set to neurodevelopmental disorder MONDO:0700092, CASP2-related
Review for gene: CASP2 was set to GREEN
Added comment: 7 individuals from 5 families:
- 4 families homozygous for PTC.
- 1 family compound heterozygote for splice site + PTC. RNA studies indicate usage of 2 cryptic splice donor sites.

5/5 have ID/dev delay
1/5 seizures
2/5 hypotonia
3/5 Lissencephaly (pachygyria + cortical thickening)
Sources: Literature
Intellectual disability v5.332 SGSM3 Zornitza Stark gene: SGSM3 was added
gene: SGSM3 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: SGSM3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SGSM3 were set to 37833060
Phenotypes for gene: SGSM3 were set to Neurodevelopmental disorder (MONDO:0700092), SGSM3-related
Review for gene: SGSM3 was set to AMBER
Added comment: PMID: 37833060
- 13 patients from 8 families of Ashkenazi Jewish origin all had the same homozygous frameshift variant (c.981dup). Predicted to cause NMD. The variant co-segregated with disease in all available family members. The affected individuals displayed mild global developmental delay and mild to moderate intellectual disability. Additional features observed included hypotonia, behavioural challenges and short stature. Considered a founder variant (1 in 52 Ashkenazi Jews carry the variant). Also present in other populations but no homozygotes in gnomAD.
Sources: Literature
Intellectual disability v5.332 AGPAT3 Zornitza Stark gene: AGPAT3 was added
gene: AGPAT3 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: AGPAT3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGPAT3 were set to 37821758
Phenotypes for gene: AGPAT3 were set to Neurodevelopmental disorder (MONDO#0700092), AGPAT3-related
Review for gene: AGPAT3 was set to AMBER
Added comment: - Single consanguineous family with four individuals with severe intellectual disability and retinitis pigmentosa
- All affected individuals were homozygous for a nonsense variant in AGPAT3, healthy unaffected individuals who were tested were heterozygous for the variant
- Overexpression of mutant transcript revealed absence of AGPAT3 protein compared to WT transcript via Western blot analysis
- KO AGPAT3 mouse demonstrated impaired neuronal migration
Sources: Literature
Intellectual disability v5.332 VCP Zornitza Stark gene: VCP was added
gene: VCP was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: VCP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VCP were set to 37883978
Phenotypes for gene: VCP were set to Neurodevelopmental disorder (MONDO: 0700092)
Review for gene: VCP was set to GREEN
Added comment: 13 unrelated individuals with childhood onset ID/DD disorder including macrocephaly, hypotonia and dysmorphic features. Non-specific / mild MRI findings.
12 de novo - 1 inherited
Sources: Literature
Intellectual disability v5.332 ZBTB47 Sarah Leigh reviewed gene: ZBTB47: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v5.332 ZBTB47 Sarah Leigh Classified gene: ZBTB47 as Amber List (moderate evidence)
Intellectual disability v5.332 ZBTB47 Sarah Leigh Gene: zbtb47 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.121 POLD3 Achchuthan Shanmugasundram Deleted their comment
Primary immunodeficiency or monogenic inflammatory bowel disease v4.121 POLD3 Achchuthan Shanmugasundram Classified gene: POLD3 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.121 POLD3 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Hannah Knight, there is one patient identified with homozygous POLD3 variant (p.Ile10Thr) and reported with a syndromic severe combined immunodeficiency (SCID) with neurodevelopmental delay and hearing loss. In addition, there is also functional evidence for this variant. Hence, this gene is promoted to amber rating.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.121 POLD3 Achchuthan Shanmugasundram Gene: pold3 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.121 POLD3 Achchuthan Shanmugasundram Classified gene: POLD3 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.121 POLD3 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Hannah Knight, there is one patient identified with homozygous POLD3 variant (p.Ile10Thr) and reported with a syndromic severe combined immunodeficiency (SCID) with neurodevelopmental delay and hearing loss. In addition, there is also functional evidence for this variant. Hence, this gene is promoted to amber rating.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.121 POLD3 Achchuthan Shanmugasundram Gene: pold3 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.120 POLD3 Achchuthan Shanmugasundram Phenotypes for gene: POLD3 were changed from Immunodeficiency with neurodevelopmental delay and hearing loss to severe combined immunodeficiency, MONDO:0015974
Primary immunodeficiency or monogenic inflammatory bowel disease v4.119 POLD3 Achchuthan Shanmugasundram reviewed gene: POLD3: Rating: AMBER; Mode of pathogenicity: None; Publications: 37030525; Phenotypes: severe combined immunodeficiency, MONDO:0015974; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.331 MYCN Sarah Leigh Publications for gene: MYCN were set to 37710961; 21224895; 8470948; 16906565; 18671284; 15821734; 18470948
Intellectual disability v5.330 MYCN Sarah Leigh Added comment: Comment on mode of pathogenicity: Gain-of-function MYCN variants have been reported (PMID: 30573562; 37710961) where the phenotypic features are to an extent opposite the phenotype of Feingold syndrome 1 (OMIM:164280) caused by loss-of-function MYCN variants.
Intellectual disability v5.330 MYCN Sarah Leigh Mode of pathogenicity for gene: MYCN was changed from to None
Intellectual disability v5.329 MYCN Sarah Leigh Publications for gene: MYCN were set to 21224895; 8470948; 16906565; 18671284; 15821734; 18470948
Primary immunodeficiency or monogenic inflammatory bowel disease v4.119 FMNL2 Achchuthan Shanmugasundram Phenotypes for gene: FMNL2 were changed from Severe very early onset inflammatory bowel disease to inflammatory bowel disease, MONDO:0005265
Primary immunodeficiency or monogenic inflammatory bowel disease v4.118 FMNL2 Achchuthan Shanmugasundram Classified gene: FMNL2 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.118 FMNL2 Achchuthan Shanmugasundram Gene: fmnl2 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.117 FMNL2 Achchuthan Shanmugasundram Mode of pathogenicity for gene: FMNL2 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Primary immunodeficiency or monogenic inflammatory bowel disease v4.116 FMNL2 Achchuthan Shanmugasundram reviewed gene: FMNL2: Rating: AMBER; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 34043722; Phenotypes: inflammatory bowel disease, MONDO:0005265; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.328 MAST4 Sarah Leigh Tag Q4_23_promote_green tag was added to gene: MAST4.
Intellectual disability v5.328 MAST4 Sarah Leigh edited their review of gene: MAST4: Added comment: MAST4 variants have not been associated with a phenotype in OMIM, Gen2Phen or MONDO to date. PMID: 36910266 reports three de novo heterozygous MAST4 missense variants in four unrelated cases, with a neurodevelopmental disorder, including cognitive delay/intellectual disability and PMID: 33057194 reports four heterozygous MAST4 missense variants in four unrelated cases and a terminating variant in an additional case, from a cohort of 31,058 parent-offspring trios of individuals with developmental disorders. Between these two publications there are five missense MAST4 variants and one terminating variant. Variant c.4412C>T (p.Thr1471Ile) was seen in three unrelated cases.; Changed rating: GREEN
Primary immunodeficiency or monogenic inflammatory bowel disease v4.116 PTPN2 Achchuthan Shanmugasundram Classified gene: PTPN2 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.116 PTPN2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are two unrelated cases and a Ptpn2 deficient mouse model in support of the association of PTPN2 to this panel. Hence, this gene can be promoted to green rating in the next GMS review.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.116 PTPN2 Achchuthan Shanmugasundram Gene: ptpn2 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.115 PTPN2 Achchuthan Shanmugasundram Phenotypes for gene: PTPN2 were changed from Lupus; arthritis; common variable immunodeficiency to Lupus; arthritis; common variable immunodeficiency; Very early onset inflammatory bowel disease
Primary immunodeficiency or monogenic inflammatory bowel disease v4.114 PTPN2 Achchuthan Shanmugasundram Publications for gene: PTPN2 were set to 32499645; 27658548
Primary immunodeficiency or monogenic inflammatory bowel disease v4.113 PTPN2 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: PTPN2.
Tag Q4_23_NHS_review tag was added to gene: PTPN2.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.113 PTPN2 Achchuthan Shanmugasundram reviewed gene: PTPN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27658548, 32499645, 32721438; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare genetic inflammatory skin disorders v3.5 NLRP1 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence available for the association of monoallelic NLRP1 variants to this panel with green rating. However, the evidence is not sufficient enough (two unrelated cases) for biallelic variants. Hence, the MOI should be changed to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' and this gene should be recommended for upgrade to green rating in the next GMS review.
Rare genetic inflammatory skin disorders v3.5 NLRP1 Achchuthan Shanmugasundram Mode of inheritance for gene: NLRP1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare genetic inflammatory skin disorders v3.4 NLRP1 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: NLRP1.
Rare genetic inflammatory skin disorders v3.4 NLRP1 Achchuthan Shanmugasundram changed review comment from: There are five unrelated cases with monoallelic NLRP1 variants and two unrelated cases with biallelic NLRP1 variants reported with inflammatory skin conditions. Some of these variants are reported to be gain-of-function.; to: There are five unrelated cases with monoallelic NLRP1 variants and two unrelated cases with biallelic NLRP1 variants reported with inflammatory skin conditions. Some of these variants are reported to be gain-of-function.

This gene has also been associated with relevant phenotypes in both OMIM and Gene2Phenotype.
Rare genetic inflammatory skin disorders v3.4 NLRP1 Achchuthan Shanmugasundram reviewed gene: NLRP1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 27662089, 27965258, 31873740; Phenotypes: Autoinflammation with arthritis and dyskeratosis, OMIM:617388, Palmoplantar carcinoma, multiple self-healing, OMIM:615225; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v4.113 NLRP1 Achchuthan Shanmugasundram changed review comment from: There are five unrelated cases with monoallelic NLRP1 variants and three unrelated cases with biallelic NLRP1 variants. Some of these variants are reported to be of gain-of-function.

This gene has been associated with multiple relevant phenotypes in both OMIM and Gene2Phenotype (eye panel).; to: There are five unrelated cases with monoallelic NLRP1 variants and three unrelated cases with biallelic NLRP1 variants. Some of these variants are reported to be gain-of-function.

This gene has been associated with multiple relevant phenotypes in both OMIM and Gene2Phenotype (eye panel).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.113 NLRP1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence available for the association of both monoallelic and biallelic variants in this gene to this panel. Hence, this gene can be promoted to green rating in the next GMS review.; to: Comment on list classification: There is sufficient evidence available for the association of both monoallelic and biallelic variants in this gene to this panel. Hence, this gene can be promoted to green rating in the next GMS review.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.113 NLRP1 Achchuthan Shanmugasundram Classified gene: NLRP1 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.113 NLRP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of both monoallelic and biallelic variants in this gene to this panel. Hence, this gene can be promoted to green rating in the next GMS review.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.113 NLRP1 Achchuthan Shanmugasundram Gene: nlrp1 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.112 NLRP1 Achchuthan Shanmugasundram Phenotypes for gene: NLRP1 were changed from Dyskeratosis, autoimmunity and arthritis; Palmoplantar carcinoma, corneal scarring; Autoinflammatory Disorders; Autoinflammation with arthritis and dyskeratosis, 617388 to Autoinflammation with arthritis and dyskeratosis, OMIM:617388; ?Respiratory papillomatosis, juvenile recurrent, congenital, OMIM:618803; Palmoplantar carcinoma, multiple self-healing, OMIM:615225; {Vitiligo-associated multiple autoimmune disease susceptibility 1}, OMIM:606579
Primary immunodeficiency or monogenic inflammatory bowel disease v4.111 NLRP1 Achchuthan Shanmugasundram Publications for gene: NLRP1 were set to 27965258; 31484767; 27662089; 29850521
Primary immunodeficiency or monogenic inflammatory bowel disease v4.110 NLRP1 Achchuthan Shanmugasundram changed review comment from: There are five unrelated cases with monoallelic NLRP1 variants and three unrelated cases with biallelic NLRP1 variants. Some of these variants are reported to be of gain-of-function.

This gene has been associated with multiple relevant phenotypes in OMIM and Gene2Phenotype (eye panel).; to: There are five unrelated cases with monoallelic NLRP1 variants and three unrelated cases with biallelic NLRP1 variants. Some of these variants are reported to be of gain-of-function.

This gene has been associated with multiple relevant phenotypes in both OMIM and Gene2Phenotype (eye panel).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.110 NLRP1 Achchuthan Shanmugasundram changed review comment from: There are five unrelated cases with monoallelic NLRP1 variants and three unrelated cases with biallelic NLRP1 variants. Some of these variants are reported to be gain-of-function variants.

This gene has been associated with multiple relevant phenotypes in OMIM and Gene2Phenotype (eye panel).; to: There are five unrelated cases with monoallelic NLRP1 variants and three unrelated cases with biallelic NLRP1 variants. Some of these variants are reported to be of gain-of-function.

This gene has been associated with multiple relevant phenotypes in OMIM and Gene2Phenotype (eye panel).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.110 NLRP1 Achchuthan Shanmugasundram Mode of pathogenicity for gene: NLRP1 was changed from None to Other
Primary immunodeficiency or monogenic inflammatory bowel disease v4.109 NLRP1 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: NLRP1.
Tag Q4_23_NHS_review tag was added to gene: NLRP1.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.109 NLRP1 Achchuthan Shanmugasundram commented on gene: NLRP1: There are five unrelated cases with monoallelic NLRP1 variants and three unrelated cases with biallelic NLRP1 variants. Some of these variants are reported to be gain-of-function variants.

This gene has been associated with multiple relevant phenotypes in OMIM and Gene2Phenotype (eye panel).
Intellectual disability v5.328 MAST4 Sarah Leigh Classified gene: MAST4 as Amber List (moderate evidence)
Intellectual disability v5.328 MAST4 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v5.328 MAST4 Sarah Leigh Gene: mast4 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.109 NLRP1 Achchuthan Shanmugasundram edited their review of gene: NLRP1: Changed mode of pathogenicity: Other
Primary immunodeficiency or monogenic inflammatory bowel disease v4.109 NLRP1 Achchuthan Shanmugasundram edited their review of gene: NLRP1: Changed publications to: 27662089, 27965258, 31484767, 31873740
Primary immunodeficiency or monogenic inflammatory bowel disease v4.109 NLRP1 Achchuthan Shanmugasundram reviewed gene: NLRP1: 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: 27662089, 27965258, 31484767, 3187374; Phenotypes: Autoinflammation with arthritis and dyskeratosis, OMIM:617388, ?Respiratory papillomatosis, juvenile recurrent, congenital, OMIM:618803, Palmoplantar carcinoma, multiple self-healing, OMIM:615225, {Vitiligo-associated multiple autoimmune disease susceptibility 1}, OMIM:606579; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Congenital fibrosis of the extraocular muscles v1.15 MYF5 Hannah Knight reviewed gene: MYF5: Rating: GREEN; Mode of pathogenicity: None; Publications: 35186005; Phenotypes: Ophthalmoplegia, external, with rib and vertebral anomalies, 618155; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.327 MAST4 Sarah Leigh Classified gene: MAST4 as Amber List (moderate evidence)
Intellectual disability v5.327 MAST4 Sarah Leigh Gene: mast4 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.326 RBL2 Sarah Leigh Tag Q4_23_promote_green tag was added to gene: RBL2.
Tag Q4_23_NHS_review tag was added to gene: RBL2.
Intellectual disability v5.326 RBL2 Sarah Leigh Classified gene: RBL2 as Amber List (moderate evidence)
Intellectual disability v5.326 RBL2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v5.326 RBL2 Sarah Leigh Gene: rbl2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.325 RBL2 Sarah Leigh edited their review of gene: RBL2: Added comment: RBL2 variants have been associated with Brunet-Wagner neurodevelopmental syndrome (OMIM:619690) but not with phenotype in Gen2Phen. To date six RBL2 variants have been reported in four unrelated cases of OMIM:619690 (PMIDs: 32105419; 33980986).; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.325 RBL2 Sarah Leigh Phenotypes for gene: RBL2 were changed from intellectual diability to Brunet-Wagner neurodevelopmental syndrome, OMIM:619690
Intellectual disability v5.324 RBL2 Sarah Leigh Publications for gene: RBL2 were set to 32105419; 9806916
Intellectual disability v5.323 FAM111A Sarah Leigh Tag Q4_23_demote_red tag was added to gene: FAM111A.
Tag Q4_23_NHS_review tag was added to gene: FAM111A.
Fetal anomalies v3.115 FAM111A Sarah Leigh Added comment: Comment on mode of inheritance: PMID: 34382758 reports an autosomal recessive case of Kenny-Caffey Syndrome Type 2. The proband had inherited FAM111A variants from his healthy parents (paternal heterozygous missense
variant c.976T>A (p.L326I) and maternal heterozygous
in-frame deletion variant c.1714_1716del (p.Ile572del,
rs779963813)).
Fetal anomalies v3.115 FAM111A Sarah Leigh Mode of inheritance for gene: FAM111A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v3.114 FAM111A Sarah Leigh Publications for gene: FAM111A were set to
Skeletal dysplasia v4.30 FAM111A Sarah Leigh Added comment: Comment on mode of inheritance: PMID: 34382758 reports an autosomal recessive case of Kenny-Caffey Syndrome Type 2. The proband had inherited FAM111A variants from his healthy parents (paternal heterozygous missense
variant c.976T>A (p.L326I) and maternal heterozygous
in-frame deletion variant c.1714_1716del (p.Ile572del,
rs779963813)).
Skeletal dysplasia v4.30 FAM111A Sarah Leigh Mode of inheritance for gene: FAM111A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v4.29 FAM111A Sarah Leigh Publications for gene: FAM111A were set to
Intellectual disability v5.323 FAM111A Sarah Leigh Publications for gene: FAM111A were set to 23684011; 23996431; 25529582; 37023242; 34382758
Intellectual disability v5.322 FAM111A Sarah Leigh changed review comment from: Intellectual disability is not a feature of Gracile bone dysplasia (OMIM: 602361) or Kenny-Caffey syndrome, type 2 (OMIM: 127000)(PMID: 23684011;23996431;25529582).; to: Intellectual disability is not a feature of Gracile bone dysplasia (OMIM: 602361) or Kenny-Caffey syndrome, type 2 (OMIM: 127000)(PMID: 23684011;23996431;25529582).
PMID: 34382758 reports an autosomal recessive case of Kenny-Caffey Syndrome Type 2. The proband had inherited FAM111A variants from his healthy parents (paternal heterozygous missense
variant c.976T>A (p.L326I) and maternal heterozygous
in-frame deletion variant c.1714_1716del (p.Ile572del,
rs779963813)).
Intellectual disability v5.322 FAM111A Sarah Leigh Publications for gene: FAM111A were set to 23684011; 25529582; 37023242
Intellectual disability v5.321 FAM111A Sarah Leigh reviewed gene: FAM111A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Primary immunodeficiency or monogenic inflammatory bowel disease v4.109 GIMAP5 Achchuthan Shanmugasundram Publications for gene: GIMAP5 were set to 33956074
Primary immunodeficiency or monogenic inflammatory bowel disease v4.108 GIMAP5 Achchuthan Shanmugasundram reviewed gene: GIMAP5: Rating: AMBER; Mode of pathogenicity: None; Publications: 29382851, 33956074; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.321 FAM111A Sarah Leigh Publications for gene: FAM111A were set to 23684011
Adult onset neurodegenerative disorder v4.39 DAO Hannah Knight reviewed gene: DAO: Rating: AMBER; Mode of pathogenicity: None; Publications: 28430856, 29895397; Phenotypes: Amyotrophic lateral sclerosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Possible mitochondrial disorder - nuclear genes v3.51 HSPA9 Hannah Knight reviewed gene: HSPA9: Rating: GREEN; Mode of pathogenicity: None; Publications: 26598328, 32869452, 35779070, 36052765; Phenotypes: Even-plus syndrome 616854; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v4.55 HSPA9 Hannah Knight reviewed gene: HSPA9: Rating: GREEN; Mode of pathogenicity: None; Publications: 26598328, 32869452, 35779070, 36052765; Phenotypes: Even-plus syndrome 616854; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital disorders of glycosylation v4.7 MAN2B2 Achchuthan Shanmugasundram Classified gene: MAN2B2 as Amber List (moderate evidence)
Congenital disorders of glycosylation v4.7 MAN2B2 Achchuthan Shanmugasundram Gene: man2b2 has been classified as Amber List (Moderate Evidence).
Congenital disorders of glycosylation v4.6 MAN2B2 Achchuthan Shanmugasundram gene: MAN2B2 was added
gene: MAN2B2 was added to Congenital disorders of glycosylation. Sources: Literature
Mode of inheritance for gene: MAN2B2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAN2B2 were set to 31775018; 35637269
Phenotypes for gene: MAN2B2 were set to congenital disorder of glycosylation, MONDO:0015286
Review for gene: MAN2B2 was set to AMBER
Added comment: There are two different cases reported with biallelic MAN2B2 variants and congenital disorders of glycosylation. The patient reported in PMID:31775018 with homozygous p.Asp38Asn variant presented with immune deficiency, dysmorphic facial features, coagulopathy, and severe developmental delay. Although the patient reported in PMID:35637269 with compound heterozygous variants (p.Ser147del and p.Glu790Lys) had severe developmental delay, dysmorphic facial features as in the previous case, this patient had new features including cleft palate and hypospadias with no immune deficiency.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v4.108 MAN2B2 Achchuthan Shanmugasundram Phenotypes for gene: MAN2B2 were changed from to congenital disorder of glycosylation, MONDO:0015286
Primary immunodeficiency or monogenic inflammatory bowel disease v4.107 MAN2B2 Achchuthan Shanmugasundram Publications for gene: MAN2B2 were set to PMID: 31775018
Primary immunodeficiency or monogenic inflammatory bowel disease v4.106 MAN2B2 Achchuthan Shanmugasundram Classified gene: MAN2B2 as Red List (low evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.106 MAN2B2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is only one case reported with immunodeficiency (PMID:31775018). The patient reported in PMID:35637269 presented with severe developmental delay and dysmorphic facial features as in the previous case, but do not present with immunodeficiency. Hence, this gene can only be rated red with current evidence.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.106 MAN2B2 Achchuthan Shanmugasundram Gene: man2b2 has been classified as Red List (Low Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.105 MAN2B2 Achchuthan Shanmugasundram edited their review of gene: MAN2B2: Changed publications to: 31775018
Primary immunodeficiency or monogenic inflammatory bowel disease v4.105 MAN2B2 Achchuthan Shanmugasundram reviewed gene: MAN2B2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: congenital disorder of glycosylation, MONDO:0015286; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v4.105 SEC61A1 Achchuthan Shanmugasundram Classified gene: SEC61A1 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.105 SEC61A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are three unrelated cases in support of the association of this gene with this panel. Hence, this gene can be promoted to green rating in the next GMS review.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.105 SEC61A1 Achchuthan Shanmugasundram Gene: sec61a1 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.104 SEC61A1 Achchuthan Shanmugasundram Phenotypes for gene: SEC61A1 were changed from SEC61A1 deficiency; Severe recurrent respiratory tract infections; Hyperuricemic nephropathy, familial juvenile, 4, 617056; Predominantly Antibody Deficiencies; Severe congenital neutropenia to SEC61A1 deficiency; Severe recurrent respiratory tract infections; Hyperuricemic nephropathy, familial juvenile, 4, 617056; Predominantly Antibody Deficiencies; Hypogammaglobulinaemia; Severe congenital neutropenia
Primary immunodeficiency or monogenic inflammatory bowel disease v4.103 SEC61A1 Achchuthan Shanmugasundram Phenotypes for gene: SEC61A1 were changed from SEC61A1 deficiency; Severe recurrent respiratory tract infections; Hyperuricemic nephropathy, familial juvenile, 4, 617056; Predominantly Antibody Deficiencies to SEC61A1 deficiency; Severe recurrent respiratory tract infections; Hyperuricemic nephropathy, familial juvenile, 4, 617056; Predominantly Antibody Deficiencies; Severe congenital neutropenia
Primary immunodeficiency or monogenic inflammatory bowel disease v4.102 SEC61A1 Achchuthan Shanmugasundram Publications for gene: SEC61A1 were set to 28782633; 32086639; 32048120; 27392076
Primary immunodeficiency or monogenic inflammatory bowel disease v4.101 SEC61A1 Achchuthan Shanmugasundram Mode of inheritance for gene: SEC61A1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v4.100 SEC61A1 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: SEC61A1.
Tag Q4_23_NHS_review tag was added to gene: SEC61A1.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.100 SEC61A1 Achchuthan Shanmugasundram reviewed gene: SEC61A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28782633, 32325141; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v4.100 CD81 Achchuthan Shanmugasundram Classified gene: CD81 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.100 CD81 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are two unrelated cases and functional evidence available in support of the association of this gene to common variable immunodeficiency (MIM #613496). Hence, this gene can be promoted to green rating in the next GMS review.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.100 CD81 Achchuthan Shanmugasundram Gene: cd81 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.99 CD81 Achchuthan Shanmugasundram Phenotypes for gene: CD81 were changed from Common variable immunodeficiency disorders (CVID); Immunodeficiency, common variable 6, 613496; hypogammaglobulinaemia; CD81 deficiency; Isolated IgG subclass deficiency; Predominantly Antibody Deficiencies; Recurrent infections, may have glomerulonephritis to Immunodeficiency, common variable, 6, OMIM:613496
Primary immunodeficiency or monogenic inflammatory bowel disease v4.98 CD81 Achchuthan Shanmugasundram Publications for gene: CD81 were set to 27250108; 14530327; 20237408; 32048120; 32086639
Primary immunodeficiency or monogenic inflammatory bowel disease v4.97 CD81 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: CD81.
Tag Q4_23_NHS_review tag was added to gene: CD81.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.97 CD81 Achchuthan Shanmugasundram reviewed gene: CD81: Rating: GREEN; Mode of pathogenicity: None; Publications: 20237408, 25739915, 35849269; Phenotypes: Immunodeficiency, common variable, 6, OMIM:613496; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v4.97 CD4 Achchuthan Shanmugasundram Classified gene: CD4 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.97 CD4 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are two unrelated cases and functional evidence in support of the association of this gene with this panel. Hence, this gene can be promoted to green rating in the next GMS review.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.97 CD4 Achchuthan Shanmugasundram Gene: cd4 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.96 CD4 Achchuthan Shanmugasundram Phenotypes for gene: CD4 were changed from Selective CD4 cell deficiency; OKT4 epitope deficiency, 613949; Absence of CD4+ T cells; exuberant, relapsing, treatment-refractory warts to Immunodeficiency 79, OMIM:619238; OKT4 epitope deficiency, OMIM:613949
Primary immunodeficiency or monogenic inflammatory bowel disease v4.95 CD4 Achchuthan Shanmugasundram edited their review of gene: CD4: Changed phenotypes to: Immunodeficiency 79, OMIM:619238, OKT4 epitope deficiency, OMIM:613949
Primary immunodeficiency or monogenic inflammatory bowel disease v4.95 CD4 Achchuthan Shanmugasundram Publications for gene: CD4 were set to 31781092
Primary immunodeficiency or monogenic inflammatory bowel disease v4.94 CD4 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: CD4.
Tag Q4_23_NHS_review tag was added to gene: CD4.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.94 CD4 Achchuthan Shanmugasundram reviewed gene: CD4: Rating: GREEN; Mode of pathogenicity: None; Publications: 31781092, 33471124; Phenotypes: Immunodeficiency 79, OMIM:619238; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v4.94 REL Achchuthan Shanmugasundram Classified gene: REL as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.94 REL Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (two unrelated cases and functional studies) for the promotion of this gene to green rating in the next GMS review.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.94 REL Achchuthan Shanmugasundram Gene: rel has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.93 REL Achchuthan Shanmugasundram Phenotypes for gene: REL were changed from Recurrent infections with bacteria, mycobacteria, salmonella and opportunistic infections; c-Rel deficiency; Immunodeficiencies affecting cellular and humoral immunity to Immunodeficiency 92, OMIM:619652
Primary immunodeficiency or monogenic inflammatory bowel disease v4.92 REL Achchuthan Shanmugasundram Publications for gene: REL were set to 32086639; 31103457; 32048120
Primary immunodeficiency or monogenic inflammatory bowel disease v4.91 REL Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: REL.
Tag Q4_23_NHS_review tag was added to gene: REL.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.91 REL Achchuthan Shanmugasundram reviewed gene: REL: Rating: GREEN; Mode of pathogenicity: None; Publications: 31103457, 34623332; Phenotypes: Immunodeficiency 92, OMIM:619652; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v4.91 FCN3 Achchuthan Shanmugasundram Classified gene: FCN3 as Red List (low evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.91 FCN3 Achchuthan Shanmugasundram Gene: fcn3 has been classified as Red List (Low Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.90 FCN3 Achchuthan Shanmugasundram Classified gene: FCN3 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.90 FCN3 Achchuthan Shanmugasundram Gene: fcn3 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.89 FCN3 Achchuthan Shanmugasundram Phenotypes for gene: FCN3 were changed from Respiratory infections, abscesses; Immunodeficiency due to ficolin 3 deficiency, 613860; Complement Deficiencies; Ficolin3 deficiency to Immunodeficiency due to ficolin 3 deficiency, OMIM:613860
Primary immunodeficiency or monogenic inflammatory bowel disease v4.88 FCN3 Achchuthan Shanmugasundram Publications for gene: FCN3 were set to 22226667; 32048120; 20971976; 19535802; 25662573; 32086639
Primary immunodeficiency or monogenic inflammatory bowel disease v4.87 FCN3 Achchuthan Shanmugasundram reviewed gene: FCN3: Rating: AMBER; Mode of pathogenicity: None; Publications: 19535802, 20971976, 22226667, 25662573, 29907670, 31408713, 32634042; Phenotypes: Immunodeficiency due to ficolin 3 deficiency, OMIM:613860; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v4.87 TRAF3IP2 Achchuthan Shanmugasundram Classified gene: TRAF3IP2 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.87 TRAF3IP2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Hannah Knight, there is sufficient evidence available for promotion of this gene to green rating in the next GMS review.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.87 TRAF3IP2 Achchuthan Shanmugasundram Gene: traf3ip2 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.86 TRAF3IP2 Achchuthan Shanmugasundram Phenotypes for gene: TRAF3IP2 were changed from Defects in Intrinsic and Innate Immunity; CMC, blepharitis, folliculitis and macroglossia; Chronic mucocutaneous candidiasis (CMC); Defects in intrinsic and innate immunity; ?Candidiasis, familial, 88 615527 to ?Candidiasis, familial, 8, OMIM:615527; Defects in Intrinsic and Innate Immunity; CMC, blepharitis, folliculitis and macroglossia; Chronic mucocutaneous candidiasis (CMC); Defects in intrinsic and innate immunity
Primary immunodeficiency or monogenic inflammatory bowel disease v4.85 TRAF3IP2 Achchuthan Shanmugasundram Phenotypes for gene: TRAF3IP2 were changed from Defects in Intrinsic and Innate Immunity; CMC, blepharitis, folliculitis and macroglossia; Chronic mucocutaneous candidiasis (CMC); Defects in intrinsic and innate immunity; Candidiasis, familial, 8 615527 to Defects in Intrinsic and Innate Immunity; CMC, blepharitis, folliculitis and macroglossia; Chronic mucocutaneous candidiasis (CMC); Defects in intrinsic and innate immunity; ?Candidiasis, familial, 88 615527
Primary immunodeficiency or monogenic inflammatory bowel disease v4.84 TRAF3IP2 Achchuthan Shanmugasundram Publications for gene: TRAF3IP2 were set to 32048120; 24120361; 32086639; 31292894; 20660351
Primary immunodeficiency or monogenic inflammatory bowel disease v4.83 TRAF3IP2 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: TRAF3IP2.
Tag Q4_23_NHS_review tag was added to gene: TRAF3IP2.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.83 TFRC Achchuthan Shanmugasundram changed review comment from: Comment on list classification: Although there were eight unrelated families reported with immunodeficiency (MIM #616740), they all harboured the same homozygous variant p.Tyr20His. Functional studies and mouse model provide supporting evidence in associating TFRC with green rating in this panel.

Although this variant is found in a homozygous region that is identified between two different families from different geographic regions in PMID:26642240, the segregation of this variant with the phenotype supports this gene-disease association. Hence, this gene can be promoted to green rating in the next GMS review.; to: Comment on list classification: Although there were eight unrelated families reported with immunodeficiency (MIM #616740), they all harboured the same homozygous variant p.Tyr20His. Functional studies and mouse model provide supporting evidence in associating TFRC with green rating in this panel.

Although this variant is found in a homozygous region that is shared between two different families from different geographic regions reported in PMID:26642240, the segregation of this variant with the phenotype supports this gene-disease association. Hence, this gene can be promoted to green rating in the next GMS review.

The 'founder-effect' tag has also been added to highlight this.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.83 TFRC Achchuthan Shanmugasundram changed review comment from: Comment on list classification: Although there were eight unrelated families reported with immunodeficiency, they all harboured the same homozygous variant p.Tyr20His. Functional studies and mouse model provide supporting evidence in associating TFRC with green rating in this panel.

Although this variant is found in a homozygous region that is identified between two different families from different geographic regions in PMID:26642240, the segregation of this variant with the phenotype supports this gene-disease association. Hence, this gene can be promoted to green rating in the next GMS review.; to: Comment on list classification: Although there were eight unrelated families reported with immunodeficiency (MIM #616740), they all harboured the same homozygous variant p.Tyr20His. Functional studies and mouse model provide supporting evidence in associating TFRC with green rating in this panel.

Although this variant is found in a homozygous region that is identified between two different families from different geographic regions in PMID:26642240, the segregation of this variant with the phenotype supports this gene-disease association. Hence, this gene can be promoted to green rating in the next GMS review.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.83 TFRC Achchuthan Shanmugasundram Phenotypes for gene: TFRC were changed from Recurrent infections, neutropenia, thrombocytopenia; Recurrent infections, thrombocytopenia; Immunodeficiencies affecting cellular and humoral immunity; Immunodeficiency 46, 616740; T cells: normal number, poor proliferation; B cells: normal number, low memory B cells; recurrent infections, neutorpaenia; thrombocytopaenia to Immunodeficiency 46, OMIM:616740
Primary immunodeficiency or monogenic inflammatory bowel disease v4.82 TFRC Achchuthan Shanmugasundram Publications for gene: TFRC were set to 32086639; 26642240; 32048120
Primary immunodeficiency or monogenic inflammatory bowel disease v4.81 TFRC Achchuthan Shanmugasundram Classified gene: TFRC as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.81 TFRC Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there were eight unrelated families reported with immunodeficiency, they all harboured the same homozygous variant p.Tyr20His. Functional studies and mouse model provide supporting evidence in associating TFRC with green rating in this panel.

Although this variant is found in a homozygous region that is identified between two different families from different geographic regions in PMID:26642240, the segregation of this variant with the phenotype supports this gene-disease association. Hence, this gene can be promoted to green rating in the next GMS review.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.81 TFRC Achchuthan Shanmugasundram Gene: tfrc has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.80 TFRC Achchuthan Shanmugasundram changed review comment from: PMID:26642240 - c.58T>C (p.Tyr20His) variant was present in homozygous state in patients A1 and A2 from the family from Kuwait and unaffected father had the same variant in heterozygous state. This variant segregated perfectly with the combined immunodeficiency phenotype in 34 available family members and was absent from multiple variant databases and 731 genotyped controls.

The same homozygous variant was found in patient B1 from Western Saudi Arabian family, while this variant was present in heterozygous state in his parents and his sister. Although the families were from different geographic regions and not known to be related, Patient B1 shares a homozygous haplotype with the five genotyped patients from Family A across a 3.3 Mb interval at chromosome 3q29-ter that includes TFRC, suggesting identical by descent inheritance of the mutation from an unknown common ancestor.

Functional evidence shows that this substitution disrupts the TfR1 internalization motif, resulting in defective receptor endocytosis and markedly increased TfR1 expression on the cell surface. Iron citrate rescued the lymphocyte defects, and expression of wild-type but not mutant TfR1 rescued impaired transferrin uptake in patient-derived fibroblasts.

In addition, transgenic mice homozygous for the human TFRC mutation Y20H were viable and recapitulated the human phenotype.


PMID:32851577 - Eight patients from six different tribes of Arab descent were identified with the same previously reported homozygous variant (p.Tyr20His) and they all presented with recurrent sinopulmonary infections, chronic diarrhea, and failure to thrive in early life.

This gene has been associated with relevant phenotypes in both OMIM (MIM #616740) and Gene2Phenotype (with 'limited' rating in the DD panel).; to: PMID:26642240 - c.58T>C (p.Tyr20His) variant was present in homozygous state in patients A1 and A2 from the family from Kuwait and unaffected father had the same variant in heterozygous state. This variant segregated perfectly with the immunodeficiency phenotype in 34 available family members and was absent from multiple variant databases and 731 genotyped controls.

The same homozygous variant was found in patient B1 from Western Saudi Arabian family, while this variant was present in heterozygous state in his parents and his sister. Although the families were from different geographic regions and not known to be related, Patient B1 shares a homozygous haplotype with the five genotyped patients from Family A across a 3.3 Mb interval at chromosome 3q29-ter that includes TFRC, suggesting identical by descent inheritance of the mutation from an unknown common ancestor.

Functional evidence shows that this substitution disrupts the TfR1 internalization motif, resulting in defective receptor endocytosis and markedly increased TfR1 expression on the cell surface. Iron citrate rescued the lymphocyte defects, and expression of wild-type but not mutant TfR1 rescued impaired transferrin uptake in patient-derived fibroblasts.

In addition, transgenic mice homozygous for the human TFRC mutation Y20H were viable and recapitulated the human phenotype.


PMID:32851577 - Eight patients from six different tribes of Arab descent were identified with the same previously reported homozygous variant (p.Tyr20His) and they all presented with recurrent sinopulmonary infections, chronic diarrhea, and failure to thrive in early life.

This gene has been associated with relevant phenotypes in both OMIM (MIM #616740) and Gene2Phenotype (with 'limited' rating in the DD panel).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.80 TFRC Achchuthan Shanmugasundram Tag founder-effect tag was added to gene: TFRC.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.80 TFRC Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: TFRC.
Tag Q4_23_NHS_review tag was added to gene: TFRC.
Mosaic skin disorders - deep sequencing v2.41 GNB2 Arina Puzriakova Classified gene: GNB2 as Amber List (moderate evidence)
Mosaic skin disorders - deep sequencing v2.41 GNB2 Arina Puzriakova Added comment: Comment on list classification: Upgraded rating from Red to Amber in line with review by Tom Cullup (GOSH) to facilitate further gathering of data where appropriate which could potentially support future promotion to Green.
Mosaic skin disorders - deep sequencing v2.41 GNB2 Arina Puzriakova Gene: gnb2 has been classified as Amber List (Moderate Evidence).
Mosaic skin disorders - deep sequencing v2.40 EGFR Arina Puzriakova changed review comment from: Comment on list classification: New gene added by Tom Cullup (GOSH). Rating Amber inline with his review. Single individual (PMID: 31745974) with nonepidermolytic keratinocytic epidermal naevi and a postzygotic variant in EGFR.; to: Comment on list classification: New gene added by Tom Cullup (GOSH). Rating Amber inline with this review to facilitate further gathering of data where appropriate which could potentially support future promotion to Green. Single individual (PMID: 31745974) with nonepidermolytic keratinocytic epidermal naevi and a postzygotic variant in EGFR.
Mosaic skin disorders - deep sequencing v2.40 EGFR Arina Puzriakova Classified gene: EGFR as Amber List (moderate evidence)
Mosaic skin disorders - deep sequencing v2.40 EGFR Arina Puzriakova Added comment: Comment on list classification: New gene added by Tom Cullup (GOSH). Rating Amber inline with his review. Single individual (PMID: 31745974) with nonepidermolytic keratinocytic epidermal naevi and a postzygotic variant in EGFR.
Mosaic skin disorders - deep sequencing v2.40 EGFR Arina Puzriakova Gene: egfr has been classified as Amber List (Moderate Evidence).
Rare genetic inflammatory skin disorders v3.4 EGFR Arina Puzriakova Phenotypes for gene: EGFR were changed from INFLAMMATORY SKIN AND BOWEL DISEASE, NEONATAL, 2, MONDO:0014481 to ?Inflammatory skin and bowel disease, neonatal, 2, OMIM:616069
Primary immunodeficiency or monogenic inflammatory bowel disease v4.80 TFRC Achchuthan Shanmugasundram reviewed gene: TFRC: Rating: GREEN; Mode of pathogenicity: None; Publications: 26642240, 32851577; Phenotypes: Immunodeficiency 46, OMIM:616740; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v4.80 SPI1 Achchuthan Shanmugasundram Phenotypes for gene: SPI1 were changed from Agammaglobulinemia to Agammaglobulinemia 10, autosomal dominant, OMIM:619707
Primary immunodeficiency or monogenic inflammatory bowel disease v4.79 SPI1 Achchuthan Shanmugasundram Mode of inheritance for gene: SPI1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v4.78 SPI1 Achchuthan Shanmugasundram Tag watchlist was removed from gene: SPI1.
Tag Q4_23_promote_green tag was added to gene: SPI1.
Tag Q4_23_NHS_review tag was added to gene: SPI1.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.78 SPI1 Achchuthan Shanmugasundram Classified gene: SPI1 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.78 SPI1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Hannah Knight, PMID:33951726 is now publicly available online and have six unrelated cases and some functional data in support of the disease association. Hence, this gene can be promoted to green rating in the next GMS review.

The 'watchlist' tag has now been removed as this gene is now recommended for promotion to green rating.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.78 SPI1 Achchuthan Shanmugasundram Gene: spi1 has been classified as Amber List (Moderate Evidence).
Hypogonadotropic hypogonadism (GMS) v3.9 PROP1 Zornitza Stark reviewed gene: PROP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15941866, 11549703; Phenotypes: Pituitary hormone deficiency, combined, 2 (MIM#262600); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hypogonadotropic hypogonadism (GMS) v3.9 NDNF Zornitza Stark reviewed gene: NDNF: Rating: AMBER; Mode of pathogenicity: None; Publications: 31883645; Phenotypes: Hypogonadotropic hypogonadism 25 with anosmia MIM#618841; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hypogonadotropic hypogonadism (GMS) v3.9 CUL4B Zornitza Stark reviewed gene: CUL4B: Rating: GREEN; Mode of pathogenicity: None; Publications: 25385192; Phenotypes: Mental retardation, X-linked, syndromic 15 (Cabezas type) 300354; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ichthyosis and erythrokeratoderma v3.18 FAM83G Arina Puzriakova Publications for gene: FAM83G were set to
Palmoplantar keratodermas v3.15 FAM83G Arina Puzriakova Publications for gene: FAM83G were set to 29138053
Palmoplantar keratodermas v3.14 FAM83G Arina Puzriakova Classified gene: FAM83G as Amber List (moderate evidence)
Palmoplantar keratodermas v3.14 FAM83G Arina Puzriakova Added comment: Comment on list classification: Upgraded rating from Red to Amber inline with expert review by Tom Cullup (GOSH) to facilitate further gathering of data where appropriate which could potentially support future promotion to Green.
Palmoplantar keratodermas v3.14 FAM83G Arina Puzriakova Gene: fam83g has been classified as Amber List (Moderate Evidence).
Ichthyosis and erythrokeratoderma v3.17 FAM83G Arina Puzriakova Classified gene: FAM83G as Amber List (moderate evidence)
Ichthyosis and erythrokeratoderma v3.17 FAM83G Arina Puzriakova Added comment: Comment on list classification: Upgraded rating from Red to Amber inline with expert review by Tom Cullup (GOSH) to facilitate further gathering of data where appropriate which could potentially support future promotion to Green.
Ichthyosis and erythrokeratoderma v3.17 FAM83G Arina Puzriakova Gene: fam83g has been classified as Amber List (Moderate Evidence).
Palmoplantar keratodermas v3.13 FLG2 Arina Puzriakova Tag Q4_23_promote_green tag was added to gene: FLG2.
Tag Q4_23_NHS_review tag was added to gene: FLG2.
Palmoplantar keratodermas v3.13 FLG2 Arina Puzriakova Classified gene: FLG2 as Amber List (moderate evidence)
Palmoplantar keratodermas v3.13 FLG2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Tom Cullup (GOSH). Based on the recommendation by the specialist team that all genes causing peeling skin syndrome should be included on this panel, and that there is sufficient evidence of a gene:disease association, this gene should be promoted to Green at the next GMS review.
Palmoplantar keratodermas v3.13 FLG2 Arina Puzriakova Gene: flg2 has been classified as Amber List (Moderate Evidence).
Palmoplantar keratodermas v3.12 FLG2 Arina Puzriakova Publications for gene: FLG2 were set to PubMed: 28884927; 29505760
Palmoplantar keratodermas v3.11 FLG2 Arina Puzriakova Phenotypes for gene: FLG2 were changed from peeling skin syndrome-6 (PSS6) (MIM 618084) to Peeling skin syndrome 6, OMIM: 618084
Ichthyosis and erythrokeratoderma v3.16 TGM5 Arina Puzriakova Publications for gene: TGM5 were set to PubMed: 16380904; 19440220; 20164844; 22036214
Palmoplantar keratodermas v3.10 TGM5 Arina Puzriakova Publications for gene: TGM5 were set to PubMed: 16380904; 19440220; 20164844; 22036214
Ichthyosis and erythrokeratoderma v3.15 TGM5 Arina Puzriakova Phenotypes for gene: TGM5 were changed from Peeling skin syndrome 2 to Peeling skin syndrome 2, OMIM:609796
Palmoplantar keratodermas v3.9 TGM5 Arina Puzriakova Phenotypes for gene: TGM5 were changed from Peeling skin syndrome 2 to Peeling skin syndrome 2, OMIM:609796
Palmoplantar keratodermas v3.8 TGM5 Arina Puzriakova Classified gene: TGM5 as Amber List (moderate evidence)
Palmoplantar keratodermas v3.8 TGM5 Arina Puzriakova Added comment: Comment on list classification: New gene added by Tom Cullup (GOSH). Based on the recommendation by the specialist team that all genes causing peeling skin syndrome should be included on this panel, and that there is sufficient evidence of a gene:disease association, this gene should be promoted to Green at the next GMS review.
Palmoplantar keratodermas v3.8 TGM5 Arina Puzriakova Gene: tgm5 has been classified as Amber List (Moderate Evidence).
Ichthyosis and erythrokeratoderma v3.14 TGM5 Arina Puzriakova Classified gene: TGM5 as Amber List (moderate evidence)
Ichthyosis and erythrokeratoderma v3.14 TGM5 Arina Puzriakova Added comment: Comment on list classification: New gene added by Tom Cullup (GOSH). Based on the recommendation by the specialist team that all genes causing peeling skin syndrome should be included on this panel, and that there is sufficient evidence of a gene:disease association, this gene should be promoted to Green at the next GMS review.
Ichthyosis and erythrokeratoderma v3.14 TGM5 Arina Puzriakova Gene: tgm5 has been classified as Amber List (Moderate Evidence).
Ichthyosis and erythrokeratoderma v3.13 TGM5 Arina Puzriakova Tag Q4_23_promote_green tag was added to gene: TGM5.
Tag Q4_23_NHS_review tag was added to gene: TGM5.
Palmoplantar keratodermas v3.7 TGM5 Arina Puzriakova Tag Q4_23_promote_green tag was added to gene: TGM5.
Tag Q4_23_NHS_review tag was added to gene: TGM5.
Palmoplantar keratodermas v3.7 SERPINB8 Arina Puzriakova Phenotypes for gene: SERPINB8 were changed from Peeling skin syndrome 5 to Peeling skin syndrome 5, OMIM:617115
Palmoplantar keratodermas v3.6 SERPINB8 Arina Puzriakova Tag Q4_23_promote_green tag was added to gene: SERPINB8.
Tag Q4_23_NHS_review tag was added to gene: SERPINB8.
Palmoplantar keratodermas v3.6 SERPINB8 Arina Puzriakova Classified gene: SERPINB8 as Amber List (moderate evidence)
Palmoplantar keratodermas v3.6 SERPINB8 Arina Puzriakova Added comment: Comment on list classification: New gene added by Tom Cullup (GOSH). Based on the recommendation by the specialist team that all genes causing peeling skin syndrome should be included on this panel, and that there is sufficient evidence of a gene:disease association, this gene should be promoted to Green at the next GMS review. Some patients exhibit diffuse yellowish hyperkeratotic palmoplantar plaques.
Palmoplantar keratodermas v3.6 SERPINB8 Arina Puzriakova Gene: serpinb8 has been classified as Amber List (Moderate Evidence).
Ichthyosis and erythrokeratoderma v3.13 SERPINB8 Arina Puzriakova Classified gene: SERPINB8 as Amber List (moderate evidence)
Ichthyosis and erythrokeratoderma v3.13 SERPINB8 Arina Puzriakova Added comment: Comment on list classification: New gene added by Tom Cullup (GOSH). Based on the recommendation by the specialist team that all genes causing peeling skin syndrome should be included on this panel, and that there is sufficient evidence of a gene:disease association, this gene should be promoted to Green at the next GMS review.
Ichthyosis and erythrokeratoderma v3.13 SERPINB8 Arina Puzriakova Gene: serpinb8 has been classified as Amber List (Moderate Evidence).
Ichthyosis and erythrokeratoderma v3.12 SERPINB8 Arina Puzriakova Phenotypes for gene: SERPINB8 were changed from Peeling skin syndrome 5 to Peeling skin syndrome 5, OMIM:617115
Ichthyosis and erythrokeratoderma v3.11 SERPINB8 Arina Puzriakova Tag Q4_23_promote_green tag was added to gene: SERPINB8.
Tag Q4_23_NHS_review tag was added to gene: SERPINB8.
Ichthyosis and erythrokeratoderma v3.11 CSTA Arina Puzriakova Tag Q4_23_promote_green tag was added to gene: CSTA.
Tag Q4_23_NHS_review tag was added to gene: CSTA.
Ichthyosis and erythrokeratoderma v3.11 CSTA Arina Puzriakova Classified gene: CSTA as Amber List (moderate evidence)
Ichthyosis and erythrokeratoderma v3.11 CSTA Arina Puzriakova Added comment: Comment on list classification: New gene added by Tom Cullup (GOSH). Based on the recommendation by the specialist team that all genes causing peeling skin syndrome should be included on this panel, and that there is sufficient evidence of a gene:disease association, this gene should be promoted to Green at the next GMS review.
Ichthyosis and erythrokeratoderma v3.11 CSTA Arina Puzriakova Gene: csta has been classified as Amber List (Moderate Evidence).
Ichthyosis and erythrokeratoderma v3.10 CSTA Arina Puzriakova Phenotypes for gene: CSTA were changed from peeling skin syndrome-4 (PSS4) to Peeling skin syndrome 4, OMIM:607936
Ichthyosis and erythrokeratoderma v3.9 CDSN Arina Puzriakova Phenotypes for gene: CDSN were changed from Hypotrichosis 2; Peeling skin syndrome 1 to Peeling skin syndrome 1, OMIM:270300
Childhood onset dystonia, chorea or related movement disorder v3.55 SLC12A3 Achchuthan Shanmugasundram Tag monogenic - polygenic was removed from gene: SLC12A3.
Tag monogenic-polygenic tag was added to gene: SLC12A3.
Ichthyosis and erythrokeratoderma v3.8 CDSN Arina Puzriakova Mode of inheritance for gene: CDSN was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Ichthyosis and erythrokeratoderma v3.7 CDSN Arina Puzriakova Classified gene: CDSN as Amber List (moderate evidence)
Ichthyosis and erythrokeratoderma v3.7 CDSN Arina Puzriakova Added comment: Comment on list classification: New gene added by Tom Cullup (GOSH). Based on the recommendation by the specialist team that all genes causing peeling skin syndrome should be included on this panel, and that there is sufficient evidence of a gene:disease association, this gene should be promoted to Green at the next GMS review.

Changing MOI from 'BOTH mono- and biallelic' to 'BIALLELIC' as monoallelic variants are associated with hypotrichosis simplex of the scalp without other abnormalities (MIM# 146520).
Ichthyosis and erythrokeratoderma v3.7 CDSN Arina Puzriakova Gene: cdsn has been classified as Amber List (Moderate Evidence).
Renal tubulopathies v4.17 SLC12A3 Achchuthan Shanmugasundram Tag monogenic - polygenic was removed from gene: SLC12A3.
Tag monogenic-polygenic tag was added to gene: SLC12A3.
Likely inborn error of metabolism v4.55 SLC12A3 Achchuthan Shanmugasundram Tag monogenic - polygenic was removed from gene: SLC12A3.
Tag monogenic-polygenic tag was added to gene: SLC12A3.
Undiagnosed metabolic disorders v1.601 SLC12A3 Achchuthan Shanmugasundram Tag monogenic - polygenic was removed from gene: SLC12A3.
Tag monogenic-polygenic tag was added to gene: SLC12A3.
Ductal plate malformation v1.27 SLC12A3 Achchuthan Shanmugasundram Tag monogenic - polygenic was removed from gene: SLC12A3.
Tag monogenic-polygenic tag was added to gene: SLC12A3.
Ichthyosis and erythrokeratoderma v3.6 CDSN Arina Puzriakova Tag Q4_23_promote_green tag was added to gene: CDSN.
Tag Q4_23_NHS_review tag was added to gene: CDSN.
Hypogonadotropic hypogonadism (GMS) v3.9 ARHGAP35 Achchuthan Shanmugasundram Classified gene: ARHGAP35 as Amber List (moderate evidence)
Hypogonadotropic hypogonadism (GMS) v3.9 ARHGAP35 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for promoting this gene to green rating in the next GMS review.
Hypogonadotropic hypogonadism (GMS) v3.9 ARHGAP35 Achchuthan Shanmugasundram Gene: arhgap35 has been classified as Amber List (Moderate Evidence).
Hypogonadotropic hypogonadism (GMS) v3.8 ARHGAP35 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: ARHGAP35.
Tag Q4_23_NHS_review tag was added to gene: ARHGAP35.
Hypogonadotropic hypogonadism (GMS) v3.8 ARHGAP35 Achchuthan Shanmugasundram gene: ARHGAP35 was added
gene: ARHGAP35 was added to Hypogonadotropic hypogonadism (GMS). Sources: Literature
Mode of inheritance for gene: ARHGAP35 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARHGAP35 were set to 36178483
Phenotypes for gene: ARHGAP35 were set to hypogonadotropic hypogonadism, MONDO:0018555
Review for gene: ARHGAP35 was set to GREEN
Added comment: 16 patients from 13 different families were reported with idiopathic hypogonadotropic hypogonadism (9 with IHH and 7 with Kallmann syndrome (IHH + anosmia)) and with monoallelic ARHGAP35 variants. Rare protein-truncating variants and missense variants were found in the RhoGAP domain of ARHGAP35 gene.

Zebrafish modeling using gnrh3:egfp phenotype assessment showed that mutant larvae with deficient arhgap35a (predominant ARHGAP35 paralog in zebrafish brain), displayed decreased GnRH3-GFP+ neuronal area, a readout for IHH. In vitro GAP activity studies showed that 1 rare missense variant (Arg1284Trp) had decreased GAP activity.

This gene has not yet been associated with this phenotype either in OMIM or in Gene2Phenotype. However, this gene has been associated with ARHGAP35-related developmental disorder in DD panel of G2P (with 'definitive' rating).
Sources: Literature
Structural eye disease v3.56 RHOA Sarah Leigh Tag watchlist was removed from gene: RHOA.
Tag mosaicism tag was added to gene: RHOA.
Tag Q4_23_promote_green tag was added to gene: RHOA.
Tag Q4_23_NHS_review tag was added to gene: RHOA.
Structural eye disease v3.56 RHOA Sarah Leigh changed review comment from: RHOA variants have been associated with ectodermal dysplasia with facial dysmorphism and acral, ocular, and brain anomalies, somatic mosaic (OMIM:618727). Ocular involvement has been reported at least three unrelated cases carrying different RHOA variants (PMID: 31821646; 31570889; 35178721).; to: RHOA variants have been associated with ectodermal dysplasia with facial dysmorphism and acral, ocular, and brain anomalies, somatic mosaic (OMIM:618727). Ocular involvement has been reported at least three unrelated cases carrying different RHOA variants (PMID: 31821646; 31570889; 35178721).
Structural eye disease v3.56 RHOA Sarah Leigh edited their review of gene: RHOA: Added comment: RHOA variants have been associated with ectodermal dysplasia with facial dysmorphism and acral, ocular, and brain anomalies, somatic mosaic (OMIM:618727). Ocular involvement has been reported at least three unrelated cases carrying different RHOA variants (PMID: 31821646; 31570889; 35178721).; Changed rating: GREEN
Structural eye disease v3.56 RHOA Sarah Leigh Classified gene: RHOA as Amber List (moderate evidence)
Structural eye disease v3.56 RHOA Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Structural eye disease v3.56 RHOA Sarah Leigh Gene: rhoa has been classified as Amber List (Moderate Evidence).
Structural eye disease v3.55 RHOA Sarah Leigh Publications for gene: RHOA were set to 31821646; 31570889
Structural eye disease v3.54 PQBP1 Sarah Leigh reviewed gene: PQBP1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Structural eye disease v3.54 PQBP1 Sarah Leigh Phenotypes for gene: PQBP1 were changed from Renpenning syndrome (can include microphthalmia/coloboma), 309500 to Renpenning syndrome, OMIM:309500; Renpenning syndrome, MONDO:0010653
Primary immunodeficiency or monogenic inflammatory bowel disease v4.77 SAMD9L Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: SAMD9L.
Tag Q4_23_NHS_review tag was added to gene: SAMD9L.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.77 SAMD9L Achchuthan Shanmugasundram Classified gene: SAMD9L as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.77 SAMD9L Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Hannah Knight, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.77 SAMD9L Achchuthan Shanmugasundram Gene: samd9l has been classified as Amber List (Moderate Evidence).
Structural eye disease v3.53 PQBP1 Sarah Leigh Publications for gene: PQBP1 were set to 17033686
Primary immunodeficiency or monogenic inflammatory bowel disease v4.76 SAMD9L Achchuthan Shanmugasundram Mode of inheritance for gene: SAMD9L was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v4.75 SAMD9L Achchuthan Shanmugasundram reviewed gene: SAMD9L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: autoinflammatory syndrome, MONDO:0019751; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v4.75 SAMD9L Achchuthan Shanmugasundram Publications for gene: SAMD9L were set to 32048120; 28202457; 32086639
Structural eye disease v3.52 NUP188 Sarah Leigh Tag watchlist was removed from gene: NUP188.
Tag Q4_23_promote_green tag was added to gene: NUP188.
Tag Q4_23_NHS_review tag was added to gene: NUP188.
Structural eye disease v3.52 NUP188 Sarah Leigh edited their review of gene: NUP188: Added comment: NUP188 biallelic terminating variants have been associated with Sandestig-Stefanova syndrome (OMIM:618804). PMID: 36158057 describes the first male case of Sandestig-Stefanova syndrome and presents a literature review, that shows that microphthalmia (8/8 cases) and bilateral congenital cataracts (6/8 cases) are commonly reported in patients with biallelic NUP188 variants.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v3.52 NUP188 Sarah Leigh Classified gene: NUP188 as Amber List (moderate evidence)
Structural eye disease v3.52 NUP188 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Structural eye disease v3.52 NUP188 Sarah Leigh Gene: nup188 has been classified as Amber List (Moderate Evidence).
Structural eye disease v3.51 NUP188 Sarah Leigh Publications for gene: NUP188 were set to 32021605; 32275884
Structural eye disease v3.50 KDM6A Sarah Leigh Tag Skewed X-inactivation tag was added to gene: KDM6A.
Tag Q4_23_promote_green tag was added to gene: KDM6A.
Tag Q4_23_NHS_review tag was added to gene: KDM6A.
Structural eye disease v3.50 KDM6A Sarah Leigh Publications for gene: KDM6A were set to 22197486; 29617172; 29300383; 23076834; 24664873; 36672956
Structural eye disease v3.49 KDM6A Sarah Leigh changed review comment from: PMID: 36672956, 29300383, 24664873, 23076834 together report four KDM6A variants in four cases (3 male, 1 female), where the subject manifests ocular phenotypes, including: long palpebral fissures, nystagmus, bilateral coloboma, unilateral microphthalmia, nystagmus, sparse eyebrows, long eyelashes, ectropion of the lower eyelids, myopia, strabismus, arched eyebrows. PMID: 22197486 reports ocular features in three cases with microdeletions that included KDM6A, together with other genes.; to: PMID: 36672956, 29300383, 24664873, 23076834 together report four KDM6A variants in four cases (3 male, 1 female), where the subject manifests ocular phenotypes, including: long palpebral fissures, nystagmus, bilateral coloboma, unilateral microphthalmia, nystagmus, sparse eyebrows, long eyelashes, ectropion of the lower eyelids, myopia, strabismus, arched eyebrows. PMID: 22197486 reports ocular features in three cases with microdeletions that included KDM6A, together with other genes.
Skewed X-inactivation has also been reported at this locus (PMID: 22197486, 23913813).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.74 JAK1 Achchuthan Shanmugasundram Classified gene: JAK1 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.74 JAK1 Achchuthan Shanmugasundram Gene: jak1 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.73 JAK1 Achchuthan Shanmugasundram Phenotypes for gene: JAK1 were changed from Susceptibility to mycobacteria and viruses, urothelial carcinoma; Hypereosinophilic syndrome; Defects in Intrinsic and Innate Immunity; Diseases of Immune Dysregulation; HSM, eosinophilic enteritis, thyroid disease, poor growth, viral infections; HSM, eosinophilia, eosinophilic enteritis, thyroid disease, poor growth, viral infections to Autoinflammation, immune dysregulation, and eosinophilia, OMIM:618999
Primary immunodeficiency or monogenic inflammatory bowel disease v4.72 JAK1 Achchuthan Shanmugasundram Publications for gene: JAK1 were set to 32086639; 28111307; 32048120; 28008925; 30671064; 32750333; 34496019; 35046931
Primary immunodeficiency or monogenic inflammatory bowel disease v4.71 JAK1 Achchuthan Shanmugasundram Publications for gene: JAK1 were set to 32086639; 28111307; 32048120
Primary immunodeficiency or monogenic inflammatory bowel disease v4.70 JAK1 Achchuthan Shanmugasundram changed review comment from: Comment on mode of pathogenicity: Two of monoallelic variants were shown to be gain-of-function, one is mosaic and the other is somatic. Hence, MOP is set as 'Other'. In addition, 'mosaicsm' and 'somatic' tags were added.; to: Comment on mode of pathogenicity: Two of monoallelic variants were shown to be gain-of-function, one is mosaic and the other is somatic. Hence, MOP is set as 'Other'. In addition, 'mosaicism' and 'somatic' tags were added.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.70 JAK1 Achchuthan Shanmugasundram Tag mosaicism tag was added to gene: JAK1.
Tag somatic tag was added to gene: JAK1.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.70 JAK1 Achchuthan Shanmugasundram Mode of pathogenicity for gene: JAK1 was changed from None to Other
Primary immunodeficiency or monogenic inflammatory bowel disease v4.69 JAK1 Achchuthan Shanmugasundram Added comment: Comment on mode of pathogenicity: Two of monoallelic variants were shown to be gain-of-function, one is mosaic and the other is somatic. Hence, MOP is set as 'Other'. In addition, 'mosaicsm' and 'somatic' tags were added.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.69 JAK1 Achchuthan Shanmugasundram Mode of pathogenicity for gene: JAK1 was changed from Other - please provide details in the comments to None
Primary immunodeficiency or monogenic inflammatory bowel disease v4.68 JAK1 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is sufficient evidence available for the association of monoallelic variants in this gene to Autoinflammation, immune dysregulation, and eosinophilia (MIM #618999). However, the evidence for the association of biallelic variants is not sufficient for green rating. Hence, the MOI is set as 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted'.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.68 JAK1 Achchuthan Shanmugasundram Mode of inheritance for gene: JAK1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v4.67 JAK1 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: JAK1.
Tag Q4_23_NHS_review tag was added to gene: JAK1.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.67 JAK1 Achchuthan Shanmugasundram reviewed gene: JAK1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 28008925, 28111307, 30671064, 32750333, 34496019, 35046931; Phenotypes: Autoinflammation, immune dysregulation, and eosinophilia, OMIM:618999; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v4.67 PSMB10 Achchuthan Shanmugasundram Classified gene: PSMB10 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.67 PSMB10 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Hannah Knight, there is sufficient evidence for the promotion of this gene to green rating in this panel.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.67 PSMB10 Achchuthan Shanmugasundram Gene: psmb10 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.66 PSMB10 Achchuthan Shanmugasundram Phenotypes for gene: PSMB10 were changed from Proteasome-associated autoinflammatory syndrome (PRAAS) to Proteasome-associated autoinflammatory syndrome 5, OMIM:619175
Primary immunodeficiency or monogenic inflammatory bowel disease v4.65 PSMB10 Achchuthan Shanmugasundram Publications for gene: PSMB10 were set to 31783057
Primary immunodeficiency or monogenic inflammatory bowel disease v4.64 PSMB10 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: PSMB10.
Tag Q4_23_NHS_review tag was added to gene: PSMB10.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.64 PSMB10 Achchuthan Shanmugasundram reviewed gene: PSMB10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Proteasome-associated autoinflammatory syndrome 5, OMIM:619175; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v4.64 NFAT5 Achchuthan Shanmugasundram Tag watchlist was removed from gene: NFAT5.
Tag Q4_23_promote_green tag was added to gene: NFAT5.
Tag Q4_23_NHS_review tag was added to gene: NFAT5.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.64 NFAT5 Achchuthan Shanmugasundram Classified gene: NFAT5 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.64 NFAT5 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.64 NFAT5 Achchuthan Shanmugasundram Gene: nfat5 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.63 NFAT5 Achchuthan Shanmugasundram Publications for gene: NFAT5 were set to 32086639; 25667416; 32048120
Primary immunodeficiency or monogenic inflammatory bowel disease v4.62 NFAT5 Achchuthan Shanmugasundram Mode of inheritance for gene: NFAT5 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v4.61 NFAT5 Achchuthan Shanmugasundram reviewed gene: NFAT5: Rating: GREEN; Mode of pathogenicity: None; Publications: 25667416, 36238298; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v4.61 IRF4 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: IRF4.
Tag Q4_23_NHS_review tag was added to gene: IRF4.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.61 IRF4 Achchuthan Shanmugasundram Phenotypes for gene: IRF4 were changed from Whipple's disease; [Skin/hair/eye pigmentation, variation in, 8] 611724 to combined immunodeficiency, MONDO:0015131
Primary immunodeficiency or monogenic inflammatory bowel disease v4.60 IRF4 Achchuthan Shanmugasundram Publications for gene: IRF4 were set to 29537367; 31953710
Primary immunodeficiency or monogenic inflammatory bowel disease v4.59 IRF4 Achchuthan Shanmugasundram Classified gene: IRF4 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.59 IRF4 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Hannah Knight, there are two different heterozygous missense variants identified from seven unrelated cases reported with hypogammaglobulinemia/ combined immunodeficiency. In addition, there is supporting functional evidence for these variants. Hence, this gene can be promoted to green rating in the next GMS review.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.59 IRF4 Achchuthan Shanmugasundram Gene: irf4 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.58 IRF4 Achchuthan Shanmugasundram reviewed gene: IRF4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: combined immunodeficiency, MONDO:0015131; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Severe microcephaly v4.41 ARF3 Achchuthan Shanmugasundram Classified gene: ARF3 as Amber List (moderate evidence)
Severe microcephaly v4.41 ARF3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are four unrelated cases reported with severe microcephaly. Hence, this gene can be promoted to green rating in this panel in the next GMS review.
Severe microcephaly v4.41 ARF3 Achchuthan Shanmugasundram Gene: arf3 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v4.40 ARF3 Achchuthan Shanmugasundram Publications for gene: ARF3 were set to 34346499
Severe microcephaly v4.39 ARF3 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: ARF3.
Severe microcephaly v4.39 ARF3 Achchuthan Shanmugasundram reviewed gene: ARF3: Rating: GREEN; Mode of pathogenicity: None; Publications: 36369169; Phenotypes: neurodevelopmental disorder, MONDO:0700092, microcephaly, MONDO:0001149; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v4.127 ARF3 Achchuthan Shanmugasundram Deleted their comment
Early onset or syndromic epilepsy v4.127 ARF3 Achchuthan Shanmugasundram Deleted their comment
Early onset or syndromic epilepsy v4.127 ARF3 Achchuthan Shanmugasundram Classified gene: ARF3 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.127 ARF3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (>3 unrelated cases and supporting functional evidence) for the promotion of this gene to green rating in this panel in the next GMS review.
Early onset or syndromic epilepsy v4.127 ARF3 Achchuthan Shanmugasundram Gene: arf3 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.126 ARF3 Achchuthan Shanmugasundram Classified gene: ARF3 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.126 ARF3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (>3 unrelated cases and supporting functional evidence) for the promotion of this gene to green rating in this panel in the next GMS review.
Early onset or syndromic epilepsy v4.126 ARF3 Achchuthan Shanmugasundram Gene: arf3 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.126 ARF3 Achchuthan Shanmugasundram Classified gene: ARF3 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.126 ARF3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (>3 unrelated cases and supporting functional evidence) for the promotion of this gene to green rating in this panel in the next GMS review.
Early onset or syndromic epilepsy v4.126 ARF3 Achchuthan Shanmugasundram Gene: arf3 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.125 ARF3 Achchuthan Shanmugasundram Tag watchlist was removed from gene: ARF3.
Tag Q4_23_promote_green tag was added to gene: ARF3.
Early onset or syndromic epilepsy v4.125 ARF3 Achchuthan Shanmugasundram Publications for gene: ARF3 were set to 34346499
Early onset or syndromic epilepsy v4.124 ARF3 Achchuthan Shanmugasundram reviewed gene: ARF3: Rating: GREEN; Mode of pathogenicity: None; Publications: 34346499, 36369169; Phenotypes: neurodevelopmental disorder, MONDO:0700092, epilepsy, MONDO:0005027; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v5.320 ARF3 Achchuthan Shanmugasundram Tag watchlist was removed from gene: ARF3.
Intellectual disability v5.320 ARF3 Achchuthan Shanmugasundram Classified gene: ARF3 as Amber List (moderate evidence)
Intellectual disability v5.320 ARF3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Intellectual disability v5.320 ARF3 Achchuthan Shanmugasundram Gene: arf3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.319 ARF3 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: ARF3.
Intellectual disability v5.319 ARF3 Achchuthan Shanmugasundram Publications for gene: ARF3 were set to 34346499; 36369169
Intellectual disability v5.319 ARF3 Achchuthan Shanmugasundram Publications for gene: ARF3 were set to 34346499
Intellectual disability v5.318 ARF3 Achchuthan Shanmugasundram reviewed gene: ARF3: Rating: GREEN; Mode of pathogenicity: None; Publications: 36369169; Phenotypes: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary ataxia with onset in adulthood v4.26 FGF14_GAA Eleanor Williams Tag Q1_23_promote_green was removed from STR: FGF14_GAA.
Tag Q1_23_expert_review was removed from STR: FGF14_GAA.
Tag Q1_23_NHS_review was removed from STR: FGF14_GAA.
Tag watchlist tag was added to STR: FGF14_GAA.
Hereditary ataxia with onset in adulthood v4.26 FGF14_GAA Eleanor Williams commented on STR: FGF14_GAA: After NHS Genomic Medicine Service consideration, the rating of this STR has not been changed and remains Amber.

Comments from review:
Agree that the expansion is likely disease causing. However only a small number of cases have been used to define the number of repeats that could be considered pathogenic. Would recommend that more cases should be identified to better define the pathogenic repeat lengths of this STR. Perhaps study in 100,000 Genomes and GMS data would provide additional cases.

Agree that alleles >250 rpts are of interest and those >300 likely to be diagnostic but concerned that Expansion Hunter will not be able to provide accurate sizing beyond a threshold well below this (~100 repeats). See Supplementary figure S2 of PMID 36493768 for an illustration of this. Can ExpansionHunterDeNovo do better using paired IRRs (PMID PMID: 32345345), or can Expansion Hunter be adapted to factor-in paired IRRs to give a better prediction of expansion size? PCR based assays will also be essential for confirmation and sizing of any repeats detected, not currently available diagnostically to our knowledge.
Likely inborn error of metabolism v4.55 SLC6A20 Eleanor Williams commented on gene: SLC6A20: Added the gene-checked tag as this is the right gene on the panel, even though it probably should be demoted.
Likely inborn error of metabolism v4.55 SLC6A20 Eleanor Williams Tag gene-checked tag was added to gene: SLC6A20.
Structural eye disease v3.49 KDM6A Sarah Leigh edited their review of gene: KDM6A: Added comment: PMID: 36672956, 29300383, 24664873, 23076834 together report four KDM6A variants in four cases (3 male, 1 female), where the subject manifests ocular phenotypes, including: long palpebral fissures, nystagmus, bilateral coloboma, unilateral microphthalmia, nystagmus, sparse eyebrows, long eyelashes, ectropion of the lower eyelids, myopia, strabismus, arched eyebrows. PMID: 22197486 reports ocular features in three cases with microdeletions that included KDM6A, together with other genes.; Changed rating: GREEN; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Structural eye disease v3.49 KDM6A Sarah Leigh Classified gene: KDM6A as Amber List (moderate evidence)
Structural eye disease v3.49 KDM6A Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Structural eye disease v3.49 KDM6A Sarah Leigh Gene: kdm6a has been classified as Amber List (Moderate Evidence).
Inherited phaeochromocytoma and paraganglioma excluding NF1 v2.2 MDH2 Terri McVeigh reviewed gene: MDH2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Inherited phaeochromocytoma and paraganglioma excluding NF1 v2.2 DLST Terri McVeigh reviewed gene: DLST: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Inherited phaeochromocytoma and paraganglioma excluding NF1 v2.2 SLC25A11 Terri McVeigh reviewed gene: SLC25A11: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v5.318 RBL2 Mike Spiller reviewed gene: RBL2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32105419, PMID: 33980986; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
DDG2P v3.76 KCNH5 Eleanor Williams Phenotypes for gene: KCNH5 were changed from INFANTILE EPILEPTIC ENCEPHALOPATHY to Developmental and epileptic encephalopathy 112, OMIM:620537
Arthrogryposis v5.19 ADAMTS15 Arina Puzriakova Phenotypes for gene: ADAMTS15 were changed from distal arthrogryposis to Arthrogryposis, distal, type 12, OMIM:620545
Arthrogryposis v5.18 ADAMTS15 Arina Puzriakova Tag gene-checked was removed from gene: ADAMTS15.
Intellectual disability v5.317 KCNH5 Arina Puzriakova Phenotypes for gene: KCNH5 were changed from developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071 to Developmental and epileptic encephalopathy 112, OMIM:620537
Early onset or syndromic epilepsy v4.122 KCNH5 Arina Puzriakova Phenotypes for gene: KCNH5 were changed from developmental and epileptic encephalopathy, MONDO:0100062; epilepsy, MONDO:0005027 to Developmental and epileptic encephalopathy 112, OMIM:620537
DDG2P v3.74 KCNH5 Arina Puzriakova Tag gene-checked was removed from gene: KCNH5.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.57 MCTS1 Boaz Palterer gene: MCTS1 was added
gene: MCTS1 was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: MCTS1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: MCTS1 were set to MSMD; non tubercular mycobacteria infection; BCGtis; BCG infection
Penetrance for gene: MCTS1 were set to Complete
Review for gene: MCTS1 was set to GREEN
Added comment: Human MCTS1-dependent translation of JAK2 is essential for IFN-γ immunity to mycobacteria
https://doi.org/10.1016/j.cell.2023.09.024

Bohlen et al. identified 6 male subjects from 5 kindreds with LOF MCTS-1 variants with MSMD.
Extensive ex-vivo functional validation and mouse model.
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v4.57 CBLB Boaz Palterer gene: CBLB was added
gene: CBLB was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: CBLB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CBLB were set to 36006710
Phenotypes for gene: CBLB were set to immunedysregulation; autoimmunity; hypothyroidism; diabetes mellitus type I; vitiligo; urticaria; HLH; ITP; autoimmune hemolytic anemia
Penetrance for gene: CBLB were set to unknown
Review for gene: CBLB was set to RED
Added comment: Janssen et al. described 3 unrelated children with early-onset autoimmunity with homozygous CBLB variants. Patient T cells exhibited hyperproliferation in response to anti-CD3 cross-linking.

Mice homozygous for the CBL-B p.H257L mutation, which corresponds to the patient’s p.H285L mutation, had T and B cell hyperproliferation in response to antigen receptor cross-linking. CblbH257L mice had increased percentages of T regulatory cells (Tregs) that had normal in vitro suppressive function.
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v4.57 FGL2 Boaz Palterer gene: FGL2 was added
gene: FGL2 was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: FGL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FGL2 were set to 36243222
Phenotypes for gene: FGL2 were set to immunedysregulation; autoimmunity; arthritis; Treg dysfunction; leukocytoclastic vasculitis
Penetrance for gene: FGL2 were set to unknown
Review for gene: FGL2 was set to RED
Added comment: One subject from one kindred with homozygous truncating FGL2 variant. Some in vitro phenotype rescue and mouse model.
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v4.56 RELA Achchuthan Shanmugasundram Classified gene: RELA as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.56 RELA Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Hannah Knight, there are at least eight unrelated cases identified with monoallelic RELA variants and reported with chronic mucocutaneous ulceration (MIM #618287). Hence, this gene can be promoted to green rating in the next GMS review.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.56 RELA Achchuthan Shanmugasundram Gene: rela has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.55 RELA Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: RELA.
Tag Q4_23_NHS_review tag was added to gene: RELA.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.55 RELA Achchuthan Shanmugasundram Publications for gene: RELA were set to 28600438; 32086639; 32048120; 29305315
Primary immunodeficiency or monogenic inflammatory bowel disease v4.54 RELA Achchuthan Shanmugasundram Mode of inheritance for gene: RELA was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.315 DOCK8 Dmitrijs Rots reviewed gene: DOCK8: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v3.46 KDM6A Sarah Leigh Publications for gene: KDM6A were set to 29617172; 29300383; 36672956
Structural eye disease v3.45 KDM6A Sarah Leigh Phenotypes for gene: KDM6A were changed from Kabuki Syndrome 2, KABUK2, 300867 to Kabuki syndrome 2, OMIM:300867; Kabuki syndrome 2, MONDO:0010465
Structural eye disease v3.44 KDM6A Sarah Leigh Publications for gene: KDM6A were set to 29617172; 29300383
Structural eye disease v3.43 GDF3 Sarah Leigh Tag Q4_23_promote_green tag was added to gene: GDF3.
Tag Q4_23_NHS_review tag was added to gene: GDF3.
Structural eye disease v3.43 GDF3 Sarah Leigh Classified gene: GDF3 as Amber List (moderate evidence)
Structural eye disease v3.43 GDF3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Structural eye disease v3.43 GDF3 Sarah Leigh Gene: gdf3 has been classified as Amber List (Moderate Evidence).
Structural eye disease v3.42 GDF3 Sarah Leigh reviewed gene: GDF3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Structural eye disease v3.42 GDF3 Sarah Leigh Phenotypes for gene: GDF3 were changed from Klippel-Feil Syndrome3, 613702; Klippel-Feil syndrome 3, autosomal dominant, 613702; Microphthalmia with coloboma 6, 613703; Microphthalmia, isolated 7, 613704 to Klippel-Feil syndrome 3, autosomal dominant, OMIM:613702; Klippel-Feil syndrome 3, autosomal dominant, MONDO:0013375; Microphthalmia with coloboma 6, OMIM:613703; microphthalmia, isolated, with coloboma 6, MONDO:0013376; Microphthalmia, isolated 7, OMIM:613704; isolated microphthalmia 7, MONDO:0013377
Structural eye disease v3.41 GDF3 Sarah Leigh Publications for gene: GDF3 were set to 19864492
Childhood onset dystonia, chorea or related movement disorder v3.53 ARX Sarah Leigh Tag Q4_23_promote_green tag was added to gene: ARX.
Early onset dystonia v1.146 ARX Sarah Leigh Classified gene: ARX as Green List (high evidence)
Early onset dystonia v1.146 ARX Sarah Leigh Gene: arx has been classified as Green List (High Evidence).
Adult onset dystonia, chorea or related movement disorder v3.16 ARX Sarah Leigh commented on gene: ARX: A review by Eldar Dedic (Independent Clinical Genetics Consultant):
Kwong, et al. (2019, PMID: 31324350) presented a Chinese family with infantile epileptic dyskinetic encephalopathy. The whole-exome-sequencing revealed ARX c.989G>A (p.Arg330His) in 13 years of age affected proband (who also suffered from dystonia), as well as in his unaffected mother and sister. Proband also had a healthy older brother who did not carry the variant. The proband’s muscle whole mitochondrial DNA analysis did not show the presence of a pathogenic variant. - Please note that ARX c.989G>A (p.Arg330His) was absent from gnomAD v2.1.1 as of December 2021 Gorman, et al. (2018, PMID: 29778428) presented 2 years of age Ohtahara syndrome male case of Romanian origin. Whole-exome-sequencing revealed ARX c.1600G>C (p.Ala534Pro) variant in a patient (who also had dystonia) and in his healthy mother (who was a low-level mosaic). The proband was negative for chromosomal array testing and had a normal brain MRI. - Please note that ARX c.1600G>C (p.Ala534Pro) was absent from gnomAD v2.1.1 as of December 2021 Charzewska, et al. (2013, PMID: 23657928) presented a family with intellectual disability and dystonia. Sequencing of ARX revealed the presence of c.4A>T (p.Ser2Cys) variant in 4 affected males (including 2 who had onset of dystonia at 2nd day of life and 12 years of age, respectively) and in 5 female carriers. - Please note that ARX c.4A>T (p.Ser2Cys) was absent from gnomAD v2.1.1 as of December 2021 Breen, et al. (2018, PMID: 29343471) presented 12 years of age male case with intellectual disability and hand dystonia. The ARX c.426_458dup (p.Gly143_Ala153dup) variant has been reported in the proband, his cousin and maternal uncle from Pakistan, both of which had hand dystonia, as well as in his unaffected mother. The patient had whole-exome-sequencing as one of the previous tests carried out. - Please note that ARX c.426_458dup (p.Gly143_Ala153dup) was absent from gnomAD v2.1.1 as of December 2021
Childhood onset dystonia, chorea or related movement disorder v3.53 ARX Sarah Leigh changed review comment from: A review by Eldar Dedic (Independent Clinical Genetics Consultant)
Kwong, et al. (2019, PMID: 31324350) presented a Chinese family with infantile epileptic dyskinetic encephalopathy. The whole-exome-sequencing revealed ARX c.989G>A (p.Arg330His) in 13 years of age affected proband (who also suffered from dystonia), as well as in his unaffected mother and sister. Proband also had a healthy older brother who did not carry the variant. The proband’s muscle whole mitochondrial DNA analysis did not show the presence of a pathogenic variant. - Please note that ARX c.989G>A (p.Arg330His) was absent from gnomAD v2.1.1 as of December 2021 Gorman, et al. (2018, PMID: 29778428) presented 2 years of age Ohtahara syndrome male case of Romanian origin. Whole-exome-sequencing revealed ARX c.1600G>C (p.Ala534Pro) variant in a patient (who also had dystonia) and in his healthy mother (who was a low-level mosaic). The proband was negative for chromosomal array testing and had a normal brain MRI. - Please note that ARX c.1600G>C (p.Ala534Pro) was absent from gnomAD v2.1.1 as of December 2021 Charzewska, et al. (2013, PMID: 23657928) presented a family with intellectual disability and dystonia. Sequencing of ARX revealed the presence of c.4A>T (p.Ser2Cys) variant in 4 affected males (including 2 who had onset of dystonia at 2nd day of life and 12 years of age, respectively) and in 5 female carriers. - Please note that ARX c.4A>T (p.Ser2Cys) was absent from gnomAD v2.1.1 as of December 2021 Breen, et al. (2018, PMID: 29343471) presented 12 years of age male case with intellectual disability and hand dystonia. The ARX c.426_458dup (p.Gly143_Ala153dup) variant has been reported in the proband, his cousin and maternal uncle from Pakistan, both of which had hand dystonia, as well as in his unaffected mother. The patient had whole-exome-sequencing as one of the previous tests carried out. - Please note that ARX c.426_458dup (p.Gly143_Ala153dup) was absent from gnomAD v2.1.1 as of December 2021; to: A review by Eldar Dedic (Independent Clinical Genetics Consultant):
Kwong, et al. (2019, PMID: 31324350) presented a Chinese family with infantile epileptic dyskinetic encephalopathy. The whole-exome-sequencing revealed ARX c.989G>A (p.Arg330His) in 13 years of age affected proband (who also suffered from dystonia), as well as in his unaffected mother and sister. Proband also had a healthy older brother who did not carry the variant. The proband’s muscle whole mitochondrial DNA analysis did not show the presence of a pathogenic variant. - Please note that ARX c.989G>A (p.Arg330His) was absent from gnomAD v2.1.1 as of December 2021 Gorman, et al. (2018, PMID: 29778428) presented 2 years of age Ohtahara syndrome male case of Romanian origin. Whole-exome-sequencing revealed ARX c.1600G>C (p.Ala534Pro) variant in a patient (who also had dystonia) and in his healthy mother (who was a low-level mosaic). The proband was negative for chromosomal array testing and had a normal brain MRI. - Please note that ARX c.1600G>C (p.Ala534Pro) was absent from gnomAD v2.1.1 as of December 2021 Charzewska, et al. (2013, PMID: 23657928) presented a family with intellectual disability and dystonia. Sequencing of ARX revealed the presence of c.4A>T (p.Ser2Cys) variant in 4 affected males (including 2 who had onset of dystonia at 2nd day of life and 12 years of age, respectively) and in 5 female carriers. - Please note that ARX c.4A>T (p.Ser2Cys) was absent from gnomAD v2.1.1 as of December 2021 Breen, et al. (2018, PMID: 29343471) presented 12 years of age male case with intellectual disability and hand dystonia. The ARX c.426_458dup (p.Gly143_Ala153dup) variant has been reported in the proband, his cousin and maternal uncle from Pakistan, both of which had hand dystonia, as well as in his unaffected mother. The patient had whole-exome-sequencing as one of the previous tests carried out. - Please note that ARX c.426_458dup (p.Gly143_Ala153dup) was absent from gnomAD v2.1.1 as of December 2021
Childhood onset dystonia, chorea or related movement disorder v3.53 ARX Sarah Leigh commented on gene: ARX: A review by Eldar Dedic (Independent Clinical Genetics Consultant)
Kwong, et al. (2019, PMID: 31324350) presented a Chinese family with infantile epileptic dyskinetic encephalopathy. The whole-exome-sequencing revealed ARX c.989G>A (p.Arg330His) in 13 years of age affected proband (who also suffered from dystonia), as well as in his unaffected mother and sister. Proband also had a healthy older brother who did not carry the variant. The proband’s muscle whole mitochondrial DNA analysis did not show the presence of a pathogenic variant. - Please note that ARX c.989G>A (p.Arg330His) was absent from gnomAD v2.1.1 as of December 2021 Gorman, et al. (2018, PMID: 29778428) presented 2 years of age Ohtahara syndrome male case of Romanian origin. Whole-exome-sequencing revealed ARX c.1600G>C (p.Ala534Pro) variant in a patient (who also had dystonia) and in his healthy mother (who was a low-level mosaic). The proband was negative for chromosomal array testing and had a normal brain MRI. - Please note that ARX c.1600G>C (p.Ala534Pro) was absent from gnomAD v2.1.1 as of December 2021 Charzewska, et al. (2013, PMID: 23657928) presented a family with intellectual disability and dystonia. Sequencing of ARX revealed the presence of c.4A>T (p.Ser2Cys) variant in 4 affected males (including 2 who had onset of dystonia at 2nd day of life and 12 years of age, respectively) and in 5 female carriers. - Please note that ARX c.4A>T (p.Ser2Cys) was absent from gnomAD v2.1.1 as of December 2021 Breen, et al. (2018, PMID: 29343471) presented 12 years of age male case with intellectual disability and hand dystonia. The ARX c.426_458dup (p.Gly143_Ala153dup) variant has been reported in the proband, his cousin and maternal uncle from Pakistan, both of which had hand dystonia, as well as in his unaffected mother. The patient had whole-exome-sequencing as one of the previous tests carried out. - Please note that ARX c.426_458dup (p.Gly143_Ala153dup) was absent from gnomAD v2.1.1 as of December 2021
Childhood onset dystonia, chorea or related movement disorder v3.53 ARX Sarah Leigh reviewed gene: ARX: Rating: GREEN; Mode of pathogenicity: None; Publications: 31324350, 29778428, 23657928, 29343471; Phenotypes: ; Mode of inheritance: None
Adult onset dystonia, chorea or related movement disorder v3.16 ARX Sarah Leigh reviewed gene: ARX: Rating: AMBER; Mode of pathogenicity: None; Publications: 31324350, 29778428, 23657928, 29343471; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Adult onset dystonia, chorea or related movement disorder v3.16 ARX Sarah Leigh Mode of inheritance for gene: ARX was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Early onset dystonia v1.145 ARX Sarah Leigh Phenotypes for gene: ARX were changed from Dystonia to Developmental and epileptic encephalopathy 1, OMIM:308350; X-linked spasticity-intellectual disability-epilepsy syndromeMONDO:0017856; Partington syndrome, OMIM:309510; Partington syndrome, MONDO:0010654
Childhood onset dystonia, chorea or related movement disorder v3.53 ARX Sarah Leigh Phenotypes for gene: ARX were changed from Partington Syndrome, 300382 to Developmental and epileptic encephalopathy 1, OMIM:308350; X-linked spasticity-intellectual disability-epilepsy syndromeMONDO:0017856; Partington syndrome, OMIM:309510; Partington syndrome, MONDO:0010654
Adult onset dystonia, chorea or related movement disorder v3.15 ARX Sarah Leigh Phenotypes for gene: ARX were changed from Partington Syndrome, OMIM:309510 to Developmental and epileptic encephalopathy 1, OMIM:308350; X-linked spasticity-intellectual disability-epilepsy syndromeMONDO:0017856; Partington syndrome, OMIM:309510; Partington syndrome, MONDO:0010654
Childhood onset dystonia, chorea or related movement disorder v3.52 ARX Sarah Leigh Publications for gene: ARX were set to
Adult onset dystonia, chorea or related movement disorder v3.14 ARX Sarah Leigh Publications for gene: ARX were set to 29343471; 17664398; 26029707
Early onset dystonia v1.144 ARX Sarah Leigh Publications for gene: ARX were set to
Primary immunodeficiency or monogenic inflammatory bowel disease v4.53 FMNL2 Hannah Knight gene: FMNL2 was added
gene: FMNL2 was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: FMNL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FMNL2 were set to 34043722
Phenotypes for gene: FMNL2 were set to Severe very early onset inflammatory bowel disease
Review for gene: FMNL2 was set to AMBER
Added comment: PMID: 34043722 reported a patient who presented with severe very early onset inflammatory bowel disease, with a de novo heterozygous FMNL2 variant (p.Leu136Pro)
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v4.53 NFAT5 Hannah Knight reviewed gene: NFAT5: Rating: GREEN; Mode of pathogenicity: None; Publications: 36238298; Phenotypes: NFAT5 haploinsufficiency; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset dystonia v1.143 FOXG1 Arina Puzriakova Phenotypes for gene: FOXG1 were changed from Dystonia to Rett Syndrome, congenital variant OMIM:613454
Early onset dystonia v1.142 FOXG1 Arina Puzriakova Publications for gene: FOXG1 were set to
Childhood onset dystonia, chorea or related movement disorder v3.51 FOXG1 Arina Puzriakova Publications for gene: FOXG1 were set to 21441262; 19564653; 19578037; 27029630
Early onset dystonia v1.141 FOXG1 Arina Puzriakova Classified gene: FOXG1 as Green List (high evidence)
Early onset dystonia v1.141 FOXG1 Arina Puzriakova Gene: foxg1 has been classified as Green List (High Evidence).
Early onset dystonia v1.140 FOXG1 Arina Puzriakova Classified gene: FOXG1 as Red List (low evidence)
Early onset dystonia v1.140 FOXG1 Arina Puzriakova Added comment: Comment on list classification: Upgrading the rating from red to green as there is enough evidence to support the gene-disease association. Also green on the childhood dystonia GMS panel (R57).
Early onset dystonia v1.140 FOXG1 Arina Puzriakova Gene: foxg1 has been classified as Red List (Low Evidence).
Early onset dystonia v1.139 FOXG1 Arina Puzriakova Mode of inheritance for gene: FOXG1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset dystonia v1.138 AFG3L2 Arina Puzriakova Classified gene: AFG3L2 as Green List (high evidence)
Early onset dystonia v1.138 AFG3L2 Arina Puzriakova Added comment: Comment on list classification: Associated with AR and AD ataxia. Dystonia can be a feature but is not typically prominent. Mean age of onset is adulthood, but has been reported in juveniles. More appropriate on ataxia panels.
However, is rated as green on equivalent GMS panels and therefore upgrading the rating from red to green on this 100K panel.
Early onset dystonia v1.138 AFG3L2 Arina Puzriakova Gene: afg3l2 has been classified as Green List (High Evidence).
Early onset dystonia v1.137 AFG3L2 Arina Puzriakova Phenotypes for gene: AFG3L2 were changed from Dystonia to Spinocerebellar ataxia 28, OMIM:610246; Spastic ataxia 5, autosomal recessive, OMIM:614487
Early onset dystonia v1.136 AFG3L2 Arina Puzriakova Mode of inheritance for gene: AFG3L2 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.315 MYCN Zornitza Stark edited their review of gene: MYCN: Added comment: PMID 37710961: Three individuals now reported with gain-of-function missense variants (identical variant in two individuals) and somewhat opposing phenotype cf Feingold. Clinical presentation includes megalencephaly, hypoplastic corpus callosum, postaxial polydactyly, intellectual disability and motor delay. Knock-in mouse model showed morphological manifestations in multiple tissues including digits, female reproductive system and kidney.; Changed publications to: 21224895, 8470948, 37710961; Changed phenotypes to: Feingold syndrome 1, Megalencephaly, intellectual disability, Neurodevelopmental disorder (MONDO:0700092), MYCN-related
Retinal disorders v4.36 CFAP20 Zornitza Stark gene: CFAP20 was added
gene: CFAP20 was added to Retinal disorders. Sources: Literature
Mode of inheritance for gene: CFAP20 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CFAP20 were set to 36329026
Phenotypes for gene: CFAP20 were set to Retinitis pigmentosa (MONDO:0019200)
Review for gene: CFAP20 was set to GREEN
Added comment: Describe 8 individuals from 4 independent families with damaging biallelic variants (homozygous or compound heterozygous) in CFAP20 that segregate with retinal dystrophy. All variants cluster to one side of the protein, with two of the residues directly contacting alpha-tubullin.

Family 1 - consanguineous set of 3 siblings from Sudan, homozygous for CFAP20 c.305G>A; p.Arg102His (they also had a homozygous variant in DYNC1LI2 however CFAP20 was considered the better candidate.
Family 2 - 3 siblings from Spain, 2 with retinal dystrophy, 1 genetically tested and has c.337C>T; p.(Arg113Trp) and c.397delC; p.(Gln133Serfs*5)
Family 3 - single affected family member compound het for c.164+1G>A and c.457A>G; p.(Arg153Gly).
Family 4 - 3 affected siblings with generalised retinopathy and variable neurological deficits with c.164+1G>A and c.257G>A; p.(Tyr86Cys)

For all families, no individuals had signs of polycystic kidney disease; however, not all individuals had kidney imaging. Visual defecit phenotype presented between adolescence and adulthood (17-56 years old).

Used HEK293T cell expression studies to demonstrate a statistically significant decline of mutated CFAP20 protein levels (with the exception of p.Arg102His). To test the specific variants, they used the C.elegans orthologues.

CFAP20 is a ciliopathy candidate. Demonstrate in zebrafish that cfap20 is required for motile cilia function, and in C. elegans, CFAP-20 maintains the structural integrity of non-motile cilia inner junctions, influencing sensory-dependent signalling and development.
Sources: Literature
Intellectual disability v5.315 MAST4 Zornitza Stark gene: MAST4 was added
gene: MAST4 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: MAST4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAST4 were set to 36910266; 33057194
Phenotypes for gene: MAST4 were set to neurodevelopmental disorder MONDO:0700092, MAST4-related
Review for gene: MAST4 was set to GREEN
Added comment: 9 individuals with de novo missense variants and ID reported altogether.

PMID: 36910266 - 4 affecteds from unrelated families, all de novo missense

2x borderline microcephaly (-2SD)
2x gross motor delay
2x dysmorphism
4x ID + seizures
3x abnormal brain MRI findings

PMID: 33057194 - 5x de novos, 4x missense + 1x PTC
Cohort of individuals with severe developmental disorder
individual phenotypic information not provided


Recurrent variants are Thr1471Ile (3x) and Ser1181Phe)
Sources: Literature
Intellectual disability v5.315 ZBTB47 Zornitza Stark gene: ZBTB47 was added
gene: ZBTB47 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: ZBTB47 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZBTB47 were set to 37743782
Phenotypes for gene: ZBTB47 were set to Neurodevelopmental disorder (MONDO#0700092), ZBTB47-related
Review for gene: ZBTB47 was set to GREEN
Added comment: PMID 37743782:
- 5 individuals with de novo missense variants, 4/5 have a recurring p.Gly477Lys. Probands have intellectual disability (5/5), seizures (5/5), hypotonia (5/5), gait abnormalities, and variable movement abnormalities (5/5).
- Missense variants are positioned close to His and Cys residues involved in forming C2H2 zinc fingers.
- No functional studies performed
Sources: Literature
Congenital disorders of glycosylation v4.3 COG3 Zornitza Stark gene: COG3 was added
gene: COG3 was added to Congenital disorders of glycosylation. Sources: Literature
Mode of inheritance for gene: COG3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COG3 were set to 37711075
Phenotypes for gene: COG3 were set to Congenital disorder of glycosylation, type IIbb, MIM# 620546
Review for gene: COG3 was set to AMBER
Added comment: Two COG3 homozygous missense variants in four individuals from two unrelated consanguineous families. Clinical phenotypes of affected individuals include global developmental delay, severe intellectual disability, microcephaly, epilepsy, facial dysmorphism, and variable neurological findings.
Sources: Literature
Hereditary neuropathy or pain disorder v3.60 MT-ND6 Dmitrijs Rots gene: MT-ND6 was added
gene: MT-ND6 was added to Hereditary neuropathy or pain disorder. Sources: Literature
Mode of inheritance for gene gene: MT-ND6 was set to MITOCHONDRIAL
Publications for gene: MT-ND6 were set to PMID: 20301353
Phenotypes for gene: MT-ND6 were set to LHON; peripheral neuropathy
Penetrance for gene: MT-ND6 were set to unknown
Mode of pathogenicity for gene: MT-ND6 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: MT-ND6 was set to GREEN
Added comment: Gene is associated with LHON, but GeneReviews states: "Neurologic abnormalities such as postural tremor, peripheral neuropathy, nonspecific myopathy, and movement disorders have been reported to be more common in individuals with LHON than in the general population. ".
Identified in our lab in a young patient with peripheral neuropathy phenotype only.
Sources: Literature
Structural eye disease v3.40 EPHA2 Sarah Leigh changed review comment from: EPHA2 variants are associated with Cataract 6, multiple types (OMIM:116600) and as definitive Gen2Phen gene for the same condition. PMID: 35918037 presents a review numerous EPHA2 variants and their associated phenotypes, together with a report of a syndromic complex microphthalmia with iris hypoplasia caused compound heterozygous EPHA2 variants. Various ocular features are reported, including microphthalmia, congenital cataracts, nystagmus, microcornea (PMID: 35918037, table 1). This article also highlights that both monoallelic and biallelic EPHA2 variants are responsible for the phenotypes reported in table 1.; to: EPHA2 variants are associated with Cataract 6, multiple types (OMIM:116600) and as definitive Gen2Phen gene for the same condition. PMID: 35918037 presents a review numerous EPHA2 variants and their associated phenotypes, together with a report of a syndromic complex microphthalmia with iris hypoplasia caused compound heterozygous EPHA2 variants. Various ocular features are reported, including microphthalmia, congenital cataracts, nystagmus, microcornea (PMID: 35918037, table 1).
Bilateral congenital or childhood onset cataracts v4.6 EPHA2 Sarah Leigh Tag Q4_23_MOI tag was added to gene: EPHA2.
Bilateral congenital or childhood onset cataracts v4.6 EPHA2 Sarah Leigh Added comment: Comment on mode of inheritance: PMID: 35918037 highlights that both monoallelic and biallelic EPHA2 variants are responsible for the phenotypes reported in table 1, therefore, the mode of inheritance for EPHA2 should be changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal at the next major review.
Bilateral congenital or childhood onset cataracts v4.6 EPHA2 Sarah Leigh Mode of inheritance for gene: EPHA2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Structural eye disease v3.40 EPHA2 Sarah Leigh Added comment: Comment on mode of inheritance: PMID: 35918037 highlights that both monoallelic and biallelic EPHA2 variants are responsible for the phenotypes reported in table 1, therefore, the mode of inheritance for EPHA2 should be changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal at the next major review.
Structural eye disease v3.40 EPHA2 Sarah Leigh Mode of inheritance for gene: EPHA2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v3.39 EPHA2 Sarah Leigh Tag Q4_23_promote_green tag was added to gene: EPHA2.
Tag Q4_23_MOI tag was added to gene: EPHA2.
Tag Q4_23_NHS_review tag was added to gene: EPHA2.
Structural eye disease v3.39 EPHA2 Sarah Leigh reviewed gene: EPHA2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Bilateral congenital or childhood onset cataracts v4.5 EPHA2 Sarah Leigh Phenotypes for gene: EPHA2 were changed from Age-Related Cortical Cataract; Cataract 6, multiple types, 116600 to Cataract 6, multiple types, OMIM:116600
Bilateral congenital or childhood onset cataracts v4.4 EPHA2 Sarah Leigh Publications for gene: EPHA2 were set to
Structural eye disease v3.39 EPHA2 Sarah Leigh Publications for gene: EPHA2 were set to
Structural eye disease v3.38 EPHA2 Sarah Leigh Phenotypes for gene: EPHA2 were changed from Cataract 6, multiple types, 116600 to Cataract 6, multiple types, OMIM:116600
Structural eye disease v3.37 SMG8 Sarah Leigh Tag Q4_23_promote_green tag was added to gene: SMG8.
Tag Q4_23_NHS_review tag was added to gene: SMG8.
Structural eye disease v3.37 SMG8 Sarah Leigh commented on gene: SMG8: SMG8 variants are associated with Alzahrani-Kuwahara syndrome (OMIM:619268) and as strong Gen2Phen gene for the same condition. So far four validated variants have been reported (PMID: 33242396& 34761517) in unrelated cases of OMIM:619268. An ocular phenotype was observed in three of these cases (strabismus, cataract & microphthalmia).
Structural eye disease v3.37 SMG8 Sarah Leigh Classified gene: SMG8 as Amber List (moderate evidence)
Structural eye disease v3.37 SMG8 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Structural eye disease v3.37 SMG8 Sarah Leigh Gene: smg8 has been classified as Amber List (Moderate Evidence).
Structural eye disease v3.36 SMG8 Sarah Leigh Classified gene: SMG8 as Amber List (moderate evidence)
Structural eye disease v3.36 SMG8 Sarah Leigh Gene: smg8 has been classified as Amber List (Moderate Evidence).
Structural eye disease v3.35 SMG8 Sarah Leigh Phenotypes for gene: SMG8 were changed from Alzahrani-Kuwahara syndrome to Alzahrani-Kuwahara syndrome, OMIM:619268
Structural eye disease v3.34 SMG8 Sarah Leigh Publications for gene: SMG8 were set to 34761517
Structural eye disease v3.33 SMG9 Sarah Leigh Publications for gene: SMG9 were set to 27018474; 33242396
Structural eye disease v3.32 SMG9 Sarah Leigh Publications for gene: SMG9 were set to 27018474
Structural eye disease v3.31 PDGFRA Sarah Leigh reviewed gene: PDGFRA: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Structural eye disease v3.31 CDH4 Sarah Leigh changed review comment from: CDH4 variants have not been associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 35034853 identified a monoallelic CDH4 variant in a case with unilateral right iris coloboma and intellectual disability, postnatal
and microcephaly. In situ hybridization showed that cdh4 was expressed in the ciliary marginal zone and
periocular mesenchyme cells in zebrafish embryos at 48 & 56 hpf (PMID: 35034853, Fig S1) and cdh4 morphants displayed
microphthalmia (FigS3), together with pleiotropic developmental defects. PMID: 15918170 had previously reported evidence of brain disorganization in a cdh4 knockdown zebrafish.; to: CDH4 variants have not been associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 35034853 identified a monoallelic CDH4 variant in a case with unilateral right iris coloboma and intellectual disability, postnatal
and microcephaly. In situ hybridization showed that cdh4 was expressed in the ciliary marginal zone and
periocular mesenchyme cells in zebrafish embryos at 48 & 56 hpf (PMID: 35034853, Fig S1) and knockdown of cdh4 morphants displayed microphthalmia (FigS3), together with pleiotropic developmental defects. PMID: 15918170 had previously reported evidence of brain disorganization in a cdh4 knockdown zebrafish.
Structural eye disease v3.31 PDGFRA Sarah Leigh Classified gene: PDGFRA as Amber List (moderate evidence)
Structural eye disease v3.31 PDGFRA Sarah Leigh Gene: pdgfra has been classified as Amber List (Moderate Evidence).
Cystic kidney disease v4.17 NEK8 Dmitrijs Rots reviewed gene: NEK8: 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: 37598857; Phenotypes: polycystic kidney disease; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autoinflammatory disorders v1.1 UBA1 Dorota Rowczenio reviewed gene: UBA1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 33108101, 36823397, 34048852, 34213531, 34340250, 33930131, 34802547, 37501758, 37223371, 36692560, 33789873, 33779074; Phenotypes: ever, chondritis, vasculitis, neutrophilic dermatosis, sterile alveolitis, progressive bone marrow failure, cytopenia; Mode of inheritance: Other; Current diagnostic: yes
Primary immunodeficiency or monogenic inflammatory bowel disease v4.53 RELA Achchuthan Shanmugasundram Phenotypes for gene: RELA were changed from Autoinflammatory disease, familial, Behcet-like-3, OMIM:618287 to Autoinflammatory disease, familial, Behcet-like-3, OMIM:618287
Primary immunodeficiency or monogenic inflammatory bowel disease v4.52 RELA Achchuthan Shanmugasundram Phenotypes for gene: RELA were changed from Mucocutaneous ulceration, chronic, 618287; RelA haplosufficiency; Mucosal ulceration, impaired NFkB activation; Immunodeficiencies affecting cellular and humoral immunity to Autoinflammatory disease, familial, Behcet-like-3, OMIM:618287
Primary immunodeficiency or monogenic inflammatory bowel disease v4.51 RELA Achchuthan Shanmugasundram reviewed gene: RELA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Autoinflammatory disease, familial, Behcet-like-3, OMIM:618287; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v4.51 POLD1 Achchuthan Shanmugasundram Classified gene: POLD1 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.51 POLD1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are three unrelated cases and functional data in support of the association of biallelic POL1D variants with immunodeficiency. Hence, this gene can be promoted to green rating in the next GMS review.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.51 POLD1 Achchuthan Shanmugasundram Gene: pold1 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.50 POLD1 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: POLD1.
Tag Q4_23_NHS_review tag was added to gene: POLD1.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.50 POLD1 Achchuthan Shanmugasundram reviewed gene: POLD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v4.50 IRF4 Hannah Knight reviewed gene: IRF4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 36917008, PMID: 36662884; Phenotypes: ?Whipple's disease; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v4.50 MAN2B2 Hannah Knight reviewed gene: MAN2B2: Rating: AMBER; Mode of pathogenicity: None; Publications: 35637269; Phenotypes: Severe developmental delay, dysmorphic facial features, immune dysregulation, developmental delay, stroke; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v4.50 PSMB10 Hannah Knight reviewed gene: PSMB10: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37600812; Phenotypes: Proteasome-associated autoinflammatory syndrome 5; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v4.50 NLRP1 Hannah Knight reviewed gene: NLRP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 31873740; Phenotypes: Autoinflammatory disease with corneal and mucosal dyskeratosis; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v4.50 GIMAP5 Hannah Knight reviewed gene: GIMAP5: Rating: AMBER; Mode of pathogenicity: None; Publications: 33956074; Phenotypes: Portal hypertension, noncirrhotic, 2, MIM# 619463; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
NARP syndrome or maternally inherited Leigh syndrome v1.1 MT-ND6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND6.
Childhood onset dystonia, chorea or related movement disorder v3.50 MT-ND6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND6.
Adult onset dystonia, chorea or related movement disorder v3.13 MT-ND6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND6.
Retinal disorders v4.36 MT-ND6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND6.
Mitochondrial disorders v4.99 MT-ND6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND6.
Likely inborn error of metabolism v4.52 MT-ND6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND6.
Undiagnosed metabolic disorders v1.601 MT-ND6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND6.
Adult onset neurodegenerative disorder v4.37 MT-ND6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND6.
Optic neuropathy v4.11 MT-ND6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND6.
Structural basal ganglia disorders v1.38 MT-ND6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND6.
Albinism or congenital nystagmus v3.1 MT-ND6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND6.
Early onset dystonia v1.135 MT-ND6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND6.
Leber hereditary optic neuropathy v2.6 MT-ND6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND6.
Infantile nystagmus v1.10 MT-ND6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND6.
Childhood onset dystonia, chorea or related movement disorder v3.50 MT-ND5 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND5.
Mitochondrial disorders v4.99 MT-ND5 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND5.
Likely inborn error of metabolism v4.52 MT-ND5 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND5.
Undiagnosed metabolic disorders v1.601 MT-ND5 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND5.
Childhood onset dystonia, chorea or related movement disorder v3.50 MT-ND4L Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND4L.
Mitochondrial disorders v4.99 MT-ND4L Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND4L.
Likely inborn error of metabolism v4.52 MT-ND4L Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND4L.
Undiagnosed metabolic disorders v1.601 MT-ND4L Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND4L.
Childhood onset dystonia, chorea or related movement disorder v3.50 MT-ND4 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND4.
Retinal disorders v4.36 MT-ND4 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND4.
Mitochondrial disorders v4.99 MT-ND4 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND4.
Intellectual disability v5.315 MT-ND4 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND4.
Likely inborn error of metabolism v4.52 MT-ND4 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND4.
Undiagnosed metabolic disorders v1.601 MT-ND4 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND4.
Optic neuropathy v4.11 MT-ND4 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND4.
Leber hereditary optic neuropathy v2.6 MT-ND4 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND4.
Childhood onset dystonia, chorea or related movement disorder v3.50 MT-ND3 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND3.
Mitochondrial disorders v4.99 MT-ND3 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND3.
Likely inborn error of metabolism v4.52 MT-ND3 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND3.
Undiagnosed metabolic disorders v1.601 MT-ND3 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND3.
Childhood onset dystonia, chorea or related movement disorder v3.50 MT-ND2 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND2.
Mitochondrial disorders v4.99 MT-ND2 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND2.
Likely inborn error of metabolism v4.52 MT-ND2 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND2.
Undiagnosed metabolic disorders v1.601 MT-ND2 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND2.
Albinism or congenital nystagmus v3.1 MT-ND2 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND2.
Infantile nystagmus v1.10 MT-ND2 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND2.
Childhood onset dystonia, chorea or related movement disorder v3.50 MT-ND1 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND1.
Adult onset dystonia, chorea or related movement disorder v3.13 MT-ND1 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND1.
Retinal disorders v4.36 MT-ND1 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND1.
Mitochondrial disorders v4.99 MT-ND1 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND1.
Intellectual disability v5.315 MT-ND1 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND1.
Likely inborn error of metabolism v4.52 MT-ND1 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND1.
Undiagnosed metabolic disorders v1.601 MT-ND1 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND1.
Optic neuropathy v4.11 MT-ND1 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND1.
Structural basal ganglia disorders v1.38 MT-ND1 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND1.
Sudden death in young people v1.15 MT-ND1 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND1.
Leber hereditary optic neuropathy v2.6 MT-ND1 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND1.
Childhood onset dystonia, chorea or related movement disorder v3.50 MT-CYB Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-CYB.
Mitochondrial disorders v4.99 MT-CYB Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-CYB.
Likely inborn error of metabolism v4.52 MT-CYB Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-CYB.
Undiagnosed metabolic disorders v1.601 MT-CYB Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-CYB.
Albinism or congenital nystagmus v3.1 MT-CYB Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-CYB.
Sudden death in young people v1.15 MT-CYB Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-CYB.
Infantile nystagmus v1.10 MT-CYB Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-CYB.
Childhood onset dystonia, chorea or related movement disorder v3.50 MT-CO3 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-CO3.
Mitochondrial disorders v4.99 MT-CO3 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-CO3.
Early onset or syndromic epilepsy v4.120 MT-CO3 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-CO3.
Likely inborn error of metabolism v4.52 MT-CO3 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-CO3.
Undiagnosed metabolic disorders v1.601 MT-CO3 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-CO3.
Albinism or congenital nystagmus v3.1 MT-CO3 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-CO3.
Infantile nystagmus v1.10 MT-CO3 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-CO3.
Acute rhabdomyolysis v1.16 MT-CO2 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-CO2.
Childhood onset dystonia, chorea or related movement disorder v3.50 MT-CO2 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-CO2.
Mitochondrial disorders v4.99 MT-CO2 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-CO2.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.50 CD8A Hannah Knight changed review comment from: PMID: 26563160 reported a third patient with this disorder. From consanguineous Portuguese family, with same homozygous variant as previously reported. Not sure whether this is enough to push gene into green category (as same variant, and Portuguese vs Spanish Gypsy heritage); to: PMID: 26563160 reported a third patient with this disorder. From consanguineous Portuguese family, with same homozygous variant as previously reported. Not sure whether this is enough to push gene into green category (as same variant, and Portuguese vs Spanish Gypsy heritage)
PMID mentioned below, but not sure if taken into account as no reference to contents of paper
Likely inborn error of metabolism v4.52 MT-CO2 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-CO2.
Undiagnosed metabolic disorders v1.601 MT-CO2 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-CO2.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.50 CD8A Hannah Knight reviewed gene: CD8A: Rating: AMBER; Mode of pathogenicity: None; Publications: 26563160; Phenotypes: CD8 deficiency familial, 608957; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and metabolic muscle disorders v3.37 MT-CO2 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-CO2.
Acute rhabdomyolysis v1.16 MT-CO1 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-CO1.
Childhood onset dystonia, chorea or related movement disorder v3.50 MT-CO1 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-CO1.
Mitochondrial disorders v4.99 MT-CO1 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-CO1.
Likely inborn error of metabolism v4.52 MT-CO1 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-CO1.
Undiagnosed metabolic disorders v1.601 MT-CO1 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-CO1.
Albinism or congenital nystagmus v3.1 MT-CO1 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-CO1.
Rhabdomyolysis and metabolic muscle disorders v3.37 MT-CO1 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-CO1.
Infantile nystagmus v1.10 MT-CO1 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-CO1.
Childhood onset dystonia, chorea or related movement disorder v3.50 MT-ATP8 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ATP8.
Mitochondrial disorders v4.99 MT-ATP8 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ATP8.
Likely inborn error of metabolism v4.52 MT-ATP8 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ATP8.
Undiagnosed metabolic disorders v1.601 MT-ATP8 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ATP8.
Skeletal muscle channelopathy v3.1 MT-ATP8 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ATP8.
Paroxysmal central nervous system disorders v3.8 MT-ATP8 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ATP8.
Skeletal Muscle Channelopathies v1.45 MT-ATP8 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ATP8.
NARP syndrome or maternally inherited Leigh syndrome v1.1 MT-ATP6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ATP6.
Childhood onset dystonia, chorea or related movement disorder v3.50 MT-ATP6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ATP6.
Hereditary neuropathy or pain disorder v3.60 MT-ATP6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ATP6.
Adult onset dystonia, chorea or related movement disorder v3.13 MT-ATP6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ATP6.
Retinal disorders v4.36 MT-ATP6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ATP6.
Hereditary ataxia with onset in adulthood v4.24 MT-ATP6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ATP6.
Mitochondrial disorders v4.99 MT-ATP6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ATP6.
Intellectual disability v5.315 MT-ATP6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ATP6.
Hereditary neuropathy v1.472 MT-ATP6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ATP6.
Likely inborn error of metabolism v4.52 MT-ATP6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ATP6.
Undiagnosed metabolic disorders v1.601 MT-ATP6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ATP6.
Adult onset neurodegenerative disorder v4.37 MT-ATP6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ATP6.
Skeletal muscle channelopathy v3.1 MT-ATP6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ATP6.
Optic neuropathy v4.11 MT-ATP6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ATP6.
Paroxysmal central nervous system disorders v3.8 MT-ATP6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ATP6.
Structural basal ganglia disorders v1.38 MT-ATP6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ATP6.
Albinism or congenital nystagmus v3.1 MT-ATP6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ATP6.
Hereditary ataxia v1.331 MT-ATP6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ATP6.
Ataxia and cerebellar anomalies - narrow panel v4.38 MT-ATP6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ATP6.
Skeletal Muscle Channelopathies v1.45 MT-ATP6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ATP6.
Infantile nystagmus v1.10 MT-ATP6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ATP6.
Structural eye disease v3.30 CDH4 Sarah Leigh Publications for gene: CDH4 were set to 35034853
Structural eye disease v3.29 CDH4 Sarah Leigh reviewed gene: CDH4: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v5.315 ERI1 Achchuthan Shanmugasundram Classified gene: ERI1 as Amber List (moderate evidence)
Intellectual disability v5.315 ERI1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are four unrelated cases with biallelic null ERI1 variants and mild intellectual disability. Hence, this gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.315 ERI1 Achchuthan Shanmugasundram Gene: eri1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.314 ERI1 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: ERI1.
Intellectual disability v5.314 ERI1 Achchuthan Shanmugasundram gene: ERI1 was added
gene: ERI1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: ERI1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERI1 were set to 36208065; 37352860
Phenotypes for gene: ERI1 were set to intellectual disability, MONDO:0001071
Review for gene: ERI1 was set to GREEN
Added comment: PMID:36208065 reported a female patient with a homozygous nonsense variant in ERI1 gene and with mild intellectual disability (ID), eyelid ptosis, and anomalies in her hands and feet (brachydactyly, clinodactyly, dysplastic/short nail of halluces, brachytelephalangy, short metacarpals, and toe syndactyly).

PMID:37352860 reported eight patients from seven unrelated families with compound heterozygous variants in ERI1 gene, of which four patients had missense variants, three had null variants and one had missense and PTC variants. The patients with missense variants had a more severe severe spondyloepimetaphyseal dysplasia, syndactyly, brachydactyly/clinodactyly/camptodactyly. The patients with null variants had mild ID and digit anomalies including brachydactyly/clinodactyly/camptodactyly. The patient with both missense and PTC variants had phenotype with short stature, syndactyly, brachydactyly/clinodactyly/camptodactyly, and delayed motor milestones and speech and generalised hypotonia.

This gene has not yet been reported with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Structural eye disease v3.29 CDH4 Sarah Leigh Classified gene: CDH4 as Amber List (moderate evidence)
Structural eye disease v3.29 CDH4 Sarah Leigh Gene: cdh4 has been classified as Amber List (Moderate Evidence).
Structural eye disease v3.28 BMPR1B Sarah Leigh Tag Q4_23_promote_green tag was added to gene: BMPR1B.
Tag Q4_23_NHS_review tag was added to gene: BMPR1B.
Structural eye disease v3.28 BMPR1B Sarah Leigh Classified gene: BMPR1B as Amber List (moderate evidence)
Structural eye disease v3.28 BMPR1B Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Structural eye disease v3.28 BMPR1B Sarah Leigh Gene: bmpr1b has been classified as Amber List (Moderate Evidence).
Structural eye disease v3.27 BMPR1B Sarah Leigh Added comment: Comment on phenotypes: Ocular coloboma has yet to be associated with OMIM:609441, OMIM:616849 or OMIM:112600.
Structural eye disease v3.27 BMPR1B Sarah Leigh Phenotypes for gene: BMPR1B were changed from Ocular coloboma to Ocular coloboma
Structural eye disease v3.26 BMPR1B Sarah Leigh commented on gene: BMPR1B
Skeletal dysplasia v4.25 ERI1 Achchuthan Shanmugasundram Classified gene: ERI1 as Amber List (moderate evidence)
Skeletal dysplasia v4.25 ERI1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for promotion of this gene to green rating in the next GMS review.
Skeletal dysplasia v4.25 ERI1 Achchuthan Shanmugasundram Gene: eri1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v4.24 ERI1 Achchuthan Shanmugasundram Tag Q4_23_NHS_review tag was added to gene: ERI1.
Skeletal dysplasia v4.24 ERI1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Tracy Lester, four patients from three different families were identified with compound heterozygous missense variants in ERI1 gene and were reported with spondyloepimetaphyseal dysplasia. In addition, another unrelated patient with a missense and a null variant was reported with spondyloepimetaphyseal dysplasia, and delayed motor milestones and speech and generalised hypotonia.; to: As reviewed by Tracy Lester, four patients from three different families were identified with compound heterozygous missense variants in ERI1 gene and were reported with spondyloepimetaphyseal dysplasia. In addition, another unrelated patient with a missense and a null variant was reported with spondyloepimetaphyseal dysplasia, and delayed motor milestones and speech and generalised hypotonia (PMID:37352860).


This gene has not yet been associated with relevantly phenotypes either in OMIM or in Gene2Phenotype.
Skeletal dysplasia v4.24 ERI1 Achchuthan Shanmugasundram commented on gene: ERI1: As reviewed by Tracy Lester, four patients from three different families were identified with compound heterozygous missense variants in ERI1 gene and were reported with spondyloepimetaphyseal dysplasia. In addition, another unrelated patient with a missense and a null variant was reported with spondyloepimetaphyseal dysplasia, and delayed motor milestones and speech and generalised hypotonia.
Skeletal dysplasia v4.24 ERI1 Achchuthan Shanmugasundram Phenotypes for gene: ERI1 were changed from spondyloepimetaphyseal dysplasia; digital anomalies to spondyloepimetaphyseal dysplasia, MONDO:0100510
Skeletal dysplasia v4.23 ERI1 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: ERI1.
Skeletal dysplasia v4.23 ERI1 Achchuthan Shanmugasundram reviewed gene: ERI1: Rating: GREEN; Mode of pathogenicity: None; Publications: 37352860; Phenotypes: spondyloepimetaphyseal dysplasia, MONDO:0100510; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Structural eye disease v3.26 ANK3 Sarah Leigh Tag Q4_23_promote_green tag was added to gene: ANK3.
Tag Q4_23_NHS_review tag was added to gene: ANK3.
Severe microcephaly v4.37 BUB1 Eleanor Williams commented on gene: BUB1
Structural eye disease v3.26 ANK3 Sarah Leigh Classified gene: ANK3 as Amber List (moderate evidence)
Structural eye disease v3.26 ANK3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Structural eye disease v3.26 ANK3 Sarah Leigh Gene: ank3 has been classified as Amber List (Moderate Evidence).
Structural eye disease v3.25 ANK3 Sarah Leigh edited their review of gene: ANK3: Added comment: ANK3 variants have been associated with Intellectual developmental disorder, autosomal recessive 37 (OMIM:615493), however, this phenotype does not include Ocular coloboma to date. PMID: 35034853 reports two monoallelic ANK3 variants in two cases whose phenotype includes ocular coloboma. The authors also present supportive ank3 knockdown experiments in zebrafish, which revealed a coloboma and/or microphthalmia phenotype.; Changed rating: GREEN
Severe microcephaly v4.37 BUB1 Eleanor Williams Tag Q4_22_promote_green was removed from gene: BUB1.
Tag Q4_23_promote_green tag was added to gene: BUB1.
Childhood onset dystonia, chorea or related movement disorder v3.50 ADAR Eleanor Williams commented on gene: ADAR
Childhood onset dystonia, chorea or related movement disorder v3.50 ADAR Eleanor Williams Tag Q4_22_MOI was removed from gene: ADAR.
Structural eye disease v3.25 ANK3 Sarah Leigh Added comment: Comment on phenotypes: Ocular coloboma has yet to be associated with OMIM:615493.
Structural eye disease v3.25 ANK3 Sarah Leigh Phenotypes for gene: ANK3 were changed from Ocular coloboma to Intellectual developmental disorder, autosomal recessive 37, OMIM:615493
Arthrogryposis v5.17 SELENON Eleanor Williams Tag Q1_23_MOI was removed from gene: SELENON.
Fetal anomalies v3.111 C1QBP Eleanor Williams commented on gene: C1QBP
Fetal anomalies v3.111 C1QBP Eleanor Williams Tag Q2_23_promote_green was removed from gene: C1QBP.
Tag Q2_23_NHS_review was removed from gene: C1QBP.
Childhood onset hereditary spastic paraplegia v4.26 SPG7 Eleanor Williams commented on gene: SPG7
Childhood onset hereditary spastic paraplegia v4.26 SPG7 Eleanor Williams Tag Q2_23_MOI was removed from gene: SPG7.
Mitochondrial disorders v4.99 SPG7 Eleanor Williams commented on gene: SPG7
Mitochondrial disorders v4.99 SPG7 Eleanor Williams Tag Q2_23_MOI was removed from gene: SPG7.
Arthrogryposis v5.17 SELENON Eleanor Williams commented on gene: SELENON
Structural eye disease v3.24 ANK3 Sarah Leigh Publications for gene: ANK3 were set to 35034853
Fetal anomalies v3.111 CDX2 Eleanor Williams commented on gene: CDX2: Removed the Q2_23_promote_green tag as has now been promoted to green.
Fetal anomalies v3.111 CDX2 Eleanor Williams Tag Q2_23_promote_green was removed from gene: CDX2.
Structural eye disease v3.23 ANK3 Sarah Leigh Classified gene: ANK3 as Amber List (moderate evidence)
Structural eye disease v3.23 ANK3 Sarah Leigh Gene: ank3 has been classified as Amber List (Moderate Evidence).
Bleeding and platelet disorders v3.3 ADAMTS13 Sarah Leigh Tag Q4_23_NHS_review tag was added to gene: ADAMTS13.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.50 PTPN2 Hannah Knight reviewed gene: PTPN2: Rating: AMBER; Mode of pathogenicity: None; Publications: 32721438; Phenotypes: Very early onset inflammatory bowel disease; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Structural eye disease v3.22 ARHGAP35 Sarah Leigh Tag Q4_23_promote_green tag was added to gene: ARHGAP35.
Tag Q4_23_NHS_review tag was added to gene: ARHGAP35.
Structural eye disease v3.22 ARHGAP35 Sarah Leigh edited their review of gene: ARHGAP35: Added comment: ARHGAP35 variants are not associated with a phenotype in OMIM, but ARHGAP35 has definitive association with ARHGAP35-related developmental disorder (monoallelic) in Gen2Phen gene. PMID: 36450800 reports four monoallelic ARHGAP35 variants in four unrelated cases.; Changed rating: GREEN
Structural eye disease v3.22 ARHGAP35 Sarah Leigh Classified gene: ARHGAP35 as Amber List (moderate evidence)
Structural eye disease v3.22 ARHGAP35 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Structural eye disease v3.22 ARHGAP35 Sarah Leigh Gene: arhgap35 has been classified as Amber List (Moderate Evidence).
Bleeding and platelet disorders v3.3 ADAMTS13 Sarah Leigh Tag Q4_23_promote_green tag was added to gene: ADAMTS13.
Bleeding and platelet disorders v3.3 ADAMTS13 Sarah Leigh Classified gene: ADAMTS13 as Amber List (moderate evidence)
Bleeding and platelet disorders v3.3 ADAMTS13 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Bleeding and platelet disorders v3.3 ADAMTS13 Sarah Leigh Gene: adamts13 has been classified as Amber List (Moderate Evidence).
Bleeding and platelet disorders v3.2 ADAMTS13 Sarah Leigh reviewed gene: ADAMTS13: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
DDG2P v3.73 ZFYVE19 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: ZFYVE19.
DDG2P v3.73 ZFYVE19 Achchuthan Shanmugasundram commented on gene: ZFYVE19: The OMIM entry for this gene is OMIM:619635, which has been cross-checked with Ensembl, HGNC and G2P. Hence, gene-checked tag has been added.
DDG2P v3.73 TUBGCP2 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: TUBGCP2.
Intellectual disability v5.313 TUBGCP2 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: TUBGCP2.
DDG2P v3.73 TTC5 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: TTC5.
DDG2P v3.73 TRIT1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: TRIT1.
Fetal anomalies v3.111 TRIT1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: TRIT1.
Early onset or syndromic epilepsy v4.120 PLA2G6 Sarah Leigh Tag Q4_23_promote_green tag was added to gene: PLA2G6.
Early onset or syndromic epilepsy v4.120 PLA2G6 Sarah Leigh edited their review of gene: PLA2G6: Changed rating: GREEN
Early onset or syndromic epilepsy v4.120 PLA2G6 Sarah Leigh commented on gene: PLA2G6: Sixteen cases of PLA2G6-associated neurodegeneration (PLAN) were examined in PMID: 30340910. Seizures were evident in 5/10 cases with infantile PLAN and in 3/6 cases with childhood PLAN. A total of nine PLA2G6 variants were associated with a phenotype that included seizures.
DDG2P v3.73 TMEM94 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: TMEM94.
DDG2P v3.73 TMEM63C Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: TMEM63C.
DDG2P v3.73 TMEM63A Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: TMEM63A.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.174 TMEM251 Achchuthan Shanmugasundram Tag new-gene-name tag was added to gene: TMEM251.
Tag gene-checked tag was added to gene: TMEM251.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.174 TMEM251 Achchuthan Shanmugasundram commented on gene: TMEM251: Added new-gene-name tag, new approved HGNC gene symbol for TMEM251 is LYSET.

The OMIM entry for this gene is OMIM:619332, which has been cross-checked with Ensembl, HGNC and G2P. Hence, gene-checked tag has been added.
Skeletal dysplasia v4.23 TMEM251 Achchuthan Shanmugasundram Tag new-gene-name tag was added to gene: TMEM251.
Tag gene-checked tag was added to gene: TMEM251.
Skeletal dysplasia v4.23 TMEM251 Achchuthan Shanmugasundram commented on gene: TMEM251
DDG2P v3.73 TMEM251 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: TMEM251.
DDG2P v3.73 TMEM251 Achchuthan Shanmugasundram commented on gene: TMEM251: The OMIM entry for this gene is OMIM:619332, which has been cross-checked with Ensembl, HGNC and G2P. Hence, gene-checked tag has been added.
DDG2P v3.73 TMEM222 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: TMEM222.
DDG2P v3.73 TMEM218 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: TMEM218.
DDG2P v3.73 TMEM163 Achchuthan Shanmugasundram commented on gene: TMEM163: The OMIM entry for this gene is OMIM:618978, which has been cross-checked with Ensembl, HGNC and G2P. Hence, gene-checked tag has been added.
Early onset or syndromic epilepsy v4.120 PLA2G6 Sarah Leigh Classified gene: PLA2G6 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.120 PLA2G6 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Early onset or syndromic epilepsy v4.120 PLA2G6 Sarah Leigh Gene: pla2g6 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.119 PLA2G6 Sarah Leigh Added comment: Comment on phenotypes: PLA2G6-associated neurodegeneration (PLAN)
Early onset or syndromic epilepsy v4.119 PLA2G6 Sarah Leigh Phenotypes for gene: PLA2G6 were changed from PLA2G6-associated neurodegeneration (PLAN); Familial cortical myoclonic tremor with epilepsy (FCMTE); Infantile neuroaxonal dystrophy 1, 256600; Neurodegeneration with brain iron accumulation 2B, 610217 to Infantile neuroaxonal dystrophy 1, OMIM:256600; neurodegeneration with brain iron accumulation 2A, MONDO:0024457; Neurodegeneration with brain iron accumulation 2B, OMIM:610217; neurodegeneration with brain iron accumulation 2B, MONDO:0012444; Parkinson disease 14, autosomal recessive, OMIM:612953; autosomal recessive Parkinson disease 14, MONDO:0013060
DDG2P v3.73 TMEM163 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: TMEM163.
DDG2P v3.73 TBC1D2B Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: TBC1D2B.
DDG2P v3.73 SPATA5L1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: SPATA5L1.
DDG2P v3.73 RNPC3 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: RNPC3.
DDG2P v3.73 PPP1R21 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: PPP1R21.
Paediatric disorders - additional genes v3.5 PAPPA2 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: PAPPA2.
Paediatric disorders - additional genes v3.5 PAPPA2 Achchuthan Shanmugasundram commented on gene: PAPPA2
DDG2P v3.73 NTNG2 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: NTNG2.
DDG2P v3.73 NHLRC2 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: NHLRC2.
Fetal anomalies v3.111 NDUFAF8 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: NDUFAF8.
DDG2P v3.73 NDUFAF8 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: NDUFAF8.
DDG2P v3.73 MMGT1 Achchuthan Shanmugasundram commented on gene: MMGT1: The OMIM entry for this gene is OMIM:301098, which has been cross-checked with Ensembl, HGNC and G2P. Hence, gene-checked tag has been added.
DDG2P v3.73 MMGT1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: MMGT1.
Intellectual disability v5.313 MMGT1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: MMGT1.
Intellectual disability v5.313 MMGT1 Achchuthan Shanmugasundram commented on gene: MMGT1
DDG2P v3.73 METTL5 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: METTL5.
White matter disorders and cerebral calcification - narrow panel v3.21 HPDL Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: HPDL.
DDG2P v3.73 HPDL Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: HPDL.
Early onset or syndromic epilepsy v4.118 PLA2G6 Sarah Leigh Tag watchlist_moi tag was added to gene: PLA2G6.
Early onset or syndromic epilepsy v4.118 HECTD4 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: HECTD4.
Early onset or syndromic epilepsy v4.118 HECTD4 Achchuthan Shanmugasundram commented on gene: HECTD4: The OMIM entry for this gene is OMIM:620209, which has been cross-checked with both Ensembl and HGNC. Hence, gene-checked tag has been added.
Childhood onset hereditary spastic paraplegia v4.26 HECTD4 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: HECTD4.
Childhood onset hereditary spastic paraplegia v4.26 HECTD4 Achchuthan Shanmugasundram commented on gene: HECTD4: The OMIM entry for this gene is OMIM:620209, which has been cross-checked with both Ensembl and HGNC. Hence, gene-checked tag has been added.
Malformations of cortical development v4.8 HECTD4 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: HECTD4.
Malformations of cortical development v4.8 HECTD4 Achchuthan Shanmugasundram commented on gene: HECTD4: The OMIM entry for this gene is OMIM:620209, which has been cross-checked with both Ensembl and HGNC. Hence, gene-checked tag has been added.
Intellectual disability v5.313 HECTD4 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: HECTD4.
Intellectual disability v5.313 HECTD4 Achchuthan Shanmugasundram commented on gene: HECTD4: The OMIM entry for this gene is OMIM:620209, which has been cross-checked with both Ensembl and HGNC. Hence, gene-checked tag has been added.
Likely inborn error of metabolism v4.52 SLC6A20 Sarah Leigh Tag refuted tag was added to gene: SLC6A20.
Tag Q4_23_demote_red tag was added to gene: SLC6A20.
Likely inborn error of metabolism v4.52 SLC6A20 Sarah Leigh edited their review of gene: SLC6A20: Added comment: The gene disease associations of SLC6A20 with Hyperglycinuria (OMIM:138500) and Iminoglycinuria, digenic (OMIM:242600) have been refuted in OMIM. The single SLC6A20 variant rs17279437 has been reclassified as a polymorphism, because it is present in 19,986 of 278,932 alleles and in 856 homozygotes in the gnomAD database (v2.1.1), for an allele frequency of 0.07165 (Personal Communication to OMIM from Hamosh, A. Baltimore, Md. 3rd April 2023).; Changed rating: RED; Changed phenotypes to: Hyperglycinuria 138500, Iminoglycinuria, digenic 242600
Undiagnosed metabolic disorders v1.601 SLC6A20 Sarah Leigh Tag refuted tag was added to gene: SLC6A20.
DDG2P v3.73 GREB1L Achchuthan Shanmugasundram Deleted their comment
DDG2P v3.73 GREB1L Achchuthan Shanmugasundram commented on gene: GREB1L: The OMIM entry for this gene is OMIM:617782, which has been cross-checked with Ensembl, HGNC and G2P. Hence, gene-checked tag has been added.
DDG2P v3.73 GREB1L Achchuthan Shanmugasundram commented on gene: GREB1L: The OMIM entry for this gene is OMIM:617782, which has been cross-checked with Ensembl, HGNC and G2P. Hence, gene-checked tag has been added.
DDG2P v3.73 GREB1L Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: GREB1L.
Undiagnosed metabolic disorders v1.601 SLC6A20 Sarah Leigh Classified gene: SLC6A20 as Red List (low evidence)
Undiagnosed metabolic disorders v1.601 SLC6A20 Sarah Leigh Gene: slc6a20 has been classified as Red List (Low Evidence).
Undiagnosed metabolic disorders v1.600 SLC6A20 Sarah Leigh edited their review of gene: SLC6A20: Added comment: The gene disease associations of SLC6A20 with Hyperglycinuria (OMIM:138500) and Iminoglycinuria, digenic (OMIM:242600) have been refuted in OMIM. The single SLC6A20 variant rs17279437 has been reclassified as a polymorphism, because it is present in 19,986 of 278,932 alleles and in 856 homozygotes in the gnomAD database (v2.1.1), for an allele frequency of 0.07165 (Personal Communication to OMIM from Hamosh, A. Baltimore, Md. 3rd April 2023).; Changed rating: RED; Changed phenotypes to: Hyperglycinuria 138500, Iminoglycinuria, digenic 242600
Skeletal ciliopathies v3.11 FAM149B1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: FAM149B1.
Skeletal ciliopathies v3.11 FAM149B1 Achchuthan Shanmugasundram commented on gene: FAM149B1
Neurological ciliopathies v3.13 FAM149B1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: FAM149B1.
Neurological ciliopathies v3.13 FAM149B1 Achchuthan Shanmugasundram commented on gene: FAM149B1
Ophthalmological ciliopathies v3.3 FAM149B1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: FAM149B1.
Ophthalmological ciliopathies v3.3 FAM149B1 Achchuthan Shanmugasundram commented on gene: FAM149B1
DDG2P v3.73 FAM149B1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: FAM149B1.
DDG2P v3.73 FAM149B1 Achchuthan Shanmugasundram commented on gene: FAM149B1: The OMIM entry for this gene is OMIM:618413, which has been cross-checked with Ensembl, HGNC and G2P. Hence, gene-checked tag has been added.
Respiratory ciliopathies including non-CF bronchiectasis v3.1 DAW1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: DAW1.
Respiratory ciliopathies including non-CF bronchiectasis v3.1 DAW1 Achchuthan Shanmugasundram commented on gene: DAW1
Laterality disorders and isomerism v3.4 DAW1 Achchuthan Shanmugasundram commented on gene: DAW1
Laterality disorders and isomerism v3.4 DAW1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: DAW1.
DDG2P v3.73 DAW1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: DAW1.
DDG2P v3.73 DAW1 Achchuthan Shanmugasundram commented on gene: DAW1: The OMIM entry for this gene is OMIM:620279, which has been cross-checked with Ensembl, HGNC and G2P. Hence, gene-checked tag has been added.
Paediatric or syndromic cardiomyopathy v3.39 SLC22A5 Eleanor Williams Tag Q4_23_MOI tag was added to gene: SLC22A5.
Paediatric or syndromic cardiomyopathy v3.39 SLC22A5 Eleanor Williams Added comment: Comment on mode of inheritance: Changing the mode of inheritance back to Both monoallelic and biallelic as this is what it is on the last signed off version of the panel (v3.0) and no change in mode of inheritance has been agreed. Also adding a tag to propose that the mode of inheritance should be changed to biallelic as proposed by Sarah Leigh.
Paediatric or syndromic cardiomyopathy v3.39 SLC22A5 Eleanor Williams Mode of inheritance for gene: SLC22A5 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v4.23 KIF24 Eleanor Williams Tag gene-checked tag was added to gene: KIF24.
Skeletal dysplasia v4.23 KIF24 Eleanor Williams commented on gene: KIF24: This gene is not currently associated with a disease phenotype in OMIM, but checked PMID:35748595 to make sure it is the same gene listed in the publication as on this panel and it is, so added the gene-checked tag
Mitochondrial disorders v4.99 COX16 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: COX16.
Rhabdomyolysis and metabolic muscle disorders v3.37 MT-CO2 Eleanor Williams commented on gene: MT-CO2: This gene is not currently associated with a disease phenotype in OMIM, but checked PMID:23616164 to make sure it is the same gene listed in the publication as on this panel and it is, so added the gene-checked tag
Mitochondrial disorders v4.99 COX16 Achchuthan Shanmugasundram commented on gene: COX16
Possible mitochondrial disorder - nuclear genes v3.49 COX16 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: COX16.
Rhabdomyolysis and metabolic muscle disorders v3.37 MT-CO2 Eleanor Williams Tag gene-checked tag was added to gene: MT-CO2.
Possible mitochondrial disorder - nuclear genes v3.49 COX16 Achchuthan Shanmugasundram commented on gene: COX16
Rhabdomyolysis and metabolic muscle disorders v3.37 MT-CO1 Eleanor Williams Tag gene-checked tag was added to gene: MT-CO1.
Mitochondrial disorder with complex IV deficiency v3.2 COX16 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: COX16.
Rhabdomyolysis and metabolic muscle disorders v3.37 MT-CO1 Eleanor Williams commented on gene: MT-CO1: This gene is not currently associated with a disease phenotype in OMIM, but checked PMID:25929793 to make sure it is the same gene listed in the publication as on this panel. The gene name in this publication is COX1 but this is an alias name for MT-CO1(https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7419) , and therefore it is likely this is the correct gene. Added the gene-checked tag
Mitochondrial disorder with complex IV deficiency v3.2 COX16 Achchuthan Shanmugasundram commented on gene: COX16
DDG2P v3.73 COX16 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: COX16.
DDG2P v3.73 COX16 Achchuthan Shanmugasundram commented on gene: COX16: The OMIM entry for this gene is OMIM:618064, which has been cross-checked with Ensembl, HGNC and G2P. Hence, gene-checked tag has been added.
Acute rhabdomyolysis v1.16 MT-CO1 Eleanor Williams commented on gene: MT-CO1
DDG2P v3.73 CEP85L Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: CEP85L.
DDG2P v3.73 CEP85L Achchuthan Shanmugasundram commented on gene: CEP85L: The OMIM entry for this gene is OMIM:618865, which has been cross-checked with Ensembl, HGNC and G2P. Hence, gene-checked tag has been added.
Paediatric or syndromic cardiomyopathy v3.38 RRAGC Eleanor Williams Tag gene-checked tag was added to gene: RRAGC.
Intellectual disability v5.313 CCDC82 Achchuthan Shanmugasundram commented on gene: CCDC82: The OMIM entry for this gene is OMIM:619870, which has been cross-checked with both Ensembl and HGNC. Hence, gene-checked tag has been added.
Paediatric or syndromic cardiomyopathy v3.38 RRAGC Eleanor Williams commented on gene: RRAGC
Intellectual disability v5.313 CCDC82 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: CCDC82.
Childhood onset hereditary spastic paraplegia v4.26 CCDC82 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: CCDC82.
Childhood onset hereditary spastic paraplegia v4.26 CCDC82 Achchuthan Shanmugasundram commented on gene: CCDC82: The OMIM entry for this gene is OMIM:619870, which has been cross-checked with both Ensembl and HGNC. Hence, gene-checked tag has been added.
Rare multisystem ciliopathy disorders v1.168 CCDC32 Achchuthan Shanmugasundram changed review comment from: The OMIM entry for this gene is OMIM:619219, which has been cross-checked with Ensembl, HGNC and G2P. Hence, gene-checked tag has been added.; to: The OMIM entry for this gene is OMIM:618941, which has been cross-checked with Ensembl, HGNC and G2P. Hence, gene-checked tag has been added.
Intellectual disability v5.313 CCDC32 Achchuthan Shanmugasundram changed review comment from: The OMIM entry for this gene is OMIM:619219, which has been cross-checked with Ensembl, HGNC and G2P. Hence, gene-checked tag has been added.; to: The OMIM entry for this gene is OMIM:618941, which has been cross-checked with Ensembl, HGNC and G2P. Hence, gene-checked tag has been added.
DDG2P v3.73 CCDC32 Achchuthan Shanmugasundram changed review comment from: The OMIM entry for this gene is OMIM:619219, which has been cross-checked with Ensembl, HGNC and G2P. Hence, gene-checked tag has been added.; to: The OMIM entry for this gene is OMIM:618941, which has been cross-checked with Ensembl, HGNC and G2P. Hence, gene-checked tag has been added.
Laterality disorders and isomerism v3.4 CCDC32 Achchuthan Shanmugasundram changed review comment from: The OMIM entry for this gene is OMIM:619219, which has been cross-checked with Ensembl, HGNC and G2P. Hence, gene-checked tag has been added.; to: The OMIM entry for this gene is OMIM:618941, which has been cross-checked with Ensembl, HGNC and G2P. Hence, gene-checked tag has been added.
Arthrogryposis v5.17 CCDC47 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: CCDC47.
Arthrogryposis v5.17 CCDC47 Achchuthan Shanmugasundram commented on gene: CCDC47
Likely inborn error of metabolism v4.52 SLC6A20 Eleanor Williams commented on gene: SLC6A20
DDG2P v3.73 CCDC47 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: CCDC47.
DDG2P v3.73 CCDC47 Achchuthan Shanmugasundram commented on gene: CCDC47: The OMIM entry for this gene is OMIM:618260, which has been cross-checked with Ensembl, HGNC and G2P. Hence, gene-checked tag has been added.
Intellectual disability v5.313 ZMYND8 Eleanor Williams commented on gene: ZMYND8
Intellectual disability v5.313 ZMYND8 Eleanor Williams Tag gene-checked tag was added to gene: ZMYND8.
Intellectual disability v5.313 TRA2B Eleanor Williams Tag gene-checked tag was added to gene: TRA2B.
Intellectual disability v5.313 TRA2B Eleanor Williams commented on gene: TRA2B
Intellectual disability v5.313 SLC32A1 Eleanor Williams commented on gene: SLC32A1
Intellectual disability v5.313 SLC32A1 Eleanor Williams Tag gene-checked tag was added to gene: SLC32A1.
Intellectual disability v5.313 SHANK1 Eleanor Williams Tag gene-checked tag was added to gene: SHANK1.
Intellectual disability v5.313 SHANK1 Eleanor Williams commented on gene: SHANK1
Intellectual disability v5.313 RBSN Eleanor Williams commented on gene: RBSN
Intellectual disability v5.313 RBSN Eleanor Williams Tag gene-checked tag was added to gene: RBSN.
Intellectual disability v5.313 POU3F2 Eleanor Williams Tag gene-checked tag was added to gene: POU3F2.
Intellectual disability v5.313 POU3F2 Eleanor Williams commented on gene: POU3F2
Intellectual disability v5.313 PLK1 Eleanor Williams Tag gene-checked tag was added to gene: PLK1.
Intellectual disability v5.313 PLK1 Eleanor Williams commented on gene: PLK1
Intellectual disability v5.313 PAN2 Eleanor Williams commented on gene: PAN2
Intellectual disability v5.313 PAN2 Eleanor Williams Tag gene-checked tag was added to gene: PAN2.
Intellectual disability v5.313 OTUD7A Eleanor Williams commented on gene: OTUD7A
Intellectual disability v5.313 OTUD7A Eleanor Williams Tag gene-checked tag was added to gene: OTUD7A.
Intellectual disability v5.313 LHX2 Eleanor Williams Tag gene-checked tag was added to gene: LHX2.
Intellectual disability v5.313 LHX2 Eleanor Williams commented on gene: LHX2
Intellectual disability v5.313 KLHL20 Eleanor Williams commented on gene: KLHL20
Intellectual disability v5.313 KLHL20 Eleanor Williams Tag gene-checked tag was added to gene: KLHL20.
Intellectual disability v5.313 KDM5A Eleanor Williams Tag gene-checked tag was added to gene: KDM5A.
Intellectual disability v5.313 KDM5A Eleanor Williams commented on gene: KDM5A
Intellectual disability v5.313 KDM2B Eleanor Williams Tag gene-checked tag was added to gene: KDM2B.
Intellectual disability v5.313 KDM2B Eleanor Williams commented on gene: KDM2B
Early onset or syndromic epilepsy v4.118 TRA2B Eleanor Williams Tag gene-checked tag was added to gene: TRA2B.
Early onset or syndromic epilepsy v4.118 TRA2B Eleanor Williams commented on gene: TRA2B
Early onset or syndromic epilepsy v4.118 SLC32A1 Eleanor Williams Tag gene-checked tag was added to gene: SLC32A1.
Early onset or syndromic epilepsy v4.118 SLC32A1 Eleanor Williams commented on gene: SLC32A1
Early onset or syndromic epilepsy v4.118 RHEB Eleanor Williams Tag gene-checked tag was added to gene: RHEB.
Early onset or syndromic epilepsy v4.118 RHEB Eleanor Williams commented on gene: RHEB: This gene is not currently associated with a disease phenotype in OMIM, but checked PMID: 33434304 to make sure it is the same gene listed in the publication as on this panel and it is, so added the gene-checked tag
Early onset or syndromic epilepsy v4.118 PLK1 Eleanor Williams commented on gene: PLK1
Early onset or syndromic epilepsy v4.118 PLK1 Eleanor Williams Tag gene-checked tag was added to gene: PLK1.
Early onset or syndromic epilepsy v4.118 OTUD7A Eleanor Williams Tag gene-checked tag was added to gene: OTUD7A.
Early onset or syndromic epilepsy v4.118 OTUD7A Eleanor Williams commented on gene: OTUD7A
Early onset or syndromic epilepsy v4.118 KLHL20 Eleanor Williams Tag gene-checked tag was added to gene: KLHL20.
Early onset or syndromic epilepsy v4.118 KLHL20 Eleanor Williams commented on gene: KLHL20
Adult onset neurodegenerative disorder v4.37 SS18L1 Eleanor Williams Tag gene-checked tag was added to gene: SS18L1.
Adult onset neurodegenerative disorder v4.37 SS18L1 Eleanor Williams commented on gene: SS18L1
DDG2P v3.73 ZMYND8 Eleanor Williams commented on gene: ZMYND8
DDG2P v3.73 ZMYND8 Eleanor Williams Tag gene-checked tag was added to gene: ZMYND8.
DDG2P v3.73 WNK3 Eleanor Williams Tag gene-checked tag was added to gene: WNK3.
DDG2P v3.73 WNK3 Eleanor Williams commented on gene: WNK3
DDG2P v3.73 WDR5 Eleanor Williams commented on gene: WDR5
DDG2P v3.73 WDR5 Eleanor Williams Tag gene-checked tag was added to gene: WDR5.
DDG2P v3.73 UPF1 Eleanor Williams Tag gene-checked tag was added to gene: UPF1.
DDG2P v3.73 UPF1 Eleanor Williams commented on gene: UPF1
DDG2P v3.73 TRA2B Eleanor Williams commented on gene: TRA2B
DDG2P v3.73 TRA2B Eleanor Williams Tag gene-checked tag was added to gene: TRA2B.
DDG2P v3.73 SLC32A1 Eleanor Williams commented on gene: SLC32A1
DDG2P v3.73 SLC32A1 Eleanor Williams Tag gene-checked tag was added to gene: SLC32A1.
DDG2P v3.73 SHROOM3 Eleanor Williams commented on gene: SHROOM3
DDG2P v3.73 SHROOM3 Eleanor Williams Tag gene-checked tag was added to gene: SHROOM3.
DDG2P v3.73 SHANK1 Eleanor Williams commented on gene: SHANK1
DDG2P v3.73 SHANK1 Eleanor Williams Tag gene-checked tag was added to gene: SHANK1.
DDG2P v3.73 RRAS Eleanor Williams Tag gene-checked tag was added to gene: RRAS.
DDG2P v3.73 RRAS Eleanor Williams commented on gene: RRAS
DDG2P v3.73 RAB14 Eleanor Williams commented on gene: RAB14
DDG2P v3.73 RAB14 Eleanor Williams Tag gene-checked tag was added to gene: RAB14.
DDG2P v3.73 PSMC5 Eleanor Williams Tag gene-checked tag was added to gene: PSMC5.
DDG2P v3.73 PSMC5 Eleanor Williams commented on gene: PSMC5
DDG2P v3.73 PAN2 Eleanor Williams commented on gene: PAN2
DDG2P v3.73 PAN2 Eleanor Williams Tag gene-checked tag was added to gene: PAN2.
DDG2P v3.73 ONECUT1 Eleanor Williams commented on gene: ONECUT1
DDG2P v3.73 ONECUT1 Eleanor Williams Tag gene-checked tag was added to gene: ONECUT1.
DDG2P v3.73 NRXN2 Eleanor Williams Tag gene-checked tag was added to gene: NRXN2.
DDG2P v3.73 NRXN2 Eleanor Williams commented on gene: NRXN2
DDG2P v3.73 MSL2 Eleanor Williams commented on gene: MSL2
DDG2P v3.73 MSL2 Eleanor Williams Tag gene-checked tag was added to gene: MSL2.
DDG2P v3.73 MIR17HG Eleanor Williams Tag gene-checked tag was added to gene: MIR17HG.
DDG2P v3.73 MIR17HG Eleanor Williams commented on gene: MIR17HG
Rare multisystem ciliopathy disorders v1.168 CCDC32 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: CCDC32.
Rare multisystem ciliopathy disorders v1.168 CCDC32 Achchuthan Shanmugasundram commented on gene: CCDC32
Intellectual disability v5.313 CCDC32 Achchuthan Shanmugasundram commented on gene: CCDC32
Laterality disorders and isomerism v3.4 CCDC32 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: CCDC32.
Laterality disorders and isomerism v3.4 CCDC32 Achchuthan Shanmugasundram commented on gene: CCDC32
Mitochondrial disorders v4.99 C2orf69 Achchuthan Shanmugasundram changed review comment from: The OMIM entry for this gene is OMIM:619219, which has been crossed checked with both Ensembl and HGNC. Hence, gene-checked tag has been added.; to: The OMIM entry for this gene is OMIM:619219, which has been cross-checked with both Ensembl and HGNC. Hence, gene-checked tag has been added.
Intellectual disability v5.313 C2orf69 Achchuthan Shanmugasundram changed review comment from: The OMIM entry for this gene is OMIM:619219, which has been crossed checked with both Ensembl and HGNC. Hence, gene-checked tag has been added.; to: The OMIM entry for this gene is OMIM:619219, which has been cross-checked with both Ensembl and HGNC. Hence, gene-checked tag has been added.
Early onset or syndromic epilepsy v4.118 C2orf69 Achchuthan Shanmugasundram changed review comment from: The OMIM entry for this gene is OMIM:619219, which has been crossed checked with both Ensembl and HGNC. Hence, gene-checked tag has been added.; to: The OMIM entry for this gene is OMIM:619219, which has been cross-checked with both Ensembl and HGNC. Hence, gene-checked tag has been added.
Possible mitochondrial disorder - nuclear genes v3.49 C2orf69 Achchuthan Shanmugasundram changed review comment from: The OMIM entry for this gene is OMIM:619219, which has been crossed checked with both Ensembl and HGNC. Hence, gene-checked tag has been added.; to: The OMIM entry for this gene is OMIM:619219, which has been cross-checked with both Ensembl and HGNC. Hence, gene-checked tag has been added.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.50 C2orf69 Achchuthan Shanmugasundram changed review comment from: The OMIM entry for this gene is OMIM:619219, which has been crossed checked with both Ensembl and HGNC. Hence, gene-checked tag has been added.; to: The OMIM entry for this gene is OMIM:619219, which has been cross-checked with both Ensembl and HGNC. Hence, gene-checked tag has been added.
White matter disorders and cerebral calcification - narrow panel v3.21 C2orf69 Achchuthan Shanmugasundram changed review comment from: The OMIM entry for this gene is OMIM:619219, which has been cross-checked with both Ensembl and HGNC. Hence, gene-checked tag has been added.; to: The OMIM entry for this gene is OMIM:619219, which has been cross-checked with both Ensembl and HGNC. Hence, gene-checked tag has been added.
DDG2P v3.73 CCDC32 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: CCDC32.
DDG2P v3.73 CCDC32 Achchuthan Shanmugasundram commented on gene: CCDC32: The OMIM entry for this gene is OMIM:619219, which has been cross-checked with Ensembl, HGNC and G2P. Hence, gene-checked tag has been added.
White matter disorders and cerebral calcification - narrow panel v3.21 C2orf69 Achchuthan Shanmugasundram changed review comment from: The OMIM entry for this gene is OMIM:619219, which has been crossed checked with both Ensembl and HGNC. Hence, gene-checked tag has been added.; to: The OMIM entry for this gene is OMIM:619219, which has been cross-checked with both Ensembl and HGNC. Hence, gene-checked tag has been added.
Mitochondrial disorders v4.99 C2orf69 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: C2orf69.
Mitochondrial disorders v4.99 C2orf69 Achchuthan Shanmugasundram commented on gene: C2orf69
Intellectual disability v5.313 C2orf69 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: C2orf69.
Intellectual disability v5.313 C2orf69 Achchuthan Shanmugasundram commented on gene: C2orf69
Early onset or syndromic epilepsy v4.118 C2orf69 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: C2orf69.
Early onset or syndromic epilepsy v4.118 C2orf69 Achchuthan Shanmugasundram commented on gene: C2orf69
Possible mitochondrial disorder - nuclear genes v3.49 C2orf69 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: C2orf69.
Possible mitochondrial disorder - nuclear genes v3.49 C2orf69 Achchuthan Shanmugasundram commented on gene: C2orf69
Primary immunodeficiency or monogenic inflammatory bowel disease v4.50 C2orf69 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: C2orf69.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.50 C2orf69 Achchuthan Shanmugasundram commented on gene: C2orf69
White matter disorders and cerebral calcification - narrow panel v3.21 C2orf69 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: C2orf69.
White matter disorders and cerebral calcification - narrow panel v3.21 C2orf69 Achchuthan Shanmugasundram commented on gene: C2orf69
Mitochondrial disorders v4.99 SPATA5 Achchuthan Shanmugasundram commented on gene: SPATA5
Intellectual disability v5.313 SPATA5 Achchuthan Shanmugasundram commented on gene: SPATA5
Early onset or syndromic epilepsy v4.118 SPATA5 Achchuthan Shanmugasundram commented on gene: SPATA5
Monogenic hearing loss v4.18 SPATA5 Achchuthan Shanmugasundram commented on gene: SPATA5
Fetal anomalies v3.111 SPATA5 Achchuthan Shanmugasundram commented on gene: SPATA5
Childhood onset dystonia, chorea or related movement disorder v3.50 SPATA5L1 Achchuthan Shanmugasundram commented on gene: SPATA5L1
Intellectual disability v5.313 SPATA5L1 Achchuthan Shanmugasundram commented on gene: SPATA5L1
Early onset or syndromic epilepsy v4.118 SPATA5L1 Achchuthan Shanmugasundram commented on gene: SPATA5L1
Monogenic hearing loss v4.18 SPATA5L1 Achchuthan Shanmugasundram commented on gene: SPATA5L1
Childhood onset hereditary spastic paraplegia v4.26 SPATA5L1 Achchuthan Shanmugasundram commented on gene: SPATA5L1
Severe microcephaly v4.37 SPATA5L1 Achchuthan Shanmugasundram commented on gene: SPATA5L1
Early onset dystonia v1.135 SPATA5L1 Achchuthan Shanmugasundram commented on gene: SPATA5L1
DDG2P v3.73 KLF7 Eleanor Williams commented on gene: KLF7
DDG2P v3.73 KLF7 Eleanor Williams Tag gene-checked tag was added to gene: KLF7.
DDG2P v3.73 KIF5B Eleanor Williams Tag gene-checked tag was added to gene: KIF5B.
DDG2P v3.73 KIF5B Eleanor Williams commented on gene: KIF5B
DDG2P v3.73 KDM2B Eleanor Williams commented on gene: KDM2B
DDG2P v3.73 KDM2B Eleanor Williams Tag gene-checked tag was added to gene: KDM2B.
DDG2P v3.73 KCNJ8 Eleanor Williams Tag gene-checked tag was added to gene: KCNJ8.
DDG2P v3.73 KCNJ8 Eleanor Williams commented on gene: KCNJ8
DDG2P v3.73 KCNH5 Eleanor Williams commented on gene: KCNH5
DDG2P v3.73 KCNH5 Eleanor Williams Tag gene-checked tag was added to gene: KCNH5.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.50 IKZF2 Eleanor Williams Tag gene-checked tag was added to gene: IKZF2.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.50 IKZF2 Eleanor Williams commented on gene: IKZF2
DDG2P v3.73 HYAL2 Eleanor Williams Tag gene-checked tag was added to gene: HYAL2.
DDG2P v3.73 HYAL2 Eleanor Williams commented on gene: HYAL2
DDG2P v3.73 HNRNPD Eleanor Williams commented on gene: HNRNPD
DDG2P v3.73 HNRNPD Eleanor Williams Tag gene-checked tag was added to gene: HNRNPD.
DDG2P v3.73 HMGB1 Eleanor Williams Tag gene-checked tag was added to gene: HMGB1.
DDG2P v3.73 HMGB1 Eleanor Williams commented on gene: HMGB1
DDG2P v3.73 GSPT2 Eleanor Williams commented on gene: GSPT2
DDG2P v3.73 GSPT2 Eleanor Williams Tag gene-checked tag was added to gene: GSPT2.
DDG2P v3.73 GNA14 Eleanor Williams Tag gene-checked tag was added to gene: GNA14.
DDG2P v3.73 GNA14 Eleanor Williams commented on gene: GNA14
DDG2P v3.73 GIGYF1 Eleanor Williams commented on gene: GIGYF1
DDG2P v3.73 GIGYF1 Eleanor Williams Tag gene-checked tag was added to gene: GIGYF1.
DDG2P v3.73 FZD5 Eleanor Williams Tag gene-checked tag was added to gene: FZD5.
DDG2P v3.73 FZD5 Eleanor Williams commented on gene: FZD5
Intellectual disability v5.313 FILIP1 Eleanor Williams Tag gene-checked tag was added to gene: FILIP1.
Intellectual disability v5.313 FILIP1 Eleanor Williams commented on gene: FILIP1
Arthrogryposis v5.17 FILIP1 Eleanor Williams Tag gene-checked tag was added to gene: FILIP1.
Arthrogryposis v5.17 FILIP1 Eleanor Williams commented on gene: FILIP1
Ataxia and cerebellar anomalies - narrow panel v4.38 FEM1C Eleanor Williams Tag gene-checked tag was added to gene: FEM1C.
Ataxia and cerebellar anomalies - narrow panel v4.38 FEM1C Eleanor Williams commented on gene: FEM1C: This gene currently has no phenotype listed in OMIM so checked PMID:36336956 to make sure the same gene name is listed. It is so added the gene-checked tag.
Hereditary neuropathy or pain disorder v3.60 DRP2 Eleanor Williams Tag gene-checked tag was added to gene: DRP2.
Hereditary neuropathy or pain disorder v3.60 DRP2 Eleanor Williams commented on gene: DRP2
Primary immunodeficiency or monogenic inflammatory bowel disease v4.50 TNFRSF9 Arina Puzriakova Phenotypes for gene: TNFRSF9 were changed from CD137 deficiency (41BB); EBV lymphoproliferation, B-cell lymphoma to Immunodeficiency 109 with lymphoproliferation, OMIM:620282
DDG2P v3.73 DDX23 Eleanor Williams Tag gene-checked tag was added to gene: DDX23.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.49 TNFRSF9 Arina Puzriakova Tag gene-checked was removed from gene: TNFRSF9.
DDG2P v3.73 DDX23 Eleanor Williams commented on gene: DDX23
Intellectual disability v5.313 SRRM2 Arina Puzriakova Phenotypes for gene: SRRM2 were changed from SRRM2-related developmental disorder (monoallelic) to Intellectual developmental disorder, autosomal dominant 72, OMIM:620439
Intellectual disability v5.312 DDX23 Eleanor Williams Tag gene-checked tag was added to gene: DDX23.
Intellectual disability v5.312 SRRM2 Arina Puzriakova Tag gene-checked was removed from gene: SRRM2.
Intellectual disability v5.312 DDX23 Eleanor Williams commented on gene: DDX23
Intellectual disability v5.312 SCAF4 Arina Puzriakova Phenotypes for gene: SCAF4 were changed from SCAF4-related Neurodevelopmental Disorder; Intellectual disability; Seizures; Behavioural abnormalities to Fliedner-Zweier syndrome, OMIM:620511
Intellectual disability v5.311 SCAF4 Arina Puzriakova Tag gene-checked was removed from gene: SCAF4.
Early onset or syndromic epilepsy v4.118 SCAF4 Arina Puzriakova Phenotypes for gene: SCAF4 were changed from SCAF4-related Neurodevelopmental Disorder; Intellectual disability; Seizures; Behavioural abnormalities to Fliedner-Zweier syndrome, OMIM:620511
Early onset or syndromic epilepsy v4.117 SCAF4 Arina Puzriakova Tag gene-checked was removed from gene: SCAF4.
White matter disorders and cerebral calcification - narrow panel v3.21 SCAF4 Arina Puzriakova Phenotypes for gene: SCAF4 were changed from SCAF4-related Neurodevelopmental Disorder; Intellectual disability; Seizures; Behavioural abnormalities to Fliedner-Zweier syndrome, OMIM:620511
White matter disorders and cerebral calcification - narrow panel v3.20 SCAF4 Arina Puzriakova Tag gene-checked was removed from gene: SCAF4.
Intellectual disability v5.311 CTR9 Eleanor Williams Tag gene-checked tag was added to gene: CTR9.
Intellectual disability v5.311 CTR9 Eleanor Williams commented on gene: CTR9
Congenital myopathy v4.31 RYR3 Arina Puzriakova Phenotypes for gene: RYR3 were changed from Nemaline myopathy, MONDO:0018958 to Congenital myopathy 20, OMIM:620310; Nemaline myopathy, MONDO:0018958
Congenital myopathy v4.30 RYR3 Arina Puzriakova Tag gene-checked was removed from gene: RYR3.
Intellectual disability v5.311 ROBO1 Arina Puzriakova Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD; intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071; Neurooculorenal syndrome, OMIM:620305
Fetal anomalies v3.111 ROBO1 Arina Puzriakova Tag gene-checked was removed from gene: ROBO1.
DDG2P v3.73 CTNND2 Eleanor Williams commented on gene: CTNND2
DDG2P v3.73 CTNND2 Eleanor Williams Tag gene-checked tag was added to gene: CTNND2.
Intellectual disability v5.310 RFX7 Arina Puzriakova Phenotypes for gene: RFX7 were changed from Intellectual disability, MONDO:0001071; Autism spectrum disorder, MONDO:0005258; Attention deficit-hyperactivity disorder, MONDO:0007743 to Intellectual developmental disorder, autosomal dominant 71, with behavioral abnormalities, OMIM:620330
Intellectual disability v5.309 RFX7 Arina Puzriakova Tag gene-checked was removed from gene: RFX7.
White matter disorders and cerebral calcification - narrow panel v3.20 CLDN5 Eleanor Williams Tag gene-checked tag was added to gene: CLDN5.
White matter disorders and cerebral calcification - narrow panel v3.20 CLDN5 Eleanor Williams commented on gene: CLDN5: This gene currently has no phenotype in OMIM but the paper PMID:36477332 mentions the same gene name so adding the gene-checked tag.
Ectodermal dysplasia v3.10 PPP1R13L Arina Puzriakova Classified gene: PPP1R13L as Amber List (moderate evidence)
Ectodermal dysplasia v3.10 PPP1R13L Arina Puzriakova Gene: ppp1r13l has been classified as Amber List (Moderate Evidence).
Ectodermal dysplasia v3.9 PPP1R13L Arina Puzriakova gene: PPP1R13L was added
gene: PPP1R13L was added to Ectodermal dysplasia. Sources: Literature
Q4_23_promote_green tags were added to gene: PPP1R13L.
Mode of inheritance for gene: PPP1R13L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPP1R13L were set to 28069640; 32666529; 35924320
Phenotypes for gene: PPP1R13L were set to Arrhythmogenic cardiomyopathy with variable ectodermal abnormalities, OMIM:620519
Review for gene: PPP1R13L was set to GREEN
Added comment: Multiple individuals reported with variants in this gene. Phenotype consists of cardiac defects and variable ectodermal abnormalities affecting hair, skin and teeth. Given this is a prominent component of the phenotype in some cases and there are a sufficient number of individuals to support this gene-disease association, there is enough evidence to promote PPP1R13L to green status at the next GMS panel update.
Sources: Literature
Intellectual disability v5.309 CLDN5 Eleanor Williams commented on gene: CLDN5
Intellectual disability v5.309 CLDN5 Eleanor Williams Tag gene-checked tag was added to gene: CLDN5.
Early onset or syndromic epilepsy v4.117 CLDN5 Eleanor Williams Tag gene-checked tag was added to gene: CLDN5.
Early onset or syndromic epilepsy v4.117 CLDN5 Eleanor Williams commented on gene: CLDN5
Limb disorders v4.11 CDX2 Eleanor Williams Tag gene-checked tag was added to gene: CDX2.
Limb disorders v4.11 CDX2 Eleanor Williams commented on gene: CDX2: This gene has no phenotype in OMIM so checked that the publication PMID: 34671974 mentions the same gene name. It does. Adding the gene-checked tag.
Fetal anomalies v3.111 CDX2 Eleanor Williams Tag gene-checked tag was added to gene: CDX2.
Fetal anomalies v3.111 CDX2 Eleanor Williams commented on gene: CDX2
Dilated Cardiomyopathy and conduction defects v1.83 PPP1R13L Arina Puzriakova Phenotypes for gene: PPP1R13L were changed from cardio-cutaneous syndrome; sudden cardiac death to Arrhythmogenic cardiomyopathy with variable ectodermal abnormalities, OMIM:620519; cardio-cutaneous syndrome; sudden cardiac death
Paediatric or syndromic cardiomyopathy v3.38 PPP1R13L Arina Puzriakova Phenotypes for gene: PPP1R13L were changed from sudden cardiac death; cardio-cutaneous syndrome to Arrhythmogenic cardiomyopathy with variable ectodermal abnormalities, OMIM:620519
Paediatric or syndromic cardiomyopathy v3.37 PPP1R13L Arina Puzriakova Tag gene-checked was removed from gene: PPP1R13L.
Acute rhabdomyolysis v1.16 OBSCN Arina Puzriakova Phenotypes for gene: OBSCN were changed from Rhabdomyolysis, myopathy to {Rhabdomyolysis, susceptibility to, 1}, OMIM:620235
Acute rhabdomyolysis v1.15 OBSCN Arina Puzriakova Tag gene-checked was removed from gene: OBSCN.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.49 MAP3K14 Arina Puzriakova Phenotypes for gene: MAP3K14 were changed from Recessive Atypical Combined Immunodeficiency; Primary Immunodeficiency with Multifaceted Aberrant Lymphoid Immunity; Low NK number and function, recurrent bacterial, viral and Cryptosporidium infections; Immunodeficiencies affecting cellular and humoral immunity to Immunodeficiency 112, OMIM:620449
Primary immunodeficiency or monogenic inflammatory bowel disease v4.48 MAP3K14 Arina Puzriakova Tag gene-checked was removed from gene: MAP3K14.
COVID-19 research v1.137 MAP3K14 Arina Puzriakova Phenotypes for gene: MAP3K14 were changed from Low NK number and function, recurrent bacterial, viral and Cryptosporidium infections; Recessive Atypical Combined Immunodeficiency; Primary Immunodeficiency with Multifaceted Aberrant Lymphoid Immunity; Immunodeficiencies affecting cellular and humoral immunity to Low NK number and function, recurrent bacterial, viral and Cryptosporidium infections; Recessive Atypical Combined Immunodeficiency; Primary Immunodeficiency with Multifaceted Aberrant Lymphoid Immunity; Immunodeficiencies affecting cellular and humoral immunity; Immunodeficiency 112, OMIM:620449
COVID-19 research v1.136 MAP3K14 Arina Puzriakova Tag gene-checked was removed from gene: MAP3K14.
Early onset or syndromic epilepsy v4.117 AGO1 Arina Puzriakova Classified gene: AGO1 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.117 AGO1 Arina Puzriakova Gene: ago1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.116 AGO1 Arina Puzriakova gene: AGO1 was added
gene: AGO1 was added to Early onset or syndromic epilepsy. Sources: Literature
Q4_23_promote_green tags were added to gene: AGO1.
Mode of inheritance for gene: AGO1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: AGO1 were set to 25356899; 30213762; 34930816
Phenotypes for gene: AGO1 were set to Neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures, OMIM:620292
Review for gene: AGO1 was set to GREEN
Added comment: Multiple individuals reported with de novo variants in this gene. About half of patients develop seizures, which may be controlled or refractory.

Given that in some patients seizures are a prominent component of their phenotype and there are a sufficient number of individuals to support this gene-disease association, there is enough evidence to promote AGO1 to green status at the next GMS panel update.
Sources: Literature
Intellectual disability v5.309 AGO1 Arina Puzriakova Tag gene-checked was removed from gene: AGO1.
Intellectual disability v5.309 AGO1 Arina Puzriakova Phenotypes for gene: AGO1 were changed from Generalized hypotonia; Global developmental delay; Intellectual disability; Autism to Neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures, OMIM:620292
Neurological ciliopathies v3.13 CBY1 Eleanor Williams Tag gene-checked tag was added to gene: CBY1.
Neurological ciliopathies v3.13 CBY1 Eleanor Williams commented on gene: CBY1
Intellectual disability v5.308 CAPRIN1 Eleanor Williams Tag gene-checked tag was added to gene: CAPRIN1.
Intellectual disability v5.308 CAPRIN1 Eleanor Williams commented on gene: CAPRIN1
Early onset or syndromic epilepsy v4.115 CAPRIN1 Eleanor Williams Tag gene-checked tag was added to gene: CAPRIN1.
Early onset or syndromic epilepsy v4.115 CAPRIN1 Eleanor Williams commented on gene: CAPRIN1
DDG2P v3.73 CAPRIN1 Eleanor Williams Tag gene-checked tag was added to gene: CAPRIN1.
DDG2P v3.73 CAPRIN1 Eleanor Williams commented on gene: CAPRIN1
DDG2P v3.73 BRSK2 Eleanor Williams Tag gene-checked tag was added to gene: BRSK2.
DDG2P v3.73 BRSK2 Eleanor Williams commented on gene: BRSK2
DDG2P v3.73 BRD4 Eleanor Williams Tag gene-checked tag was added to gene: BRD4.
DDG2P v3.73 BRD4 Eleanor Williams commented on gene: BRD4
Childhood onset dystonia, chorea or related movement disorder v3.50 ARFGEF3 Eleanor Williams Tag gene-checked tag was added to gene: ARFGEF3.
Childhood onset dystonia, chorea or related movement disorder v3.50 ARFGEF3 Eleanor Williams changed review comment from: No phenotype in OMIM. Checked that the publication PMID:33098801 mentions this gene in the supplementary material (page 55) and the 3 cases reported by Zornitza Stark.; to: No phenotype in OMIM. Checked that the publication PMID:33098801 mentions this gene in the supplementary material (page 55) and the 3 cases reported by Zornitza Stark. Adding the gene-checked tag.
Childhood onset dystonia, chorea or related movement disorder v3.50 ARFGEF3 Eleanor Williams commented on gene: ARFGEF3
DDG2P v3.73 KIAA0391 Achchuthan Shanmugasundram commented on gene: KIAA0391: Added new-gene-name tag, new approved HGNC gene symbol for KIAA0391 is PRORP.
DDG2P v3.73 HIST1H2AC Achchuthan Shanmugasundram commented on gene: HIST1H2AC: Added new-gene-name tag, new approved HGNC gene symbol for HIST1H2AC is H2AC6.
DDG2P v3.73 ARHGAP35 Eleanor Williams commented on gene: ARHGAP35
DDG2P v3.73 WARS Achchuthan Shanmugasundram commented on gene: WARS: Added new-gene-name tag, new approved HGNC gene symbol for WARS is WARS1.
DDG2P v3.73 ARHGAP35 Eleanor Williams Tag gene-checked tag was added to gene: ARHGAP35.
DDG2P v3.73 ARF3 Eleanor Williams commented on gene: ARF3
DDG2P v3.73 TMEM251 Achchuthan Shanmugasundram commented on gene: TMEM251: Added new-gene-name tag, new approved HGNC gene symbol for TMEM251 is LYSET.
DDG2P v3.73 ARF3 Eleanor Williams Tag gene-checked tag was added to gene: ARF3.
DDG2P v3.73 TARS Achchuthan Shanmugasundram commented on gene: TARS: Added new-gene-name tag, new approved HGNC gene symbol for TARS is TARS1.
DDG2P v3.73 AMOTL1 Eleanor Williams commented on gene: AMOTL1
DDG2P v3.73 AMOTL1 Eleanor Williams Tag gene-checked tag was added to gene: AMOTL1.
DDG2P v3.73 SPATA5L1 Achchuthan Shanmugasundram commented on gene: SPATA5L1: Added new-gene-name tag, new approved HGNC gene symbol for SPATA5L1 is AFG2B.
DDG2P v3.73 SPATA5 Achchuthan Shanmugasundram commented on gene: SPATA5: Added new-gene-name tag, new approved HGNC gene symbol for SPATA5 is AFG2A.
DDG2P v3.73 SARS Achchuthan Shanmugasundram commented on gene: SARS: Added new-gene-name tag, new approved HGNC gene symbol for SARS is SARS1.
DDG2P v3.73 RARS Achchuthan Shanmugasundram commented on gene: RARS: Added new-gene-name tag, new approved HGNC gene symbol for RARS is RARS1.
DDG2P v3.73 ADAMTS9 Eleanor Williams commented on gene: ADAMTS9
DDG2P v3.73 NARS Achchuthan Shanmugasundram commented on gene: NARS: Added new-gene-name tag, new approved HGNC gene symbol for NARS is NARS1.
DDG2P v3.73 ADAMTS9 Eleanor Williams Tag gene-checked tag was added to gene: ADAMTS9.
DDG2P v3.73 MYLPF Achchuthan Shanmugasundram commented on gene: MYLPF: Added new-gene-name tag, new approved HGNC gene symbol for MYLPF is MYL11.
DDG2P v3.73 MTSS1L Achchuthan Shanmugasundram commented on gene: MTSS1L: Added new-gene-name tag, new approved HGNC gene symbol for MTSS1L is MTSS2.
DDG2P v3.73 H3F3B Achchuthan Shanmugasundram commented on gene: H3F3B: Added new-gene-name tag, new approved HGNC gene symbol for H3F3B is H3-3B.
DDG2P v3.73 ATP5A1 Achchuthan Shanmugasundram commented on gene: ATP5A1: Added new-gene-name tag, new approved HGNC gene symbol for ATP5A1 is ATP5F1A.
Retinal disorders v4.36 CTNND1 Achchuthan Shanmugasundram Classified gene: CTNND1 as Amber List (moderate evidence)
Retinal disorders v4.36 CTNND1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of monoallelic variants in this gene to familial exudative vitreoretinopathy. Hence, this gene can be promoted to green rating in the next GMS update.
Retinal disorders v4.36 CTNND1 Achchuthan Shanmugasundram Gene: ctnnd1 has been classified as Amber List (Moderate Evidence).
Retinal disorders v4.35 CTNND1 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: CTNND1.
Retinal disorders v4.35 CTNND1 Achchuthan Shanmugasundram gene: CTNND1 was added
gene: CTNND1 was added to Retinal disorders. Sources: Literature
Mode of inheritance for gene: CTNND1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTNND1 were set to 35700046
Phenotypes for gene: CTNND1 were set to exudative vitreoretinopathy, MONDO:0019516
Review for gene: CTNND1 was set to GREEN
Added comment: Of 140 probands of familial exudative vitreoretinopathy (FEVR) families that had whole exome sequencing, three patients were reported with three different heterozygous variants in CTNND1 gene. In addition, inducible deletion of Ctnnd1 in the postnatal mouse endothelial cells (ECs) exhibited typical phenotypes of FEVR with reactive gliosis.

This gene has not yet been associated with this FEVR phenotype either in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.308 SRSF1 Achchuthan Shanmugasundram Classified gene: SRSF1 as Amber List (moderate evidence)
Intellectual disability v5.308 SRSF1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (15 unrelated cases and functional evidence) for the promotion of this gene to green rating in the next GMS review.
Intellectual disability v5.308 SRSF1 Achchuthan Shanmugasundram Gene: srsf1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.307 SRSF1 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: SRSF1.
Intellectual disability v5.307 SRSF1 Achchuthan Shanmugasundram gene: SRSF1 was added
gene: SRSF1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: SRSF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SRSF1 were set to 37071997
Phenotypes for gene: SRSF1 were set to Neurodevelopmental disorder with dysmorphic facies and behavioral abnormalities, OMIM:620489
Review for gene: SRSF1 was set to GREEN
Added comment: There are 17 individuals from 16 different families were reported with 15 different monoallelic variants (mostly de novo) in SRSF1 gene. They were reported with a neurodevelopmental disorder mainly comprising neurological abnormalities such as intellectual disability/ developmental delay, motor delay, speech delay, and behavioural disorders and facial dysmorphisms. Intellectual disability was present in 16 of 17 individuals (3 severe, 2 moderate, 3 mild to moderate, 3 mild, 1 borderline and 4 unknown severity), while the remaining one had learning disability.

Functional testing of a subset of variants in Drosophila supported pathogenicity in most, but 2 missense variants showed no functional effect and were classified VUS.

This gene has already been associated with neurodevelopmental disorder in both OMIM (MIM #620489) and Gene2Phenotype ('limited' rating in the DD panel).
Sources: Literature
Childhood onset hereditary spastic paraplegia v4.26 SPTSSA Achchuthan Shanmugasundram Classified gene: SPTSSA as Amber List (moderate evidence)
Childhood onset hereditary spastic paraplegia v4.26 SPTSSA Achchuthan Shanmugasundram Gene: sptssa has been classified as Amber List (Moderate Evidence).
Childhood onset hereditary spastic paraplegia v4.25 SPTSSA Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There are two unrelated cases (with the same variant) in support of the association of this gene with the autosomal dominant spastic paraplegia. Although there is only one case with the autosomal recessive condition, homozygous knockout mouse model is available in support of the association. Functional evidence is also available for both homozygous and heterozygous variants.

Hence, the rating should be amber and the MOI should be set to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal'.
Childhood onset hereditary spastic paraplegia v4.25 SPTSSA Achchuthan Shanmugasundram Mode of inheritance for gene: SPTSSA was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v4.24 SPTSSA Achchuthan Shanmugasundram edited their review of gene: SPTSSA: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v4.24 SPTSSA Achchuthan Shanmugasundram changed review comment from: Two unrelated patients were identified with the same de novo missense heterozygous variant (p.Thr51Ile) and the third patient was identified with a homozygous truncation variant (c.171_172del) in SPTSSA gene. All these patients were reported with a complex form of paediatric-onset hereditary spastic paraplegia associated with progressive motor impairment and spasticity and variable language/cognitive impact.

Functional studies in fibroblasts showed dysregulation of the sphingolipid (SL) synthesis pathway, showing that both variants impair ORMDL regulation of the pathway leading to various levels of increased SL. Over expression of human SPTSSA was shown to lead to motor development in Drosophila, rescued by expression of ORMDL for WT SPTSSA but not mutant SPTSSA. The heterozygous p.Thr51Ile variant was shown to impact regulation more than the homozygous truncation variant, while the truncated region was previously shown to be important for ORMDL regulation.

Mice model with a homozygous knockout of the functional equivalent sptssb had early onset ataxia and died prematurely, with evidence of axonic degeneration.
Sources: Literature; to: Two unrelated patients were identified with the same de novo missense heterozygous variant (p.Thr51Ile) and the third patient was identified with a homozygous truncation variant (c.171_172del) in SPTSSA gene. All these patients were reported with a complex form of paediatric-onset hereditary spastic paraplegia associated with progressive motor impairment and spasticity and variable language/cognitive impact (PMID:36718090).

Functional studies in fibroblasts showed dysregulation of the sphingolipid (SL) synthesis pathway, showing that both variants impair ORMDL regulation of the pathway leading to various levels of increased SL. Over expression of human SPTSSA was shown to lead to motor development in Drosophila, rescued by expression of ORMDL for WT SPTSSA but not mutant SPTSSA. The heterozygous p.Thr51Ile variant was shown to impact regulation more than the homozygous truncation variant, while the truncated region was previously shown to be important for ORMDL regulation (PMID:36718090).

Mice model with homozygous ssSPTa null mutants are embryonic lethal (PMID:33662400). However, homozygous knockout of the functional equivalent ssSPTb had early onset ataxia and died prematurely, with evidence of axonic degeneration (PMID:26438849).

This gene has already been associated with relevant phenotypes in OMIM (MIMs #620416 & #620417).
Sources: Literature
Childhood onset hereditary spastic paraplegia v4.24 SPTSSA Achchuthan Shanmugasundram edited their review of gene: SPTSSA: Changed publications to: 26438849, 33662400, 36718090
Childhood onset hereditary spastic paraplegia v4.24 SPTSSA Achchuthan Shanmugasundram changed review comment from: Two unrelated patients were identified with the same heterozygous variant (p.Thr51Ile) and the third patient was identified with a homozygous variant (c.171_172del) in SPTSSA gene. All these patients were reported with a complex form of paediatric-onset hereditary spastic paraplegia associated with progressive motor impairment and spasticity and variable language/cognitive impact.
Sources: Literature; to: Two unrelated patients were identified with the same de novo missense heterozygous variant (p.Thr51Ile) and the third patient was identified with a homozygous truncation variant (c.171_172del) in SPTSSA gene. All these patients were reported with a complex form of paediatric-onset hereditary spastic paraplegia associated with progressive motor impairment and spasticity and variable language/cognitive impact.

Functional studies in fibroblasts showed dysregulation of the sphingolipid (SL) synthesis pathway, showing that both variants impair ORMDL regulation of the pathway leading to various levels of increased SL. Over expression of human SPTSSA was shown to lead to motor development in Drosophila, rescued by expression of ORMDL for WT SPTSSA but not mutant SPTSSA. The heterozygous p.Thr51Ile variant was shown to impact regulation more than the homozygous truncation variant, while the truncated region was previously shown to be important for ORMDL regulation.

Mice model with a homozygous knockout of the functional equivalent sptssb had early onset ataxia and died prematurely, with evidence of axonic degeneration.
Sources: Literature
Childhood onset hereditary spastic paraplegia v4.24 SPTSSA Achchuthan Shanmugasundram changed review comment from: Sources: Literature; to: Two unrelated patients were identified with the same heterozygous variant (p.Thr51Ile) and the third patient was identified with a homozygous variant (c.171_172del) in SPTSSA gene. All these patients were reported with a complex form of paediatric-onset hereditary spastic paraplegia associated with progressive motor impairment and spasticity and variable language/cognitive impact.
Sources: Literature
Childhood onset hereditary spastic paraplegia v4.24 SPTSSA Achchuthan Shanmugasundram gene: SPTSSA was added
gene: SPTSSA was added to Childhood onset hereditary spastic paraplegia. Sources: Literature
Mode of inheritance for gene: SPTSSA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPTSSA were set to 36718090
Phenotypes for gene: SPTSSA were set to Spastic paraplegia 90A, autosomal dominant, OMIM:620416; ?Spastic paraplegia 90B, autosomal recessive, OMIM:620417
Review for gene: SPTSSA was set to AMBER
Added comment: Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v4.48 CR2 Achchuthan Shanmugasundram Tag Q4_23_NHS_review tag was added to gene: CR2.
Cytopenia - NOT Fanconi anaemia v3.4 CXCR2 Achchuthan Shanmugasundram Tag Q4_23_NHS_review tag was added to gene: CXCR2.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.48 CXCR2 Achchuthan Shanmugasundram Tag Q4_23_NHS_review tag was added to gene: CXCR2.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.48 IRF2BP2 Achchuthan Shanmugasundram Tag Q4_23_NHS_review tag was added to gene: IRF2BP2.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.48 HMOX1 Achchuthan Shanmugasundram Tag Q4_23_NHS_review tag was added to gene: HMOX1.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.48 HYOU1 Achchuthan Shanmugasundram Tag Q4_23_NHS_review tag was added to gene: HYOU1.
Skeletal dysplasia v4.23 AXIN1 Achchuthan Shanmugasundram Classified gene: AXIN1 as Amber List (moderate evidence)
Skeletal dysplasia v4.23 AXIN1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Skeletal dysplasia v4.23 AXIN1 Achchuthan Shanmugasundram Gene: axin1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v4.22 AXIN1 Achchuthan Shanmugasundram Phenotypes for gene: AXIN1 were changed from Syndromic disease, (MONDO:0002254), AXIN1-related; skeletal dysplasia to neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome, MONDO:0018681
Skeletal dysplasia v4.21 AXIN1 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: AXIN1.
Skeletal dysplasia v4.21 AXIN1 Achchuthan Shanmugasundram reviewed gene: AXIN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 37582359; Phenotypes: neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome, MONDO:0018681; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v4.48 HYOU1 Achchuthan Shanmugasundram Classified gene: HYOU1 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.48 HYOU1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As listed in the review of Hannah Knight, there are three cases reported with biallelic HYOU1 variants and with phagocytic defects and/ or immunodeficiency. Hence, this gene can be promoted to green rating in the next GMS review.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.48 HYOU1 Achchuthan Shanmugasundram Gene: hyou1 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.47 HYOU1 Achchuthan Shanmugasundram Phenotypes for gene: HYOU1 were changed from Hypoglycemia, inflammatory complications; Congenital defects of phagocyte number or function; Immunodeficiency 59 and hypoglycemia, 233600 to ?Immunodeficiency 59 and hypoglycemia, OMIM:233600; Hypoglycemia, inflammatory complications; Congenital defects of phagocyte number or function
Primary immunodeficiency or monogenic inflammatory bowel disease v4.46 HYOU1 Achchuthan Shanmugasundram Publications for gene: HYOU1 were set to 32048120; 32086639; 27913302
Primary immunodeficiency or monogenic inflammatory bowel disease v4.45 HYOU1 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: HYOU1.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.45 HYOU1 Achchuthan Shanmugasundram reviewed gene: HYOU1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ?Immunodeficiency 59 and hypoglycemia, OMIM:233600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v4.45 HMOX1 Achchuthan Shanmugasundram Classified gene: HMOX1 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.45 HMOX1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As listed in the review of Hannah Knight, there are more than three unrelated cases with biallelic HMOX1 variants reported with asplenia. In addition, recurrent infections, recurrent fever, generalized erythematous rash, hemolysis, inflammation, nephritis, and joint pain were reported in these cases. Hence, this gene can be promoted to green rating in the next GMS review.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.45 HMOX1 Achchuthan Shanmugasundram Gene: hmox1 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.44 HMOX1 Achchuthan Shanmugasundram Deleted their comment
Primary immunodeficiency or monogenic inflammatory bowel disease v4.44 HMOX1 Achchuthan Shanmugasundram Phenotypes for gene: HMOX1 were changed from Hemolysis, nephritis, inflammation; Defects in Intrinsic and Innate Immunity; amyloidosis to Heme oxygenase-1 deficiency, OMIM:614034; Hemolysis, nephritis, inflammation; Defects in Intrinsic and Innate Immunity; amyloidosis
Primary immunodeficiency or monogenic inflammatory bowel disease v4.43 HMOX1 Achchuthan Shanmugasundram Publications for gene: HMOX1 were set to 9884342; 21088618; 22023467; 26526137; 3306677
Primary immunodeficiency or monogenic inflammatory bowel disease v4.42 HMOX1 Achchuthan Shanmugasundram Added comment: Comment on publications: As listed in the review of Hannah Knight, there are more than three unrelated cases with biallelic HMOX1 variants reported with asplenia. In addition, recurrent infections, recurrent fever, generalized erythematous rash, hemolysis, inflammation, nephritis, and joint pain were reported in these cases. Hence, this gene can be promoted to green rating in the next GMS review.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.42 HMOX1 Achchuthan Shanmugasundram Publications for gene: HMOX1 were set to 9884342; 21088618
Primary immunodeficiency or monogenic inflammatory bowel disease v4.41 HMOX1 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: HMOX1.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.41 HMOX1 Achchuthan Shanmugasundram reviewed gene: HMOX1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Heme oxygenase-1 deficiency, OMIM:614034; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v4.41 FCN3 Hannah Knight changed review comment from: PMID: 32634042 appears to show a new patient with biallelic variants - can't access paper however; to: PMID: 32634042 appears to show a new patient with biallelic variants - can't access paper however
Primary immunodeficiency or monogenic inflammatory bowel disease v4.41 FCN3 Hannah Knight reviewed gene: FCN3: Rating: AMBER; Mode of pathogenicity: None; Publications: 32634042; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v4.41 CD81 Hannah Knight reviewed gene: CD81: Rating: AMBER; Mode of pathogenicity: None; Publications: 35849269; Phenotypes: Immunodeficiency, common variable, 6; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v4.41 CD4 Hannah Knight reviewed gene: CD4: Rating: AMBER; Mode of pathogenicity: None; Publications: 33471124; Phenotypes: Immunodeficiency 79; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v4.41 TRAF3IP2 Hannah Knight reviewed gene: TRAF3IP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34289170, 33825088, 33359359; Phenotypes: ?Candidiasis, familial, 8; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v4.41 TFRC Hannah Knight reviewed gene: TFRC: Rating: GREEN; Mode of pathogenicity: None; Publications: 32851577; Phenotypes: Immunodeficiency 46; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cytopenia - NOT Fanconi anaemia v3.4 SRP19 Hannah Knight gene: SRP19 was added
gene: SRP19 was added to Cytopenia - NOT Fanconi anaemia. Sources: Literature
Mode of inheritance for gene: SRP19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SRP19 were set to 36223592
Phenotypes for gene: SRP19 were set to Severe congenital neutropenia
Review for gene: SRP19 was set to AMBER
Added comment: PMID: 36223592 - a novel homozygous variant in SRP19 was identified in 2 related pedigrees with 5 patients affected (c.189+5G>A) + functional studies
Sources: Literature
Cytopenia - NOT Fanconi anaemia v3.4 SRPRA Hannah Knight gene: SRPRA was added
gene: SRPRA was added to Cytopenia - NOT Fanconi anaemia. Sources: Literature
Mode of inheritance for gene: SRPRA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SRPRA were set to 36223592
Phenotypes for gene: SRPRA were set to Severe congenital neutropenia
Review for gene: SRPRA was set to AMBER
Added comment: PMID: 36223592 - A novel heterozygous de novo variant in SRPRA was found in 1 pedigree with 1 patient (p.Gln464Glu) - results in an amino acid exchange (glutamine to glutamic acid, position 464) in an alpha helix loop close to the GTPase active center known to mediate interaction with the cognate-binding partner, SRP54 (known cause of SCN)
+ functional studies
Sources: Literature
Cytopenia - NOT Fanconi anaemia v3.4 SEC61A1 Hannah Knight gene: SEC61A1 was added
gene: SEC61A1 was added to Cytopenia - NOT Fanconi anaemia. Sources: Literature
Mode of inheritance for gene: SEC61A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SEC61A1 were set to 32325141; 27392076
Phenotypes for gene: SEC61A1 were set to Severe congenital neutropenia; Tubulointerstitial kidney disease, autosomal dominant, 5
Review for gene: SEC61A1 was set to AMBER
Added comment: PMID: 32325141 - reported a patient with a de novo variant in this gene, presenting with severe congenital neutropenia and recurrent infections
PMID: 27392076 - neutropenia previously reported in a father and daughter with tubulointerstitial kidney disease due to a heterozygous SEC61A1 variant
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v4.41 SEC61A1 Hannah Knight reviewed gene: SEC61A1: Rating: AMBER; Mode of pathogenicity: None; Publications: 32325141; Phenotypes: Severe congenital neutropenia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v4.41 SAMD9L Hannah Knight reviewed gene: SAMD9L: Rating: GREEN; Mode of pathogenicity: None; Publications: 31874111, 36969289; Phenotypes: SAMD9L-associated autoinflammatory disease; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v4.41 IRF2BP2 Achchuthan Shanmugasundram Classified gene: IRF2BP2 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.41 IRF2BP2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Hannah Knight, there are four unrelated cases in support of the association of monoallelic IRF2BP2 variants with immunodeficiency. Hence, this gene can be promoted to green rating in the next GMS review.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.41 IRF2BP2 Achchuthan Shanmugasundram Gene: irf2bp2 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.40 IRF2BP2 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: IRF2BP2.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.40 IRF2BP2 Achchuthan Shanmugasundram reviewed gene: IRF2BP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ?Immunodeficiency, common variable, 14, OMIM:617765; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Adult onset leukodystrophy v3.21 OCRL Sarah Leigh Tag Q4_23_demote_amber tag was added to gene: OCRL.
Tag Q4_23_expert_review tag was added to gene: OCRL.
Adult onset leukodystrophy v3.21 OCRL Sarah Leigh reviewed gene: OCRL: Rating: AMBER; Mode of pathogenicity: None; Publications: 16722554; Phenotypes: ; Mode of inheritance: None
Adult onset leukodystrophy v3.21 OCRL Sarah Leigh Publications for gene: OCRL were set to 27159321; 25527826; 28334938; 20301621; 24357685; 33517444
Adult onset leukodystrophy v3.20 HMGCL Sarah Leigh Tag Q4_23_demote_amber tag was added to gene: HMGCL.
Tag Q4_23_expert_review tag was added to gene: HMGCL.
Adult onset leukodystrophy v3.20 HMGCL Sarah Leigh reviewed gene: HMGCL: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Adult onset leukodystrophy v3.20 HMGCL Sarah Leigh Publications for gene: HMGCL were set to 27159321; 25527826; 28334938; 20301621; 24357685
Adult onset leukodystrophy v3.19 HMGCL Sarah Leigh Phenotypes for gene: HMGCL were changed from HMG-CoA lyase deficiency, 246450 to HMG-CoA lyase deficiency, OMIM:246450; 3-hydroxy-3-methylglutaric aciduria, MONDO:0009520
Mitochondrial disorders v4.99 SLC52A3 Sarah Leigh Classified gene: SLC52A3 as Amber List (moderate evidence)
Mitochondrial disorders v4.99 SLC52A3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Mitochondrial disorders v4.99 SLC52A3 Sarah Leigh Gene: slc52a3 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v4.98 SLC52A3 Sarah Leigh Tag Q4_23_promote_green tag was added to gene: SLC52A3.
Tag Q4_23_MOI tag was added to gene: SLC52A3.
Mitochondrial disorders v4.98 SLC52A3 Sarah Leigh Phenotypes for gene: SLC52A3 were changed from Brown-Vialetto-Van Laere syndrome 1, 211530 to Brown-Vialetto-Van Laere syndrome 1, OMIM:211530; Brown-Vialetto-van Laere syndrome 1, MONDO:0024537
Mitochondrial disorders v4.97 SLC52A3 Sarah Leigh edited their review of gene: SLC52A3: Changed rating: GREEN
Mitochondrial disorders v4.97 SLC52A3 Sarah Leigh edited their review of gene: SLC52A3: Added comment: PMIDs 29053833 & 29193829 report a total of 11 unrelated cases of Brown-Vialetto-Van Laere syndrome 1 (OMIM:211530) carrying a total of 14 SLC52A3 variants. Functional studies and histological observations allow the authors to conclude that the resultant riboflavin transporter deficiency associated with the SLC52A3 variants, causes a mitochondrial dysfunction. Furthermore, the loss of the SLC52A2/SLC52A3 homologue in Drosophila melanogaster resulted in abnormal mitochondrial membrane potential, respiratory chain activity and morphology.
Nine of the SLC52A3 variants occur as either homozygotes or as compound heterozygotes in PMID: 29053833, a further five variants are seen as heterozygotes. The authors comment that the heterozygous individuals did not differ substantially in phenotype including age of presentation from the rest of the cohort of mutation-positive cases.; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mitochondrial disorders v4.97 SLC52A2 Sarah Leigh changed review comment from: PMIDs 29053833 & 29193829 characterize six unrelated cases of Brown-Vialetto-Van Laere syndrome 2 (OMIM:614707) carrying a total of SLC52A2 variants. Functional studies and histological observations allow the authors to conclude that the resultant riboflavin transporter deficiency associated with the SLC52A2 variants, causes a mitochondrial dysfunction. Furthermore, the loss of the SLC52A2/SLC52A3 homologue in Drosophila melanogaster resulted in abnormal mitochondrial membrane potential, respiratory chain activity and morphology.; to: PMIDs 29053833 & 29193829 characterize six unrelated cases of Brown-Vialetto-Van Laere syndrome 2 (OMIM:614707) carrying a total of nine SLC52A2 variants. Functional studies and histological observations allow the authors to conclude that the resultant riboflavin transporter deficiency associated with the SLC52A2 variants, causes a mitochondrial dysfunction. Furthermore, the loss of the SLC52A2/SLC52A3 homologue in Drosophila melanogaster resulted in abnormal mitochondrial membrane potential, respiratory chain activity and morphology.
Mitochondrial disorders v4.97 SLC52A2 Sarah Leigh changed review comment from: PMIDs 29053833 & 29193829 characterize six unrelated cases of Brown-Vialetto-Van Laere syndrome 2 (OMIM:614707) carrying a total of SLC52A2 variants. Functional studies and histological observations allow the authors to conclude that the resultant riboflavin transporter deficiency associated with the SLC52A2 variants, causes a mitochondrial dysfunction.; to: PMIDs 29053833 & 29193829 characterize six unrelated cases of Brown-Vialetto-Van Laere syndrome 2 (OMIM:614707) carrying a total of SLC52A2 variants. Functional studies and histological observations allow the authors to conclude that the resultant riboflavin transporter deficiency associated with the SLC52A2 variants, causes a mitochondrial dysfunction. Furthermore, the loss of the SLC52A2/SLC52A3 homologue in Drosophila melanogaster resulted in abnormal mitochondrial membrane potential, respiratory chain activity and morphology.
Mitochondrial disorders v4.97 SLC52A3 Sarah Leigh Publications for gene: SLC52A3 were set to
DDG2P v3.73 FBN1 Achchuthan Shanmugasundram changed review comment from: The DDG2P confidence category for the disease Marfan Syndrome, biallelic, OMIM:154700 is definitive. The allelic requirement and mutation consequence are biallelic_autosomal and altered gene product structure (PMIDs: 17568394; 27582083; 31950671).

The DDG2P confidence category for the disease MARFAN SYNDROME, OMIM:154700 is definitive. The allelic requirement and mutation consequence are monoallelic_autosomal and absent gene product (PMIDs: 8428751; 8504310; 1631074; 7611299; 21594993; 7762551; 18412115; 1301946; 15287423; 15032979; 8430317; 8040326; 8101042; 9101298; 8406497; 11175294; 10766875; 17492313; 21594992; 17366579; 11702223; 9837823; 1569206; 8136837; 9241263; 7633409; 20082464; 10441597; 7911051; 20979188; 8281141; 1852208).

The DDG2P confidence category for the disease SHPRINTZEN-GOLDBERG CRANIOSYNOSTOSIS SYNDROME, OMIM:182212 is definitive. The allelic requirement and mutation consequence are monoallelic_autosomal and altered gene product structure (PMIDs: 8428751; 8504310; 1631074; 7611299; 7762551; 21594993; 18412115; 1301946; 15032979; 15287423; 8430317; 8040326; 8071963; 8101042; 9101298; 8406497; 11175294; 10766875; 17492313; 21594992; 23103230; 23023332; 17568394; 17366579; 11702223; 9837823; 1569206; 8136837; 9241263; 7633409; 20082464; 10441597; 8281141; 20979188; 7911051; 16333834; 1852208).

The DDG2P confidence category for the disease WEILL-MARCHESANI SYNDROME AUTOSOMAL DOMINANT, OMIM:608328 is limited. The allelic requirement and mutation consequence are monoallelic_autosomal and altered gene product structure (PMIDs: 12525539;23897642).; to: The DDG2P confidence category for the disease Marfan Syndrome, biallelic, OMIM:154700 is definitive. The allelic requirement and mutation consequence are biallelic_autosomal and altered gene product structure (PMIDs: 17568394; 27582083; 31950671).

The DDG2P confidence category for the disease MARFAN SYNDROME, OMIM:154700 is definitive. The allelic requirement and mutation consequence are monoallelic_autosomal and absent gene product (PMIDs: 8428751; 8504310; 1631074; 7611299; 21594993; 7762551; 18412115; 1301946; 15287423; 15032979; 8430317; 8040326; 8101042; 9101298; 8406497; 11175294; 10766875; 17492313; 21594992; 17366579; 11702223; 9837823; 1569206; 8136837; 9241263; 7633409; 20082464; 10441597; 7911051; 20979188; 8281141; 1852208).

The DDG2P confidence category for the disease SHPRINTZEN-GOLDBERG CRANIOSYNOSTOSIS SYNDROME, OMIM:182212 is definitive. The allelic requirement and mutation consequence are monoallelic_autosomal and altered gene product structure (PMIDs: 8428751; 8504310; 1631074; 7611299; 7762551; 21594993; 18412115; 1301946; 15032979; 15287423; 8430317; 8040326; 8071963; 8101042; 9101298; 8406497; 11175294; 10766875; 17492313; 21594992; 23103230; 23023332; 17568394; 17366579; 11702223; 9837823; 1569206; 8136837; 9241263; 7633409; 20082464; 10441597; 8281141; 20979188; 7911051; 16333834; 1852208).

The DDG2P confidence category for the disease WEILL-MARCHESANI SYNDROME AUTOSOMAL DOMINANT, OMIM:608328 is limited. The allelic requirement and mutation consequence are monoallelic_autosomal and altered gene product structure (PMIDs: 12525539; 23897642).
DDG2P v3.73 FBN1 Achchuthan Shanmugasundram changed review comment from: The DDG2P confidence category for the disease Marfan Syndrome, biallelic, OMIM:154700 is definitive. The allelic requirement and mutation consequence are biallelic_autosomal and altered gene product structure (PMIDs: 17568394;27582083;31950671).

The DDG2P confidence category for the disease MARFAN SYNDROME, OMIM:154700 is definitive. The allelic requirement and mutation consequence are monoallelic_autosomal and absent gene product (PMIDs: 8428751;8504310;1631074;7611299;21594993;7762551;18412115;1301946;15287423;15032979;8430317;8040326;8101042;9101298;8406497;11175294;10766875;17492313;21594992;17366579;11702223;9837823;1569206;8136837;9241263;7633409;20082464;10441597;7911051;20979188;8281141;1852208).

The DDG2P confidence category for the disease SHPRINTZEN-GOLDBERG CRANIOSYNOSTOSIS SYNDROME, OMIM:182212 is definitive. The allelic requirement and mutation consequence are monoallelic_autosomal and altered gene product structure (PMIDs: 8428751;8504310;1631074;7611299;7762551;21594993;18412115;1301946;15032979;15287423;8430317;8040326;8071963;8101042;9101298;8406497;11175294;10766875;17492313;21594992;23103230;23023332;17568394;17366579;11702223;9837823;1569206;8136837;9241263;7633409;20082464;10441597;8281141;20979188;7911051;16333834;1852208).

The DDG2P confidence category for the disease WEILL-MARCHESANI SYNDROME AUTOSOMAL DOMINANT, OMIM:608328 is limited. The allelic requirement and mutation consequence are monoallelic_autosomal and altered gene product structure (PMIDs: 12525539;23897642).; to: The DDG2P confidence category for the disease Marfan Syndrome, biallelic, OMIM:154700 is definitive. The allelic requirement and mutation consequence are biallelic_autosomal and altered gene product structure (PMIDs: 17568394; 27582083; 31950671).

The DDG2P confidence category for the disease MARFAN SYNDROME, OMIM:154700 is definitive. The allelic requirement and mutation consequence are monoallelic_autosomal and absent gene product (PMIDs: 8428751; 8504310; 1631074; 7611299; 21594993; 7762551; 18412115; 1301946; 15287423; 15032979; 8430317; 8040326; 8101042; 9101298; 8406497; 11175294; 10766875; 17492313; 21594992; 17366579; 11702223; 9837823; 1569206; 8136837; 9241263; 7633409; 20082464; 10441597; 7911051; 20979188; 8281141; 1852208).

The DDG2P confidence category for the disease SHPRINTZEN-GOLDBERG CRANIOSYNOSTOSIS SYNDROME, OMIM:182212 is definitive. The allelic requirement and mutation consequence are monoallelic_autosomal and altered gene product structure (PMIDs: 8428751; 8504310; 1631074; 7611299; 7762551; 21594993; 18412115; 1301946; 15032979; 15287423; 8430317; 8040326; 8071963; 8101042; 9101298; 8406497; 11175294; 10766875; 17492313; 21594992; 23103230; 23023332; 17568394; 17366579; 11702223; 9837823; 1569206; 8136837; 9241263; 7633409; 20082464; 10441597; 8281141; 20979188; 7911051; 16333834; 1852208).

The DDG2P confidence category for the disease WEILL-MARCHESANI SYNDROME AUTOSOMAL DOMINANT, OMIM:608328 is limited. The allelic requirement and mutation consequence are monoallelic_autosomal and altered gene product structure (PMIDs: 12525539;23897642).
Mitochondrial disorders v4.96 SLC52A2 Sarah Leigh Tag Q4_23_promote_green tag was added to gene: SLC52A2.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.40 REL Hannah Knight reviewed gene: REL: Rating: AMBER; Mode of pathogenicity: None; Publications: 34623332; Phenotypes: Immunodeficiency 92; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v4.96 SLC52A2 Sarah Leigh edited their review of gene: SLC52A2: Added comment: PMIDs 29053833 & 29193829 characterize six unrelated cases of Brown-Vialetto-Van Laere syndrome 2 (OMIM:614707) carrying a total of SLC52A2 variants. Functional studies and histological observations allow the authors to conclude that the resultant riboflavin transporter deficiency associated with the SLC52A2 variants, causes a mitochondrial dysfunction.; Changed rating: GREEN
Primary immunodeficiency or monogenic inflammatory bowel disease v4.40 POLD3 Hannah Knight gene: POLD3 was added
gene: POLD3 was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: POLD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLD3 were set to 37030525
Phenotypes for gene: POLD3 were set to Immunodeficiency with neurodevelopmental delay and hearing loss
Review for gene: POLD3 was set to AMBER
Added comment: PMID: 37030525 - homozygous POLD3 variant (p.Ile10Thr) in a consanguinous Lebanese family, presenting with a syndromic severe combined immunodeficiency (SCID) with neurodevelopmental delay and hearing loss
Sources: Literature
Cytopenia - NOT Fanconi anaemia v3.4 CXCR2 Achchuthan Shanmugasundram Phenotypes for gene: CXCR2 were changed from ?WHIM syndrome 2 to ?WHIM syndrome 2, OMIM:619407
Cytopenia - NOT Fanconi anaemia v3.3 CXCR2 Achchuthan Shanmugasundram Classified gene: CXCR2 as Amber List (moderate evidence)
Cytopenia - NOT Fanconi anaemia v3.3 CXCR2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Hannah Knight, there are five unrelated cases available in support of the association of biallelic CXCR2 variants to this panel. Hence, this gene can be promoted to green rating in the next GMS review.
Cytopenia - NOT Fanconi anaemia v3.3 CXCR2 Achchuthan Shanmugasundram Gene: cxcr2 has been classified as Amber List (Moderate Evidence).
Cytopenia - NOT Fanconi anaemia v3.2 CXCR2 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: CXCR2.
Cytopenia - NOT Fanconi anaemia v3.2 CXCR2 Achchuthan Shanmugasundram reviewed gene: CXCR2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ?WHIM syndrome 2, OMIM:619407; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v4.40 POLD1 Hannah Knight reviewed gene: POLD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33140240; Phenotypes: Polymerase d 1 deficiency; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v4.40 CXCR2 Achchuthan Shanmugasundram Classified gene: CXCR2 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.40 CXCR2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Hannah Knight, there are five unrelated cases with biallelic CXCR2 variants. Hence, this gene can be promoted to green rating in the next GMS review.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.40 CXCR2 Achchuthan Shanmugasundram Gene: cxcr2 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.39 CXCR2 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: CXCR2.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.39 CXCR2 Achchuthan Shanmugasundram reviewed gene: CXCR2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ?WHIM syndrome 2, OMIM:619407; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v4.96 SLC52A2 Sarah Leigh Classified gene: SLC52A2 as Amber List (moderate evidence)
Mitochondrial disorders v4.96 SLC52A2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Mitochondrial disorders v4.96 SLC52A2 Sarah Leigh Gene: slc52a2 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.39 CR2 Achchuthan Shanmugasundram edited their review of gene: CR2: Changed phenotypes to: ?Immunodeficiency, common variable, 7, OMIM:614699
Primary immunodeficiency or monogenic inflammatory bowel disease v4.39 CR2 Achchuthan Shanmugasundram Phenotypes for gene: CR2 were changed from Immunodeficiency, common variable, 7, 614699; Lupus; Immunodeficiency, common variable, 7; Common variable immunodeficiency disorders (CVID); Isolated IgG subclass deficiency; hypogammaglobulinaemia; Recurrent infections; Predominantly Antibody Deficiencies to ?Immunodeficiency, common variable, 7, OMIM:614699
Primary immunodeficiency or monogenic inflammatory bowel disease v4.38 CR2 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: CR2.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.38 CR2 Achchuthan Shanmugasundram Classified gene: CR2 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.38 CR2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Hannah Knight, there are three unrelated cases in support of the association of CR2 to immunodeficiency. Hence, this gene can be promoted to Green in the next GMS review.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.38 CR2 Achchuthan Shanmugasundram Gene: cr2 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.37 CR2 Achchuthan Shanmugasundram reviewed gene: CR2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ?Immunodeficiency, common variable, 7, OMIM: 614699; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v5.17 ACTC1 Achchuthan Shanmugasundram Classified gene: ACTC1 as Amber List (moderate evidence)
Arthrogryposis v5.17 ACTC1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (five unrelated families) available in support of the association of ACTC1 with distal arthrogryposis and hence this gene can be promoted to green rating in the next GMS review.
Arthrogryposis v5.17 ACTC1 Achchuthan Shanmugasundram Gene: actc1 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v5.16 ACTC1 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: ACTC1.
Arthrogryposis v5.16 ACTC1 Achchuthan Shanmugasundram gene: ACTC1 was added
gene: ACTC1 was added to Arthrogryposis. Sources: Literature
Mode of inheritance for gene: ACTC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ACTC1 were set to 37457373
Phenotypes for gene: ACTC1 were set to distal arthrogryposis, MONDO:0019942
Review for gene: ACTC1 was set to GREEN
Added comment: Eight individuals from five unrelated families were identified with five different heterozygous missense variants in ACTC1 gene and they were reported with distal arthrogryposis. The clinical presentations included multiple congenital contractures, neck pterygia, scoliosis, and congenital heart defects/cardiomyopathy, short stature.

This gene has been associated with cardiac phenotypes in both OMIM and Gene2Phenotype, but not yet with distal arthrogryposis in either resources.
Sources: Literature
Familial tumours of the nervous system v1.3 LZTFL1 Eleanor Williams Tag curated_removed tag was added to gene: LZTFL1.
Familial tumours of the nervous system v1.3 LZTR1 Eleanor Williams reviewed gene: LZTR1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Familial tumours of the nervous system v1.3 LZTFL1 Eleanor Williams commented on gene: LZTFL1
Familial tumours of the nervous system v1.2 LZTR1 Eleanor Williams gene: LZTR1 was added
gene: LZTR1 was added to Familial tumours of the nervous system. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: LZTR1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Familial tumours of the nervous system v1.2 LZTFL1 Eleanor Williams Source Expert Review Removed was added to LZTFL1.
Rating Changed from Green List (high evidence) to No List (delete)
Paediatric disorders - additional genes v3.5 TOR1AIP1 Arina Puzriakova Tag Q4_22_promote_green was removed from gene: TOR1AIP1.
Paediatric disorders - additional genes v3.5 PLXND1 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: PLXND1.
Paediatric disorders - additional genes v3.5 PAPPA2 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: PAPPA2.
Paediatric disorders - additional genes v3.5 FOXI3 Arina Puzriakova Tag Q4_22_promote_green was removed from gene: FOXI3.
Paediatric disorders - additional genes v3.5 TOR1AIP1 Arina Puzriakova commented on gene: TOR1AIP1: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Paediatric disorders - additional genes v3.5 PLXND1 Arina Puzriakova reviewed gene: PLXND1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric disorders - additional genes v3.5 PAPPA2 Arina Puzriakova edited their review of gene: PAPPA2: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Paediatric disorders - additional genes v3.5 FOXI3 Arina Puzriakova commented on gene: FOXI3: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.
Paediatric disorders - additional genes v3.4 TOR1AIP1 Arina Puzriakova Source Expert Review Green was added to TOR1AIP1.
Source NHS GMS was added to TOR1AIP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v3.4 PLXND1 Arina Puzriakova Source Expert Review Green was added to PLXND1.
Source NHS GMS was added to PLXND1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v3.4 PAPPA2 Arina Puzriakova Source Expert Review Green was added to PAPPA2.
Source NHS GMS was added to PAPPA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v3.4 FOXI3 Arina Puzriakova Source Expert Review Green was added to FOXI3.
Source NHS GMS was added to FOXI3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v3.37 TBX20 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: TBX20.
Tag Q2_23_NHS_review was removed from gene: TBX20.
Paediatric or syndromic cardiomyopathy v3.37 RRAGC Arina Puzriakova Tag Q2_23_promote_green was removed from gene: RRAGC.
Tag Q2_23_NHS_review was removed from gene: RRAGC.
Paediatric or syndromic cardiomyopathy v3.37 TBX20 Arina Puzriakova reviewed gene: TBX20: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Paediatric or syndromic cardiomyopathy v3.37 RRAGC Arina Puzriakova edited their review of gene: RRAGC: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Paediatric or syndromic cardiomyopathy v3.36 TBX20 Arina Puzriakova Source NHS GMS was added to TBX20.
Source Expert Review Green was added to TBX20.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v3.36 RRAGC Arina Puzriakova Source Expert Review Green was added to RRAGC.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset dystonia, chorea or related movement disorder v3.13 GBA James Polke reviewed gene: GBA: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Gaucher; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v4.37 TLR7 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: TLR7.
Early onset or syndromic epilepsy v4.115 UBAP2L Arina Puzriakova Tag Q1_23_promote_green was removed from gene: UBAP2L.
Early onset or syndromic epilepsy v4.115 TRA2B Arina Puzriakova Tag Q2_23_promote_green was removed from gene: TRA2B.
Early onset or syndromic epilepsy v4.115 STXBP1 Arina Puzriakova Phenotypes for gene: STXBP1 were changed from Developmental and epileptic encephalopathy 4, OMIM:612164; developmental and epileptic encephalopathy, 4, MONDO:0012812 to Developmental and epileptic encephalopathy 4, OMIM:612164
Early onset or syndromic epilepsy v4.114 STXBP1 Arina Puzriakova Tag Q1_23_MOI was removed from gene: STXBP1.
Early onset or syndromic epilepsy v4.114 ST3GAL3 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: ST3GAL3.
Early onset or syndromic epilepsy v4.114 SLC39A8 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: SLC39A8.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.37 TBX1 Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: TBX1.
Tag Q1_23_NHS_review was removed from gene: TBX1.
Early onset or syndromic epilepsy v4.114 SLC32A1 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: SLC32A1.
Early onset or syndromic epilepsy v4.114 SATB2 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: SATB2.
Early onset or syndromic epilepsy v4.114 SARS Arina Puzriakova Tag Q1_23_promote_green was removed from gene: SARS.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.37 IRF7 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: IRF7.
Early onset or syndromic epilepsy v4.114 RHEB Arina Puzriakova Tag Q2_23_promote_green was removed from gene: RHEB.
Early onset or syndromic epilepsy v4.114 RAC3 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: RAC3.
Early onset or syndromic epilepsy v4.114 PPFIBP1 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: PPFIBP1.
Early onset or syndromic epilepsy v4.114 PLXNA1 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: PLXNA1.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.37 IKZF2 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: IKZF2.
Early onset or syndromic epilepsy v4.114 PLK1 Arina Puzriakova Phenotypes for gene: PLK1 were changed from Epilepsy; microcephaly; intellectual disability to developmental and epileptic encephalopathy, MONDO:0100062
Early onset or syndromic epilepsy v4.113 PLK1 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: PLK1.
Early onset or syndromic epilepsy v4.113 OTUD7A Arina Puzriakova Phenotypes for gene: OTUD7A were changed from Epileptic encephalopathy, intellectual disability to developmental and epileptic encephalopathy, MONDO:0100062
Primary immunodeficiency or monogenic inflammatory bowel disease v4.37 C2orf69 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: C2orf69.
Early onset or syndromic epilepsy v4.112 OTUD7A Arina Puzriakova Tag Q2_23_promote_green was removed from gene: OTUD7A.
Early onset or syndromic epilepsy v4.112 NUP214 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: NUP214.
Early onset or syndromic epilepsy v4.112 NEDD4L Arina Puzriakova Tag Q1_23_promote_green was removed from gene: NEDD4L.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.37 ALPK1 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: ALPK1.
Early onset or syndromic epilepsy v4.112 MED11 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: MED11.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.37 TLR7 Arina Puzriakova edited their review of gene: TLR7: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.37 TBX1 Arina Puzriakova commented on gene: TBX1: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.37 IRF7 Arina Puzriakova edited their review of gene: IRF7: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Primary immunodeficiency or monogenic inflammatory bowel disease v4.37 IKZF2 Arina Puzriakova edited their review of gene: IKZF2: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Primary immunodeficiency or monogenic inflammatory bowel disease v4.37 C2orf69 Arina Puzriakova edited their review of gene: C2orf69: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Primary immunodeficiency or monogenic inflammatory bowel disease v4.37 ALPK1 Arina Puzriakova edited their review of gene: ALPK1: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Early onset or syndromic epilepsy v4.112 MAGI2 Arina Puzriakova Tag disputed tag was added to gene: MAGI2.
Early onset or syndromic epilepsy v4.112 MAGI2 Arina Puzriakova Tag Q1_23_demote_red was removed from gene: MAGI2.
Early onset or syndromic epilepsy v4.112 KPTN Arina Puzriakova Tag Q1_23_promote_green was removed from gene: KPTN.
Early onset or syndromic epilepsy v4.112 KLHL20 Arina Puzriakova Tag Q4_22_promote_green was removed from gene: KLHL20.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.36 TLR7 Achchuthan Shanmugasundram Source Expert Review Green was added to TLR7.
Source NHS GMS was added to TLR7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.36 TBX1 Achchuthan Shanmugasundram Source Expert Review Green was added to TBX1.
Source NHS GMS was added to TBX1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.36 IRF7 Achchuthan Shanmugasundram Source Expert Review Green was added to IRF7.
Source NHS GMS was added to IRF7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.36 IKZF2 Achchuthan Shanmugasundram Source Expert Review Green was added to IKZF2.
Source NHS GMS was added to IKZF2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.36 C2orf69 Achchuthan Shanmugasundram Source Expert Review Green was added to C2orf69.
Source NHS GMS was added to C2orf69.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.36 ALPK1 Achchuthan Shanmugasundram Source Expert Review Green was added to ALPK1.
Source NHS GMS was added to ALPK1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.112 GRM7 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: GRM7.
Early onset or syndromic epilepsy v4.112 GRIA2 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: GRIA2.
Intellectual disability v5.306 GCSH Arina Puzriakova Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to Multiple mitochondrial dysfunctions syndrome 7, OMIM:620423; Glycine encephalopathy; Transient neonatal hyperglycinemia
Early onset or syndromic epilepsy v4.112 GCSH Arina Puzriakova Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to Multiple mitochondrial dysfunctions syndrome 7, OMIM:620423; Glycine encephalopathy; Transient neonatal hyperglycinemia
Likely inborn error of metabolism v4.52 GCSH Arina Puzriakova Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to Multiple mitochondrial dysfunctions syndrome 7, OMIM:620423; Glycine encephalopathy; Transient neonatal hyperglycinemia
Congenital disorders of glycosylation v4.3 ST3GAL3 Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: ST3GAL3.
Congenital disorders of glycosylation v4.3 ST3GAL3 Arina Puzriakova edited their review of gene: ST3GAL3: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Early onset or syndromic epilepsy v4.111 GCSH Arina Puzriakova Tag Q1_23_promote_green was removed from gene: GCSH.
Early onset or syndromic epilepsy v4.111 GABRB1 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: GABRB1.
Congenital disorders of glycosylation v4.2 ST3GAL3 Achchuthan Shanmugasundram Source Expert Review Green was added to ST3GAL3.
Source NHS GMS was added to ST3GAL3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.111 FRMD5 Arina Puzriakova Tag Q4_22_promote_green was removed from gene: FRMD5.
Early onset or syndromic epilepsy v4.111 FOXRED1 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: FOXRED1.
Early onset or syndromic epilepsy v4.111 FGFR3 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: FGFR3.
Early onset or syndromic epilepsy v4.111 EXT2 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: EXT2.
Early onset or syndromic epilepsy v4.111 ENTPD1 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: ENTPD1.
Early onset or syndromic epilepsy v4.111 DPH5 Arina Puzriakova Phenotypes for gene: DPH5 were changed from DPH5-related neurodevelopmental disorder to Neurodevelopmental disorder with short stature, prominent forehead, and feeding difficulties, OMIM:620070
Early onset or syndromic epilepsy v4.110 DPH5 Arina Puzriakova Tag Q4_22_promote_green was removed from gene: DPH5.
Early onset or syndromic epilepsy v4.110 DOLK Arina Puzriakova Tag watchlist was removed from gene: DOLK.
Tag Q1_23_promote_green was removed from gene: DOLK.
Early onset or syndromic epilepsy v4.110 DEPDC5 Arina Puzriakova Tag Q1_23_MOI was removed from gene: DEPDC5.
Early onset or syndromic epilepsy v4.110 CUX2 Arina Puzriakova Tag Q1_23_MOI was removed from gene: CUX2.
Tag Q1_23_NHS_review was removed from gene: CUX2.
Early onset or syndromic epilepsy v4.110 CPLX1 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: CPLX1.
Early onset or syndromic epilepsy v4.110 CLDN5 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: CLDN5.
Early onset or syndromic epilepsy v4.110 CHD4 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: CHD4.
Early onset or syndromic epilepsy v4.110 CAPRIN1 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: CAPRIN1.
Early onset or syndromic epilepsy v4.110 C2orf69 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: C2orf69.
Early onset or syndromic epilepsy v4.110 BAP1 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: BAP1.
Early onset or syndromic epilepsy v4.110 ATP5O Arina Puzriakova Tag Q2_23_promote_green was removed from gene: ATP5O.
Likely inborn error of metabolism v4.51 SPG7 Achchuthan Shanmugasundram Tag Q2_23_MOI was removed from gene: SPG7.
Early onset or syndromic epilepsy v4.110 ASXL3 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: ASXL3.
Likely inborn error of metabolism v4.51 PNPLA2 Achchuthan Shanmugasundram Deleted their comment
Likely inborn error of metabolism v4.51 PNPLA2 Achchuthan Shanmugasundram Deleted their comment
Likely inborn error of metabolism v4.51 PNPLA2 Achchuthan Shanmugasundram Deleted their comment
Likely inborn error of metabolism v4.51 PNPLA2 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: PNPLA2.
Likely inborn error of metabolism v4.51 OGDH Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: OGDH.
Likely inborn error of metabolism v4.51 LETM1 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: LETM1.
Likely inborn error of metabolism v4.51 GCSH Achchuthan Shanmugasundram Deleted their comment
Likely inborn error of metabolism v4.51 GCSH Achchuthan Shanmugasundram Deleted their comment
Likely inborn error of metabolism v4.51 GCSH Achchuthan Shanmugasundram Deleted their comment
Likely inborn error of metabolism v4.51 GCSH Achchuthan Shanmugasundram Deleted their comment
Likely inborn error of metabolism v4.51 GCSH Achchuthan Shanmugasundram Deleted their comment
Likely inborn error of metabolism v4.51 GCSH Achchuthan Shanmugasundram Deleted their comment
Likely inborn error of metabolism v4.51 GCSH Achchuthan Shanmugasundram Deleted their comment
Likely inborn error of metabolism v4.51 GCSH Achchuthan Shanmugasundram Deleted their comment
Likely inborn error of metabolism v4.51 GCSH Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: GCSH.
Likely inborn error of metabolism v4.51 CRLS1 Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: CRLS1.
Likely inborn error of metabolism v4.51 ATP5O Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: ATP5O.
Likely inborn error of metabolism v4.51 SPG7 Arina Puzriakova reviewed gene: SPG7: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Likely inborn error of metabolism v4.51 PNPLA2 Arina Puzriakova reviewed gene: PNPLA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v4.51 OGDH Arina Puzriakova reviewed gene: OGDH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v4.51 LETM1 Arina Puzriakova reviewed gene: LETM1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v4.51 GCSH Arina Puzriakova reviewed gene: GCSH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v4.51 CRLS1 Arina Puzriakova reviewed gene: CRLS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v4.51 ATP5O Arina Puzriakova commented on gene: ATP5O: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Likely inborn error of metabolism v4.50 SPG7 Achchuthan Shanmugasundram Mode of inheritance for gene SPG7 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Likely inborn error of metabolism v4.50 PNPLA2 Achchuthan Shanmugasundram Source NHS GMS was added to PNPLA2.
Source Expert Review Green was added to PNPLA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v4.50 OGDH Achchuthan Shanmugasundram Source Expert Review Green was added to OGDH.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v4.50 LETM1 Achchuthan Shanmugasundram Source NHS GMS was added to LETM1.
Source Expert Review Green was added to LETM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v4.50 GCSH Achchuthan Shanmugasundram Source Expert Review Green was added to GCSH.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v4.50 CRLS1 Achchuthan Shanmugasundram Source NHS GMS was added to CRLS1.
Source Expert Review Green was added to CRLS1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v4.50 ATP5O Achchuthan Shanmugasundram Source NHS GMS was added to ATP5O.
Source Expert Review Green was added to ATP5O.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.110 CPA6 Arina Puzriakova Tag for-review was removed from gene: CPA6.
Tag Q2_23_demote_red was removed from gene: CPA6.
Tag Q2_23_NHS_review was removed from gene: CPA6.
Tag Q2_23_expert_review was removed from gene: CPA6.
Tag refuted tag was added to gene: CPA6.
Early onset or syndromic epilepsy v4.110 UBAP2L Arina Puzriakova reviewed gene: UBAP2L: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v4.110 TRA2B Arina Puzriakova reviewed gene: TRA2B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v4.110 STXBP1 Arina Puzriakova reviewed gene: STXBP1: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v4.110 ST3GAL3 Arina Puzriakova reviewed gene: ST3GAL3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v4.110 SLC39A8 Arina Puzriakova reviewed gene: SLC39A8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v4.110 SLC32A1 Arina Puzriakova reviewed gene: SLC32A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v4.110 SATB2 Arina Puzriakova reviewed gene: SATB2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v4.110 SARS Arina Puzriakova commented on gene: SARS: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v4.110 RHEB Arina Puzriakova edited their review of gene: RHEB: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v4.110 RAC3 Arina Puzriakova edited their review of gene: RAC3: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v4.110 PPFIBP1 Arina Puzriakova reviewed gene: PPFIBP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v4.110 PLXNA1 Arina Puzriakova reviewed gene: PLXNA1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v4.110 PLK1 Arina Puzriakova reviewed gene: PLK1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v4.110 OTUD7A Arina Puzriakova reviewed gene: OTUD7A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v4.110 NUP214 Arina Puzriakova reviewed gene: NUP214: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v4.110 NEDD4L Arina Puzriakova reviewed gene: NEDD4L: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v4.110 MED11 Arina Puzriakova reviewed gene: MED11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v4.110 MAGI2 Arina Puzriakova reviewed gene: MAGI2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Early onset or syndromic epilepsy v4.110 KPTN Arina Puzriakova reviewed gene: KPTN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v4.110 KLHL20 Arina Puzriakova edited their review of gene: KLHL20: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v4.110 GRM7 Arina Puzriakova reviewed gene: GRM7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v4.110 GRIA2 Arina Puzriakova reviewed gene: GRIA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v4.110 GCSH Arina Puzriakova reviewed gene: GCSH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v4.110 GABRB1 Arina Puzriakova reviewed gene: GABRB1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v4.110 FRMD5 Arina Puzriakova commented on gene: FRMD5: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v4.110 FOXRED1 Arina Puzriakova reviewed gene: FOXRED1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v4.110 FGFR3 Arina Puzriakova reviewed gene: FGFR3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v4.110 EXT2 Arina Puzriakova reviewed gene: EXT2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v4.110 ENTPD1 Arina Puzriakova reviewed gene: ENTPD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v4.110 DPH5 Arina Puzriakova reviewed gene: DPH5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v4.110 DOLK Arina Puzriakova reviewed gene: DOLK: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v4.110 DEPDC5 Arina Puzriakova reviewed gene: DEPDC5: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v4.110 CUX2 Arina Puzriakova reviewed gene: CUX2: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v4.110 CPLX1 Arina Puzriakova reviewed gene: CPLX1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v4.110 CPA6 Arina Puzriakova reviewed gene: CPA6: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Early onset or syndromic epilepsy v4.110 CLDN5 Arina Puzriakova reviewed gene: CLDN5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v4.110 CHD4 Arina Puzriakova reviewed gene: CHD4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v4.110 CAPRIN1 Arina Puzriakova reviewed gene: CAPRIN1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v4.110 C2orf69 Arina Puzriakova edited their review of gene: C2orf69: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v4.110 BAP1 Arina Puzriakova reviewed gene: BAP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v4.110 ATP5O Arina Puzriakova commented on gene: ATP5O: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v4.110 ASXL3 Arina Puzriakova reviewed gene: ASXL3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.174 SOX6 Eleanor Williams Tag Q2_23_promote_green was removed from gene: SOX6.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.174 RSPRY1 Eleanor Williams Tag Q2_23_promote_green was removed from gene: RSPRY1.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.174 PRRX1 Eleanor Williams Tag Q2_23_promote_green was removed from gene: PRRX1.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.174 NFIX Eleanor Williams Tag Q2_23_promote_green was removed from gene: NFIX.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.174 MAN2B1 Eleanor Williams Tag Q2_23_promote_green was removed from gene: MAN2B1.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.174 KAT6B Eleanor Williams Tag Q2_23_promote_green was removed from gene: KAT6B.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.174 IL6ST Eleanor Williams Tag Q2_23_promote_green was removed from gene: IL6ST.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.174 IFT140 Eleanor Williams Tag Q2_23_promote_green was removed from gene: IFT140.
Early onset or syndromic epilepsy v4.109 UBAP2L Arina Puzriakova Source NHS GMS was added to UBAP2L.
Source Expert Review Green was added to UBAP2L.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.109 TRA2B Arina Puzriakova Source NHS GMS was added to TRA2B.
Source Expert Review Green was added to TRA2B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.109 STXBP1 Arina Puzriakova Mode of inheritance for gene STXBP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v4.109 ST3GAL3 Arina Puzriakova Source Expert Review Green was added to ST3GAL3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.109 SLC39A8 Arina Puzriakova Source NHS GMS was added to SLC39A8.
Source Expert Review Green was added to SLC39A8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.174 FGF9 Eleanor Williams Tag Q2_23_promote_green was removed from gene: FGF9.
Early onset or syndromic epilepsy v4.109 SLC32A1 Arina Puzriakova Source NHS GMS was added to SLC32A1.
Source Expert Review Green was added to SLC32A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.109 SATB2 Arina Puzriakova Source NHS GMS was added to SATB2.
Source Expert Review Green was added to SATB2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.109 SARS Arina Puzriakova Source NHS GMS was added to SARS.
Source Expert Review Green was added to SARS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.109 RHEB Arina Puzriakova Source NHS GMS was added to RHEB.
Source Expert Review Green was added to RHEB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.109 RAC3 Arina Puzriakova Source NHS GMS was added to RAC3.
Source Expert Review Green was added to RAC3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.109 PPFIBP1 Arina Puzriakova Source NHS GMS was added to PPFIBP1.
Source Expert Review Green was added to PPFIBP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.109 PLXNA1 Arina Puzriakova Source NHS GMS was added to PLXNA1.
Source Expert Review Green was added to PLXNA1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.109 PLK1 Arina Puzriakova Source NHS GMS was added to PLK1.
Source Expert Review Green was added to PLK1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.109 OTUD7A Arina Puzriakova Source NHS GMS was added to OTUD7A.
Source Expert Review Green was added to OTUD7A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.109 NUP214 Arina Puzriakova Source NHS GMS was added to NUP214.
Source Expert Review Green was added to NUP214.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.109 NEDD4L Arina Puzriakova Source Expert Review Green was added to NEDD4L.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.109 MED11 Arina Puzriakova Source NHS GMS was added to MED11.
Source Expert Review Green was added to MED11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.109 MAGI2 Arina Puzriakova Source Expert Review Red was added to MAGI2.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Early onset or syndromic epilepsy v4.109 KPTN Arina Puzriakova Source Expert Review Green was added to KPTN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.109 KLHL20 Arina Puzriakova Source NHS GMS was added to KLHL20.
Source Expert Review Green was added to KLHL20.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.109 GRM7 Arina Puzriakova Source NHS GMS was added to GRM7.
Source Expert Review Green was added to GRM7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.109 GRIA2 Arina Puzriakova Source Expert Review Green was added to GRIA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.109 GCSH Arina Puzriakova Source Expert Review Green was added to GCSH.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.109 GABRB1 Arina Puzriakova Source Expert Review Green was added to GABRB1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.174 FBXO11 Eleanor Williams Tag Q2_23_promote_green was removed from gene: FBXO11.
Early onset or syndromic epilepsy v4.109 FRMD5 Arina Puzriakova Source NHS GMS was added to FRMD5.
Source Expert Review Green was added to FRMD5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.109 FOXRED1 Arina Puzriakova Source Expert Review Green was added to FOXRED1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.109 FGFR3 Arina Puzriakova Source Expert Review Green was added to FGFR3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.109 EXT2 Arina Puzriakova Source NHS GMS was added to EXT2.
Source Expert Review Green was added to EXT2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.109 ENTPD1 Arina Puzriakova Source NHS GMS was added to ENTPD1.
Source Expert Review Green was added to ENTPD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.109 DPH5 Arina Puzriakova Source NHS GMS was added to DPH5.
Source Expert Review Green was added to DPH5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.109 DOLK Arina Puzriakova Source Expert Review Green was added to DOLK.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.109 DEPDC5 Arina Puzriakova Mode of inheritance for gene DEPDC5 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v4.109 CUX2 Arina Puzriakova Mode of inheritance for gene CUX2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v4.109 CPLX1 Arina Puzriakova Source NHS GMS was added to CPLX1.
Source Expert Review Green was added to CPLX1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.109 CPA6 Arina Puzriakova Source Expert Review Red was added to CPA6.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Early onset or syndromic epilepsy v4.109 CLDN5 Arina Puzriakova Source NHS GMS was added to CLDN5.
Source Expert Review Green was added to CLDN5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.109 CHD4 Arina Puzriakova Source NHS GMS was added to CHD4.
Source Expert Review Green was added to CHD4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.109 CAPRIN1 Arina Puzriakova Source NHS GMS was added to CAPRIN1.
Source Expert Review Green was added to CAPRIN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.109 C2orf69 Arina Puzriakova Source NHS GMS was added to C2orf69.
Source Expert Review Green was added to C2orf69.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.109 BAP1 Arina Puzriakova Source NHS GMS was added to BAP1.
Source Expert Review Green was added to BAP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.174 FBN1 Eleanor Williams Tag Q2_23_promote_green was removed from gene: FBN1.
Early onset or syndromic epilepsy v4.109 ATP5O Arina Puzriakova Source Expert Review Green was added to ATP5O.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v4.109 ASXL3 Arina Puzriakova Source NHS GMS was added to ASXL3.
Source Expert Review Green was added to ASXL3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.174 CDK13 Eleanor Williams Tag Q2_23_promote_green was removed from gene: CDK13.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.174 BCL11B Eleanor Williams Tag Q2_23_promote_green was removed from gene: BCL11B.
Tag Q2_23_NHS_review was removed from gene: BCL11B.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.174 ARID1B Eleanor Williams Tag Q2_23_promote_green was removed from gene: ARID1B.
Malformations of cortical development v4.8 COL4A2 Nour Elkhateeb gene: COL4A2 was added
gene: COL4A2 was added to Malformations of cortical development. Sources: Literature
Mode of inheritance for gene: COL4A2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: COL4A2 were set to 30413629; 36324412; 22333902
Phenotypes for gene: COL4A2 were set to Malformations of cortical development; Schizencephaly; porencephaly; polymicrogyria; focal cortical dysplasia; nodular heterotopia
Added comment: COL4A2 variants are commonly associated with cortical malformations (Schizencephaly, porencephaly, polymicrogyria, focal cortical dysplasia, and nodular heterotopia) in literature.
COL4A2 variants are associated with porencephaly. however, it is not included in the R87 Cerebral malformation panel (indications as per the national genomic test directory include "
Cerebral malformation such as cortical malformation or porencephaly with features suggestive of a monogenic cause"
Sources: Literature
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.174 AHDC1 Eleanor Williams Tag Q2_23_promote_green was removed from gene: AHDC1.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.174 ADAMTSL4 Eleanor Williams Tag Q2_23_promote_green was removed from gene: ADAMTSL4.
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.174 SOX6 Eleanor Williams edited their review of gene: SOX6: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.174 RSPRY1 Eleanor Williams edited their review of gene: RSPRY1: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.174 PRRX1 Eleanor Williams edited their review of gene: PRRX1: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.174 NFIX Eleanor Williams edited their review of gene: NFIX: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.174 MAN2B1 Eleanor Williams reviewed gene: MAN2B1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.174 KAT6B Eleanor Williams edited their review of gene: KAT6B: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.174 IL6ST Eleanor Williams reviewed gene: IL6ST: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.174 IFT140 Eleanor Williams edited their review of gene: IFT140: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.174 FGF9 Eleanor Williams edited their review of gene: FGF9: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.174 FBXO11 Eleanor Williams reviewed gene: FBXO11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.174 FBN1 Eleanor Williams edited their review of gene: FBN1: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.174 CDK13 Eleanor Williams reviewed gene: CDK13: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.174 BCL11B Eleanor Williams reviewed gene: BCL11B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.174 ARID1B Eleanor Williams reviewed gene: ARID1B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.174 AHDC1 Eleanor Williams edited their review of gene: AHDC1: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.174 ADAMTSL4 Eleanor Williams edited their review of gene: ADAMTSL4: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary diffuse gastric cancer v1.3 CTNNA1 Arina Puzriakova reviewed gene: CTNNA1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.173 SOX6 Eleanor Williams Source Expert Review Green was added to SOX6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.173 RSPRY1 Eleanor Williams Source Expert Review Green was added to RSPRY1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.173 PRRX1 Eleanor Williams Source Expert Review Green was added to PRRX1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.173 NFIX Eleanor Williams Source Expert Review Green was added to NFIX.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.173 MAN2B1 Eleanor Williams Source Expert Review Green was added to MAN2B1.
Source NHS GMS was added to MAN2B1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.173 KAT6B Eleanor Williams Source Expert Review Green was added to KAT6B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.173 IL6ST Eleanor Williams Source Expert Review Green was added to IL6ST.
Source NHS GMS was added to IL6ST.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.173 IFT140 Eleanor Williams Source Expert Review Green was added to IFT140.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.173 FGF9 Eleanor Williams Source Expert Review Green was added to FGF9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.173 FBXO11 Eleanor Williams Source Expert Review Green was added to FBXO11.
Source NHS GMS was added to FBXO11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.173 FBN1 Eleanor Williams Source Expert Review Green was added to FBN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.173 CDK13 Eleanor Williams Source Expert Review Green was added to CDK13.
Source NHS GMS was added to CDK13.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.173 BCL11B Eleanor Williams Source Expert Review Green was added to BCL11B.
Source NHS GMS was added to BCL11B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.173 ARID1B Eleanor Williams Source Expert Review Green was added to ARID1B.
Source NHS GMS was added to ARID1B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.173 AHDC1 Eleanor Williams Source Expert Review Green was added to AHDC1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rare syndromic craniosynostosis or isolated multisuture synostosis v4.173 ADAMTSL4 Eleanor Williams Source Expert Review Green was added to ADAMTSL4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary diffuse gastric cancer v1.2 CTNNA1 Arina Puzriakova gene: CTNNA1 was added
gene: CTNNA1 was added to CDH1-related cancer syndrome. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: CTNNA1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Malformations of cortical development v4.8 COL4A1 Nour Elkhateeb gene: COL4A1 was added
gene: COL4A1 was added to Malformations of cortical development. Sources: Literature
Mode of inheritance for gene: COL4A1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: COL4A1 were set to 30837194; 37157232; 30413629; 36324412
Phenotypes for gene: COL4A1 were set to Malformations of cortical development; Schizencephaly; porencephaly; polymicrogyria; focal cortical dysplasia; nodular heterotopia
Review for gene: COL4A1 was set to GREEN
Added comment: COL4A1 variants are commonly associated with cortical malformations (Schizencephaly, porencephaly, polymicrogyria, focal cortical dysplasia, and nodular heterotopia) in literature. further information available on Genreviews Plaisier E, Ronco P. COL4A1-Related Disorders. 2009 Jun 25 [Updated 2016 Jul 7]. In: Adam MP, Mirzaa GM, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK7046/
COL4A1 variants are associated with porencephaly. however, it is not included in the R87 Cerebral malformation panel (indications as per the national genomic test directory include "
Cerebral malformation such as cortical malformation or porencephaly with features suggestive of a monogenic cause"
Sources: Literature
Intellectual disability v5.305 ZNF292 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: ZNF292.
Tag Q1_23_NHS_review was removed from gene: ZNF292.
Intellectual disability v5.305 ZMYND8 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: ZMYND8.
Intellectual disability v5.305 ZMYM3 Arina Puzriakova Phenotypes for gene: ZMYM3 were changed from X-linked mental retardation to Intellectual developmental disorder, X-linked 112, OMIM:301111
Skeletal ciliopathies v3.11 PRKACB Eleanor Williams Tag Q2_23_promote_green was removed from gene: PRKACB.
Skeletal ciliopathies v3.11 PRKACA Eleanor Williams Tag Q2_23_promote_green was removed from gene: PRKACA.
Intellectual disability v5.304 ZMYM3 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: ZMYM3.
Skeletal ciliopathies v3.11 INTU Eleanor Williams Tag Q2_23_promote_green was removed from gene: INTU.
Skeletal ciliopathies v3.11 PRKACB Eleanor Williams reviewed gene: PRKACB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal ciliopathies v3.11 PRKACA Eleanor Williams reviewed gene: PRKACA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal ciliopathies v3.11 INTU Eleanor Williams reviewed gene: INTU: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal ciliopathies v3.10 PRKACB Eleanor Williams Source Expert Review Green was added to PRKACB.
Source NHS GMS was added to PRKACB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal ciliopathies v3.10 PRKACA Eleanor Williams Source Expert Review Green was added to PRKACA.
Source NHS GMS was added to PRKACA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal ciliopathies v3.10 INTU Eleanor Williams Source Expert Review Green was added to INTU.
Source NHS GMS was added to INTU.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rhabdomyolysis and metabolic muscle disorders v3.37 OBSCN Eleanor Williams changed review comment from: The rating of this gene has been updated to green and the mode of inheritance set to "BIALLELIC, autosomal or pseudoautosomal" following NHS Genomic Medicine Service approval.NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to "BIALLELIC, autosomal or pseudoautosomal" following NHS Genomic Medicine Service approval.
Rhabdomyolysis and metabolic muscle disorders v3.37 MT-CO2 Eleanor Williams changed review comment from: The rating of this gene has been updated to green and the mode of inheritance set to "MITOCHONDRIAL" following NHS Genomic Medicine Service approval.NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to "MITOCHONDRIAL" following NHS Genomic Medicine Service approval.
Rhabdomyolysis and metabolic muscle disorders v3.37 MT-CO1 Eleanor Williams changed review comment from: The rating of this gene has been updated to green and the mode of inheritance set to "MITOCHONDRIAL" following NHS Genomic Medicine Service approval.NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to "MITOCHONDRIAL" following NHS Genomic Medicine Service approval.
Rhabdomyolysis and metabolic muscle disorders v3.37 FLAD1 Eleanor Williams changed review comment from: The rating of this gene has been updated to green and the mode of inheritance set to "BIALLELIC, autosomal or pseudoautosomal" following NHS Genomic Medicine Service approval.NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to "BIALLELIC, autosomal or pseudoautosomal" following NHS Genomic Medicine Service approval.
Rhabdomyolysis and metabolic muscle disorders v3.37 DGUOK Eleanor Williams changed review comment from: The rating of this gene has been updated to green and the mode of inheritance set to "BIALLELIC, autosomal or pseudoautosomal" following NHS Genomic Medicine Service approval.NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to "BIALLELIC, autosomal or pseudoautosomal" following NHS Genomic Medicine Service approval.
Rhabdomyolysis and metabolic muscle disorders v3.37 COQ8A Eleanor Williams changed review comment from: The rating of this gene has been updated to green and the mode of inheritance set to "BIALLELIC, autosomal or pseudoautosomal" following NHS Genomic Medicine Service approval.NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to "BIALLELIC, autosomal or pseudoautosomal" following NHS Genomic Medicine Service approval.
Rhabdomyolysis and metabolic muscle disorders v3.37 COQ4 Eleanor Williams changed review comment from: The rating of this gene has been updated to green and the mode of inheritance set to "BIALLELIC, autosomal or pseudoautosomal" following NHS Genomic Medicine Service approval.NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to "BIALLELIC, autosomal or pseudoautosomal" following NHS Genomic Medicine Service approval.
Rhabdomyolysis and metabolic muscle disorders v3.37 CHKB Eleanor Williams changed review comment from: The rating of this gene has been updated to green and the mode of inheritance set to "BIALLELIC, autosomal or pseudoautosomal" following NHS Genomic Medicine Service approval.NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to "BIALLELIC, autosomal or pseudoautosomal" following NHS Genomic Medicine Service approval.
Rhabdomyolysis and metabolic muscle disorders v3.37 AMPD1 Eleanor Williams changed review comment from: The rating of this gene has been updated to green and the mode of inheritance set to "BIALLELIC, autosomal or pseudoautosomal" following NHS Genomic Medicine Service approval.NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to "BIALLELIC, autosomal or pseudoautosomal" following NHS Genomic Medicine Service approval.
Rhabdomyolysis and metabolic muscle disorders v3.37 MLIP Eleanor Williams changed review comment from: The rating of this gene has been updated to green and the mode of inheritance set to "BIALLELIC, autosomal or pseudoautosomal" following NHS Genomic Medicine Service approval.NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to "BIALLELIC, autosomal or pseudoautosomal" following NHS Genomic Medicine Service approval.
Intellectual disability v5.304 WIPI2 Arina Puzriakova Phenotypes for gene: WIPI2 were changed from ?Intellectual developmental disorder with short stature and variable skeletal anomalies 618453 to Intellectual developmental disorder with short stature and variable skeletal anomalies, OMIM:618453
Limb disorders v4.11 PRKACA Eleanor Williams Tag Q2_23_promote_green was removed from gene: PRKACA.
Intellectual disability v5.303 WIPI2 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: WIPI2.
Limb disorders v4.11 GNAS Eleanor Williams Tag Q4_22_MOI was removed from gene: GNAS.
Limb disorders v4.11 CDX2 Eleanor Williams Tag Q2_23_promote_green was removed from gene: CDX2.
Limb disorders v4.11 PRKACA Eleanor Williams reviewed gene: PRKACA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Limb disorders v4.11 GNAS Eleanor Williams reviewed gene: GNAS: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Limb disorders v4.11 CDX2 Eleanor Williams reviewed gene: CDX2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v4.108 UBAP2L Arina Puzriakova Phenotypes for gene: UBAP2L were changed from Delayed speech and language development; Motor delay; Intellectual disability; Autistic behavior; Seizures; Microcephaly; Abnormality of head or neck; Short stature; Abnormality of the skeletal system to Neurodevelopmental disorder with impaired language, behavioral abnormalities, and dysmorphic facies, OMIM:620494
Limb disorders v4.10 PRKACA Eleanor Williams Source NHS GMS was added to PRKACA.
Source Expert Review Green was added to PRKACA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Limb disorders v4.10 GNAS Eleanor Williams Source NHS GMS was added to GNAS.
Mode of inheritance for gene GNAS was changed from MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Limb disorders v4.10 CDX2 Eleanor Williams Source NHS GMS was added to CDX2.
Source Expert Review Green was added to CDX2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.303 UBAP2L Arina Puzriakova Phenotypes for gene: UBAP2L were changed from Delayed speech and language development; Motor delay; Intellectual disability; Autistic behavior; Seizures; Microcephaly; Abnormality of head or neck; Short stature; Abnormality of the skeletal system to Neurodevelopmental disorder with impaired language, behavioral abnormalities, and dysmorphic facies, OMIM:620494
Intellectual disability v5.302 UBAP2L Arina Puzriakova Tag Q1_23_promote_green was removed from gene: UBAP2L.
Intellectual disability v5.302 TRA2B Arina Puzriakova Tag Q2_23_promote_green was removed from gene: TRA2B.
Intellectual disability v5.302 TMEM147 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: TMEM147.
Intellectual disability v5.302 TCEAL1 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: TCEAL1.
Intellectual disability v5.302 TAF4 Arina Puzriakova Phenotypes for gene: TAF4 were changed from intellectual disability, MONDO:0001071 to Intellectual developmental disorder, autosomal dominant 73, OMIM:620450
Intellectual disability v5.301 TAF4 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: TAF4.
Intellectual disability v5.301 TAF2 Arina Puzriakova Phenotypes for gene: TAF2 were changed from Mental retardation, autosomal recessive 40, 615599 to Mental retardation, autosomal recessive 40, OMIM:615599
Intellectual disability v5.300 TAF2 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: TAF2.
Intellectual disability v5.300 SUFU Arina Puzriakova Tag watchlist_moi was removed from gene: SUFU.
Tag Q4_22_MOI was removed from gene: SUFU.
Tag Q4_22_promote_green was removed from gene: SUFU.
Tag Q4_22_expert_review was removed from gene: SUFU.
Rhabdomyolysis and metabolic muscle disorders v3.37 DGUOK Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: DGUOK.
Tag Q3_23_NHS_review was removed from gene: DGUOK.
Intellectual disability v5.300 STXBP1 Arina Puzriakova Tag Q1_23_MOI was removed from gene: STXBP1.
Intellectual disability v5.300 SLC32A1 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: SLC32A1.
Intellectual disability v5.300 SHANK1 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: SHANK1.
Rhabdomyolysis and metabolic muscle disorders v3.37 OBSCN Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: OBSCN.
Tag Q3_23_NHS_review was removed from gene: OBSCN.
Intellectual disability v5.300 SEMA6B Arina Puzriakova Tag Q1_23_promote_green was removed from gene: SEMA6B.
Intellectual disability v5.300 SARS Arina Puzriakova Tag Q1_23_promote_green was removed from gene: SARS.
Intellectual disability v5.300 ROR2 Arina Puzriakova Tag Q4_22_demote_red was removed from gene: ROR2.
Tag Q4_22_NHS_review was removed from gene: ROR2.
Rhabdomyolysis and metabolic muscle disorders v3.37 MT-CO2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: MT-CO2.
Tag Q3_23_NHS_review was removed from gene: MT-CO2.
Intellectual disability v5.300 ROBO1 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: ROBO1.
Intellectual disability v5.300 RBSN Arina Puzriakova Tag Q1_23_promote_green was removed from gene: RBSN.
Intellectual disability v5.300 PRKAR1B Arina Puzriakova 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, OMIM:619680
Intellectual disability v5.299 PRKAR1B Arina Puzriakova Tag watchlist was removed from gene: PRKAR1B.
Tag Q2_23_promote_green was removed from gene: PRKAR1B.
Rhabdomyolysis and metabolic muscle disorders v3.37 MT-CO1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: MT-CO1.
Tag Q3_23_NHS_review was removed from gene: MT-CO1.
Childhood onset hereditary spastic paraplegia v4.23 PPFIBP1 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: PPFIBP1.
Tag Q4_23_promote_green tag was added to gene: PPFIBP1.
Severe microcephaly v4.37 PPFIBP1 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: PPFIBP1.
Tag Q4_23_promote_green tag was added to gene: PPFIBP1.
Rhabdomyolysis and metabolic muscle disorders v3.37 FLAD1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: FLAD1.
Tag Q3_23_NHS_review was removed from gene: FLAD1.
White matter disorders and cerebral calcification - narrow panel v3.20 PPFIBP1 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: PPFIBP1.
Tag Q4_23_promote_green tag was added to gene: PPFIBP1.
White matter disorders and cerebral calcification - narrow panel v3.20 PPFIBP1 Arina Puzriakova Entity copied from Early onset or syndromic epilepsy v4.107
White matter disorders and cerebral calcification - narrow panel v3.20 PPFIBP1 Arina Puzriakova gene: PPFIBP1 was added
gene: PPFIBP1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature,Expert Review Amber
Q2_23_promote_green tags were added to gene: PPFIBP1.
Mode of inheritance for gene: PPFIBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPFIBP1 were set to 35830857; 30214071
Phenotypes for gene: PPFIBP1 were set to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Penetrance for gene: PPFIBP1 were set to Complete
Childhood onset hereditary spastic paraplegia v4.23 PPFIBP1 Arina Puzriakova Entity copied from Early onset or syndromic epilepsy v4.107
Childhood onset hereditary spastic paraplegia v4.23 PPFIBP1 Arina Puzriakova gene: PPFIBP1 was added
gene: PPFIBP1 was added to Childhood onset hereditary spastic paraplegia. Sources: Literature,Expert Review Amber
Q2_23_promote_green tags were added to gene: PPFIBP1.
Mode of inheritance for gene: PPFIBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPFIBP1 were set to 35830857; 30214071
Phenotypes for gene: PPFIBP1 were set to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Penetrance for gene: PPFIBP1 were set to Complete
Severe microcephaly v4.37 PPFIBP1 Arina Puzriakova Entity copied from Early onset or syndromic epilepsy v4.107
Severe microcephaly v4.37 PPFIBP1 Arina Puzriakova gene: PPFIBP1 was added
gene: PPFIBP1 was added to Severe microcephaly. Sources: Literature,Expert Review Amber
Q2_23_promote_green tags were added to gene: PPFIBP1.
Mode of inheritance for gene: PPFIBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPFIBP1 were set to 35830857; 30214071
Phenotypes for gene: PPFIBP1 were set to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Penetrance for gene: PPFIBP1 were set to Complete
Rhabdomyolysis and metabolic muscle disorders v3.37 COQ8A Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: COQ8A.
Tag Q3_23_NHS_review was removed from gene: COQ8A.
Rhabdomyolysis and metabolic muscle disorders v3.37 COQ4 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: COQ4.
Tag Q3_23_NHS_review was removed from gene: COQ4.
Rhabdomyolysis and metabolic muscle disorders v3.37 CHKB Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: CHKB.
Tag Q3_23_NHS_review was removed from gene: CHKB.
Rhabdomyolysis and metabolic muscle disorders v3.37 AMPD1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: AMPD1.
Tag Q3_23_NHS_review was removed from gene: AMPD1.
Rhabdomyolysis and metabolic muscle disorders v3.37 MLIP Achchuthan Shanmugasundram Tag Q4_22_promote_green was removed from gene: MLIP.
Rhabdomyolysis and metabolic muscle disorders v3.37 OBSCN Eleanor Williams edited their review of gene: OBSCN: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to "BIALLELIC, autosomal or pseudoautosomal" following NHS Genomic Medicine Service approval.NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and metabolic muscle disorders v3.37 MT-CO2 Eleanor Williams reviewed gene: MT-CO2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MITOCHONDRIAL
Rhabdomyolysis and metabolic muscle disorders v3.37 MT-CO1 Eleanor Williams reviewed gene: MT-CO1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MITOCHONDRIAL
Rhabdomyolysis and metabolic muscle disorders v3.37 MLIP Eleanor Williams reviewed gene: MLIP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and metabolic muscle disorders v3.37 FLAD1 Eleanor Williams reviewed gene: FLAD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and metabolic muscle disorders v3.37 DGUOK Eleanor Williams reviewed gene: DGUOK: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and metabolic muscle disorders v3.37 COQ8A Eleanor Williams reviewed gene: COQ8A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and metabolic muscle disorders v3.37 COQ4 Eleanor Williams reviewed gene: COQ4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and metabolic muscle disorders v3.37 CHKB Eleanor Williams reviewed gene: CHKB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and metabolic muscle disorders v3.37 AMPD1 Eleanor Williams reviewed gene: AMPD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and metabolic muscle disorders v3.36 OBSCN Achchuthan Shanmugasundram Source Expert Review Green was added to OBSCN.
Source NHS GMS was added to OBSCN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rhabdomyolysis and metabolic muscle disorders v3.36 MT-CO2 Achchuthan Shanmugasundram Source Expert Review Green was added to MT-CO2.
Source NHS GMS was added to MT-CO2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rhabdomyolysis and metabolic muscle disorders v3.36 MT-CO1 Achchuthan Shanmugasundram Source Expert Review Green was added to MT-CO1.
Source NHS GMS was added to MT-CO1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rhabdomyolysis and metabolic muscle disorders v3.36 MLIP Achchuthan Shanmugasundram Source Expert Review Green was added to MLIP.
Source NHS GMS was added to MLIP.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rhabdomyolysis and metabolic muscle disorders v3.36 FLAD1 Achchuthan Shanmugasundram Source Expert Review Green was added to FLAD1.
Source NHS GMS was added to FLAD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rhabdomyolysis and metabolic muscle disorders v3.36 DGUOK Achchuthan Shanmugasundram Source Expert Review Green was added to DGUOK.
Source NHS GMS was added to DGUOK.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rhabdomyolysis and metabolic muscle disorders v3.36 COQ8A Achchuthan Shanmugasundram Source Expert Review Green was added to COQ8A.
Source NHS GMS was added to COQ8A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rhabdomyolysis and metabolic muscle disorders v3.36 COQ4 Achchuthan Shanmugasundram Source Expert Review Green was added to COQ4.
Source NHS GMS was added to COQ4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rhabdomyolysis and metabolic muscle disorders v3.36 CHKB Achchuthan Shanmugasundram Source Expert Review Green was added to CHKB.
Source NHS GMS was added to CHKB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rhabdomyolysis and metabolic muscle disorders v3.36 AMPD1 Achchuthan Shanmugasundram Source Expert Review Green was added to AMPD1.
Source NHS GMS was added to AMPD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v4.8 RAC3 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' following NHS Genomic Medicine Service approval.
Malformations of cortical development v4.8 RAC3 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated togreenand the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' following NHS Genomic Medicine Service approval.
Malformations of cortical development v4.8 SLC35A2 Achchuthan Shanmugasundram Tag Q4_22_promote_green was removed from gene: SLC35A2.
Skeletal dysplasia v4.20 KIF24 Eleanor Williams Tag Q4_22_promote_green was removed from gene: KIF24.
Skeletal dysplasia v4.20 GPX4 Eleanor Williams Tag Q2_23_promote_green was removed from gene: GPX4.
Skeletal dysplasia v4.20 GNAS Eleanor Williams Tag Q4_22_MOI was removed from gene: GNAS.
Skeletal dysplasia v4.20 FGF9 Eleanor Williams Tag Q2_23_promote_green was removed from gene: FGF9.
Skeletal dysplasia v4.20 DDRGK1 Eleanor Williams Tag Q1_23_promote_green was removed from gene: DDRGK1.
Skeletal dysplasia v4.20 KIF24 Eleanor Williams reviewed gene: KIF24: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v4.20 GPX4 Eleanor Williams edited their review of gene: GPX4: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v4.20 GNAS Eleanor Williams edited their review of gene: GNAS: Added comment: The mode of inheritance of this gene has been updated to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v4.20 FGF9 Eleanor Williams edited their review of gene: FGF9: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v4.20 DDRGK1 Eleanor Williams reviewed gene: DDRGK1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Malformations of cortical development v4.8 RAC3 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: RAC3.
Skeletal dysplasia v4.19 KIF24 Eleanor Williams Source NHS GMS was added to KIF24.
Source Expert Review Green was added to KIF24.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v4.19 GPX4 Eleanor Williams Source Expert Review Green was added to GPX4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v4.19 GNAS Eleanor Williams Mode of inheritance for gene GNAS was changed from MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v4.19 FGF9 Eleanor Williams Source Expert Review Green was added to FGF9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v4.19 DDRGK1 Eleanor Williams Source NHS GMS was added to DDRGK1.
Source Expert Review Green was added to DDRGK1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v4.8 DEPDC5 Achchuthan Shanmugasundram Tag Q1_23_MOI was removed from gene: DEPDC5.
Malformations of cortical development v4.8 SLC35A2 Eleanor Williams reviewed gene: SLC35A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Malformations of cortical development v4.8 RAC3 Eleanor Williams reviewed gene: RAC3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Malformations of cortical development v4.8 DEPDC5 Eleanor Williams reviewed gene: DEPDC5: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Malformations of cortical development v4.7 SLC35A2 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC35A2.
Source NHS GMS was added to SLC35A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v4.7 RAC3 Achchuthan Shanmugasundram Source Expert Review Green was added to RAC3.
Source NHS GMS was added to RAC3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v4.7 DEPDC5 Achchuthan Shanmugasundram Mode of inheritance for gene DEPDC5 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Distal myopathies v3.14 ADSSL1 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: ADSSL1.
Distal myopathies v3.14 ADSSL1 Eleanor Williams reviewed gene: ADSSL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Distal myopathies v3.13 ADSSL1 Achchuthan Shanmugasundram Source Expert Review Green was added to ADSSL1.
Source NHS GMS was added to ADSSL1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v3.19 ENTPD1 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: ENTPD1.
White matter disorders and cerebral calcification - narrow panel v3.19 CLDN5 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: CLDN5.
Intellectual disability v5.299 PPFIBP1 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: PPFIBP1.
Intellectual disability v5.299 POU3F2 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: POU3F2.
Intellectual disability v5.299 PLXNA1 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: PLXNA1.
Intellectual disability v5.299 PLK1 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: PLK1.
White matter disorders and cerebral calcification - narrow panel v3.19 C2orf69 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: C2orf69.
Intellectual disability v5.299 PAX6 Arina Puzriakova Tag Q1_23_demote_red was removed from gene: PAX6.
Tag Q1_23_NHS_review was removed from gene: PAX6.
Intellectual disability v5.299 PAN2 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: PAN2.
White matter disorders and cerebral calcification - narrow panel v3.19 ENTPD1 Eleanor Williams reviewed gene: ENTPD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v3.19 CLDN5 Eleanor Williams reviewed gene: CLDN5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
White matter disorders and cerebral calcification - narrow panel v3.19 C2orf69 Eleanor Williams reviewed gene: C2orf69: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.299 OTUD7A Arina Puzriakova Phenotypes for gene: OTUD7A were changed from Epileptic encephalopathy, intellectual disability, no OMIM# yet to developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071
Intellectual disability v5.298 OTUD7A Arina Puzriakova Tag Q2_23_promote_green was removed from gene: OTUD7A.
Intellectual disability v5.298 NUP214 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: NUP214.
Intellectual disability v5.298 MTSS1L Arina Puzriakova Phenotypes for gene: MTSS1L were changed from Global developmental delay; Intellectual disability; Ophthalmological anomalies; Microcephaly; Mild facial dysmorphisms to Intellectual developmental disorder with ocular anomalies and distinctive facial features, OMIM:620086
White matter disorders and cerebral calcification - narrow panel v3.18 ENTPD1 Achchuthan Shanmugasundram Source NHS GMS was added to ENTPD1.
Source Expert Review Green was added to ENTPD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v3.18 CLDN5 Achchuthan Shanmugasundram Source NHS GMS was added to CLDN5.
Source Expert Review Green was added to CLDN5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v3.18 C2orf69 Achchuthan Shanmugasundram Source NHS GMS was added to C2orf69.
Source Expert Review Green was added to C2orf69.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.297 MTSS1L Arina Puzriakova Tag Q4_22_promote_green was removed from gene: MTSS1L.
Early onset or syndromic epilepsy v4.107 MED11 Arina Puzriakova Phenotypes for gene: MED11 were changed from MED11-associated neurodevelopmental disorder to Neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalities, OMIM:620327
Severe microcephaly v4.36 MED11 Arina Puzriakova Phenotypes for gene: MED11 were changed from MED11-associated neurodevelopmental disorder to Neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalities, OMIM:620327
Intellectual disability v5.297 MED11 Arina Puzriakova Phenotypes for gene: MED11 were changed from MED11-associated neurodevelopmental disorder to Neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalities, OMIM:620327
Intellectual disability v5.296 MED11 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: MED11.
Intellectual disability v5.296 MAN2C1 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: MAN2C1.
Intellectual disability v5.296 LHX2 Arina Puzriakova Phenotypes for gene: LHX2 were changed from neurodevelopmental disorder to neurodevelopmental disorder, MONDO:0700092
Ataxia and cerebellar anomalies - narrow panel v4.38 TECPR2 Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: TECPR2.
Ataxia and cerebellar anomalies - narrow panel v4.38 SPTAN1 Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: SPTAN1.
Intellectual disability v5.295 LHX2 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: LHX2.
Intellectual disability v5.295 KLHL20 Arina Puzriakova Tag Q4_22_promote_green was removed from gene: KLHL20.
Intellectual disability v5.295 KIF4A Arina Puzriakova Tag Q2_23_promote_green was removed from gene: KIF4A.
Intellectual disability v5.295 KDM5A Arina Puzriakova Phenotypes for gene: KDM5A were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION; autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071 to autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071
Ataxia and cerebellar anomalies - narrow panel v4.38 SPG7 Achchuthan Shanmugasundram Tag Q2_23_MOI was removed from gene: SPG7.
Intellectual disability v5.294 KDM5A Arina Puzriakova Tag Q2_23_promote_green was removed from gene: KDM5A.
Tag Q2_23_NHS_review was removed from gene: KDM5A.
Intellectual disability v5.294 KDM2B Arina Puzriakova Tag Q2_23_promote_green was removed from gene: KDM2B.
Ataxia and cerebellar anomalies - narrow panel v4.38 SLC52A2 Achchuthan Shanmugasundram Tag Q4_22_promote_green was removed from gene: SLC52A2.
Ataxia and cerebellar anomalies - narrow panel v4.38 SLC25A46 Achchuthan Shanmugasundram Tag Q4_22_promote_green was removed from gene: SLC25A46.
Intellectual disability v5.294 KCNK3 Arina Puzriakova Tag Q4_22_promote_green was removed from gene: KCNK3.
Intellectual disability v5.294 ITPR1 Arina Puzriakova Tag Q2_23_MOI was removed from gene: ITPR1.
Tag Q2_23_NHS_review was removed from gene: ITPR1.
Ataxia and cerebellar anomalies - narrow panel v4.38 SCN2A Achchuthan Shanmugasundram Tag Q4_22_promote_green was removed from gene: SCN2A.
Early onset or syndromic epilepsy v4.106 IQSEC2 Arina Puzriakova Publications for gene: IQSEC2 were set to Shoubridge et al (2010) Nat Genet 42(6): 486-8
Early onset or syndromic epilepsy v4.105 IQSEC2 Arina Puzriakova Phenotypes for gene: IQSEC2 were changed from Mental retardation, X-linked 1 to Intellectual developmental disorder, X-linked 1, OMIM:309530
Intellectual disability v5.294 IQSEC2 Arina Puzriakova Phenotypes for gene: IQSEC2 were changed from Mental retardation, X-linked 1, 309530; non-syndromic X-linked intellectual disability; Rett like phenotype in males; MENTAL RETARDATION X-LINKED TYPE 1 (MRX1) to Intellectual developmental disorder, X-linked 1, OMIM:309530
Ataxia and cerebellar anomalies - narrow panel v4.38 NPTX1 Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: NPTX1.
Intellectual disability v5.293 IQSEC2 Arina Puzriakova Tag Q2_23_MOI was removed from gene: IQSEC2.
Ataxia and cerebellar anomalies - narrow panel v4.38 NFASC Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: NFASC.
Intellectual disability v5.293 INTS11 Arina Puzriakova Phenotypes for gene: INTS11 were changed from Complex neurodevelopmental disorder, MONDO:0100038 to Neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities, OMIM:620428
Ataxia and cerebellar anomalies - narrow panel v4.38 INTS11 Arina Puzriakova Phenotypes for gene: INTS11 were changed from Complex neurodevelopmental disorder, MONDO:0100038 to Neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities, OMIM:620428
Severe microcephaly v4.35 INTS11 Arina Puzriakova Phenotypes for gene: INTS11 were changed from Complex neurodevelopmental disorder, MONDO:0100038 to Neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities, OMIM:620428
Ataxia and cerebellar anomalies - narrow panel v4.37 MAG Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: MAG.
Intellectual disability v5.292 INTS11 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: INTS11.
Intellectual disability v5.292 HUWE1 Arina Puzriakova Tag Q2_23_MOI was removed from gene: HUWE1.
Ataxia and cerebellar anomalies - narrow panel v4.37 INTS11 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: INTS11.
Intellectual disability v5.292 HIST1H4E Arina Puzriakova Tag Q1_23_promote_green was removed from gene: HIST1H4E.
Early onset or syndromic epilepsy v4.104 HECTD4 Arina Puzriakova Classified gene: HECTD4 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v4.104 HECTD4 Arina Puzriakova Gene: hectd4 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v4.103 HECTD4 Arina Puzriakova Deleted their comment
Early onset or syndromic epilepsy v4.103 HECTD4 Arina Puzriakova Tag Q4_23_promote_green tag was added to gene: HECTD4.
Ataxia and cerebellar anomalies - narrow panel v4.37 GRN Achchuthan Shanmugasundram Tag Q4_22_promote_green was removed from gene: GRN.
Childhood onset hereditary spastic paraplegia v4.22 HECTD4 Arina Puzriakova Deleted their comment
Malformations of cortical development v4.6 HECTD4 Arina Puzriakova Tag Q4_23_promote_green tag was added to gene: HECTD4.
Malformations of cortical development v4.6 HECTD4 Arina Puzriakova Deleted their comment
Childhood onset hereditary spastic paraplegia v4.22 HECTD4 Arina Puzriakova Classified gene: HECTD4 as Amber List (moderate evidence)
Childhood onset hereditary spastic paraplegia v4.22 HECTD4 Arina Puzriakova Gene: hectd4 has been classified as Amber List (Moderate Evidence).
Childhood onset hereditary spastic paraplegia v4.21 HECTD4 Arina Puzriakova Tag Q4_23_promote_green tag was added to gene: HECTD4.
Malformations of cortical development v4.6 HECTD4 Arina Puzriakova Classified gene: HECTD4 as Amber List (moderate evidence)
Malformations of cortical development v4.6 HECTD4 Arina Puzriakova Gene: hectd4 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v4.5 HECTD4 Arina Puzriakova Entity copied from Intellectual disability - microarray and sequencing v5.292
Malformations of cortical development v4.5 HECTD4 Arina Puzriakova gene: HECTD4 was added
gene: HECTD4 was added to Malformations of cortical development. Sources: Literature,NHS GMS,Expert Review Green
Mode of inheritance for gene: HECTD4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HECTD4 were set to 36401616
Phenotypes for gene: HECTD4 were set to Neurodevelopmental disorder with seizures, spasticity, and complete or partial agenesis of the corpus callosum, OMIM:620250
Childhood onset hereditary spastic paraplegia v4.21 HECTD4 Arina Puzriakova Entity copied from Intellectual disability - microarray and sequencing v5.292
Childhood onset hereditary spastic paraplegia v4.21 HECTD4 Arina Puzriakova gene: HECTD4 was added
gene: HECTD4 was added to Childhood onset hereditary spastic paraplegia. Sources: Literature,NHS GMS,Expert Review Green
Mode of inheritance for gene: HECTD4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HECTD4 were set to 36401616
Phenotypes for gene: HECTD4 were set to Neurodevelopmental disorder with seizures, spasticity, and complete or partial agenesis of the corpus callosum, OMIM:620250
Early onset or syndromic epilepsy v4.103 HECTD4 Arina Puzriakova Entity copied from Intellectual disability - microarray and sequencing v5.292
Early onset or syndromic epilepsy v4.103 HECTD4 Arina Puzriakova gene: HECTD4 was added
gene: HECTD4 was added to Early onset or syndromic epilepsy. Sources: Literature,NHS GMS,Expert Review Green
Mode of inheritance for gene: HECTD4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HECTD4 were set to 36401616
Phenotypes for gene: HECTD4 were set to Neurodevelopmental disorder with seizures, spasticity, and complete or partial agenesis of the corpus callosum, OMIM:620250
Ataxia and cerebellar anomalies - narrow panel v4.37 FRMD5 Achchuthan Shanmugasundram Tag Q4_22_promote_green was removed from gene: FRMD5.
Ataxia and cerebellar anomalies - narrow panel v4.37 FMR1 Achchuthan Shanmugasundram Tag Q4_22_demote_red was removed from gene: FMR1.
Ataxia and cerebellar anomalies - narrow panel v4.37 FEM1C Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: FEM1C.
Ataxia and cerebellar anomalies - narrow panel v4.37 COQ4 Achchuthan Shanmugasundram Tag Q4_22_promote_green was removed from gene: COQ4.
Ataxia and cerebellar anomalies - narrow panel v4.37 SUFU Achchuthan Shanmugasundram Tag watchlist_moi was removed from gene: SUFU.
Tag Q4_22_MOI was removed from gene: SUFU.
Tag Q4_22_promote_green was removed from gene: SUFU.
Tag Q4_22_expert_review was removed from gene: SUFU.
Ataxia and cerebellar anomalies - narrow panel v4.37 TECPR2 Eleanor Williams reviewed gene: TECPR2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.37 SUFU Eleanor Williams reviewed gene: SUFU: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.37 SPTAN1 Eleanor Williams reviewed gene: SPTAN1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - narrow panel v4.37 SPG7 Eleanor Williams edited their review of gene: SPG7: Added comment: The mode of inheritance of this gene has been updated to"BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal"following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.37 SLC52A2 Eleanor Williams reviewed gene: SLC52A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.37 SLC25A46 Eleanor Williams reviewed gene: SLC25A46: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.37 SCN2A Eleanor Williams reviewed gene: SCN2A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - narrow panel v4.37 NPTX1 Eleanor Williams reviewed gene: NPTX1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - narrow panel v4.37 NFASC Eleanor Williams reviewed gene: NFASC: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.37 MAG Eleanor Williams reviewed gene: MAG: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.37 INTS11 Eleanor Williams reviewed gene: INTS11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.37 GRN Eleanor Williams reviewed gene: GRN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.37 FRMD5 Eleanor Williams reviewed gene: FRMD5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Ataxia and cerebellar anomalies - narrow panel v4.37 FMR1 Eleanor Williams reviewed gene: FMR1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v4.37 FEM1C Eleanor Williams reviewed gene: FEM1C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - narrow panel v4.37 COQ4 Eleanor Williams reviewed gene: COQ4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.36 SUFU Achchuthan Shanmugasundram Mode of inheritance for gene SUFU was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.292 HECTD4 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: HECTD4.
Intellectual disability v5.292 GRM7 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: GRM7.
Intellectual disability v5.292 GRIA1 Arina Puzriakova Tag watchlist_moi tag was added to gene: GRIA1.
Mitochondrial disorders v4.95 LETM1 Sarah Leigh Tag Q2_23_promote_green was removed from gene: LETM1.
Mitochondrial disorders v4.95 IDH3A Sarah Leigh Tag Q2_23_promote_green was removed from gene: IDH3A.
Mitochondrial disorders v4.95 IDH3A Sarah Leigh Deleted their comment
Mitochondrial disorders v4.95 CRLS1 Sarah Leigh Tag Q1_23_promote_green was removed from gene: CRLS1.
Intellectual disability v5.292 GRIA1 Arina Puzriakova Tag Autism Spectrum Disorder was removed from gene: GRIA1.
Tag Q2_23_promote_green was removed from gene: GRIA1.
Mitochondrial disorders v4.95 C2orf69 Sarah Leigh Tag Q2_23_promote_green was removed from gene: C2orf69.
Intellectual disability v5.292 GCSH Arina Puzriakova Tag Q1_23_promote_green was removed from gene: GCSH.
Mitochondrial disorders v4.95 ATP5O Sarah Leigh Tag Q2_23_promote_green was removed from gene: ATP5O.
Intellectual disability v5.292 FRMD5 Arina Puzriakova Tag Q4_22_promote_green was removed from gene: FRMD5.
Ataxia and cerebellar anomalies - narrow panel v4.35 TECPR2 Achchuthan Shanmugasundram Source Expert Review Green was added to TECPR2.
Source NHS GMS was added to TECPR2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v4.35 SUFU Achchuthan Shanmugasundram Source Expert Review Green was added to SUFU.
Source NHS GMS was added to SUFU.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v4.35 SPTAN1 Achchuthan Shanmugasundram Source Expert Review Green was added to SPTAN1.
Source NHS GMS was added to SPTAN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v4.35 SPG7 Achchuthan Shanmugasundram Source NHS GMS was added to SPG7.
Mode of inheritance for gene SPG7 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v4.35 SLC52A2 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC52A2.
Source NHS GMS was added to SLC52A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v4.35 SLC25A46 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC25A46.
Source NHS GMS was added to SLC25A46.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v4.35 SCN2A Achchuthan Shanmugasundram Source Expert Review Green was added to SCN2A.
Source NHS GMS was added to SCN2A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v4.35 NPTX1 Achchuthan Shanmugasundram Source Expert Review Green was added to NPTX1.
Source NHS GMS was added to NPTX1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v4.35 NFASC Achchuthan Shanmugasundram Source Expert Review Green was added to NFASC.
Source NHS GMS was added to NFASC.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v4.35 MAG Achchuthan Shanmugasundram Source Expert Review Green was added to MAG.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.292 FLNA Arina Puzriakova Tag Q2_23_demote_red was removed from gene: FLNA.
Ataxia and cerebellar anomalies - narrow panel v4.35 INTS11 Achchuthan Shanmugasundram Source Expert Review Green was added to INTS11.
Source NHS GMS was added to INTS11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v4.35 GRN Achchuthan Shanmugasundram Source Expert Review Green was added to GRN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v4.35 FRMD5 Achchuthan Shanmugasundram Source Expert Review Green was added to FRMD5.
Source NHS GMS was added to FRMD5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v4.35 FMR1 Achchuthan Shanmugasundram Source Expert Review Red was added to FMR1.
Source NHS GMS was added to FMR1.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Ataxia and cerebellar anomalies - narrow panel v4.35 FEM1C Achchuthan Shanmugasundram Source Expert Review Green was added to FEM1C.
Source NHS GMS was added to FEM1C.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v4.35 COQ4 Achchuthan Shanmugasundram Source Expert Review Green was added to COQ4.
Source NHS GMS was added to COQ4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.292 FILIP1 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: FILIP1.
Intellectual disability v5.292 ENTPD1 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: ENTPD1.
Mitochondrial disorders v4.95 OGDH Sarah Leigh Tag Q2_23_promote_green was removed from gene: OGDH.
Intellectual disability v5.292 DPH5 Arina Puzriakova Phenotypes for gene: DPH5 were changed from DPH5-related neurodevelopmental disorder to Neurodevelopmental disorder with short stature, prominent forehead, and feeding difficulties, OMIM:620070
Mitochondrial disorders v4.95 ETFB Sarah Leigh Tag Q2_23_promote_green was removed from gene: ETFB.
Intellectual disability v5.291 DPH5 Arina Puzriakova Tag Q4_22_promote_green was removed from gene: DPH5.
Mitochondrial disorders v4.95 ETFA Sarah Leigh Tag Q2_23_promote_green was removed from gene: ETFA.
Intellectual disability v5.291 DDX23 Arina Puzriakova Phenotypes for gene: DDX23 were changed from Neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment, OMIM:620066 to Global developmental delay with speech and behavioral abnormalities, MONDO:0030995
Mitochondrial disorders v4.95 COASY Sarah Leigh Tag Q2_23_promote_green was removed from gene: COASY.
Mitochondrial disorders v4.95 SPG7 Sarah Leigh commented on gene: SPG7: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Mitochondrial disorders v4.95 OGDH Sarah Leigh edited their review of gene: OGDH: Added comment: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber. This gene is not associated with primary mitochondrial disease. Consensus opinion from the 3 specialist mitochondrial providers.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v4.95 LETM1 Sarah Leigh edited their review of gene: LETM1: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v4.95 IDH3A Sarah Leigh edited their review of gene: IDH3A: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v4.95 ETFB Sarah Leigh edited their review of gene: ETFB: Added comment: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber. This gene is not associated with primary mitochondrial disease. Consensus opinion from the 3 specialist mitochondrial providers.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v4.95 ETFA Sarah Leigh edited their review of gene: ETFA: Added comment: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber. This gene is not associated with primary mitochondrial disease. Consensus opinion from the 3 specialist mitochondrial providers.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v4.95 CRLS1 Sarah Leigh reviewed gene: CRLS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v4.95 COASY Sarah Leigh edited their review of gene: COASY: Added comment: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber. This gene is not associated with primary mitochondrial disease. Consensus opinion from the 3 specialist mitochondrial providers.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v4.95 C2orf69 Sarah Leigh reviewed gene: C2orf69: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v4.95 ATP5O Sarah Leigh reviewed gene: ATP5O: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders v4.94 SPG7 Sarah Leigh Source NHS GMS was added to SPG7.
Mode of inheritance for gene SPG7 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mitochondrial disorders v4.94 OGDH Sarah Leigh Source NHS GMS was added to OGDH.
Mitochondrial disorders v4.94 LETM1 Sarah Leigh Source Expert Review Green was added to LETM1.
Source NHS GMS was added to LETM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v4.94 IDH3A Sarah Leigh Source Expert Review Green was added to IDH3A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v4.94 CRLS1 Sarah Leigh Source Expert Review Green was added to CRLS1.
Source NHS GMS was added to CRLS1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v4.94 C2orf69 Sarah Leigh Source Expert Review Green was added to C2orf69.
Source NHS GMS was added to C2orf69.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v4.94 ATP5O Sarah Leigh Source Expert Review Green was added to ATP5O.
Source NHS GMS was added to ATP5O.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v4.34 DOHH Arina Puzriakova Phenotypes for gene: DOHH were changed from DOHH associated neurodevelopmental disorder to Neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment, OMIM:620066
Intellectual disability v5.290 DOHH Arina Puzriakova Phenotypes for gene: DOHH were changed from DOHH associated neurodevelopmental disorder to Neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment, OMIM:620066
Intellectual disability v5.289 DDX23 Arina Puzriakova Phenotypes for gene: DDX23 were changed from Global developmental delay with speech and behavioral abnormalities, MONDO:0030995 to Neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment, OMIM:620066
Intellectual disability v5.288 DOHH Arina Puzriakova Tag Q4_22_MOI was removed from gene: DOHH.
Tag Q4_22_promote_green was removed from gene: DOHH.
Intellectual disability v5.288 DDX23 Arina Puzriakova Phenotypes for gene: DDX23 were changed from Developmental disorder to Global developmental delay with speech and behavioral abnormalities, MONDO:0030995
Intellectual disability v5.287 DDX23 Arina Puzriakova Tag watchlist was removed from gene: DDX23.
Tag Q2_23_promote_green was removed from gene: DDX23.
Intellectual disability v5.287 CTR9 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: CTR9.
Intellectual disability v5.287 CPLX1 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: CPLX1.
Intellectual disability v5.287 CLDN5 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: CLDN5.
Intellectual disability v5.287 CCDC82 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: CCDC82.
Intellectual disability v5.287 CAPRIN1 Arina Puzriakova Phenotypes for gene: CAPRIN1 were changed from Global developmental delay; Delayed speech and language development; Intellectual disability; Autistic behaviour; Seizures to Global developmental delay; Delayed speech and language development; Intellectual disability; Autistic behaviour; Seizures
Intellectual disability v5.287 CAPRIN1 Arina Puzriakova Phenotypes for gene: CAPRIN1 were changed from AUTISM OR INTELLECTUAL DISABILITY to Global developmental delay; Delayed speech and language development; Intellectual disability; Autistic behaviour; Seizures
Intellectual disability v5.286 CAPRIN1 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: CAPRIN1.
Intellectual disability v5.286 C2orf69 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: C2orf69.
Intellectual disability v5.286 BUB1 Arina Puzriakova Tag Q4_22_promote_green was removed from gene: BUB1.
Intellectual disability v5.286 BAP1 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: BAP1.
Intellectual disability v5.286 ZNF292 Arina Puzriakova reviewed gene: ZNF292: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v5.286 ZMYND8 Arina Puzriakova reviewed gene: ZMYND8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.286 ZMYM3 Arina Puzriakova reviewed gene: ZMYM3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v5.286 WIPI2 Arina Puzriakova reviewed gene: WIPI2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 UBAP2L Arina Puzriakova reviewed gene: UBAP2L: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v5.286 TRA2B Arina Puzriakova reviewed gene: TRA2B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.286 TMEM147 Arina Puzriakova reviewed gene: TMEM147: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 TCEAL1 Arina Puzriakova reviewed gene: TCEAL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v5.286 TAF4 Arina Puzriakova reviewed gene: TAF4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.286 TAF2 Arina Puzriakova reviewed gene: TAF2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 SUFU Arina Puzriakova commented on gene: SUFU: After NHS Genomic Medicine Service consideration, the rating of this gene has been updated to Green but the mode of inheritance has been set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal. Additional comments from reviewing GLHs: 'Consensus view: Monoallelic and biallelic'.
Intellectual disability v5.286 STXBP1 Arina Puzriakova reviewed gene: STXBP1: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.286 SLC32A1 Arina Puzriakova reviewed gene: SLC32A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.286 SHANK1 Arina Puzriakova reviewed gene: SHANK1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.286 SEMA6B Arina Puzriakova reviewed gene: SEMA6B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.286 SARS Arina Puzriakova commented on gene: SARS: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Intellectual disability v5.286 ROR2 Arina Puzriakova edited their review of gene: ROR2: Added comment: The rating of this gene has been updated to Red following NHS Genomic Medicine Service approval.; Changed rating: RED
Intellectual disability v5.286 ROBO1 Arina Puzriakova reviewed gene: ROBO1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 RBSN Arina Puzriakova reviewed gene: RBSN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 PRKAR1B Arina Puzriakova reviewed gene: PRKAR1B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.286 PPFIBP1 Arina Puzriakova reviewed gene: PPFIBP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 POU3F2 Arina Puzriakova reviewed gene: POU3F2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v5.286 PLXNA1 Arina Puzriakova reviewed gene: PLXNA1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.286 PLK1 Arina Puzriakova reviewed gene: PLK1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 PAX6 Arina Puzriakova reviewed gene: PAX6: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v5.286 PAN2 Arina Puzriakova reviewed gene: PAN2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 OTUD7A Arina Puzriakova reviewed gene: OTUD7A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 NUP214 Arina Puzriakova reviewed gene: NUP214: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 MTSS1L Arina Puzriakova commented on gene: MTSS1L: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Intellectual disability v5.286 MED11 Arina Puzriakova reviewed gene: MED11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 MAN2C1 Arina Puzriakova reviewed gene: MAN2C1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 LHX2 Arina Puzriakova reviewed gene: LHX2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v5.286 KLHL20 Arina Puzriakova edited their review of gene: KLHL20: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.286 KIF4A Arina Puzriakova reviewed gene: KIF4A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.286 KDM5A Arina Puzriakova reviewed gene: KDM5A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.286 KDM2B Arina Puzriakova reviewed gene: KDM2B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.286 KCNK3 Arina Puzriakova edited their review of gene: KCNK3: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v5.286 ITPR1 Arina Puzriakova edited their review of gene: ITPR1: Added comment: The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.286 IQSEC2 Arina Puzriakova reviewed gene: IQSEC2: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v5.286 INTS11 Arina Puzriakova edited their review of gene: INTS11: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 HUWE1 Arina Puzriakova reviewed gene: HUWE1: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v5.286 HIST1H4E Arina Puzriakova reviewed gene: HIST1H4E: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v5.286 HECTD4 Arina Puzriakova reviewed gene: HECTD4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 GRM7 Arina Puzriakova reviewed gene: GRM7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 GRIA1 Arina Puzriakova edited their review of gene: GRIA1: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.286 GCSH Arina Puzriakova reviewed gene: GCSH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 FRMD5 Arina Puzriakova commented on gene: FRMD5: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Intellectual disability v5.286 FLNA Arina Puzriakova reviewed gene: FLNA: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v5.286 FILIP1 Arina Puzriakova reviewed gene: FILIP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 ENTPD1 Arina Puzriakova edited their review of gene: ENTPD1: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v5.286 DPH5 Arina Puzriakova reviewed gene: DPH5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 DOHH Arina Puzriakova reviewed gene: DOHH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 DDX23 Arina Puzriakova reviewed gene: DDX23: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.286 CTR9 Arina Puzriakova reviewed gene: CTR9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.286 CPLX1 Arina Puzriakova reviewed gene: CPLX1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 CLDN5 Arina Puzriakova reviewed gene: CLDN5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.286 CCDC82 Arina Puzriakova reviewed gene: CCDC82: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 CAPRIN1 Arina Puzriakova reviewed gene: CAPRIN1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.286 C2orf69 Arina Puzriakova edited their review of gene: C2orf69: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 BUB1 Arina Puzriakova edited their review of gene: BUB1: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.286 BAP1 Arina Puzriakova reviewed gene: BAP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v5.286 ZNF292 Arina Puzriakova Source NHS GMS was added to ZNF292.
Source Expert Review Green was added to ZNF292.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 ZMYND8 Arina Puzriakova Source NHS GMS was added to ZMYND8.
Source Expert Review Green was added to ZMYND8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 ZMYM3 Arina Puzriakova Source NHS GMS was added to ZMYM3.
Source Expert Review Green was added to ZMYM3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 WIPI2 Arina Puzriakova Source NHS GMS was added to WIPI2.
Source Expert Review Green was added to WIPI2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 UBAP2L Arina Puzriakova Source NHS GMS was added to UBAP2L.
Source Expert Review Green was added to UBAP2L.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 TRA2B Arina Puzriakova Source NHS GMS was added to TRA2B.
Source Expert Review Green was added to TRA2B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 TMEM147 Arina Puzriakova Source NHS GMS was added to TMEM147.
Source Expert Review Green was added to TMEM147.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 TCEAL1 Arina Puzriakova Source NHS GMS was added to TCEAL1.
Source Expert Review Green was added to TCEAL1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 TAF4 Arina Puzriakova Source NHS GMS was added to TAF4.
Source Expert Review Green was added to TAF4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 TAF2 Arina Puzriakova Source NHS GMS was added to TAF2.
Source Expert Review Green was added to TAF2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 SUFU Arina Puzriakova Source NHS GMS was added to SUFU.
Source Expert Review Green was added to SUFU.
Mode of inheritance for gene SUFU was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 STXBP1 Arina Puzriakova Source NHS GMS was added to STXBP1.
Mode of inheritance for gene STXBP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.286 SLC32A1 Arina Puzriakova Source NHS GMS was added to SLC32A1.
Source Expert Review Green was added to SLC32A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 SHANK1 Arina Puzriakova Source NHS GMS was added to SHANK1.
Source Expert Review Green was added to SHANK1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 SEMA6B Arina Puzriakova Source NHS GMS was added to SEMA6B.
Source Expert Review Green was added to SEMA6B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 SARS Arina Puzriakova Source NHS GMS was added to SARS.
Source Expert Review Green was added to SARS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 ROR2 Arina Puzriakova Source Expert Review Red was added to ROR2.
Source NHS GMS was added to ROR2.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Intellectual disability v5.286 ROBO1 Arina Puzriakova Source NHS GMS was added to ROBO1.
Source Expert Review Green was added to ROBO1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 RBSN Arina Puzriakova Source NHS GMS was added to RBSN.
Source Expert Review Green was added to RBSN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 PRKAR1B Arina Puzriakova Source NHS GMS was added to PRKAR1B.
Source Expert Review Green was added to PRKAR1B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 PPFIBP1 Arina Puzriakova Source NHS GMS was added to PPFIBP1.
Source Expert Review Green was added to PPFIBP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 POU3F2 Arina Puzriakova Source NHS GMS was added to POU3F2.
Source Expert Review Green was added to POU3F2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 PLXNA1 Arina Puzriakova Source NHS GMS was added to PLXNA1.
Source Expert Review Green was added to PLXNA1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 PLK1 Arina Puzriakova Source NHS GMS was added to PLK1.
Source Expert Review Green was added to PLK1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 PAX6 Arina Puzriakova Source Expert Review Red was added to PAX6.
Source NHS GMS was added to PAX6.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Intellectual disability v5.286 PAN2 Arina Puzriakova Source NHS GMS was added to PAN2.
Source Expert Review Green was added to PAN2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 OTUD7A Arina Puzriakova Source NHS GMS was added to OTUD7A.
Source Expert Review Green was added to OTUD7A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 NUP214 Arina Puzriakova Source NHS GMS was added to NUP214.
Source Expert Review Green was added to NUP214.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 MTSS1L Arina Puzriakova Source NHS GMS was added to MTSS1L.
Source Expert Review Green was added to MTSS1L.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 MED11 Arina Puzriakova Source NHS GMS was added to MED11.
Source Expert Review Green was added to MED11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 MAN2C1 Arina Puzriakova Source NHS GMS was added to MAN2C1.
Source Expert Review Green was added to MAN2C1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 LHX2 Arina Puzriakova Source NHS GMS was added to LHX2.
Source Expert Review Green was added to LHX2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 KLHL20 Arina Puzriakova Source NHS GMS was added to KLHL20.
Source Expert Review Green was added to KLHL20.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 KIF4A Arina Puzriakova Source NHS GMS was added to KIF4A.
Source Expert Review Green was added to KIF4A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 KDM5A Arina Puzriakova Source NHS GMS was added to KDM5A.
Source Expert Review Green was added to KDM5A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 KDM2B Arina Puzriakova Source NHS GMS was added to KDM2B.
Source Expert Review Green was added to KDM2B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 KCNK3 Arina Puzriakova Source NHS GMS was added to KCNK3.
Source Expert Review Green was added to KCNK3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 ITPR1 Arina Puzriakova Source NHS GMS was added to ITPR1.
Mode of inheritance for gene ITPR1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.286 IQSEC2 Arina Puzriakova Source NHS GMS was added to IQSEC2.
Mode of inheritance for gene IQSEC2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v5.286 INTS11 Arina Puzriakova Source NHS GMS was added to INTS11.
Source Expert Review Green was added to INTS11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 HUWE1 Arina Puzriakova Source NHS GMS was added to HUWE1.
Mode of inheritance for gene HUWE1 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v5.286 HIST1H4E Arina Puzriakova Source NHS GMS was added to HIST1H4E.
Source Expert Review Green was added to HIST1H4E.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 HECTD4 Arina Puzriakova Source NHS GMS was added to HECTD4.
Source Expert Review Green was added to HECTD4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 GRM7 Arina Puzriakova Source NHS GMS was added to GRM7.
Source Expert Review Green was added to GRM7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 GRIA1 Arina Puzriakova Source NHS GMS was added to GRIA1.
Source Expert Review Green was added to GRIA1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 GCSH Arina Puzriakova Source NHS GMS was added to GCSH.
Source Expert Review Green was added to GCSH.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 FRMD5 Arina Puzriakova Source NHS GMS was added to FRMD5.
Source Expert Review Green was added to FRMD5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 FLNA Arina Puzriakova Source Expert Review Red was added to FLNA.
Source NHS GMS was added to FLNA.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Intellectual disability v5.286 FILIP1 Arina Puzriakova Source NHS GMS was added to FILIP1.
Source Expert Review Green was added to FILIP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 ENTPD1 Arina Puzriakova Source NHS GMS was added to ENTPD1.
Source Expert Review Green was added to ENTPD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 DPH5 Arina Puzriakova Source NHS GMS was added to DPH5.
Source Expert Review Green was added to DPH5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 DOHH Arina Puzriakova Source NHS GMS was added to DOHH.
Source Expert Review Green was added to DOHH.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 DDX23 Arina Puzriakova Source NHS GMS was added to DDX23.
Source Expert Review Green was added to DDX23.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 CTR9 Arina Puzriakova Source NHS GMS was added to CTR9.
Source Expert Review Green was added to CTR9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 CPLX1 Arina Puzriakova Source NHS GMS was added to CPLX1.
Source Expert Review Green was added to CPLX1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 CLDN5 Arina Puzriakova Source NHS GMS was added to CLDN5.
Source Expert Review Green was added to CLDN5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 CCDC82 Arina Puzriakova Source NHS GMS was added to CCDC82.
Source Expert Review Green was added to CCDC82.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 CAPRIN1 Arina Puzriakova Source NHS GMS was added to CAPRIN1.
Source Expert Review Green was added to CAPRIN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 C2orf69 Arina Puzriakova Source NHS GMS was added to C2orf69.
Source Expert Review Green was added to C2orf69.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 BUB1 Arina Puzriakova Source NHS GMS was added to BUB1.
Source Expert Review Green was added to BUB1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v5.286 BAP1 Arina Puzriakova Source NHS GMS was added to BAP1.
Source Expert Review Green was added to BAP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v4.100 TBX1 Sarah Leigh Tag Q1_23_promote_green was removed from gene: TBX1.
Clefting v4.100 RAD21 Sarah Leigh Tag Q4_22_promote_green was removed from gene: RAD21.
Clefting v4.100 TBX1 Sarah Leigh reviewed gene: TBX1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Clefting v4.100 RAD21 Sarah Leigh reviewed gene: RAD21: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Clefting v4.99 TBX1 Sarah Leigh Source Expert Review Green was added to TBX1.
Source NHS GMS was added to TBX1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v4.99 RAD21 Sarah Leigh Source Expert Review Green was added to RAD21.
Source NHS GMS was added to RAD21.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v3.50 NUP54 Sarah Leigh Tag Q2_23_promote_green was removed from gene: NUP54.
Childhood onset dystonia, chorea or related movement disorder v3.50 COX20 Sarah Leigh Tag Q1_23_promote_green was removed from gene: COX20.
Childhood onset dystonia, chorea or related movement disorder v3.50 ARFGEF3 Sarah Leigh Tag Q2_23_promote_green was removed from gene: ARFGEF3.
Childhood onset dystonia, chorea or related movement disorder v3.50 NUP54 Sarah Leigh reviewed gene: NUP54: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v3.50 COX20 Sarah Leigh reviewed gene: COX20: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v3.50 ARFGEF3 Sarah Leigh reviewed gene: ARFGEF3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Childhood onset dystonia, chorea or related movement disorder v3.50 ADAR Sarah Leigh reviewed gene: ADAR: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v3.49 NUP54 Sarah Leigh Source NHS GMS was added to NUP54.
Source Expert Review Green was added to NUP54.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v3.49 COX20 Sarah Leigh Source NHS GMS was added to COX20.
Source Expert Review Green was added to COX20.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v3.49 ARFGEF3 Sarah Leigh Source NHS GMS was added to ARFGEF3.
Source Expert Review Green was added to ARFGEF3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v3.49 ADAR Sarah Leigh Source NHS GMS was added to ADAR.
Mode of inheritance for gene ADAR was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v3.9 RET Sarah Leigh Deleted their comment
Skeletal dysplasia v4.18 ERI1 Tracy Lester edited their review of gene: ERI1: Added comment: >3 cases confirmed; Changed rating: GREEN
Skeletal dysplasia v4.18 ERI1 Tracy Lester gene: ERI1 was added
gene: ERI1 was added to Skeletal dysplasia. Sources: NHS GMS
Mode of inheritance for gene: ERI1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERI1 were set to 37352860
Phenotypes for gene: ERI1 were set to spondyloepimetaphyseal dysplasia; digital anomalies
Penetrance for gene: ERI1 were set to unknown
Mode of pathogenicity for gene: ERI1 was set to Other
Added comment: In this study, the authors uncovered a phenotypic dichotomy in eight individuals from seven unrelated families with different types of ERI1 variants and highlighted the association of missense variants with spondyloepimetaphyseal dysplasia (SEMD), which is a group of skeletal diseases characterized by anomalies in spine and long tubular bones.In contrast, the affected individuals with bi-allelic null variants showed mild intellectual disability and digital anomalies. The detailed evaluation of the skeletal phenotypes of Eri1 knockout (KO) mice and the in vitro chondrogenesis of affected-individual-derived induced pluripotent stem cells (iPSCs) supported the functional involvement of ERI1 in skeletal development. Analyses using ERI1 KO HeLa cells
and affected-individual-derived cells demonstrated functional conservation of ERI1 with its mouse ortholog in 5.8S rRNA maturation and histone mRNAs decay. The 5.8S
rRNA maturation is involved in ribosome biogenesis, defects of which are known to cause ribosomopathies characterized by skeletal dysplasia.12–15 Our study leads to the findings of an SEMD associated with ribosomopathy and established a framework for understanding the molecular mechanisms underlying the ERI1 phenotypic dichotomy.

Missense variants reported to affect residues 134,150, 155, 298 and 299. All cases with biallelic missense variants had short stature, epiphyseal, spinal and digit anomalies, as well as other variable kidney and cardiac anomalies. One case with a LOF and a missense was reported with these features and intellectual disability/developmental delay. The 3 cases with biallelic LOF variants had ID/DD, digital anomalies without the other (height varied from 8th centile to normal).
Sources: NHS GMS
Hereditary neuropathy or pain disorder v3.60 VCP Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: VCP.
Hereditary neuropathy or pain disorder v3.60 VAPB Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: VAPB.
Hereditary neuropathy or pain disorder v3.60 UBA1 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: UBA1.
Hereditary neuropathy or pain disorder v3.60 TECPR2 Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: TECPR2.
Hereditary neuropathy or pain disorder v3.60 SLC25A46 Achchuthan Shanmugasundram Phenotypes for gene: SLC25A46 were changed from Neuropathy, hereditary motor and sensory, type VIB, OMIM:616505; Pontocerebellar hypoplasia, type 1E, OMIM:619303, MONDO:0030260 to Neuropathy, hereditary motor and sensory, type VIB, OMIM:616505; Pontocerebellar hypoplasia, type 1E, OMIM:619303, MONDO:0030260
Hereditary neuropathy or pain disorder v3.59 SLC25A46 Achchuthan Shanmugasundram Phenotypes for gene: SLC25A46 were changed from Neuropathy, hereditary motor and sensory, type VIB, MIM# 616505; Pontocerebellar hypoplasia, type 1E, MIM# 619303, MONDO:0030260 to Neuropathy, hereditary motor and sensory, type VIB, OMIM:616505; Pontocerebellar hypoplasia, type 1E, OMIM:619303, MONDO:0030260
Hereditary neuropathy or pain disorder v3.58 SLC25A46 Achchuthan Shanmugasundram edited their review of gene: SLC25A46: Changed phenotypes to: Neuropathy, hereditary motor and sensory, type VIB, OMIM:616505, Pontocerebellar hypoplasia, type 1E, OMIM:619303, MONDO:0030260
Hereditary neuropathy or pain disorder v3.58 SLC25A46 Achchuthan Shanmugasundram Tag Q4_22_promote_green was removed from gene: SLC25A46.
Hereditary neuropathy or pain disorder v3.58 SCO2 Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: SCO2.
Hereditary neuropathy or pain disorder v3.58 MYH14 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: MYH14.
Hereditary neuropathy or pain disorder v3.58 MAG Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: MAG.
Hereditary neuropathy or pain disorder v3.58 GBF1 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: GBF1.
Hereditary neuropathy or pain disorder v3.58 DRP2 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: DRP2.
Hereditary neuropathy or pain disorder v3.58 COX20 Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: COX20.
Hereditary neuropathy or pain disorder v3.58 ACOX1 Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: ACOX1.
Hereditary neuropathy or pain disorder v3.58 VCP Sarah Leigh reviewed gene: VCP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary neuropathy or pain disorder v3.58 VAPB Sarah Leigh reviewed gene: VAPB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v3.58 UBA1 Sarah Leigh reviewed gene: UBA1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Hereditary neuropathy or pain disorder v3.58 TECPR2 Sarah Leigh reviewed gene: TECPR2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v3.58 SLC25A46 Sarah Leigh reviewed gene: SLC25A46: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v3.58 SCO2 Sarah Leigh reviewed gene: SCO2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v3.58 MYH14 Sarah Leigh reviewed gene: MYH14: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v3.58 MAG Sarah Leigh reviewed gene: MAG: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v3.58 GBF1 Sarah Leigh reviewed gene: GBF1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v3.58 DRP2 Sarah Leigh reviewed gene: DRP2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Hereditary neuropathy or pain disorder v3.58 COX20 Sarah Leigh reviewed gene: COX20: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v3.58 ACOX1 Sarah Leigh reviewed gene: ACOX1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary neuropathy or pain disorder v3.57 VCP Achchuthan Shanmugasundram Source Expert Review Green was added to VCP.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v3.57 VAPB Achchuthan Shanmugasundram Source Expert Review Green was added to VAPB.
Source NHS GMS was added to VAPB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v3.57 UBA1 Achchuthan Shanmugasundram Source Expert Review Green was added to UBA1.
Source NHS GMS was added to UBA1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v3.57 TECPR2 Achchuthan Shanmugasundram Source Expert Review Green was added to TECPR2.
Source NHS GMS was added to TECPR2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v3.57 SLC25A46 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC25A46.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v3.57 SCO2 Achchuthan Shanmugasundram Source Expert Review Green was added to SCO2.
Source NHS GMS was added to SCO2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v3.57 MYH14 Achchuthan Shanmugasundram Source Expert Review Green was added to MYH14.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v3.57 MAG Achchuthan Shanmugasundram Source Expert Review Green was added to MAG.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v3.57 GBF1 Achchuthan Shanmugasundram Source Expert Review Green was added to GBF1.
Source NHS GMS was added to GBF1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v3.57 DRP2 Achchuthan Shanmugasundram Source Expert Review Green was added to DRP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v3.57 COX20 Achchuthan Shanmugasundram Source Expert Review Green was added to COX20.
Source NHS GMS was added to COX20.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v3.57 ACOX1 Achchuthan Shanmugasundram Source Expert Review Green was added to ACOX1.
Source NHS GMS was added to ACOX1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset leukodystrophy v3.18 SPG21 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: SPG21.
Adult onset leukodystrophy v3.18 ADAR Achchuthan Shanmugasundram Tag Q4_22_demote_red was removed from gene: ADAR.
Adult onset leukodystrophy v3.18 SPG21 Sarah Leigh edited their review of gene: SPG21: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Adult onset leukodystrophy v3.18 ADAR Sarah Leigh reviewed gene: ADAR: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v3.17 SPG21 Achchuthan Shanmugasundram Source Expert Review Green was added to SPG21.
Source NHS GMS was added to SPG21.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset leukodystrophy v3.17 ADAR Achchuthan Shanmugasundram Source Expert Review Red was added to ADAR.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Unexplained young onset end-stage renal disease v3.9 RET Achchuthan Shanmugasundram Tag Q2_23_MOI was removed from gene: RET.
Unexplained young onset end-stage renal disease v3.9 RET Achchuthan Shanmugasundram Deleted their comment
Unexplained young onset end-stage renal disease v3.9 RET Achchuthan Shanmugasundram commented on gene: RET: The mode of inheritance of this gene has been updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Unexplained young onset end-stage renal disease v3.8 RET Sarah Leigh commented on gene: RET: The mode of inheritance of this gene has been updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Unexplained young onset end-stage renal disease v3.7 RET Sarah Leigh edited their review of gene: RET: Added comment: The mode of inheritance of this gene has been updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Unexplained young onset end-stage renal disease v3.6 RET Achchuthan Shanmugasundram changed review comment from: Comment on MOI: Renal agenesis (MIM #191830) is caused by biallelic variants in ITGA8 rather than by biallelic RET variants as suggested in the reviews below. OMIM clearly associates renal agenesis with ITGA8. Biallelic variants in RET has only been associated with renal agenesis in Gene2Phenotype with 'limited' rating, which requires clinical review/. This association was based on OMIM entry and do not have any associated publications. In addition, all other renal related conditions are monoallelic. Hence the MOI should be changed to monoallelic.; to: Comment on MOI: Renal agenesis (MIM #191830) is caused by biallelic variants in ITGA8 rather than by biallelic RET variants as suggested in the reviews below. OMIM clearly associates renal agenesis with ITGA8. Biallelic variants in RET has only been associated with renal agenesis in Gene2Phenotype with 'limited' rating, which requires clinical review. This association was based on OMIM entry and do not have any associated publications. In addition, all other renal related conditions are monoallelic. Hence the MOI should be changed to monoallelic.
Unexplained young onset end-stage renal disease v3.6 RET Achchuthan Shanmugasundram Source NHS GMS was added to RET.
Mode of inheritance for gene RET was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cystic kidney disease v4.17 TULP3 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: TULP3.
Tag Q2_23_NHS_review was removed from gene: TULP3.
Cystic kidney disease v4.17 ALG5 Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: ALG5.
Tag Q1_23_NHS_review was removed from gene: ALG5.
Cystic kidney disease v4.17 TULP3 Achchuthan Shanmugasundram commented on gene: TULP3: The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Cystic kidney disease v4.17 ALG5 Achchuthan Shanmugasundram reviewed gene: ALG5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Childhood onset hereditary spastic paraplegia v4.20 WASHC5 Sarah Leigh Tag Q1_23_demote_red was removed from gene: WASHC5.
Tag Q1_23_expert_review was removed from gene: WASHC5.
Childhood onset hereditary spastic paraplegia v4.20 TECPR2 Sarah Leigh Tag Q1_23_promote_green was removed from gene: TECPR2.
Childhood onset hereditary spastic paraplegia v4.20 TECPR2 Sarah Leigh changed review comment from: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomalfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v4.20 SPTAN1 Sarah Leigh Tag Q1_23_promote_green was removed from gene: SPTAN1.
Childhood onset hereditary spastic paraplegia v4.20 SPTAN1 Sarah Leigh changed review comment from: The rating of this gene has been updated toGreenand the mode of inheritance set toMONOALLELIC, autosomal or pseudoautosomal, NOT imprintedfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v4.20 RNF170 Sarah Leigh Tag Q1_23_promote_green was removed from gene: RNF170.
Childhood onset hereditary spastic paraplegia v4.20 RNF170 Sarah Leigh changed review comment from: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomalfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v4.20 RAB3GAP2 Sarah Leigh Tag Q1_23_promote_green was removed from gene: RAB3GAP2.
Childhood onset hereditary spastic paraplegia v4.20 RAB3GAP2 Sarah Leigh changed review comment from: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomalfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v4.20 MAG Sarah Leigh Tag Q1_23_promote_green was removed from gene: MAG.
Childhood onset hereditary spastic paraplegia v4.20 MAG Sarah Leigh changed review comment from: The rating of this gene has been updated toGreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomalfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosoma lfollowing NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v4.20 DDX3X Sarah Leigh Tag Q4_22_promote_green was removed from gene: DDX3X.
Childhood onset hereditary spastic paraplegia v4.20 DDX3X Sarah Leigh changed review comment from: The rating of this gene has been updated toGreenand the mode of inheritance set toX-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Green and the mode of inheritance set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v4.20 CTNNB1 Sarah Leigh Tag Q4_22_promote_green was removed from gene: CTNNB1.
Childhood onset hereditary spastic paraplegia v4.20 CTNNB1 Sarah Leigh changed review comment from: The rating of this gene has been updated toGreenand the mode of inheritance set toMONOALLELIC, autosomal or pseudoautosomal, imprinted status unknownfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v4.20 WASHC5 Sarah Leigh reviewed gene: WASHC5: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Childhood onset hereditary spastic paraplegia v4.20 TECPR2 Sarah Leigh reviewed gene: TECPR2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v4.20 SPTAN1 Sarah Leigh reviewed gene: SPTAN1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Childhood onset hereditary spastic paraplegia v4.20 SPG7 Sarah Leigh commented on gene: SPG7: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v4.20 RNF170 Sarah Leigh reviewed gene: RNF170: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v4.20 RAB3GAP2 Sarah Leigh reviewed gene: RAB3GAP2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v4.20 MAG Sarah Leigh reviewed gene: MAG: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v4.20 DDX3X Sarah Leigh reviewed gene: DDX3X: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Childhood onset hereditary spastic paraplegia v4.20 CTNNB1 Sarah Leigh reviewed gene: CTNNB1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Childhood onset hereditary spastic paraplegia v4.19 WASHC5 Sarah Leigh Source Expert Review Red was added to WASHC5.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Childhood onset hereditary spastic paraplegia v4.19 TECPR2 Sarah Leigh Source Expert Review Green was added to TECPR2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v4.19 SPTAN1 Sarah Leigh Source Expert Review Green was added to SPTAN1.
Source NHS GMS was added to SPTAN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v4.19 SPG7 Sarah Leigh Mode of inheritance for gene SPG7 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v4.19 RNF170 Sarah Leigh Source Expert Review Green was added to RNF170.
Source NHS GMS was added to RNF170.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v4.19 RAB3GAP2 Sarah Leigh Source Expert Review Green was added to RAB3GAP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v4.19 MAG Sarah Leigh Source Expert Review Green was added to MAG.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v4.19 DDX3X Sarah Leigh Source Expert Review Green was added to DDX3X.
Source NHS GMS was added to DDX3X.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v4.19 CTNNB1 Sarah Leigh Source Expert Review Green was added to CTNNB1.
Source NHS GMS was added to CTNNB1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset hereditary spastic paraplegia v3.19 SPTAN1 Sarah Leigh Tag Q1_23_promote_green was removed from gene: SPTAN1.
Adult onset hereditary spastic paraplegia v3.19 COQ4 Sarah Leigh Tag Q4_22_promote_green was removed from gene: COQ4.
Adult onset hereditary spastic paraplegia v3.19 SPTAN1 Sarah Leigh reviewed gene: SPTAN1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Adult onset hereditary spastic paraplegia v3.19 SPG7 Sarah Leigh commented on gene: SPG7: The mode of inheritance of this gene has been updated to XX following NHS Genomic Medicine Service approval.
Adult onset hereditary spastic paraplegia v3.19 COQ4 Sarah Leigh reviewed gene: COQ4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Adult onset hereditary spastic paraplegia v3.18 SPTAN1 Sarah Leigh Source Expert Review Green was added to SPTAN1.
Source NHS GMS was added to SPTAN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset hereditary spastic paraplegia v3.18 SPG7 Sarah Leigh Mode of inheritance for gene SPG7 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Adult onset hereditary spastic paraplegia v3.18 COQ4 Sarah Leigh Source Expert Review Green was added to COQ4.
Source NHS GMS was added to COQ4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset neurodegenerative disorder v4.37 VRK1 Sarah Leigh Tag Q2_23_promote_green was removed from gene: VRK1.
Adult onset neurodegenerative disorder v4.37 SS18L1 Sarah Leigh Tag Q2_23_promote_green was removed from gene: SS18L1.
Adult onset neurodegenerative disorder v4.37 SS18L1 Sarah Leigh changed review comment from: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.
Cystic kidney disease v4.16 TULP3 Achchuthan Shanmugasundram Source Expert Review Green was added to TULP3.
Source NHS GMS was added to TULP3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Cystic kidney disease v4.16 ALG5 Achchuthan Shanmugasundram Source Expert Review Green was added to ALG5.
Source NHS GMS was added to ALG5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset neurodegenerative disorder v4.37 SPG7 Sarah Leigh Tag Q2_23_promote_green was removed from gene: SPG7.
Tag Q2_23_MOI was removed from gene: SPG7.
Adult onset neurodegenerative disorder v4.37 SPG21 Sarah Leigh Tag Q2_23_promote_green was removed from gene: SPG21.
Adult onset neurodegenerative disorder v4.37 PSAP Sarah Leigh Tag Q2_23_promote_green was removed from gene: PSAP.
Adult onset neurodegenerative disorder v4.37 NEK1 Sarah Leigh Tag Q1_23_promote_green was removed from gene: NEK1.
Adult onset neurodegenerative disorder v4.37 GBE1 Sarah Leigh Tag Q2_23_promote_green was removed from gene: GBE1.
Adult onset neurodegenerative disorder v4.37 DNAJB2 Sarah Leigh Tag Q2_23_promote_green was removed from gene: DNAJB2.
Adult onset neurodegenerative disorder v4.37 GRN Sarah Leigh Tag Q4_22_MOI was removed from gene: GRN.
Adult onset neurodegenerative disorder v4.37 VRK1 Sarah Leigh reviewed gene: VRK1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Adult onset neurodegenerative disorder v4.37 SS18L1 Sarah Leigh edited their review of gene: SS18L1: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult onset neurodegenerative disorder v4.37 SPG7 Sarah Leigh commented on gene: SPG7: The rating of this gene has been updated to Green and the mode of inheritance set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Adult onset neurodegenerative disorder v4.37 SPG21 Sarah Leigh edited their review of gene: SPG21: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Adult onset neurodegenerative disorder v4.37 PSAP Sarah Leigh edited their review of gene: PSAP: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Adult onset neurodegenerative disorder v4.37 NEK1 Sarah Leigh edited their review of gene: NEK1: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult onset neurodegenerative disorder v4.37 GRN Sarah Leigh reviewed gene: GRN: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Adult onset neurodegenerative disorder v4.37 GBE1 Sarah Leigh edited their review of gene: GBE1: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Adult onset neurodegenerative disorder v4.37 DNAJB2 Sarah Leigh edited their review of gene: DNAJB2: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Adult onset neurodegenerative disorder v4.36 VRK1 Sarah Leigh Source Expert Review Green was added to VRK1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset neurodegenerative disorder v4.36 SS18L1 Sarah Leigh Source Expert Review Green was added to SS18L1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset neurodegenerative disorder v4.36 SPG7 Sarah Leigh Source Expert Review Green was added to SPG7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset neurodegenerative disorder v4.36 SPG21 Sarah Leigh Source Expert Review Green was added to SPG21.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset neurodegenerative disorder v4.36 PSAP Sarah Leigh Source NHS GMS was added to PSAP.
Source Expert Review Green was added to PSAP.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset neurodegenerative disorder v4.36 NEK1 Sarah Leigh Source Expert Review Green was added to NEK1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset neurodegenerative disorder v4.36 GRN Sarah Leigh Mode of inheritance for gene GRN was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Adult onset neurodegenerative disorder v4.36 GBE1 Sarah Leigh Source NHS GMS was added to GBE1.
Source Expert Review Green was added to GBE1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset neurodegenerative disorder v4.36 DNAJB2 Sarah Leigh Source NHS GMS was added to DNAJB2.
Source Expert Review Green was added to DNAJB2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary ataxia with onset in adulthood v4.24 COQ4 Sarah Leigh Tag Q4_22_promote_green was removed from gene: COQ4.
Hereditary ataxia with onset in adulthood v4.24 GRN Sarah Leigh Tag Q4_22_promote_green was removed from gene: GRN.
Hereditary ataxia with onset in adulthood v4.24 SPTAN1 Sarah Leigh Tag Q1_23_promote_green was removed from gene: SPTAN1.
Hereditary ataxia with onset in adulthood v4.24 GRM1 Sarah Leigh Tag Q4_22_MOI was removed from gene: GRM1.
Hereditary ataxia with onset in adulthood v4.24 SPG7 Sarah Leigh Tag Q2_23_MOI was removed from gene: SPG7.
Hereditary ataxia with onset in adulthood v4.24 TERT Sarah Leigh Tag Q4_22_demote_red was removed from gene: TERT.
Hereditary ataxia with onset in adulthood v4.24 SPTAN1 Sarah Leigh changed review comment from: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Hereditary ataxia with onset in adulthood v4.24 GRN Sarah Leigh changed review comment from: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Hereditary ataxia with onset in adulthood v4.24 COQ4 Sarah Leigh changed review comment from: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Hereditary ataxia with onset in adulthood v4.24 TERT Sarah Leigh reviewed gene: TERT: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary ataxia with onset in adulthood v4.24 SPTAN1 Sarah Leigh reviewed gene: SPTAN1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia with onset in adulthood v4.24 SPG7 Sarah Leigh commented on gene: SPG7: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Hereditary ataxia with onset in adulthood v4.24 GRN Sarah Leigh reviewed gene: GRN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood v4.24 GRM1 Sarah Leigh reviewed gene: GRM1: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood v4.24 COQ4 Sarah Leigh reviewed gene: COQ4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood v4.23 TERT Sarah Leigh Source Expert Review Red was added to TERT.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Hereditary ataxia with onset in adulthood v4.23 SPTAN1 Sarah Leigh Source NHS GMS was added to SPTAN1.
Source Expert Review Green was added to SPTAN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary ataxia with onset in adulthood v4.23 SPG7 Sarah Leigh Mode of inheritance for gene SPG7 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood v4.23 GRN Sarah Leigh Source Expert Review Green was added to GRN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary ataxia with onset in adulthood v4.23 GRM1 Sarah Leigh Mode of inheritance for gene GRM1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood v4.23 COQ4 Sarah Leigh Source NHS GMS was added to COQ4.
Source Expert Review Green was added to COQ4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Arthrogryposis v5.15 KIF21A Sarah Leigh Tag Q1_23_promote_green was removed from gene: KIF21A.
Tag Q1_23_NHS_review was removed from gene: KIF21A.
Arthrogryposis v5.15 KCNK3 Sarah Leigh Tag Q4_22_promote_green was removed from gene: KCNK3.
Arthrogryposis v5.15 FILIP1 Sarah Leigh Tag Q2_23_promote_green was removed from gene: FILIP1.
Tag Q2_23_NHS_review was removed from gene: FILIP1.
Arthrogryposis v5.15 COL25A1 Sarah Leigh Tag Q1_23_promote_green was removed from gene: COL25A1.
Arthrogryposis v5.15 SELENON Sarah Leigh reviewed gene: SELENON: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v5.15 KIF21A Sarah Leigh reviewed gene: KIF21A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v5.15 KCNK3 Sarah Leigh reviewed gene: KCNK3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Arthrogryposis v5.15 FILIP1 Sarah Leigh reviewed gene: FILIP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v5.15 COL25A1 Sarah Leigh reviewed gene: COL25A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v5.14 SELENON Sarah Leigh Source NHS GMS was added to SELENON.
Mode of inheritance for gene SELENON was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v5.14 KIF21A Sarah Leigh Source Expert Review Green was added to KIF21A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Arthrogryposis v5.14 KCNK3 Sarah Leigh Source NHS GMS was added to KCNK3.
Source Expert Review Green was added to KCNK3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Arthrogryposis v5.14 FILIP1 Sarah Leigh Source NHS GMS was added to FILIP1.
Source Expert Review Green was added to FILIP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Arthrogryposis v5.14 COL25A1 Sarah Leigh Source NHS GMS was added to COL25A1.
Source Expert Review Green was added to COL25A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.111 ECHS1 Sarah Leigh Tag Q2_23_promote_green was removed from gene: ECHS1.
Tag Q2_23_NHS_review was removed from gene: ECHS1.
Fetal anomalies v3.111 GATB Sarah Leigh Tag Q2_23_promote_green was removed from gene: GATB.
Tag Q2_23_NHS_review was removed from gene: GATB.
Fetal anomalies v3.111 IBA57 Sarah Leigh Tag Q2_23_promote_green was removed from gene: IBA57.
Tag Q2_23_NHS_review was removed from gene: IBA57.
Fetal anomalies v3.111 KIF21A Sarah Leigh Tag Q2_23_promote_green was removed from gene: KIF21A.
Tag Q2_23_NHS_review was removed from gene: KIF21A.
Fetal anomalies v3.111 MECOM Sarah Leigh Tag Q2_23_promote_green was removed from gene: MECOM.
Tag Q2_23_NHS_review was removed from gene: MECOM.
Fetal anomalies v3.111 MTFMT Sarah Leigh Tag Q2_23_promote_green was removed from gene: MTFMT.
Tag Q2_23_NHS_review was removed from gene: MTFMT.
Fetal anomalies v3.111 MYL9 Sarah Leigh Tag Q2_23_promote_green was removed from gene: MYL9.
Fetal anomalies v3.111 NDUFA6 Sarah Leigh Tag Q2_23_promote_green was removed from gene: NDUFA6.
Tag Q2_23_NHS_review was removed from gene: NDUFA6.
Fetal anomalies v3.111 NDUFAF8 Sarah Leigh Tag Q2_23_promote_green was removed from gene: NDUFAF8.
Tag Q2_23_NHS_review was removed from gene: NDUFAF8.
Fetal anomalies v3.111 NDUFB10 Sarah Leigh Tag Q2_23_promote_green was removed from gene: NDUFB10.
Tag Q2_23_NHS_review was removed from gene: NDUFB10.
Fetal anomalies v3.111 NDUFB3 Sarah Leigh Tag Q2_23_promote_green was removed from gene: NDUFB3.
Tag Q2_23_NHS_review was removed from gene: NDUFB3.
Fetal anomalies v3.111 NDUFS1 Sarah Leigh Tag Q2_23_promote_green was removed from gene: NDUFS1.
Tag Q2_23_NHS_review was removed from gene: NDUFS1.
Fetal anomalies v3.111 PC Sarah Leigh Tag Q2_23_promote_green was removed from gene: PC.
Tag Q2_23_NHS_review was removed from gene: PC.
Fetal anomalies v3.111 PDHB Sarah Leigh Tag Q2_23_promote_green was removed from gene: PDHB.
Tag Q2_23_NHS_review was removed from gene: PDHB.
Fetal anomalies v3.111 PDHX Sarah Leigh Tag Q2_23_promote_green was removed from gene: PDHX.
Tag Q2_23_NHS_review was removed from gene: PDHX.
Fetal anomalies v3.111 PET100 Sarah Leigh Tag Q2_23_promote_green was removed from gene: PET100.
Tag Q2_23_NHS_review was removed from gene: PET100.
Fetal anomalies v3.111 PLXND1 Sarah Leigh Tag Q1_23_promote_green was removed from gene: PLXND1.
Fetal anomalies v3.111 PNPLA8 Sarah Leigh Tag Q2_23_promote_green was removed from gene: PNPLA8.
Tag Q2_23_NHS_review was removed from gene: PNPLA8.
Fetal anomalies v3.111 PRKACA Sarah Leigh Tag Q2_23_promote_green was removed from gene: PRKACA.
Fetal anomalies v3.111 PRKACB Sarah Leigh Tag Q2_23_promote_green was removed from gene: PRKACB.
Fetal anomalies v3.111 QRSL1 Sarah Leigh Tag Q2_23_promote_green was removed from gene: QRSL1.
Tag Q2_23_NHS_review was removed from gene: QRSL1.
Fetal anomalies v3.111 RAB11A Sarah Leigh Tag Q2_23_promote_green was removed from gene: RAB11A.
Tag Q2_23_NHS_review was removed from gene: RAB11A.
Fetal anomalies v3.111 RMND1 Sarah Leigh Tag Q2_23_promote_green was removed from gene: RMND1.
Tag Q2_23_NHS_review was removed from gene: RMND1.
Fetal anomalies v3.111 SCUBE3 Sarah Leigh Tag Q2_23_promote_green was removed from gene: SCUBE3.
Tag Q2_23_NHS_review was removed from gene: SCUBE3.
Fetal anomalies v3.111 SLC25A46 Sarah Leigh Tag Q2_23_promote_green was removed from gene: SLC25A46.
Tag Q2_23_NHS_review was removed from gene: SLC25A46.
Fetal anomalies v3.111 TK2 Sarah Leigh Tag Q2_23_promote_green was removed from gene: TK2.
Tag Q2_23_NHS_review was removed from gene: TK2.
Fetal anomalies v3.111 UQCRFS1 Sarah Leigh Tag Q2_23_promote_green was removed from gene: UQCRFS1.
Tag Q2_23_NHS_review was removed from gene: UQCRFS1.
Fetal anomalies v3.111 WLS Sarah Leigh Tag Q2_23_promote_green was removed from gene: WLS.
Fetal anomalies v3.111 ZMYM2 Sarah Leigh Tag Q2_23_promote_green was removed from gene: ZMYM2.
Tag Q2_23_NHS_review was removed from gene: ZMYM2.
Fetal anomalies v3.111 EARS2 Sarah Leigh Tag Q2_23_promote_green was removed from gene: EARS2.
Tag Q2_23_NHS_review was removed from gene: EARS2.
Fetal anomalies v3.111 DNA2 Sarah Leigh Tag Q2_23_promote_green was removed from gene: DNA2.
Tag Q2_23_NHS_review was removed from gene: DNA2.
Fetal anomalies v3.111 DARS2 Sarah Leigh Tag Q2_23_promote_green was removed from gene: DARS2.
Tag Q2_23_NHS_review was removed from gene: DARS2.
Fetal anomalies v3.111 COQ7 Sarah Leigh Tag Q2_23_promote_green was removed from gene: COQ7.
Tag Q2_23_NHS_review was removed from gene: COQ7.
Fetal anomalies v3.111 CLCN4 Sarah Leigh Tag Q2_23_promote_green was removed from gene: CLCN4.
Tag Q2_23_NHS_review was removed from gene: CLCN4.
Fetal anomalies v3.111 CLCN4 Sarah Leigh changed review comment from: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Green and the mode of inheritance set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) following NHS Genomic Medicine Service approval.
Fetal anomalies v3.111 C19orf70 Sarah Leigh Tag Q2_23_promote_green was removed from gene: C19orf70.
Tag Q2_23_NHS_review was removed from gene: C19orf70.
Fetal anomalies v3.111 ATP5O Sarah Leigh Tag Q2_23_promote_green was removed from gene: ATP5O.
Tag Q2_23_NHS_review was removed from gene: ATP5O.
Fetal anomalies v3.111 AGTR1 Sarah Leigh Tag Q2_23_promote_green was removed from gene: AGTR1.
Tag Q2_23_NHS_review was removed from gene: AGTR1.
Fetal anomalies v3.111 AARS2 Sarah Leigh Tag Q2_23_promote_green was removed from gene: AARS2.
Tag Q2_23_NHS_review was removed from gene: AARS2.
Fetal anomalies v3.111 ZMYM2 Sarah Leigh reviewed gene: ZMYM2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v3.111 WLS Sarah Leigh reviewed gene: WLS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.111 UQCRFS1 Sarah Leigh reviewed gene: UQCRFS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.111 TK2 Sarah Leigh reviewed gene: TK2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.111 SLC25A46 Sarah Leigh reviewed gene: SLC25A46: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.111 SCUBE3 Sarah Leigh edited their review of gene: SCUBE3: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.111 RMND1 Sarah Leigh reviewed gene: RMND1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.111 RAB11A Sarah Leigh reviewed gene: RAB11A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v3.111 QRSL1 Sarah Leigh reviewed gene: QRSL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.111 PRKACB Sarah Leigh reviewed gene: PRKACB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v3.111 PRKACA Sarah Leigh reviewed gene: PRKACA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v3.111 PNPLA8 Sarah Leigh reviewed gene: PNPLA8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.111 PLXND1 Sarah Leigh reviewed gene: PLXND1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.111 PET100 Sarah Leigh reviewed gene: PET100: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.111 PDHX Sarah Leigh reviewed gene: PDHX: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.111 PDHB Sarah Leigh reviewed gene: PDHB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.111 PC Sarah Leigh reviewed gene: PC: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.111 NDUFS1 Sarah Leigh reviewed gene: NDUFS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.111 NDUFB3 Sarah Leigh reviewed gene: NDUFB3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.111 NDUFB10 Sarah Leigh reviewed gene: NDUFB10: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.111 NDUFAF8 Sarah Leigh reviewed gene: NDUFAF8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.111 NDUFA6 Sarah Leigh reviewed gene: NDUFA6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.111 MYL9 Sarah Leigh reviewed gene: MYL9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.111 MTFMT Sarah Leigh reviewed gene: MTFMT: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.111 MECOM Sarah Leigh reviewed gene: MECOM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v3.111 KIF21A Sarah Leigh reviewed gene: KIF21A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.111 KDM5C Sarah Leigh reviewed gene: KDM5C: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Fetal anomalies v3.111 IBA57 Sarah Leigh reviewed gene: IBA57: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.111 GATB Sarah Leigh reviewed gene: GATB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.111 ECHS1 Sarah Leigh reviewed gene: ECHS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.111 EARS2 Sarah Leigh reviewed gene: EARS2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.111 DNA2 Sarah Leigh reviewed gene: DNA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.111 DARS2 Sarah Leigh reviewed gene: DARS2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.111 COQ7 Sarah Leigh reviewed gene: COQ7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.111 CLCN4 Sarah Leigh reviewed gene: CLCN4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Fetal anomalies v3.111 CDX2 Sarah Leigh reviewed gene: CDX2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v3.111 C1QBP Sarah Leigh reviewed gene: C1QBP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.111 C19orf70 Sarah Leigh reviewed gene: C19orf70: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.111 ATP5O Sarah Leigh reviewed gene: ATP5O: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.111 AGTR1 Sarah Leigh reviewed gene: AGTR1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.111 AARS2 Sarah Leigh reviewed gene: AARS2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v3.110 KDM5C Sarah Leigh Tag Q4_22_MOI was removed from gene: KDM5C.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.35 SPI1 Hannah Knight reviewed gene: SPI1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33951726; Phenotypes: Agammaglobulinemia 10, autosomal dominant; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v3.110 ZMYM2 Sarah Leigh Source Expert Review Green was added to ZMYM2.
Source NHS GMS was added to ZMYM2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 WLS Sarah Leigh Source Expert Review Green was added to WLS.
Source NHS GMS was added to WLS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 UQCRFS1 Sarah Leigh Source Expert Review Green was added to UQCRFS1.
Source NHS GMS was added to UQCRFS1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 TK2 Sarah Leigh Source Expert Review Green was added to TK2.
Source NHS GMS was added to TK2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 SLC25A46 Sarah Leigh Source Expert Review Green was added to SLC25A46.
Source NHS GMS was added to SLC25A46.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 SCUBE3 Sarah Leigh Source Expert Review Green was added to SCUBE3.
Source NHS GMS was added to SCUBE3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 RMND1 Sarah Leigh Source Expert Review Green was added to RMND1.
Source NHS GMS was added to RMND1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 RAB11A Sarah Leigh Source Expert Review Green was added to RAB11A.
Source NHS GMS was added to RAB11A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 QRSL1 Sarah Leigh Source Expert Review Green was added to QRSL1.
Source NHS GMS was added to QRSL1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 PRKACB Sarah Leigh Source Expert Review Green was added to PRKACB.
Source NHS GMS was added to PRKACB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 PRKACA Sarah Leigh Source Expert Review Green was added to PRKACA.
Source NHS GMS was added to PRKACA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 PNPLA8 Sarah Leigh Source Expert Review Green was added to PNPLA8.
Source NHS GMS was added to PNPLA8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 PLXND1 Sarah Leigh Source Expert Review Green was added to PLXND1.
Source NHS GMS was added to PLXND1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 PET100 Sarah Leigh Source Expert Review Green was added to PET100.
Source NHS GMS was added to PET100.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 PDHX Sarah Leigh Source Expert Review Green was added to PDHX.
Source NHS GMS was added to PDHX.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 PDHB Sarah Leigh Source Expert Review Green was added to PDHB.
Source NHS GMS was added to PDHB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 PC Sarah Leigh Source Expert Review Green was added to PC.
Source NHS GMS was added to PC.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 NDUFS1 Sarah Leigh Source Expert Review Green was added to NDUFS1.
Source NHS GMS was added to NDUFS1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 NDUFB3 Sarah Leigh Source Expert Review Green was added to NDUFB3.
Source NHS GMS was added to NDUFB3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 NDUFB10 Sarah Leigh Source Expert Review Green was added to NDUFB10.
Source NHS GMS was added to NDUFB10.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 NDUFAF8 Sarah Leigh Source Expert Review Green was added to NDUFAF8.
Source NHS GMS was added to NDUFAF8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 NDUFA6 Sarah Leigh Source Expert Review Green was added to NDUFA6.
Source NHS GMS was added to NDUFA6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 MYL9 Sarah Leigh Source Expert Review Green was added to MYL9.
Source NHS GMS was added to MYL9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 MTFMT Sarah Leigh Source Expert Review Green was added to MTFMT.
Source NHS GMS was added to MTFMT.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 MECOM Sarah Leigh Source Expert Review Green was added to MECOM.
Source NHS GMS was added to MECOM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 KIF21A Sarah Leigh Source Expert Review Green was added to KIF21A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 KDM5C Sarah Leigh Source NHS GMS was added to KDM5C.
Mode of inheritance for gene KDM5C was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Fetal anomalies v3.110 IBA57 Sarah Leigh Source Expert Review Green was added to IBA57.
Source NHS GMS was added to IBA57.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 GATB Sarah Leigh Source Expert Review Green was added to GATB.
Source NHS GMS was added to GATB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 ECHS1 Sarah Leigh Source Expert Review Green was added to ECHS1.
Source NHS GMS was added to ECHS1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 EARS2 Sarah Leigh Source Expert Review Green was added to EARS2.
Source NHS GMS was added to EARS2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 DNA2 Sarah Leigh Source Expert Review Green was added to DNA2.
Source NHS GMS was added to DNA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 DARS2 Sarah Leigh Source Expert Review Green was added to DARS2.
Source NHS GMS was added to DARS2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 COQ7 Sarah Leigh Source Expert Review Green was added to COQ7.
Source NHS GMS was added to COQ7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 CLCN4 Sarah Leigh Source Expert Review Green was added to CLCN4.
Source NHS GMS was added to CLCN4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 CDX2 Sarah Leigh Source Expert Review Green was added to CDX2.
Source NHS GMS was added to CDX2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 C1QBP Sarah Leigh Source Expert Review Green was added to C1QBP.
Source NHS GMS was added to C1QBP.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 C19orf70 Sarah Leigh Source Expert Review Green was added to C19orf70.
Source NHS GMS was added to C19orf70.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 ATP5O Sarah Leigh Source Expert Review Green was added to ATP5O.
Source NHS GMS was added to ATP5O.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 AGTR1 Sarah Leigh Source Expert Review Green was added to AGTR1.
Source NHS GMS was added to AGTR1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v3.110 AARS2 Sarah Leigh Source Expert Review Green was added to AARS2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Neurological ciliopathies v3.13 TOGARAM1 Sarah Leigh Tag Q2_23_promote_green was removed from gene: TOGARAM1.
Neurological ciliopathies v3.13 SUFU Sarah Leigh Tag watchlist_moi was removed from gene: SUFU.
Tag Q4_22_MOI was removed from gene: SUFU.
Tag Q4_22_promote_green was removed from gene: SUFU.
Tag Q4_22_expert_review was removed from gene: SUFU.
Neurological ciliopathies v3.13 SUFU Sarah Leigh Mode of inheritance for gene: SUFU was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Neurological ciliopathies v3.12 IFT74 Sarah Leigh Tag Q2_23_promote_green was removed from gene: IFT74.
Neurological ciliopathies v3.12 CBY1 Sarah Leigh Tag Q2_23_promote_green was removed from gene: CBY1.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.35 RELA Hannah Knight reviewed gene: RELA: Rating: GREEN; Mode of pathogenicity: None; Publications: 28600438, 29305315, 32969189, 35412596, 36926348; Phenotypes: Autoinflammatory disease, familial, Behcet-like-3; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Neurological ciliopathies v3.12 TOGARAM1 Sarah Leigh edited their review of gene: TOGARAM1: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Neurological ciliopathies v3.12 SUFU Sarah Leigh reviewed gene: SUFU: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Neurological ciliopathies v3.12 IFT74 Sarah Leigh edited their review of gene: IFT74: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Neurological ciliopathies v3.12 CBY1 Sarah Leigh edited their review of gene: CBY1: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Neurological ciliopathies v3.11 TOGARAM1 Sarah Leigh Source Expert Review Green was added to TOGARAM1.
Source NHS GMS was added to TOGARAM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Neurological ciliopathies v3.11 SUFU Sarah Leigh Source Expert Review Green was added to SUFU.
Source NHS GMS was added to SUFU.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Neurological ciliopathies v3.11 IFT74 Sarah Leigh Source Expert Review Green was added to IFT74.
Source NHS GMS was added to IFT74.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Neurological ciliopathies v3.11 CBY1 Sarah Leigh Source Expert Review Green was added to CBY1.
Source NHS GMS was added to CBY1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v4.33 WLS Sarah Leigh Tag Q2_23_promote_green was removed from gene: WLS.
Severe microcephaly v4.33 TRAPPC10 Sarah Leigh Tag Q2_23_promote_green was removed from gene: TRAPPC10.
Severe microcephaly v4.33 SARS Sarah Leigh Tag Q1_23_promote_green was removed from gene: SARS.
Severe microcephaly v4.33 NUP214 Sarah Leigh Tag Q1_23_promote_green was removed from gene: NUP214.
Severe microcephaly v4.33 INTS11 Sarah Leigh Tag Q2_23_promote_green was removed from gene: INTS11.
Severe microcephaly v4.33 GRM7 Sarah Leigh Tag Q2_23_promote_green was removed from gene: GRM7.
Severe microcephaly v4.33 DOHH Sarah Leigh Tag Q4_22_MOI was removed from gene: DOHH.
Tag Q4_22_promote_green was removed from gene: DOHH.
Severe microcephaly v4.33 ARPC4 Sarah Leigh Tag Q2_23_promote_green was removed from gene: ARPC4.
Severe microcephaly v4.33 WLS Sarah Leigh reviewed gene: WLS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v4.33 TRAPPC10 Sarah Leigh reviewed gene: TRAPPC10: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v4.33 SARS Sarah Leigh reviewed gene: SARS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v4.33 NUP214 Sarah Leigh edited their review of gene: NUP214: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v4.33 INTS11 Sarah Leigh reviewed gene: INTS11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v4.33 GRM7 Sarah Leigh reviewed gene: GRM7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v4.33 DOHH Sarah Leigh commented on gene: DOHH: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Severe microcephaly v4.33 ARPC4 Sarah Leigh reviewed gene: ARPC4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Severe microcephaly v4.32 WLS Sarah Leigh Source Expert Review Green was added to WLS.
Source NHS GMS was added to WLS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v4.32 TRAPPC10 Sarah Leigh Source Expert Review Green was added to TRAPPC10.
Source NHS GMS was added to TRAPPC10.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v4.32 SARS Sarah Leigh Source Expert Review Green was added to SARS.
Source NHS GMS was added to SARS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v4.32 NUP214 Sarah Leigh Source Expert Review Green was added to NUP214.
Source NHS GMS was added to NUP214.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v4.32 INTS11 Sarah Leigh Source Expert Review Green was added to INTS11.
Source NHS GMS was added to INTS11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v4.32 GRM7 Sarah Leigh Source Expert Review Green was added to GRM7.
Source NHS GMS was added to GRM7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v4.32 DOHH Sarah Leigh Source Expert Review Green was added to DOHH.
Source NHS GMS was added to DOHH.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v4.32 ARPC4 Sarah Leigh Source Expert Review Green was added to ARPC4.
Source NHS GMS was added to ARPC4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.35 JAK1 Hannah Knight changed review comment from: Now four families reported, and variants seem to cluster.
PMID: 28111307 - mother and two sons with immune disorder. De novo variant in mother, also in both children (p.A634D)
PMID: 32750333 - early-onset multi-organ immune dysregulation resulting from a mosaic variant not found in either parent (p.S703I)
PMID: 34496019 - somatic variant found in a patient with hypereosinophilia (p.R629_S632delinsSA)
PMID: 35046931 - novel variant (p.H596D) in an individual with a unique autoinflammatory keratinization disease

Also one report of biallelic disease in 2016 (PMID: 28008925), but none others since then; to: Now four families reported, and variants seem to cluster.
PMID: 28111307 - mother and two sons with immune disorder. De novo variant in mother, also in both children (p.A634D)
PMID: 32750333 - early-onset multi-organ immune dysregulation resulting from a mosaic variant not found in either parent (p.S703I)
PMID: 34496019 - somatic variant found in a patient with hypereosinophilia (p.R629_S632delinsSA)
PMID: 35046931 - novel variant (p.H596D) in an individual with a unique autoinflammatory keratinization disease

Also one report of biallelic disease in 2016 (PMID: 28008925), but none others since then
Primary immunodeficiency or monogenic inflammatory bowel disease v4.35 JAK1 Hannah Knight reviewed gene: JAK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28111307, 32750333, 34496019, 35046931; Phenotypes: Autoinflammation, immune dysregulation, and eosinophilia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal disorders v4.34 SGSH Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: SGSH.
Tag Q2_23_NHS_review was removed from gene: SGSH.
Retinal disorders v4.34 PDSS1 Achchuthan Shanmugasundram Tag Q4_22_MOI was removed from gene: PDSS1.
Tag Q4_22_promote_green was removed from gene: PDSS1.
Retinal disorders v4.34 LAMP2 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: LAMP2.
Tag Q2_23_NHS_review was removed from gene: LAMP2.
Retinal disorders v4.34 COQ2 Achchuthan Shanmugasundram Tag Q4_22_MOI was removed from gene: COQ2.
Tag Q4_22_promote_green was removed from gene: COQ2.
Retinal disorders v4.34 AIPL1 Achchuthan Shanmugasundram Tag Q4_22_MOI was removed from gene: AIPL1.
Retinal disorders v4.34 SGSH Achchuthan Shanmugasundram commented on gene: SGSH: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Retinal disorders v4.34 PDSS1 Achchuthan Shanmugasundram reviewed gene: PDSS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v4.34 LAMP2 Achchuthan Shanmugasundram commented on gene: LAMP2: The rating of this gene has been updated to Green and the mode of inheritance set to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' following NHS Genomic Medicine Service approval.
Retinal disorders v4.34 COQ2 Achchuthan Shanmugasundram reviewed gene: COQ2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v4.34 AIPL1 Achchuthan Shanmugasundram reviewed gene: AIPL1: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Retinal disorders v4.33 SGSH Achchuthan Shanmugasundram Source Expert Review Green was added to SGSH.
Source NHS GMS was added to SGSH.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v4.33 PDSS1 Achchuthan Shanmugasundram Source Expert Review Green was added to PDSS1.
Source NHS GMS was added to PDSS1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v4.33 LAMP2 Achchuthan Shanmugasundram Source Expert Review Green was added to LAMP2.
Source NHS GMS was added to LAMP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v4.33 COQ2 Achchuthan Shanmugasundram Source Expert Review Green was added to COQ2.
Source NHS GMS was added to COQ2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v4.33 AIPL1 Achchuthan Shanmugasundram Mode of inheritance for gene AIPL1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Ophthalmological ciliopathies v3.3 SUFU Achchuthan Shanmugasundram Tag watchlist_moi was removed from gene: SUFU.
Tag Q4_22_MOI was removed from gene: SUFU.
Tag Q4_22_promote_green was removed from gene: SUFU.
Tag Q4_22_expert_review was removed from gene: SUFU.
Ophthalmological ciliopathies v3.3 SUFU Achchuthan Shanmugasundram reviewed gene: SUFU: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ophthalmological ciliopathies v3.2 SUFU Achchuthan Shanmugasundram Source Expert Review Green was added to SUFU.
Source NHS GMS was added to SUFU.
Mode of inheritance for gene SUFU was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.35 IRF2BP2 Hannah Knight reviewed gene: IRF2BP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27016798, 33864888, 34451894, 36193988; Phenotypes: ?Immunodeficiency, common variable, 14; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary isolated diabetes insipidus v1.4 AQP1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been demoted from Green to Grey in R440 Neuropophyseal diabetes insipidus, as agreed with the NHS Genomic Medicine Service.; to: The rating of this gene has been updated from Green to Grey in R440 Neuropophyseal diabetes insipidus, as agreed with the NHS Genomic Medicine Service.
Hereditary isolated diabetes insipidus v1.4 AQP1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been demoted from Green to Grey in R440 Neuropophyseal diabetes insipidus, as agreed with the NHS Genomic Medicine Service.; to: The rating of this gene has been demoted from Green to Grey in R440 Neuropophyseal diabetes insipidus, as agreed with the NHS Genomic Medicine Service.