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Intellectual disability v6.13 RNU4-2 Eleanor Williams commented on gene: RNU4-2
Intellectual disability v6.13 ZBTB47 Eleanor Williams Tag gene-checked tag was added to gene: ZBTB47.
Intellectual disability v6.13 KDM5A Eleanor Williams Phenotypes for gene: KDM5A were changed from autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071 to autism spectrum disorder, MONDO:0005258; intellectual disability, MONDO:0001071; El Hayek-Chahrour neurodevelopmental syndrome, OMIM:620820
Intellectual disability v6.12 KDM5A Eleanor Williams Tag gene-checked was removed from gene: KDM5A.
Intellectual disability v6.12 TMEM63B Eleanor Williams Tag gene-checked tag was added to gene: TMEM63B.
Intellectual disability v6.12 PPP1R3F Eleanor Williams Tag gene-checked tag was added to gene: PPP1R3F.
Intellectual disability v6.12 MAST4 Eleanor Williams Tag gene-checked tag was added to gene: MAST4.
Intellectual disability v6.12 RAB5C Eleanor Williams Tag gene-checked tag was added to gene: RAB5C.
Intellectual disability v6.12 PABPC1 Eleanor Williams Tag gene-checked tag was added to gene: PABPC1.
Intellectual disability v6.12 MYH10 Eleanor Williams Tag gene-checked tag was added to gene: MYH10.
Intellectual disability v6.12 DHX9 Eleanor Williams Tag gene-checked tag was added to gene: DHX9.
Intellectual disability v6.12 CNOT9 Eleanor Williams Tag gene-checked tag was added to gene: CNOT9.
Intellectual disability v6.12 CDK16 Eleanor Williams Tag gene-checked tag was added to gene: CDK16.
Intellectual disability v6.12 ARF3 Eleanor Williams Tag gene-checked tag was added to gene: ARF3.
Intellectual disability v6.12 MAST3 Sarah Leigh Tag Q2_24_NHS_review tag was added to gene: MAST3.
Intellectual disability v6.12 MAST3 Sarah Leigh Tag Q2_24_MOI was removed from gene: MAST3.
Intellectual disability v6.12 MAST3 Sarah Leigh Entity copied from Early onset or syndromic epilepsy v5.10
Intellectual disability v6.12 MAST3 Sarah Leigh gene: MAST3 was added
gene: MAST3 was added to Intellectual disability. Sources: Expert Review Amber,Literature
Q2_24_promote_green, Q2_24_MOI tags were added to gene: MAST3.
Mode of inheritance for gene: MAST3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MAST3 were set to 34185323; 35095415
Mode of pathogenicity for gene: MAST3 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v6.11 FAM111A Achchuthan Shanmugasundram Tag Q4_23_demote_red was removed from gene: FAM111A.
Tag Q4_23_NHS_review was removed from gene: FAM111A.
Tag Q4_23_expert_review was removed from gene: FAM111A.
Intellectual disability v6.11 DPP6 Achchuthan Shanmugasundram Tag Q4_23_demote_red was removed from gene: DPP6.
Tag Q4_23_NHS_review was removed from gene: DPP6.
Tag Q4_23_expert_review was removed from gene: DPP6.
Intellectual disability v6.11 ZBTB47 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ZBTB47.
Intellectual disability v6.11 VCP Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: VCP.
Intellectual disability v6.11 TEFM Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: TEFM.
Intellectual disability v6.11 SRSF1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SRSF1.
Intellectual disability v6.11 SHQ1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SHQ1.
Intellectual disability v6.11 RPL10 Achchuthan Shanmugasundram Tag Q4_23_MOI was removed from gene: RPL10.
Intellectual disability v6.11 RELN Achchuthan Shanmugasundram Tag Q4_23_MOI was removed from gene: RELN.
Intellectual disability v6.11 RBL2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: RBL2.
Tag Q4_23_NHS_review was removed from gene: RBL2.
Intellectual disability v6.11 RAP1B Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: RAP1B.
Intellectual disability v6.11 MYH10 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: MYH10.
Intellectual disability v6.11 MAST4 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: MAST4.
Intellectual disability v6.11 KMT2B Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: KMT2B.
Intellectual disability v6.11 ERI1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ERI1.
Intellectual disability v6.11 COX11 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: COX11.
Intellectual disability v6.11 CLDN11 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CLDN11.
Intellectual disability v6.11 CLCN6 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CLCN6.
Intellectual disability v6.11 CDK16 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CDK16.
Tag Q4_23_NHS_review was removed from gene: CDK16.
Intellectual disability v6.11 CASP2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CASP2.
Intellectual disability v6.11 ARF3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ARF3.
Intellectual disability v6.11 ACACA Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ACACA.
Intellectual disability v6.11 FAR1 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: FAR1.
Intellectual disability v6.11 U2AF2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: U2AF2.
Tag Q3_23_NHS_review was removed from gene: U2AF2.
Intellectual disability v6.11 TTI1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: TTI1.
Intellectual disability v6.11 TSPOAP1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: TSPOAP1.
Intellectual disability v6.11 TMEM63B Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: TMEM63B.
Intellectual disability v6.11 SLC30A9 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: SLC30A9.
Intellectual disability v6.11 RPS6KA3 Achchuthan Shanmugasundram Tag Q3_23_MOI was removed from gene: RPS6KA3.
Intellectual disability v6.11 RAB5C Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: RAB5C.
Intellectual disability v6.11 PSMC3 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PSMC3.
Intellectual disability v6.11 PPP1R3F Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PPP1R3F.
Intellectual disability v6.11 PIP5K1C Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PIP5K1C.
Intellectual disability v6.11 PABPC1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PABPC1.
Tag Q3_23_MOI was removed from gene: PABPC1.
Tag Q3_23_phenotype was removed from gene: PABPC1.
Intellectual disability v6.11 NR2F2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: NR2F2.
Tag Q3_23_NHS_review was removed from gene: NR2F2.
Intellectual disability v6.11 NEUROG1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: NEUROG1.
Tag Q3_23_NHS_review was removed from gene: NEUROG1.
Intellectual disability v6.11 LETM1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: LETM1.
Tag Q3_23_MOI was removed from gene: LETM1.
Intellectual disability v6.11 KCNH5 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: KCNH5.
Intellectual disability v6.11 ESAM Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: ESAM.
Tag Q3_23_NHS_review was removed from gene: ESAM.
Intellectual disability v6.11 EIF4A2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: EIF4A2.
Intellectual disability v6.11 DHX9 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: DHX9.
Intellectual disability v6.11 DAGLA Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: DAGLA.
Intellectual disability v6.11 CNOT9 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: CNOT9.
Intellectual disability v6.11 ATP6V0C Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: ATP6V0C.
Tag Q3_23_NHS_review was removed from gene: ATP6V0C.
Intellectual disability v6.11 AGTPBP1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: AGTPBP1.
Intellectual disability v6.11 ZBTB47 Sarah Leigh edited their review of gene: ZBTB47: 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
Intellectual disability v6.11 VCP Sarah Leigh reviewed gene: VCP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 U2AF2 Sarah Leigh reviewed gene: U2AF2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 TTI1 Sarah Leigh commented on gene: TTI1: 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 v6.11 TSPOAP1 Sarah Leigh edited their review of gene: TSPOAP1: 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
Intellectual disability v6.11 TMEM63B Sarah Leigh reviewed gene: TMEM63B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 TEFM Sarah Leigh reviewed gene: TEFM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v6.11 SRSF1 Sarah Leigh reviewed gene: SRSF1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 SLC30A9 Sarah Leigh edited their review of gene: SLC30A9: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v6.11 SHQ1 Sarah Leigh edited their review of gene: SHQ1: 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
Intellectual disability v6.11 RPS6KA3 Sarah Leigh reviewed gene: RPS6KA3: 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 v6.11 RPL10 Sarah Leigh commented on gene: RPL10: The mode of inheritance of this gene has been updated to X-LINKED: hemizygous mutation in males, biallelic mutations in females following NHS Genomic Medicine Service approval.
Intellectual disability v6.11 RELN Sarah Leigh reviewed gene: RELN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v6.11 RBL2 Sarah Leigh commented on gene: RBL2: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Intellectual disability v6.11 RAP1B Sarah Leigh reviewed gene: RAP1B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 RAB5C Sarah Leigh reviewed gene: RAB5C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 PSMC3 Sarah Leigh reviewed gene: PSMC3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 PPP1R3F Sarah Leigh reviewed gene: PPP1R3F: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v6.11 PIP5K1C Sarah Leigh reviewed gene: PIP5K1C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 PABPC1 Sarah Leigh edited their review of gene: PABPC1: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v6.11 NR2F2 Sarah Leigh reviewed gene: NR2F2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 NEUROG1 Sarah Leigh reviewed gene: NEUROG1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v6.11 MYH10 Sarah Leigh reviewed gene: MYH10: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 MAST4 Sarah Leigh edited their review of gene: MAST4: 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
Intellectual disability v6.11 LETM1 Sarah Leigh commented on gene: LETM1: 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 v6.11 KMT2B Sarah Leigh reviewed gene: KMT2B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v6.11 KCNH5 Sarah Leigh reviewed gene: KCNH5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 FAR1 Sarah Leigh commented on gene: FAR1: 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.
Intellectual disability v6.11 FAM111A Sarah Leigh commented on gene: FAM111A: The rating of this gene has been updated to red following NHS Genomic Medicine Service approval.
Intellectual disability v6.11 ESAM Sarah Leigh reviewed gene: ESAM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v6.11 ERI1 Sarah Leigh reviewed gene: ERI1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v6.11 EIF4A2 Sarah Leigh commented on gene: EIF4A2: The rating of this gene has been updated to Green and the mode of inheritance set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval
Intellectual disability v6.11 DPP6 Sarah Leigh reviewed gene: DPP6: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v6.11 DHX9 Sarah Leigh reviewed gene: DHX9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 DAGLA Sarah Leigh reviewed gene: DAGLA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 COX11 Sarah Leigh edited their review of gene: COX11: 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
Intellectual disability v6.11 CNOT9 Sarah Leigh reviewed gene: CNOT9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 CLDN11 Sarah Leigh reviewed gene: CLDN11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 CLCN6 Sarah Leigh commented on gene: CLCN6: 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.
Intellectual disability v6.11 CDK16 Sarah Leigh commented on gene: CDK16: The rating of this gene has been updated to green and the mode of inheritance updated to X-LINKED: hemizygous mutation in males, biallelic mutations in females following NHS Genomic Medicine Service approval.
Intellectual disability v6.11 CASP2 Sarah Leigh edited their review of gene: CASP2: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v6.11 ATP6V0C Sarah Leigh reviewed gene: ATP6V0C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v6.11 ARF3 Sarah Leigh reviewed gene: ARF3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v6.11 AGTPBP1 Sarah Leigh reviewed gene: AGTPBP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v6.11 ACACA Sarah Leigh edited their review of gene: ACACA: 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
Intellectual disability v6.10 ZBTB47 Achchuthan Shanmugasundram Source Expert Review Green was added to ZBTB47.
Source NHS GMS was added to ZBTB47.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 VCP Achchuthan Shanmugasundram Source Expert Review Green was added to VCP.
Source NHS GMS was added to VCP.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 U2AF2 Achchuthan Shanmugasundram Source Expert Review Green was added to U2AF2.
Source NHS GMS was added to U2AF2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 TTI1 Achchuthan Shanmugasundram Source Expert Review Green was added to TTI1.
Source NHS GMS was added to TTI1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 TSPOAP1 Achchuthan Shanmugasundram Source Expert Review Green was added to TSPOAP1.
Source NHS GMS was added to TSPOAP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 TMEM63B Achchuthan Shanmugasundram Source Expert Review Green was added to TMEM63B.
Source NHS GMS was added to TMEM63B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 TEFM Achchuthan Shanmugasundram Source Expert Review Green was added to TEFM.
Source NHS GMS was added to TEFM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 SRSF1 Achchuthan Shanmugasundram Source Expert Review Green was added to SRSF1.
Source NHS GMS was added to SRSF1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 SLC30A9 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC30A9.
Source NHS GMS was added to SLC30A9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 SHQ1 Achchuthan Shanmugasundram Source Expert Review Green was added to SHQ1.
Source NHS GMS was added to SHQ1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 RPS6KA3 Achchuthan Shanmugasundram Source NHS GMS was added to RPS6KA3.
Mode of inheritance for gene RPS6KA3 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 v6.10 RPL10 Achchuthan Shanmugasundram Source NHS GMS was added to RPL10.
Mode of inheritance for gene RPL10 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v6.10 RELN Achchuthan Shanmugasundram Source NHS GMS was added to RELN.
Mode of inheritance for gene RELN was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v6.10 RBL2 Achchuthan Shanmugasundram Source Expert Review Green was added to RBL2.
Source NHS GMS was added to RBL2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 RAP1B Achchuthan Shanmugasundram Source Expert Review Green was added to RAP1B.
Source NHS GMS was added to RAP1B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 RAB5C Achchuthan Shanmugasundram Source Expert Review Green was added to RAB5C.
Source NHS GMS was added to RAB5C.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 PSMC3 Achchuthan Shanmugasundram Source Expert Review Green was added to PSMC3.
Source NHS GMS was added to PSMC3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 PPP1R3F Achchuthan Shanmugasundram Source Expert Review Green was added to PPP1R3F.
Source NHS GMS was added to PPP1R3F.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 PIP5K1C Achchuthan Shanmugasundram Source Expert Review Green was added to PIP5K1C.
Source NHS GMS was added to PIP5K1C.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 PABPC1 Achchuthan Shanmugasundram Source Expert Review Green was added to PABPC1.
Source NHS GMS was added to PABPC1.
Mode of inheritance for gene PABPC1 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 v6.10 NR2F2 Achchuthan Shanmugasundram Source Expert Review Green was added to NR2F2.
Source NHS GMS was added to NR2F2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 NEUROG1 Achchuthan Shanmugasundram Source Expert Review Green was added to NEUROG1.
Source NHS GMS was added to NEUROG1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 MYH10 Achchuthan Shanmugasundram Source Expert Review Green was added to MYH10.
Source NHS GMS was added to MYH10.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 MAST4 Achchuthan Shanmugasundram Source Expert Review Green was added to MAST4.
Source NHS GMS was added to MAST4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 LETM1 Achchuthan Shanmugasundram 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)
Intellectual disability v6.10 KMT2B Achchuthan Shanmugasundram Source Expert Review Green was added to KMT2B.
Source NHS GMS was added to KMT2B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 KCNH5 Achchuthan Shanmugasundram Source Expert Review Green was added to KCNH5.
Source NHS GMS was added to KCNH5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 FAR1 Achchuthan Shanmugasundram Source NHS GMS was added to FAR1.
Mode of inheritance for gene FAR1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Intellectual disability v6.10 FAM111A Achchuthan Shanmugasundram Source Expert Review Red was added to FAM111A.
Source NHS GMS was added to FAM111A.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Intellectual disability v6.10 ESAM Achchuthan Shanmugasundram Source Expert Review Green was added to ESAM.
Source NHS GMS was added to ESAM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 ERI1 Achchuthan Shanmugasundram Source Expert Review Green was added to ERI1.
Source NHS GMS was added to ERI1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 EIF4A2 Achchuthan Shanmugasundram Source Expert Review Green was added to EIF4A2.
Source NHS GMS was added to EIF4A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 DPP6 Achchuthan Shanmugasundram Source Expert Review Red was added to DPP6.
Source NHS GMS was added to DPP6.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Intellectual disability v6.10 DHX9 Achchuthan Shanmugasundram Source Expert Review Green was added to DHX9.
Source NHS GMS was added to DHX9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 DAGLA Achchuthan Shanmugasundram Source Expert Review Green was added to DAGLA.
Source NHS GMS was added to DAGLA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 COX11 Achchuthan Shanmugasundram Source Expert Review Green was added to COX11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 CNOT9 Achchuthan Shanmugasundram Source Expert Review Green was added to CNOT9.
Source NHS GMS was added to CNOT9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 CLDN11 Achchuthan Shanmugasundram Source Expert Review Green was added to CLDN11.
Source NHS GMS was added to CLDN11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 CLCN6 Achchuthan Shanmugasundram Source Expert Review Green was added to CLCN6.
Source NHS GMS was added to CLCN6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 CDK16 Achchuthan Shanmugasundram Source Expert Review Green was added to CDK16.
Source NHS GMS was added to CDK16.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 CASP2 Achchuthan Shanmugasundram Source Expert Review Green was added to CASP2.
Source NHS GMS was added to CASP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 ATP6V0C Achchuthan Shanmugasundram Source Expert Review Green was added to ATP6V0C.
Source NHS GMS was added to ATP6V0C.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 ARF3 Achchuthan Shanmugasundram Source Expert Review Green was added to ARF3.
Source NHS GMS was added to ARF3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 AGTPBP1 Achchuthan Shanmugasundram Source Expert Review Green was added to AGTPBP1.
Source NHS GMS was added to AGTPBP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.10 ACACA Achchuthan Shanmugasundram Source Expert Review Green was added to ACACA.
Source NHS GMS was added to ACACA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v6.9 DPP6 Arina Puzriakova Phenotypes for gene: DPP6 were changed from autosomal dominant microcephaly and mental retardation; Mental retardation, autosomal dominant 33, 616311 to Intellectual developmental disorder, autosomal dominant 33, OMIM:616311
Intellectual disability v6.8 TTI1 Arina Puzriakova Added comment: Comment on phenotypes: Relevant phenotype now listed in OMIM (Neurodevelopmental disorder with microcephaly and movement abnormalities, OMIM:620445)
Intellectual disability v6.8 TTI1 Arina Puzriakova Phenotypes for gene: TTI1 were changed from neurodevelopmental disorder with microcephaly to Neurodevelopmental disorder with microcephaly and movement abnormalities, OMIM:620445
Intellectual disability v6.7 CASP2 Arina Puzriakova Phenotypes for gene: CASP2 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, OMIM:620653
Intellectual disability v6.6 SPTBN4 Arina Puzriakova Phenotypes for gene: SPTBN4 were changed from Neurodevelopmental disorder with hypotonia, neuropathy, and deafness MIM#617519 to Neurodevelopmental disorder with hypotonia, neuropathy, and deafness, OMIM:617519
Intellectual disability v6.5 ISCA-46292-Loss Arina Puzriakova reviewed Region: ISCA-46292-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v6.5 ISCA-46743-Loss Arina Puzriakova changed review comment from: The rating of this region 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. Evidence: multiple unrelated cases curated in ClinGen plus several others - sufficient evidence for this region. Phenotype: syndromic intellectual disability (congenital anomalies, behavioural problems and facial dysmorphism), seizures in about 30%. Modulated phenotype in females is reported.; to: The rating of this region 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. Evidence: two cases (PMID: 30158690; 33758131) with intragenic STAG2 deletions but listed as sufficient evidence in ClinGen. Region encompasses STAG2 and some of XIAP. Phenotype: holoprosencephaly and/or developmental delay/ID based on LOF of STAG2 gene. Affected females are reported.
Intellectual disability v6.5 ISCA-46743-Gain Arina Puzriakova reviewed Region: ISCA-46743-Gain: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v6.5 ISCA-46743-Loss Arina Puzriakova reviewed Region: ISCA-46743-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v6.5 ISCA-46292-Loss Arina Puzriakova Publications for Region: ISCA-46292-Loss were set to
Intellectual disability v6.4 ISCA-46743-Loss Arina Puzriakova Publications for Region: ISCA-46743-Loss were set to
Intellectual disability v6.3 ISCA-46743-Gain Arina Puzriakova Publications for Region: ISCA-46743-Gain were set to
Intellectual disability v6.2 ISCA-46292-Loss Arina Puzriakova Region: ISCA-46292-Loss was added
Region: ISCA-46292-Loss was added to Intellectual disability. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46292-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v6.2 ISCA-46743-Loss Arina Puzriakova Region: ISCA-46743-Loss was added
Region: ISCA-46743-Loss was added to Intellectual disability. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46743-Loss was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v6.2 ISCA-46743-Gain Arina Puzriakova Region: ISCA-46743-Gain was added
Region: ISCA-46743-Gain was added to Intellectual disability. Sources: Expert Review Green,ClinGen
Mode of inheritance for Region: ISCA-46743-Gain was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v6.1 Achchuthan Shanmugasundram Panel version 6.0 has been signed off on 2024-05-01
Intellectual disability v6.0 Achchuthan Shanmugasundram promoted panel to version 6.0
Intellectual disability v5.558 Arina Puzriakova Panel name changed from Intellectual disability - microarray and sequencing to Intellectual disability
List of related panels changed from Coarse facial features including Coffin-Siris-like disorders; ID; Moderate; severe or profound intellectual disability; Schizophrenia plus additional features; Intellectual disability - microarray; fragile X and sequencing; Intellectual disability; R29 to Coarse facial features including Coffin-Siris-like disorders; ID; Moderate; severe or profound intellectual disability; Schizophrenia plus additional features; Intellectual disability - microarray; fragile X and sequencing; Intellectual disability - microarray and sequencing; R29
Intellectual disability v5.557 DIP2B Dmitrijs Rots reviewed gene: DIP2B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v5.557 ADGRL1 Dmitrijs Rots gene: ADGRL1 was added
gene: ADGRL1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: ADGRL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ADGRL1 were set to PubMed: 35907405
Phenotypes for gene: ADGRL1 were set to Developmental delay, behavioral abnormalities, and neuropsychiatric disorders
Review for gene: ADGRL1 was set to GREEN
Added comment: More than 10 cases described in PubMed: 35907405
Sources: Literature
Intellectual disability v5.557 ZNFX1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: ZNFX1.
Intellectual disability v5.557 RNPC3 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: RNPC3.
Intellectual disability v5.557 FILIP1 Achchuthan Shanmugasundram Tag gene-checked was removed from gene: FILIP1.
Intellectual disability v5.557 OTUD7A Achchuthan Shanmugasundram Tag gene-checked was removed from gene: OTUD7A.
Intellectual disability v5.557 CEP295 Achchuthan Shanmugasundram Phenotypes for gene: CEP295 were changed from Seckel syndrome 11, OMIM # 620767 to Seckel syndrome 11, OMIM:620767
Intellectual disability v5.556 CEP295 Achchuthan Shanmugasundram Classified gene: CEP295 as Amber List (moderate evidence)
Intellectual disability v5.556 CEP295 Achchuthan Shanmugasundram Gene: cep295 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.555 CEP295 Achchuthan Shanmugasundram reviewed gene: CEP295: Rating: AMBER; Mode of pathogenicity: None; Publications: 38154379; Phenotypes: Seckel syndrome 11, OMIM:620767; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.555 DOCK4 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: DOCK4.
Intellectual disability v5.555 DOCK4 Achchuthan Shanmugasundram Classified gene: DOCK4 as Amber List (moderate evidence)
Intellectual disability v5.555 DOCK4 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, PMID:38526744 reported seven unrelated individuals with heterozygous variants and with developmental delay or intellectual disability, of which four had ID. Three of them with ID had heterozygous variants, while one had compound heterozygous variants. There is also some functional evidence available.

Hence, this gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.555 DOCK4 Achchuthan Shanmugasundram Gene: dock4 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.554 DOCK4 Achchuthan Shanmugasundram Phenotypes for gene: DOCK4 were changed from neuronevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neuronevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.554 DOCK4 Achchuthan Shanmugasundram Phenotypes for gene: DOCK4 were changed from DOCK4-related neurodevelopmental disorder (MONDO:0060490) to neuronevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.553 DOCK4 Achchuthan Shanmugasundram reviewed gene: DOCK4: Rating: GREEN; Mode of pathogenicity: None; Publications: 38526744; Phenotypes: neuronevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.553 GTF3C5 Achchuthan Shanmugasundram Publications for gene: GTF3C5 were set to 38520561; 35503477
Intellectual disability v5.552 GTF3C5 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Zornitza Stark, PMID:35503477 reported a proband with profound developmental delay and PMID:38520561 reported three families with syndromic intellectual disability (ID was mild in one family). There is also functional evidence and evidence from zebrafish model in support of the disease association.

Hence, the gene can be promoted to green rating in the next GMS review.; to: Comment on list classification: As reviewed by Zornitza Stark, PMID:35503477 reported a proband with profound developmental delay and PMID:38520561 reported three families with syndromic intellectual disability (ID was mild in one family). There is also functional evidence and evidence from zebrafish model in support of the disease association.

Hence, this gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.552 GTF3C5 Achchuthan Shanmugasundram edited their review of gene: GTF3C5: Changed publications to: 35503477, 38520561
Intellectual disability v5.552 GTF3C5 Achchuthan Shanmugasundram Classified gene: GTF3C5 as Amber List (moderate evidence)
Intellectual disability v5.552 GTF3C5 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, PMID:35503477 reported a proband with profound developmental delay and PMID:38520561 reported three families with syndromic intellectual disability (ID was mild in one family). There is also functional evidence and evidence from zebrafish model in support of the disease association.

Hence, the gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.552 GTF3C5 Achchuthan Shanmugasundram Gene: gtf3c5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.551 GTF3C5 Achchuthan Shanmugasundram Phenotypes for gene: GTF3C5 were changed from neurodevelopmental disorder MONDO:0700092, GTF3C5-related to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.550 GTF3C5 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: GTF3C5.
Intellectual disability v5.550 GTF3C5 Achchuthan Shanmugasundram reviewed gene: GTF3C5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.550 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Stromme syndrome 243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome to Stromme syndrome, OMIM:243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome
Intellectual disability v5.549 GMNN Arina Puzriakova Phenotypes for gene: GMNN were changed from Meier-Gorlin syndrome 6, 616835 to Meier-Gorlin syndrome 6, OMIM:616835
Intellectual disability v5.548 IGF1 Arina Puzriakova Phenotypes for gene: IGF1 were changed from Growth retardation with deafness and mental retardation due to IGF1 deficiency, 608747; INSULIN-LIKE GROWTH FACTOR I DEFICIENCY (IGF1 DEFICIENCY) to Insulin-like growth factor I deficiency, OMIM:608747
Intellectual disability v5.547 LIG4 Arina Puzriakova Phenotypes for gene: LIG4 were changed from LIG4 syndrome, OMIM:606593 to LIG4 syndrome, OMIM:606593
Intellectual disability v5.547 LIG4 Arina Puzriakova Phenotypes for gene: LIG4 were changed from LIG4 syndrome, 606593{Multiple myeloma, resistance to}, 254500Severe combined immunodeficiency with sensitivity to ionizing radiation, 602450; LIG4 SYNDROME to LIG4 syndrome, OMIM:606593
Intellectual disability v5.546 ORC1 Arina Puzriakova Phenotypes for gene: ORC1 were changed from Meier-Gorlin syndrome 1, 224690; MEIER-GORLIN SYNDROME 1 to Meier-Gorlin syndrome 1, OMIM:224690
Intellectual disability v5.545 ORC4 Arina Puzriakova Phenotypes for gene: ORC4 were changed from Meier-Gorlin syndrome 2, 613800 to Meier-Gorlin syndrome 2, OMIM:613800
Intellectual disability v5.544 ORC6 Arina Puzriakova Phenotypes for gene: ORC6 were changed from Meier-Gorlin syndrome 3, 613803 to Meier-Gorlin syndrome 3, OMIM:613803
Intellectual disability v5.543 PCNT Arina Puzriakova Phenotypes for gene: PCNT were changed from Microcephalic osteodysplastic primordial dwarfism, type II, 210720 -3; MICROCEPHALIC OSTEODYSPLASTIC PRIMORDIAL DWARFISM, TYPE II to Microcephalic osteodysplastic primordial dwarfism, type II, OMIM:210720
Intellectual disability v5.542 RNU4ATAC Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Gene2Phenotype confirmed gene with ID HPO to Lowry-Wood syndrome, OMIM:226960; Microcephalic osteodysplastic primordial dwarfism, type I, OMIM:210710; Roifman syndrome, OMIM:616651
Intellectual disability v5.541 TRAIP Arina Puzriakova Phenotypes for gene: TRAIP were changed from Seckel syndrome 9, 616777 to Seckel syndrome 9, OMIM:616777
Intellectual disability v5.540 XRCC4 Arina Puzriakova Phenotypes for gene: XRCC4 were changed from PRIMORDIAL DWARFISM to Short stature, microcephaly, and endocrine dysfunction, OMIM:616541
Intellectual disability v5.539 CDC6 Arina Puzriakova Phenotypes for gene: CDC6 were changed from MEIER-GORLIN SYNDROME 5 to Meier-Gorlin syndrome 5, OMIM:613805
Intellectual disability v5.538 CDT1 Arina Puzriakova Phenotypes for gene: CDT1 were changed from MEIER-GORLIN SYNDROME 4 to Meier-Gorlin syndrome 4, OMIM:613804
Intellectual disability v5.537 ATR Arina Puzriakova Phenotypes for gene: ATR were changed from Seckel syndrome 1, 210600Cutaneous telangiectasia and cancer syndrome, familial, 614564; SECKEL SYNDROME TYPE 1 (SCKL1) to Seckel syndrome 1, OMIM:210600
Intellectual disability v5.536 FEM1B Zornitza Stark edited their review of gene: FEM1B: Added comment: Five individuals reported now with same recurrent missense variant, NM_015322.5:c.377G>A NP_056137.1:p.(Arg126Gln). Affected individuals shared a severe neurodevelopmental disorder with behavioral phenotypes and a variable set of malformations, including brain anomalies, clubfeet, skeletal abnormalities, and facial dysmorphism. Overexpression of the the FEM1BR126Q variant but not FEM1B wild-type protein, during mouse brain development, resulted in delayed neuronal migration of the target cells.; Changed rating: GREEN; Changed publications to: 31036916, 38465576; Changed phenotypes to: Syndromic disease MONDO:0002254, FEM1B-related
Intellectual disability v5.536 RNU4-2 Zornitza Stark gene: RNU4-2 was added
gene: RNU4-2 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: RNU4-2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RNU4-2 were set to 38645094
Phenotypes for gene: RNU4-2 were set to Neurodevelopmental disorder, MONDO:0700092, RNU4-2 related
Review for gene: RNU4-2 was set to GREEN
Added comment: Over 100 individuals reported with NND and heterozygous variants in a 18 bp region of RNU4-2 mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and Stem III). The vast majority of individuals (77.3%) have the same highly recurrent single base-pair insertion (n.64_65insT). Variants in this region likely explain 0.41% of individuals with NDD.
Sources: Literature
Intellectual disability v5.536 ACBD6 Arina Puzriakova Added comment: Comment on phenotypes: This gene now has a relevant phenotype listed in OMIM (MIM# 620785)
Intellectual disability v5.536 ACBD6 Arina Puzriakova Phenotypes for gene: ACBD6 were changed from Neurodevelopmental disorder, MONDO:0700092 to Neurodevelopmental disorder with progressive movement abnormalities, OMIM:620785
Intellectual disability v5.535 GLI3 Arina Puzriakova Tag Q2_24_demote_amber tag was added to gene: GLI3.
Tag Q2_24_NHS_review tag was added to gene: GLI3.
Intellectual disability v5.535 GLI3 Arina Puzriakova Phenotypes for gene: GLI3 were changed from Greig cephalopolysyndactyly syndrome, 175700Pallister-Hall syndrome, 146510Polydactyly, preaxial, type IV, 174700Polydactyly, postaxial, types A1 and B, 174200{Hypothalamic hamartomas, somatic}, 241800; GREIG CEPHALOPOLYSYNDACTYLY SYNDROME to Greig cephalopolysyndactyly syndrome, OMIM:175700; Pallister-Hall syndrome, OMIM:146510
Intellectual disability v5.534 GLI3 Arina Puzriakova Publications for gene: GLI3 were set to
Intellectual disability v5.533 GLI3 Arina Puzriakova Classified gene: GLI3 as Green List (high evidence)
Intellectual disability v5.533 GLI3 Arina Puzriakova Added comment: Comment on list classification: Reassessed in view of the Red review by Tracy Lester on this Green gene

Rarely, individuals with Greig cephalopolysyndactyly syndrome or GLI3-Related Pallister-Hall syndrome have been found to have intellectual disability (PMID: 12414818; 14708104; 14608643; 34296525). This is usually observed in the most severely affected individuals and those with large deletions encompassing GLI3. The majority of patients have normal psychomotor development or only some mild delays. All GLI3-related disorders are more likely to be recognised in context of other features such as skeletal abnormalities.

Overall, I therefore agree that this gene could be demoted to Amber at the next GMS panel update.
Intellectual disability v5.533 GLI3 Arina Puzriakova Gene: gli3 has been classified as Green List (High Evidence).
Intellectual disability v5.532 CPA6 Arina Puzriakova Tag refuted tag was added to gene: CPA6.
Intellectual disability v5.532 CPA6 Arina Puzriakova commented on gene: CPA6
Intellectual disability v5.532 KCNB2 Zornitza Stark gene: KCNB2 was added
gene: KCNB2 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: KCNB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNB2 were set to 38503299
Phenotypes for gene: KCNB2 were set to neurodevelopmental disorder MONDO:0700092, KCNB2-related
Review for gene: KCNB2 was set to GREEN
Added comment: 7 individuals, all missense
5 de novo + 1x inherited from father who has hypotonia + 1x from asymptomatic father

2/5 MRI anomalies
2/5 cardiac anomalies
2/7 urogenital anomalies
7/7 with ID
2/7 epilepsy
2/7 hypotonia
Sources: Literature
Intellectual disability v5.532 GTF3C5 Zornitza Stark gene: GTF3C5 was added
gene: GTF3C5 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: GTF3C5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTF3C5 were set to 38520561; 35503477
Phenotypes for gene: GTF3C5 were set to neurodevelopmental disorder MONDO:0700092, GTF3C5-related
Review for gene: GTF3C5 was set to GREEN
Added comment: 4 families/probands with syndromic ID. Loss of function is the expected mechanism.
PMID: 38520561 - Biallelic variants identified (3 missense & 1 stopgain) in 4 individuals from 3 families presenting with multisystem developmental syndrome including the features: growth retardation, developmental delay, intellectual disability, dental anomalies, cerebellar malformations, delayed bone age, skeletal anomalies, and facial dysmorphism. Gene-disease relationship supported by: reduced protein expression in patient cells, yeast assays, and a zebrafish model
PMID: 35503477 - 1 proband with biallelic missense variants and hypomelanosis of Ito, seizures, growth retardation, abnormal brain MRI, developmental delay, and facial dysmorphism
Sources: Literature
Intellectual disability v5.532 DOCK4 Zornitza Stark gene: DOCK4 was added
gene: DOCK4 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: DOCK4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DOCK4 were set to 38526744
Phenotypes for gene: DOCK4 were set to DOCK4-related neurodevelopmental disorder (MONDO:0060490)
Review for gene: DOCK4 was set to GREEN
Added comment: 7 unrelated individuals reported with heterozygous variants (missense or null variants) in DOCK4. The individuals either had ID or DD between mild and moderate with brain abnormalities. Two of the individuals are reportedly compound heterozygous.

Functional assay neuro-2A Dock4 knockout cells by using the Alt-R CRISPR-Cas9 system utilizing two different guide RNAs (ko1 and ko2) and one nonspecific control guide RNA (C: control). The assay depicted the loss of function mechanism in the presence of either p.Arg853Leu and p.Asp946_Lys1966delinsValSer* (described as 945VS).
Sources: Literature
Intellectual disability v5.532 PLXNB2 Zornitza Stark gene: PLXNB2 was added
gene: PLXNB2 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: PLXNB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLXNB2 were set to 38458752
Phenotypes for gene: PLXNB2 were set to Syndromic disease MONDO:0002254, PLXNB2 -related
Review for gene: PLXNB2 was set to GREEN
Added comment: 8 individuals from 6 families with core features of amelogenesis imperfecta and sensorineural hearing loss. Intellectual disability, ocular disease, ear developmental abnormalities and lymphoedema were also present in multiple cases. WES and WGS identified biallelic pathogenic variants in PLXNB2 (missense, nonsense, splice and a multiexon deletion variants). Variants segregated with disease.

PLXNB2 is a large transmembrane semaphorin receptor protein, and semaphorin-plexin signalling controls cellular interactions that are critical during development as well as in adult life stages. Plxnb2 expression was detected in differentiating ameloblasts in mice. Human phenotype overlaps with that seen in Plxnb2 knockout mice.
Sources: Literature
Intellectual disability v5.532 CEP295 Zornitza Stark edited their review of gene: CEP295: Changed rating: GREEN
Intellectual disability v5.532 CEP295 Zornitza Stark gene: CEP295 was added
gene: CEP295 was added to Intellectual disability - microarray and sequencing. Sources: Expert Review
Mode of inheritance for gene: CEP295 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP295 were set to 38154379
Phenotypes for gene: CEP295 were set to Seckel syndrome 11, OMIM # 620767
Added comment: 4 children from 2 unrelated families with Seckel-like syndrome - severe primary microcephaly, short stature, developmental delay, intellectual disability, facial deformities, and abnormalities of fingers and toes. WES identified biallelic pathogenic variants in CEP295 gene (p(Q544∗) and p(R1520∗); p(R55Efs∗49) and p(P562L)).

Patient-derived fibroblasts and CEP295-depleted U2OS and RPE1 cells were used to clarify the underlying mechanisms. Depletion of CEP295 resulted in a decrease in the numbers of centrioles and centrosomes and triggered p53-dependent G1 cell cycle arrest. Loss of CEP295 caused extensive primary ciliary defects in both patient-derived fibroblasts and RPE1 cells. The results from complementary experiments revealed that the wild-type CEP295, but not the mutant protein, can correct the developmental defects of the centrosome/centriole and cilia in the patient-derived skin fibroblasts.
Sources: Expert Review
Intellectual disability v5.532 SMAD3 Achchuthan Shanmugasundram changed review comment from: Two out of six cases with single nucleotide variants from DECIPHER database (https://www.deciphergenomics.org/gene/SMAD3/patient-overlap/snvs )were reported with global developmental delay. However, intellectual disability or global developmental delay were not reported as clinical presentations in patients with Loeys-Dietz syndrome 3 (MIM #613795).; to: Two out of six cases with single nucleotide variants from DECIPHER database (https://www.deciphergenomics.org/gene/SMAD3/patient-overlap/snvs) were reported with global developmental delay. However, intellectual disability or global developmental delay were not reported as clinical presentations in patients with Loeys-Dietz syndrome 3 (MIM #613795). Hence the rating should remain amber with current evidence.
Intellectual disability v5.532 SMAD3 Achchuthan Shanmugasundram reviewed gene: SMAD3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.532 ZFX Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has now been associated with phenotype in OMIM (MIM #301118), but not yet in Gene2Phenotype.
Intellectual disability v5.532 ZFX Achchuthan Shanmugasundram Phenotypes for gene: ZFX were changed from X-linked neurodevelopmental disorder with recurrent facial gestalt to Intellectual developmental disorder, X-linked syndromic 37, OMIM:301118
Intellectual disability v5.531 GAN Arina Puzriakova changed review comment from: Comment on list classification: Biallelic variants in the GAN gene cause giant axonal neuropathy, characterised by abnormalities in the peripheral and central nervous systems. Though extent of CNS involvement can vary, intellectual disability has been reported in at least 3 unrelated cases to date (PMID: 18595793; 19231187). Therefore, this gene should be promoted to Green at the next GMS panel update.; to: Comment on list classification: Biallelic variants in the GAN gene cause giant axonal neuropathy, characterised by abnormalities in the peripheral and central nervous systems. Though extent of CNS involvement can vary, intellectual disability has been reported in at least 3 unrelated cases (PMID: 18595793; 19231187). Therefore, this gene should be promoted to Green at the next GMS panel update.
Intellectual disability v5.531 GAN Arina Puzriakova Tag Q2_24_promote_green tag was added to gene: GAN.
Tag Q2_24_NHS_review tag was added to gene: GAN.
Intellectual disability v5.531 GAN Arina Puzriakova Publications for gene: GAN were set to
Intellectual disability v5.530 GAN Arina Puzriakova Classified gene: GAN as Amber List (moderate evidence)
Intellectual disability v5.530 GAN Arina Puzriakova Added comment: Comment on list classification: Biallelic variants in the GAN gene cause giant axonal neuropathy, characterised by abnormalities in the peripheral and central nervous systems. Though extent of CNS involvement can vary, intellectual disability has been reported in at least 3 unrelated cases to date (PMID: 18595793; 19231187). Therefore, this gene should be promoted to Green at the next GMS panel update.
Intellectual disability v5.530 GAN Arina Puzriakova Gene: gan has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.529 GAN Arina Puzriakova Mode of inheritance for gene: GAN was changed from to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.528 GAN Arina Puzriakova Phenotypes for gene: GAN were changed from to Giant axonal neuropathy-1, OMIM:256850
Intellectual disability v5.527 SEPHS1 Arina Puzriakova Classified gene: SEPHS1 as Amber List (moderate evidence)
Intellectual disability v5.527 SEPHS1 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.
Intellectual disability v5.527 SEPHS1 Arina Puzriakova Gene: sephs1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.526 SEPHS1 Arina Puzriakova Classified gene: SEPHS1 as Amber List (moderate evidence)
Intellectual disability v5.526 SEPHS1 Arina Puzriakova Gene: sephs1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.525 SEPHS1 Arina Puzriakova gene: SEPHS1 was added
gene: SEPHS1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Q2_24_promote_green tags were added to gene: SEPHS1.
Mode of inheritance for gene: SEPHS1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SEPHS1 were set to 38531365
Phenotypes for gene: SEPHS1 were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: SEPHS1 was set to GREEN
Added comment: Mullegama et al. (2024) reported 9 individuals from 8 families with developmental delay, growth and feeding problems, hypotonia, and dysmorphic features, all with heterozygous missense variants in SEPHS1. Eight individuals shared different missense variants at the same p.Arg371 residue in SEPHS1 (p.Arg371Trp, p.Arg371Gln, and p.Arg371Gly); seven of these variants were confirmed as de novo (one unknown). Functional studies showed that variants at the Arg371 residue impact direct protein-protein interactions of SEPSH1 and enhance cell proliferation by modulating ROS homeostasis.
Sources: Literature
Intellectual disability v5.524 ADA Arina Puzriakova Phenotypes for gene: ADA were changed from Severe combined immunodeficiency due to ADA deficiency, 102700; Adenosine deaminase deficiency, partial, 102700 to Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700
Intellectual disability v5.523 FRYL Arina Puzriakova Classified gene: FRYL as Amber List (moderate evidence)
Intellectual disability v5.523 FRYL Arina Puzriakova Added comment: Comment on list classification: Rating Amber as overall the evidence is borderline. Only one recent study (PMID:38479391) has reported an disease association for FRYL, with variable phenotypes and results from functional studies, as well as variants in other genes in several cases. Additional studies are required to conclusively corroborate causality (added watchlist tag).
Intellectual disability v5.523 FRYL Arina Puzriakova Gene: fryl has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.522 FRYL Arina Puzriakova gene: FRYL was added
gene: FRYL was added to Intellectual disability - microarray and sequencing. Sources: Literature
watchlist tags were added to gene: FRYL.
Mode of inheritance for gene: FRYL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FRYL were set to 38479391
Phenotypes for gene: FRYL were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: FRYL was set to AMBER
Added comment: New association linking this gene to disease which is not yet listed in OMIM or Gene2Phenotype. There are no sequence variants in Decipher and ClinVar shows only a single pathogenic frameshift variant (c.1224del, p.Lys409fs) for FRYL-associated neurodevelopmental disorder, amongst multiple SNVs which are mostly missense VUS or B/LB.

Pan et al., 2024 (PMID: 38479391) reported 14 individuals with heterozygous variant in FRYL who presented with DD/ID, dysmorphic features, and other congenital anomalies in multiple systems. Except for DD/ID which was the only universal feature, observed phenotypes were variable and nonspecific.

Variants were confirmed de novo in all except one individual (duo testing excluded paternal inheritance although it was present at low frequency in gnomAD). Variant types include missense (5), fs/stop-gain (8) and canonical splice (1). Modelling 4/5 patient missense variants using flies showed that only one serves as a severe LoF variant, two others behave as partial LoF variants, and one variant had no functional impact (only variant not confirmed as de novo indicating this is a VUS). Four individuals also had P/LP variants in other genes (SF3B4, DHCR7, SLC6A19, SDHA) which could at least partially explain their phenotypes, and a further four harboured additional VUSs.
Sources: Literature
Intellectual disability v5.521 DENND5B Sarah Leigh Classified gene: DENND5B as Amber List (moderate evidence)
Intellectual disability v5.521 DENND5B 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 v5.521 DENND5B Sarah Leigh Gene: dennd5b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.520 DENND5B Sarah Leigh Tag Q2_24_promote_green tag was added to gene: DENND5B.
Tag Q2_24_NHS_review tag was added to gene: DENND5B.
Intellectual disability v5.520 DENND5B Sarah Leigh gene: DENND5B was added
gene: DENND5B was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: DENND5B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: DENND5B were set to 38387458
Phenotypes for gene: DENND5B were set to DENND5B associated neurodevelopmental disorder
Review for gene: DENND5B was set to GREEN
Added comment: DENND5B variants have not previously been associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 38387458 reports five de novo missense variants in five unrelated cases. The carriers of these DENND5B variants have a neurodevelopmental disorder, which is characterized by psychomotor delay (5/5 cases), intellectual disability, ranging from severe to mild (3/5 cases, although one of the negative cases was a 2 year old child, who was considered to be too young to make the assessment, although the DD/intellectual disability phenotype was considered to be moderate in this case), epilepsy (2/5 cases) and hypotonia (4/5 cases). The authors of PMID: 38387458 also report the functional effects of the DENND5B variants, which revealed defective intracellular vesicle trafficking, with significant impairment of lipid uptake and distribution. They conclude that this effect is likely to be caused by the predicted disruption of protein folding in the variant DENND5B peptide.
Sources: Literature
Intellectual disability v5.519 TBC1D2B Sarah Leigh Tag watchlist was removed from gene: TBC1D2B.
Tag Q2_24_promote_green tag was added to gene: TBC1D2B.
Tag Q2_24_NHS_review tag was added to gene: TBC1D2B.
Intellectual disability v5.519 TBC1D2B Sarah Leigh Classified gene: TBC1D2B as Amber List (moderate evidence)
Intellectual disability v5.519 TBC1D2B 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 v5.519 TBC1D2B Sarah Leigh Gene: tbc1d2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.518 TBC1D2B Sarah Leigh reviewed gene: TBC1D2B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v5.518 TBC1D2B Sarah Leigh Publications for gene: TBC1D2B were set to 32623794
Intellectual disability v5.517 TBC1D2B Sarah Leigh Phenotypes for gene: TBC1D2B were changed from Global developmental delay; Intellectual disability; Seizures; Gingival overgrowth; Behavioral abnormality; Abnormality of the mandible; Abnormality of brain morphology; Abnormality of the eye; Hearing abnormality to Neurodevelopmental disorder with seizures and gingival overgrowth, OMIM:619323; neurodevelopmental disorder with seizures and gingival overgrowth, MONDO:0859148
Intellectual disability v5.515 ASCC3 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a relevant phenotype listed in OMIM (Intellectual developmental disorder, autosomal recessive 81, OMIM:620700)
Intellectual disability v5.515 ASCC3 Arina Puzriakova Phenotypes for gene: ASCC3 were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION to Intellectual developmental disorder, autosomal recessive 81, OMIM:620700
Intellectual disability v5.514 ASCC3 Arina Puzriakova Tag gene-checked was removed from gene: ASCC3.
Intellectual disability v5.514 PTRHD1 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a relevant phenotype listed in OMIM (Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities, OMIM:620747)
Intellectual disability v5.514 PTRHD1 Arina Puzriakova Phenotypes for gene: PTRHD1 were changed from Intellectual disability; Parkinsonism to Neurodevelopmental disorder with early-onset parkinsonism and behavioral abnormalities, OMIM:620747
Intellectual disability v5.513 PTRHD1 Arina Puzriakova Tag gene-checked was removed from gene: PTRHD1.
Intellectual disability v5.513 SLC32A1 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a relevant phenotype listed in OMIM (Developmental and epileptic encephalopathy 114, OMIM:620774)
Intellectual disability v5.513 SLC32A1 Arina Puzriakova Phenotypes for gene: SLC32A1 were changed from developmental and epileptic encephalopathy, MONDO:0100062 to Developmental and epileptic encephalopathy 114, OMIM:620774
Intellectual disability v5.512 SLC32A1 Arina Puzriakova Tag gene-checked was removed from gene: SLC32A1.
Intellectual disability v5.512 BRD4 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a phenotype listed in OMIM (Cornelia de Lange syndrome 6, OMIM:620568)
Intellectual disability v5.512 BRD4 Arina Puzriakova Phenotypes for gene: BRD4 were changed from Intellectual disability; Microcephaly; Abnormal heart morphology; Abnormality of the face to Cornelia de Lange syndrome 6, OMIM:620568
Intellectual disability v5.511 BRD4 Arina Puzriakova Tag gene-checked was removed from gene: BRD4.
Intellectual disability v5.511 CAPRIN1 Arina Puzriakova Publications for gene: CAPRIN1 were set to 23849776; 35979925; 36136249
Intellectual disability v5.510 CAPRIN1 Arina Puzriakova Added comment: Comment on phenotypes: Gene-checked tag removed as this gene now has a phenotype listed in OMIM (Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, OMIM:620636)
Intellectual disability v5.510 CAPRIN1 Arina Puzriakova Phenotypes for gene: CAPRIN1 were changed from Global developmental delay; Delayed speech and language development; Intellectual disability; Autistic behaviour; Seizures to Neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline, OMIM:620636
Intellectual disability v5.509 CAPRIN1 Arina Puzriakova Tag gene-checked was removed from gene: CAPRIN1.
Intellectual disability v5.509 WNK3 Arina Puzriakova Phenotypes for gene: WNK3 were changed from X-linked intellectual disability, MONDO:0100284 to Prieto syndrome, OMIM:309610; Intellectual disability, MONDO:0001071
Intellectual disability v5.508 WNK3 Arina Puzriakova Tag gene-checked was removed from gene: WNK3.
Intellectual disability v5.508 C12orf4 Arina Puzriakova Phenotypes for gene: C12orf4 were changed from Autosomal recessive intellectual disability to Intellectual developmental disorder, autosomal recessive 66, OMIM:618221
Intellectual disability v5.507 C12orf4 Arina Puzriakova commented on gene: C12orf4
Intellectual disability v5.507 C12orf4 Arina Puzriakova Tag new-gene-name tag was added to gene: C12orf4.
Intellectual disability v5.507 IKBKG Arina Puzriakova Phenotypes for gene: IKBKG were changed from Incontinentia pigmenti, type II, 308300Ectodermal dysplasia, hypohidrotic, with immune deficiency, 300291Ectodermal, dysplasia, anhidrotic, lymphedema and immunodeficiency, 300301Immunodeficiency, isolated, 300584{Atypical mycobacteriosis, familial}, 300636Invasive pneumococcal disease, recurrent isolated, 2, 300640; INCONTINENTIA PIGMENTI (IP) to Incontinentia pigmenti, OMIM:308300
Intellectual disability v5.506 ZFX Tracy Lester reviewed gene: ZFX: Rating: GREEN; Mode of pathogenicity: None; Publications: 38325380; Phenotypes: Intellectual disability, developmental delay, behavioural abnormalities, hypotonia, dysmorphic facies; 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 v5.506 CLEC16A Arina Puzriakova Tag Q1_24_promote_green tag was added to gene: CLEC16A.
Intellectual disability v5.506 GLI3 Tracy Lester reviewed gene: GLI3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v5.506 SRCAP Arina Puzriakova Phenotypes for gene: SRCAP were changed from Floating-Harbor syndrome, 136140; FLOATING-HARBOR SYNDROME to Developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities, OMIM:619595; Floating-Harbor syndrome, OMIM:136140
Intellectual disability v5.505 ABHD5 Arina Puzriakova Phenotypes for gene: ABHD5 were changed from Chanarin-Dorfman syndrome, 275630; CHANARIN-DORFMAN SYNDROME (CDS) to Chanarin-Dorfman syndrome, OMIM:275630
Intellectual disability v5.504 STAMBP Arina Puzriakova Phenotypes for gene: STAMBP were changed from MICROCEPHALY CAPILLARY MALFORMATION (MIC-CAP) SYNDROME to Microcephaly-capillary malformation syndrome, OMIM:614261
Intellectual disability v5.503 PIK3R2 Arina Puzriakova Phenotypes for gene: PIK3R2 were changed from Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome, 603387; MEGALENCEPHALY-POLYMICROGYRIA-POLYDACTYLY-HYDROCEPHALUS SYNDROME 1 to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, OMIM:603387
Intellectual disability v5.502 ROBO1 Arina Puzriakova Tag watchlist_moi tag was added to gene: ROBO1.
Intellectual disability v5.502 CLEC16A Sarah Leigh edited their review of gene: CLEC16A: Added comment: Heterozygous CLEC16A variants have been identified as a genetic risk factor for several autoimmune disorders and for Parkinson disease (PMID: 37175930). PMID: 36538041 reports the neurological effect of homozygous terminating CLEC16A variants in two families. In family 1, the first child died at 5 months, he had progressive microcephaly, failure to thrive and cranial CT showed brain atrophy, dilatation of both central and peripheral liquor spaces, hypoplasia of the corpus callosum (no genetic testing was done), the third pregnancy was terminated (17 weeks of gestation) after prenatal ultrasound showed ventriculomegaly, agenesis of corpus callosum (no genetic testing was done), the fourth pregnancy was also terminated (22 weeks of gestation) as the prenatal ultrasound showed agenesis of corpus callosum. This fetus was homozygous for NM_001243403.1(CLEC16A):c.2062 + 5G > A, RT-PRC showed that this variant resulted in the deletion of exon 19 and a frame shift. Both parents and an unaffected sibling were heterozygous for this variant. In family 2, a single affected child was homozygous for NM_001243403.1(CLEC16A):c.-4_12del, p.Met1fs*. This child had progressive microcephaly, failure to thrive, severe global developmental delay, global brain atrophy and died at 6 years. There is no genetic data from the parents or unaffected siblings in Family 2. PMID: 37175930, also presents zebrafish experiments, where mutagenesis of
clec16a by CRISPR–Cas9 resulted in accumulated acidic/phagolysosome compartments, in neurons
and microglia, and dysregulated mitophagy. This was rescued by wild type CLEC16A, but not by the C-terminal truncated variant. The authors conclude that dysregulation of CLEC16A-mediated endosomal sorting is associated with neurodegeneration.; Changed rating: GREEN; Changed publications to: 36538041; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.502 CLEC16A Sarah Leigh Classified gene: CLEC16A as Amber List (moderate evidence)
Intellectual disability v5.502 CLEC16A Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be green on this panel.
Intellectual disability v5.502 CLEC16A Sarah Leigh Gene: clec16a has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.501 CLEC16A Sarah Leigh Publications for gene: CLEC16A were set to 36538041
Intellectual disability v5.500 CLEC16A Sarah Leigh Publications for gene: CLEC16A were set to PMID: 36538041
Intellectual disability v5.500 CLEC16A Sarah Leigh Classified gene: CLEC16A as Amber List (moderate evidence)
Intellectual disability v5.500 CLEC16A Sarah Leigh Gene: clec16a has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.499 ZFHX3 Sarah Leigh edited their review of gene: ZFHX3: Added comment: Personal communication from Nour Elkhateeb (Clinical Fellow in Genomics, Genomics England): we have data about 12 individuals with nonsense/frameshift/exon deletions in ZFHX3. Five of the variants are located in exon 9/10 or exon 9, which has been shown to harbour the highest density of pathogenic variants (PMID: 38412861). Eleven of these cases presented with developmental delay / intellectual disability and a range of other features, including dysmorphology, seizures and failure to thrive.; Changed publications to: 38412861
Intellectual disability v5.499 ZFHX3 Sarah Leigh Tag Q1_24_promote_green tag was added to gene: ZFHX3.
Tag Q1_24_NHS_review tag was added to gene: ZFHX3.
Intellectual disability v5.499 ZFHX3 Sarah Leigh reviewed gene: ZFHX3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v5.499 ZFHX3 Sarah Leigh Classified gene: ZFHX3 as Amber List (moderate evidence)
Intellectual disability v5.499 ZFHX3 Sarah Leigh Gene: zfhx3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.498 ZFHX3 Sarah Leigh gene: ZFHX3 was added
gene: ZFHX3 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: ZFHX3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ZFHX3 were set to 38412861; 38035881; 37292950
Phenotypes for gene: ZFHX3 were set to syndromic intellectual disability
Intellectual disability v5.497 SOX9 Tracy Lester reviewed gene: SOX9: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Skeletal dysplasia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.497 SPATA5 Arina Puzriakova Phenotypes for gene: SPATA5 were changed from Epilepsy, hearing loss, and mental retardation syndrome, 616577 to Neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities, OMIM:616577
Intellectual disability v5.496 SNF8 Achchuthan Shanmugasundram Classified gene: SNF8 as Amber List (moderate evidence)
Intellectual disability v5.496 SNF8 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are three unrelated cases with intellectual disability and hence this gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.496 SNF8 Achchuthan Shanmugasundram Gene: snf8 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.495 SNF8 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: SNF8.
Intellectual disability v5.495 SNF8 Achchuthan Shanmugasundram changed review comment from: PMID:38423010 reported nine individuals from six families presenting with a spectrum of neurodevelopmental/ neurodegenerative features caused by biallelic variants in SNF8. The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy with leukoencephalopathy and early death in three of those cases. Two individuals died too young to develop epilepsy. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous. Functional studies using fibroblasts derived from patients and zebrafish model showed loss of function as the disease mechanism.
Sources: Literature; to: PMID:38423010 reported nine individuals from six families presenting with a spectrum of neurodevelopmental/ neurodegenerative features caused by biallelic variants in SNF8.

The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy with leukoencephalopathy and early death in three of those cases. Two individuals died too young to develop epilepsy. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous.

Functional studies using fibroblasts derived from patients and zebrafish model showed loss of function as the disease mechanism.

This gene has not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.495 SNF8 Achchuthan Shanmugasundram gene: SNF8 was added
gene: SNF8 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: SNF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNF8 were set to 38423010
Phenotypes for gene: SNF8 were set to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Review for gene: SNF8 was set to GREEN
Added comment: PMID:38423010 reported nine individuals from six families presenting with a spectrum of neurodevelopmental/ neurodegenerative features caused by biallelic variants in SNF8. The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy with leukoencephalopathy and early death in three of those cases. Two individuals died too young to develop epilepsy. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous. Functional studies using fibroblasts derived from patients and zebrafish model showed loss of function as the disease mechanism.
Sources: Literature
Intellectual disability v5.494 CCBE1 Arina Puzriakova Phenotypes for gene: CCBE1 were changed from Hennekam lymphangiectasia-lymphedema syndrome, 235510; HENNEKAM LYMPHANGIECTASIA-LYMPHEDEMA SYNDROME (HLLS) to Hennekam lymphangiectasia-lymphedema syndrome 1, OMIM:235510
Intellectual disability v5.493 DYNC2H1 Arina Puzriakova commented on gene: DYNC2H1: - PMID: 22589734 (2012) - A 29 Mb deletion encompassing DYNC2H1 was found in one patient with syndromic hirschsprung disease which included moderate mental retardation, mild hydrocephalus, microcephaly, cardiomyopathy and congenital hypotonia. Other candidate genes in this region include CNTN5 and CARD17. Skeletal findings that are typical for DYNC2H1 are not reported.

Comment on publications: PMID: 22589734 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques
Intellectual disability v5.493 DYNC2H1 Arina Puzriakova Publications for gene: DYNC2H1 were set to
Intellectual disability v5.492 ZNFX1 Sarah Leigh Tag Q1_24_promote_green tag was added to gene: ZNFX1.
Tag Q1_24_NHS_review tag was added to gene: ZNFX1.
Intellectual disability v5.492 ZNFX1 Sarah Leigh Classified gene: ZNFX1 as Amber List (moderate evidence)
Intellectual disability v5.492 ZNFX1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be green on this panel.
Intellectual disability v5.492 ZNFX1 Sarah Leigh Gene: znfx1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.491 ZNFX1 Sarah Leigh edited their review of gene: ZNFX1: Added comment: ZNFX1 variants are associated with Immunodeficiency 91 and hyperinflammation (OMIM:619644). Neurological involvement has been observed in at least 11 patients with OMIM:619644 (PMID:33876776;33872655). Of these, four had seizures, three had developmental regression, and one had developmental delay. The incidence of neurological involvement could be higher, but the mortality of affected children is high; in PMID:33872655 11/15 cases were deceased, with seven of these not surviving to 3 months of age.; Changed rating: GREEN
Intellectual disability v5.491 ZNFX1 Sarah Leigh gene: ZNFX1 was added
gene: ZNFX1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: ZNFX1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNFX1 were set to 33876776; 33872655
Phenotypes for gene: ZNFX1 were set to Immunodeficiency 91 and hyperinflammation, OMIM:619644; immunodeficiency 91 and hyperinflammation, MONDO:0030491
Review for gene: ZNFX1 was set to AMBER
Added comment: Sources: Literature
Intellectual disability v5.490 SRPX2 Arina Puzriakova Phenotypes for gene: SRPX2 were changed from Rolandic epilepsy, mental retardation, and speech dyspraxia, 300643 -3; ROLANDIC EPILEPSY WITH SPEECH DYSPRAXIA AND MENTAL RETARDATION X-LINKED (RESDX) to ?Rolandic epilepsy, impaired intellectual development, and speech dyspraxia, OMIM:300643
Intellectual disability v5.489 SMARCAL1 Arina Puzriakova Phenotypes for gene: SMARCAL1 were changed from Gene2Phenotype confirmed gene with ID HPO to Schimke immunoosseous dysplasia, OMIM:242900
Intellectual disability v5.488 SMARCAL1 Arina Puzriakova Publications for gene: SMARCAL1 were set to
Intellectual disability v5.487 SMARCAL1 Arina Puzriakova edited their review of gene: SMARCAL1: Changed phenotypes to: Schimke immunoosseous dysplasia, OMIM:242900
Intellectual disability v5.487 SMARCAL1 Arina Puzriakova reviewed gene: SMARCAL1: Rating: ; Mode of pathogenicity: None; Publications: 28796785, 20301550; Phenotypes: ; Mode of inheritance: None
Intellectual disability v5.487 ZFX Sarah Leigh changed review comment from: A single ZFX variant has been associated with a neurodevelopmental disorder, that has a Rett syndrome-like phenotype disorder, in a 14 year old male. The ZFX variant was allelic with another X-linked variant in SHROOM4. These variants were inherited from the mother, who had random X inactivation pattern (PMID: 26740508).
PMID: 38325380 reports 11 ZFX variants in 18 subjects from 16 unrelated families (14 males and 4 females) with an X-linked neurodevelopmental disorder with recurrent facial gestalt. Seven variants were truncating and the remaining were missense variants within the Zinc finger array. In the pedigree of family 6 (figure 3, PMID: 38325380), it was apparent that there were female carriers of the ZFX variant (GRCh38 chrX: 24229396A>G, c.2438A>G, p.Tyr774Cys) with hyperparathyroidism and two affected males and one affected female, with the neurodevelopmental disorder. It appeared that skewed X-inactivation in the female carriers was responsible for the different phenotypic features. The association between ZFX variants and a novel neurodevelopmental disorder, was further supported by functional studies showing altered transcriptional activity in missense variants and altered behavior in a zebrafish loss-of-function model.; to: To date, germline variants in ZFX have not been associated with a phenotype in OMIM or Gen2Phen.
A single ZFX variant has been associated with a neurodevelopmental disorder, that has a Rett syndrome-like phenotype disorder, in a 14 year old male. The ZFX variant was allelic with another X-linked variant in SHROOM4. These variants were inherited from the mother, who had random X inactivation pattern (PMID: 26740508).
PMID: 38325380 reports 11 ZFX variants in 18 subjects from 16 unrelated families (14 males and 4 females) with an X-linked neurodevelopmental disorder with recurrent facial gestalt. Seven variants were truncating and the remaining were missense variants within the Zinc finger array. In the pedigree of family 6 (figure 3, PMID: 38325380), it was apparent that there were female carriers of the ZFX variant (GRCh38 chrX: 24229396A>G, c.2438A>G, p.Tyr774Cys) with hyperparathyroidism and two affected males and one affected female, with the neurodevelopmental disorder. It appeared that skewed X-inactivation in the female carriers was responsible for the different phenotypic features. The association between ZFX variants and a novel neurodevelopmental disorder, was further supported by functional studies showing altered transcriptional activity in missense variants and altered behavior in a zebrafish loss-of-function model.
Intellectual disability v5.487 ZFX Sarah Leigh Phenotypes for gene: ZFX were changed from to X-linked neurodevelopmental disorder with recurrent facial gestalt
Intellectual disability v5.486 ZFX Sarah Leigh Publications for gene: ZFX were set to 26350204; 26740508
Intellectual disability v5.486 ZFX Sarah Leigh Classified gene: ZFX as Amber List (moderate evidence)
Intellectual disability v5.486 ZFX Sarah Leigh Added comment: Comment on list classification: There is sufficient evidence for this gene to be green on this panel.
Intellectual disability v5.486 ZFX Sarah Leigh Gene: zfx has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.485 ZFX Sarah Leigh Tag Q1_24_promote_green tag was added to gene: ZFX.
Tag Q1_24_NHS_review tag was added to gene: ZFX.
Intellectual disability v5.485 ZFX Sarah Leigh reviewed gene: ZFX: Rating: GREEN; Mode of pathogenicity: None; Publications: 38325380; Phenotypes: X-linked neurodevelopmental disorder with recurrent facial gestalt; 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 v5.485 AFF2 Arina Puzriakova Phenotypes for gene: AFF2 were changed from Mental retardation, X-linked, FRAXE type, 309548; FRAXE Syndrome; FRAGILE X-E MENTAL RETARDATION SYNDROME (FRAXE) to Intellectual developmental disorder, X-linked 109, OMIM:309548; Fragile XE syndrome (FRAXE)
Intellectual disability v5.484 PPP2R2B Arina Puzriakova Publications for gene: PPP2R2B were set to
Intellectual disability v5.483 PPP2R2B Arina Puzriakova edited their review of gene: PPP2R2B: Added comment: - PMID: 25356899 (2014) - missense variant (c.413G>C, p.Arg138Pro) in the PPP2R2B gene identified in a 7-year-old boy with moderate ID, intractable seizures and autistic features. Otherwise limited information provided.

Comment on publications: PMID: 25356899 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques; Changed publications to: 25356899; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.483 NXF5 Arina Puzriakova Classified gene: NXF5 as Red List (low evidence)
Intellectual disability v5.483 NXF5 Arina Puzriakova Added comment: Comment on list classification: Maintaining Red rating as evidence linking this gene to ID is not definitive since patient variants have involved multiple genes and no cases of SNVs in the NXF5 gene have been reported.
Intellectual disability v5.483 NXF5 Arina Puzriakova Gene: nxf5 has been classified as Red List (Low Evidence).
Intellectual disability v5.482 NXF5 Arina Puzriakova Added comment: Comment on publications: PMID: 23675524 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques
Intellectual disability v5.482 NXF5 Arina Puzriakova Publications for gene: NXF5 were set to 11566096; 26350204; 23675524; 22030050; 20096387
Intellectual disability v5.481 NXF5 Arina Puzriakova Publications for gene: NXF5 were set to 11566096; 26350204; 23675524; 22030050
Intellectual disability v5.480 NXF5 Arina Puzriakova reviewed gene: NXF5: Rating: ; Mode of pathogenicity: None; Publications: 11566096, 20096387, 22030050, 23675524; Phenotypes: ; Mode of inheritance: None
Intellectual disability v5.480 NHEJ1 Arina Puzriakova Phenotypes for gene: NHEJ1 were changed from Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation to Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, OMIM:611291
Intellectual disability v5.479 KIRREL3 Arina Puzriakova Added comment: Comment on publications: New publication added - PMID:25902260. This paper was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques

Provides review of cases in literature and functional studies demonstrating brain expressed proteins that interact with the KIRREL3 using yeast two-hybrid screening supporting a link to neurological and cognitive disorders. They also show KIRREL3 localisation to the Golgi complex and synaptic secretary vesicles.
Intellectual disability v5.479 KIRREL3 Arina Puzriakova Publications for gene: KIRREL3 were set to 22965935; 19012874; 29271092; 37605258; 33853164
Intellectual disability v5.478 KIF26B Arina Puzriakova Phenotypes for gene: KIF26B were changed from to Progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis
Intellectual disability v5.477 INTS1 Arina Puzriakova Phenotypes for gene: INTS1 were changed from Neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies, 618571; Hypotonia; Global developmental delay; Cataract; Abnormality of the skeletal system to Neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies, OMIM:618571
Intellectual disability v5.476 INTS1 Arina Puzriakova Publications for gene: INTS1 were set to 28542170; 30622326; 17544522
Intellectual disability v5.475 INTS8 Arina Puzriakova Phenotypes for gene: INTS8 were changed from to ?Neurodevelopmental disorder with cerebellar hypoplasia and spasticity, OMIM:618572
Intellectual disability v5.474 EFNB1 Arina Puzriakova Classified gene: EFNB1 as Amber List (moderate evidence)
Intellectual disability v5.474 EFNB1 Arina Puzriakova Added comment: Comment on list classification: Upgrading from Red to Amber as a literature search did reveal evidence to suggest that some individuals may develop intellectual deficits. However, in most affected cases this was a mild presentation and there are more prominent and recognisable features observed in the general group of EFNB1-related cases which are more likely to inform diagnostic testing (e.g. craniosynostosis and clefting).
Intellectual disability v5.474 EFNB1 Arina Puzriakova Gene: efnb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.473 EFNB1 Arina Puzriakova Added comment: Comment on publications: PMID: 25679214 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques
Intellectual disability v5.473 EFNB1 Arina Puzriakova Publications for gene: EFNB1 were set to 23335590
Intellectual disability v5.472 EFNB1 Arina Puzriakova reviewed gene: EFNB1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23335590, 25679214, 27650623, 31088393, 24520368; Phenotypes: Craniofrontonasal dysplasia, OMIM:304110; 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 v5.472 EFNB1 Arina Puzriakova Phenotypes for gene: EFNB1 were changed from Gene2Phenotype confirmed gene with ID HPO to Craniofrontonasal dysplasia, OMIM:304110
Intellectual disability v5.471 EFNB1 Arina Puzriakova Publications for gene: EFNB1 were set to
Intellectual disability v5.470 DYNC2H1 Arina Puzriakova Phenotypes for gene: DYNC2H1 were changed from Short-rib thoracic dysplasia 3 with or without polydactyly, 613091 to Short-rib thoracic dysplasia 3 with or without polydactyly, OMIM:613091
Intellectual disability v5.469 KCNA1 Achchuthan Shanmugasundram Phenotypes for gene: KCNA1 were changed from Episodic ataxia/myokymia syndrome, OMIM:160120 to Episodic ataxia/myokymia syndrome, OMIM:160120
Intellectual disability v5.469 KCNA1 Achchuthan Shanmugasundram Phenotypes for gene: KCNA1 were changed from Episodic ataxia/myokymia syndrome, 160120 to Episodic ataxia/myokymia syndrome, OMIM:160120
Intellectual disability v5.468 KCNA1 Achchuthan Shanmugasundram Publications for gene: KCNA1 were set to 27730449; 30055040; 34778950
Intellectual disability v5.468 KCNA1 Achchuthan Shanmugasundram Publications for gene: KCNA1 were set to 27730449
Intellectual disability v5.467 KCNA1 Achchuthan Shanmugasundram Mode of inheritance for gene: KCNA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.466 KCNA1 Achchuthan Shanmugasundram Classified gene: KCNA1 as Amber List (moderate evidence)
Intellectual disability v5.466 KCNA1 Achchuthan Shanmugasundram Gene: kcna1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.465 KCNA1 Achchuthan Shanmugasundram reviewed gene: KCNA1: Rating: AMBER; Mode of pathogenicity: None; Publications: 30055040, 34778950; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.465 CTNND2 Arina Puzriakova commented on gene: CTNND2
Intellectual disability v5.465 CTNND2 Arina Puzriakova Phenotypes for gene: CTNND2 were changed from to CTNND2-related neurodevelopmental disorder
Intellectual disability v5.464 CTNND2 Arina Puzriakova Mode of inheritance for gene: CTNND2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v5.463 CLIC2 Arina Puzriakova Tag disputed tag was added to gene: CLIC2.
Intellectual disability v5.463 CLIC2 Arina Puzriakova Phenotypes for gene: CLIC2 were changed from Intellectual developmental disorder, X-linked syndromic 32 , OMIM:300886 to Intellectual developmental disorder, X-linked syndromic 32, OMIM:300886
Intellectual disability v5.462 CLIC2 Arina Puzriakova Phenotypes for gene: CLIC2 were changed from Mental retardation, X-linked, syndromic 32, 300886 to Intellectual developmental disorder, X-linked syndromic 32 , OMIM:300886
Intellectual disability v5.461 ARHGEF6 Arina Puzriakova changed review comment from: PMID: 22511880 (2012) - a variant in the ARHGEF6 gene (p.I444N) was identified in a male patient with autism. However, this individual harboured variants in other genes (UBE3B) that were likely to explain their phenotype so conclusions about the consequence of the ARHGEF6 variant cannot be made in this case.

Comment on publications: PMID: 22511880 (2012) was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques; to: PMID: 22511880 (2012) - a variant in the ARHGEF6 gene (p.I444N) was identified in a male patient with autism. However, this individual harboured variants in other genes (UBE3B) that were likely to explain their phenotype so conclusions about the consequence of the ARHGEF6 variant cannot be made in this case.

Comment on publications: PMIDs: 22511880 (2012) and 26177020 (2015) were identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques
Intellectual disability v5.461 ARHGEF6 Arina Puzriakova Publications for gene: ARHGEF6 were set to 21989057; 20861843; 17304053; 11017088; 26177020; 22511880
Intellectual disability v5.461 ARHGEF6 Arina Puzriakova Publications for gene: ARHGEF6 were set to 21989057; 20861843; 17304053; 11017088; 26177020
Intellectual disability v5.460 ARHGEF6 Arina Puzriakova commented on gene: ARHGEF6: PMID: 22511880 (2012) - a variant in the ARHGEF6 gene (p.I444N) was identified in a male patient with autism. However, this individual harboured variants in other genes (UBE3B) that were likely to explain their phenotype so conclusions about the consequence of the ARHGEF6 variant cannot be made in this case.

Comment on publications: PMID: 22511880 (2012) was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques
Intellectual disability v5.460 ARHGEF6 Arina Puzriakova Publications for gene: ARHGEF6 were set to 21989057; 20861843; 17304053; 11017088
Intellectual disability v5.459 ARHGEF6 Arina Puzriakova Phenotypes for gene: ARHGEF6 were changed from Mental retardation, X-linked 46, 300436; Mental Retardation, X-linked; MENTAL RETARDATION X-LINKED TYPE 46 to Intellectual developmental disorder, X-linked 46, OMIM:300436
Intellectual disability v5.458 CAMSAP1 Achchuthan Shanmugasundram Classified gene: CAMSAP1 as Amber List (moderate evidence)
Intellectual disability v5.458 CAMSAP1 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 v5.458 CAMSAP1 Achchuthan Shanmugasundram Gene: camsap1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.457 CAMSAP1 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: CAMSAP1.
Intellectual disability v5.457 CAMSAP1 Achchuthan Shanmugasundram gene: CAMSAP1 was added
gene: CAMSAP1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: CAMSAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAMSAP1 were set to 36283405
Phenotypes for gene: CAMSAP1 were set to Cortical dysplasia, complex, with other brain malformations 12, OMIM:620316
Review for gene: CAMSAP1 was set to GREEN
Added comment: Seven children from five unrelated families were identified with either homozygous or compound heterozygous CAMSAP1 variants and were reported with a severe neurodevelopmental disorder apparent from infancy. Clinical features of the syndrome include a characteristic craniofacial appearance, primary microcephaly, lissencephaly, agenesis or severe hypogenesis of the corpus callosum, severe or profound global developmental delay, cortical visual impairment, and seizures.

This gene has been associated with relevant phenotypes in both OMIM (MIM #620316) and in Gene2Phenotype (with 'moderate' rating in the DD panel).
Sources: Literature
Intellectual disability v5.456 BAZ2B Achchuthan Shanmugasundram Classified gene: BAZ2B as Amber List (moderate evidence)
Intellectual disability v5.456 BAZ2B 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 v5.456 BAZ2B Achchuthan Shanmugasundram Gene: baz2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.455 BAZ2B Achchuthan Shanmugasundram Phenotypes for gene: BAZ2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.455 BAZ2B Achchuthan Shanmugasundram Phenotypes for gene: BAZ2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.455 BAZ2B Achchuthan Shanmugasundram Phenotypes for gene: BAZ2B were changed from developmental delay, intellectual disability and autism spectrum disorder to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.454 BAZ2B Achchuthan Shanmugasundram Publications for gene: BAZ2B were set to 31999386; 37872713
Intellectual disability v5.454 BAZ2B Achchuthan Shanmugasundram Publications for gene: BAZ2B were set to 31999386; 37872713
Intellectual disability v5.454 BAZ2B Achchuthan Shanmugasundram Publications for gene: BAZ2B were set to PMID: 31999386
Intellectual disability v5.453 BAZ2B Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: BAZ2B.
Intellectual disability v5.453 BAZ2B Achchuthan Shanmugasundram reviewed gene: BAZ2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 37872713; Phenotypes: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.453 KCNA1 Tracy Lester reviewed gene: KCNA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30055040, 34778950; Phenotypes: epileptic encephalopathy, ataxia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.453 LRRC32 Achchuthan Shanmugasundram Classified gene: LRRC32 as Amber List (moderate evidence)
Intellectual disability v5.453 LRRC32 Achchuthan Shanmugasundram Gene: lrrc32 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.452 LRRC32 Achchuthan Shanmugasundram Publications for gene: LRRC32 were set to 30976112
Intellectual disability v5.451 LRRC32 Achchuthan Shanmugasundram reviewed gene: LRRC32: Rating: AMBER; Mode of pathogenicity: None; Publications: 30976112, 35656379; Phenotypes: Cleft palate, proliferative retinopathy, and developmental delay, OMIM:619074; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.451 ACBD6 Jana Jezkova reviewed gene: ACBD6: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 37951597; Phenotypes: HP:0001263, HP:0001249; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.451 MADD Sarah Leigh Phenotypes for gene: MADD were changed from Neurodevelopmental disorder with dysmorphic facies, impaired speech and hypotonia, 619005; DEEAH syndrome, 619004 to DEEAH syndrome, OMIM:619004; deeah syndrome, MONDO:0033561: Neurodevelopmental disorder with dysmorphic facies, impaired speech and hypotonia, OMIM:619005; neurodevelopmental disorder with dysmorphic facies, impaired speech, and hypotonia, MONDO:0033562
Intellectual disability v5.450 DHX37 Sarah Leigh changed review comment from: Comment on mode of inheritance: The mode of inheritance for DHX37 on the Intellectual disability panel should be biallelic as monoallelic variant have not been associated with intellectual disability.; to: Comment on mode of inheritance: The mode of inheritance for DHX37 on the Intellectual disability panel should be biallelic as monoallelic variants have not been associated with intellectual disability.
Intellectual disability v5.450 ABCC9 Sarah Leigh Mode of pathogenicity for gene: ABCC9 was changed from None to None
Intellectual disability v5.450 ABCC9 Sarah Leigh Mode of pathogenicity for gene: ABCC9 was changed from Other to None
Intellectual disability v5.449 ABCC9 Tracy Lester edited their review of gene: ABCC9: Added comment: This gene is currently green for monoallelic inheritance but the associated review relates to cases with biallelic inheritance. The MOI for this gene should be amended to biallelic only. Monoallelic variants are associated with Cantu syndrome which is not primarily an ID disorder or DCM.; Changed rating: GREEN
Intellectual disability v5.449 DHX37 Sarah Leigh Tag Q1_24_MOI tag was added to gene: DHX37.
Tag Q1_24_NHS_review tag was added to gene: DHX37.
Intellectual disability v5.449 DHX37 Sarah Leigh Added comment: Comment on mode of inheritance: The mode of inheritance for DHX37 on the Intellectual disability panel should be biallelic as monoallelic variant have not been associated with intellectual disability.
Intellectual disability v5.449 DHX37 Sarah Leigh Mode of inheritance for gene: DHX37 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.448 DHX37 Sarah Leigh edited their review of gene: DHX37: Added comment: Biallelic DHX37 variants have been associated with Neurodevelopmental disorder with brain anomalies and with or without vertebral or cardiac anomalies (OMIM:618731). Five DHX37 variants have been reported in three unrelated cases of OMIM:618731. Zebra fish models, support the role of DHX37 variants in aberrant behaviors (PMID: 24027265); Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.448 ABCC9 Sarah Leigh Added comment: Comment on mode of pathogenicity: Loss of function variants do cause the phenotype of Intellectual disability and myopathy syndrome (OMIM:619719) , which is relevant to this panel.
Intellectual disability v5.448 ABCC9 Sarah Leigh Mode of pathogenicity for gene: ABCC9 was changed from to Other
Intellectual disability v5.447 DHX37 Sarah Leigh Publications for gene: DHX37 were set to 26539891; 31256877
Intellectual disability v5.446 ABCC9 Sarah Leigh Tag watchlist_moi was removed from gene: ABCC9.
Tag Q1_24_MOI tag was added to gene: ABCC9.
Tag Q1_24_NHS_review tag was added to gene: ABCC9.
Intellectual disability v5.446 ABCC9 Sarah Leigh Phenotypes for gene: ABCC9 were changed from Cardiomyopathy, dilated, 10, 608569; Atrial fibrillation, familial, 12, 614050; Hypertrichotic osteochondrodysplasia, 239850; CANTU SYNDROME HYPERTRICHOTIC OSTEOCHONDRODYSPLASIA to Intellectual disability and myopathy syndrome, OMIM:619719; intellectual disability and myopathy syndrome, MONDO:0859224
Intellectual disability v5.445 ABCC9 Sarah Leigh changed review comment from: Seven homozygous loss of function ABCC9 variants have been reported in seven unrelated cases of Intellectual disability and myopathy syndrome (OMIM:619719)(PMID: 31575858; 38217872). In vivo studies of abcc9 LoF in zebrafish, revealed an exacerbated motor response to pentylenetetrazole, a pro-convulsive drug, consistent with impaired neurodevelopment associated with an increased seizure susceptibility.(PMID: 38217872).; to: Seven homozygous loss of function ABCC9 variants have been reported in seven unrelated cases of Intellectual disability and myopathy syndrome (OMIM:619719)(PMID: 31575858; 38217872). In vivo studies of abcc9 LoF in zebrafish, revealed an exacerbated motor response to pentylenetetrazole, a pro-convulsive drug, consistent with impaired neurodevelopment associated with an increased seizure susceptibility.(PMID: 38217872). Heterozygous parents of the cases, did not show a consistent phenotype, although intrauterine death was reported in two families (PMID: 38217872). In family 4 the fetus was homozygous for c.1858C>T, p.(Arg620Ter) and in family 8 the parents were both heterozygous for c.2140_2141del, p.(Leu714SerfsTer7), but analysis of the fetus was not possible.
Intellectual disability v5.445 ABCC9 Sarah Leigh reviewed gene: ABCC9: Rating: GREEN; Mode of pathogenicity: None; Publications: 38217872; Phenotypes: Intellectual disability and myopathy syndrome, OMIM:619719, intellectual disability and myopathy syndrome, MONDO:0859224; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.445 ABCC9 Sarah Leigh Publications for gene: ABCC9 were set to 25529582; 24896178; 31575858; 38217872
Intellectual disability v5.444 ABCC9 Sarah Leigh Publications for gene: ABCC9 were set to 25529582; 24896178; 31575858
Intellectual disability v5.443 ABCC9 Sarah Leigh Publications for gene: ABCC9 were set to
Intellectual disability v5.442 MADD Sarah Leigh edited their review of gene: MADD: Added comment: Comments from Karen Stals (Royal Devon and Exeter Hospital), 4 Dec 2023: Apnoea a presenting feature in 13/14 patients with MADD-related disorder with biallelic MADD variants in Schneeberger et al 2020 PMID: 32761064. Identified biallelic variants in this gene in a patient with a consistent phenotype.; Changed rating: GREEN; Changed publications to: 32761064
Intellectual disability v5.442 KIRREL3 Sarah Leigh Tag Q1_24_promote_green tag was added to gene: KIRREL3.
Intellectual disability v5.442 KIRREL3 Sarah Leigh Phenotypes for gene: KIRREL3 were changed from Mental retardation, autosomal dominant 4, 612581; MENTAL RETARDATION AUTOSOMAL DOMINANT TYPE 4 (MRD4) to Intellectual developmental disorder, autosomal dominant 4, OMIM:612581; intellectual disability, autosomal dominant 4, MONDO:0012947
Intellectual disability v5.441 KIRREL3 Sarah Leigh changed review comment from: At least 15 missense KIRREL3 variants have been reported in 17 unrelated cases with a neurodevelopmental disorder, that includes intellectual disability ranging from mild to severe (PMID: 19012874; 29271092; 33853164; 33853164). Table 1 in PMID: 37605258, lists KIRREL3 variants and demonstrates that the variants maybe either de novo (9/16) or inherited from one of the parents (7/9). (PMID: 37605258). The KIRREL3 variants are either absent from control databases or are present at a very low frequency.; to: At least 12 missense KIRREL3 variants have been reported in 12 unrelated cases with a neurodevelopmental disorder, that includes intellectual disability ranging from mild to severe (PMID: 29271092; 33853164; 33853164). Table 1 in PMID: 37605258, reviews KIRREL3 variants and demonstrates that the variants maybe either de novo (4/11) or inherited from one of the parents (7/11)(mode of inheritance was unknown for one of the variants). The KIRREL3 variants are either absent from controls or are present at a very low frequency. However, the three variants reported in PMID: 19012874, were shown to be present in publicly databases at a high frequency (see KIRREL3 OMIM entry).
Intellectual disability v5.441 KIRREL3 Sarah Leigh Classified gene: KIRREL3 as Amber List (moderate evidence)
Intellectual disability v5.441 KIRREL3 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 v5.441 KIRREL3 Sarah Leigh Gene: kirrel3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.440 KIRREL3 Sarah Leigh reviewed gene: KIRREL3: Rating: GREEN; Mode of pathogenicity: None; Publications: 29271092; Phenotypes: ; Mode of inheritance: None
Intellectual disability v5.440 KIRREL3 Sarah Leigh Publications for gene: KIRREL3 were set to 22965935; 19012874; 29271092; 29271092; 37605258
Intellectual disability v5.439 KIRREL3 Sarah Leigh Publications for gene: KIRREL3 were set to 22965935; 19012874; 29271092; 29271092:37605258
Intellectual disability v5.438 KIRREL3 Sarah Leigh Publications for gene: KIRREL3 were set to 22965935; 19012874; 33853164; 37605258
Intellectual disability v5.437 KIRREL3 Sarah Leigh Publications for gene: KIRREL3 were set to 22965935; 19012874; 33853164; 33853164; 37605258
Intellectual disability v5.436 KIRREL3 Sarah Leigh Publications for gene: KIRREL3 were set to 22965935; 19012874; 33853164
Intellectual disability v5.435 KIRREL3 Sarah Leigh Mode of inheritance for gene: KIRREL3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.434 TUSC3 Arina Puzriakova Publications for gene: TUSC3 were set to
Intellectual disability v5.433 TUSC3 Arina Puzriakova Phenotypes for gene: TUSC3 were changed from Mental retardation, autosomal recessive 7, 611093; MENTAL RETARDATION AUTOSOMAL RECESSIVE TYPE 7 (MRT7) to Intellectual developmental disorder, autosomal recessive 7, OMIM:611093
Intellectual disability v5.432 CC2D1A Arina Puzriakova Publications for gene: CC2D1A were set to
Intellectual disability v5.431 CC2D1A Arina Puzriakova Phenotypes for gene: CC2D1A were changed from Mental retardation, autosomal recessive 3, 608443; MENTAL RETARDATION AUTOSOMAL RECESSIVE TYPE 3 (MRT3) to Intellectual developmental disorder, autosomal recessive 3, OMIM:608443
Intellectual disability v5.430 RARS Arina Puzriakova Publications for gene: RARS were set to 31814314; 28905880; 24777941; 30500859
Intellectual disability v5.429 LRRC32 Hannah Knight reviewed gene: LRRC32: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 35656379; Phenotypes: Cleft palate, proliferative retinopathy, and developmental delay; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.429 RARS Arina Puzriakova Phenotypes for gene: RARS were changed from Cerebral hypomyelination; Global developmental delay; Intellectual disability; Seizures; Cerebral atrophy; Nystagmus; Ataxia; Feeding difficulties to Leukodystrophy, hypomyelinating, 9, OMIM:616140
Intellectual disability v5.428 ASPM Arina Puzriakova Publications for gene: ASPM were set to
Intellectual disability v5.427 ASPM Arina Puzriakova Phenotypes for gene: ASPM were changed from Microcephaly 5, primary, autosomal recessive, 608716; PRIMARY AUTOSOMAL RECESSIVE MICROCEPHALY to Microcephaly 5, primary, autosomal recessive, OMIM:608716
Intellectual disability v5.426 RARS Arina Puzriakova Publications for gene: RARS were set to 31814314; 28905880; 24777941
Intellectual disability v5.425 WDR62 Arina Puzriakova Publications for gene: WDR62 were set to
Intellectual disability v5.424 WDR62 Arina Puzriakova Phenotypes for gene: WDR62 were changed from Microcephaly, Cortical Malformations, and Mental Retardation; Microcephaly 2, primary, autosomal recessive, with or without cortical malformations, 604317; MICROCEPHALY CORTICAL MALFORMATIONS AND MENTAL RETARDATION (MCMMR) to Microcephaly 2, primary, autosomal recessive, with or without cortical malformations, OMIM:604317
Intellectual disability v5.423 MCPH1 Arina Puzriakova Publications for gene: MCPH1 were set to
Intellectual disability v5.422 MCPH1 Arina Puzriakova Phenotypes for gene: MCPH1 were changed from genetic heterogeneity Microcephaly 1, primary, autosomal recessive, 251200; MICROCEPHALY PRIMARY TYPE 1 (MCPH1) to Microcephaly 1, primary, autosomal recessive, OMIM:251200
Intellectual disability v5.421 HSD17B10 Arina Puzriakova Added comment: Comment on mode of inheritance: Should be updated from 'XL, biallelic in females' to 'XL, monoallelic in females' as female patients harbouring heterozygous variants have been described. Some carrier females shown to have mild to moderate developmental delay or intellectual disability (PMIDs: 12112118; 16148061; 22127393; 34765396)
Intellectual disability v5.421 HSD17B10 Arina Puzriakova Mode of inheritance for gene: HSD17B10 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.420 HSD17B10 Arina Puzriakova Tag Q1_24_MOI tag was added to gene: HSD17B10.
Intellectual disability v5.420 HSD17B10 Arina Puzriakova Publications for gene: HSD17B10 were set to
Intellectual disability v5.419 HSD17B10 Arina Puzriakova Phenotypes for gene: HSD17B10 were changed from 17-beta-hydroxysteroid dehydrogenase X deficiency, 300438Mental retardation, X-linked syndromic 10, 300220Mental retardation, X-linked 17/31, microduplication, 300705; 2-METHYL-3-HYDROXYBUTYRYL-COA DEHYDROGENASE DEFICIENCY (MHBD DEFICIENCY) to HSD10 mitochondrial disease, OMIM:300438
Intellectual disability v5.418 COL4A3BP Arina Puzriakova Publications for gene: COL4A3BP were set to 25533962; 33347465; 34688657; 36976648; 37892645
Intellectual disability v5.417 COL4A3BP Arina Puzriakova Publications for gene: COL4A3BP were set to 25533962; 33347465; 34688657; 36976648; 37892645
Intellectual disability v5.417 COL4A3BP Arina Puzriakova Publications for gene: COL4A3BP were set to 25533962; 33347465
Intellectual disability v5.416 COL4A3BP Arina Puzriakova Phenotypes for gene: COL4A3BP were changed from INTELLECTUAL DISABILITY to Intellectual developmental disorder, autosomal dominant 34, OMIM:616351
Intellectual disability v5.415 COL4A3BP Arina Puzriakova Publications for gene: COL4A3BP were set to 25533962
Intellectual disability v5.414 GAN Tracy Lester reviewed gene: GAN: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301315; Phenotypes: Intellectual disability, developmental delay, neuropathy, hypotonia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.414 KCNA3 Achchuthan Shanmugasundram Classified gene: KCNA3 as Amber List (moderate evidence)
Intellectual disability v5.414 KCNA3 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reported in PMID:37964487 and reviewed by Gavin Ryan, 12 patients had developmental delays, of which nine patients had mild, moderate or severe intellectual disability. Hence, this gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.414 KCNA3 Achchuthan Shanmugasundram Gene: kcna3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.413 KCNA3 Achchuthan Shanmugasundram Phenotypes for gene: KCNA3 were changed from Neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to Neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.413 KCNA3 Achchuthan Shanmugasundram Phenotypes for gene: KCNA3 were changed from Neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to Neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.413 KCNA3 Achchuthan Shanmugasundram Phenotypes for gene: KCNA3 were changed from Intellectual disability; Developmental Delay; Epilepsy to Neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.412 KCNA3 Achchuthan Shanmugasundram Publications for gene: KCNA3 were set to 37964487
Intellectual disability v5.412 KCNA3 Achchuthan Shanmugasundram Publications for gene: KCNA3 were set to PMID: 37964487
Intellectual disability v5.411 KCNA3 Achchuthan Shanmugasundram Tag Q1_24_NHS_review tag was added to gene: KCNA3.
Intellectual disability v5.411 KCNA3 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: KCNA3.
Intellectual disability v5.411 KCNA3 Achchuthan Shanmugasundram reviewed gene: KCNA3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.411 LGI3 Achchuthan Shanmugasundram changed review comment from: PMID:35948005 reported sixteen individuals from eight unrelated families with loss-of-function (LoF) bi-allelic variants in LGI3. All of them exhibited a potentially clinically recognizable peripheral nerve hyperexcitability syndrome (PNHS) trait characterized by global developmental delay, intellectual disability, distal deformities with diminished reflexes, visible facial myokymia, and distinctive electromyographic features suggestive of motor nerve instability. All sixteen patients had global developmental delay and all thirteen tested patients had mild or moderate intellectual disability. Lgi3-null mice showed reduced and mis-localized Kv1 channel complexes in myelinated peripheral axons.

This gene has been associated with relevant phenotype in OMIM (MIM #620007), but not yet in Gene2Phenotype.
Sources: Literature; to: PMID:35948005 reported sixteen individuals from eight unrelated families with loss-of-function (LoF) bi-allelic variants in LGI3. All of them exhibited a potentially clinically recognizable peripheral nerve hyperexcitability syndrome (PNHS) trait characterized by global developmental delay, intellectual disability, distal deformities with diminished reflexes, visible facial myokymia, and distinctive electromyographic features suggestive of motor nerve instability. All sixteen patients had global developmental delay and all thirteen tested patients had mild or moderate intellectual disability.

Lgi3-null mice showed reduced and mis-localized Kv1 channel complexes in myelinated peripheral axons.

This gene has been associated with relevant phenotypes in OMIM (MIM #620007), but not yet in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.411 LGI3 Achchuthan Shanmugasundram Classified gene: LGI3 as Amber List (moderate evidence)
Intellectual disability v5.411 LGI3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (eight unrelated families and mouse model) for the promotion of this gene to green rating in the next GMS review.
Intellectual disability v5.411 LGI3 Achchuthan Shanmugasundram Gene: lgi3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.410 LGI3 Achchuthan Shanmugasundram Tag Q1_24_promote_green tag was added to gene: LGI3.
Intellectual disability v5.410 LGI3 Achchuthan Shanmugasundram gene: LGI3 was added
gene: LGI3 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: LGI3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LGI3 were set to 35948005
Phenotypes for gene: LGI3 were set to Intellectual developmental disorder with muscle tone abnormalities and distal skeletal defects, OMIM:620007
Review for gene: LGI3 was set to GREEN
Added comment: PMID:35948005 reported sixteen individuals from eight unrelated families with loss-of-function (LoF) bi-allelic variants in LGI3. All of them exhibited a potentially clinically recognizable peripheral nerve hyperexcitability syndrome (PNHS) trait characterized by global developmental delay, intellectual disability, distal deformities with diminished reflexes, visible facial myokymia, and distinctive electromyographic features suggestive of motor nerve instability. All sixteen patients had global developmental delay and all thirteen tested patients had mild or moderate intellectual disability. Lgi3-null mice showed reduced and mis-localized Kv1 channel complexes in myelinated peripheral axons.

This gene has been associated with relevant phenotype in OMIM (MIM #620007), but not yet in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.409 KCNA3 Gavin Ryan gene: KCNA3 was added
gene: KCNA3 was added to Intellectual disability - microarray and sequencing. Sources: Expert Review
Mode of inheritance for gene: KCNA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNA3 were set to PMID: 37964487
Phenotypes for gene: KCNA3 were set to Intellectual disability; Developmental Delay; Epilepsy
Penetrance for gene: KCNA3 were set to unknown
Review for gene: KCNA3 was set to GREEN
Added comment: Soldovieri et al identified 14 de novo missense variants in KCNA3 gene. The majority of individuals presented with ID, developmental delay, and epilepsy, amongst other features. Functional studies showed loss-of-function effects for some variants and possible gain-of-function for others. One of these variants has also been identified in NHS GMS WGS patient with consistent features.
Sources: Expert Review
Intellectual disability v5.409 BAZ2B Dmitrijs Rots gene: BAZ2B was added
gene: BAZ2B was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: BAZ2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BAZ2B were set to PMID: 31999386
Phenotypes for gene: BAZ2B were set to developmental delay, intellectual disability and autism spectrum disorder
Review for gene: BAZ2B was set to GREEN
Added comment: BAZ2B gene is intolerant to LoF variants in population (pLI=1) and PMID: 31999386 described that de novo LoF variants are statistically enriched among NDD cases & summarize 10 cases. Enough evidence for the green rating.
Sources: Literature
Intellectual disability v5.409 ABCC9 Tracy Lester reviewed gene: ABCC9: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability v5.409 MTSS1L Achchuthan Shanmugasundram edited their review of gene: MTSS1L: Changed phenotypes to: Intellectual developmental disorder with ocular anomalies and distinctive facial features, OMIM:620086
Intellectual disability v5.409 MTSS1L Achchuthan Shanmugasundram changed review comment from: Added new-gene-name tag, new approved HGNC gene symbol for MTSS1L is MTSS2.; to: New approved HGNC gene symbol for MTSS1L is MTSS2.
Intellectual disability v5.409 MTSS1L Achchuthan Shanmugasundram commented on gene: MTSS1L
Intellectual disability v5.409 PRODH Arina Puzriakova Phenotypes for gene: PRODH were changed from Hyperprolinemia, type I, OMIM; 239500; {Schizophrenia, susceptibility to, OMIM:4}, 600850 to Hyperprolinemia, type I, OMIM:239500; {Schizophrenia, susceptibility to, OMIM:4}, 600850
Intellectual disability v5.408 PRICKLE1 Arina Puzriakova Phenotypes for gene: PRICKLE1 were changed from Progressive myoclonic epilepsy 1B OMIM:612437; epilepsy, progressive myoclonic, 1B MONDO:0012904 to Epilepsy, progressive myoclonic 1B, OMIM:612437
Intellectual disability v5.407 PRX Arina Puzriakova Phenotypes for gene: PRX were changed from Dejerine-Sottas disease, 145900; Charcot-Marie-Tooth disease, type 4F, 614895 to Charcot-Marie-Tooth disease, type 4F, OMIM:614895; Dejerine-Sottas disease, OMIM:145900
Intellectual disability v5.406 MTOR Sarah Leigh Publications for gene: MTOR were set to 26542245; 27830187; 25851998; 28892148; DOI: 10.4137/JGE.S12583; 27159400
Intellectual disability v5.405 DHX37 Tracy Lester reviewed gene: DHX37: Rating: GREEN; Mode of pathogenicity: None; Publications: 26539891, 31256877, 35982159; Phenotypes: Intellectual disability, developmental delay; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability v5.405 FAM111A Achchuthan Shanmugasundram Tag Q4_23_expert_review tag was added to gene: FAM111A.
Intellectual disability v5.405 ACBD6 Arina Puzriakova Classified gene: ACBD6 as Amber List (moderate evidence)
Intellectual disability v5.405 ACBD6 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.
Intellectual disability v5.405 ACBD6 Arina Puzriakova Gene: acbd6 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.404 ACBD6 Arina Puzriakova Publications for gene: ACBD6 were set to 21937992; 32108178
Intellectual disability v5.403 ACBD6 Arina Puzriakova Phenotypes for gene: ACBD6 were changed from Intellectual disability to Neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.402 ACBD6 Arina Puzriakova Tag Q1_24_promote_green tag was added to gene: ACBD6.
Intellectual disability v5.402 ACBD6 Arina Puzriakova edited their review of gene: ACBD6: Added comment: - PMID: 21937992 (2011) - single individuals with a p.G22fs variant in the ACBD6 gene, presenting with mild ID, microcephaly, facial dysmorphism, spasticity. Limited additional information.

- PMID: 32108178 (2020) - two unrelated individuals with neurodevelopmental disorder (moderate ID is noted but otherwise limited clinical information) and carrying homozygous LoF variants in the ACBD6 gene (1 frameshift, 1 canonical splice). One individual also carried an allelic homozygous variant in the PRDX6 gene (unlikely but unknown disease consequence). Skin-derived patient fibroblasts showed reduced ACBD6 expression and N-myristoylation deficiency.

- PMID: 36457943 (2023) - two Thai siblings presenting with profound ID, morbid obesity, pancytopenia with severe recurrent infections, diabetes mellitus, cirrhosis, and renal failure, leading to deaths in their early 30s. Sequencing showed a novel homozygous single bp duplication (c.360dup; p.Leu121Thrfs*27) in the ACBD6 gene. Parents were heterozygous carriers.

- PMID: 37951597 (2023) - 45 previously undiagnosed individuals from 28 families with a neurodevelopmental syndrome including a complex and progressive movement disorder phenotype. Cardinal clinical features include moderate-to-severe GDD/ID (45/45), facial dysmorphism (38/40), HC <2nd percentile (21/31), weight >50th percentile (20/34), mild cerebellar ataxia (35/41), limb spasticity/hypertonia (31/41), gait abnormalities (33/35), dystonia (30/32) and variable epilepsy (13/29).

Homozygous ACBD6 variants were identified by WES in all cases, including 18 predicted LoF, 1 missense and 1 inframe insertion. Knockout studies in zebrafish recapitulate clinical features reported in patients such as movement disorders, seizures, and facial dysmorphology, while inactivation of acbd6 in X. tropicalis predominantly caused embryo death while surviving tadpoles demonstrated microcephaly, reduced movement, eye abnormalities, and brain structure differences.; Changed rating: GREEN; Changed publications to: 21937992, 32108178, 36457943, 37951597; Changed phenotypes to: Neurodevelopmental disorder, MONDO:0700092; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.402 ACBD6 Arina Puzriakova Added comment: Comment on publications: PMID: 32108178 (2020) paper was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques
Intellectual disability v5.402 ACBD6 Arina Puzriakova Publications for gene: ACBD6 were set to 21937992; 32108178
Intellectual disability v5.401 KIRREL3 Dmitrijs Rots reviewed gene: KIRREL3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37605258; Phenotypes: NDD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.401 ACBD6 Sarah Leigh Classified gene: ACBD6 as Amber List (moderate evidence)
Intellectual disability v5.401 ACBD6 Sarah Leigh Gene: acbd6 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.401 ACBD6 Sarah Leigh Classified gene: ACBD6 as Amber List (moderate evidence)
Intellectual disability v5.401 ACBD6 Sarah Leigh Gene: acbd6 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.400 ACBD6 Sarah Leigh edited their review of gene: ACBD6: Added comment: ACBD6 variants have not been associated with a phenotype in OMIM, and as an autosomal recessive condition with Limited strength in Gen2Phen. Three variants have been reported in three unrelated cases with intellectual disability, however, in one of these carriers the ACBD6 variant was allelic with PRDX6 gene c.136del; p.(ValCysfs*23), therefore the contribution of the ACBD6 variant to intellectual disability is uncertain in this case (PMID: 21937992, 32108178).; Changed rating: AMBER
Intellectual disability v5.400 ACBD6 Sarah Leigh Publications for gene: ACBD6 were set to 21937992
Intellectual disability v5.399 RPL10 Achchuthan Shanmugasundram Phenotypes for gene: RPL10 were changed from Intellectual developmental disorder, X-linked syndromic 35, OMIM:300998 to Intellectual developmental disorder, X-linked syndromic 35, OMIM:300998
Intellectual disability v5.399 RPL10 Achchuthan Shanmugasundram Phenotypes for gene: RPL10 were changed from Mental retardation, X-linked, syndromic, 35, 300998 to Intellectual developmental disorder, X-linked syndromic 35, OMIM:300998
Intellectual disability v5.398 RPL10 Achchuthan Shanmugasundram Publications for gene: RPL10 were set to 25316788; 25316788; 25316788; 35876338
Intellectual disability v5.398 RPL10 Achchuthan Shanmugasundram Publications for gene: RPL10 were set to 25316788; 25316788; 25316788; 35876338
Intellectual disability v5.398 RPL10 Achchuthan Shanmugasundram Publications for gene: RPL10 were set to 25316788; 25316788; 25316788; 35876338
Intellectual disability v5.397 RPL10 Achchuthan Shanmugasundram Publications for gene: RPL10 were set to 25316788; 25316788; 25316788; 35876338
Intellectual disability v5.397 RPL10 Achchuthan Shanmugasundram Publications for gene: RPL10 were set to 25316788
Intellectual disability v5.396 RPL10 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: As reviewed by Sarah Leigh and Dmitrijs Rots, all the cases reported previously in literature and recently in PMID:35876338 were males with hemizygous RPL10 variants. The females were carriers and showed fully skewed X inactivation of the mutation-bearing X chromosomes.

In addition, this gene has been associated with relevant phenotypes in both OMIM (MIM #300998) and Gene2Phenotype (with 'definitive' rating on the DD panel). The MOI has been recorded as 'X-linked recessive' in OMIM.

The MOI should therefore be updated from 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' to 'X-LINKED: hemizygous mutation in males, biallelic mutations in females' in the next GMS review.
Intellectual disability v5.396 RPL10 Achchuthan Shanmugasundram Mode of inheritance for gene: RPL10 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v5.395 RPL10 Achchuthan Shanmugasundram Tag Q4_23_MOI tag was added to gene: RPL10.
Intellectual disability v5.395 RPL10 Achchuthan Shanmugasundram reviewed gene: RPL10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, X-linked syndromic 35, OMIM:300998; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.395 RELN Achchuthan Shanmugasundram changed review comment from: Comment on mode of inheritance: The MOI should be updated from "BIALLELIC, autosomal or pseudoautosomal"to "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" as there are three unrelated cases with monoallelic RELN variants and intellectual disability reported in the literature.; to: Comment on mode of inheritance: The MOI should be updated from "BIALLELIC, autosomal or pseudoautosomal" to "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" in the next GMS review as there are three unrelated cases with monoallelic RELN variants and intellectual disability reported in the literature.
Intellectual disability v5.395 RELN Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: The MOI should be updated from "BIALLELIC, autosomal or pseudoautosomal"to "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" as there are three unrelated cases with monoallelic RELN variants and intellectual disability reported in the literature.
Intellectual disability v5.395 RELN Achchuthan Shanmugasundram Mode of inheritance for gene: RELN was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.394 RELN Achchuthan Shanmugasundram Phenotypes for gene: RELN were changed from Lissencephaly 2 (Norman-Roberts type), OMIM:257320; neurodevelopmental disorder, MONDO:0700092 to Lissencephaly 2 (Norman-Roberts type), OMIM:257320; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.394 RELN Achchuthan Shanmugasundram Phenotypes for gene: RELN were changed from Lissencephaly 2 (Norman-Roberts type), OMIM:257320; neurodevelopmental disorder, MONDO:0700092 to Lissencephaly 2 (Norman-Roberts type), OMIM:257320; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.393 RELN Achchuthan Shanmugasundram Tag Q4_23_MOI tag was added to gene: RELN.
Intellectual disability v5.393 RELN Achchuthan Shanmugasundram Phenotypes for gene: RELN were changed from Lissencephaly 2 (Norman-Roberts type), OMIM:257320; neurodevelopmental disorder, MONDO:0700092 to Lissencephaly 2 (Norman-Roberts type), OMIM:257320; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.393 RELN Achchuthan Shanmugasundram Phenotypes for gene: RELN were changed from Lissencephaly 2 (Norman-Roberts type), OMIM:257320; neurodevelopmental disorder, MONDO:0700092 to Lissencephaly 2 (Norman-Roberts type), OMIM:257320; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.393 RELN Achchuthan Shanmugasundram Phenotypes for gene: RELN were changed from Lissencephaly 2 (Norman-Roberts type), 257320; LISSENCEPHALY 2 to Lissencephaly 2 (Norman-Roberts type), OMIM:257320; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.392 RELN Achchuthan Shanmugasundram Publications for gene: RELN were set to
Intellectual disability v5.391 RELN Achchuthan Shanmugasundram reviewed gene: RELN: Rating: GREEN; Mode of pathogenicity: None; Publications: 35769015; Phenotypes: Lissencephaly 2 (Norman-Roberts type), OMIM:257320, neurodevelopmental disorder, MONDO:0700092; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.391 CLDN11 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.391 CLDN11 Achchuthan Shanmugasundram Classified gene: CLDN11 as Amber List (moderate evidence)
Intellectual disability v5.391 CLDN11 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (three unrelated patients) for the promotion of this gene to green rating in the next GMS review.
Intellectual disability v5.391 CLDN11 Achchuthan Shanmugasundram Gene: cldn11 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.390 CLDN11 Achchuthan Shanmugasundram Classified gene: CLDN11 as Amber List (moderate evidence)
Intellectual disability v5.390 CLDN11 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (three unrelated patients) for the promotion of this gene to green rating in the next GMS review.
Intellectual disability v5.390 CLDN11 Achchuthan Shanmugasundram Gene: cldn11 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.389 CLDN11 Achchuthan Shanmugasundram Tag Q4_23_promote_green tag was added to gene: CLDN11.
Intellectual disability v5.389 CLDN11 Achchuthan Shanmugasundram gene: CLDN11 was added
gene: CLDN11 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: CLDN11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CLDN11 were set to 33313762
Phenotypes for gene: CLDN11 were set to Leukodystrophy, hypomyelinating, 22, OMIM:619328
Review for gene: CLDN11 was set to GREEN
Added comment: PMID:33313762 reported three unrelated individuals with early-onset spastic movement disorder, expressive speech disorder and eye abnormalities including hypermetropia. These patients exhibit global developmental delay, particularly motor and speech delay. Intellectual disability was maximally mild in two of three individuals and the intelligence is in a low-normal range in third individual, although IQ testing was not performed in them.

Two different heterozygous de novo stop-loss variants were identified in these patients. One of the variants did not lead to a loss of CLDN11 expression on RNA level in fibroblasts indicating this transcript is not subject to nonsense-mediated decay and most likely translated into an extended protein.

This gene has been associated with hypomyelinating leukodystrophy in OMIM, which includes global developmental delay and impaired intellectual development (mild) as clinical presentations. However, this gene has not yet been associated with phenotypes in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.388 RARB Achchuthan Shanmugasundram Mode of pathogenicity for gene: RARB was changed from None to None
Intellectual disability v5.388 RARB Achchuthan Shanmugasundram Mode of pathogenicity for gene: RARB was changed from None to None
Intellectual disability v5.387 RARB Achchuthan Shanmugasundram Mode of pathogenicity for gene: RARB was changed from None to None
Intellectual disability v5.388 RARB Achchuthan Shanmugasundram Mode of pathogenicity for gene: RARB was changed from None to None
Intellectual disability v5.388 RARB Achchuthan Shanmugasundram Mode of pathogenicity for gene: RARB was changed from None to None
Intellectual disability v5.388 RARB Achchuthan Shanmugasundram Mode of pathogenicity for gene: RARB was changed from None to None
Intellectual disability v5.387 RARB Achchuthan Shanmugasundram Mode of pathogenicity for gene: RARB was changed from None to None
Intellectual disability v5.387 RARB Achchuthan Shanmugasundram Mode of pathogenicity for gene: RARB was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to None
Intellectual disability v5.386 RARB Achchuthan Shanmugasundram Publications for gene: RARB were set to 17506106; 24075189; 25457163; 27120018; 30281527; 30880327
Intellectual disability v5.386 RARB Achchuthan Shanmugasundram Publications for gene: RARB were set to 17506106; 24075189; 25457163; 27120018; 30281527; 30880327
Intellectual disability v5.386 RARB Achchuthan Shanmugasundram Publications for gene: RARB were set to 17506106; 24075189; 25457163; 27120018; 30281527; 30880327
Intellectual disability v5.385 RARB Achchuthan Shanmugasundram Publications for gene: RARB were set to 17506106; 24075189; 25457163; 27120018; 30281527; 30880327
Intellectual disability v5.385 RARB Achchuthan Shanmugasundram Publications for gene: RARB were set to 24075189
Intellectual disability v5.384 RARB Achchuthan Shanmugasundram Phenotypes for gene: RARB were changed from Microphthalmia, syndromic 12, OMIM:615524; neurodevelopmental disorder, MONDO:0700092 to Microphthalmia, syndromic 12, OMIM:615524; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.384 RARB Achchuthan Shanmugasundram Phenotypes for gene: RARB were changed from Microphthalmia, syndromic 12, OMIM:615524; neurodevelopmental disorder, MONDO:0700092 to Microphthalmia, syndromic 12, OMIM:615524; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.383 RARB Achchuthan Shanmugasundram Phenotypes for gene: RARB were changed from MICROPHTHALMIA AND DIAPHRAGMATIC HERNIA to Microphthalmia, syndromic 12, OMIM:615524; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.382 COX11 Sarah Leigh Classified gene: COX11 as Amber List (moderate evidence)
Intellectual disability v5.382 COX11 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 v5.382 COX11 Sarah Leigh Gene: cox11 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.381 RARB Achchuthan Shanmugasundram Mode of pathogenicity for gene: RARB 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
Intellectual disability v5.380 COX11 Sarah Leigh commented on gene: COX11: The three unrelated case of Mitochondrial complex IV deficiency, nuclear type 23 (OMIM:620275) so far reported, all had significant cognitive impairment and 2/3 of the cases had hypotonia (PMID: 36030551;38068960).
Intellectual disability v5.380 YARS Achchuthan Shanmugasundram changed review comment from: As reviewed by Sarah Leigh, none of the previously reported cases presented with intellectual disability, although the family reported in PMID:30304524 had expressive language delay and the older brother reported in PMID:27633801 had mild delays.

As reviewed by Dmitrijs Rots, all 12 patients from six families identified with homozygous p.Arg367Trp variant had neurodevelopmental phenotype including intellectual disability. As all these families were identified with the same homozygous variant, the rating should remain amber. However, 'watchlist' tag has been added to review this gene in future with any new evidence.; to: As reviewed by Sarah Leigh, none of the previously reported cases presented with intellectual disability, although the family reported in PMID:30304524 had expressive language delay and the older brother reported in PMID:27633801 had mild delays.

As reviewed by Dmitrijs Rots, all 12 patients from six families identified with homozygous p.Arg367Trp variant had neurodevelopmental phenotype including intellectual disability. As all these families were identified with the same homozygous variant, the rating should remain amber.
Intellectual disability v5.380 YARS Achchuthan Shanmugasundram reviewed gene: YARS: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Infantile-onset multisystem neurologic, endocrine, and pancreatic disease 2, OMIM:619418; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.380 COX11 Sarah Leigh Entity copied from Mitochondrial disorders v4.142
Intellectual disability v5.380 COX11 Sarah Leigh gene: COX11 was added
gene: COX11 was added to Intellectual disability - microarray and sequencing. Sources: NHS GMS,Expert Review Amber
Q4_23_promote_green tags were added to gene: COX11.
Mode of inheritance for gene: COX11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COX11 were set to 36030551; 38068960
Phenotypes for gene: COX11 were set to Mitochondrial complex IV deficiency, nuclear type 23, OMIM:620275; Mitochondrial complex IV deficiency, nuclear type 23, MONDO:0859520
Intellectual disability v5.379 CLCN6 Sarah Leigh Added comment: Comment on mode of pathogenicity: PMID 33217309 reports gain of function associated with CLCN6 variants.
Intellectual disability v5.379 CLCN6 Sarah Leigh Mode of pathogenicity for gene: CLCN6 was changed from None to None
Intellectual disability v5.378 CLCN6 Sarah Leigh Classified gene: CLCN6 as Amber List (moderate evidence)
Intellectual disability v5.378 CLCN6 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 v5.378 CLCN6 Sarah Leigh Gene: clcn6 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.377 CLCN6 Sarah Leigh Tag Q4_23_promote_green tag was added to gene: CLCN6.
Intellectual disability v5.377 CLCN6 Sarah Leigh edited their review of gene: CLCN6: Added comment: Review copied from Neuronal ceroid lipofuscinosis panel: PMID 33217309: Three unrelated families reported with recurrent GOF de novo c.1658A>G (p.Tyr553Cys) and severe developmental delay with pronounced generalized hypotonia, respiratory insufficiency, and variable neurodegeneration and diffusion restriction in cerebral peduncles, midbrain, and/or brainstem in MRI scans. Previously, monoallelic variants reported in 3 families with BPEI, but functional data/segregation not compelling. Mouse knockout model has features of NCL (Zornitza Stark (Australian Genomics), 9 Dec 2020).; Changed rating: GREEN; 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
Intellectual disability v5.377 CLCN6 Sarah Leigh gene: CLCN6 was added
gene: CLCN6 was added to Intellectual disability - microarray and sequencing. Sources: Other
Mode of inheritance for gene: CLCN6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CLCN6 were set to 29667327; 26658788; 25794116; 21107136; 33217309; 16950870
Phenotypes for gene: CLCN6 were set to Neurodegeneration, childhood-onset, hypotonia, respiratory insufficiency and brain imaging abnormalities OMIM:619173
Review for gene: CLCN6 was set to RED
Added comment: Sources: Other
Intellectual disability v5.376 TRIT1 Eleanor Williams Phenotypes for gene: TRIT1 were changed from Combined oxidative phosphorylation deficiency 35, OMIM:617873 to Combined oxidative phosphorylation deficiency 35, OMIM:617873; combined oxidative phosphorylation deficiency 35, MONDO:0054742
Intellectual disability v5.375 ASL Eleanor Williams Phenotypes for gene: ASL were changed from Argininosuccinic aciduria 207900 to Argininosuccinic aciduria, OMIM:207900; argininosuccinic aciduria, MONDO:0008815
Intellectual disability v5.374 COG3 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Zornitza Stark, there are two unrelated cases reported with biallelic COG3 variants and hence this gene should be rated amber with current evidence.; to: Comment on list classification: As reviewed by Zornitza Stark, there are two unrelated families reported with biallelic COG3 variants and hence this gene should be rated amber with current evidence.
Intellectual disability v5.374 COG3 Achchuthan Shanmugasundram Entity copied from Congenital disorders of glycosylation v4.16
Intellectual disability v5.374 COG3 Achchuthan Shanmugasundram gene: COG3 was added
gene: COG3 was added to Intellectual disability - microarray and sequencing. Sources: Literature,Expert Review Amber
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, OMIM:620546
Intellectual disability v5.373 SGSM3 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Zornitza Stark, there are eight families reported with the same variant from the same Ashkenazi Jewish ancestry and the variant co-segregated with the disease in all family members.

The 'founder-effect' tag has been added as 1 in 52 Ashkenazi Jews carry the variant.; to: Comment on list classification: As reviewed by Zornitza Stark, there are eight families reported with the same variant from the same Ashkenazi Jewish ancestry and the variant co-segregated with the disease in all family members. This gene should therefore be rated amber with the current evidence.

The 'founder-effect' tag has been added as 1 in 52 Ashkenazi Jews carry the variant.
Intellectual disability v5.373 SGSM3 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.373 SGSM3 Achchuthan Shanmugasundram Classified gene: SGSM3 as Amber List (moderate evidence)
Intellectual disability v5.373 SGSM3 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there are eight families reported with the same variant from the same Ashkenazi Jewish ancestry and the variant co-segregated with the disease in all family members.

The 'founder-effect' tag has been added as 1 in 52 Ashkenazi Jews carry the variant.
Intellectual disability v5.373 SGSM3 Achchuthan Shanmugasundram Gene: sgsm3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.373 SGSM3 Achchuthan Shanmugasundram Classified gene: SGSM3 as No list
Intellectual disability v5.373 SGSM3 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there are eight families reported with the same variant from the same Ashkenazi Jewish ancestry and the variant co-segregated with the disease in all family members.

The 'founder-effect' tag has been added as 1 in 52 Ashkenazi Jews carry the variant.
Intellectual disability v5.373 SGSM3 Achchuthan Shanmugasundram Gene: sgsm3 has been removed from the panel.
Intellectual disability v5.372 SGSM3 Achchuthan Shanmugasundram Tag founder-effect tag was added to gene: SGSM3.
Intellectual disability v5.372 SGSM3 Achchuthan Shanmugasundram Phenotypes for gene: SGSM3 were changed from Neurodevelopmental disorder (MONDO:0700092), SGSM3-related to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.371 SGSM3 Achchuthan Shanmugasundram reviewed gene: SGSM3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.371 SHQ1 Sarah Leigh Entity copied from Childhood onset dystonia, chorea or related movement disorder v3.61
Intellectual disability v5.371 SHQ1 Sarah Leigh gene: SHQ1 was added
gene: SHQ1 was added to Intellectual disability - microarray and sequencing. Sources: Literature,Expert Review Amber
Q4_23_promote_green tags were added to gene: SHQ1.
Mode of inheritance for gene: SHQ1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SHQ1 were set to 34542157; 29178645; 36810590; 36847845; 36416405; 37475611; 36189577
Phenotypes for gene: SHQ1 were set to ?Dystonia 35, childhood-onset, OMIM:619921; dystonia 35, childhood-onset, MONDO:0030958; Neurodevelopmental disorder with dystonia and seizures, OMIM:619922; neurodevelopmental disorder with dystonia and seizures, MONDO:0859258
Intellectual disability v5.370 FBXW11 Sarah Leigh Phenotypes for gene: FBXW11 were changed from Global developmental delay; Intellectual disability; Abnormality of the eye; Abnormality of the head; Abnormality of digit; Neurodevelopmental, jaw, eye, and digital syndrome MIM#618914 to Neurodevelopmental, jaw, eye, and digital syndrome, OMIM:618914; neurodevelopmental, jaw, eye, and digital syndrome, MONDO:003005
Intellectual disability v5.369 TRPC5 Sarah Leigh changed review comment from: To date, TRPC5 variants have not been associated with a phenotype in OMIM, however, Gen2Phen lists TRPC5 as having an Limited association with the phenotype of TRPC5-related neurodevelopmental disorder. Six TRPC5 have been reported to be associated with a neurodevelopmental disorder, which has a range of phenotypic features, including intellectual disability and autism spectrum disorder (PMIDs: 36323681;33504798;28191890;23033978).; to: To date, TRPC5 variants have not been associated with a phenotype in OMIM, however, Gen2Phen lists TRPC5 as having an Limited association with the phenotype of TRPC5-related neurodevelopmental disorder. Six TRPC5 variants have been reported to be associated with a neurodevelopmental disorder, which has a range of phenotypic features, including intellectual disability and autism spectrum disorder (PMIDs: 36323681;33504798;28191890;23033978).
Intellectual disability v5.369 TRPC5 Sarah Leigh Classified gene: TRPC5 as Amber List (moderate evidence)
Intellectual disability v5.369 TRPC5 Sarah Leigh Added comment: Comment on list classification: This gene is rated amber, despite six published variants being reported in unrelated cases with a neurodevelopmental disorder, this is because it is unclear in the publications, how many of these cases actually have intellectual disability.
Intellectual disability v5.369 TRPC5 Sarah Leigh Gene: trpc5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.368 TRPC5 Sarah Leigh commented on gene: TRPC5: To date, TRPC5 variants have not been associated with a phenotype in OMIM, however, Gen2Phen lists TRPC5 as having an Limited association with the phenotype of TRPC5-related neurodevelopmental disorder. Six TRPC5 have been reported to be associated with a neurodevelopmental disorder, which has a range of phenotypic features, including intellectual disability and autism spectrum disorder (PMIDs: 36323681;33504798;28191890;23033978).
Intellectual disability v5.368 TRPC5 Sarah Leigh Classified gene: TRPC5 as Amber List (moderate evidence)
Intellectual disability v5.368 TRPC5 Sarah Leigh Gene: trpc5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.367 AGPAT3 Achchuthan Shanmugasundram Classified gene: AGPAT3 as Amber List (moderate evidence)
Intellectual disability v5.367 AGPAT3 Achchuthan Shanmugasundram Gene: agpat3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.366 AGPAT3 Achchuthan Shanmugasundram Classified gene: AGPAT3 as Amber List (moderate evidence)
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
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
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
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
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.
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.
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.
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
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.
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.
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
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
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.
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
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
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
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
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.
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
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.
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
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
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
Intellectual disability v5.335 DPP6 Ivone Leong commented on gene: DPP6
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.
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
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
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.
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
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
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).
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
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
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).
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.
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
Intellectual disability v5.321 FAM111A Sarah Leigh Publications for gene: FAM111A were set to 23684011
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
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
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
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
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
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
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.
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.
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.
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
Intellectual disability v5.313 TUBGCP2 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: TUBGCP2.
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
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.
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.
Intellectual disability v5.313 CCDC82 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: CCDC82.
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.
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
Intellectual disability v5.313 CCDC32 Achchuthan Shanmugasundram commented on gene: CCDC32
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.
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
Intellectual disability v5.313 SPATA5 Achchuthan Shanmugasundram commented on gene: SPATA5
Intellectual disability v5.313 SPATA5L1 Achchuthan Shanmugasundram commented on gene: SPATA5L1
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
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.
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
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
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.
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.
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
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
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
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
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
Intellectual disability v5.304 ZMYM3 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: ZMYM3.
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
Intellectual disability v5.303 WIPI2 Arina Puzriakova Tag Q2_23_promote_green was removed from gene: WIPI2.
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.
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.
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.
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.
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.
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.
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
Intellectual disability v5.297 MTSS1L Arina Puzriakova Tag Q4_22_promote_green was removed from gene: MTSS1L.
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
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
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.
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.
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
Intellectual disability v5.293 IQSEC2 Arina Puzriakova Tag Q2_23_MOI was removed from gene: IQSEC2.
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
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.
Intellectual disability v5.292 HIST1H4E Arina Puzriakova Tag Q1_23_promote_green was removed from gene: HIST1H4E.
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.
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.
Intellectual disability v5.292 GCSH Arina Puzriakova Tag Q1_23_promote_green was removed from gene: GCSH.
Intellectual disability v5.292 FRMD5 Arina Puzriakova Tag Q4_22_promote_green was removed from gene: FRMD5.
Intellectual disability v5.292 FLNA Arina Puzriakova Tag Q2_23_demote_red was removed from gene: FLNA.
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.
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
Intellectual disability v5.291 DPH5 Arina Puzriakova Tag Q4_22_promote_green was removed from gene: DPH5.
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
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)
Intellectual disability v5.285 HECTD4 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.285 HECTD4 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.285 SPATA5L1 Achchuthan Shanmugasundram Tag new-gene-name tag was added to gene: SPATA5L1.
Intellectual disability v5.285 SPATA5 Achchuthan Shanmugasundram Tag new-gene-name tag was added to gene: SPATA5.
Intellectual disability v5.285 RAB5C Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Zornitza Stark, there is sufficient evidence for this gene to be promoted to green rating at the next GMS update.; to: Comment on list classification: As reviewed by Zornitza Stark, there is sufficient evidence (12 unrelated cases) for this gene to be promoted to green rating at the next GMS update.
Intellectual disability v5.285 RAB5C Achchuthan Shanmugasundram Classified gene: RAB5C as Amber List (moderate evidence)
Intellectual disability v5.285 RAB5C Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is sufficient evidence for this gene to be promoted to green rating at the next GMS update.
Intellectual disability v5.285 RAB5C Achchuthan Shanmugasundram Gene: rab5c has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.284 RAB5C Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: RAB5C.
Intellectual disability v5.284 ESAM Achchuthan Shanmugasundram changed review comment from: As reviewed by Julia Baptista, PMID:36996813 reported the identification of biallelic ESAM variants in 13 individuals from eight unrelated families, which included four foetuses. All nine born individuals had profound global developmental delay/ unspecified intellectual disability, epilepsy, absent or severely delayed speech, varying degrees of spasticity, ventriculomegaly, and ICH/ cerebral calcifications, the latter being also observed in the foetuses.

This gene has been associated with relevant phenotypes in OMIM (MIM #620371), but not yet in Gene2Phenotype.; to: As reviewed by Julia Baptista, PMID:36996813 reported the identification of biallelic ESAM variants in 13 individuals from eight unrelated families, which included four foetuses. All nine live-born individuals had profound global developmental delay/ unspecified intellectual disability, epilepsy, absent or severely delayed speech, varying degrees of spasticity, ventriculomegaly, and ICH/ cerebral calcifications, the latter being also observed in the foetuses.

This gene has been associated with relevant phenotypes in OMIM (MIM #620371), but not yet in Gene2Phenotype.
Intellectual disability v5.284 ESAM Achchuthan Shanmugasundram Classified gene: ESAM as Amber List (moderate evidence)
Intellectual disability v5.284 ESAM Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to green rating in the next GMS review.
Intellectual disability v5.284 ESAM Achchuthan Shanmugasundram Gene: esam has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.283 ESAM Achchuthan Shanmugasundram Phenotypes for gene: ESAM were changed from severe ID; seizures, spasticity to Neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity, OMIM:620371
Intellectual disability v5.282 ESAM Achchuthan Shanmugasundram Publications for gene: ESAM were set to PMID: 36996813
Intellectual disability v5.281 ESAM Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: ESAM.
Tag Q3_23_NHS_review tag was added to gene: ESAM.
Intellectual disability v5.281 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
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Classified gene: PPP1R3F as Amber List (moderate evidence)
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Added comment: Comment on list classification: There are at least nine patients reported with intellectual disability and with hemizygious PPP1R3F variants and hence this gene should be promoted to green rating at the next GMS review.
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Gene: ppp1r3f has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Classified gene: PPP1R3F as Amber List (moderate evidence)
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Added comment: Comment on list classification: There are at least nine patients reported with intellectual disability and with hemizygious PPP1R3F variants and hence this gene should be promoted to green rating at the next GMS review.
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Gene: ppp1r3f has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Classified gene: PPP1R3F as Amber List (moderate evidence)
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Added comment: Comment on list classification: There are at least nine patients reported with intellectual disability and with hemizygious PPP1R3F variants and hence this gene should be promoted to green rating at the next GMS review.
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Gene: ppp1r3f has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Classified gene: PPP1R3F as Amber List (moderate evidence)
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Added comment: Comment on list classification: There are at least nine patients reported with intellectual disability and with hemizygious PPP1R3F variants and hence this gene should be promoted to green rating at the next GMS review.
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Gene: ppp1r3f has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Classified gene: PPP1R3F as Amber List (moderate evidence)
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Added comment: Comment on list classification: There are at least nine patients reported with intellectual disability and with hemizygious PPP1R3F variants and hence this gene should be promoted to green rating at the next GMS review.
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Gene: ppp1r3f has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Classified gene: PPP1R3F as Amber List (moderate evidence)
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Added comment: Comment on list classification: There are at least nine patients reported with intellectual disability and with hemizygious PPP1R3F variants and hence this gene should be promoted to green rating at the next GMS review.
Intellectual disability v5.281 PPP1R3F Achchuthan Shanmugasundram Gene: ppp1r3f has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.280 PPP1R3F Achchuthan Shanmugasundram Phenotypes for gene: PPP1R3F were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.279 PPP1R3F Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: PPP1R3F.
Intellectual disability v5.279 PPP1R3F Achchuthan Shanmugasundram Phenotypes for gene: PPP1R3F were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.280 PPP1R3F Achchuthan Shanmugasundram Phenotypes for gene: PPP1R3F were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.280 PPP1R3F Achchuthan Shanmugasundram Phenotypes for gene: PPP1R3F were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.280 PPP1R3F Achchuthan Shanmugasundram Phenotypes for gene: PPP1R3F were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.279 PPP1R3F Achchuthan Shanmugasundram Phenotypes for gene: PPP1R3F were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.278 PPP1R3F Achchuthan Shanmugasundram Phenotypes for gene: PPP1R3F were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.279 PPP1R3F Achchuthan Shanmugasundram Phenotypes for gene: PPP1R3F were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071Neurodevelopmental Disorder, MONDO:0700092,PPP1R3F-related to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.278 PPP1R3F Achchuthan Shanmugasundram Phenotypes for gene: PPP1R3F were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071Neurodevelopmental Disorder, MONDO:0700092,PPP1R3F-related to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071Neurodevelopmental Disorder, MONDO:0700092,PPP1R3F-related
Intellectual disability v5.278 PPP1R3F Achchuthan Shanmugasundram Phenotypes for gene: PPP1R3F were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071Neurodevelopmental Disorder, MONDO:0700092,PPP1R3F-related to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071Neurodevelopmental Disorder, MONDO:0700092,PPP1R3F-related
Intellectual disability v5.278 PPP1R3F Achchuthan Shanmugasundram Phenotypes for gene: PPP1R3F were changed from Neurodevelopmental Disorder, MONDO:0700092,PPP1R3F-related to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071Neurodevelopmental Disorder, MONDO:0700092,PPP1R3F-related
Intellectual disability v5.277 PPP1R3F Achchuthan Shanmugasundram reviewed gene: PPP1R3F: Rating: GREEN; Mode of pathogenicity: None; Publications: 37531237; Phenotypes: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.277 NR2F2 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: NR2F2.
Tag Q3_23_NHS_review tag was added to gene: NR2F2.
Intellectual disability v5.277 NR2F2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.277 NR2F2 Achchuthan Shanmugasundram Classified gene: NR2F2 as Amber List (moderate evidence)
Intellectual disability v5.277 NR2F2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to green rating in the next GMS review.
Intellectual disability v5.277 NR2F2 Achchuthan Shanmugasundram Gene: nr2f2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.277 NR2F2 Achchuthan Shanmugasundram Classified gene: NR2F2 as Amber List (moderate evidence)
Intellectual disability v5.277 NR2F2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to green rating in the next GMS review.
Intellectual disability v5.277 NR2F2 Achchuthan Shanmugasundram Gene: nr2f2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.276 NR2F2 Achchuthan Shanmugasundram changed review comment from: This gene is an established gene for congenital heart defects (MIM #615779) and disorder of sexual differentiation (MIM #618901). This gene has been associated with these two phenotypes in both OMIM and Gene2Phenotype.

PMID:29663647 - An 11-month old boy was reported with global developmental delay, dysmorphic features, coarctation of the aorta, and ventricular septal defect and was identified with pathogenic NR2F2 variant.

PMID:37500725 - 16 previously unreported unrelated individuals (and a mildly affected mosaic mother of one of them) with rare heterozygous variants (majority are de novo variants) were reviewed in this publication and they had variable clinical presentations including intrauterine growth restriction (IUGR), CHD, CDH, genital anomalies, DSD, developmental delays, hypotonia, feeding difficulties, failure to thrive, congenital and acquired microcephaly, dysmorphic facial features, renal failure, hearing loss, strabismus, asplenia, and vascular malformations. All 14 for whom data is available had motor delays and 13 had speech delay. One of them had global developmental delay, one had mild intellectual disability and four had learning disabilities.; to: This gene is an established gene for congenital heart defects (MIM #615779) and disorder of sexual differentiation (MIM #618901). This gene has been associated with these two phenotypes in both OMIM and Gene2Phenotype. Some patients with CHD (MIM #615779) are reported with developmental delays in the OMIM record.

PMID:29663647 - An 11-month old boy was reported with global developmental delay, dysmorphic features, coarctation of the aorta, and ventricular septal defect and was identified with pathogenic NR2F2 variant.

PMID:37500725 - 16 previously unreported unrelated individuals (and a mildly affected mosaic mother of one of them) with rare heterozygous variants (majority are de novo variants) were reviewed in this publication and they had variable clinical presentations including intrauterine growth restriction (IUGR), CHD, CDH, genital anomalies, DSD, developmental delays, hypotonia, feeding difficulties, failure to thrive, congenital and acquired microcephaly, dysmorphic facial features, renal failure, hearing loss, strabismus, asplenia, and vascular malformations. All 14 for whom data is available had motor delays and 13 had speech delay. One of them had global developmental delay, one had mild intellectual disability and four had learning disabilities.
Intellectual disability v5.276 NR2F2 Achchuthan Shanmugasundram changed review comment from: This gene is an established gene for congenital heart defects (MIM #615779) and disorder of sexual differentiation (MIM #618901).

PMID:29663647 - An 11-month old boy was reported with global developmental delay, dysmorphic features, coarctation of the aorta, and ventricular septal defect and was identified with pathogenic NR2F2 variant.

PMID:37500725 - 16 previously unreported unrelated individuals (and a mildly affected mosaic mother of one of them) with rare heterozygous variants (majority are de novo variants) were reviewed in this publication and they had variable clinical presentations including intrauterine growth restriction (IUGR), CHD, CDH, genital anomalies, DSD, developmental delays, hypotonia, feeding difficulties, failure to thrive, congenital and acquired microcephaly, dysmorphic facial features, renal failure, hearing loss, strabismus, asplenia, and vascular malformations. All 14 for whom data is available had motor delays and 13 had speech delay. One of them had global developmental delay, one had mild intellectual disability and four had learning disabilities.; to: This gene is an established gene for congenital heart defects (MIM #615779) and disorder of sexual differentiation (MIM #618901). This gene has been associated with these two phenotypes in both OMIM and Gene2Phenotype.

PMID:29663647 - An 11-month old boy was reported with global developmental delay, dysmorphic features, coarctation of the aorta, and ventricular septal defect and was identified with pathogenic NR2F2 variant.

PMID:37500725 - 16 previously unreported unrelated individuals (and a mildly affected mosaic mother of one of them) with rare heterozygous variants (majority are de novo variants) were reviewed in this publication and they had variable clinical presentations including intrauterine growth restriction (IUGR), CHD, CDH, genital anomalies, DSD, developmental delays, hypotonia, feeding difficulties, failure to thrive, congenital and acquired microcephaly, dysmorphic facial features, renal failure, hearing loss, strabismus, asplenia, and vascular malformations. All 14 for whom data is available had motor delays and 13 had speech delay. One of them had global developmental delay, one had mild intellectual disability and four had learning disabilities.
Intellectual disability v5.276 NR2F2 Achchuthan Shanmugasundram Publications for gene: NR2F2 were set to 29663647; 37500725
Intellectual disability v5.276 NR2F2 Achchuthan Shanmugasundram Publications for gene: NR2F2 were set to 29663647; 37500725
Intellectual disability v5.276 NR2F2 Achchuthan Shanmugasundram Publications for gene: NR2F2 were set to
Intellectual disability v5.275 NR2F2 Achchuthan Shanmugasundram Mode of inheritance for gene: NR2F2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.275 NR2F2 Achchuthan Shanmugasundram Mode of inheritance for gene: NR2F2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.275 NR2F2 Achchuthan Shanmugasundram Mode of inheritance for gene: NR2F2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.275 NR2F2 Achchuthan Shanmugasundram Mode of inheritance for gene: NR2F2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.274 NR2F2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.274 NR2F2 Achchuthan Shanmugasundram commented on gene: NR2F2: This gene is an established gene for congenital heart defects (MIM #615779) and disorder of sexual differentiation (MIM #618901).

PMID:29663647 - An 11-month old boy was reported with global developmental delay, dysmorphic features, coarctation of the aorta, and ventricular septal defect and was identified with pathogenic NR2F2 variant.

PMID:37500725 - 16 previously unreported unrelated individuals (and a mildly affected mosaic mother of one of them) with rare heterozygous variants (majority are de novo variants) were reviewed in this publication and they had variable clinical presentations including intrauterine growth restriction (IUGR), CHD, CDH, genital anomalies, DSD, developmental delays, hypotonia, feeding difficulties, failure to thrive, congenital and acquired microcephaly, dysmorphic facial features, renal failure, hearing loss, strabismus, asplenia, and vascular malformations. All 14 for whom data is available had motor delays and 13 had speech delay. One of them had global developmental delay, one had mild intellectual disability and four had learning disabilities.
Intellectual disability v5.274 NR2F2 Achchuthan Shanmugasundram reviewed gene: NR2F2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29663647, 37500725; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.274 U2AF2 Achchuthan Shanmugasundram Phenotypes for gene: U2AF2 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.274 U2AF2 Achchuthan Shanmugasundram Phenotypes for gene: U2AF2 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.275 U2AF2 Achchuthan Shanmugasundram Phenotypes for gene: U2AF2 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.274 U2AF2 Achchuthan Shanmugasundram Phenotypes for gene: U2AF2 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.275 U2AF2 Achchuthan Shanmugasundram Phenotypes for gene: U2AF2 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.275 U2AF2 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: U2AF2.
Tag Q3_23_NHS_review tag was added to gene: U2AF2.
Intellectual disability v5.275 U2AF2 Achchuthan Shanmugasundram Phenotypes for gene: U2AF2 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.274 U2AF2 Achchuthan Shanmugasundram Publications for gene: U2AF2 were set to 28135719; 31785789; 33057194; 34112922; 36747105; 37092751; 37134193
Intellectual disability v5.275 U2AF2 Achchuthan Shanmugasundram Phenotypes for gene: U2AF2 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.275 U2AF2 Achchuthan Shanmugasundram Phenotypes for gene: U2AF2 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.274 U2AF2 Achchuthan Shanmugasundram Phenotypes for gene: U2AF2 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.274 U2AF2 Achchuthan Shanmugasundram Phenotypes for gene: U2AF2 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.274 U2AF2 Achchuthan Shanmugasundram Phenotypes for gene: U2AF2 were changed from Developmental disorders to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.274 U2AF2 Achchuthan Shanmugasundram Publications for gene: U2AF2 were set to 28135719; 31785789; 33057194; 34112922; 36747105; 37092751; 37134193
Intellectual disability v5.274 U2AF2 Achchuthan Shanmugasundram Publications for gene: U2AF2 were set to 28135719; 31785789; 33057194; 34112922; 36747105; 37092751; 37134193
Intellectual disability v5.274 U2AF2 Achchuthan Shanmugasundram Publications for gene: U2AF2 were set to 28135719; 31785789; 33057194; 34112922; 36747105; 37092751; 37134193
Intellectual disability v5.273 U2AF2 Achchuthan Shanmugasundram Publications for gene: U2AF2 were set to 28135719; 31785789; 33057194; 34112922; 36747105; 37092751; 37134193
Intellectual disability v5.273 U2AF2 Achchuthan Shanmugasundram Publications for gene: U2AF2 were set to 28135719; 31785789; 33057194; 34112922; 36747105; 37092751; 37134193
Intellectual disability v5.273 U2AF2 Achchuthan Shanmugasundram Publications for gene: U2AF2 were set to 33057194
Intellectual disability v5.272 U2AF2 Achchuthan Shanmugasundram edited their review of gene: U2AF2: Changed publications to: 28135719, 31785789, 33057194, 34112922, 36747105, 37092751, 37134193
Intellectual disability v5.272 U2AF2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.272 U2AF2 Achchuthan Shanmugasundram Classified gene: U2AF2 as Amber List (moderate evidence)
Intellectual disability v5.272 U2AF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Celia Duff, there is sufficient evidence (>3 unrelated cases) available for the association of this gene with global developmental delay, intellectual disability and epilepsy. Hence, this gene should be promoted to green rating at the next GMS review.
Intellectual disability v5.272 U2AF2 Achchuthan Shanmugasundram Gene: u2af2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.272 U2AF2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.272 U2AF2 Achchuthan Shanmugasundram Classified gene: U2AF2 as Amber List (moderate evidence)
Intellectual disability v5.272 U2AF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Celia Duff, there is sufficient evidence (>3 unrelated cases) available for the association of this gene with global developmental delay, intellectual disability and epilepsy. Hence, this gene should be promoted to green rating at the next GMS review.
Intellectual disability v5.272 U2AF2 Achchuthan Shanmugasundram Gene: u2af2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.272 U2AF2 Achchuthan Shanmugasundram Classified gene: U2AF2 as Amber List (moderate evidence)
Intellectual disability v5.272 U2AF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Celia Duff, there is sufficient evidence (>3 unrelated cases) available for the association of this gene with global developmental delay, intellectual disability and epilepsy. Hence, this gene should be promoted to green rating at the next GMS review.
Intellectual disability v5.272 U2AF2 Achchuthan Shanmugasundram Gene: u2af2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.271 U2AF2 Achchuthan Shanmugasundram reviewed gene: U2AF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 28135719, 31785789, 34112922, 36747105, 37092751, 37134193; Phenotypes: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.271 MT-ND4 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing tag was added to gene: MT-ND4.
Intellectual disability v5.271 MT-ND1 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing tag was added to gene: MT-ND1.
Intellectual disability v5.271 MT-ATP6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing tag was added to gene: MT-ATP6.
Intellectual disability v5.271 PPP1R3F Zornitza Stark gene: PPP1R3F was added
gene: PPP1R3F was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: PPP1R3F was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PPP1R3F were set to 37531237
Phenotypes for gene: PPP1R3F were set to Neurodevelopmental Disorder, MONDO:0700092,PPP1R3F-related
Review for gene: PPP1R3F was set to GREEN
Added comment: 13 unrelated hemizygous individuals reported with functional evidence
Sources: Literature
Intellectual disability v5.271 RAB5C Zornitza Stark gene: RAB5C was added
gene: RAB5C was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: RAB5C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAB5C were set to 37552066
Phenotypes for gene: RAB5C were set to Neurodevelopmental disorder MONDO:0700092, RAB5C-related
Review for gene: RAB5C was set to GREEN
Added comment: 12 individuals with nine different heterozygous de novo variants in RAB5C.
9 with missense, 1 inframe duplication and 2 stop-gains (clinically more severe).
All have mild-severe ID, 4/12 have epilepsy, 6/12 have macrocephaly (more than 3 SD).
Sources: Literature
Intellectual disability v5.271 NR2F2 Katherine Lachlan reviewed gene: NR2F2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37500725; Phenotypes: intrauterine growth restriction (IUGR), CHD, CDH, genital anomalies, DSD, developmental delays, hypotonia, feeding difficulties, failure to thrive, congenital and acquired microcephaly, dysmorphic facial features, renal failure, hearing loss, strabismus, asplenia, vascular malformations; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.271 ATM Zornitza Stark reviewed gene: ATM: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Ataxia-telangiectasia, MIM#208900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.271 ESAM Julia Baptista gene: ESAM was added
gene: ESAM was added to Intellectual disability - microarray and sequencing. Sources: Literature,Expert Review
Mode of inheritance for gene: ESAM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ESAM were set to PMID: 36996813
Phenotypes for gene: ESAM were set to severe ID; seizures, spasticity
Review for gene: ESAM was set to GREEN
Added comment: Lecca et al 2023 reported thirteen patients from eight unrelated families with biallelic loss of function variants (nonsense, frameshift, canonical splice site, all predicted to result in a transcript targeted for nonsense-mediated decay). Protein staining assays in one of the brain fetal samples confirmed loss the loss of protein.
The phenotype reported in this cohort is of a severe neurodevelopmental disorder with brain anomalies (calcifications, hydrocephalus, enlarged ventricles, cerebral atrophy, etc), and dysmorphic features.
Sources: Literature, Expert Review
Intellectual disability v5.271 TP63 Arina Puzriakova Phenotypes for gene: TP63 were changed from Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome; 3, 604292; Split-hand/foot malformation 4, 605289; Hay-Wells syndrome, 106260; ADULT syndrome, 103285; Limb-mammary syndrome, 603543; Rapp-Hodgkin syndrome, 129400; Orofacial cleft 8, 129400 to ADULT syndrome, OMIM:103285; Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3, OMIM:604292; Hay-Wells syndrome, OMIM:106260; Limb-mammary syndrome, OMIM:603543; Orofacial cleft 8, OMIM:618149; Rapp-Hodgkin syndrome, OMIM:129400; Split-hand/foot malformation 4, OMIM:605289
Intellectual disability v5.270 ERMARD Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.270 ERMARD Achchuthan Shanmugasundram Classified gene: ERMARD as Red List (low evidence)
Intellectual disability v5.270 ERMARD Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Arina Puzriakova, this gene has been demoted from amber to red.
Intellectual disability v5.270 ERMARD Achchuthan Shanmugasundram Gene: ermard has been classified as Red List (Low Evidence).
Intellectual disability v5.270 ERMARD Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.270 ERMARD Achchuthan Shanmugasundram Classified gene: ERMARD as Red List (low evidence)
Intellectual disability v5.270 ERMARD Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Arina Puzriakova, this gene has been demoted from amber to red.
Intellectual disability v5.270 ERMARD Achchuthan Shanmugasundram Gene: ermard has been classified as Red List (Low Evidence).
Intellectual disability v5.270 ERMARD Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.270 ERMARD Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.270 ERMARD Achchuthan Shanmugasundram Classified gene: ERMARD as Red List (low evidence)
Intellectual disability v5.270 ERMARD Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Arina Puzriakova, this gene has been demoted from amber to red.
Intellectual disability v5.270 ERMARD Achchuthan Shanmugasundram Gene: ermard has been classified as Red List (Low Evidence).
Intellectual disability v5.269 ERMARD Achchuthan Shanmugasundram Classified gene: ERMARD as Red List (low evidence)
Intellectual disability v5.269 ERMARD Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Arina Puzriakova, this gene has been demoted to red.
Intellectual disability v5.269 ERMARD Achchuthan Shanmugasundram Gene: ermard has been classified as Red List (Low Evidence).
Intellectual disability v5.269 ERMARD Achchuthan Shanmugasundram Classified gene: ERMARD as Red List (low evidence)
Intellectual disability v5.269 ERMARD Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Arina Puzriakova, this gene has been demoted to red.
Intellectual disability v5.269 ERMARD Achchuthan Shanmugasundram Gene: ermard has been classified as Red List (Low Evidence).
Intellectual disability v5.268 U2AF2 celia duff changed review comment from: Literature evidence Ref1-5, identification of affected patients in the diagnostic setting (CVA database, 19:55661148:C>T ) and further accounts in open access databases (ClinVar and LOVD), make this gene suitable for clinical review and upgrading to a green gene status on relevant panels. It is associated with a phenotype encompassing dysmorphism, epilepsy, developmental delay, intellectual disability, and brain malformation Ref1-5. There is a recent publication that proposes an extension of this phenotype to include hypomyelination leukodystrophy Ref6. A loss of function mechanism has been suggested, associated with disruption of RNA recognition motifs required for the function of U2AF2 as a pre-mRNA splicing factor Ref4. At least one recurrent pathogenic variant has been identified by this review U2AF2 c.445C>T p.(Arg149Trp). U2AF2 is constrained for missense in gnomAD Z=4.71.
total variants reported
1) De novo U2AF2 (NM_007279.3:c.445C>T p.(Arg149Trp)) recurrent variant; 1x patient in Hiraide (PubMed: 34112922), 1x patient in Kittock (PubMed: 37092751), 2x patients in Kaplanis (Pubmed: 33057194), 7x patients in the Leiden Open Variation Database (LOVD, https://www.lovd.nl/), 1x patient in house BGL and 4x additional on CVA
2) De novo U2AF2 c.603G>T; 1 patient in Wang 2023 (PubMed: 36747105)
3) De novo U2AF2 c.470C>T p.Pro157Leu) in Kuroda (PubMed: 37134193)
4) 9x additional pathogenic or likely pathogenic variants on LOVD
5) 2x additional likely pathogenic variants on ClinVar

References
1.       PubMed: 28135719 McRae (2017)-DDD data
2.       PubMed: 31785789 Turner (2019)-DDD data
3.       PubMed: 34112922 Hiraide (2021) de novo U2AF2 c.445C>T p.R149W
4.       PubMed: 36747105 Wang (2023) de novo U2AF2 c.603G>T, p.163_201del
5.       PubMed: 37092751 Kittock (2023) de novo U2AF2 c.445C>T p.R149W
Possible emerging phenotype of hypomyelinating leukodystrophy
6.       PubMed: 37134193 Kuroda (2023); to: Literature evidence Ref1-5, identification of affected patients in the diagnostic setting (CVA database, 19:55661148:C>T ) and further accounts in open access databases (ClinVar and LOVD), make this gene suitable for clinical review and upgrading to a green gene status on relevant panels. It is associated with a phenotype encompassing dysmorphism, epilepsy, developmental delay, intellectual disability, and brain malformation Ref1-5. There is a recent publication that proposes an extension of this phenotype to include hypomyelination leukodystrophy Ref6. A loss of function mechanism has been suggested, associated with disruption of RNA recognition motifs required for the function of U2AF2 as a pre-mRNA splicing factor Ref4. At least one recurrent pathogenic variant has been identified by this review U2AF2 c.445C>T p.(Arg149Trp). U2AF2 is constrained for missense in gnomAD Z=4.71.
total variants/patients identified
1) De novo U2AF2 (NM_007279.3:c.445C>T p.(Arg149Trp)) recurrent variant; 1x patient in Hiraide (PubMed: 34112922), 1x patient in Kittock (PubMed: 37092751), 2x patients in Kaplanis (Pubmed: 33057194), 7x patients in the Leiden Open Variation Database (LOVD, https://www.lovd.nl/), 1x patient in house BGL and 4x additional on CVA
2) De novo U2AF2 c.603G>T; 1 patient in Wang 2023 (PubMed: 36747105)
3) De novo U2AF2 c.470C>T p.Pro157Leu) in Kuroda (PubMed: 37134193)
4) 9x additional pathogenic or likely pathogenic variants on LOVD
5) 2x additional likely pathogenic variants on ClinVar
6) We are collaborating with a researcher in the USA with a cohort of 40+ cases.


References
1.       PubMed: 28135719 McRae (2017)-DDD data
2.       PubMed: 31785789 Turner (2019)-DDD data
3.       PubMed: 34112922 Hiraide (2021) de novo U2AF2 c.445C>T p.R149W
4.       PubMed: 36747105 Wang (2023) de novo U2AF2 c.603G>T, p.163_201del
5.       PubMed: 37092751 Kittock (2023) de novo U2AF2 c.445C>T p.R149W
Possible emerging phenotype of hypomyelinating leukodystrophy
6.       PubMed: 37134193 Kuroda (2023)
Intellectual disability v5.268 U2AF2 celia duff reviewed gene: U2AF2: Rating: GREEN; Mode of pathogenicity: None; Publications: (PMID: 28135719):(PMID: 31785789):(PMID: 34112922):(PMID: 36747105):(PMID: 37092751):(PMID 37134193); Phenotypes: intellectual disability, global developmental delay, dysmorphism, epilepsy, brain malformation, microcephaly, possible emerging phenotype of hypomyelinating leukodystrophy.; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability v5.268 NEUROG1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.268 NEUROG1 Achchuthan Shanmugasundram Classified gene: NEUROG1 as Amber List (moderate evidence)
Intellectual disability v5.268 NEUROG1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are four unrelated cases reported with global developmental delay/ intellectual disability. Hence, this gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.268 NEUROG1 Achchuthan Shanmugasundram Gene: neurog1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.268 NEUROG1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.268 NEUROG1 Achchuthan Shanmugasundram Classified gene: NEUROG1 as Amber List (moderate evidence)
Intellectual disability v5.268 NEUROG1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are four unrelated cases reported with global developmental delay/ intellectual disability. Hence, this gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.268 NEUROG1 Achchuthan Shanmugasundram Gene: neurog1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.268 NEUROG1 Achchuthan Shanmugasundram Classified gene: NEUROG1 as Amber List (moderate evidence)
Intellectual disability v5.268 NEUROG1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are four unrelated cases reported with global developmental delay/ intellectual disability. Hence, this gene can be promoted to green rating in the next GMS review.
Intellectual disability v5.268 NEUROG1 Achchuthan Shanmugasundram Gene: neurog1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.267 NEUROG1 Achchuthan Shanmugasundram Publications for gene: NEUROG1 were set to 23419067; 26077850; 33439489; 36647078
Intellectual disability v5.267 NEUROG1 Achchuthan Shanmugasundram Publications for gene: NEUROG1 were set to 23419067; 26077850; 33439489; 36647078
Intellectual disability v5.267 NEUROG1 Achchuthan Shanmugasundram Publications for gene: NEUROG1 were set to 23419067; 26077850; 33439489; 36647078
Intellectual disability v5.267 NEUROG1 Achchuthan Shanmugasundram Publications for gene: NEUROG1 were set to 23419067; 26077850; 33439489; 36647078
Intellectual disability v5.266 NEUROG1 Achchuthan Shanmugasundram Phenotypes for gene: NEUROG1 were changed from Cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay, OMIM:620469 to Cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay, OMIM:620469
Intellectual disability v5.267 NEUROG1 Achchuthan Shanmugasundram Publications for gene: NEUROG1 were set to 23419067; 26077850; 33439489; 36647078
Intellectual disability v5.267 NEUROG1 Achchuthan Shanmugasundram Publications for gene: NEUROG1 were set to 23419067; 26077850; 33439489; 36647078
Intellectual disability v5.267 NEUROG1 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: NEUROG1.
Tag Q3_23_NHS_review tag was added to gene: NEUROG1.
Intellectual disability v5.267 NEUROG1 Achchuthan Shanmugasundram Publications for gene: NEUROG1 were set to 23419067; 26077850; 33439489; 36647078
Intellectual disability v5.267 NEUROG1 Achchuthan Shanmugasundram Publications for gene: NEUROG1 were set to 23419067; 26077850; 33439489; 36647078
Intellectual disability v5.267 NEUROG1 Achchuthan Shanmugasundram Publications for gene: NEUROG1 were set to 36647078; 33439489; 23419067; 26077850
Intellectual disability v5.266 NEUROG1 Achchuthan Shanmugasundram Phenotypes for gene: NEUROG1 were changed from Cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay, OMIM:620469 to Cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay, OMIM:620469
Intellectual disability v5.266 NEUROG1 Achchuthan Shanmugasundram Phenotypes for gene: NEUROG1 were changed from Cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay, OMIM:620469 to Cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay, OMIM:620469
Intellectual disability v5.266 NEUROG1 Achchuthan Shanmugasundram Phenotypes for gene: NEUROG1 were changed from Cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay, OMIM:620469 to Cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay, OMIM:620469
Intellectual disability v5.266 NEUROG1 Achchuthan Shanmugasundram Phenotypes for gene: NEUROG1 were changed from Cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay, OMIM:620469 to Cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay, OMIM:620469
Intellectual disability v5.265 NEUROG1 Achchuthan Shanmugasundram Phenotypes for gene: NEUROG1 were changed from Cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay, OMIM:620469 to Cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay, OMIM:620469
Intellectual disability v5.265 NEUROG1 Achchuthan Shanmugasundram Phenotypes for gene: NEUROG1 were changed from developmental delay; behavioural problems; cranial dysinnervation; absent corneal reflex to Cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay, OMIM:620469
Intellectual disability v5.264 NEUROG1 Achchuthan Shanmugasundram reviewed gene: NEUROG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23419067, 26077850, 33439489, 36647078; Phenotypes: Cranial dysinnervation disorder, congenital, with absent corneal reflex and developmental delay, OMIM:620469; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.264 CMIP Sarah Leigh reviewed gene: CMIP: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v5.264 CMIP Sarah Leigh Classified gene: CMIP as Red List (low evidence)
Intellectual disability v5.264 CMIP Sarah Leigh Gene: cmip has been classified as Red List (Low Evidence).
Intellectual disability v5.263 UQCRB Arina Puzriakova Phenotypes for gene: UQCRB were changed from Mitochondrial complex III deficiency, nuclear type 3, 615158 to Mitochondrial complex III deficiency, nuclear type 3, OMIM:615158
Intellectual disability v5.262 CMIP Sarah Leigh Publications for gene: CMIP were set to PMID: 22689534; 28504353
Intellectual disability v5.261 ATP6V0C Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.261 ATP6V0C Achchuthan Shanmugasundram Classified gene: ATP6V0C as Amber List (moderate evidence)
Intellectual disability v5.261 ATP6V0C Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (17 unrelated cases) for this gene to be promoted to green rating in the next GMS review.
Intellectual disability v5.261 ATP6V0C Achchuthan Shanmugasundram Gene: atp6v0c has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.261 ATP6V0C Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.261 ATP6V0C Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence available (17 unrelated cases) for this gene to be promoted to green rating in the next GMS review.; to: Comment on list classification: There is sufficient evidence available (17 unrelated cases) for this gene to be promoted to green rating in the next GMS review.
Intellectual disability v5.261 ATP6V0C Achchuthan Shanmugasundram Classified gene: ATP6V0C as Amber List (moderate evidence)
Intellectual disability v5.261 ATP6V0C Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (17 unrelated cases) for this gene to be promoted to green rating in the next GMS review.
Intellectual disability v5.261 ATP6V0C Achchuthan Shanmugasundram Gene: atp6v0c has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.261 ATP6V0C Achchuthan Shanmugasundram Classified gene: ATP6V0C as Amber List (moderate evidence)
Intellectual disability v5.261 ATP6V0C Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (17 unrelated cases) for this gene to be promoted to green rating in the next GMS review.
Intellectual disability v5.261 ATP6V0C Achchuthan Shanmugasundram Gene: atp6v0c has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.260 ATP6V0C Achchuthan Shanmugasundram Phenotypes for gene: ATP6V0C were changed from Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465 to Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465
Intellectual disability v5.260 ATP6V0C Achchuthan Shanmugasundram Phenotypes for gene: ATP6V0C were changed from Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465 to Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465
Intellectual disability v5.261 ATP6V0C Achchuthan Shanmugasundram Phenotypes for gene: ATP6V0C were changed from Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465 to Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465
Intellectual disability v5.261 ATP6V0C Achchuthan Shanmugasundram Phenotypes for gene: ATP6V0C were changed from Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465 to Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465
Intellectual disability v5.261 ATP6V0C Achchuthan Shanmugasundram Phenotypes for gene: ATP6V0C were changed from Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465 to Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465
Intellectual disability v5.261 ATP6V0C Achchuthan Shanmugasundram Phenotypes for gene: ATP6V0C were changed from Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465 to Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465
Intellectual disability v5.260 ATP6V0C Achchuthan Shanmugasundram Phenotypes for gene: ATP6V0C were changed from Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465 to Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465
Intellectual disability v5.260 ATP6V0C Achchuthan Shanmugasundram Tag watchlist was removed from gene: ATP6V0C.
Tag Q3_23_promote_green tag was added to gene: ATP6V0C.
Tag Q3_23_NHS_review tag was added to gene: ATP6V0C.
Intellectual disability v5.260 ATP6V0C Achchuthan Shanmugasundram Publications for gene: ATP6V0C were set to 24623842; 33090716; 33190975; 36074901; 37161035
Intellectual disability v5.260 ATP6V0C Achchuthan Shanmugasundram Phenotypes for gene: ATP6V0C were changed from Epilepsy; Intellectual Disability; microcephaly to Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465
Intellectual disability v5.260 ATP6V0C Achchuthan Shanmugasundram Publications for gene: ATP6V0C were set to 24623842; 33090716; 33190975; 36074901; 37161035
Intellectual disability v5.260 ATP6V0C Achchuthan Shanmugasundram Publications for gene: ATP6V0C were set to 24623842; 33090716; 33190975; 36074901; 37161035
Intellectual disability v5.259 ATP6V0C Achchuthan Shanmugasundram Publications for gene: ATP6V0C were set to 24623842; 33090716; 33190975; 36074901; 37161035
Intellectual disability v5.259 ATP6V0C Achchuthan Shanmugasundram Publications for gene: ATP6V0C were set to 24623842; 33190975; 33090716; 36074901; 37161035
Intellectual disability v5.258 ATP6V0C Achchuthan Shanmugasundram Publications for gene: ATP6V0C were set to 24623842; 33190975; 33090716; 36074901; 37161035
Intellectual disability v5.258 ATP6V0C Achchuthan Shanmugasundram Publications for gene: ATP6V0C were set to 33190975; 33090716
Intellectual disability v5.257 ATP6V0C Achchuthan Shanmugasundram edited their review of gene: ATP6V0C: Changed publications to: 24623842, 33190975, 36074901, 37161035
Intellectual disability v5.257 ATP6V0C Achchuthan Shanmugasundram changed review comment from: 17 of 32 total patients had impaired intellectual development.; to: PMID:36074901 - 16 of 27 patients identified with monoallelic ATP6V0C variants, including a patient each from PMID:24623842 and PMID:33190975 had impaired intellectual development, while 21 patients had developmental delay.

PMID:37161035 - One of three patients identified with monoallelic ATP6V0C variant had impaired intellectual development and language delay, while another had developmental delay and speech delay.

This gene has been associated with relevant phenotypes in OMIM (MIM #620465) and Gene2Phenotype (with 'strong' rating in the DD panel).
Intellectual disability v5.257 ATP6V0C Achchuthan Shanmugasundram edited their review of gene: ATP6V0C: Changed publications to: 24623842, 33190975, 35600075, 36074901, 37161035
Intellectual disability v5.257 ATP6V0C Achchuthan Shanmugasundram reviewed gene: ATP6V0C: Rating: GREEN; Mode of pathogenicity: None; Publications: 33190975, 35600075, 36074901, 37161035; Phenotypes: Epilepsy, early-onset, 3, with or without developmental delay, OMIM:620465; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.257 PTCH1 Arina Puzriakova Phenotypes for gene: PTCH1 were changed from Basal cell nevus syndrome, 109400Basal cell carcinoma, somatic, 605462Holoprosencephaly-7, 610828; HOLOPROSENCEPHALY-7 to Holoprosencephaly 7, OMIM:610828
Intellectual disability v5.256 NEUROG1 Julia Baptista gene: NEUROG1 was added
gene: NEUROG1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: NEUROG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEUROG1 were set to 36647078; 33439489; 23419067; 26077850
Phenotypes for gene: NEUROG1 were set to developmental delay; behavioural problems; cranial dysinnervation; absent corneal reflex
Review for gene: NEUROG1 was set to GREEN
Added comment: Five affected individuals from four independently reported families (Middle Eastern, Portuguese, Indian and Turkish backgrounds) with biallelic microdeletion, missense, nonsense or frameshift variants.

Affected individuals present at birth or in early infancy with corneal opacities due to absent blinking, sensorineural deafness associated with hypoplastic or malformed cochlea and hypoplasia or agenesis of CN VIII was reported. Developmental delay, poor speech, autistic behavior and dysmorphic facial features were also present.
Sources: Literature
Intellectual disability v5.256 ATP6V0C Julia Baptista reviewed gene: ATP6V0C: Rating: GREEN; Mode of pathogenicity: None; Publications: 36074901; Phenotypes: Epilepsy, Intellectual Disability, Microcephaly; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.256 DNAH14 Sarah Leigh Publications for gene: DNAH14 were set to 35438214
Intellectual disability v5.256 DNAH14 Sarah Leigh Classified gene: DNAH14 as Red List (low evidence)
Intellectual disability v5.256 DNAH14 Sarah Leigh Gene: dnah14 has been classified as Red List (Low Evidence).
Intellectual disability v5.255 DNAH14 Sarah Leigh reviewed gene: DNAH14: Rating: RED; Mode of pathogenicity: None; Publications: 26036949, 30125339, 26636390, 32848021; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.255 FAM111A Tracy Lester reviewed gene: FAM111A: Rating: RED; Mode of pathogenicity: None; Publications: 23684011, 37023242; Phenotypes: Skeletal dysplasia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.255 CMIP Tord Jonson edited their review of gene: CMIP: Changed phenotypes to: HP:0012759 Neurodevelopmental abnormality, HP:0000717 Autism, HP:0007018 Attention deficit hyperactivity disorder, HP:0001250 Seizure, HP:0011471 Gastrostomy tube feeding in infancy
Intellectual disability v5.255 CMIP Tord Jonson changed review comment from: CMIP (MANE Select NM_198390) loss of function-variants (deletions) have been reported in two studies that describes patients with syndromic ASD and co-morbid gastrointestinal issues. See Van der Aa et al., 2012, Haploinsufficiency of CMIP in a girl with autism spectrum disorder and developmental delay due to a de novo deletion on chromosome 16q23.2 (PMID: 22689534); and Luo et al., 2017, CMIP haploinsufficiency in two patients with autism spectrum disorder and co-occurring gastrointestinal issues (PMID: 28504353). In addition, we have observed a local case with a de novo deletion encompassing only the genes CMIP and GAN in a patient with gastrostomy, intellectual disability, autism, ADHD and seizures.
Sources: Other; to: CMIP (MANE Select NM_198390) loss of function-variants (deletions) have been reported in two studies that describes patients with syndromic ASD and co-morbid gastrointestinal issues. See Van der Aa et al., 2012, Haploinsufficiency of CMIP in a girl with autism spectrum disorder and developmental delay due to a de novo deletion on chromosome 16q23.2 (PMID: 22689534); and Luo et al., 2017, CMIP haploinsufficiency in two patients with autism spectrum disorder and co-occurring gastrointestinal issues (PMID: 28504353). In addition, we have observed a local case with a de novo deletion encompassing only the genes CMIP and GAN in a patient with gastrostomy, intellectual disability, autism, ADHD and seizures.
Intellectual disability v5.255 CMIP Tord Jonson gene: CMIP was added
gene: CMIP was added to Intellectual disability - microarray and sequencing. Sources: Other
Mode of inheritance for gene: CMIP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CMIP were set to PMID: 22689534; 28504353
Phenotypes for gene: CMIP were set to HP:0012759; HP:0000717; HP:0007018; HP:0001250; HP:0011471
Penetrance for gene: CMIP were set to unknown
Review for gene: CMIP was set to GREEN
gene: CMIP was marked as current diagnostic
Added comment: CMIP (MANE Select NM_198390) loss of function-variants (deletions) have been reported in two studies that describes patients with syndromic ASD and co-morbid gastrointestinal issues. See Van der Aa et al., 2012, Haploinsufficiency of CMIP in a girl with autism spectrum disorder and developmental delay due to a de novo deletion on chromosome 16q23.2 (PMID: 22689534); and Luo et al., 2017, CMIP haploinsufficiency in two patients with autism spectrum disorder and co-occurring gastrointestinal issues (PMID: 28504353). In addition, we have observed a local case with a de novo deletion encompassing only the genes CMIP and GAN in a patient with gastrostomy, intellectual disability, autism, ADHD and seizures.
Sources: Other
Intellectual disability v5.255 PABPC1 Sarah Leigh Tag Q3_23_phenotype tag was added to gene: PABPC1.
Intellectual disability v5.255 PABPC1 Sarah Leigh edited their review of gene: PABPC1: Added comment: PABPC1 variants have not been associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 35511136 reports four de novo PABPC1 variants in four unrelated cases with a phenotype of global DD, movement coordination disorders,
seizures, behavioral disorders and mild facial dysmorphisms. Intellectual disability ranged in the cases from profound (1/4), IQ: 61 (1/4) and IQ: 79 (2/4). Seizures were apparent in the all of the three cases where it was assessed.
Molecular modeling of the variants suggested that they would result in a reduced binding affinity to the messenger RNA metabolism-related protein - PAIP2. This predicted effect was seen in coimmunoprecipitation assays between variant PABPC1 and PAIP2 (PMID: 35511136). Further functional studies in PMID: 35511136, showed that the proliferation of neural progenitor cells in Pabpc1 knockdown mouse embryo brains were decreased, this effect was rescued by the wild-type Pabpc1, but not by the variants c.1691A>G (p.Glu564Gly) or c.1709T>C (p.Ile570Thr).
Other variants were identified in 3/4 cases in PMID: 35511136, two of these had a ACMG VUS classification (RBBP4: c.845A>G, p.(Asn282Ser), IGF2R: c.1850G>A p.Cys617Tyr), while the third variant was monoallelic, whereas bialleic variants in this gene are associated with disease (KDM5B: c.2265dupA, p.(Tyr755*))(PMID: 35511136, table 1).; Changed rating: GREEN
Intellectual disability v5.255 PABPC1 Sarah Leigh Tag Q3_23_promote_green tag was added to gene: PABPC1.
Tag Q3_23_MOI tag was added to gene: PABPC1.
Intellectual disability v5.255 PABPC1 Sarah Leigh Classified gene: PABPC1 as Amber List (moderate evidence)
Intellectual disability v5.255 PABPC1 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 v5.255 PABPC1 Sarah Leigh Gene: pabpc1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.254 CLCNKA Sarah Leigh Phenotypes for gene: CLCNKA were changed from Bartter syndrome, type 4b, digenic, 613090; Infantile Bartter syndrome with sensorineural deafness, intellectual disability to Bartter syndrome, type 4b, digenic, OMIM:613090; Bartter disease type 4B, MONDO:0000909
Intellectual disability v5.253 CLCNKA Sarah Leigh Publications for gene: CLCNKA were set to
Intellectual disability v5.253 CLCNKA Sarah Leigh Added comment: Comment on mode of inheritance: Digenic CLCNKA & CLCNKB variants are associated with Bartter syndrome, type 4b, digenic (OMIM:613090)(PMID: 15044642;18310267;32488762). The current GMS rare disease bioinformatic pipeline does not allow for interpretation of digenic events.
Intellectual disability v5.253 CLCNKA Sarah Leigh Mode of inheritance for gene: CLCNKA was changed from to Other
Intellectual disability v5.252 CLCNKB Sarah Leigh Added comment: Comment on mode of inheritance: The mode of inheritance for CLCNKB should be BIALLELIC, autosomal or pseudoautosomal. Although digenic CLCNKB & CLCNKA variants are associated with Bartter syndrome, type 4b, digenic (OMIM:613090), the current GMS rare disease bioinformatic pipeline does not allow for interpretation of digenic events.
Intellectual disability v5.252 CLCNKB Sarah Leigh Mode of inheritance for gene: CLCNKB was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.251 CLCNKB Sarah Leigh Tag digenic was removed from gene: CLCNKB.
Tag monogenic-polygenic tag was added to gene: CLCNKB.
Intellectual disability v5.251 MKL2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.251 MKL2 Achchuthan Shanmugasundram Classified gene: MKL2 as Amber List (moderate evidence)
Intellectual disability v5.251 MKL2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As there are only two unrelated cases reported so far, this gene should be rated amber for now.
Intellectual disability v5.251 MKL2 Achchuthan Shanmugasundram Gene: mkl2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.250 MKL2 Achchuthan Shanmugasundram Phenotypes for gene: MKL2 were changed from neurodevelopmental disorder, MONDO:0700092 to neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.250 MKL2 Achchuthan Shanmugasundram Phenotypes for gene: MKL2 were changed from neurodevelopmental disorder, MONDO:0700092 to neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.250 MKL2 Achchuthan Shanmugasundram Phenotypes for gene: MKL2 were changed from neurodevelopmental disorder, MONDO:0700092 to neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.249 MKL2 Achchuthan Shanmugasundram Phenotypes for gene: MKL2 were changed from neurodevelopmental disorder, MONDO:0700092 to neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.249 MKL2 Achchuthan Shanmugasundram Phenotypes for gene: MKL2 were changed from neurodevelopmental phenotype with dysmorphic features to neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.249 MKL2 Achchuthan Shanmugasundram Publications for gene: MKL2 were set to 37013900
Intellectual disability v5.249 MKL2 Achchuthan Shanmugasundram Publications for gene: MKL2 were set to 37013900
Intellectual disability v5.248 MKL2 Achchuthan Shanmugasundram Publications for gene: MKL2 were set to 37013900
Intellectual disability v5.248 MKL2 Achchuthan Shanmugasundram Publications for gene: MKL2 were set to PMID:37013900
Intellectual disability v5.247 MKL2 Achchuthan Shanmugasundram commented on gene: MKL2: PMID:37013900 - Two unrelated paediatric cases with de novo variants in MKL2 gene (p.Arg103Gly & p.Ala91Pro) were reported with mild dysmorphic features, severe intellectual disability, global developmental delays, speech apraxia, and impulse control issues. Functional studies in a Drosophila model suggest a gain of function disease mechanism.
Intellectual disability v5.247 MKL2 Achchuthan Shanmugasundram reviewed gene: MKL2: 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: 37013900; Phenotypes: neurodevelopmental disorder, MONDO:0700092; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.247 ATG4D Achchuthan Shanmugasundram Classified gene: ATG4D as Amber List (moderate evidence)
Intellectual disability v5.247 ATG4D Achchuthan Shanmugasundram Added comment: Comment on list classification: There are two unrelated cases with mild cognitive impairment and hence this gene should be rated amber with the current evidence.
Intellectual disability v5.247 ATG4D Achchuthan Shanmugasundram Gene: atg4d has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.246 ATG4D Achchuthan Shanmugasundram changed review comment from: PMID:36765070 - Three individuals from two different families were reported with a neurodevelopmental disorder and identified with compound heterozygous variants in ATG4D gene (family 1: :c.266G>A/ p.Ser89Asn & c.839A>G/ p.Tyr280Cys; family 2: c.1310_1328del/ p.Asp437Alafs*37 & c.1066G>A/ p.Asp356Asn). Patient from family 1 and one of two patients from family 2 had mild cognitive impairment.

This gene has been associated with relevant phenotypes in Gene2Phenotype (with 'limited' rating in the DD panel), but not yet in OMIM.; to: PMID:36765070 - Three individuals from two different families were reported with a neurodevelopmental disorder and identified with compound heterozygous variants in ATG4D gene (family 1: :c.266G>A/ p.Ser89Asn & c.839A>G/ p.Tyr280Cys; family 2: c.1310_1328del/ p.Asp437Alafs*37 & c.1066G>A/ p.Asp356Asn). Patient from family 1 and one of two patients from family 2 had mild cognitive impairment. Based on the clinical, bioinformatic, and functional data, the authors also concluded that bi-allelic loss-of-function variants in ATG4D contribute to the pathogenesis of syndromic neurodevelopmental disorder.

This gene has been associated with relevant phenotypes in Gene2Phenotype (with 'limited' rating in the DD panel), but not yet in OMIM.
Intellectual disability v5.246 ATG4D Achchuthan Shanmugasundram changed review comment from: PMID:36765070 - Three individuals from two different families were reported with a neurodevelopmental disorder and identified with compound heterozygous variants in ATG4D gene (family 1: :c.266G>A/ p.Ser89Asn & c.839A>G/ p.Tyr280Cys; family 2: c.1310_1328del/ p.Asp437Alafs*37 & c.1066G>A/ p.Asp356Asn). Patient from family 1 and one of two patients from family 2 had cognitive impairment.

This gene has been associated with relevant phenotypes in Gene2Phenotype (with 'limited' rating in the DD panel), but not yet in OMIM.; to: PMID:36765070 - Three individuals from two different families were reported with a neurodevelopmental disorder and identified with compound heterozygous variants in ATG4D gene (family 1: :c.266G>A/ p.Ser89Asn & c.839A>G/ p.Tyr280Cys; family 2: c.1310_1328del/ p.Asp437Alafs*37 & c.1066G>A/ p.Asp356Asn). Patient from family 1 and one of two patients from family 2 had mild cognitive impairment.

This gene has been associated with relevant phenotypes in Gene2Phenotype (with 'limited' rating in the DD panel), but not yet in OMIM.
Intellectual disability v5.246 ATG4D Achchuthan Shanmugasundram Phenotypes for gene: ATG4D were changed from neurodevelopmental disorder, MONDO:0700092 to neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.246 ATG4D Achchuthan Shanmugasundram Phenotypes for gene: ATG4D were changed from neurodevelopmental disorder characterized by speech and motor impairment to neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.245 ATG4D Achchuthan Shanmugasundram edited their review of gene: ATG4D: Changed rating: AMBER; Changed publications to: 36765070; Changed phenotypes to: neurodevelopmental disorder, MONDO:0700092; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.245 AKT3 Arina Puzriakova Phenotypes for gene: AKT3 were changed from Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome, 603387; HEMIMEGALENCEPHALY AKT3 to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2, OMIM:615937
Intellectual disability v5.244 ATG4D Achchuthan Shanmugasundram commented on gene: ATG4D
Intellectual disability v5.244 PSMC3 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.244 PSMC3 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.244 PSMC3 Achchuthan Shanmugasundram Classified gene: PSMC3 as Amber List (moderate evidence)
Intellectual disability v5.244 PSMC3 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene can be promoted to green rating at the next GMS review.
Intellectual disability v5.244 PSMC3 Achchuthan Shanmugasundram Gene: psmc3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.243 PSMC3 Achchuthan Shanmugasundram Added comment: 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".
Intellectual disability v5.243 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
Intellectual disability v5.243 PSMC3 Achchuthan Shanmugasundram Added comment: 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".
Intellectual disability v5.243 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
Intellectual disability v5.243 PSMC3 Achchuthan Shanmugasundram Added comment: 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".
Intellectual disability v5.243 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
Intellectual disability v5.242 PSMC3 Achchuthan Shanmugasundram Phenotypes for gene: PSMC3 were changed from ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092 to ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.242 PSMC3 Achchuthan Shanmugasundram Phenotypes for gene: PSMC3 were changed from ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092 to ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.242 PSMC3 Achchuthan Shanmugasundram Phenotypes for gene: PSMC3 were changed from ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092 to ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.242 PSMC3 Achchuthan Shanmugasundram Phenotypes for gene: PSMC3 were changed from ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092 to ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.242 PSMC3 Achchuthan Shanmugasundram Phenotypes for gene: PSMC3 were changed from ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092 to ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.242 PSMC3 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: PSMC3.
Intellectual disability v5.242 PSMC3 Achchuthan Shanmugasundram Phenotypes for gene: PSMC3 were changed from ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092 to ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.242 PSMC3 Achchuthan Shanmugasundram Phenotypes for gene: PSMC3 were changed from ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092 to ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.242 PSMC3 Achchuthan Shanmugasundram Phenotypes for gene: PSMC3 were changed from ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092 to ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.242 PSMC3 Achchuthan Shanmugasundram Phenotypes for gene: PSMC3 were changed from ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092 to ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.241 PSMC3 Achchuthan Shanmugasundram Phenotypes for gene: PSMC3 were changed from neurodevelopmental delay to ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v5.241 PSMC3 Achchuthan Shanmugasundram Publications for gene: PSMC3 were set to 32500975; 37256937
Intellectual disability v5.241 PSMC3 Achchuthan Shanmugasundram Publications for gene: PSMC3 were set to 32500975; 37256937
Intellectual disability v5.241 PSMC3 Achchuthan Shanmugasundram Publications for gene: PSMC3 were set to 32500975; 37256937
Intellectual disability v5.240 PSMC3 Achchuthan Shanmugasundram Publications for gene: PSMC3 were set to 32500975; 37256937
Intellectual disability v5.240 PSMC3 Achchuthan Shanmugasundram Publications for gene: PSMC3 were set to PMID: 37256937
Intellectual disability v5.239 PSMC3 Achchuthan Shanmugasundram reviewed gene: PSMC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 32500975, 37256937; Phenotypes: ?Deafness, cataract, impaired intellectual development, and polyneuropathy, OMIM:619354, neurodevelopmental disorder, MONDO:0700092; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.239 KCNH5 Achchuthan Shanmugasundram Phenotypes for gene: KCNH5 were changed from developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071 to developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071
Intellectual disability v5.240 KCNH5 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.240 KCNH5 Achchuthan Shanmugasundram Classified gene: KCNH5 as Amber List (moderate evidence)
Intellectual disability v5.240 KCNH5 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Dmitrijs Rots, there is sufficient evidence for the association of this gene to intellectual disability. Hence, this gene can be promoted to green rating at the next GMS review.
Intellectual disability v5.240 KCNH5 Achchuthan Shanmugasundram Gene: kcnh5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.241 KCNH5 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.241 KCNH5 Achchuthan Shanmugasundram Phenotypes for gene: KCNH5 were changed from developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071 to developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071
Intellectual disability v5.241 KCNH5 Achchuthan Shanmugasundram Classified gene: KCNH5 as Amber List (moderate evidence)
Intellectual disability v5.241 KCNH5 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Dmitrijs Rots, there is sufficient evidence for the association of this gene to intellectual disability. Hence, this gene can be promoted to green rating at the next GMS review.
Intellectual disability v5.241 KCNH5 Achchuthan Shanmugasundram Gene: kcnh5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.240 KCNH5 Achchuthan Shanmugasundram Phenotypes for gene: KCNH5 were changed from developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071 to developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071
Intellectual disability v5.240 KCNH5 Achchuthan Shanmugasundram Phenotypes for gene: KCNH5 were changed from developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071 to developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071
Intellectual disability v5.240 KCNH5 Achchuthan Shanmugasundram Classified gene: KCNH5 as Amber List (moderate evidence)
Intellectual disability v5.240 KCNH5 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Dmitrijs Rots, there is sufficient evidence for the association of this gene to intellectual disability. Hence, this gene can be promoted to green rating at the next GMS review.
Intellectual disability v5.240 KCNH5 Achchuthan Shanmugasundram Gene: kcnh5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.239 KCNH5 Achchuthan Shanmugasundram Publications for gene: KCNH5 were set to 23647072; 35874597; 36307226; 24133262
Intellectual disability v5.239 KCNH5 Achchuthan Shanmugasundram Publications for gene: KCNH5 were set to 23647072; 35874597; 36307226; 24133262
Intellectual disability v5.239 KCNH5 Achchuthan Shanmugasundram Publications for gene: KCNH5 were set to 23647072; 35874597; 36307226; 24133262
Intellectual disability v5.240 KCNH5 Achchuthan Shanmugasundram Phenotypes for gene: KCNH5 were changed from developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071 to developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071
Intellectual disability v5.239 KCNH5 Achchuthan Shanmugasundram Publications for gene: KCNH5 were set to 23647072; 35874597; 36307226; 24133262
Intellectual disability v5.240 KCNH5 Achchuthan Shanmugasundram Phenotypes for gene: KCNH5 were changed from developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071 to developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071
Intellectual disability v5.239 KCNH5 Achchuthan Shanmugasundram Publications for gene: KCNH5 were set to 23647072; 35874597; 36307226; 24133262
Intellectual disability v5.239 KCNH5 Achchuthan Shanmugasundram Phenotypes for gene: KCNH5 were changed from developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071 to developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071
Intellectual disability v5.239 KCNH5 Achchuthan Shanmugasundram Phenotypes for gene: KCNH5 were changed from INFANTILE EPILEPTIC ENCEPHALOPATHY to developmental and epileptic encephalopathy, MONDO:0100062; intellectual disability, MONDO:0001071
Intellectual disability v5.238 KCNH5 Achchuthan Shanmugasundram Publications for gene: KCNH5 were set to 23647072; 35874597; 36307226; 24133262
Intellectual disability v5.239 KCNH5 Achchuthan Shanmugasundram Publications for gene: KCNH5 were set to 23647072; 35874597; 36307226; 24133262
Intellectual disability v5.238 KCNH5 Achchuthan Shanmugasundram Publications for gene: KCNH5 were set to 23647072; 35874597; 36307226; 24133262
Intellectual disability v5.238 KCNH5 Achchuthan Shanmugasundram Mode of pathogenicity for gene: KCNH5 was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v5.238 KCNH5 Achchuthan Shanmugasundram Publications for gene: KCNH5 were set to 23647072
Intellectual disability v5.238 KCNH5 Achchuthan Shanmugasundram Mode of pathogenicity for gene: KCNH5 was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v5.238 KCNH5 Achchuthan Shanmugasundram Mode of pathogenicity for gene: KCNH5 was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v5.237 KCNH5 Achchuthan Shanmugasundram Mode of pathogenicity for gene: KCNH5 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
Intellectual disability v5.236 KCNH5 Achchuthan Shanmugasundram Mode of inheritance for gene: KCNH5 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.236 KCNH5 Achchuthan Shanmugasundram Mode of inheritance for gene: KCNH5 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.235 KCNH5 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: KCNH5.
Intellectual disability v5.235 KCNH5 Achchuthan Shanmugasundram reviewed gene: KCNH5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23647072, 35874597, 36307226, 24133262; Phenotypes: developmental and epileptic encephalopathy, MONDO:0100062, intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.235 CLCNKB Sarah Leigh Tag polygenic was removed from gene: CLCNKB.
Tag digenic tag was added to gene: CLCNKB.
Intellectual disability v5.235 CLCNKB Sarah Leigh Phenotypes for gene: CLCNKB were changed from Bartter syndrome, type 3, 607364Bartter syndrome, type 4b, digenic, 613090; BARTTER SYNDROME TYPE 4B to Bartter syndrome, type 3, OMIM:607364; Bartter disease type 3, MONDO:0011822; Bartter syndrome, type 4b, digenic, OMIM:613090; Bartter disease type 4B, MONDO:0000909
Intellectual disability v5.234 LETM1 Sarah Leigh changed review comment from: LETM1 variants has been associated with Neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction, OMIM:620089 and as moderate Gen2Phen gene for LETM1-related neurodevelopmental disorder.
PMID: 36055214 reports 10 LETM1 variants in 18 patients from 11 unrelated families with childhood-onset neurodegeneration with multisystem involvement, many of whom were gathered using the GeneMatcher Program. The most common clinical features of this cohort, where an assessment could be made, were: mitochondrial respiratory complex deficiencies 11/11 (100%), global developmental delay / intellectual disability 17/18 (94%), bilateral sensorineural hearing loss 11/14 (78%) , impaired vision 10/10 (100%), cerebellar ataxia 7/9 (78%), seizures 10/15 (67%), hypotonia 11/18 (61%) (PMID: 36055214, figure 1c).; to: LETM1 variants have been associated with Neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction, OMIM:620089 and as moderate Gen2Phen gene for LETM1-related neurodevelopmental disorder.
PMID: 36055214 reports 10 LETM1 variants in 18 patients from 11 unrelated families with childhood-onset neurodegeneration with multisystem involvement, many of whom were gathered using the GeneMatcher Program. The most common clinical features of this cohort, where an assessment could be made, were: mitochondrial respiratory complex deficiencies 11/11 (100%), global developmental delay / intellectual disability 17/18 (94%), bilateral sensorineural hearing loss 11/14 (78%) , impaired vision 10/10 (100%), cerebellar ataxia 7/9 (78%), seizures 10/15 (67%), hypotonia 11/18 (61%) (PMID: 36055214, figure 1c).
Intellectual disability v5.234 SLC22A5 Sarah Leigh Mode of inheritance for gene: SLC22A5 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.233 SLC22A5 Sarah Leigh changed review comment from: Comment on mode of inheritance: The mode of inheritance for SLC22A5 variants should be BOTH Monoallelic and Biallelic. Although, most of the evidence for symptoms associated SLC22A5 are seen in a patients with biallelic variants (HGNC:10969, OMIM:603377, Gen2Phen, Orphanet:118781, ClinGen), a few individuals heterozygous for SLC22A5 variants have been seen with a milder phenotype (PMID: 10545605; 11261427).; to: Comment on mode of inheritance: The mode of inheritance for SLC22A5 variants should be BIALLELIC, autosomal or pseudoautosomal. Although, heterozygous SLC22A5 variants have been seen in a few cases, these are detectable biochemically and are not associated with clear clinical presentation (PMID: 10545605; 11261427).
Intellectual disability v5.233 RPS6KA3 Arina Puzriakova Tag Q3_23_MOI tag was added to gene: RPS6KA3.
Intellectual disability v5.233 RPS6KA3 Arina Puzriakova Publications for gene: RPS6KA3 were set to
Intellectual disability v5.232 RPS6KA3 Arina Puzriakova Added comment: Comment on mode of inheritance: Should be updated from XLR to XLD (monoallelic variants in females may cause disease) at the next GMS panel update as several affected female carriers have been reported. ID in female carriers can range from mild to severe which is within the scope of the panel (PMIDs: 12210291; 12030896; 12558110; 17318637). This would also match the current MOI on other GMS panels and OMIM.
Intellectual disability v5.232 RPS6KA3 Arina Puzriakova Mode of inheritance for gene: RPS6KA3 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.231 RPS6KA3 Arina Puzriakova Phenotypes for gene: RPS6KA3 were changed from Coffin-Lowry syndrome, 303600Mental retardation, X-linked 19, 300844; COFFIN-LOWRY SYNDROME (CLS) to Coffin-Lowry syndrome, OMIM:303600; Intellectual developmental disorder, X-linked 19, OMIM:300844
Intellectual disability v5.230 KCNH5 Dmitrijs Rots reviewed gene: KCNH5: 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: PMID: 36307226, 35874597; Phenotypes: Neurodevelopmental disorder and Epilepsy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.230 LETM1 Sarah Leigh Entity copied from Ataxia and cerebellar anomalies - narrow panel v4.27
Intellectual disability v5.230 LETM1 Sarah Leigh gene: LETM1 was added
gene: LETM1 was added to Intellectual disability - microarray and sequencing. Sources: Expert Review Amber,Expert Review
Q3_23_promote_green, Q3_23_MOI tags were added to gene: LETM1.
Mode of inheritance for gene: LETM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LETM1 were set to 36055214; 33815143
Phenotypes for gene: LETM1 were set to Neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction, OMIM:620089
Intellectual disability v5.229 SLC25A24 Sarah Leigh Publications for gene: SLC25A24 were set to
Intellectual disability v5.228 SLC25A24 Sarah Leigh Phenotypes for gene: SLC25A24 were changed from to Fontaine progeroid syndrome, OMIM; 612289; Fontaine progeroid syndrome, MONDO:0012853
Intellectual disability v5.227 SLC22A5 Sarah Leigh Publications for gene: SLC22A5 were set to 9916797; 10425211; 15714519; 10480371; 9700603; 2235122; 20027113; 9634512; 11058897; 3974805; 10051646
Intellectual disability v5.227 SLC22A5 Sarah Leigh Added comment: Comment on mode of inheritance: The mode of inheritance for SLC22A5 variants should be BOTH Monoallelic and Biallelic. Although, most of the evidence for symptoms associated SLC22A5 are seen in a patients with biallelic variants (HGNC:10969, OMIM:603377, Gen2Phen, Orphanet:118781, ClinGen), a few individuals heterozygous for SLC22A5 variants have been seen with a milder phenotype (PMID: 10545605; 11261427).
Intellectual disability v5.227 SLC22A5 Sarah Leigh Mode of inheritance for gene: SLC22A5 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.226 SLC22A5 Sarah Leigh Phenotypes for gene: SLC22A5 were changed from Carnitine deficiency, systemic primary, 212140 to Carnitine deficiency, systemic primary, OMIM:212140; systemic primary carnitine deficiency disease, MONDO:0008919
Intellectual disability v5.225 AGTPBP1 Achchuthan Shanmugasundram Classified gene: AGTPBP1 as Amber List (moderate evidence)
Intellectual disability v5.225 AGTPBP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to green rating at the next major update.
Intellectual disability v5.225 AGTPBP1 Achchuthan Shanmugasundram Gene: agtpbp1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.224 AGTPBP1 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: AGTPBP1.
Intellectual disability v5.224 AGTPBP1 Achchuthan Shanmugasundram changed review comment from: PMID:30420557 reported the identification of either homozygous or compound heterozygous variants in AGTPBP1 gene in 13 individuals from 10 unrelated families with infantile‐onset neurodegeneration. Impaired intellectual development was severe in several patients: Two had severe cognitive delay, one had profound cognitive delay, five had no speech and four had no visual recognition. In addition, functional studies with mouse models have recapitulated the human phenotype.

This gene has been associated with relevant phenotypes in both OMIM (MIM #618276) and Gene2Phenotype (on DD panel with 'definitive' rating).
Sources: Literature; to: PMID:30420557 reported the identification of either homozygous or compound heterozygous variants in AGTPBP1 gene in 13 individuals from 10 unrelated families with infantile‐onset neurodegeneration. Impaired intellectual development was severe in several patients: Two had severe cognitive delay, one had profound cognitive delay, five had no speech and four had no visual recognition. In addition, functional studies with mouse models have recapitulated the human phenotype.

This gene has been associated with relevant phenotypes in both OMIM (MIM #618276) and Gene2Phenotype (on DD panel with 'definitive' rating).
Sources: Literature
Intellectual disability v5.224 AGTPBP1 Achchuthan Shanmugasundram changed review comment from: PMID:30420557 reported the identification of either homozygous or compound heterozygous variants in AGTPBP1 gene in 13 individuals from 10 unrelated families with infantile‐onset neurodegeneration. Impaired intellectual development was severe, and several patients were unable to speak or have eye contact.

This gene has been associated with relevant phenotypes in both OMIM (MIM #618276) and Gene2Phenotype (on DD panel with 'definitive' rating).
Sources: Literature; to: PMID:30420557 reported the identification of either homozygous or compound heterozygous variants in AGTPBP1 gene in 13 individuals from 10 unrelated families with infantile‐onset neurodegeneration. Impaired intellectual development was severe in several patients: Two had severe cognitive delay, one had profound cognitive delay, five had no speech and four had no visual recognition. In addition, functional studies with mouse models have recapitulated the human phenotype.

This gene has been associated with relevant phenotypes in both OMIM (MIM #618276) and Gene2Phenotype (on DD panel with 'definitive' rating).
Sources: Literature
Intellectual disability v5.224 AGTPBP1 Achchuthan Shanmugasundram gene: AGTPBP1 was added
gene: AGTPBP1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: AGTPBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGTPBP1 were set to 30420557
Phenotypes for gene: AGTPBP1 were set to Neurodegeneration, childhood-onset, with cerebellar atrophy, OMIM:618276
Review for gene: AGTPBP1 was set to GREEN
Added comment: PMID:30420557 reported the identification of either homozygous or compound heterozygous variants in AGTPBP1 gene in 13 individuals from 10 unrelated families with infantile‐onset neurodegeneration. Impaired intellectual development was severe, and several patients were unable to speak or have eye contact.

This gene has been associated with relevant phenotypes in both OMIM (MIM #618276) and Gene2Phenotype (on DD panel with 'definitive' rating).
Sources: Literature
Intellectual disability v5.223 ZNF292 Achchuthan Shanmugasundram reviewed gene: ZNF292: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Intellectual developmental disorder, autosomal dominant 64, OMIM:619188; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.223 PIP5K1C Achchuthan Shanmugasundram Classified gene: PIP5K1C as Amber List (moderate evidence)
Intellectual disability v5.223 PIP5K1C Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (nine unrelated cases and supporting functional evidence) for promoting this gene to green rating in the next GMS review.
Intellectual disability v5.223 PIP5K1C Achchuthan Shanmugasundram Gene: pip5k1c has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.222 PIP5K1C Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: PIP5K1C.
Intellectual disability v5.222 PIP5K1C Achchuthan Shanmugasundram gene: PIP5K1C was added
gene: PIP5K1C was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: PIP5K1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PIP5K1C were set to 37451268
Phenotypes for gene: PIP5K1C were set to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Review for gene: PIP5K1C was set to GREEN
Added comment: Three de novo heterozygous missense variants in PIP5K1C (p.Glu146Lys, p.Tyr205Cys & p.Tyr221Cys) were identified in nine unrelated children exhibiting intellectual disability, developmental delay, acquired microcephaly, seizures, visual abnormalities, and dysmorphic features. Intellectual disability was reported in all nine children and seizures were present in seven children, of which three had developmental and epileptic encephalopathy. In addition, there is functional evidence available, which includes an in vivo zebrafish model that recapitulates the human phenotype (developmental defects affecting the forebrain, including the eyes, as well as craniofacial abnormalities) (PMID:37451268).

This gene has been associated with another phenotype (Lethal congenital contractural syndrome 3, MIM #611369) in both OMIM and Gene2Phenotype, but not yet associated with this neurodevelopmental disorders in either databases.
Sources: Literature
Intellectual disability v5.221 TMEM63B Achchuthan Shanmugasundram Classified gene: TMEM63B as Amber List (moderate evidence)
Intellectual disability v5.221 TMEM63B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (17 unrelated cases) in support of promoting this gene to green rating in the next GMS review.
Intellectual disability v5.221 TMEM63B Achchuthan Shanmugasundram Gene: tmem63b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.220 TMEM63B Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: TMEM63B.
Intellectual disability v5.220 TMEM63B Achchuthan Shanmugasundram gene: TMEM63B was added
gene: TMEM63B was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: TMEM63B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TMEM63B were set to 37421948
Phenotypes for gene: TMEM63B were set to developmental and epileptic encephalopathy, MONDO:0100062
Review for gene: TMEM63B was set to GREEN
Added comment: PMID:37421948 - 17 unrelated individuals with severe early-onset developmental and epileptic encephalopathy (DEE), intellectual disability, and severe motor and cortical visual impairment were identified with ten distinct heterozygous variants inTMEM63B. The variants occurred de novo in 16/17 individuals for whom parental DNA was available and either missense or in-frame. All individuals had global developmental delay, with moderate-to-profound intellectual disability and severe motor impairment.
Sources: Literature
Intellectual disability v5.219 DHX9 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.219 DHX9 Achchuthan Shanmugasundram Classified gene: DHX9 as Amber List (moderate evidence)
Intellectual disability v5.219 DHX9 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (eight unrelated cases) in support of promoting this gene to green rating at the next GMS review.
Intellectual disability v5.219 DHX9 Achchuthan Shanmugasundram Gene: dhx9 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.219 DHX9 Achchuthan Shanmugasundram Classified gene: DHX9 as Amber List (moderate evidence)
Intellectual disability v5.219 DHX9 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (eight unrelated cases) in support of promoting this gene to green rating at the next GMS review.
Intellectual disability v5.219 DHX9 Achchuthan Shanmugasundram Gene: dhx9 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.218 DHX9 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: DHX9.
Intellectual disability v5.218 DHX9 Achchuthan Shanmugasundram gene: DHX9 was added
gene: DHX9 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: DHX9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DHX9 were set to 37467750
Phenotypes for gene: DHX9 were set to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Review for gene: DHX9 was set to GREEN
Added comment: PMID:37467750 - 17 unrelated individuals were identified with de novo, ultra-rare, heterozygous missense or loss-of-function DHX9 variants, of which 14 individuals were reported with a neurodevelopmental disorder (NDD) and three were reported with Charcot-Marie-Tooth disease (CMT). All 14 cases with NDD had developmental delay, of which eight were reported with intellectual disability (4 severe, 1 moderate, 3 mild). Two cases did not have ID, one had borderline ID and three cases were too young (0-5 years old).
Sources: Literature
Intellectual disability v5.217 CNOT9 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: CNOT9.
Intellectual disability v5.217 CNOT9 Achchuthan Shanmugasundram Classified gene: CNOT9 as Amber List (moderate evidence)
Intellectual disability v5.217 CNOT9 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (seven unrelated cases) for this gene to be promoted to Green at the next major update.
Intellectual disability v5.217 CNOT9 Achchuthan Shanmugasundram Gene: cnot9 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.216 CNOT9 Achchuthan Shanmugasundram gene: CNOT9 was added
gene: CNOT9 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: CNOT9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CNOT9 were set to 37092538
Phenotypes for gene: CNOT9 were set to intellectual disability, MONDO:0001071
Review for gene: CNOT9 was set to GREEN
Added comment: PMID:37092538 - Seven unrelated individuals with de novo variants in CNOT9 gene (one individual each with variants p.Arg46Gly, p.Pro131Leu and p.Arg227His and four individuals with p.Arg292Trp) were reported with a neurodevelopmental disorder. All affected persons have intellectual disability (three severe, three mild and one unclassified) and five of them have seizures.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Classified gene: SLC30A9 as Amber List (moderate evidence)
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are six unrelated families with Intellectual disability/ global developmental delay reported with biallelic variants in this gene. Hence, this gene can be promoted to Green at the next major update.
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Gene: slc30a9 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Classified gene: SLC30A9 as Amber List (moderate evidence)
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are six unrelated families with Intellectual disability/ global developmental delay reported with biallelic variants in this gene. Hence, this gene can be promoted to Green at the next major update.
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Gene: slc30a9 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There are six unrelated families with Intellectual disability/ global developmental delay reported with biallelic variants in this gene. Hence, this gene can be promoted to Green at the next major update.; to: Comment on list classification: There are six unrelated families with Intellectual disability/ global developmental delay reported with biallelic variants in this gene. Hence, this gene can be promoted to Green at the next major update.
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There are six unrelated families with Intellectual disability/ global developmental delay reported with biallelic variants in this gene. Hence, this gene can be promoted to Green at the next major update.; to: Comment on list classification: There are six unrelated families with Intellectual disability/ global developmental delay reported with biallelic variants in this gene. Hence, this gene can be promoted to Green at the next major update.
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Classified gene: SLC30A9 as Amber List (moderate evidence)
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are six unrelated families with Intellectual disability/ global developmental delay reported with biallelic variants in this gene. Hence, this gene can be promoted to Green at the next major update.
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Gene: slc30a9 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Classified gene: SLC30A9 as Amber List (moderate evidence)
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are six unrelated families with Intellectual disability/ global developmental delay reported with biallelic variants in this gene. Hence, this gene can be promoted to Green at the next major update.
Intellectual disability v5.215 SLC30A9 Achchuthan Shanmugasundram Gene: slc30a9 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.214 SLC30A9 Achchuthan Shanmugasundram Phenotypes for gene: SLC30A9 were changed from Birk-Landau-Perez syndrome, OMIM:617595 to Birk-Landau-Perez syndrome, OMIM:617595
Intellectual disability v5.214 SLC30A9 Achchuthan Shanmugasundram Phenotypes for gene: SLC30A9 were changed from Birk-Landau-Perez syndrome, OMIM:617595 to Birk-Landau-Perez syndrome, OMIM:617595
Intellectual disability v5.213 SLC30A9 Achchuthan Shanmugasundram Phenotypes for gene: SLC30A9 were changed from Birk-Landau-Perez syndrome, OMIM:617595 to Birk-Landau-Perez syndrome, OMIM:617595
Intellectual disability v5.213 SLC30A9 Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: SLC30A9.
Intellectual disability v5.213 SLC30A9 Achchuthan Shanmugasundram Phenotypes for gene: SLC30A9 were changed from Birk-Landau-Perez syndrome, OMIM:617595 to Birk-Landau-Perez syndrome, OMIM:617595
Intellectual disability v5.213 SLC30A9 Achchuthan Shanmugasundram Phenotypes for gene: SLC30A9 were changed from ?Birk-Landau-Perez syndrome 617595 to Birk-Landau-Perez syndrome, OMIM:617595
Intellectual disability v5.212 SLC30A9 Achchuthan Shanmugasundram Publications for gene: SLC30A9 were set to 28334855
Intellectual disability v5.211 SLC30A9 Achchuthan Shanmugasundram reviewed gene: SLC30A9: Rating: GREEN; Mode of pathogenicity: None; Publications: 28334855, 34716203, 37041080; Phenotypes: Birk-Landau-Perez syndrome, OMIM:617595; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.211 DAGLA Achchuthan Shanmugasundram Mode of pathogenicity for gene: DAGLA was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v5.211 DAGLA Achchuthan Shanmugasundram Mode of pathogenicity for gene: DAGLA was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v5.211 DAGLA Achchuthan Shanmugasundram Mode of pathogenicity for gene: DAGLA was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v5.211 DAGLA Achchuthan Shanmugasundram Mode of pathogenicity for gene: DAGLA was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v5.211 DAGLA Achchuthan Shanmugasundram Mode of pathogenicity for gene: DAGLA was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v5.210 DAGLA Achchuthan Shanmugasundram Mode of pathogenicity for gene: DAGLA was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v5.210 DAGLA Achchuthan Shanmugasundram Mode of pathogenicity for gene: DAGLA was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v5.210 DAGLA Achchuthan Shanmugasundram Mode of pathogenicity for gene: DAGLA was changed from Other to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram edited their review of gene: DAGLA: 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
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram changed review comment from: As reviewed by Irina Ziravecka, there are nine children from eight unrelated families reported with heterozygous de novo variants in DAGLA gene and presenting with a neuro-ocular phenotype characterized by developmental delay, ataxia and complex oculomotor abnormality. Of these nine children, five had intellectual disability and one had low average IQ. In addition, the functional data suggests potential mechanisms include DAGLA haploinsufficiency at the plasma membrane or dominant negative effect (PMID:35737950).; to: As reviewed by Irina Ziravecka, there are nine children from eight unrelated families reported with heterozygous de novo variants in DAGLA gene and presenting with a neuro-ocular phenotype characterized by developmental delay, ataxia and complex oculomotor abnormality. Of these nine children, five had intellectual disability and one had low average IQ. In addition, the functional data suggests potential mechanisms include DAGLA haploinsufficiency at the plasma membrane or dominant negative effect (PMID:35737950).

This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Tag Q3_23_promote_green tag was added to gene: DAGLA.
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Phenotypes for gene: DAGLA were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Phenotypes for gene: DAGLA were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Phenotypes for gene: DAGLA were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Phenotypes for gene: DAGLA were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Phenotypes for gene: DAGLA were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Phenotypes for gene: DAGLA were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.209 DAGLA Achchuthan Shanmugasundram Phenotypes for gene: DAGLA were changed from developmental delay; ataxia; complex oculomotor abnormality to intellectual disability, MONDO:0001071
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Classified gene: DAGLA as Amber List (moderate evidence)
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Added comment: Comment on list classification: There are more than 3 unrelated cases associating monoallelic variants in this gene to intellectual disability. Hence, this gene can be promoted to Green rating at the next GMS update.
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Gene: dagla has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Classified gene: DAGLA as Amber List (moderate evidence)
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Added comment: Comment on list classification: There are more than 3 unrelated cases associating monoallelic variants in this gene to intellectual disability. Hence, this gene can be promoted to Green rating at the next GMS update.
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Gene: dagla has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Classified gene: DAGLA as Amber List (moderate evidence)
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Added comment: Comment on list classification: There are more than 3 unrelated cases associating monoallelic variants in this gene to intellectual disability. Hence, this gene can be promoted to Green rating at the next GMS update.
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Gene: dagla has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Classified gene: DAGLA as Amber List (moderate evidence)
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Added comment: Comment on list classification: There are more than 3 unrelated cases associating monoallelic variants in this gene to intellectual disability. Hence, this gene can be promoted to Green rating at the next GMS update.
Intellectual disability v5.208 DAGLA Achchuthan Shanmugasundram Gene: dagla has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.207 DAGLA Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.207 DAGLA Achchuthan Shanmugasundram Classified gene: DAGLA as Amber List (moderate evidence)
Intellectual disability v5.207 DAGLA Achchuthan Shanmugasundram Added comment: Comment on list classification: There are more than 3 unrelated cases associating monoallelic variants in this gene to intellectual disability. Hence, this gene can be promoted to Green rating at the next GMS update.
Intellectual disability v5.207 DAGLA Achchuthan Shanmugasundram Gene: dagla has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.207 DAGLA Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.207 DAGLA Achchuthan Shanmugasundram Classified gene: DAGLA as Amber List (moderate evidence)
Intellectual disability v5.207 DAGLA Achchuthan Shanmugasundram Added comment: Comment on list classification: There are more than 3 unrelated cases associating monoallelic variants in this gene to intellectual disability. Hence, this gene can be promoted to Green rating at the next GMS update.
Intellectual disability v5.207 DAGLA Achchuthan Shanmugasundram Gene: dagla has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.207 DAGLA Achchuthan Shanmugasundram Classified gene: DAGLA as Amber List (moderate evidence)
Intellectual disability v5.207 DAGLA Achchuthan Shanmugasundram Added comment: Comment on list classification: There are more than 3 unrelated cases associating monoallelic variants in this gene to intellectual disability. Hence, this gene can be promoted to Green rating at the next GMS update.
Intellectual disability v5.207 DAGLA Achchuthan Shanmugasundram Gene: dagla has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.206 DAGLA Achchuthan Shanmugasundram Publications for gene: DAGLA were set to 35737950
Intellectual disability v5.206 DAGLA Achchuthan Shanmugasundram Publications for gene: DAGLA were set to PMID: 35737950
Intellectual disability v5.205 DAGLA Achchuthan Shanmugasundram changed review comment from: As reviewed by Irina Ziravecka, there are nine children from eight unrelated families reported with heterozygous de novo variants in DAGLA gene and presenting with a neuro-ocular phenotype characterized by developmental delay, ataxia and complex oculomotor abnormality. Of these nine children, five had intellectual disability and one had low average IQ (PMID:35737950).; to: As reviewed by Irina Ziravecka, there are nine children from eight unrelated families reported with heterozygous de novo variants in DAGLA gene and presenting with a neuro-ocular phenotype characterized by developmental delay, ataxia and complex oculomotor abnormality. Of these nine children, five had intellectual disability and one had low average IQ. In addition, the functional data suggests potential mechanisms include DAGLA haploinsufficiency at the plasma membrane or dominant negative effect (PMID:35737950).
Intellectual disability v5.205 DAGLA Achchuthan Shanmugasundram changed review comment from: As reviewed by Irina Ziravecka, there are nine children from eight unrelated families reported with heterozygous variants in DAGLA gene and presenting with a neuro-ocular phenotype characterized by developmental delay, ataxia and complex oculomotor abnormality. Of these nine children, five had intellectual disability and one had low average IQ (PMID:35737950).; to: As reviewed by Irina Ziravecka, there are nine children from eight unrelated families reported with heterozygous de novo variants in DAGLA gene and presenting with a neuro-ocular phenotype characterized by developmental delay, ataxia and complex oculomotor abnormality. Of these nine children, five had intellectual disability and one had low average IQ (PMID:35737950).
Intellectual disability v5.205 DAGLA Achchuthan Shanmugasundram reviewed gene: DAGLA: Rating: GREEN; Mode of pathogenicity: None; Publications: 35737950; Phenotypes: intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.205 BUB1 Arina Puzriakova Phenotypes for gene: BUB1 were changed from Congenital microcephaly; Global developmental delay; Intellectual disability; Abnormal heart morphology; Growth delay to Microcephaly 30, primary, autosomal recessive, OMIM:620183
Intellectual disability v5.204 BUB1 Arina Puzriakova commented on gene: BUB1
Intellectual disability v5.204 BUB1 Arina Puzriakova Tag Q4_22_MOI was removed from gene: BUB1.
Intellectual disability v5.204 DAGLA Irina Ziravecka gene: DAGLA was added
gene: DAGLA was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: DAGLA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DAGLA were set to PMID: 35737950
Phenotypes for gene: DAGLA were set to developmental delay; ataxia; complex oculomotor abnormality
Mode of pathogenicity for gene: DAGLA was set to Other
Review for gene: DAGLA was set to GREEN
Added comment: PMID: 35737950 - nine children from eight families with heterozygous, de novo truncating variants in the last exon of DAGLA with a neuro-ocular phenotype.
Sources: Literature
Intellectual disability v5.204 PTPA Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.204 PTPA Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.204 PTPA Achchuthan Shanmugasundram Classified gene: PTPA as Amber List (moderate evidence)
Intellectual disability v5.204 PTPA Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are two unrelated cases with intellectual disability and hence this gene should be rated amber.
Intellectual disability v5.204 PTPA Achchuthan Shanmugasundram Gene: ptpa has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.203 PTPA Achchuthan Shanmugasundram Classified gene: PTPA as Amber List (moderate evidence)
Intellectual disability v5.203 PTPA Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are two unrelated cases with intellectual disability and hence this gene should be rated amber.
Intellectual disability v5.203 PTPA Achchuthan Shanmugasundram Gene: ptpa has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.203 PTPA Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.203 PTPA Achchuthan Shanmugasundram Classified gene: PTPA as Amber List (moderate evidence)
Intellectual disability v5.203 PTPA Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are two unrelated cases with intellectual disability and hence this gene should be rated amber.
Intellectual disability v5.203 PTPA Achchuthan Shanmugasundram Gene: ptpa has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.203 PTPA Achchuthan Shanmugasundram Classified gene: PTPA as Amber List (moderate evidence)
Intellectual disability v5.203 PTPA Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, there are two unrelated cases with intellectual disability and hence this gene should be rated amber.
Intellectual disability v5.203 PTPA Achchuthan Shanmugasundram Gene: ptpa has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.202 PTPA Achchuthan Shanmugasundram Phenotypes for gene: PTPA were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.202 PTPA Achchuthan Shanmugasundram Phenotypes for gene: PTPA were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.201 PTPA Achchuthan Shanmugasundram Phenotypes for gene: PTPA were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.201 PTPA Achchuthan Shanmugasundram Phenotypes for gene: PTPA were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.201 PTPA Achchuthan Shanmugasundram Phenotypes for gene: PTPA were changed from Intellectual disability; Parkinsonism to Intellectual disability, MONDO:0001071
Intellectual disability v5.200 PTPA Achchuthan Shanmugasundram reviewed gene: PTPA: Rating: AMBER; Mode of pathogenicity: None; Publications: 36073231; Phenotypes: Intellectual disability, MONDO:0001071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Classified gene: FOXR1 as Amber List (moderate evidence)
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is one case with global developmental delay and supporting functional evidence including mouse model. Hence, this gene should be rated amber.
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Gene: foxr1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Zornitza Stark, there is one case with global developmental delay and supporting functional evidence including mouse model. Hence, this gene should be rated amber.; to: Comment on list classification: As reviewed by Zornitza Stark, there is one case with global developmental delay supported by functional evidence including mouse model. Hence, this gene should be rated amber.
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Classified gene: FOXR1 as Amber List (moderate evidence)
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is one case with global developmental delay and supporting functional evidence including mouse model. Hence, this gene should be rated amber.
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Gene: foxr1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Classified gene: FOXR1 as Amber List (moderate evidence)
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is one case with global developmental delay and supporting functional evidence including mouse model. Hence, this gene should be rated amber.
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Gene: foxr1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Classified gene: FOXR1 as Amber List (moderate evidence)
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is one case with global developmental delay and supporting functional evidence including mouse model. Hence, this gene should be rated amber.
Intellectual disability v5.200 FOXR1 Achchuthan Shanmugasundram Gene: foxr1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Classified gene: FOXR1 as Amber List (moderate evidence)
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is one case with global developmental delay and supporting functional evidence including mouse model. Hence, this gene should be rated amber.
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Gene: foxr1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Classified gene: FOXR1 as Amber List (moderate evidence)
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is one case with global developmental delay and supporting functional evidence including mouse model. Hence, this gene should be rated amber.
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Gene: foxr1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Classified gene: FOXR1 as Amber List (moderate evidence)
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is one case with global developmental delay and supporting functional evidence including mouse model. Hence, this gene should be rated amber.
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Gene: foxr1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Classified gene: FOXR1 as Amber List (moderate evidence)
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is one case with global developmental delay and supporting functional evidence including mouse model. Hence, this gene should be rated amber.
Intellectual disability v5.199 FOXR1 Achchuthan Shanmugasundram Gene: foxr1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.198 FOXR1 Achchuthan Shanmugasundram Phenotypes for gene: FOXR1 were changed from Global developmental delay, HP:0001263; microcephaly, MONDO:0001149; Brain atrophy, HP:0012444 to Global developmental delay, HP:0001263; microcephaly, MONDO:0001149; Brain atrophy, HP:0012444
Intellectual disability v5.198 FOXR1 Achchuthan Shanmugasundram Phenotypes for gene: FOXR1 were changed from Global developmental delay, HP:0001263; microcephaly, MONDO:0001149; Brain atrophy, HP:0012444 to Global developmental delay, HP:0001263; microcephaly, MONDO:0001149; Brain atrophy, HP:0012444
Intellectual disability v5.198 FOXR1 Achchuthan Shanmugasundram Phenotypes for gene: FOXR1 were changed from Global developmental delay, HP:0001263; microcephaly, MONDO:0001149; Brain atrophy, HP:0012444 to Global developmental delay, HP:0001263; microcephaly, MONDO:0001149; Brain atrophy, HP:0012444
Intellectual disability v5.198 FOXR1 Achchuthan Shanmugasundram Phenotypes for gene: FOXR1 were changed from Global developmental delay, HP:0001263; microcephaly, MONDO:0001149; Brain atrophy, HP:0012444 to Global developmental delay, HP:0001263; microcephaly, MONDO:0001149; Brain atrophy, HP:0012444
Intellectual disability v5.197 FOXR1 Achchuthan Shanmugasundram Phenotypes for gene: FOXR1 were changed from Global developmental delay, HP:0001263; microcephaly, MONDO:0001149; Brain atrophy, HP:0012444 to Global developmental delay, HP:0001263; microcephaly, MONDO:0001149; Brain atrophy, HP:0012444
Intellectual disability v5.197 FOXR1 Achchuthan Shanmugasundram Phenotypes for gene: FOXR1 were changed from Postnatal microcephaly, progressive brain atrophy and global developmental delay to Global developmental delay, HP:0001263; microcephaly, MONDO:0001149; Brain atrophy, HP:0012444
Intellectual disability v5.196 FOXR1 Achchuthan Shanmugasundram edited their review of gene: FOXR1: Changed phenotypes to: Global developmental delay, HP:0001263, microcephaly, MONDO:0001149, Brain atrophy, HP:0012444
Intellectual disability v5.196 FOXR1 Achchuthan Shanmugasundram reviewed gene: FOXR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 34723967; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.196 KDM6B Sarah Leigh Phenotypes for gene: KDM6B were changed from Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities, 618505 to Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities, OMIM:618505; neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities, MONDO:0032790
Intellectual disability v5.195 KDM6B Sarah Leigh Publications for gene: KDM6B were set to 21937992; 31124279
Intellectual disability v5.194 DALRD3 Arina Puzriakova Classified gene: DALRD3 as Amber List (moderate evidence)
Intellectual disability v5.194 DALRD3 Arina Puzriakova Added comment: Comment on list classification: New gene added by Konstantinos Varvagiannis. Rating Amber as this is a good candidate gene but only a single family has been reported to date with variants. Additional evidence needed prior to adding the gene as diagnostic-grade.
Intellectual disability v5.194 DALRD3 Arina Puzriakova Gene: dalrd3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.193 SMCHD1 Arina Puzriakova Mode of inheritance for gene: SMCHD1 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.191 PSMC3 Dmitrijs Rots gene: PSMC3 was added
gene: PSMC3 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: PSMC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSMC3 were set to PMID: 37256937
Phenotypes for gene: PSMC3 were set to neurodevelopmental delay
Mode of pathogenicity for gene: PSMC3 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: PSMC3 was set to GREEN
Added comment: 23 individuals with NDD due to 15 different de novo missense variants in PMID: 37256937.
Sources: Literature
Intellectual disability v5.191 MKL2 Dmitrijs Rots gene: MKL2 was added
gene: MKL2 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: MKL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MKL2 were set to PMID:37013900
Phenotypes for gene: MKL2 were set to neurodevelopmental phenotype with dysmorphic features
Mode of pathogenicity for gene: MKL2 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: MKL2 was set to GREEN
Added comment: 2 cases with de novo missense GoF variants in MRTFB (previously known as MKL2) + functional evidence
Sources: Literature
Intellectual disability v5.191 EIF4A2 Sarah Leigh Classified gene: EIF4A2 as Amber List (moderate evidence)
Intellectual disability v5.191 EIF4A2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rating Green at the major review.
Intellectual disability v5.191 EIF4A2 Sarah Leigh Gene: eif4a2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.190 EIF4A2 Sarah Leigh gene: EIF4A2 was added
gene: EIF4A2 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Q3_23_promote_green tags were added to gene: EIF4A2.
Mode of inheritance for gene: EIF4A2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: EIF4A2 were set to 36528028
Phenotypes for gene: EIF4A2 were set to Neurodevelopmental disorder
Review for gene: EIF4A2 was set to GREEN
Added comment: EIF4A2 has not been associated with a phenotype in OMIM, Gen2Phen or Mondo at the time of reporting. PMID: 36528028 reports the findings of an international collaboration through Matchmaker Exchange, where EIF4A2 variants are found in cases with neurodevelopmental disorder characterized by intellectual disability, hypotonia, and epilepsy. A total of 15 EIF4A2 variants have been reported in PMID: 36528028, with 12 variants occurring as de novo monoallelic in 12 individuals and 3 as biallelic in two unrelated cases (one as homozygote and the other as compound heterozygous). Severe intellectual was seen in 6/10 unrelated cases where an assessment was made, epilepsy was evident in 10/14 unrelated cases and 13/14 cases had hyptonia. Functional studies were also presented and it would appear that both loss and gain functions maybe associated with EIF4A2 variants.
Sources: Literature
Intellectual disability v5.189 TTI1 Sarah Leigh Classified gene: TTI1 as Amber List (moderate evidence)
Intellectual disability v5.189 TTI1 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 v5.189 TTI1 Sarah Leigh Gene: tti1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.188 TTI1 Sarah Leigh Tag Q3_23_promote_green tag was added to gene: TTI1.
Intellectual disability v5.188 TTI1 Sarah Leigh gene: TTI1 was added
gene: TTI1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: TTI1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTI1 were set to 36724785
Phenotypes for gene: TTI1 were set to neurodevelopmental disorder with microcephaly
Review for gene: TTI1 was set to GREEN
Added comment: TTI1 has not previously been associated with a phenotype in OMIM, Gen2Phen or MONDO. At least 2 variants have been reported. PMID: 36724785 reported 15 TTI1 variants as either homozygotes (2 families) or compound heterozygotes (7 families) in cases with a neurodevelopmental disorder with microcephaly. In all cases the parents were heterozygous carriers of the TTI1 variant identified in the affected child. Development delay was observed in all of the families (9/9), moderate to severe intellectual disability was evident in all families where it could be assessed (8/8) and severe microcephaly was present in members of 5/9 families. Supportive functional results were also presented.
Sources: Literature
Intellectual disability v5.187 TSPOAP1 Sarah Leigh Tag Q3_23_promote_green tag was added to gene: TSPOAP1.
Intellectual disability v5.187 TSPOAP1 Sarah Leigh Entity copied from Childhood onset dystonia, chorea or related movement disorder v3.13
Intellectual disability v5.187 TSPOAP1 Sarah Leigh gene: TSPOAP1 was added
gene: TSPOAP1 was added to Intellectual disability - microarray and sequencing. Sources: Literature,Expert Review Amber
Mode of inheritance for gene: TSPOAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TSPOAP1 were set to 33539324
Phenotypes for gene: TSPOAP1 were set to Dystonia, intellectual disability and cerebellar atrophy
Intellectual disability v5.186 SRRM2 Sarah Leigh Added comment: Comment on publications: www.hindawi.com/journals/humu/2023/6633248
Intellectual disability v5.186 SRRM2 Sarah Leigh Publications for gene: SRRM2 were set to 35567594; 33057194
Intellectual disability v5.185 GRM7 Achchuthan Shanmugasundram Classified gene: GRM7 as Amber List (moderate evidence)
Intellectual disability v5.185 GRM7 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (six unrelated cases and supporting mouse model) for this gene to be promoted to GREEN rating at the next GMS review.
Intellectual disability v5.185 GRM7 Achchuthan Shanmugasundram Gene: grm7 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.184 GRM7 Achchuthan Shanmugasundram Publications for gene: GRM7 were set to 32248644; 32286009
Intellectual disability v5.184 GRM7 Achchuthan Shanmugasundram edited their review of gene: GRM7: Changed publications to: 32248644, 32286009
Intellectual disability v5.184 GRM7 Achchuthan Shanmugasundram Publications for gene: GRM7 were set to 32248644; 32286009
Intellectual disability v5.184 GRM7 Achchuthan Shanmugasundram Publications for gene: GRM7 were set to 2248644; 32286009
Intellectual disability v5.183 GRM7 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: GRM7.
Intellectual disability v5.183 GRM7 Achchuthan Shanmugasundram gene: GRM7 was added
gene: GRM7 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: GRM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRM7 were set to 2248644; 32286009
Phenotypes for gene: GRM7 were set to Neurodevelopmental disorder with seizures, hypotonia, and brain abnormalities, OMIM:618922
Review for gene: GRM7 was set to GREEN
Added comment: PMID:32286009 reported eleven individuals from six unrelated families identified with three different biallelic variants and presenting with a neurodevelopmental disorder comprising severe to profound global developmental delays, intellectual disability, seizures, hypotonia, microcephaly and brain abnormalities. This is also supported by functional evidence from knockout mouse models, where absence of metabotropic glutamate receptor 7 alters the phenotypes within the domains of social behavior, associative learning, motor function, epilepsy and sleep (PMID:32248644).

This gene has also been associated with relevant phenotypes in both OMIM (MIM #618922) and in Gene2Phenotype (with 'strong' rating in the DD panel).
Sources: Literature
Intellectual disability v5.182 CCDC82 Achchuthan Shanmugasundram changed review comment from: As reviewed by Konstantinos Varvagiannis, there is more than three unrelated cases with biallelic variants in CCDC82 presenting with a neurodevelopmental disorder comprising intellectual disability/ global developmental delay. Hence, this gene should be rated GREEN at the next GMS review.; to: As reviewed by Konstantinos Varvagiannis, there are more than three unrelated cases with biallelic variants in CCDC82 presenting with a neurodevelopmental disorder comprising intellectual disability/ global developmental delay. Hence, this gene should be rated GREEN at the next GMS review.
Intellectual disability v5.182 CCDC82 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: CCDC82.
Intellectual disability v5.182 CCDC82 Achchuthan Shanmugasundram Classified gene: CCDC82 as Amber List (moderate evidence)
Intellectual disability v5.182 CCDC82 Achchuthan Shanmugasundram Gene: ccdc82 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.182 CCDC82 Achchuthan Shanmugasundram Classified gene: CCDC82 as Amber List (moderate evidence)
Intellectual disability v5.182 CCDC82 Achchuthan Shanmugasundram Gene: ccdc82 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.181 CCDC82 Achchuthan Shanmugasundram Phenotypes for gene: CCDC82 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.182 CCDC82 Achchuthan Shanmugasundram Phenotypes for gene: CCDC82 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.181 CCDC82 Achchuthan Shanmugasundram Phenotypes for gene: CCDC82 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.181 CCDC82 Achchuthan Shanmugasundram Phenotypes for gene: CCDC82 were changed from Global developmental delay; Intellectual disability; Spastic paraparesis to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.180 CCDC82 Achchuthan Shanmugasundram commented on gene: CCDC82: As reviewed by Konstantinos Varvagiannis, there is more than three unrelated cases with biallelic variants in CCDC82 presenting with a neurodevelopmental disorder comprising intellectual disability/ global developmental delay. Hence, this gene should be rated GREEN at the next GMS review.
Intellectual disability v5.180 CCDC82 Achchuthan Shanmugasundram reviewed gene: CCDC82: Rating: GREEN; Mode of pathogenicity: None; Publications: 27457812, 28397838, 35118659, 35373332; Phenotypes: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.180 FLNA Sarah Leigh edited their review of gene: FLNA: Changed rating: RED
Intellectual disability v5.180 FLNA Sarah Leigh reviewed gene: FLNA: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v5.180 FLNA Sarah Leigh Tag Q2_23_demote_red tag was added to gene: FLNA.
Intellectual disability v5.180 FLNA Sarah Leigh Publications for gene: FLNA were set to
Intellectual disability v5.179 UBE3C Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.179 UBE3C Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: UBE3C.
Intellectual disability v5.179 UBE3C Achchuthan Shanmugasundram Classified gene: UBE3C as Amber List (moderate evidence)
Intellectual disability v5.179 UBE3C Achchuthan Shanmugasundram Added comment: Comment on list classification: There are two unrelated cases associating biallelic variants in UBE3C gene with intellectual disability. Hence, this gene should be rated AMBER.
Intellectual disability v5.179 UBE3C Achchuthan Shanmugasundram Gene: ube3c has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.179 UBE3C Achchuthan Shanmugasundram Classified gene: UBE3C as Amber List (moderate evidence)
Intellectual disability v5.179 UBE3C Achchuthan Shanmugasundram Added comment: Comment on list classification: There are two unrelated cases associating biallelic variants in UBE3C gene with intellectual disability. Hence, this gene should be rated AMBER.
Intellectual disability v5.179 UBE3C Achchuthan Shanmugasundram Gene: ube3c has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.178 UBE3C Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: UBE3C.
Intellectual disability v5.178 UBE3C Achchuthan Shanmugasundram gene: UBE3C was added
gene: UBE3C was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: UBE3C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UBE3C were set to 36401616
Phenotypes for gene: UBE3C were set to Neurodevelopmental disorder with absent speech and movement and behavioral abnormalities, OMIM:620270
Review for gene: UBE3C was set to AMBER
Added comment: PMID:36401616 reported three patients from two unrelated families with homozygous variants in UBE3C gene and presenting with syndromic neurodevelopmental, seizure, and movement disorders and neurobehavioral phenotypes. All three patients had severe intellectual disability. The RNA studies in some patients with LoF variants provided evidence for the LoF effect.
Sources: Literature
Intellectual disability v5.177 HECTD4 Achchuthan Shanmugasundram Classified gene: HECTD4 as Amber List (moderate evidence)
Intellectual disability v5.177 HECTD4 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (five unrelated families) for this gene to be promoted to GREEN rating at the next major update.
Intellectual disability v5.177 HECTD4 Achchuthan Shanmugasundram Gene: hectd4 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.177 HECTD4 Achchuthan Shanmugasundram Classified gene: HECTD4 as Amber List (moderate evidence)
Intellectual disability v5.177 HECTD4 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (five unrelated families) for this gene to be promoted to GREEN rating at the next major update.
Intellectual disability v5.177 HECTD4 Achchuthan Shanmugasundram Gene: hectd4 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.177 HECTD4 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.177 HECTD4 Achchuthan Shanmugasundram Classified gene: HECTD4 as Amber List (moderate evidence)
Intellectual disability v5.177 HECTD4 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (five unrelated families) for this gene to be promoted to GREEN rating at the next major update.
Intellectual disability v5.177 HECTD4 Achchuthan Shanmugasundram Gene: hectd4 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.176 HECTD4 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: HECTD4.
Intellectual disability v5.176 HECTD4 Achchuthan Shanmugasundram Classified gene: HECTD4 as Amber List (moderate evidence)
Intellectual disability v5.176 HECTD4 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (five unrelated families) for this gene to be promoted to GREEN rating at the next major update.
Intellectual disability v5.176 HECTD4 Achchuthan Shanmugasundram Gene: hectd4 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.175 HECTD4 Achchuthan Shanmugasundram gene: HECTD4 was added
gene: HECTD4 was added to Intellectual disability - microarray and sequencing. Sources: Literature
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
Review for gene: HECTD4 was set to GREEN
Added comment: PMID:36401616 reported seven patients from five unrelated families with either homozygous (3 families) or compound heterozygous variants (2 families) in HECTD4 gene and presenting with syndromic neurodevelopmental, seizure, and movement disorders and neurobehavioral phenotypes. All seven patients had severe (4 cases) or moderate (3 cases) intellectual disability.
Sources: Literature
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Classified gene: TRA2B as Amber List (moderate evidence)
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (11 unrelated cases) for this gene to be rated GREEN at the next GMS review.
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Gene: tra2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Classified gene: TRA2B as Amber List (moderate evidence)
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (11 unrelated cases) for this gene to be rated GREEN at the next GMS review.
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Gene: tra2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Classified gene: TRA2B as Amber List (moderate evidence)
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (11 unrelated cases) for this gene to be rated GREEN at the next GMS review.
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Gene: tra2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Classified gene: TRA2B as Amber List (moderate evidence)
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (11 unrelated cases) for this gene to be rated GREEN at the next GMS review.
Intellectual disability v5.174 TRA2B Achchuthan Shanmugasundram Gene: tra2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.173 TRA2B Achchuthan Shanmugasundram Classified gene: TRA2B as Amber List (moderate evidence)
Intellectual disability v5.173 TRA2B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (11 unrelated cases) for this gene to be rated GREEN at the next GMS review.
Intellectual disability v5.173 TRA2B Achchuthan Shanmugasundram Gene: tra2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.173 TRA2B Achchuthan Shanmugasundram Classified gene: TRA2B as Amber List (moderate evidence)
Intellectual disability v5.173 TRA2B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (11 unrelated cases) for this gene to be rated GREEN at the next GMS review.
Intellectual disability v5.173 TRA2B Achchuthan Shanmugasundram Gene: tra2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.172 TRA2B Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: TRA2B.
Intellectual disability v5.172 TRA2B Achchuthan Shanmugasundram Phenotypes for gene: TRA2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.172 TRA2B Achchuthan Shanmugasundram Phenotypes for gene: TRA2B were changed from neurodevelopmental disorder, MONDO:0700092; epilepsy, MONDO:0005027 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.171 TRA2B Achchuthan Shanmugasundram edited their review of gene: TRA2B: Changed phenotypes to: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071
Intellectual disability v5.171 TRA2B Achchuthan Shanmugasundram changed review comment from: This gene has already been associated with phenotypes in Gene2Phenotype (with 'moderate' rating in the DD panel), but not in OMIM.
Sources: Literature; to: PMID:36549593 reported 12 individuals from 11 unrelated families identified with 11 different heterozygous variants in TRA2B gene. The variants arose de novo in 10 families, while the variant was inherited from father to son in one family. 6 variants were expected to disrupt the translation start site in exon 1 (start-loss variants), 3 were expected to disrupt the splicing process at the exon 2/3 boundary (splice-affecting variants), and the remaining 2 were expected to produce a premature stop codon (truncating variants).

These patients presented with a neurodevelopmental disorder comprising developmental delay/ intellectual disability (in all patients), axial or global hypotonia (10 patients), delayed motor milestones (all patients), behavioural issues (8 patients), speech impairment (9 patients), epilepsy (7 patients, initial presentation as infantile spasms in 6 and unclassified epileptic encephalopathy in 1), brain abnormalities (10 patients) and microcephaly (5 patients). The degree of ID was severe to profound for 6 individuals, moderate to severe for 2 and mild to moderate for 3.

In addition, functional studies in mice showed that heterozygous knockout mice developed normal, while complete knockout mice cannot develop embryonically.

This gene has already been associated with phenotypes in Gene2Phenotype (with 'moderate' rating in the DD panel), but not in OMIM.
Sources: Literature
Intellectual disability v5.171 TRA2B Achchuthan Shanmugasundram gene: TRA2B was added
gene: TRA2B was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: TRA2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRA2B were set to 36549593
Phenotypes for gene: TRA2B were set to neurodevelopmental disorder, MONDO:0700092; epilepsy, MONDO:0005027
Review for gene: TRA2B was set to GREEN
Added comment: This gene has already been associated with phenotypes in Gene2Phenotype (with 'moderate' rating in the DD panel), but not in OMIM.
Sources: Literature
Intellectual disability v5.170 ZMYND8 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.170 ZMYND8 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.170 ZMYND8 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.170 ATG4D Dmitrijs Rots gene: ATG4D was added
gene: ATG4D was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: ATG4D was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATG4D were set to 36765070
Phenotypes for gene: ATG4D were set to neurodevelopmental disorder characterized by speech and motor impairment
Review for gene: ATG4D was set to GREEN
Added comment: Morimoto et al., described 3 cases from 2 families with ATG4D biallelic variants and provided some functional evidence.
No data about homozygous or compound heterozygous with two rare variants in ATG4D in gnomAD database.
Sources: Literature
Intellectual disability v5.170 CLDN5 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.170 CLDN5 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.170 CLDN5 Achchuthan Shanmugasundram Classified gene: CLDN5 as Amber List (moderate evidence)
Intellectual disability v5.170 CLDN5 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be rated GREEN in the next GMS review.
Intellectual disability v5.170 CLDN5 Achchuthan Shanmugasundram Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.170 CLDN5 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: CLDN5.
Intellectual disability v5.170 CLDN5 Achchuthan Shanmugasundram Classified gene: CLDN5 as Amber List (moderate evidence)
Intellectual disability v5.170 CLDN5 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be rated GREEN in the next GMS review.
Intellectual disability v5.170 CLDN5 Achchuthan Shanmugasundram Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.169 CLDN5 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.169 CLDN5 Achchuthan Shanmugasundram Classified gene: CLDN5 as Amber List (moderate evidence)
Intellectual disability v5.169 CLDN5 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be rated GREEN in the next GMS review.
Intellectual disability v5.169 CLDN5 Achchuthan Shanmugasundram Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.169 CLDN5 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.169 CLDN5 Achchuthan Shanmugasundram Classified gene: CLDN5 as Amber List (moderate evidence)
Intellectual disability v5.169 CLDN5 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be rated GREEN in the next GMS review.
Intellectual disability v5.169 CLDN5 Achchuthan Shanmugasundram Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.169 CLDN5 Achchuthan Shanmugasundram Classified gene: CLDN5 as Amber List (moderate evidence)
Intellectual disability v5.169 CLDN5 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be rated GREEN in the next GMS review.
Intellectual disability v5.169 CLDN5 Achchuthan Shanmugasundram Gene: cldn5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.168 CLDN5 Achchuthan Shanmugasundram Phenotypes for gene: CLDN5 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.168 CLDN5 Achchuthan Shanmugasundram Phenotypes for gene: CLDN5 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.168 CLDN5 Achchuthan Shanmugasundram Phenotypes for gene: CLDN5 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.167 CLDN5 Achchuthan Shanmugasundram Phenotypes for gene: CLDN5 were changed from epilepsy, MONDO:0005027 to intellectual disability, MONDO:0001071
Intellectual disability v5.166 CLDN5 Achchuthan Shanmugasundram edited their review of gene: CLDN5: Changed phenotypes to: intellectual disability, MONDO:0001071
Intellectual disability v5.166 CLDN5 Achchuthan Shanmugasundram changed review comment from: PMID: 36477332 identified de novo heterozygous missense variants in CLDN5 in fifteen unrelated patients who presented with a shared constellation of features including developmental delay, seizures (primarily infantile onset focal epilepsy), microcephaly and a recognizable pattern of pontine atrophy and brain calcifications.
Sources: Literature; to: PMID:36477332 reported the identification of de novo heterozygous missense variants in CLDN5 in 15 unrelated patients who presented with a number of clinical features including developmental delay including intellectual disability, seizures (primarily infantile onset focal epilepsy), microcephaly and a recognisable pattern of pontine atrophy and brain calcifications. All seven living patients over four years of age were reported to have intellectual disability.

In addition, functional studies from zebrafish model also provided parallel evidence that CLDN5 variants cause a neurodevelopmental disorder involving disruption of the blood brain barrier and impaired neuronal function.

This gene has been associated with relevant phenotypes in Gene2Phenotype (CLDN5-related neurodevelopmental disorder with 'limited' rating in the DD panel), but not in OMIM.
Sources: Literature
Intellectual disability v5.166 CLDN5 Achchuthan Shanmugasundram edited their review of gene: CLDN5: Changed phenotypes to: intellectual disability, MONDO:0001071tual
Intellectual disability v5.166 CLDN5 Achchuthan Shanmugasundram gene: CLDN5 was added
gene: CLDN5 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: CLDN5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CLDN5 were set to 36477332
Phenotypes for gene: CLDN5 were set to epilepsy, MONDO:0005027
Review for gene: CLDN5 was set to GREEN
Added comment: PMID: 36477332 identified de novo heterozygous missense variants in CLDN5 in fifteen unrelated patients who presented with a shared constellation of features including developmental delay, seizures (primarily infantile onset focal epilepsy), microcephaly and a recognizable pattern of pontine atrophy and brain calcifications.
Sources: Literature
Intellectual disability v5.165 KDM2B Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.165 KDM2B Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.165 KDM2B Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.165 TCEAL1 Achchuthan Shanmugasundram Classified gene: TCEAL1 as Amber List (moderate evidence)
Intellectual disability v5.165 TCEAL1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (7 unrelated cases) for this gene to be rated GREEN at the next GMS review.
Intellectual disability v5.165 TCEAL1 Achchuthan Shanmugasundram Gene: tceal1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.165 TCEAL1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.165 TCEAL1 Achchuthan Shanmugasundram Classified gene: TCEAL1 as Amber List (moderate evidence)
Intellectual disability v5.165 TCEAL1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (7 unrelated cases) for this gene to be rated GREEN at the next GMS review.
Intellectual disability v5.165 TCEAL1 Achchuthan Shanmugasundram Gene: tceal1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.164 TCEAL1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.164 TCEAL1 Achchuthan Shanmugasundram Classified gene: TCEAL1 as Amber List (moderate evidence)
Intellectual disability v5.164 TCEAL1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (7 unrelated cases) for this gene to be rated GREEN at the next GMS review.
Intellectual disability v5.164 TCEAL1 Achchuthan Shanmugasundram Gene: tceal1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.164 TCEAL1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.164 TCEAL1 Achchuthan Shanmugasundram Classified gene: TCEAL1 as Amber List (moderate evidence)
Intellectual disability v5.164 TCEAL1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (7 unrelated cases) for this gene to be rated GREEN at the next GMS review.
Intellectual disability v5.164 TCEAL1 Achchuthan Shanmugasundram Gene: tceal1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.164 TCEAL1 Achchuthan Shanmugasundram Classified gene: TCEAL1 as Amber List (moderate evidence)
Intellectual disability v5.164 TCEAL1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (7 unrelated cases) for this gene to be rated GREEN at the next GMS review.
Intellectual disability v5.164 TCEAL1 Achchuthan Shanmugasundram Gene: tceal1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.163 TCEAL1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: TCEAL1.
Intellectual disability v5.163 TCEAL1 Achchuthan Shanmugasundram changed review comment from: PMID:36368327 reported seven unrelated individuals with de novo variants (2 nonsense, 2 frameshift, 2 CNVs & 1 missense variants) in TCEAL1 gene and presenting with an X-linked dominant neurodevelopmental disorder. All these seven individuals had intellectual disability (mild to severe). The other major clinical presentations include hypotonia, abnormal gait, speech impairment, autistic-like behavior, and mildly dysmorphic facial features.

This gene is associated with relevant phenotypes in OMIM (MIM #301094), but not in Gene2Phenotype.
Sources: Literature; to: PMID:36368327 reported seven unrelated individuals with de novo variants (2 nonsense, 2 frameshift, 2 CNVs & 1 missense variants) in TCEAL1 gene and presenting with an X-linked dominant neurodevelopmental disorder. All these seven individuals had intellectual disability (mild to severe). The other major clinical presentations include hypotonia, abnormal gait, speech impairment, autistic-like behaviour, and mildly dysmorphic facial features.

This gene is associated with relevant phenotypes in OMIM (MIM #301094), but not in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.163 TCEAL1 Achchuthan Shanmugasundram gene: TCEAL1 was added
gene: TCEAL1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: TCEAL1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: TCEAL1 were set to 36368327
Phenotypes for gene: TCEAL1 were set to Neurodevelopmental disorder with gait disturbance, dysmorphic facies and behavioral abnormalities, X-linked, OMIM:301094
Review for gene: TCEAL1 was set to GREEN
Added comment: PMID:36368327 reported seven unrelated individuals with de novo variants (2 nonsense, 2 frameshift, 2 CNVs & 1 missense variants) in TCEAL1 gene and presenting with an X-linked dominant neurodevelopmental disorder. All these seven individuals had intellectual disability (mild to severe). The other major clinical presentations include hypotonia, abnormal gait, speech impairment, autistic-like behavior, and mildly dysmorphic facial features.

This gene is associated with relevant phenotypes in OMIM (MIM #301094), but not in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.162 FEM1C Achchuthan Shanmugasundram changed review comment from: Comment on list classification: This gene should be rated AMBER as there are two unrelated cases of intellectual disability reported (one in literature and another from Diagnostic Discovery initiative).; to: Comment on list classification: This gene should be rated AMBER as there are two unrelated cases of intellectual disability (one in literature and another from Diagnostic Discovery initiative).
Intellectual disability v5.162 FEM1C Achchuthan Shanmugasundram Classified gene: FEM1C as Amber List (moderate evidence)
Intellectual disability v5.162 FEM1C Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are two unrelated cases of intellectual disability reported (one in literature and another from Diagnostic Discovery initiative).
Intellectual disability v5.162 FEM1C Achchuthan Shanmugasundram Gene: fem1c has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.161 FEM1C Achchuthan Shanmugasundram changed review comment from: This gene should be rated RED as there is only one clear case of intellectual disability reported in literature.

PMID:36336956 reported a 9 year-old boy with severe global developmental delay, lack of speech, pyramidal signs and limb ataxia and identified with a heterozygous de novo missense variant c.376G>C (p.Asp126His) in the FEM1C gene. Cognitive assessment performed at 9 years of age showed that he has moderate intellectual disability.

De novo variant in the same residue (p.Asp126Val) has also been associated with an uncharacterised developmental disorder in PMID:28135719.

An additional case with a diagnostically reported de novo variant in this gene and a compatible phenotype including intellectual disability and ataxia was identified in the internal Genomics England Clinical Variant Archive (CVA) by the Diagnostic Discovery initiative.

This gene has not yet been associated with relevant phenotypes in OMIM or in Gene2Phenotype.
Sources: Literature; to: PMID:36336956 reported a 9 year-old boy with severe global developmental delay, lack of speech, pyramidal signs and limb ataxia and identified with a heterozygous de novo missense variant c.376G>C (p.Asp126His) in the FEM1C gene. Cognitive assessment performed at 9 years of age showed that he has moderate intellectual disability.

De novo variant in the same residue (p.Asp126Val) has also been associated with an uncharacterised developmental disorder in PMID:28135719.

An additional case with a diagnostically reported de novo variant in this gene and a compatible phenotype including intellectual disability and ataxia was identified in the internal Genomics England Clinical Variant Archive (CVA) by the Diagnostic Discovery initiative.

This gene has not yet been associated with relevant phenotypes in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.161 FEM1C Achchuthan Shanmugasundram changed review comment from: This gene should be rated RED as there is only one clear case of intellectual disability reported in literature.

PMID:36336956 reported a 9 year-old boy with severe global developmental delay, lack of speech, pyramidal signs and limb ataxia and identified with a heterozygous de novo missense variant c.376G>C (p.Asp126His) in the FEM1C gene. Cognitive assessment performed at 9 years of age showed that he has moderate intellectual disability.

De novo variant in the same residue (p.Asp126Val) has also been associated with an uncharacterised developmental disorder in PMID:28135719.

This gene has not yet been associated with relevant phenotypes in OMIM or in Gene2Phenotype.
Sources: Literature; to: This gene should be rated RED as there is only one clear case of intellectual disability reported in literature.

PMID:36336956 reported a 9 year-old boy with severe global developmental delay, lack of speech, pyramidal signs and limb ataxia and identified with a heterozygous de novo missense variant c.376G>C (p.Asp126His) in the FEM1C gene. Cognitive assessment performed at 9 years of age showed that he has moderate intellectual disability.

De novo variant in the same residue (p.Asp126Val) has also been associated with an uncharacterised developmental disorder in PMID:28135719.

An additional case with a diagnostically reported de novo variant in this gene and a compatible phenotype including intellectual disability and ataxia was identified in the internal Genomics England Clinical Variant Archive (CVA) by the Diagnostic Discovery initiative.

This gene has not yet been associated with relevant phenotypes in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.161 FEM1C Achchuthan Shanmugasundram edited their review of gene: FEM1C: Changed rating: AMBER
Intellectual disability v5.161 POU3F2 Sarah Leigh Classified gene: POU3F2 as Amber List (moderate evidence)
Intellectual disability v5.161 POU3F2 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 v5.161 POU3F2 Sarah Leigh Gene: pou3f2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.161 POU3F2 Sarah Leigh Classified gene: POU3F2 as Amber List (moderate evidence)
Intellectual disability v5.161 POU3F2 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 v5.161 POU3F2 Sarah Leigh Gene: pou3f2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.160 POU3F2 Sarah Leigh gene: POU3F2 was added
gene: POU3F2 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Q2_23_promote_green tags were added to gene: POU3F2.
Mode of inheritance for gene: POU3F2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: POU3F2 were set to 37207645
Phenotypes for gene: POU3F2 were set to neurodevelopmental delay with hyperphagic obesity
Review for gene: POU3F2 was set to GREEN
Added comment: Not associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 37207645 reports eight POU3F2 variants in the unrelated cases of neurodevelopmental delay with hyperphagic obesity, with no other variants detected in other candidate genes. Intellectual disability was apparent in 6/7 of these cases from infancy to early childhood. The remaining variant : NM_005604.4 c.135C>A, p.Tyr45* was found in a mother and son, where the son was classified as having intellectual disability, the mother did not. Excluding the mother and son, all of the remaining cases carrying POU3F2 variants had neurodevelopmental delay.
Sources: Literature
Intellectual disability v5.159 ETFB Sarah Leigh Publications for gene: ETFB were set to 30847515; 11980892; 25778941; 24360804; 27021474; 28489334; 30089828; 36495139
Intellectual disability v5.158 ETFB Sarah Leigh Publications for gene: ETFB were set to 0
Intellectual disability v5.157 ETFB Sarah Leigh Phenotypes for gene: ETFB were changed from GLUTARIC ACIDURIA TYPE 2B to Glutaric acidemia IIB, OMIM:231680; multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282
Intellectual disability v5.156 ETFA Sarah Leigh Phenotypes for gene: ETFA were changed from GLUTARIC ACIDURIA TYPE 2A to Glutaric acidemia IIA, OMIM:231680; multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282
Intellectual disability v5.155 NUP214 Eleanor Williams Tag Q2_23_promote_green tag was added to gene: NUP214.
Intellectual disability v5.155 NUP214 Eleanor Williams commented on gene: NUP214: After consultation with the Genomics England clinical team it has been decided that there is just enough evidence to promote this gene to green as there are 4 unrelated families and developmental delay is reported in all.
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: FILIP1.
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Classified gene: FILIP1 as Amber List (moderate evidence)
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (3 unrelated families) for this gene to be promoted to GREEN rating at the next major update.
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Gene: filip1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram changed review comment from: PMID:36344539 reported a single male with biallelic variant in FILIP1 (c.2665C > T/ p.Arg889Ter) gene and presenting with distal arthrogryposis and mild learning disability.

PMID:37163662 reported five individuals from four unrelated families with four different biallelic variants in FILIP1 gene. The main symptoms in childhood included delayed motor milestones (all four families), delayed speech development (three families), intellectual disability (three families), contractures (2 families), clubfeet (2 families) and microcephaly (2 families). As one of the patients died at the age of 13 months, intellectual disability and speech delay were not evaluated.

This gene has not been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature; to: PMID:36344539 reported a single male with biallelic variant in FILIP1 (c.2665C > T/ p.Arg889Ter) gene and presenting with distal arthrogryposis and mild learning disability.

PMID:37163662 reported five individuals from four unrelated families with four different biallelic variants in FILIP1 gene. The main symptoms in childhood included delayed motor milestones (all four families), delayed speech development (three families), intellectual disability (three families), contractures (2 families), clubfeet (2 families) and microcephaly (2 families). As one of the patients died at the age of 13 months, intellectual disability and speech delay were not evaluated.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Classified gene: FILIP1 as Amber List (moderate evidence)
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (3 unrelated families) for this gene to be promoted to GREEN rating at the next major update.
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Gene: filip1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Classified gene: FILIP1 as Amber List (moderate evidence)
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (3 unrelated families) for this gene to be promoted to GREEN rating at the next major update.
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Gene: filip1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Classified gene: FILIP1 as Amber List (moderate evidence)
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (3 unrelated families) for this gene to be promoted to GREEN rating at the next major update.
Intellectual disability v5.155 FILIP1 Achchuthan Shanmugasundram Gene: filip1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.154 FILIP1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.154 FILIP1 Achchuthan Shanmugasundram Classified gene: FILIP1 as Amber List (moderate evidence)
Intellectual disability v5.154 FILIP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (3 unrelated families) for this gene to be promoted to GREEN rating at the next major update.
Intellectual disability v5.154 FILIP1 Achchuthan Shanmugasundram Gene: filip1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.154 FILIP1 Achchuthan Shanmugasundram Classified gene: FILIP1 as Amber List (moderate evidence)
Intellectual disability v5.154 FILIP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (3 unrelated families) for this gene to be promoted to GREEN rating at the next major update.
Intellectual disability v5.154 FILIP1 Achchuthan Shanmugasundram Gene: filip1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.153 FILIP1 Achchuthan Shanmugasundram changed review comment from: Sources: Literature; to: PMID:36344539 reported a single male with biallelic variant in FILIP1 (c.2665C > T/ p.Arg889Ter) gene and presenting with distal arthrogryposis and mild learning disability.

PMID:37163662 reported five individuals from four unrelated families with four different biallelic variants in FILIP1 gene. The main symptoms in childhood included delayed motor milestones (all four families), delayed speech development (three families), intellectual disability (three families), contractures (2 families), clubfeet (2 families) and microcephaly (2 families). As one of the patients died at the age of 13 months, intellectual disability and speech delay were not evaluated.

This gene has not been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v5.153 FILIP1 Achchuthan Shanmugasundram gene: FILIP1 was added
gene: FILIP1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: FILIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FILIP1 were set to 36344539; 37163662
Phenotypes for gene: FILIP1 were set to intellectual disability, MONDO:0001071
Review for gene: FILIP1 was set to GREEN
Added comment: Sources: Literature
Intellectual disability v5.152 FLNA Tracy Lester reviewed gene: FLNA: Rating: RED; Mode of pathogenicity: None; Publications: 20301392; Phenotypes: Skeletal dysplasia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.152 TAF4 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence available to promote this gene to GREEN at the next major update.; to: Comment on list classification: There is sufficient evidence available to promote this gene to GREEN rating at the next major update.
Intellectual disability v5.152 TAF4 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.152 TAF4 Achchuthan Shanmugasundram Classified gene: TAF4 as Amber List (moderate evidence)
Intellectual disability v5.152 TAF4 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available to promote this gene to GREEN at the next major update.
Intellectual disability v5.152 TAF4 Achchuthan Shanmugasundram Gene: taf4 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.152 TAF4 Achchuthan Shanmugasundram Classified gene: TAF4 as Amber List (moderate evidence)
Intellectual disability v5.152 TAF4 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available to promote this gene to GREEN at the next major update.
Intellectual disability v5.152 TAF4 Achchuthan Shanmugasundram Gene: taf4 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.151 INTS11 Arina Puzriakova Phenotypes for gene: INTS11 were changed from intellectual disability, MONDO:0001071 to Complex neurodevelopmental disorder, MONDO:0100038
Intellectual disability v5.150 INTS11 Arina Puzriakova commented on gene: INTS11
Intellectual disability v5.150 TAF4 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: TAF4.
Intellectual disability v5.150 PRKACB Arina Puzriakova Phenotypes for gene: PRKACB were changed from Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability to Cardioacrofacial dysplasia 2, OMIM:619143
Intellectual disability v5.149 TAF4 Achchuthan Shanmugasundram Phenotypes for gene: TAF4 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.149 TAF4 Achchuthan Shanmugasundram Phenotypes for gene: TAF4 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.148 TAF4 Achchuthan Shanmugasundram Phenotypes for gene: TAF4 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.149 TAF4 Achchuthan Shanmugasundram Phenotypes for gene: TAF4 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.147 TAF4 Achchuthan Shanmugasundram Publications for gene: TAF4 were set to 27026076; 28191890; 33875846; 35904126
Intellectual disability v5.148 TAF4 Achchuthan Shanmugasundram Phenotypes for gene: TAF4 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.148 TAF4 Achchuthan Shanmugasundram Phenotypes for gene: TAF4 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.148 TAF4 Achchuthan Shanmugasundram Phenotypes for gene: TAF4 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.147 TAF4 Achchuthan Shanmugasundram Publications for gene: TAF4 were set to 27026076; 28191890; 33875846; 35904126
Intellectual disability v5.148 TAF4 Achchuthan Shanmugasundram Phenotypes for gene: TAF4 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.148 TAF4 Achchuthan Shanmugasundram Phenotypes for gene: TAF4 were changed from intellectual disability, MONDO:0001071 to intellectual disability, MONDO:0001071
Intellectual disability v5.148 TAF4 Achchuthan Shanmugasundram Phenotypes for gene: TAF4 were changed from Developmental disorder to intellectual disability, MONDO:0001071
Intellectual disability v5.147 TAF4 Achchuthan Shanmugasundram Publications for gene: TAF4 were set to 27026076; 28191890; 33875846; 35904126
Intellectual disability v5.147 TAF4 Achchuthan Shanmugasundram Publications for gene: TAF4 were set to 27026076; 28191890; 33875846; 35904126
Intellectual disability v5.147 TAF4 Achchuthan Shanmugasundram Publications for gene: TAF4 were set to 27026076; 28191890; 33875846; 35904126
Intellectual disability v5.147 TAF4 Achchuthan Shanmugasundram Publications for gene: TAF4 were set to 27026076; 28191890; 33875846; 35904126
Intellectual disability v5.147 TAF4 Achchuthan Shanmugasundram Publications for gene: TAF4 were set to 27026076; 28191890; 33875846; 35904126
Intellectual disability v5.147 TAF4 Achchuthan Shanmugasundram Publications for gene: TAF4 were set to 33875846; 28191890; 27026076
Intellectual disability v5.146 TAF4 Achchuthan Shanmugasundram Mode of inheritance for gene: TAF4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.146 TAF4 Achchuthan Shanmugasundram Mode of inheritance for gene: TAF4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.146 TAF4 Achchuthan Shanmugasundram Mode of inheritance for gene: TAF4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.146 TAF4 Achchuthan Shanmugasundram Mode of inheritance for gene: TAF4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.146 TAF4 Achchuthan Shanmugasundram Mode of inheritance for gene: TAF4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.146 TAF4 Achchuthan Shanmugasundram Mode of inheritance for gene: TAF4 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.145 TAF4 Achchuthan Shanmugasundram reviewed gene: TAF4: Rating: GREEN; Mode of pathogenicity: None; Publications: 28191890, 33875846, 35904126; Phenotypes: intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Classified gene: ZMYND8 as Amber List (moderate evidence)
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases) for this gene to be rated GREEN at the next major update.
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Gene: zmynd8 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Classified gene: ZMYND8 as Amber List (moderate evidence)
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases) for this gene to be rated GREEN at the next major update.
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Gene: zmynd8 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Classified gene: ZMYND8 as Amber List (moderate evidence)
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases) for this gene to be rated GREEN at the next major update.
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Gene: zmynd8 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Classified gene: ZMYND8 as Amber List (moderate evidence)
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases) for this gene to be rated GREEN at the next major update.
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Gene: zmynd8 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Classified gene: ZMYND8 as Amber List (moderate evidence)
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases) for this gene to be rated GREEN at the next major update.
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Gene: zmynd8 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: ZMYND8.
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Classified gene: ZMYND8 as Amber List (moderate evidence)
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases) for this gene to be rated GREEN at the next major update.
Intellectual disability v5.145 ZMYND8 Achchuthan Shanmugasundram Gene: zmynd8 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.144 ZMYND8 Achchuthan Shanmugasundram Mode of inheritance for gene: ZMYND8 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.144 ZMYND8 Achchuthan Shanmugasundram Mode of inheritance for gene: ZMYND8 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.144 ZMYND8 Achchuthan Shanmugasundram Mode of inheritance for gene: ZMYND8 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.144 ZMYND8 Achchuthan Shanmugasundram Mode of inheritance for gene: ZMYND8 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.144 ZMYND8 Achchuthan Shanmugasundram Mode of inheritance for gene: ZMYND8 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.144 ZMYND8 Achchuthan Shanmugasundram Mode of inheritance for gene: ZMYND8 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.144 ZMYND8 Achchuthan Shanmugasundram Mode of inheritance for gene: ZMYND8 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.143 ZMYND8 Achchuthan Shanmugasundram edited their review of gene: ZMYND8: Added comment: As reviewed by Konstantinos Varvagiannis, PMID:35916866 reported intellectual disability in10 out of 11 unrelated cases, of which one patient had profound ID and two had moderate ID.

This gene has not yet been associated with phenotypes in OMIM, but has been reported in Gene2Phenotype (with 'moderate' rating in the DD panel).; Changed phenotypes to: intellectual disability, MONDO:0001071
Intellectual disability v5.143 ZMYND8 Achchuthan Shanmugasundram reviewed gene: ZMYND8: Rating: GREEN; Mode of pathogenicity: None; Publications: 32530565, 35916866; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.143 ZMYND15 Achchuthan Shanmugasundram Publications for gene: ZMYND15 were set to 35916866; 32530565
Intellectual disability v5.142 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.141 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.143 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.142 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.141 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.141 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.142 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.142 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.141 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.142 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.141 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14 OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.140 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14 OMIM:615842
Intellectual disability v5.141 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.141 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14, OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.141 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14 OMIM:615842 to ?Spermatogenic failure 14, OMIM:615842
Intellectual disability v5.140 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14 OMIM:615842 to ?Spermatogenic failure 14 OMIM:615842
Intellectual disability v5.140 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14 OMIM:615842 to ?Spermatogenic failure 14 OMIM:615842
Intellectual disability v5.140 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14 OMIM:615842 to ?Spermatogenic failure 14 OMIM:615842
Intellectual disability v5.140 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from ?Spermatogenic failure 14 OMIM:615842 to ?Spermatogenic failure 14 OMIM:615842
Intellectual disability v5.140 ZMYND15 Achchuthan Shanmugasundram Phenotypes for gene: ZMYND15 were changed from Delayed speech and language development; Motor delay; Intellectual disability; Abnormality of cardiovascular system morphology; Hearing abnormality; Abnormality of vision; Abnormality of the face; Seizures to ?Spermatogenic failure 14 OMIM:615842
Intellectual disability v5.139 ZMYND15 Achchuthan Shanmugasundram commented on gene: ZMYND15
Intellectual disability v5.139 ZMYND15 Achchuthan Shanmugasundram Classified gene: ZMYND15 as No list
Intellectual disability v5.139 ZMYND15 Achchuthan Shanmugasundram Gene: zmynd15 has been removed from the panel.
Intellectual disability v5.139 ZMYND15 Achchuthan Shanmugasundram Classified gene: ZMYND15 as No list
Intellectual disability v5.139 ZMYND15 Achchuthan Shanmugasundram Gene: zmynd15 has been removed from the panel.
Intellectual disability v5.139 ZMYND15 Achchuthan Shanmugasundram Classified gene: ZMYND15 as No list
Intellectual disability v5.139 ZMYND15 Achchuthan Shanmugasundram Gene: zmynd15 has been removed from the panel.
Intellectual disability v5.139 ZMYND15 Achchuthan Shanmugasundram Classified gene: ZMYND15 as No list
Intellectual disability v5.139 ZMYND15 Achchuthan Shanmugasundram Gene: zmynd15 has been removed from the panel.
Intellectual disability v5.139 ZMYND15 Achchuthan Shanmugasundram Classified gene: ZMYND15 as No list
Intellectual disability v5.139 ZMYND15 Achchuthan Shanmugasundram Gene: zmynd15 has been removed from the panel.
Intellectual disability v5.138 ZMYND15 Achchuthan Shanmugasundram Classified gene: ZMYND15 as No list
Intellectual disability v5.138 ZMYND15 Achchuthan Shanmugasundram Gene: zmynd15 has been removed from the panel.
Intellectual disability v5.138 ZMYND15 Achchuthan Shanmugasundram Classified gene: ZMYND15 as No list
Intellectual disability v5.138 ZMYND15 Achchuthan Shanmugasundram Gene: zmynd15 has been removed from the panel.
Intellectual disability v5.138 ZMYND15 Achchuthan Shanmugasundram Classified gene: ZMYND15 as No list
Intellectual disability v5.138 ZMYND15 Achchuthan Shanmugasundram Gene: zmynd15 has been removed from the panel.
Intellectual disability v5.137 ZMYND15 Achchuthan Shanmugasundram Tag curated_removed tag was added to gene: ZMYND15.
Intellectual disability v5.137 PRSS12 Achchuthan Shanmugasundram changed review comment from: Comment on gene classification - This gene should remain as Green rating as there are four unrelated cases and two different variants reported.

PMID:12459588 - Two unrelated families with the same variant (4bp homozygous deletion) and with intellectual disability. Although the cases were thought to be unrelated, they had the same haplotype across the PRSS12 locus, suggesting either distant consanguinity or a founder effect in the Algerian population.

PMID:25529582 - Two unrelated cases with homozygous c.2389C>T/ p.Arg797Cys variants and with severe intellectual disability reported in the Deciphering Developmental Disorders (DDD) study.

In addition, this gene has been associated with intellectual disability in both OMIM (MIM #249500) and Gene2Phenotype (with 'Definitive' rating in the DD panel).; to: Comment on gene classification - This gene should remain as Green as there are four unrelated cases and two different variants reported.

PMID:12459588 - Two unrelated families with the same variant (4bp homozygous deletion) and with intellectual disability. Although the cases were thought to be unrelated, they had the same haplotype across the PRSS12 locus, suggesting either distant consanguinity or a founder effect in the Algerian population.

PMID:25529582 - Two unrelated cases with homozygous c.2389C>T/ p.Arg797Cys variants and with severe intellectual disability reported in the Deciphering Developmental Disorders (DDD) study.

In addition, this gene has been associated with intellectual disability in both OMIM (MIM #249500) and Gene2Phenotype (with 'Definitive' rating in the DD panel).
Intellectual disability v5.137 PRSS12 Achchuthan Shanmugasundram changed review comment from: PMID:12459588 - Two unrelated families with the same variant (4bp homozygous deletion) and with intellectual disability. Although the cases were thought to be unrelated, they had the same haplotype across the PRSS12 locus, suggesting either distant consanguinity or a founder effect in the Algerian population.

PMID:25529582 - Two unrelated cases with homozygous c.2389C>T/ p.Arg797Cys variants and with severe intellectual disability reported in the Deciphering Developmental Disorders (DDD) study.

In addition, this gene has been associated with intellectual disability in both OMIM (MIM #249500) and Gene2Phenotype (with 'Definitive' rating in the DD panel).; to: Comment on gene classification - This gene should remain as Green rating as there are four unrelated cases and two different variants reported.

PMID:12459588 - Two unrelated families with the same variant (4bp homozygous deletion) and with intellectual disability. Although the cases were thought to be unrelated, they had the same haplotype across the PRSS12 locus, suggesting either distant consanguinity or a founder effect in the Algerian population.

PMID:25529582 - Two unrelated cases with homozygous c.2389C>T/ p.Arg797Cys variants and with severe intellectual disability reported in the Deciphering Developmental Disorders (DDD) study.

In addition, this gene has been associated with intellectual disability in both OMIM (MIM #249500) and Gene2Phenotype (with 'Definitive' rating in the DD panel).
Intellectual disability v5.137 PRSS12 Achchuthan Shanmugasundram changed review comment from: PMID:12459588 - Two unrelated families with the same variant (4bp homozygous deletion) and with intellectual disability. Although the cases were thought to be unrelated, they had the same haplotype across the PRSS12 locus, suggesting either distant consanguinity or a founder effect in the Algerian population.

PMID:25529582 - Two unrelated cases with homozygous c.2389C>T/ p.Arg797Cys variants and with severe intellectual disability reported in the Deciphering Developmental Disorders (DDD) study.

In addition, this gene has been associated with intellectual disability in both OMIM (MIM #249500) and Gene2Phenotype (with 'Definitive' rating in the DD panel).; to: PMID:12459588 - Two unrelated families with the same variant (4bp homozygous deletion) and with intellectual disability. Although the cases were thought to be unrelated, they had the same haplotype across the PRSS12 locus, suggesting either distant consanguinity or a founder effect in the Algerian population.

PMID:25529582 - Two unrelated cases with homozygous c.2389C>T/ p.Arg797Cys variants and with severe intellectual disability reported in the Deciphering Developmental Disorders (DDD) study.

In addition, this gene has been associated with intellectual disability in both OMIM (MIM #249500) and Gene2Phenotype (with 'Definitive' rating in the DD panel).
Intellectual disability v5.137 PRSS12 Achchuthan Shanmugasundram reviewed gene: PRSS12: Rating: GREEN; Mode of pathogenicity: None; Publications: 12459588, 25529582; Phenotypes: Intellectual developmental disorder, autosomal recessive 1, OMIM:249500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: MAN2C1.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Classified gene: MAN2C1 as Amber List (moderate evidence)
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Gene: man2c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Classified gene: MAN2C1 as Amber List (moderate evidence)
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Gene: man2c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Classified gene: MAN2C1 as Amber List (moderate evidence)
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Gene: man2c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.; to: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN rating at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Classified gene: MAN2C1 as Amber List (moderate evidence)
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Gene: man2c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Classified gene: MAN2C1 as Amber List (moderate evidence)
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Gene: man2c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Classified gene: MAN2C1 as Amber List (moderate evidence)
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Gene: man2c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Classified gene: MAN2C1 as Amber List (moderate evidence)
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Gene: man2c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Classified gene: MAN2C1 as Amber List (moderate evidence)
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Gene: man2c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Classified gene: MAN2C1 as Amber List (moderate evidence)
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Gene: man2c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Classified gene: MAN2C1 as Amber List (moderate evidence)
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Gene: man2c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Classified gene: MAN2C1 as Amber List (moderate evidence)
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next major update.
Intellectual disability v5.137 MAN2C1 Achchuthan Shanmugasundram Gene: man2c1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.136 MAN2C1 Achchuthan Shanmugasundram Phenotypes for gene: MAN2C1 were changed from Congenital disorder of deglycosylation 2, OMIM:619775 to Congenital disorder of deglycosylation 2, OMIM:619775
Intellectual disability v5.136 MAN2C1 Achchuthan Shanmugasundram Phenotypes for gene: MAN2C1 were changed from Congenital disorder of deglycosylation 2, OMIM:619775 to Congenital disorder of deglycosylation 2, OMIM:619775
Intellectual disability v5.136 MAN2C1 Achchuthan Shanmugasundram Phenotypes for gene: MAN2C1 were changed from Congenital disorder of deglycosylation 2, OMIM:619775 to Congenital disorder of deglycosylation 2, OMIM:619775
Intellectual disability v5.136 MAN2C1 Achchuthan Shanmugasundram Phenotypes for gene: MAN2C1 were changed from Congenital disorder of deglycosylation 2, OMIM:619775 to Congenital disorder of deglycosylation 2, OMIM:619775
Intellectual disability v5.136 MAN2C1 Achchuthan Shanmugasundram Phenotypes for gene: MAN2C1 were changed from Congenital disorder of deglycosylation 2, OMIM:619775 to Congenital disorder of deglycosylation 2, OMIM:619775
Intellectual disability v5.136 MAN2C1 Achchuthan Shanmugasundram Phenotypes for gene: MAN2C1 were changed from Congenital disorder of deglycosylation 2, OMIM:619775 to Congenital disorder of deglycosylation 2, OMIM:619775
Intellectual disability v5.136 MAN2C1 Achchuthan Shanmugasundram Phenotypes for gene: MAN2C1 were changed from Global developmental delay; Intellectual disability; Abnormality of nervous system morphology; Abnormality of the corpus callosum; Ventriculomegaly; Polymicrogyria; Abnormality of the face; Macrocephaly to Congenital disorder of deglycosylation 2, OMIM:619775
Intellectual disability v5.135 MAN2C1 Achchuthan Shanmugasundram commented on gene: MAN2C1: As reviewed by Konstantinos Varvagiannis, there are three unrelated cases reported with intellectual disability in PMID:35045343.

In addition, this gene has been associated with relevant phenotypes in both OMIM (MIM #619775) and Gene2Phenotype (with 'strong' rating in DD panel).
Intellectual disability v5.135 MAN2C1 Achchuthan Shanmugasundram reviewed gene: MAN2C1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35045343; Phenotypes: Congenital disorder of deglycosylation 2, OMIM:619775; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.135 FAAH2 Achchuthan Shanmugasundram changed review comment from: As reviewed already, there are two cases reported in PMIDs: 25885783 & 34645488. Additional cases were reported in PMIDs: 20655035 & 23352160, however without much clinical details. Hence, the rating should remain amber.; to: As reviewed already, there are two cases reported in PMIDs: 25885783 & 34645488. Additional cases were reported in PMIDs: 20655035 & 23352160, however without much clinical details. Hence, the rating should remain amber.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Intellectual disability v5.135 FAAH2 Achchuthan Shanmugasundram Mode of inheritance for gene: FAAH2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.135 FAAH2 Achchuthan Shanmugasundram Mode of inheritance for gene: FAAH2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.134 FAAH2 Achchuthan Shanmugasundram Mode of inheritance for gene: FAAH2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.135 FAAH2 Achchuthan Shanmugasundram Mode of inheritance for gene: FAAH2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.135 FAAH2 Achchuthan Shanmugasundram Mode of inheritance for gene: FAAH2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.134 FAAH2 Achchuthan Shanmugasundram Mode of inheritance for gene: FAAH2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.134 FAAH2 Achchuthan Shanmugasundram Publications for gene: FAAH2 were set to 25885783; 20655035; 34645488
Intellectual disability v5.134 FAAH2 Achchuthan Shanmugasundram Mode of inheritance for gene: FAAH2 was changed from BIALLELIC, autosomal or pseudoautosomal to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.134 FAAH2 Achchuthan Shanmugasundram Publications for gene: FAAH2 were set to 25885783; 20655035; 34645488
Intellectual disability v5.134 FAAH2 Achchuthan Shanmugasundram Publications for gene: FAAH2 were set to 25885783; 20655035; 34645488
Intellectual disability v5.133 FAAH2 Achchuthan Shanmugasundram Publications for gene: FAAH2 were set to 25885783; 20655035; 34645488
Intellectual disability v5.134 FAAH2 Achchuthan Shanmugasundram Publications for gene: FAAH2 were set to 25885783; 20655035; 34645488
Intellectual disability v5.134 FAAH2 Achchuthan Shanmugasundram Publications for gene: FAAH2 were set to 25885783; 20655035; 34645488
Intellectual disability v5.134 FAAH2 Achchuthan Shanmugasundram Publications for gene: FAAH2 were set to 25885783; 20655035; 34645488
Intellectual disability v5.134 FAAH2 Achchuthan Shanmugasundram Publications for gene: FAAH2 were set to 25885783; 20655035; 34645488
Intellectual disability v5.133 FAAH2 Achchuthan Shanmugasundram Publications for gene: FAAH2 were set to 25885783; 20655035; 34645488
Intellectual disability v5.133 FAAH2 Achchuthan Shanmugasundram Publications for gene: FAAH2 were set to 25885783; 20655035
Intellectual disability v5.133 FAAH2 Achchuthan Shanmugasundram Mode of inheritance for gene: FAAH2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.133 FAAH2 Achchuthan Shanmugasundram Mode of inheritance for gene: FAAH2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.132 FAAH2 Achchuthan Shanmugasundram Mode of inheritance for gene: FAAH2 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.131 FAAH2 Achchuthan Shanmugasundram reviewed gene: FAAH2: Rating: AMBER; Mode of pathogenicity: None; Publications: 25885783, 34645488; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.131 ITPR1 Arina Puzriakova Phenotypes for gene: ITPR1 were changed from Gillespie syndrome 206700 to Gillespie syndrome, OMIM:206700; Spinocerebellar ataxia 15, OMIM:606658; Spinocerebellar ataxia 29, congenital nonprogressive, OMIM:117360
Intellectual disability v5.130 ITPR1 Arina Puzriakova Added comment: Comment on mode of inheritance: Should be updated from 'biallelic' to 'both mono- and biallelic' at the next GMS panel update inline with the review by Tracy Lester. Although not observed in all, some patients do exhibit cognitive deficits which may be an early and severe feature. There are sufficient unrelated cases with heterozygous variants and ID (associated with either Gillespie or SCA) to warrant including this MOI on this panel.
Intellectual disability v5.130 ITPR1 Arina Puzriakova Mode of inheritance for gene: ITPR1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.129 ITPR1 Arina Puzriakova Publications for gene: ITPR1 were set to 22986007
Intellectual disability v5.128 ITPR1 Arina Puzriakova Tag Q2_23_MOI tag was added to gene: ITPR1.
Tag Q2_23_NHS_review tag was added to gene: ITPR1.
Intellectual disability v5.128 BLM Arina Puzriakova Phenotypes for gene: BLM were changed from Bloom syndrome, 210900; BLOOM SYNDROME to Bloom syndrome, OMIM:210900
Intellectual disability v5.128 BLM Arina Puzriakova Publications for gene: BLM were set to
Intellectual disability v5.127 BLM Arina Puzriakova reviewed gene: BLM: Rating: ; Mode of pathogenicity: None; Publications: 22514588, 23552953, 36646944; Phenotypes: ; Mode of inheritance: None
Intellectual disability v5.127 NSF Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene is now associated with a relevant phenotype in OMIM (MIM #619340), but not in Gene2Phenotype.
Intellectual disability v5.127 NSF Achchuthan Shanmugasundram Phenotypes for gene: NSF were changed from Developmental and epileptic encephalopathy 96, OMIM:619340 to Developmental and epileptic encephalopathy 96, OMIM:619340
Intellectual disability v5.127 NSF Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene is now associated with a relevant phenotype in OMIM (MIM #619340), but not in Gene2Phenotype.
Intellectual disability v5.127 NSF Achchuthan Shanmugasundram Phenotypes for gene: NSF were changed from Developmental and epileptic encephalopathy 96, OMIM:619340 to Developmental and epileptic encephalopathy 96, OMIM:619340
Intellectual disability v5.127 NSF Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene is now associated with a relevant phenotype in OMIM (MIM #619340), but not in Gene2Phenotype.
Intellectual disability v5.127 NSF Achchuthan Shanmugasundram Phenotypes for gene: NSF were changed from Developmental and epileptic encephalopathy 96, OMIM:619340 to Developmental and epileptic encephalopathy 96, OMIM:619340
Intellectual disability v5.127 NSF Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.127 NSF Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene is now associated with a relevant phenotype in OMIM (MIM #619340), but not in Gene2Phenotype.
Intellectual disability v5.127 NSF Achchuthan Shanmugasundram Phenotypes for gene: NSF were changed from Developmental and epileptic encephalopathy 96, OMIM:619340 to Developmental and epileptic encephalopathy 96, OMIM:619340
Intellectual disability v5.126 NSF Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.126 NSF Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene is now associated with a relevant phenotype in OMIM (MIM #619340), but not in Gene2Phenotype.
Intellectual disability v5.126 NSF Achchuthan Shanmugasundram Phenotypes for gene: NSF were changed from Developmental and epileptic encephalopathy 96, OMIM:619340 to Developmental and epileptic encephalopathy 96, OMIM:619340
Intellectual disability v5.126 NSF Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene is now associated with a relevant phenotype in OMIM (MIM #619340), but not in Gene2Phenotype.
Intellectual disability v5.126 NSF Achchuthan Shanmugasundram Phenotypes for gene: NSF were changed from Seizures; EEG with burst suppression; Global developmental delay; Intellectual disability to Developmental and epileptic encephalopathy 96, OMIM:619340
Intellectual disability v5.125 NSF Achchuthan Shanmugasundram reviewed gene: NSF: Rating: RED; Mode of pathogenicity: None; Publications: 36645181; Phenotypes: Developmental and epileptic encephalopathy 96, OMIM:619340; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.125 NSF Achchuthan Shanmugasundram Publications for gene: NSF were set to 31675180; 36645181
Intellectual disability v5.125 NSF Achchuthan Shanmugasundram Publications for gene: NSF were set to 31675180
Intellectual disability v5.124 ENTPD1 Achchuthan Shanmugasundram Publications for gene: ENTPD1 were set to 21937992; 24482476; 29691679; 30652007; 35471564; 35758610
Intellectual disability v5.124 ENTPD1 Achchuthan Shanmugasundram Publications for gene: ENTPD1 were set to 21937992; 24482476; 29691679; 30652007; 35471564; 35758610
Intellectual disability v5.124 ENTPD1 Achchuthan Shanmugasundram Publications for gene: ENTPD1 were set to 21937992; 24482476; 29691679; 30652007; 35471564; 35758610
Intellectual disability v5.124 ENTPD1 Achchuthan Shanmugasundram Publications for gene: ENTPD1 were set to 21937992; 24482476; 29691679; 30652007; 35471564
Intellectual disability v5.123 ENTPD1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: ENTPD1.
Intellectual disability v5.123 ENTPD1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Konstantinos Varvagiannis, PMID:35471564 reported 27 cases from 17 families with a complex childhood-onset neurodevelopmental disorder characterised by intellectual disability/ developmental delay and spastic paraplegia in all individuals, white matter abnormalities in 12 individuals and epilepsy in 7 individuals.

In addition, this gene has been associated with autosomal recessive intellectual developmental disorder in Gene2phenotype with 'limited' rating and ID has been included as part of the SPG64 phenotype in OMIM. ; to: As reviewed by Konstantinos Varvagiannis, PMID:35471564 reported 27 cases from 17 families with biallelic variants in ENTPD1 and with a complex childhood-onset neurodevelopmental disorder characterised by intellectual disability/ developmental delay and spastic paraplegia in all individuals, white matter abnormalities in 12 individuals and epilepsy in 7 individuals.

PMID:35758610 reported two siblings with biallelic variants in ENTPD1. The proband was mildly intellectually disabled and her brother was moderately clinically disabled based on clinical observations.

In addition, this gene has been associated with autosomal recessive intellectual developmental disorder in Gene2phenotype with 'limited' rating and ID has been included as part of the SPG64 phenotype in OMIM.
Intellectual disability v5.123 COASY Sarah Leigh Phenotypes for gene: COASY were changed from Neurodegeneration with brain iron accumulation 6, OMIM:615643; neurodegeneration with brain iron accumulation 6, MONDO:0014290 to Neurodegeneration with brain iron accumulation 6, OMIM:615643; neurodegeneration with brain iron accumulation 6, MONDO:0014290; Pontocerebellar hypoplasia, type 12, OMIM:618266; pontocerebellar hypoplasia, type 12, MONDO:0032643
Intellectual disability v5.122 ENTPD1 Achchuthan Shanmugasundram edited their review of gene: ENTPD1: Changed publications to: 35471564, 35758610
Intellectual disability v5.122 COASY Sarah Leigh Publications for gene: COASY were set to 24360804
Intellectual disability v5.121 ENTPD1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Konstantinos Varvagiannis, PMID35471564 reported 27 cases from 17 families with a complex childhood-onset neurodevelopmental disorder characterised by intellectual disability/ developmental delay and spastic paraplegia in all individuals, white matter abnormalities in 12 individuals and epilepsy in 7 individuals.

In addition, this gene has been associated with autosomal recessive intellectual developmental disorder in Gene2phenotype with 'limited' rating and ID has been included as part of the SPG64 phenotype in OMIM. ; to: As reviewed by Konstantinos Varvagiannis, PMID:35471564 reported 27 cases from 17 families with a complex childhood-onset neurodevelopmental disorder characterised by intellectual disability/ developmental delay and spastic paraplegia in all individuals, white matter abnormalities in 12 individuals and epilepsy in 7 individuals.

In addition, this gene has been associated with autosomal recessive intellectual developmental disorder in Gene2phenotype with 'limited' rating and ID has been included as part of the SPG64 phenotype in OMIM.
Intellectual disability v5.121 ENTPD1 Achchuthan Shanmugasundram Classified gene: ENTPD1 as Amber List (moderate evidence)
Intellectual disability v5.121 ENTPD1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to Green rating at the next major update.
Intellectual disability v5.121 ENTPD1 Achchuthan Shanmugasundram Gene: entpd1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.120 ENTPD1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Konstantinos Varvagiannis, PMID35471564 reported 27 cases from 17 families with a complex childhood-onset neurodevelopmental disorder characterised by intellectual disability/ developmental delay and spastic paraplegia in all individuals, white matter abnormalities in 12 individuals and epilepsy in 7 individuals.

In addition, this gene has been associated with autosomal recessive intellectual developmental disorder in Gene2phenotype with 'limited' rating and ID has been includes as part of the SPG64 phenotype in OMIM. ; to: As reviewed by Konstantinos Varvagiannis, PMID35471564 reported 27 cases from 17 families with a complex childhood-onset neurodevelopmental disorder characterised by intellectual disability/ developmental delay and spastic paraplegia in all individuals, white matter abnormalities in 12 individuals and epilepsy in 7 individuals.

In addition, this gene has been associated with autosomal recessive intellectual developmental disorder in Gene2phenotype with 'limited' rating and ID has been included as part of the SPG64 phenotype in OMIM.
Intellectual disability v5.120 ENTPD1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Konstantinos Varvagiannis, PMID35471564 reported 27 cases from 17 families with a complex childhood-onset neurodevelopmental disorder characterised by intellectual disability/ developmental delay and spastic paraplegia in all individuals, white matter abnormalities in 12 individuals and epilepsy in 7 individuals. Hence, this gene can be promoted to Green in the next major update.; to: As reviewed by Konstantinos Varvagiannis, PMID35471564 reported 27 cases from 17 families with a complex childhood-onset neurodevelopmental disorder characterised by intellectual disability/ developmental delay and spastic paraplegia in all individuals, white matter abnormalities in 12 individuals and epilepsy in 7 individuals.

In addition, this gene has been associated with autosomal recessive intellectual developmental disorder in Gene2phenotype with 'limited' rating and ID has been includes as part of the SPG64 phenotype in OMIM.
Intellectual disability v5.120 ENTPD1 Achchuthan Shanmugasundram Publications for gene: ENTPD1 were set to 21937992; 24482476; 29691679; 30652007; 35471564
Intellectual disability v5.120 ENTPD1 Achchuthan Shanmugasundram Publications for gene: ENTPD1 were set to 21937992; 24482476; 29691679; 30652007; 35471564
Intellectual disability v5.120 ENTPD1 Achchuthan Shanmugasundram Publications for gene: ENTPD1 were set to 21937992; 24482476; 29691679; 30652007; 35471564
Intellectual disability v5.120 ENTPD1 Achchuthan Shanmugasundram Publications for gene: ENTPD1 were set to 21937992; 24482476; 29691679; 30652007; 35471564
Intellectual disability v5.120 ENTPD1 Achchuthan Shanmugasundram Publications for gene: ENTPD1 were set to 21937992; 24482476; 29691679; 30652007
Intellectual disability v5.119 ENTPD1 Achchuthan Shanmugasundram Classified gene: ENTPD1 as Amber List (moderate evidence)
Intellectual disability v5.119 ENTPD1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Konstantinos Varvagiannis, PMID35471564 reported 27 cases from 17 families with a complex childhood-onset neurodevelopmental disorder characterised by intellectual disability/ developmental delay and spastic paraplegia in all individuals, white matter abnormalities in 12 individuals and epilepsy in 7 individuals. Hence, this gene can be promoted to Green in the next major update.
Intellectual disability v5.119 ENTPD1 Achchuthan Shanmugasundram Gene: entpd1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.118 ENTPD1 Achchuthan Shanmugasundram reviewed gene: ENTPD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35471564; Phenotypes: Spastic paraplegia 64, autosomal recessive, OMIM:615683; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.118 COASY Sarah Leigh Phenotypes for gene: COASY were changed from Neurodegeneration with brain iron accumulation 6, 615643 to Neurodegeneration with brain iron accumulation 6, OMIM:615643; neurodegeneration with brain iron accumulation 6, MONDO:0014290
Intellectual disability v5.117 SUFU Arina Puzriakova Tag Q4_22_expert_review tag was added to gene: SUFU.
Intellectual disability v5.117 RNF13 Arina Puzriakova Phenotypes for gene: RNF13 were changed from Cortical visual impairment; Epileptic encephalopathy, early infantile, 73, 618379; Failure to thrive; Seizures; Congenital microcephaly; Abnormal muscle tone; Feeding difficulties; Intellectual disability; Global developmental delay; Sensorineural hearing impairment to Developmental and epileptic encephalopathy 73, OMIM:618379
Intellectual disability v5.116 CHMP3 Arina Puzriakova Classified gene: CHMP3 as Red List (low evidence)
Intellectual disability v5.116 CHMP3 Arina Puzriakova Added comment: Comment on list classification: Rating Red for now as only a single case has been reported to date.
Intellectual disability v5.116 CHMP3 Arina Puzriakova Gene: chmp3 has been classified as Red List (Low Evidence).
Intellectual disability v5.115 CHMP3 Arina Puzriakova gene: CHMP3 was added
gene: CHMP3 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: CHMP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHMP3 were set to 35710109
Phenotypes for gene: CHMP3 were set to Complex spastic quadriplegia associated with developmental delay and seizures
Added comment: Cohen-Barak et al., 2022 (PMID: 35710109) reported on a consanguineous family, in which five individuals presented with intellectual and progressive motor disabilities, seizures and spastic quadriplegia, associated with a homozygous variant in CHMP3. Patient derived fibroblasts expressed ultrastructural and molecular features of impaired autophagy, partially rescued by ectopic expression of WT-CHMP3.
Sources: Literature
Intellectual disability v5.114 RAC3 Arina Puzriakova Publications for gene: RAC3 were set to 29276006; 30293988
Intellectual disability v5.113 RAC3 Arina Puzriakova Classified gene: RAC3 as Green List (high evidence)
Intellectual disability v5.113 RAC3 Arina Puzriakova Gene: rac3 has been classified as Green List (High Evidence).
Intellectual disability v5.112 RAC3 Arina Puzriakova All sources for gene: RAC3 were removed
Intellectual disability v5.112 RAC3 Arina Puzriakova All sources for gene: RAC3 were removed
Intellectual disability v5.111 GRIN2B Arina Puzriakova Publications for gene: GRIN2B were set to
Intellectual disability v5.110 GRIN2B Arina Puzriakova Phenotypes for gene: GRIN2B were changed from Mental Retardation, Dominant; Mental retardation, autosomal dominant 6, 613970; AUTISM to Intellectual developmental disorder, autosomal dominant 6, with or without seizures, OMIM:613970; Developmental and epileptic encephalopathy 27, OMIM:616139
Intellectual disability v5.109 LHX2 Sarah Leigh Classified gene: LHX2 as Amber List (moderate evidence)
Intellectual disability v5.109 LHX2 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 v5.109 LHX2 Sarah Leigh Gene: lhx2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.108 LHX2 Sarah Leigh gene: LHX2 was added
gene: LHX2 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Q2_23_promote_green tags were added to gene: LHX2.
Mode of inheritance for gene: LHX2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: LHX2 were set to 37057675
Phenotypes for gene: LHX2 were set to neurodevelopmental disorder
Review for gene: LHX2 was set to GREEN
Added comment: Not associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 37057675 reports 17 predominanly de novo LHX2 variants in a panel of patients with a variable neurodevelopmental disorder. Haploinsufficiency and functional studies are supportive of a loss-of-function pathogenic action of the reported LHX2 variants.
Sources: Literature
Intellectual disability v5.107 ITPR1 Tracy Lester edited their review of gene: ITPR1: Added comment: PMID:29925855 - All 7 EOA patients with ITPR1 de novo variants (3 from cohort #1; 4 from cohort #2) presented with infantile onset cerebellar ataxia starting before the age of 2 years, including delayed motor milestones (Table 2). Cognitive deficits of variable degree were observed in 3 out of 4 patients where this information was available, reaching from only mild dyscalculia (P2) to severe intellectual disability with a speech vocabulary of only a few words (P7 at age 12 years). In contrast, patient P1 showed normal intelligence with an IQ of 97.

PMID:27108797 - Here, we report that both recessive and dominant ITPR1 mutations cause Gillespie syndrome. ITPR1 is a predominant isoform in the brain among the three types of ITPRs and is strongly expressed in cerebellar Purkinje cells.31 Mice with complete homozygosity for Itpr1 ablation suffer from severe epilepsy and ataxia and die either in utero or before weaning.32 Consistently, ITPR1 mutations have been reported to cause cerebellar diseases including late-onset spinocerebellar ataxia type 15 (SCA15 [MIM: 606658]),33 congenital nonprogressive spinocerebellar ataxia and mild cognitive impairment (SCA29 [MIM: 117360]),34 infantile-onset cerebellar ataxia with mild cognitive deficit,35 and childhood-onset ataxic cerebellar palsy with moderate intellectual disability36 (see ITPR1 schematic diagram in Figure 3A).
Affected individuals had similar iris anomalies and neonatal ataxia with progressive cerebellar atrophy (Figure 2). Moderate to severe intellectual disabilities were noted in the three individuals with recessive mutations (F1:II1, F2:II1, and F3:II1; Table 1). In contrast, the affected individual F4:II1 aged 18 years and harboring the de novo c.7687_7689del mutation was reported to have normal intelligence (Table 1).

As de novo variants are associated with ID/DD the inheritance should be updated to be BOTH AD and AR.; Set current diagnostic: yes
Intellectual disability v5.107 ITPR1 Tracy Lester reviewed gene: ITPR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 29925855, 27108797; Phenotypes: developmental delay, intellectual disability, hypotonia, ataxia, cerebellar malformatons; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v5.107 SLC32A1 Achchuthan Shanmugasundram Classified gene: SLC32A1 as Amber List (moderate evidence)
Intellectual disability v5.107 SLC32A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (four unrelated cases and supporting functional studies) for this gene to be promoted to GREEN at the next GMS update.
Intellectual disability v5.107 SLC32A1 Achchuthan Shanmugasundram Gene: slc32a1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.107 SLC32A1 Achchuthan Shanmugasundram Classified gene: SLC32A1 as Amber List (moderate evidence)
Intellectual disability v5.107 SLC32A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (four unrelated cases and supporting functional studies) for this gene to be promoted to GREEN at the next GMS update.
Intellectual disability v5.107 SLC32A1 Achchuthan Shanmugasundram Gene: slc32a1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.107 SLC32A1 Achchuthan Shanmugasundram Classified gene: SLC32A1 as Amber List (moderate evidence)
Intellectual disability v5.107 SLC32A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (four unrelated cases and supporting functional studies) for this gene to be promoted to GREEN at the next GMS update.
Intellectual disability v5.107 SLC32A1 Achchuthan Shanmugasundram Gene: slc32a1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.106 SLC32A1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.106 SLC32A1 Achchuthan Shanmugasundram Classified gene: SLC32A1 as Amber List (moderate evidence)
Intellectual disability v5.106 SLC32A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (four unrelated cases and supporting functional studies) for this gene to be promoted to GREEN at the next GMS update.
Intellectual disability v5.106 SLC32A1 Achchuthan Shanmugasundram Gene: slc32a1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.106 SLC32A1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.106 SLC32A1 Achchuthan Shanmugasundram Classified gene: SLC32A1 as Amber List (moderate evidence)
Intellectual disability v5.106 SLC32A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (four unrelated cases and supporting functional studies) for this gene to be promoted to GREEN at the next GMS update.
Intellectual disability v5.106 SLC32A1 Achchuthan Shanmugasundram Gene: slc32a1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.106 SLC32A1 Achchuthan Shanmugasundram Classified gene: SLC32A1 as Amber List (moderate evidence)
Intellectual disability v5.106 SLC32A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (four unrelated cases and supporting functional studies) for this gene to be promoted to GREEN at the next GMS update.
Intellectual disability v5.106 SLC32A1 Achchuthan Shanmugasundram Gene: slc32a1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.105 SLC32A1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: SLC32A1.
Intellectual disability v5.105 SLC32A1 Achchuthan Shanmugasundram changed review comment from: PMID:36073542 reported four unrelated patients with four different de novo missense variants in SLC32A1 gene reported with global developmental delay, moderate-to-severe intellectual disability, infantile-onset epilepsy within the first 18 months of life, and a choreiform, dystonic, or dyskinetic movement disorder.

In silico modeling and functional analyses showed that these variants can impair GABAergic neurotransmission through at least two mechanisms, by affecting synaptic vesicle filling and by altering synaptic short-term plasticity.
Sources: Literature; to: PMID:36073542 reported four unrelated patients with four different de novo missense variants in SLC32A1 gene reported with global developmental delay, moderate-to-severe intellectual disability, infantile-onset epilepsy within the first 18 months of life, and a choreiform, dystonic, or dyskinetic movement disorder.

In silico modeling and functional analyses showed that these variants can impair GABAergic neurotransmission through at least two mechanisms, by affecting synaptic vesicle filling and by altering synaptic short-term plasticity.

Although this gene has not yet been associated with phenotypes in OMIM, it has been added to Gene2Phenotype with 'moderate' rating in the DD panel.

Sources: Literature
Intellectual disability v5.105 SLC32A1 Achchuthan Shanmugasundram gene: SLC32A1 was added
gene: SLC32A1 was added to Intellectual disability - microarray and sequencing. Sources: Literature
Mode of inheritance for gene: SLC32A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC32A1 were set to 36073542
Phenotypes for gene: SLC32A1 were set to developmental and epileptic encephalopathy, MONDO:0100062
Review for gene: SLC32A1 was set to GREEN
Added comment: PMID:36073542 reported four unrelated patients with four different de novo missense variants in SLC32A1 gene reported with global developmental delay, moderate-to-severe intellectual disability, infantile-onset epilepsy within the first 18 months of life, and a choreiform, dystonic, or dyskinetic movement disorder.

In silico modeling and functional analyses showed that these variants can impair GABAergic neurotransmission through at least two mechanisms, by affecting synaptic vesicle filling and by altering synaptic short-term plasticity.
Sources: Literature
Intellectual disability v5.104 CSTF2 Achchuthan Shanmugasundram Phenotypes for gene: CSTF2 were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.104 CSTF2 Achchuthan Shanmugasundram Phenotypes for gene: CSTF2 were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.103 CSTF2 Achchuthan Shanmugasundram Phenotypes for gene: CSTF2 were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.104 CSTF2 Achchuthan Shanmugasundram Phenotypes for gene: CSTF2 were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.104 CSTF2 Achchuthan Shanmugasundram Phenotypes for gene: CSTF2 were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.103 CSTF2 Achchuthan Shanmugasundram Phenotypes for gene: CSTF2 were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.103 CSTF2 Achchuthan Shanmugasundram Phenotypes for gene: CSTF2 were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.103 CSTF2 Achchuthan Shanmugasundram Phenotypes for gene: CSTF2 were changed from Intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071
Intellectual disability v5.103 CSTF2 Achchuthan Shanmugasundram Phenotypes for gene: CSTF2 were changed from to Intellectual disability, MONDO:0001071
Intellectual disability v5.102 CSTF2 Achchuthan Shanmugasundram Publications for gene: CSTF2 were set to 26350204; 32816001
Intellectual disability v5.102 CSTF2 Achchuthan Shanmugasundram Publications for gene: CSTF2 were set to 26350204; 32816001
Intellectual disability v5.102 CSTF2 Achchuthan Shanmugasundram Publications for gene: CSTF2 were set to 26350204; 32816001
Intellectual disability v5.102 CSTF2 Achchuthan Shanmugasundram Publications for gene: CSTF2 were set to 26350204; 32816001
Intellectual disability v5.102 CSTF2 Achchuthan Shanmugasundram Publications for gene: CSTF2 were set to 26350204; 32816001
Intellectual disability v5.102 CSTF2 Achchuthan Shanmugasundram Publications for gene: CSTF2 were set to 26350204; 32816001
Intellectual disability v5.102 CSTF2 Achchuthan Shanmugasundram Publications for gene: CSTF2 were set to 26350204
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Mode of inheritance for gene: CSTF2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.101 CSTF2 Achchuthan Shanmugasundram Mode of inheritance for gene: CSTF2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.101 CSTF2 Achchuthan Shanmugasundram Mode of inheritance for gene: CSTF2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.101 CSTF2 Achchuthan Shanmugasundram Mode of inheritance for gene: CSTF2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Mode of inheritance for gene: CSTF2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Classified gene: CSTF2 as Amber List (moderate evidence)
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark (Australian Genomics), there is one family with intellectual disability, supported by functional studies. This gene should therefore be promoted to AMBER in this panel.
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Gene: cstf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Mode of inheritance for gene: CSTF2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.101 CSTF2 Achchuthan Shanmugasundram Mode of inheritance for gene: CSTF2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Classified gene: CSTF2 as Amber List (moderate evidence)
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark (Australian Genomics), there is one family with intellectual disability, supported by functional studies. This gene should therefore be promoted to AMBER in this panel.
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Gene: cstf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Classified gene: CSTF2 as Amber List (moderate evidence)
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark (Australian Genomics), there is one family with intellectual disability, supported by functional studies. This gene should therefore be promoted to AMBER in this panel.
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Gene: cstf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.100 CSTF2 Achchuthan Shanmugasundram Mode of inheritance for gene: CSTF2 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.99 CSTF2 Achchuthan Shanmugasundram Classified gene: CSTF2 as Amber List (moderate evidence)
Intellectual disability v5.99 CSTF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark (Australian Genomics), there is one family with intellectual disability, supported by functional studies. This gene should therefore be promoted to AMBER in this panel.
Intellectual disability v5.99 CSTF2 Achchuthan Shanmugasundram Gene: cstf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.99 CSTF2 Achchuthan Shanmugasundram Classified gene: CSTF2 as Amber List (moderate evidence)
Intellectual disability v5.99 CSTF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark (Australian Genomics), there is one family with intellectual disability, supported by functional studies. This gene should therefore be promoted to AMBER in this panel.
Intellectual disability v5.99 CSTF2 Achchuthan Shanmugasundram Gene: cstf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.99 CSTF2 Achchuthan Shanmugasundram Classified gene: CSTF2 as Amber List (moderate evidence)
Intellectual disability v5.99 CSTF2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark (Australian Genomics), there is one family with intellectual disability, supported by functional studies. This gene should therefore be promoted to AMBER in this panel.
Intellectual disability v5.99 CSTF2 Achchuthan Shanmugasundram Gene: cstf2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.98 CSTF2 Achchuthan Shanmugasundram reviewed gene: CSTF2: Rating: AMBER; Mode of pathogenicity: None; Publications: 32816001; Phenotypes: Intellectual disability, MONDO:0001071; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v5.98 HIST1H4E Ronnie Wright reviewed gene: HIST1H4E: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability v5.98 SRRM2 Alistair Pagnamenta reviewed gene: SRRM2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35567594, 33057194; Phenotypes: Intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.98 PRKAR1B Achchuthan Shanmugasundram Classified gene: PRKAR1B as Amber List (moderate evidence)
Intellectual disability v5.98 PRKAR1B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN rating at the next GMS update.
Intellectual disability v5.98 PRKAR1B Achchuthan Shanmugasundram Gene: prkar1b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.98 PRKAR1B Achchuthan Shanmugasundram Classified gene: PRKAR1B as Amber List (moderate evidence)
Intellectual disability v5.98 PRKAR1B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN rating at the next GMS update.
Intellectual disability v5.98 PRKAR1B Achchuthan Shanmugasundram Gene: prkar1b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.98 PRKAR1B Achchuthan Shanmugasundram Classified gene: PRKAR1B as Amber List (moderate evidence)
Intellectual disability v5.98 PRKAR1B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN rating at the next GMS update.
Intellectual disability v5.98 PRKAR1B Achchuthan Shanmugasundram Gene: prkar1b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.97 PRKAR1B Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.97 PRKAR1B Achchuthan Shanmugasundram Classified gene: PRKAR1B as Amber List (moderate evidence)
Intellectual disability v5.97 PRKAR1B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN rating at the next GMS update.
Intellectual disability v5.97 PRKAR1B Achchuthan Shanmugasundram Gene: prkar1b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.97 PRKAR1B Achchuthan Shanmugasundram Classified gene: PRKAR1B as Amber List (moderate evidence)
Intellectual disability v5.97 PRKAR1B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN rating at the next GMS update.
Intellectual disability v5.97 PRKAR1B Achchuthan Shanmugasundram Gene: prkar1b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.96 PRKAR1B Achchuthan Shanmugasundram Publications for gene: PRKAR1B were set to 25414040; 33833410
Intellectual disability v5.96 PRKAR1B Achchuthan Shanmugasundram Phenotypes for gene: PRKAR1B were changed from Marbach-Schaaf neurodevelopmental syndrome, OMIM:619680 to Global developmental delay; Intellectual disability; Autism; Attention deficit hyperactivity disorder; Aggressive behavior; Abnormality of movement; Upslanted palpebral fissure
Intellectual disability v5.96 PRKAR1B Achchuthan Shanmugasundram Publications for gene: PRKAR1B were set to 25414040; 33833410
Intellectual disability v5.96 PRKAR1B Achchuthan Shanmugasundram Publications for gene: PRKAR1B were set to 25414040; 33833410
Intellectual disability v5.97 PRKAR1B Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: PRKAR1B.
Intellectual disability v5.97 PRKAR1B Achchuthan Shanmugasundram Phenotypes for gene: PRKAR1B were changed from Marbach-Schaaf neurodevelopmental syndrome, OMIM:619680 to Marbach-Schaaf neurodevelopmental syndrome, OMIM:619680
Intellectual disability v5.96 PRKAR1B Achchuthan Shanmugasundram Phenotypes for gene: PRKAR1B were changed from Marbach-Schaaf neurodevelopmental syndrome, OMIM:619680 to Marbach-Schaaf neurodevelopmental syndrome, OMIM:619680
Intellectual disability v5.96 PRKAR1B Achchuthan Shanmugasundram 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 v5.95 PRKAR1B Achchuthan Shanmugasundram Publications for gene: PRKAR1B were set to 25414040; 33833410
Intellectual disability v5.95 PRKAR1B Achchuthan Shanmugasundram Publications for gene: PRKAR1B were set to 25414040; 33833410
Intellectual disability v5.96 PRKAR1B Achchuthan Shanmugasundram Publications for gene: PRKAR1B were set to 25414040; 33833410
Intellectual disability v5.95 PRKAR1B Achchuthan Shanmugasundram Publications for gene: PRKAR1B were set to 25414040; 33833410
Intellectual disability v5.95 PRKAR1B Achchuthan Shanmugasundram Publications for gene: PRKAR1B were set to 25414040; 33833410
Intellectual disability v5.95 PRKAR1B Achchuthan Shanmugasundram Publications for gene: PRKAR1B were set to https://doi.org/10.1101/2020.09.10.20190314; 25414040
Intellectual disability v5.94 PRKAR1B Achchuthan Shanmugasundram Mode of inheritance for gene: PRKAR1B was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.94 PRKAR1B Achchuthan Shanmugasundram Mode of inheritance for gene: PRKAR1B was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.94 PRKAR1B Achchuthan Shanmugasundram Mode of inheritance for gene: PRKAR1B was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.94 PRKAR1B Achchuthan Shanmugasundram Mode of inheritance for gene: PRKAR1B was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.94 PRKAR1B Achchuthan Shanmugasundram Mode of inheritance for gene: PRKAR1B was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.93 PRKAR1B Achchuthan Shanmugasundram reviewed gene: PRKAR1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 33833410; Phenotypes: Marbach-Schaaf neurodevelopmental syndrome, OMIM:619680; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Konstantinos Varvagiannis, all individuals reported in PMID:35830857 (16 individuals from 12 families) shared a core phenotype of global developmental delay/intellectual disability (GDD/ID) and epilepsy. 15 were affected by profound or severe GDD/ID (15/16). They had not acquired speech (15/16) and showed impaired motor development (15/16).

This gene has already been associated with relevant phenotypes in both OMIM (MIM #620024) and Gene2Phenotype (with 'strong' rating in the DD panel).; to: As reviewed by Konstantinos Varvagiannis, all individuals (16 individuals from 12 families) reported in PMID:35830857 shared a core phenotype of global developmental delay/intellectual disability (GDD/ID) and epilepsy. 15 were affected by profound or severe GDD/ID (15/16). They had not acquired speech (15/16) and showed impaired motor development (15/16).

This gene has already been associated with relevant phenotypes in both OMIM (MIM #620024) and Gene2Phenotype (with 'strong' rating in the DD panel).
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Konstantinos Varvagiannis, all individuals reported in PMID:35830857 shared a core phenotype of global developmental delay/intellectual disability (GDD/ID) and epilepsy. 15 were affected by profound or severe GDD/ID (15/16). They had not acquired speech (15/16) and showed impaired motor development (15/16).

This gene has already been associated with relevant phenotypes in both OMIM (MIM #620024) and Gene2Phenotype (with 'strong' rating in the DD panel).; to: As reviewed by Konstantinos Varvagiannis, all individuals reported in PMID:35830857 (16 individuals from 12 families) shared a core phenotype of global developmental delay/intellectual disability (GDD/ID) and epilepsy. 15 were affected by profound or severe GDD/ID (15/16). They had not acquired speech (15/16) and showed impaired motor development (15/16).

This gene has already been associated with relevant phenotypes in both OMIM (MIM #620024) and Gene2Phenotype (with 'strong' rating in the DD panel).
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Classified gene: PPFIBP1 as Amber List (moderate evidence)
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN rating at the next GMS update.
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Gene: ppfibp1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Classified gene: PPFIBP1 as Amber List (moderate evidence)
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN rating at the next GMS update.
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Gene: ppfibp1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Classified gene: PPFIBP1 as Amber List (moderate evidence)
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN rating at the next GMS update.
Intellectual disability v5.93 PPFIBP1 Achchuthan Shanmugasundram Gene: ppfibp1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.92 PPFIBP1 Achchuthan Shanmugasundram Classified gene: PPFIBP1 as Amber List (moderate evidence)
Intellectual disability v5.92 PPFIBP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN rating at the next GMS update.
Intellectual disability v5.92 PPFIBP1 Achchuthan Shanmugasundram Gene: ppfibp1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.92 PPFIBP1 Achchuthan Shanmugasundram Classified gene: PPFIBP1 as Amber List (moderate evidence)
Intellectual disability v5.92 PPFIBP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN rating at the next GMS update.
Intellectual disability v5.92 PPFIBP1 Achchuthan Shanmugasundram Gene: ppfibp1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.91 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024 to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.92 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024 to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.91 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024 to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.91 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024 to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.92 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024 to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.91 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024 to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.91 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024 to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.92 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024 to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.91 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024 to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.91 PPFIBP1 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: PPFIBP1.
Intellectual disability v5.91 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024 to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.91 PPFIBP1 Achchuthan Shanmugasundram Phenotypes for gene: PPFIBP1 were changed from Global developmental delay; Intellectual disability; Microcephaly; Seizures; Abnormality of brain morphology; Abnormality of the cerebral white matter; Cerebral calcification; Abnormal cortical gyration; Hypertonia; Spastic tetraplegia; Generalized hypotonia; Small for gestational age; Growth delay; Failure to thrive; Feeding difficulties; abnormal heart morphology; Hearing abnormality; Cryptorchidism; Abnormality of vision to Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.90 PPFIBP1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Konstantinos Varvagiannis, all individuals reported in PMID:35830857 shared a core phenotype of global developmental delay/intellectual disability (GDD/ID) and epilepsy. 15 were affected by profound or severe GDD/ID (15/16). They had not acquired speech (15/16) and showed impaired motor development (15/16).; to: As reviewed by Konstantinos Varvagiannis, all individuals reported in PMID:35830857 shared a core phenotype of global developmental delay/intellectual disability (GDD/ID) and epilepsy. 15 were affected by profound or severe GDD/ID (15/16). They had not acquired speech (15/16) and showed impaired motor development (15/16).

This gene has already been associated with relevant phenotypes in both OMIM (MIM #620024) and Gene2Phenotype (with 'strong' rating in the DD panel).
Intellectual disability v5.90 PPFIBP1 Achchuthan Shanmugasundram edited their review of gene: PPFIBP1: Changed phenotypes to: Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities, OMIM:620024
Intellectual disability v5.90 PPFIBP1 Achchuthan Shanmugasundram reviewed gene: PPFIBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35830857; Phenotypes: intellectual disability, MONDO:0001071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v5.90 KDM2B Achchuthan Shanmugasundram Classified gene: KDM2B as Amber List (moderate evidence)
Intellectual disability v5.90 KDM2B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN rating at the next GMS update.
Intellectual disability v5.90 KDM2B Achchuthan Shanmugasundram Gene: kdm2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.89 KDM2B Achchuthan Shanmugasundram Classified gene: KDM2B as Amber List (moderate evidence)
Intellectual disability v5.89 KDM2B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN rating at the next GMS update.
Intellectual disability v5.89 KDM2B Achchuthan Shanmugasundram Gene: kdm2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.89 KDM2B Achchuthan Shanmugasundram Classified gene: KDM2B as Amber List (moderate evidence)
Intellectual disability v5.89 KDM2B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN rating at the next GMS update.
Intellectual disability v5.89 KDM2B Achchuthan Shanmugasundram Gene: kdm2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.89 KDM2B Achchuthan Shanmugasundram Classified gene: KDM2B as Amber List (moderate evidence)
Intellectual disability v5.89 KDM2B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN rating at the next GMS update.
Intellectual disability v5.89 KDM2B Achchuthan Shanmugasundram Gene: kdm2b has been classified as Amber List (Moderate Evidence).
Intellectual disability v5.88 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.88 KDM2B Achchuthan Shanmugasundram Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v5.88