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Intellectual disability v9.344 UNC13A Arina Puzriakova changed review comment from: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Intellectual disability v9.316 ISCA-37433-Loss Arina Puzriakova commented on Region: ISCA-37433-Loss: The rating of this gene has been updated to Grey (removed) following NHS Genomic Medicine Service approval.
Intellectual disability v9.315 ISCA-37433-Gain Arina Puzriakova commented on Region: ISCA-37433-Gain: The rating of this gene has been updated to Grey (removed) following NHS Genomic Medicine Service approval.
Intellectual disability v9.314 ISCA-37404-Loss Arina Puzriakova commented on Region: ISCA-37404-Loss: The rating of this gene has been updated to Grey (removed) following NHS Genomic Medicine Service approval.
Intellectual disability v9.313 ISCA-37404-Gain Arina Puzriakova commented on Region: ISCA-37404-Gain: The rating of this gene has been updated to Grey (removed) following NHS Genomic Medicine Service approval.
Intellectual disability v9.312 ISCA-37448-Loss Arina Puzriakova commented on Region: ISCA-37448-Loss: The rating of this region has been updated to Green following NHS Genomic Medicine Service approval.
Intellectual disability v9.311 ISCA-46300-Loss Arina Puzriakova commented on Region: ISCA-46300-Loss: The rating of this region has been updated to Green following NHS Genomic Medicine Service approval.
Intellectual disability v9.310 ISCA-46296-Loss Arina Puzriakova commented on Region: ISCA-46296-Loss: The rating of this region has been updated to Green following NHS Genomic Medicine Service approval.
Intellectual disability v9.309 ISCA-37498-Loss Arina Puzriakova commented on Region: ISCA-37498-Loss: The rating of this region has been updated to Green following NHS Genomic Medicine Service approval.
Intellectual disability v9.303 WBP4 Arina Puzriakova Tag Q4_24_NHS_review was removed from gene: WBP4.
Tag Q4_24_promote_green was removed from gene: WBP4.
Intellectual disability v9.303 UPF1 Arina Puzriakova Tag Q3_25_promote_green was removed from gene: UPF1.
Tag Q3_25_NHS_review was removed from gene: UPF1.
Intellectual disability v9.303 UNC13A Arina Puzriakova Tag Q3_25_promote_green was removed from gene: UNC13A.
Tag Q3_25_NHS_review was removed from gene: UNC13A.
Intellectual disability v9.302 UGGT1 Arina Puzriakova Tag Q3_25_promote_green was removed from gene: UGGT1.
Tag Q3_25_NHS_review was removed from gene: UGGT1.
Intellectual disability v9.301 TAOK2 Arina Puzriakova Tag Q1_25_ NHS_review was removed from gene: TAOK2.
Tag Q1_25_ promote_green was removed from gene: TAOK2.
Intellectual disability v9.301 SF1 Arina Puzriakova Tag Q3_25_promote_green was removed from gene: SF1.
Tag Q3_25_NHS_review was removed from gene: SF1.
Intellectual disability v9.301 SEL1L Arina Puzriakova Tag Q2_25_ promote_green was removed from gene: SEL1L.
Tag Q2_25_ NHS_review was removed from gene: SEL1L.
Intellectual disability v9.301 RREB1 Arina Puzriakova Tag Q3_25_promote_green was removed from gene: RREB1.
Tag Q3_25_NHS_review was removed from gene: RREB1.
Intellectual disability v9.300 MED16 Arina Puzriakova Tag Q3_25_promote_green was removed from gene: MED16.
Tag Q3_25_NHS_review was removed from gene: MED16.
Intellectual disability v9.300 KDM5B Arina Puzriakova Tag Q2_25_ MOI was removed from gene: KDM5B.
Tag Q2_25_expert_review was removed from gene: KDM5B.
Tag Q2_25_ NHS_review was removed from gene: KDM5B.
Intellectual disability v9.300 FBXO22 Arina Puzriakova Tag Q2_25_ promote_green was removed from gene: FBXO22.
Tag Q2_25_ NHS_review was removed from gene: FBXO22.
Intellectual disability v9.299 EPB41L3 Arina Puzriakova Tag Q2_25_ promote_green was removed from gene: EPB41L3.
Tag Q2_25_ NHS_review was removed from gene: EPB41L3.
Intellectual disability v9.299 EMX2 Arina Puzriakova Tag Q3_25_expert_review was removed from gene: EMX2.
Tag Q3_25_NHS_review was removed from gene: EMX2.
Tag Q3_25_demote_amber was removed from gene: EMX2.
Intellectual disability v9.299 EEF1D Arina Puzriakova Tag Q2_25_ promote_green was removed from gene: EEF1D.
Tag Q2_25_ NHS_review was removed from gene: EEF1D.
Intellectual disability v9.299 DDX39B Arina Puzriakova Tag Q2_25_ promote_green was removed from gene: DDX39B.
Tag Q2_25_ NHS_review was removed from gene: DDX39B.
Intellectual disability v9.299 CELF4 Arina Puzriakova changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber. Additional comments from reviewing GLHs: GnomAD data would make this difficult to classify variants. All ClinVar variants are VUS.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber. Additional comments from reviewing GLHs: gnomAD data would make this difficult to classify variants. All ClinVar variants are VUS.
Intellectual disability v9.299 TUBGCP2 Arina Puzriakova commented on gene: TUBGCP2: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v9.299 TNR Arina Puzriakova commented on gene: TNR: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v9.299 SPAST Arina Puzriakova edited their review of gene: SPAST: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v9.299 SOD1 Arina Puzriakova commented on gene: SOD1: 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 v9.299 SLC5A7 Arina Puzriakova commented on gene: SLC5A7: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v9.299 RSPRY1 Arina Puzriakova commented on gene: RSPRY1: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v9.299 RNU5B-1 Arina Puzriakova commented on gene: RNU5B-1: 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 v9.299 PTBP1 Arina Puzriakova commented on gene: PTBP1: 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.
Intellectual disability v9.299 PPP2R2B Arina Puzriakova edited their review of gene: PPP2R2B: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v9.299 MAP4K4 Arina Puzriakova edited their review of gene: MAP4K4: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v9.299 KIRREL3 Arina Puzriakova edited their review of gene: KIRREL3: Added comment: The rating of this gene has been updated to red following NHS Genomic Medicine Service approval.; Changed rating: RED
Intellectual disability v9.299 KIAA0556 Arina Puzriakova commented on gene: KIAA0556: 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 v9.299 KDM5B Arina Puzriakova commented on gene: KDM5B: The mode of inheritance of this gene has been updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Intellectual disability v9.299 INPP4A Arina Puzriakova edited their review of gene: INPP4A: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v9.299 GTF3C3 Arina Puzriakova commented on gene: GTF3C3: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v9.299 EXOSC8 Arina Puzriakova commented on gene: EXOSC8: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v9.299 EPB41L3 Arina Puzriakova commented on gene: EPB41L3: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v9.299 ELFN1 Arina Puzriakova commented on gene: ELFN1: 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 v9.299 EEF1D Arina Puzriakova commented on gene: EEF1D: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v9.299 CCT6A Arina Puzriakova commented on gene: CCT6A: 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 v9.299 C12orf66 Arina Puzriakova commented on gene: C12orf66: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v9.299 ATM Arina Puzriakova edited their review of gene: ATM: Added comment: The rating of this gene has been updated to red following NHS Genomic Medicine Service approval.; Changed rating: RED
Intellectual disability v9.299 ASCC3 Arina Puzriakova edited their review of gene: ASCC3: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v9.298 WDR47 Arina Puzriakova Source NHS GMS was added to WDR47.
Source Expert Review Green was added to WDR47.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 WBP4 Arina Puzriakova Source NHS GMS was added to WBP4.
Source Expert Review Green was added to WBP4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 WARS Arina Puzriakova Source NHS GMS was added to WARS.
Source Expert Review Green was added to WARS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 VPS33A Arina Puzriakova Source NHS GMS was added to VPS33A.
Source Expert Review Green was added to VPS33A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 UPF1 Arina Puzriakova Source NHS GMS was added to UPF1.
Source Expert Review Green was added to UPF1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 UNC13A Arina Puzriakova Source NHS GMS was added to UNC13A.
Source Expert Review Green was added to UNC13A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 UGGT1 Arina Puzriakova Source NHS GMS was added to UGGT1.
Source Expert Review Green was added to UGGT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 UBR5 Arina Puzriakova Source NHS GMS was added to UBR5.
Source Expert Review Green was added to UBR5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 TUBGCP2 Arina Puzriakova Source NHS GMS was added to TUBGCP2.
Source Expert Review Green was added to TUBGCP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 TSPAN7 Arina Puzriakova Source NHS GMS was added to TSPAN7.
Source Expert Review Amber was added to TSPAN7.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Intellectual disability v9.298 TNR Arina Puzriakova Source NHS GMS was added to TNR.
Source Expert Review Green was added to TNR.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 TFG Arina Puzriakova Source NHS GMS was added to TFG.
Source Expert Review Green was added to TFG.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 TARS2 Arina Puzriakova Source NHS GMS was added to TARS2.
Source Expert Review Green was added to TARS2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 TAOK2 Arina Puzriakova Source NHS GMS was added to TAOK2.
Source Expert Review Green was added to TAOK2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 SUPV3L1 Arina Puzriakova Source NHS GMS was added to SUPV3L1.
Source Expert Review Green was added to SUPV3L1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 SPOUT1 Arina Puzriakova Source NHS GMS was added to SPOUT1.
Source Expert Review Green was added to SPOUT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 SPAST Arina Puzriakova Source NHS GMS was added to SPAST.
Source Expert Review Green was added to SPAST.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 SOD1 Arina Puzriakova Source NHS GMS was added to SOD1.
Source Expert Review Green was added to SOD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 SMARCA1 Arina Puzriakova Source NHS GMS was added to SMARCA1.
Source Expert Review Green was added to SMARCA1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 SLC5A7 Arina Puzriakova Source NHS GMS was added to SLC5A7.
Source Expert Review Green was added to SLC5A7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 SF1 Arina Puzriakova Source NHS GMS was added to SF1.
Source Expert Review Green was added to SF1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 SEL1L Arina Puzriakova Source NHS GMS was added to SEL1L.
Source Expert Review Green was added to SEL1L.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 RSPRY1 Arina Puzriakova Source NHS GMS was added to RSPRY1.
Source Expert Review Green was added to RSPRY1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 RREB1 Arina Puzriakova Source NHS GMS was added to RREB1.
Source Expert Review Green was added to RREB1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 RNU5B-1 Arina Puzriakova Source NHS GMS was added to RNU5B-1.
Source Expert Review Green was added to RNU5B-1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 RNU2-2P Arina Puzriakova Source NHS GMS was added to RNU2-2P.
Source Expert Review Green was added to RNU2-2P.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 PTRH2 Arina Puzriakova Source NHS GMS was added to PTRH2.
Source Expert Review Green was added to PTRH2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 PPP2R5C Arina Puzriakova Source NHS GMS was added to PPP2R5C.
Source Expert Review Green was added to PPP2R5C.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 PPP2R2B Arina Puzriakova Source NHS GMS was added to PPP2R2B.
Source Expert Review Green was added to PPP2R2B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 PPOX Arina Puzriakova Source NHS GMS was added to PPOX.
Source Expert Review Green was added to PPOX.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 PNPLA8 Arina Puzriakova Source NHS GMS was added to PNPLA8.
Source Expert Review Green was added to PNPLA8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 OPA1 Arina Puzriakova Source NHS GMS was added to OPA1.
Source Expert Review Green was added to OPA1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 NOTCH3 Arina Puzriakova Source NHS GMS was added to NOTCH3.
Source Expert Review Green was added to NOTCH3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 NHLRC2 Arina Puzriakova Source NHS GMS was added to NHLRC2.
Source Expert Review Green was added to NHLRC2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 NAV3 Arina Puzriakova Source NHS GMS was added to NAV3.
Source Expert Review Green was added to NAV3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 NAA20 Arina Puzriakova Source NHS GMS was added to NAA20.
Source Expert Review Green was added to NAA20.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 MRPL49 Arina Puzriakova Source NHS GMS was added to MRPL49.
Source Expert Review Green was added to MRPL49.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 MED12L Arina Puzriakova Source NHS GMS was added to MED12L.
Source Expert Review Green was added to MED12L.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 MAP4K4 Arina Puzriakova Source NHS GMS was added to MAP4K4.
Source Expert Review Green was added to MAP4K4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 MAG Arina Puzriakova Source NHS GMS was added to MAG.
Source Expert Review Green was added to MAG.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 LAMC3 Arina Puzriakova Source NHS GMS was added to LAMC3.
Source Expert Review Red was added to LAMC3.
Mode of inheritance for gene LAMC3 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rating Changed from Green List (high evidence) to Red List (low evidence)
Intellectual disability v9.298 KIAA0556 Arina Puzriakova Source NHS GMS was added to KIAA0556.
Source Expert Review Green was added to KIAA0556.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 KDM5B Arina Puzriakova Source NHS GMS was added to KDM5B.
Mode of inheritance for gene KDM5B was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v9.298 INPP4A Arina Puzriakova Source NHS GMS was added to INPP4A.
Source Expert Review Green was added to INPP4A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 HNRNPC Arina Puzriakova Source NHS GMS was added to HNRNPC.
Source Expert Review Green was added to HNRNPC.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 GTF3C3 Arina Puzriakova Source NHS GMS was added to GTF3C3.
Source Expert Review Green was added to GTF3C3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 GPATCH11 Arina Puzriakova Source NHS GMS was added to GPATCH11.
Source Expert Review Green was added to GPATCH11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 FLVCR1 Arina Puzriakova Source NHS GMS was added to FLVCR1.
Source Expert Review Green was added to FLVCR1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 FBXO22 Arina Puzriakova Source NHS GMS was added to FBXO22.
Source Expert Review Green was added to FBXO22.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 EXOSC8 Arina Puzriakova Source NHS GMS was added to EXOSC8.
Source Expert Review Green was added to EXOSC8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 EPB41L3 Arina Puzriakova Source NHS GMS was added to EPB41L3.
Source Expert Review Green was added to EPB41L3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 EMX2 Arina Puzriakova Source NHS GMS was added to EMX2.
Source Expert Review Amber was added to EMX2.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Intellectual disability v9.298 ELFN1 Arina Puzriakova Source NHS GMS was added to ELFN1.
Source Expert Review Green was added to ELFN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 EEFSEC Arina Puzriakova Source NHS GMS was added to EEFSEC.
Source Expert Review Green was added to EEFSEC.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 EEF1D Arina Puzriakova Source NHS GMS was added to EEF1D.
Source Expert Review Green was added to EEF1D.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 DDX39B Arina Puzriakova Source NHS GMS was added to DDX39B.
Source Expert Review Green was added to DDX39B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 CRNKL1 Arina Puzriakova Source NHS GMS was added to CRNKL1.
Source Expert Review Green was added to CRNKL1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 CDK9 Arina Puzriakova Source NHS GMS was added to CDK9.
Source Expert Review Green was added to CDK9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 CCT6A Arina Puzriakova Source NHS GMS was added to CCT6A.
Source Expert Review Green was added to CCT6A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 C12orf66 Arina Puzriakova Source NHS GMS was added to C12orf66.
Source Expert Review Green was added to C12orf66.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 ATM Arina Puzriakova Source NHS GMS was added to ATM.
Source Expert Review Red was added to ATM.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Intellectual disability v9.298 ASCC3 Arina Puzriakova Source NHS GMS was added to ASCC3.
Source Expert Review Green was added to ASCC3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.256 SLITRK2 Ida Ertmanska Tag Q1_26_promote_green tag was added to gene: SLITRK2.
Tag Q1_26_NHS_review tag was added to gene: SLITRK2.
Intellectual disability v9.253 PHF12 Ida Ertmanska Tag Q1_26_NHS_review tag was added to gene: PHF12.
Intellectual disability v9.236 SLITRK2 Mike Spiller gene: SLITRK2 was added
gene: SLITRK2 was added to Intellectual disability. Sources: NHS GMS,Literature
Mode of inheritance for gene: SLITRK2 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: SLITRK2 were set to PMID: 35840571
Review for gene: SLITRK2 was set to GREEN
Added comment: Gene is associated with Intellectual developmental disorder, X-linked 111 (OMIM 301107).
Association based on PMID: 35840571 - 7 probands, 6 male one female. Female de novo, males mix of de novo and maternally inherited. ID levels range from borderline-severe, 5 patients moderate-severe.
One LOF, others missenses distributed through the gene. Missenses well supported by mouse data including inability to rescue KO phenotypes, as well as HEK293 transcfection studies..

Also 2 hemizygous LOF on CVA with consistent phenotypes (NHS GMS).
Sources: NHS GMS, Literature
Intellectual disability v9.172 ISCA-37448-Loss Arina Puzriakova changed review comment from: https://search.clinicalgenome.org/kb/gene-dosage/region/ISCA-37448

ClinGen review: Deletion of the 15q11.2 (BP1-BP2) region has historically been reported in association with highly variable clinical phenotypes. Features observed in carrier patients referred for clinical genome wide copy number testing have been relatively nonspecific, including developmental delay/intellectual disability (DD/ID), epilepsy, autism spectrum disorder (ASD), schizophrenia, congenital heart disease (CHD), and variable dysmorphic features, which are also generally common in this patient population. This deletion has been shown to be enriched in the clinical population across multiple case-control studies. However, in the clinical setting, it is often inherited from unaffected carriers, and the deletion is also observed in the general population at a relatively high frequency (0.14 - 0.39%; PMID: 25217958, 30767844). The expression of any phenotype associated with this deletion has been estimated to be between 8-10%. This has led to a high level of variability in how this region is reported clinically.

Large cohort studies involving 15q11.2 (BP1-BP2) deletion carriers from the general population have consistently demonstrated that individuals who carry this deletion perform worse on cognitive function tests than non-carrier individuals. This difference has been reported to be significant, but with a mild effect size, consistent with the deletion being a susceptibility locus for neurodevelopmental phenotypes. Additionally, these studies suggest ascertainment bias may be responsible for the association of this deletion with the more severe clinical phenotypes (ID, epilepsy, ASD and CHD) observed in cases identified through clinical testing.

Collectively, the current literature is consistent with the 15q11.2 (BP1-BP2) deletion having a subclinical, but measurable, effect on neurocognitive function. Other reported clinical associations are not conclusively established, and likely reflect a bias of ascertainment. Therefore, there is sufficient evidence for haploinsufficiency of this region.


Additional comments from Genomics England Clinical team: There are significant issues with penetrance for these but I understand the NHS would still report them in the context of disease (https://www.acgs.uk.com/media/12443/uk-practice-guidelines-for-variant-classification-v1-2023.pdf). Therefore, agree with the recommendations.
Sources: ClinGen; to: https://search.clinicalgenome.org/kb/gene-dosage/region/ISCA-37448

ClinGen review (Last Evaluated:04/12/2021): Deletion of the 15q11.2 (BP1-BP2) region has historically been reported in association with highly variable clinical phenotypes. Features observed in carrier patients referred for clinical genome wide copy number testing have been relatively nonspecific, including developmental delay/intellectual disability (DD/ID), epilepsy, autism spectrum disorder (ASD), schizophrenia, congenital heart disease (CHD), and variable dysmorphic features, which are also generally common in this patient population. This deletion has been shown to be enriched in the clinical population across multiple case-control studies. However, in the clinical setting, it is often inherited from unaffected carriers, and the deletion is also observed in the general population at a relatively high frequency (0.14 - 0.39%; PMID: 25217958, 30767844). The expression of any phenotype associated with this deletion has been estimated to be between 8-10%. This has led to a high level of variability in how this region is reported clinically.

Large cohort studies involving 15q11.2 (BP1-BP2) deletion carriers from the general population have consistently demonstrated that individuals who carry this deletion perform worse on cognitive function tests than non-carrier individuals. This difference has been reported to be significant, but with a mild effect size, consistent with the deletion being a susceptibility locus for neurodevelopmental phenotypes. Additionally, these studies suggest ascertainment bias may be responsible for the association of this deletion with the more severe clinical phenotypes (ID, epilepsy, ASD and CHD) observed in cases identified through clinical testing.

Collectively, the current literature is consistent with the 15q11.2 (BP1-BP2) deletion having a subclinical, but measurable, effect on neurocognitive function. Other reported clinical associations are not conclusively established, and likely reflect a bias of ascertainment. Therefore, there is sufficient evidence for haploinsufficiency of this region.


Additional comments from Genomics England Clinical team: There are significant issues with penetrance for these but I understand the NHS would still report them in the context of disease (https://www.acgs.uk.com/media/12443/uk-practice-guidelines-for-variant-classification-v1-2023.pdf). Therefore, agree with the recommendations.
Sources: ClinGen
Intellectual disability v9.172 ISCA-37448-Loss Arina Puzriakova Region: ISCA-37448-Loss was added
Region: ISCA-37448-Loss was added to Intellectual disability. Sources: ClinGen
Q3_25_promote_green tags were added to Region: ISCA-37448-Loss.
Mode of inheritance for Region: ISCA-37448-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for Region: ISCA-37448-Loss were set to 31451536; 24352232; 30767844; 31665216
Review for Region: ISCA-37448-Loss was set to GREEN
Added comment: https://search.clinicalgenome.org/kb/gene-dosage/region/ISCA-37448

ClinGen review: Deletion of the 15q11.2 (BP1-BP2) region has historically been reported in association with highly variable clinical phenotypes. Features observed in carrier patients referred for clinical genome wide copy number testing have been relatively nonspecific, including developmental delay/intellectual disability (DD/ID), epilepsy, autism spectrum disorder (ASD), schizophrenia, congenital heart disease (CHD), and variable dysmorphic features, which are also generally common in this patient population. This deletion has been shown to be enriched in the clinical population across multiple case-control studies. However, in the clinical setting, it is often inherited from unaffected carriers, and the deletion is also observed in the general population at a relatively high frequency (0.14 - 0.39%; PMID: 25217958, 30767844). The expression of any phenotype associated with this deletion has been estimated to be between 8-10%. This has led to a high level of variability in how this region is reported clinically.

Large cohort studies involving 15q11.2 (BP1-BP2) deletion carriers from the general population have consistently demonstrated that individuals who carry this deletion perform worse on cognitive function tests than non-carrier individuals. This difference has been reported to be significant, but with a mild effect size, consistent with the deletion being a susceptibility locus for neurodevelopmental phenotypes. Additionally, these studies suggest ascertainment bias may be responsible for the association of this deletion with the more severe clinical phenotypes (ID, epilepsy, ASD and CHD) observed in cases identified through clinical testing.

Collectively, the current literature is consistent with the 15q11.2 (BP1-BP2) deletion having a subclinical, but measurable, effect on neurocognitive function. Other reported clinical associations are not conclusively established, and likely reflect a bias of ascertainment. Therefore, there is sufficient evidence for haploinsufficiency of this region.


Additional comments from Genomics England Clinical team: There are significant issues with penetrance for these but I understand the NHS would still report them in the context of disease (https://www.acgs.uk.com/media/12443/uk-practice-guidelines-for-variant-classification-v1-2023.pdf). Therefore, agree with the recommendations.
Sources: ClinGen
Intellectual disability v9.139 PTBP1 Arina Puzriakova Tag Q3_25_NHS_review was removed from gene: PTBP1.
Intellectual disability v9.139 PTBP1 Arina Puzriakova gene: PTBP1 was added
gene: PTBP1 was added to Intellectual disability. Sources: Literature,Expert Review Amber,NHS GMS
Q3_25_promote_green, Q3_25_NHS_review tags were added to gene: PTBP1.
Mode of inheritance for gene: PTBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTBP1 were set to 40965981
Phenotypes for gene: PTBP1 were set to Neurodevelopmental disorder, MONDO:0700092
Penetrance for gene: PTBP1 were set to unknown
Intellectual disability v9.118 SF1 Achchuthan Shanmugasundram Tag Q3_25_NHS_review tag was added to gene: SF1.
Intellectual disability v9.104 EMX2 Eleanor Williams Tag Q3_25_NHS_review tag was added to gene: EMX2.
Intellectual disability v9.99 UGGT1 Achchuthan Shanmugasundram Tag Q3_25_promote_green tag was added to gene: UGGT1.
Tag Q3_25_NHS_review tag was added to gene: UGGT1.
Intellectual disability v9.87 UPF1 Achchuthan Shanmugasundram Tag Q3_25_promote_green tag was added to gene: UPF1.
Tag Q3_25_NHS_review tag was added to gene: UPF1.
Intellectual disability v9.63 UNC13A Achchuthan Shanmugasundram Tag Q3_25_promote_green tag was added to gene: UNC13A.
Tag Q3_25_NHS_review tag was added to gene: UNC13A.
Intellectual disability v9.56 MED16 Achchuthan Shanmugasundram Tag Q3_25_promote_green tag was added to gene: MED16.
Tag Q3_25_NHS_review tag was added to gene: MED16.
Intellectual disability v9.55 RREB1 Achchuthan Shanmugasundram Tag Q3_25_promote_green tag was added to gene: RREB1.
Tag Q3_25_NHS_review tag was added to gene: RREB1.
Intellectual disability v9.51 MED16 Karen Stals gene: MED16 was added
gene: MED16 was added to Intellectual disability. Sources: NHS GMS
Mode of inheritance for gene: MED16 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MED16 were set to PMID: 40081376
Phenotypes for gene: MED16 were set to developmental delay; multiple congenital abnormalities; Medopathy
Penetrance for gene: MED16 were set to unknown
Review for gene: MED16 was set to GREEN
gene: MED16 was marked as current diagnostic
Added comment: 25 individuals from 18 families reported with biallelic MED16 variants with multiple congenital anomalies (MCAs)-intellectual disability syndrome. Intellectual disability, speech delay, and/or motor delay of variable severity were constant and associated with variable combinations of craniofacial defects (micro/retrognathia, cleft palate, and preauricular tags), anomalies of the extremities, and heart defects (predominantly tetralogy of Fallot). Visual impairment, deafness, and magnetic resonance imaging (MRI) abnormalities were also frequent. 8 predicted protein-truncating and 18 missense or in-frame duplication variants identified.
Sources: NHS GMS
Intellectual disability v9.46 RNU5B-1 Arina Puzriakova gene: RNU5B-1 was added
gene: RNU5B-1 was added to Intellectual disability. Sources: Literature
Q3_25_promote_green tags were added to gene: RNU5B-1.
Mode of inheritance for gene: RNU5B-1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RNU5B-1 were set to 40379786; 40442284
Phenotypes for gene: RNU5B-1 were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: RNU5B-1 was set to GREEN
Added comment: At least 19 individuals with de novo and/or recurrent variants in RNU5B-1 and a neurodevelopmental disorder characterised by ID/DD, brain MRI abnormalities, hypotonia, microcephaly or macrocephaly, failure to thrive, and in some cases seizures.

PMID: 40379786 (2025) - 15 unrelated probands with heterozygous variants in RNU5B-1. Clinical data was available for 9 individuals who presented with a neurodevelopmental disorder including severe ID/DD (although one patient had normal cognition but attention difficulties) and brain MRI abnormalities. Other features were variable and include hypotonia, epilepsy, ocular abnormalities, acquired microcephaly or macrocephaly and other variable congenital abnormalities. Variants typically arose de novo on the maternal allele and cluster in regions critical for splicing. Functional studies demonstrate variant-specific splicing abnormalities in patient-derived cells which may underline the clinical variability observed in patients.

PMID: 40442284 (2025) - 9 unrelated individuals with de novo variants in RNU5B-1 and a neurodevelopmental disorder characterised by GDD/ID, macrocephaly, eye abnormalities, seizures, hypotonia and failure to thrive, among other variable features - based on 6 cases where phenotype information was available. Variants were again found in regions critical for splicing.

Both studies investigated participants of the 100KGP and/or NHS GMS (6 in PMID: 40379786 and 5 in PMID: 40442284) so likely refer to the same individuals.
Sources: Literature
Intellectual disability v9.28 KDM5B Arina Puzriakova Tag Q2_25_expert_review tag was added to gene: KDM5B.
Tag Q2_25_ demote_amber tag was added to gene: KDM5B.
Tag Q2_25_ NHS_review tag was added to gene: KDM5B.
Intellectual disability v9.21 RAB3A Sarah Leigh Tag Q2_25_ promote_green was removed from gene: RAB3A.
Tag Q2_25_ NHS_review was removed from gene: RAB3A.
Intellectual disability v9.21 RAB3A Sarah Leigh gene: RAB3A was added
gene: RAB3A was added to Intellectual disability. Sources: Research,Expert Review Amber
Q2_25_ promote_green, Q2_25_ NHS_review tags were added to gene: RAB3A.
Mode of inheritance for gene: RAB3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAB3A were set to 36928819; 40166812
Phenotypes for gene: RAB3A were set to RAB3A associated cerebellar ataxia; pyramidal features; neurodevelopmental delay
Penetrance for gene: RAB3A were set to Complete
Intellectual disability v9.18 FBXO22 Achchuthan Shanmugasundram Tag Q2_25_ promote_green tag was added to gene: FBXO22.
Tag Q2_25_ NHS_review tag was added to gene: FBXO22.
Intellectual disability v9.11 SEL1L Achchuthan Shanmugasundram Tag Q2_25_ promote_green tag was added to gene: SEL1L.
Tag Q2_25_ NHS_review tag was added to gene: SEL1L.
Intellectual disability v9.5 EPB41L3 Arina Puzriakova Tag Q2_25_ promote_green tag was added to gene: EPB41L3.
Tag Q2_25_ NHS_review tag was added to gene: EPB41L3.
Intellectual disability v9.2 EEF1D Arina Puzriakova Tag Q2_25_ promote_green tag was added to gene: EEF1D.
Tag Q2_25_ NHS_review tag was added to gene: EEF1D.
Intellectual disability v8.237 DDX39B Achchuthan Shanmugasundram Tag Q2_25_ promote_green tag was added to gene: DDX39B.
Tag Q2_25_ NHS_review tag was added to gene: DDX39B.
Intellectual disability v8.163 AFF2_GCC Sarah Leigh STR: AFF2_GCC was added
STR: AFF2_GCC was added to Intellectual disability. Sources: Literature
STR, NGS Not Validated tags were added to STR: AFF2_GCC.
Mode of inheritance for STR: AFF2_GCC was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for STR: AFF2_GCC were set to 8334699; 8023854; 21739600; 9299237; 11171404; 11923441; 19136466; 2356291
Phenotypes for STR: AFF2_GCC were set to Intellectual developmental disorder, X-linked 109, OMIM:309548; FRAXE intellectual disability, MONDO:0010659
Review for STR: AFF2_GCC was set to GREEN
Added comment: AFF2 transcribed from the forwards strand, which means that the repeated sequence is the forward strand sequence.

AFF2_GCC is on https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r3

AFF2_GCC is on https://stripy.org/database

AFF2_GCC is on DRAGON 4.02.

The coordinates and pathogenic ranges of the sequence repeats were obtained from
https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r3 and DRAGON 4.02/

There is enough evidence for this STR to be green on this panel.

This STR has not been approved by NHS STR working group and is not NGS Not Validated
Sources: Literature
Intellectual disability v8.162 THAP11_CAG Sarah Leigh Added comment: Comment on list classification: This STR has not been approved by NHS STR working group and is not NGS Not Validated
Intellectual disability v8.161 THAP11_CAG Sarah Leigh STR: THAP11_CAG was added
STR: THAP11_CAG was added to Intellectual disability. Sources: Literature
STR, NGS Not Validated tags were added to STR: THAP11_CAG.
Mode of inheritance for STR: THAP11_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for STR: THAP11_CAG were set to 37148549; 38757579; 39441143
Phenotypes for STR: THAP11_CAG were set to Spinocerebellar ataxia 51, OMIM:620947
Review for STR: THAP11_CAG was set to RED
Added comment: THAP11 transcribed from the forward strand.
THAP11_CAG is not on https://gnomad.broadinstitute.org/short-tandem-repeats?dataset=gnomad_r3
THAP11_CAG is not is not DRAGON 4.02 or other previous versions.
The coordinates and pathogenic ranges of the sequence repeats were obtained from https://stripy.org/database/THAP11

This STR has not been approved by NHS STR working group and is not NGS Not Validated
Sources: Literature
Intellectual disability v8.116 TDP1 Sarah Leigh gene: TDP1 was added
gene: TDP1 was added to Intellectual disability. Sources: Expert Review Amber,South West GLH,UKGTN,Emory Genetics Laboratory,Expert list,NHS GMS
founder-effect tags were added to gene: TDP1.
Mode of inheritance for gene: TDP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TDP1 were set to 12244316; 31182267; 39576382
Phenotypes for gene: TDP1 were set to ?Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1, OMIM:607250
Intellectual disability v8.97 TBC1D7 Sarah Leigh Tag Q3_24_promote_green was removed from gene: TBC1D7.
Tag Q3_24_NHS_review was removed from gene: TBC1D7.
Intellectual disability v8.97 LINC01578 Sarah Leigh Tag Q3_24_promote_green was removed from gene: LINC01578.
Tag Q3_24_NHS_review was removed from gene: LINC01578.
Intellectual disability v8.97 LRRC7 Sarah Leigh Tag Q3_24_promote_green was removed from gene: LRRC7.
Tag Q3_24_NHS_review was removed from gene: LRRC7.
Intellectual disability v8.97 MSL2 Sarah Leigh Tag Q3_24_promote_green was removed from gene: MSL2.
Tag Q3_24_NHS_review was removed from gene: MSL2.
Intellectual disability v8.97 PI4K2A Sarah Leigh Tag Q3_24_promote_green was removed from gene: PI4K2A.
Tag Q3_24_NHS_review was removed from gene: PI4K2A.
Intellectual disability v8.97 CIAO1 Sarah Leigh Tag Q3_24_promote_green was removed from gene: CIAO1.
Tag Q3_24_NHS_review was removed from gene: CIAO1.
Intellectual disability v8.97 DDX17 Sarah Leigh Tag Q3_24_promote_green was removed from gene: DDX17.
Tag Q3_24_NHS_review was removed from gene: DDX17.
Intellectual disability v8.97 FIBP Sarah Leigh Tag Q3_24_promote_green was removed from gene: FIBP.
Tag Q3_24_NHS_review was removed from gene: FIBP.
Intellectual disability v8.97 PLEKHG2 Sarah Leigh commented on gene: PLEKHG2: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v8.97 LINC01578 Sarah Leigh commented on gene: LINC01578: 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.
Intellectual disability v8.97 FIBP Sarah Leigh commented on gene: FIBP: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v8.97 CIAO1 Sarah Leigh commented on gene: CIAO1: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v8.97 B9D1 Sarah Leigh edited their review of gene: B9D1: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v8.97 ATXN7L3 Sarah Leigh commented on gene: ATXN7L3: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v8.97 WDR83OS Sarah Leigh Source NHS GMS was added to WDR83OS.
Source Expert Review Green was added to WDR83OS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 TRMT5 Sarah Leigh Source NHS GMS was added to TRMT5.
Source Expert Review Green was added to TRMT5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 TBC1D7 Sarah Leigh Source NHS GMS was added to TBC1D7.
Source Expert Review Green was added to TBC1D7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 SRPK3 Sarah Leigh Source NHS GMS was added to SRPK3.
Source Expert Review Green was added to SRPK3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 SLC4A10 Sarah Leigh Source NHS GMS was added to SLC4A10.
Source Expert Review Green was added to SLC4A10.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 RBBP5 Sarah Leigh Source NHS GMS was added to RBBP5.
Source Expert Review Green was added to RBBP5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 PSMC5 Sarah Leigh Source NHS GMS was added to PSMC5.
Source Expert Review Green was added to PSMC5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 PLEKHG2 Sarah Leigh Source NHS GMS was added to PLEKHG2.
Source Expert Review Green was added to PLEKHG2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 MSL2 Sarah Leigh Source NHS GMS was added to MSL2.
Source Expert Review Green was added to MSL2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 MARK2 Sarah Leigh Source NHS GMS was added to MARK2.
Source Expert Review Green was added to MARK2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 MAPKAPK5 Sarah Leigh Source NHS GMS was added to MAPKAPK5.
Source Expert Review Green was added to MAPKAPK5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 LRRC7 Sarah Leigh Source NHS GMS was added to LRRC7.
Source Expert Review Green was added to LRRC7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 LINC01578 Sarah Leigh Source NHS GMS was added to LINC01578.
Source Expert Review Green was added to LINC01578.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 IREB2 Sarah Leigh Source NHS GMS was added to IREB2.
Source Expert Review Green was added to IREB2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 HDAC3 Sarah Leigh Source NHS GMS was added to HDAC3.
Source Expert Review Green was added to HDAC3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 GNAI2 Sarah Leigh Source NHS GMS was added to GNAI2.
Source Expert Review Green was added to GNAI2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 GEMIN4 Sarah Leigh Source NHS GMS was added to GEMIN4.
Source Expert Review Green was added to GEMIN4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 FZR1 Sarah Leigh Source NHS GMS was added to FZR1.
Source Expert Review Green was added to FZR1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 FUK Sarah Leigh Source NHS GMS was added to FUK.
Source Expert Review Green was added to FUK.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 FRA10AC1 Sarah Leigh Source NHS GMS was added to FRA10AC1.
Source Expert Review Green was added to FRA10AC1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 FOSL2 Sarah Leigh Source NHS GMS was added to FOSL2.
Source Expert Review Green was added to FOSL2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 FIBP Sarah Leigh Source NHS GMS was added to FIBP.
Source Expert Review Green was added to FIBP.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 DHRSX Sarah Leigh Source NHS GMS was added to DHRSX.
Source Expert Review Green was added to DHRSX.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 DDX17 Sarah Leigh Source NHS GMS was added to DDX17.
Source Expert Review Green was added to DDX17.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 CRELD1 Sarah Leigh Source NHS GMS was added to CRELD1.
Source Expert Review Green was added to CRELD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 CIAO1 Sarah Leigh Source NHS GMS was added to CIAO1.
Source Expert Review Green was added to CIAO1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 CCDC88A Sarah Leigh Source NHS GMS was added to CCDC88A.
Source Expert Review Green was added to CCDC88A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 BORCS8 Sarah Leigh Source NHS GMS was added to BORCS8.
Source Expert Review Green was added to BORCS8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 B9D1 Sarah Leigh Source NHS GMS was added to B9D1.
Source Expert Review Green was added to B9D1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.97 ATXN7L3 Sarah Leigh Source NHS GMS was added to ATXN7L3.
Source Expert Review Green was added to ATXN7L3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.48 TAOK2 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: TAOK2.
Tag Q1_25_ promote_green tag was added to gene: TAOK2.
Intellectual disability v8.41 WBP4 Sarah Leigh gene: WBP4 was added
gene: WBP4 was added to Intellectual disability. Sources: Literature
Q4_24_NHS_review, Q4_22_promote_green tags were added to gene: WBP4.
Mode of inheritance for gene: WBP4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WBP4 were set to Neurodevelopemental disorder with hypotonia, feeding difficulties, facial dysmorphism, and brain abnormalities, OMIM:620852; neurodevelopmental disorder with hypotonia, feeding difficulties, facial dysmorphism, and brain abnormalities, MONDO:0971043
Review for gene: WBP4 was set to GREEN
Added comment: WBP4 variants have been associated with Neurodevelopemental disorder with hypotonia, feeding difficulties, facial dysmorphism, and brain abnormalities (OMIM:620852). PMID: 37963460 reports four apparently loss of function WBP4 variants in four unrelated cases.
Sources: Literature
Intellectual disability v8.36 ATXN7L3 Achchuthan Shanmugasundram Tag Q3_24_NHS_review was removed from gene: ATXN7L3.
Tag Q3_24_MOI was removed from gene: ATXN7L3.
Intellectual disability v8.20 LINC01578 Sarah Leigh Tag new-gene-name tag was added to gene: LINC01578.
Tag Q3_24_promote_green tag was added to gene: LINC01578.
Tag Q3_24_NHS_review tag was added to gene: LINC01578.
Intellectual disability v8.9 PI4K2A Achchuthan Shanmugasundram Tag Q3_24_promote_green tag was added to gene: PI4K2A.
Tag Q3_24_NHS_review tag was added to gene: PI4K2A.
Intellectual disability v8.6 PI4K2A Tracy Lester gene: PI4K2A was added
gene: PI4K2A was added to Intellectual disability. Sources: NHS GMS
Mode of inheritance for gene: PI4K2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PI4K2A were set to 30564627; 35880319; 32418222
Phenotypes for gene: PI4K2A were set to Intellectual disability; developmental delay; seizures
Penetrance for gene: PI4K2A were set to unknown
Review for gene: PI4K2A was set to GREEN
Added comment: At least three cases have been reported with biallelic variants in this gene and a neurodevelopmental disorder
35880319 - Two patients with PI4K2A deficiency (homozygous variants) were identified by exome sequencing, presenting with developmental and epileptic-dyskinetic encephalopathy. Neuroimaging showed corpus callosum dysgenesis, diffuse white matter volume loss, and hypoplastic vermis. In addition to NDD, we observed recurrent infections and death at toddler age.
30564627 - We report a family of Saudi Arabian ancestry with two children presenting with global developmental delay, dystonia, disturbed sleep, and heat intolerance. By genome sequencing, we identified a nonsense variant in the first exon of PI4K2A that was homozygous in both affected individuals and was absent from, or heterozygous in, seven unaffected siblings.
32418222 - a homozygous missense variant of uncertain significance was suggested to be responsible for some features in a case with NDD and metabolic cutis laxa.
Sources: NHS GMS
Intellectual disability v8.6 PLA2G16 Eleanor Williams Tag Q3_24_promote_green was removed from gene: PLA2G16.
Tag Q3_24_NHS_review was removed from gene: PLA2G16.
Intellectual disability v8.5 PLA2G16 Eleanor Williams gene: PLA2G16 was added
gene: PLA2G16 was added to Intellectual disability. Sources: Expert list,Expert Review Amber
new-gene-name, Q3_24_promote_green, Q3_24_NHS_review tags were added to gene: PLA2G16.
Mode of inheritance for gene: PLA2G16 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLA2G16 were set to 37919452
Phenotypes for gene: PLA2G16 were set to Associated with Lipodystrophy, familial partial, type 9, OMIM:620683; lipodystrophy, familial partial, type 9, MONDO:0958034
Intellectual disability v7.64 TRMT5 Arina Puzriakova Tag Q3_24_NHS_review was removed from gene: TRMT5.
Intellectual disability v7.64 TRMT5 Arina Puzriakova gene: TRMT5 was added
gene: TRMT5 was added to Intellectual disability. Sources: Expert list,Expert Review Amber
Q3_24_promote_green, Q3_24_NHS_review tags were added to gene: TRMT5.
Mode of inheritance for gene: TRMT5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRMT5 were set to 35342985; 26189817; 29021354
Phenotypes for gene: TRMT5 were set to Peripheral neuropathy with variable spasticity, exercise intolerance, and developmental delay, OMIM:616539
Penetrance for gene: TRMT5 were set to Complete
Intellectual disability v7.61 DDX17 Achchuthan Shanmugasundram Tag Q3_24_promote_green tag was added to gene: DDX17.
Tag Q3_24_NHS_review tag was added to gene: DDX17.
Intellectual disability v7.61 KIF5B Tracy Lester gene: KIF5B was added
gene: KIF5B was added to Intellectual disability. Sources: NHS GMS
Mode of inheritance for gene: KIF5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF5B were set to 36018820; 35342932
Phenotypes for gene: KIF5B were set to kyphomelic dysplasia; hypotonia; developmental delay; intellectual disability
Penetrance for gene: KIF5B were set to unknown
Review for gene: KIF5B was set to AMBER
Added comment: PMID: 35342932 - 3 de novo missense variants reported in 4 subjects with a syndromic skeletal disorder characterized by kyphomelic dysplasia, hypotonia and DD/ID
PMID: 36018820 - 3 more missense variants reported in individuals with a clinically wide phenotypic spectrum ranging from dilated cardiomyopathy with adult-onset ophthalmoplegia and progressive skeletal myopathy to a neurodevelopmental condition characterized by severe hypotonia with or without seizures. In vitro and in vivo analyses provide evidence that the identified disease-associated KIF5B variants disrupt lysosomal, autophagosome and mitochondrial organization, and impact cilium biogenesis. All variants, and one of the previously reported missense changes, were shown to affect multiple developmental processes in zebrafish.
Sources: NHS GMS
Intellectual disability v7.51 LRRC7 Achchuthan Shanmugasundram Tag Q3_24_promote_green tag was added to gene: LRRC7.
Tag Q3_24_NHS_review tag was added to gene: LRRC7.
Intellectual disability v7.41 SOX9 Achchuthan Shanmugasundram Tag Q2_24_demote_amber was removed from gene: SOX9.
Tag Q2_24_NHS_review was removed from gene: SOX9.
Intellectual disability v7.41 GLI3 Achchuthan Shanmugasundram Tag Q2_24_demote_amber was removed from gene: GLI3.
Tag Q2_24_NHS_review was removed from gene: GLI3.
Intellectual disability v7.41 TBC1D2B Achchuthan Shanmugasundram Tag Q2_24_promote_green was removed from gene: TBC1D2B.
Tag Q2_24_NHS_review was removed from gene: TBC1D2B.
Intellectual disability v7.41 MAST3 Achchuthan Shanmugasundram Tag Q2_24_promote_green was removed from gene: MAST3.
Tag Q2_24_NHS_review was removed from gene: MAST3.
Intellectual disability v7.41 ITSN1 Achchuthan Shanmugasundram Tag Q2_24_promote_green was removed from gene: ITSN1.
Tag Q2_24_NHS_review was removed from gene: ITSN1.
Intellectual disability v7.41 GAN Achchuthan Shanmugasundram Tag Q2_24_promote_green was removed from gene: GAN.
Tag Q2_24_NHS_review was removed from gene: GAN.
Intellectual disability v7.41 DENND5B Achchuthan Shanmugasundram Tag Q2_24_promote_green was removed from gene: DENND5B.
Tag Q2_24_NHS_review was removed from gene: DENND5B.
Intellectual disability v7.41 ZNFX1 Achchuthan Shanmugasundram Tag Q1_24_promote_green was removed from gene: ZNFX1.
Tag Q1_24_NHS_review was removed from gene: ZNFX1.
Intellectual disability v7.41 ZFX Achchuthan Shanmugasundram Tag Q1_24_promote_green was removed from gene: ZFX.
Tag Q1_24_NHS_review was removed from gene: ZFX.
Intellectual disability v7.41 ZFHX3 Achchuthan Shanmugasundram Tag Q1_24_promote_green was removed from gene: ZFHX3.
Tag Q1_24_NHS_review was removed from gene: ZFHX3.
Intellectual disability v7.41 KCNA3 Achchuthan Shanmugasundram Tag Q1_24_promote_green was removed from gene: KCNA3.
Tag Q1_24_NHS_review was removed from gene: KCNA3.
Intellectual disability v7.41 DHX37 Achchuthan Shanmugasundram Tag Q1_24_MOI was removed from gene: DHX37.
Tag Q1_24_NHS_review was removed from gene: DHX37.
Intellectual disability v7.41 ABCC9 Achchuthan Shanmugasundram Tag Q1_24_MOI was removed from gene: ABCC9.
Tag Q1_24_NHS_review was removed from gene: ABCC9.
Intellectual disability v7.41 ZFX Achchuthan Shanmugasundram edited their review of gene: ZFX: 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: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v7.41 WDR5 Achchuthan Shanmugasundram commented on gene: WDR5: 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.
Intellectual disability v7.41 STX1A Achchuthan Shanmugasundram commented on gene: STX1A: 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.
Intellectual disability v7.41 SNF8 Achchuthan Shanmugasundram commented on gene: SNF8: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v7.41 PLXNB2 Achchuthan Shanmugasundram commented on gene: PLXNB2: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v7.41 LGI3 Achchuthan Shanmugasundram commented on gene: LGI3: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v7.41 KCNB2 Achchuthan Shanmugasundram commented on gene: KCNB2: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v7.41 KCNA3 Achchuthan Shanmugasundram commented on gene: KCNA3: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v7.41 ITSN1 Achchuthan Shanmugasundram commented on gene: ITSN1: 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 v7.41 GTF3C5 Achchuthan Shanmugasundram commented on gene: GTF3C5: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v7.41 FEM1B Achchuthan Shanmugasundram commented on gene: FEM1B: The rating of this gene has been updated to green and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Intellectual disability v7.41 FAM177A1 Achchuthan Shanmugasundram commented on gene: FAM177A1: 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 v7.41 EZH1 Achchuthan Shanmugasundram commented on gene: EZH1: 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 v7.41 DOCK4 Achchuthan Shanmugasundram commented on gene: DOCK4: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v7.41 CAMSAP1 Achchuthan Shanmugasundram commented on gene: CAMSAP1: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v7.41 CAMK2D Achchuthan Shanmugasundram commented on gene: CAMK2D: 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.
Intellectual disability v7.41 BAZ2B Achchuthan Shanmugasundram commented on gene: BAZ2B: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v7.41 ADGRL1 Achchuthan Shanmugasundram commented on gene: ADGRL1: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v7.40 ZNFX1 Achchuthan Shanmugasundram Source NHS GMS was added to ZNFX1.
Source Expert Review Green was added to ZNFX1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v7.40 ZFX Achchuthan Shanmugasundram Source NHS GMS was added to ZFX.
Source Expert Review Green was added to ZFX.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v7.40 ZFHX3 Achchuthan Shanmugasundram Source NHS GMS was added to ZFHX3.
Source Expert Review Green was added to ZFHX3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v7.40 WDR5 Achchuthan Shanmugasundram Source NHS GMS was added to WDR5.
Source Expert Review Green was added to WDR5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v7.40 TBC1D2B Achchuthan Shanmugasundram Source NHS GMS was added to TBC1D2B.
Source Expert Review Green was added to TBC1D2B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v7.40 STX1A Achchuthan Shanmugasundram Source NHS GMS was added to STX1A.
Source Expert Review Green was added to STX1A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v7.40 SOX9 Achchuthan Shanmugasundram Source Expert Review Amber was added to SOX9.
Source NHS GMS was added to SOX9.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Intellectual disability v7.40 SNF8 Achchuthan Shanmugasundram Source NHS GMS was added to SNF8.
Source Expert Review Green was added to SNF8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v7.40 SEPHS1 Achchuthan Shanmugasundram Source NHS GMS was added to SEPHS1.
Source Expert Review Green was added to SEPHS1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v7.40 RNU4-2 Achchuthan Shanmugasundram Source NHS GMS was added to RNU4-2.
Source Expert Review Green was added to RNU4-2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v7.40 PLXNB2 Achchuthan Shanmugasundram Source NHS GMS was added to PLXNB2.
Source Expert Review Green was added to PLXNB2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v7.40 MAST3 Achchuthan Shanmugasundram Source NHS GMS was added to MAST3.
Source Expert Review Green was added to MAST3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v7.40 LGI3 Achchuthan Shanmugasundram Source NHS GMS was added to LGI3.
Source Expert Review Green was added to LGI3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v7.40 KIRREL3 Achchuthan Shanmugasundram Source NHS GMS was added to KIRREL3.
Source Expert Review Green was added to KIRREL3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v7.40 KCNB2 Achchuthan Shanmugasundram Source NHS GMS was added to KCNB2.
Source Expert Review Green was added to KCNB2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v7.40 KCNA3 Achchuthan Shanmugasundram Source NHS GMS was added to KCNA3.
Source Expert Review Green was added to KCNA3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v7.40 ITSN1 Achchuthan Shanmugasundram Source NHS GMS was added to ITSN1.
Source Expert Review Green was added to ITSN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v7.40 HSD17B10 Achchuthan Shanmugasundram Source NHS GMS was added to HSD17B10.
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, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v7.40 GTF3C5 Achchuthan Shanmugasundram Source NHS GMS was added to GTF3C5.
Source Expert Review Green was added to GTF3C5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v7.40 GLI3 Achchuthan Shanmugasundram Source Expert Review Amber was added to GLI3.
Source NHS GMS was added to GLI3.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Intellectual disability v7.40 GAN Achchuthan Shanmugasundram Source NHS GMS was added to GAN.
Source Expert Review Green was added to GAN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v7.40 FEM1B Achchuthan Shanmugasundram Source NHS GMS was added to FEM1B.
Source Expert Review Green was added to FEM1B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v7.40 FAM177A1 Achchuthan Shanmugasundram Source NHS GMS was added to FAM177A1.
Source Expert Review Green was added to FAM177A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v7.40 EZH1 Achchuthan Shanmugasundram Source NHS GMS was added to EZH1.
Source Expert Review Green was added to EZH1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v7.40 DOCK4 Achchuthan Shanmugasundram Source NHS GMS was added to DOCK4.
Source Expert Review Green was added to DOCK4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v7.40 DHX37 Achchuthan Shanmugasundram Source NHS GMS was added to DHX37.
Mode of inheritance for gene DHX37 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v7.40 DENND5B Achchuthan Shanmugasundram Source NHS GMS was added to DENND5B.
Source Expert Review Green was added to DENND5B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v7.40 CLEC16A Achchuthan Shanmugasundram Source NHS GMS was added to CLEC16A.
Source Expert Review Green was added to CLEC16A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v7.40 CAMSAP1 Achchuthan Shanmugasundram Source NHS GMS was added to CAMSAP1.
Source Expert Review Green was added to CAMSAP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v7.40 CAMK2D Achchuthan Shanmugasundram Source NHS GMS was added to CAMK2D.
Source Expert Review Green was added to CAMK2D.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v7.40 BAZ2B Achchuthan Shanmugasundram Source NHS GMS was added to BAZ2B.
Source Expert Review Green was added to BAZ2B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v7.40 ANO4 Achchuthan Shanmugasundram Source NHS GMS was added to ANO4.
Source Expert Review Green was added to ANO4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v7.40 ADGRL1 Achchuthan Shanmugasundram Source NHS GMS was added to ADGRL1.
Source Expert Review Green was added to ADGRL1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v7.40 ACBD6 Achchuthan Shanmugasundram Source NHS GMS was added to ACBD6.
Source Expert Review Green was added to ACBD6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v7.40 ABCC9 Achchuthan Shanmugasundram Source NHS GMS was added to ABCC9.
Mode of inheritance for gene ABCC9 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v7.14 CIAO1 Sarah Leigh gene: CIAO1 was added
gene: CIAO1 was added to Intellectual disability. Sources: Literature,Expert Review Amber
Q3_24_promote_green, Q3_24_NHS_review tags were added to gene: CIAO1.
Mode of inheritance for gene: CIAO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CIAO1 were set to 38950322
Phenotypes for gene: CIAO1 were set to CIAO1 associated neuromuscular disorder
Intellectual disability v7.13 FIBP Sarah Leigh Tag Q3_24_promote_green tag was added to gene: FIBP.
Tag Q3_24_NHS_review tag was added to gene: FIBP.
Intellectual disability v7.2 ATXN7L3 Sarah Leigh Tag Q3_24_promote_green tag was added to gene: ATXN7L3.
Tag Q3_24_NHS_review tag was added to gene: ATXN7L3.
Tag Q3_24_MOI tag was added to gene: ATXN7L3.
Intellectual disability v6.75 MSL2 Achchuthan Shanmugasundram Tag Q3_24_NHS_review tag was added to gene: MSL2.
Intellectual disability v6.52 TBC1D7 Achchuthan Shanmugasundram Tag watchlist was removed from gene: TBC1D7.
Tag Q3_24_promote_green tag was added to gene: TBC1D7.
Tag Q3_24_NHS_review tag was added to gene: TBC1D7.
Intellectual disability v6.50 RNU4-2 Arina Puzriakova changed review comment from: Greene et al. 2024 (PMID: 38821540) reported on 73 unrelated cases with a neurodevelopmental disorder associated with heterozygous variants in the RNU4-2 gene, overlapping findings in PMID:38645094 (still currently in preprint). Participants were identified through their enrolment in various cohorts including the 100,000 Genomes Project, NHSE Genomic Medicine Service (GMS), and NIHR BioResource.

Almost all variants were acquired de novo, with the exception of one variant that was inherited from an affected mother and 16 probands with unknown inheritance due to lack of parental genotype data.
Variants cluster in two regions of RNU4-2 (n.62–70 and n.73–79) but the majority of cases harboured a recurrent variant, n.64_65insT.

Clinical presentation was predominantly characterised by intellectual disability, but other observed features include microcephaly, proportionate short stature, hypotonia, seizures and motor delay.; to: Greene et al. 2024 (PMID: 38821540) reported on 73 unrelated cases with a neurodevelopmental disorder associated with heterozygous variants in the RNU4-2 gene, overlapping findings in PMID: 38645094 (still currently in preprint). Participants were identified through their enrolment in various cohorts including the 100,000 Genomes Project, NHSE Genomic Medicine Service (GMS), and NIHR BioResource.

Almost all variants were acquired de novo, with the exception of one variant that was inherited from an affected mother and 16 probands with unknown inheritance due to lack of parental genotype data.
Variants cluster in two regions of RNU4-2 (n.62–70 and n.73–79) but the majority of cases harboured a recurrent variant, n.64_65insT.

Clinical presentation was predominantly characterised by intellectual disability, but other observed features include microcephaly, proportionate short stature, hypotonia, seizures and motor delay.
Intellectual disability v6.50 RNU4-2 Arina Puzriakova changed review comment from: Second paper by Greene et al. 2024 (PMID: 38821540) reported on 73 unrelated cases with a neurodevelopmental disorder associated with heterozygous variants in the RNU4-2 gene, overlapping findings with the PMID: 38645094 paper (still currently in preprint). Participants were identified through their enrolment in various cohorts including the 100,000 Genomes Project, NHSE Genomic Medicine Service (GMS), and NIHR BioResource.

Almost all variants were acquired de novo, with the exception of one variant that was inherited from an affected mother and 16 probands with unknown inheritance due to lack of parental genotype data.
Variants cluster in two regions of RNU4-2 (n.62–70 and n.73–79) but the majority of cases harboured a recurrent variant, n.64_65insT.

Clinical presentation was predominantly characterised by intellectual disability, but other observed features include microcephaly, proportionate short stature, hypotonia, seizures and motor delay.; to: Greene et al. 2024 (PMID: 38821540) reported on 73 unrelated cases with a neurodevelopmental disorder associated with heterozygous variants in the RNU4-2 gene, overlapping findings in PMID:38645094 (still currently in preprint). Participants were identified through their enrolment in various cohorts including the 100,000 Genomes Project, NHSE Genomic Medicine Service (GMS), and NIHR BioResource.

Almost all variants were acquired de novo, with the exception of one variant that was inherited from an affected mother and 16 probands with unknown inheritance due to lack of parental genotype data.
Variants cluster in two regions of RNU4-2 (n.62–70 and n.73–79) but the majority of cases harboured a recurrent variant, n.64_65insT.

Clinical presentation was predominantly characterised by intellectual disability, but other observed features include microcephaly, proportionate short stature, hypotonia, seizures and motor delay.
Intellectual disability v6.40 SOX9 Sarah Leigh Tag Q2_24_demote_amber tag was added to gene: SOX9.
Tag Q2_24_NHS_review tag was added to gene: SOX9.
Intellectual disability v6.18 ITSN1 Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: ITSN1.
Tag Q2_24_NHS_review tag was added to gene: ITSN1.
Intellectual disability v6.12 MAST3 Sarah Leigh Tag Q2_24_NHS_review tag was added to gene: MAST3.
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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 v6.5 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 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 v5.531 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 v5.520 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 v5.519 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 v5.499 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 v5.492 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 v5.485 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 v5.449 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 v5.446 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 v5.411 KCNA3 Achchuthan Shanmugasundram Tag Q1_24_NHS_review tag was added to gene: KCNA3.
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 v5.410 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 v5.380 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 v5.355 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 v5.353 ACACA Sarah Leigh Tag Q4_23_NHS_review was removed from gene: ACACA.
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 v5.335 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 v5.326 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 v5.323 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 v5.305 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 v5.300 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 v5.299 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 v5.294 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 ITPR1 Arina Puzriakova Tag Q2_23_MOI was removed from gene: ITPR1.
Tag Q2_23_NHS_review was removed from gene: ITPR1.
Intellectual disability v5.286 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 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 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 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 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 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 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 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 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 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 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 v5.281 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 v5.277 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 v5.275 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 v5.267 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 v5.260 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 v5.128 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 v5.25 KDM5A Achchuthan Shanmugasundram Tag Q2_23_NHS_review tag was added to gene: KDM5A.
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene has sufficient evidence (four unrelated cases) to be promoted to GREEN at the next NHS GMS review.
Intellectual disability v4.118 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene has sufficient evidence (four unrelated cases) to be promoted to GREEN at the next NHS GMS review.
Intellectual disability v4.118 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene has sufficient evidence (four unrelated cases) to be promoted to GREEN at the next NHS GMS review.
Intellectual disability v4.118 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene has sufficient evidence (four unrelated cases) to be promoted to GREEN at the next NHS GMS review.
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene has sufficient evidence (four unrelated cases) to be promoted to GREEN at the next NHS GMS review.
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene has sufficient evidence (four unrelated cases) to be promoted to GREEN at the next NHS GMS review.
Intellectual disability v4.118 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene has sufficient evidence (four unrelated cases) to be promoted to GREEN at the next NHS GMS review.
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene has sufficient evidence (four unrelated cases) to be promoted to GREEN at the next NHS GMS review.
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene has sufficient evidence (four unrelated cases) to be promoted to GREEN at the next NHS GMS review.
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene has sufficient evidence (four unrelated cases) to be promoted to GREEN at the next NHS GMS review.
Intellectual disability v4.117 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene has sufficient evidence (four unrelated cases) to be promoted to GREEN at the next NHS GMS review.
Intellectual disability v4.54 ISCA-37423-Loss Arina Puzriakova edited their review of Region: ISCA-37423-Loss: Added comment: Following Genomics England clinical review and NHS Genomic Medicine Service approval, the genomic coordinates of this region were updated based on ClinGen Region Curation Results (version on 05 Aug 2022).; Changed rating: GREEN
Intellectual disability v4.54 ISCA-37423-Gain Arina Puzriakova edited their review of Region: ISCA-37423-Gain: Added comment: Following Genomics England clinical review and NHS Genomic Medicine Service approval, the genomic coordinates and triplosensitivity score (from 3 to 2) of this region were updated based on ClinGen Region Curation Results (version on 05 Aug 2022). Regardless of the change in triplosensitivity score, it was deemed appropriate for this regions to remain green as evidence to support pathogenicity remains.; Changed rating: GREEN
Intellectual disability v4.53 CUX2 Arina Puzriakova Tag Q3_21_NHS_review was removed from gene: CUX2.
Intellectual disability v4.53 PRODH Arina Puzriakova Tag Q2_22_rating was removed from gene: PRODH.
Tag Q2_22_expert_review was removed from gene: PRODH.
Tag Q2_22_NHS_review was removed from gene: PRODH.
Intellectual disability v4.53 ZBTB7A Arina Puzriakova Tag Q2_22_rating was removed from gene: ZBTB7A.
Tag Q2_22_NHS_review was removed from gene: ZBTB7A.
Intellectual disability v4.53 THUMPD1 Arina Puzriakova Tag Q2_22_rating was removed from gene: THUMPD1.
Tag Q2_22_NHS_review was removed from gene: THUMPD1.
Intellectual disability v4.53 SNORD118 Arina Puzriakova Tag Q2_22_rating was removed from gene: SNORD118.
Tag Q2_22_NHS_review was removed from gene: SNORD118.
Intellectual disability v4.53 SCAF4 Arina Puzriakova Tag Q2_22_rating was removed from gene: SCAF4.
Tag Q2_22_NHS_review was removed from gene: SCAF4.
Intellectual disability v4.53 NAPB Arina Puzriakova Tag Q2_22_rating was removed from gene: NAPB.
Tag Q2_22_NHS_review was removed from gene: NAPB.
Intellectual disability v4.53 MED13 Arina Puzriakova Tag Q2_22_rating was removed from gene: MED13.
Tag Q2_22_NHS_review was removed from gene: MED13.
Intellectual disability v4.53 CELF2 Arina Puzriakova Tag Q2_22_rating was removed from gene: CELF2.
Tag Q2_22_NHS_review was removed from gene: CELF2.
Intellectual disability v4.53 ZMYM2 Arina Puzriakova Tag Q3_22_rating was removed from gene: ZMYM2.
Tag Q3_22_NHS_review was removed from gene: ZMYM2.
Intellectual disability v4.53 TAF8 Arina Puzriakova Tag Q3_22_rating was removed from gene: TAF8.
Tag Q3_22_NHS_review was removed from gene: TAF8.
Intellectual disability v4.53 STT3A Arina Puzriakova Tag Q3_22_MOI was removed from gene: STT3A.
Tag Q3_22_NHS_review was removed from gene: STT3A.
Intellectual disability v4.53 HK1 Arina Puzriakova Tag Q3_22_MOI was removed from gene: HK1.
Tag Q3_22_NHS_review was removed from gene: HK1.
Intellectual disability v4.53 DOCK8 Arina Puzriakova Tag Q3_22_rating was removed from gene: DOCK8.
Tag Q3_22_MOI was removed from gene: DOCK8.
Tag Q3_22_NHS_review was removed from gene: DOCK8.
Tag Q3_22_expert_review was removed from gene: DOCK8.
Intellectual disability v4.53 CUL3 Arina Puzriakova Tag Q3_22_rating was removed from gene: CUL3.
Tag Q3_22_NHS_review was removed from gene: CUL3.
Intellectual disability v4.53 ATP6V0A1 Arina Puzriakova Tag Q3_22_rating was removed from gene: ATP6V0A1.
Tag Q3_22_NHS_review was removed from gene: ATP6V0A1.
Intellectual disability v4.53 ANK3 Arina Puzriakova Tag Q3_22_rating was removed from gene: ANK3.
Tag Q3_22_MOI was removed from gene: ANK3.
Tag Q3_22_NHS_review was removed from gene: ANK3.
Intellectual disability v4.53 RAP1GDS1 Arina Puzriakova edited their review of gene: RAP1GDS1: Added comment: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Amber.; Changed rating: AMBER
Intellectual disability v4.53 SCAF4 Arina Puzriakova edited their review of gene: SCAF4: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v4.53 NAPB Arina Puzriakova edited their review of gene: NAPB: 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
Intellectual disability v4.53 KDM5C Arina Puzriakova commented on gene: KDM5C: The mode of inheritance of this gene has been updated 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.
Intellectual disability v4.53 HSPD1 Arina Puzriakova commented on gene: HSPD1: The mode of inheritance of this gene has been updated to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Intellectual disability v4.53 DHDDS Arina Puzriakova commented on gene: DHDDS: The mode of inheritance of this gene has been updated to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.
Intellectual disability v4.53 CELF2 Arina Puzriakova edited their review of gene: CELF2: 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
Intellectual disability v4.53 BSCL2 Arina Puzriakova commented on gene: BSCL2: The mode of inheritance of this gene has been updated to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Intellectual disability v4.53 ARHGEF9 Arina Puzriakova commented on gene: ARHGEF9: The mode of inheritance of this gene has been updated 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.
Intellectual disability v4.53 AP1S2 Arina Puzriakova commented on gene: AP1S2: The mode of inheritance of this gene has been updated 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.
Intellectual disability v4.53 AFF3 Arina Puzriakova edited their review of gene: AFF3: 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 rating: GREEN
Intellectual disability v4.53 ACER3 Arina Puzriakova commented on gene: ACER3: 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 v4.53 WNK3 Arina Puzriakova commented on gene: WNK3: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Intellectual disability v4.53 TAF8 Arina Puzriakova edited their review of gene: TAF8: 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
Intellectual disability v4.53 STT3A Arina Puzriakova commented on gene: STT3A: The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Intellectual disability v4.53 POLRMT Arina Puzriakova edited their review of gene: POLRMT: Added comment: 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.; Changed rating: GREEN
Intellectual disability v4.53 OGDHL Arina Puzriakova edited their review of gene: OGDHL: 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
Intellectual disability v4.53 NSRP1 Arina Puzriakova edited their review of gene: NSRP1: 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
Intellectual disability v4.53 HMGB1 Arina Puzriakova edited their review of gene: HMGB1: 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
Intellectual disability v4.53 EDEM3 Arina Puzriakova edited their review of gene: EDEM3: 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
Intellectual disability v4.53 CUL3 Arina Puzriakova edited their review of gene: CUL3: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v4.53 BLOC1S1 Arina Puzriakova edited their review of gene: BLOC1S1: 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
Intellectual disability v4.53 ATG7 Arina Puzriakova edited their review of gene: ATG7: 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
Intellectual disability v4.53 ALKBH8 Arina Puzriakova commented on gene: ALKBH8: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Intellectual disability v4.52 ZMYM2 Arina Puzriakova Source NHS GMS was added to ZMYM2.
Source Expert Review Green was added to ZMYM2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 ZC4H2 Arina Puzriakova Source NHS GMS was added to ZC4H2.
Mode of inheritance for gene ZC4H2 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 v4.52 ZBTB7A Arina Puzriakova Source NHS GMS was added to ZBTB7A.
Source Expert Review Green was added to ZBTB7A.
Mode of inheritance for gene ZBTB7A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 WNK3 Arina Puzriakova Source NHS GMS was added to WNK3.
Source Expert Review Green was added to WNK3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 TPP2 Arina Puzriakova Source NHS GMS was added to TPP2.
Source Expert Review Green was added to TPP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 TMEM63C Arina Puzriakova Source NHS GMS was added to TMEM63C.
Source Expert Review Green was added to TMEM63C.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 TIAM1 Arina Puzriakova Source NHS GMS was added to TIAM1.
Source Expert Review Green was added to TIAM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 THUMPD1 Arina Puzriakova Source NHS GMS was added to THUMPD1.
Source Expert Review Green was added to THUMPD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 TAF8 Arina Puzriakova Source NHS GMS was added to TAF8.
Source Expert Review Green was added to TAF8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 STT3A Arina Puzriakova Source NHS GMS was added to STT3A.
Mode of inheritance for gene STT3A was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v4.52 SRRM2 Arina Puzriakova Source NHS GMS was added to SRRM2.
Source Expert Review Green was added to SRRM2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 SPRED2 Arina Puzriakova Source NHS GMS was added to SPRED2.
Source Expert Review Green was added to SPRED2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 SPATA5L1 Arina Puzriakova Source NHS GMS was added to SPATA5L1.
Source Expert Review Green was added to SPATA5L1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 SNORD118 Arina Puzriakova Source NHS GMS was added to SNORD118.
Source Expert Review Green was added to SNORD118.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 SLC38A3 Arina Puzriakova Source NHS GMS was added to SLC38A3.
Source Expert Review Green was added to SLC38A3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 SLC12A5 Arina Puzriakova Source NHS GMS was added to SLC12A5.
Mode of inheritance for gene SLC12A5 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.52 SCAF4 Arina Puzriakova Source NHS GMS was added to SCAF4.
Source Expert Review Green was added to SCAF4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 RAB11A Arina Puzriakova Source NHS GMS was added to RAB11A.
Source Expert Review Green was added to RAB11A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 PRPF8 Arina Puzriakova Source NHS GMS was added to PRPF8.
Source Expert Review Green was added to PRPF8.
Mode of inheritance for gene PRPF8 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 PRODH Arina Puzriakova Source Expert Review Amber was added to PRODH.
Source NHS GMS was added to PRODH.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Intellectual disability v4.52 PRDM13 Arina Puzriakova Source NHS GMS was added to PRDM13.
Source Expert Review Green was added to PRDM13.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 PHF14 Arina Puzriakova Source NHS GMS was added to PHF14.
Intellectual disability v4.52 PEX6 Arina Puzriakova Source NHS GMS was added to PEX6.
Mode of inheritance for gene PEX6 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v4.52 PDZD8 Arina Puzriakova Source NHS GMS was added to PDZD8.
Source Expert Review Green was added to PDZD8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 OGDHL Arina Puzriakova Source NHS GMS was added to OGDHL.
Source Expert Review Green was added to OGDHL.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 NSRP1 Arina Puzriakova Source NHS GMS was added to NSRP1.
Source Expert Review Green was added to NSRP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 NRCAM Arina Puzriakova Source NHS GMS was added to NRCAM.
Source Expert Review Green was added to NRCAM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 MED13 Arina Puzriakova Source NHS GMS was added to MED13.
Source Expert Review Green was added to MED13.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 KDM5C Arina Puzriakova Source NHS GMS was added to KDM5C.
Mode of inheritance for gene KDM5C was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v4.52 HSPD1 Arina Puzriakova Source NHS GMS was added to HSPD1.
Mode of inheritance for gene HSPD1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.52 HMGB1 Arina Puzriakova Source NHS GMS was added to HMGB1.
Source Expert Review Green was added to HMGB1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 HK1 Arina Puzriakova Source NHS GMS was added to HK1.
Mode of inheritance for gene HK1 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v4.52 GLRA2 Arina Puzriakova Source NHS GMS was added to GLRA2.
Source Expert Review Green was added to GLRA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 FBXW7 Arina Puzriakova Source NHS GMS was added to FBXW7.
Source Expert Review Green was added to FBXW7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 FBXO28 Arina Puzriakova Source NHS GMS was added to FBXO28.
Source Expert Review Green was added to FBXO28.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 EMC1 Arina Puzriakova Source NHS GMS was added to EMC1.
Mode of inheritance for gene EMC1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v4.52 EDEM3 Arina Puzriakova Source NHS GMS was added to EDEM3.
Source Expert Review Green was added to EDEM3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 DTYMK Arina Puzriakova Source NHS GMS was added to DTYMK.
Source Expert Review Green was added to DTYMK.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 DROSHA Arina Puzriakova Source NHS GMS was added to DROSHA.
Intellectual disability v4.52 DOCK8 Arina Puzriakova Source Expert Review Amber was added to DOCK8.
Source NHS GMS was added to DOCK8.
Mode of inheritance for gene DOCK8 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Intellectual disability v4.52 DHDDS Arina Puzriakova Source NHS GMS was added to DHDDS.
Mode of inheritance for gene DHDDS was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v4.52 CUL3 Arina Puzriakova Source NHS GMS was added to CUL3.
Source Expert Review Green was added to CUL3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 COG5 Arina Puzriakova Source NHS GMS was added to COG5.
Mode of inheritance for gene COG5 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.52 CHKA Arina Puzriakova Source NHS GMS was added to CHKA.
Source Expert Review Green was added to CHKA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 CELF2 Arina Puzriakova Source NHS GMS was added to CELF2.
Source Expert Review Green was added to CELF2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 CCDC32 Arina Puzriakova Source NHS GMS was added to CCDC32.
Source Expert Review Green was added to CCDC32.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 CACNA2D1 Arina Puzriakova Source NHS GMS was added to CACNA2D1.
Source Expert Review Green was added to CACNA2D1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 CACNA1A Arina Puzriakova Source NHS GMS was added to CACNA1A.
Mode of inheritance for gene CACNA1A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v4.52 BSCL2 Arina Puzriakova Source NHS GMS was added to BSCL2.
Mode of inheritance for gene BSCL2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.52 BLOC1S1 Arina Puzriakova Source NHS GMS was added to BLOC1S1.
Source Expert Review Green was added to BLOC1S1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 ATP6V0A1 Arina Puzriakova Source NHS GMS was added to ATP6V0A1.
Source Expert Review Green was added to ATP6V0A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 ATP2B1 Arina Puzriakova Source NHS GMS was added to ATP2B1.
Source Expert Review Green was added to ATP2B1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 ATG7 Arina Puzriakova Source NHS GMS was added to ATG7.
Source Expert Review Green was added to ATG7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 ARHGEF9 Arina Puzriakova Source NHS GMS was added to ARHGEF9.
Mode of inheritance for gene ARHGEF9 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 v4.52 AP1S2 Arina Puzriakova Source NHS GMS was added to AP1S2.
Mode of inheritance for gene AP1S2 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 v4.52 ANK3 Arina Puzriakova Source NHS GMS was added to ANK3.
Source Expert Review Green was added to ANK3.
Mode of inheritance for gene ANK3 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 ALKBH8 Arina Puzriakova Source NHS GMS was added to ALKBH8.
Source Expert Review Green was added to ALKBH8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 AFF3 Arina Puzriakova Source NHS GMS was added to AFF3.
Source Expert Review Green was added to AFF3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 ADD1 Arina Puzriakova Source NHS GMS was added to ADD1.
Source Expert Review Green was added to ADD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 ACO2 Arina Puzriakova Source NHS GMS was added to ACO2.
Mode of inheritance for gene ACO2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v4.52 ACER3 Arina Puzriakova Source NHS GMS was added to ACER3.
Source Expert Review Green was added to ACER3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.51 KDM2B Mike Spiller gene: KDM2B was added
gene: KDM2B was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: KDM2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KDM2B were set to PMID: 36322151; 35128353; 35710456
Review for gene: KDM2B was set to GREEN
Added comment: van Jaarsveld et al 2022 PMID: 36322151

Majority of variants are missense, strong evidence for hotspot in CXXC domain.(7 different de Novo missenses + 1 de Novo in frame del. Same inframe del also found de novo in NHS GMS patient. All absent from gnomAD, region highly constrained).

Also 3 LOF SNVs and 3 patients with deletions including this gene, although not all are de novo and most also have potential alternate causes.

All have developmental delay. Almost all have intellectual disability ranging from mild to moderate, speech delay common..7 with cardiac abnormalities, 4 with kidney abnormalities.

Also 2 variants published in this region in PMID: 35710456, 35904121.

KDM2B methylation episignature recorded. CXXC variants show strong clustering, highly distinct from control dataset. LOF variants (including dels) also reported to show distinct episignature from controls, and from CXXC variants. While the data supports a KDM2B LOF episignature, this is not as clear, and may not be as specific, as the CXXC signature.

Mouse model also supports importance of CXXC domain, with mice heterozygous for CXXC-deleted KDM2B showing neurological defects (PMID: 35128353).

Evidence very strong for CXXC missenses less clear for haploinsufficiency.

Overall sufficient evidence from cases and episignature evidence to include as green for ID.
Sources: Literature
Intellectual disability v4.33 ZNF292 Sarah Leigh Tag Q1_23_promote_green tag was added to gene: ZNF292.
Tag Q1_23_NHS_review tag was added to gene: ZNF292.
Intellectual disability v4.32 PAX6 Sarah Leigh Tag Q1_23_demote_red tag was added to gene: PAX6.
Tag Q1_23_NHS_review tag was added to gene: PAX6.
Intellectual disability v4.9 SUFU Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update under a MONOALLELIC inheritance pattern only, unless the NHS GMS working group disagree and feel the MOI should include both mono- and biallelic variants based on the current evidence.
Intellectual disability v3.1743 ROR2 Arina Puzriakova Tag Q4_22_demote_red tag was added to gene: ROR2.
Tag Q4_22_NHS_review tag was added to gene: ROR2.
Intellectual disability v3.1729 HK1 Eleanor Williams Tag Q3_22_MOI tag was added to gene: HK1.
Tag Q3_22_NHS_review tag was added to gene: HK1.
Intellectual disability v3.1716 ANK3 Sarah Leigh Tag Q2_22_MOI tag was added to gene: ANK3.
Tag Q3_22_rating tag was added to gene: ANK3.
Tag Q3_22_NHS_review tag was added to gene: ANK3.
Intellectual disability v3.1711 DOCK8 Sarah Leigh Tag Q3_22_rating tag was added to gene: DOCK8.
Tag Q3_22_MOI tag was added to gene: DOCK8.
Tag Q3_22_NHS_review tag was added to gene: DOCK8.
Tag Q3_22_expert_review tag was added to gene: DOCK8.
Intellectual disability v3.1660 STT3A Arina Puzriakova Tag Q3_22_NHS_review tag was added to gene: STT3A.
Intellectual disability v3.1656 TAF8 Arina Puzriakova Tag Q3_22_NHS_review tag was added to gene: TAF8.
Intellectual disability v3.1638 POLRMT Arina Puzriakova gene: POLRMT was added
gene: POLRMT was added to Intellectual disability. Sources: NHS GMS,Expert Review Amber
Q3_22_rating tags were added to gene: POLRMT.
Mode of inheritance for gene: POLRMT was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: POLRMT were set to 24386581; 33602924
Phenotypes for gene: POLRMT were set to Combined oxidative phosphorylation deficiency 55, OMIM:619743
Intellectual disability v3.1609 ATP6V0A1 Sarah Leigh Tag Q3_22_rating tag was added to gene: ATP6V0A1.
Tag Q3_22_NHS_review tag was added to gene: ATP6V0A1.
Intellectual disability v3.1600 ZMYM2 Sarah Leigh Tag Q3_22_rating tag was added to gene: ZMYM2.
Tag Q3_22_NHS_review tag was added to gene: ZMYM2.
Intellectual disability v3.1599 CUL3 Sarah Leigh Tag Q3_22_rating tag was added to gene: CUL3.
Tag Q3_22_NHS_review tag was added to gene: CUL3.
Intellectual disability v3.1590 MED13 Catherine Snow Tag Q2_22_rating tag was added to gene: MED13.
Tag Q2_22_NHS_review tag was added to gene: MED13.
Intellectual disability v3.1582 SNORD118 Sarah Leigh Tag Q2_22_rating tag was added to gene: SNORD118.
Tag Q2_22_NHS_review tag was added to gene: SNORD118.
Intellectual disability v3.1581 SCAF4 Sarah Leigh Tag watchlist was removed from gene: SCAF4.
Tag Q2_22_rating tag was added to gene: SCAF4.
Tag Q2_22_NHS_review tag was added to gene: SCAF4.
Intellectual disability v3.1578 PRODH Sarah Leigh Tag Q2_22_NHS_review tag was added to gene: PRODH.
Intellectual disability v3.1574 THUMPD1 Sarah Leigh Tag Q2_22_rating tag was added to gene: THUMPD1.
Tag Q2_22_NHS_review tag was added to gene: THUMPD1.
Intellectual disability v3.1571 ZBTB7A Sarah Leigh Tag Q2_22_rating tag was added to gene: ZBTB7A.
Tag Q2_22_NHS_review tag was added to gene: ZBTB7A.
Intellectual disability v3.1570 CELF2 Arina Puzriakova Tag Q2_22_rating tag was added to gene: CELF2.
Tag Q2_22_NHS_review tag was added to gene: CELF2.
Intellectual disability v3.1541 NAPB Arina Puzriakova gene: NAPB was added
gene: NAPB was added to Intellectual disability. Sources: Expert Review Amber,NHS GMS
Q2_22_rating, Q2_22_NHS_review tags were added to gene: NAPB.
Mode of inheritance for gene: NAPB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAPB were set to 28097321; 33189936; 26235277; 21040848
Phenotypes for gene: NAPB were set to Early infantile epileptic encephalopathy
Penetrance for gene: NAPB were set to unknown
Intellectual disability v3.1519 FAR1 Sarah Leigh Tag to_be_confirmed_NHSE tag was added to gene: FAR1.
Intellectual disability v3.1519 SMARCA5 Ivone Leong Tag Q2_21_rating was removed from gene: SMARCA5.
Tag Q2_21_NHS_review was removed from gene: SMARCA5.
Intellectual disability v3.1519 HNMT Ivone Leong Tag Q3_21_rating was removed from gene: HNMT.
Tag Q3_21_NHS_review was removed from gene: HNMT.
Intellectual disability v3.1519 ERBB4 Ivone Leong Tag Q2_21_rating was removed from gene: ERBB4.
Tag Q2_21_NHS_review was removed from gene: ERBB4.
Intellectual disability v3.1519 UFSP2 Sarah Leigh commented on gene: UFSP2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1519 TMEM222 Sarah Leigh commented on gene: TMEM222: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1519 SPTBN1 Sarah Leigh commented on gene: SPTBN1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1519 SNIP1 Sarah Leigh commented on gene: SNIP1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1519 SCYL1 Sarah Leigh commented on gene: SCYL1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1519 PCDHGC4 Sarah Leigh commented on gene: PCDHGC4: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1519 ERBB4 Sarah Leigh commented on gene: ERBB4: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1519 CEP85L Sarah Leigh commented on gene: CEP85L: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1519 ATP9A Sarah Leigh commented on gene: ATP9A: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1519 AGO1 Sarah Leigh commented on gene: AGO1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1519 AFG3L2 Sarah Leigh commented on gene: AFG3L2: The mode of inheritance of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1519 POLR3B Ivone Leong Source NHS GMS was added to POLR3B.
Mode of inheritance for gene POLR3B was changed from BIALLELIC, autosomal or pseudoautosomal to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v3.1519 PHF6 Ivone Leong Source NHS GMS was added to PHF6.
Mode of inheritance for gene PHF6 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 v3.1519 MED12 Ivone Leong Source NHS GMS was added to MED12.
Mode of inheritance for gene MED12 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 v3.1519 HCCS Ivone Leong Source NHS GMS was added to HCCS.
Mode of inheritance for gene HCCS 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 v3.1519 GRIK2 Ivone Leong Source NHS GMS was added to GRIK2.
Mode of inheritance for gene GRIK2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v3.1519 CLPB Ivone Leong Source NHS GMS was added to CLPB.
Mode of inheritance for gene CLPB was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v3.1519 AFG3L2 Ivone Leong Source NHS GMS was added to AFG3L2.
Intellectual disability v3.1515 PPP2R2B_CAG Arina Puzriakova Normal Number of Repeats for PPP2R2B_CAG was changed from 32 to 33.
Pathogenic Number of Repeats for PPP2R2B_CAG was changed from 51 to 43.
Source NHS GMS was added to STR: PPP2R2B_CAG.
Intellectual disability v3.1515 FXN_GAA Arina Puzriakova Source NHS GMS was added to STR: FXN_GAA.
Intellectual disability v3.1515 FMR1_CGG Arina Puzriakova Source NHS GMS was added to STR: FMR1_CGG.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Intellectual disability v3.1515 DMPK_CTG Arina Puzriakova Normal Number of Repeats for DMPK_CTG was changed from 38 to 35.
Source NHS GMS was added to STR: DMPK_CTG.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Intellectual disability v3.1515 CSTB_CCCCGCCCCGCG Arina Puzriakova Normal Number of Repeats for CSTB_CCCCGCCCCGCG was changed from 30 to 18.
Source NHS GMS was added to STR: CSTB_CCCCGCCCCGCG.
Intellectual disability v3.1515 C9orf72_GGGGCC Arina Puzriakova Normal Number of Repeats for C9orf72_GGGGCC was changed from 30 to 24.
Pathogenic Number of Repeats for C9orf72_GGGGCC was changed from 30 to 200.
Source NHS GMS was added to STR: C9orf72_GGGGCC.
Intellectual disability v3.1515 ATXN7_CAG Arina Puzriakova Normal Number of Repeats for ATXN7_CAG was changed from 34 to 28.
Pathogenic Number of Repeats for ATXN7_CAG was changed from 36 to 37.
Source NHS GMS was added to STR: ATXN7_CAG.
Intellectual disability v3.1515 ATXN3_CAG Arina Puzriakova Normal Number of Repeats for ATXN3_CAG was changed from 44 to 45.
Source NHS GMS was added to STR: ATXN3_CAG.
Intellectual disability v3.1515 ATXN2_CAG Arina Puzriakova Normal Number of Repeats for ATXN2_CAG was changed from 31 to 32.
Pathogenic Number of Repeats for ATXN2_CAG was changed from 33 to 35.
Source NHS GMS was added to STR: ATXN2_CAG.
Intellectual disability v3.1515 ATXN10_ATTCT Arina Puzriakova Normal Number of Repeats for ATXN10_ATTCT was changed from 32 to 33.
Source NHS GMS was added to STR: ATXN10_ATTCT.
Intellectual disability v3.1515 ATXN1_CAG Arina Puzriakova Normal Number of Repeats for ATXN1_CAG was changed from 35 to 36.
Pathogenic Number of Repeats for ATXN1_CAG was changed from 44 to 45.
Source NHS GMS was added to STR: ATXN1_CAG.
Intellectual disability v3.1510 CACNB4 Sarah Leigh commented on gene: CACNB4: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed
Intellectual disability v3.1510 CNOT3 Sarah Leigh commented on gene: CNOT3: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed
Intellectual disability v3.1510 ZNF335 Sarah Leigh commented on gene: ZNF335: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed
Intellectual disability v3.1510 MFSD2A Sarah Leigh commented on gene: MFSD2A: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed
Intellectual disability v3.1510 MAPRE2 Sarah Leigh commented on gene: MAPRE2: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed
Intellectual disability v3.1510 SCAMP5 Sarah Leigh commented on gene: SCAMP5: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed
Intellectual disability v3.1510 KAT8 Sarah Leigh commented on gene: KAT8: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed
Intellectual disability v3.1510 GPC4 Sarah Leigh commented on gene: GPC4: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed
Intellectual disability v3.1510 KDM6B Sarah Leigh commented on gene: KDM6B: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed
Intellectual disability v3.1510 CDK19 Sarah Leigh commented on gene: CDK19: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed
Intellectual disability v3.1510 EXT2 Sarah Leigh commented on gene: EXT2: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed
Intellectual disability v3.1510 TOR1A Sarah Leigh commented on gene: TOR1A: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed
Intellectual disability v3.1510 LMBRD2 Sarah Leigh commented on gene: LMBRD2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 ALG14 Sarah Leigh commented on gene: ALG14: After NHSGenomic Medicine Service consideration, the rating of this gene has not been changed.
Intellectual disability v3.1510 SLC12A6 Sarah Leigh commented on gene: SLC12A6: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed
Intellectual disability v3.1510 COG4 Sarah Leigh commented on gene: COG4: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed
Intellectual disability v3.1510 SCN8A Sarah Leigh commented on gene: SCN8A: Just 2 families reported with possible AR inheritance: v rare - all het parents seem to have features so prob ok to keep as monoallelic only (source NHS Genomic Medicine Service).
Intellectual disability v3.1510 SCN8A Sarah Leigh commented on gene: SCN8A: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed
Intellectual disability v3.1510 AGO2 Sarah Leigh commented on gene: AGO2: Green rating is for monoallelic MOI only, many cases reported with speech delay and variable ID (source NHS Genomic Medicine Service).
Intellectual disability v3.1510 FA2H Sarah Leigh commented on gene: FA2H: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 MGP Sarah Leigh commented on gene: MGP: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 LGI4 Sarah Leigh commented on gene: LGI4: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 ATL1 Sarah Leigh commented on gene: ATL1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 ANKH Sarah Leigh commented on gene: ANKH: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 AFG3L2 Sarah Leigh commented on gene: AFG3L2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 LMNB1 Sarah Leigh commented on gene: LMNB1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 TFE3 Sarah Leigh commented on gene: TFE3: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 PIGQ Sarah Leigh commented on gene: PIGQ: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 SETD1A Sarah Leigh commented on gene: SETD1A: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 CDH2 Sarah Leigh commented on gene: CDH2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 PUM1 Sarah Leigh commented on gene: PUM1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 RALGAPA1 Sarah Leigh commented on gene: RALGAPA1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 RARS Sarah Leigh commented on gene: RARS: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 SLC5A6 Sarah Leigh commented on gene: SLC5A6: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 SNX27 Sarah Leigh commented on gene: SNX27: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 TTC5 Sarah Leigh commented on gene: TTC5: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 TET3 Sarah Leigh commented on gene: TET3: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 SUZ12 Sarah Leigh commented on gene: SUZ12: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 SOX6 Sarah Leigh commented on gene: SOX6: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 SLC1A1 Sarah Leigh commented on gene: SLC1A1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 SFXN4 Sarah Leigh commented on gene: SFXN4: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 SBF1 Sarah Leigh commented on gene: SBF1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 SARS2 Sarah Leigh commented on gene: SARS2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 RSRC1 Sarah Leigh commented on gene: RSRC1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 PIGS Sarah Leigh commented on gene: PIGS: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 PIGK Sarah Leigh commented on gene: PIGK: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 OXR1 Sarah Leigh commented on gene: OXR1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 NRROS Sarah Leigh commented on gene: NRROS: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 NOVA2 Sarah Leigh commented on gene: NOVA2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 MTHFS Sarah Leigh commented on gene: MTHFS: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 GALNT2 Sarah Leigh commented on gene: GALNT2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 EARS2 Sarah Leigh commented on gene: EARS2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 CNTNAP1 Sarah Leigh commented on gene: CNTNAP1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 B9D2 Sarah Leigh commented on gene: B9D2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 ADARB1 Sarah Leigh commented on gene: ADARB1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 RNF113A Sarah Leigh commented on gene: RNF113A: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 GAD1 Sarah Leigh commented on gene: GAD1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 ALG9 Sarah Leigh commented on gene: ALG9: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 CDK19 Sarah Leigh commented on gene: CDK19: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 AHCY Sarah Leigh commented on gene: AHCY: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 PIGP Sarah Leigh commented on gene: PIGP: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 RNF13 Sarah Leigh commented on gene: RNF13: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 C2CD3 Sarah Leigh commented on gene: C2CD3: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 ATP1A2 Sarah Leigh commented on gene: ATP1A2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 ABAT Sarah Leigh commented on gene: ABAT: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1510 ADAM22 Sarah Leigh commented on gene: ADAM22: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Intellectual disability v3.1509 CACNB4 Arina Puzriakova Source NHS GMS was added to CACNB4.
Intellectual disability v3.1509 CNOT3 Arina Puzriakova Source NHS GMS was added to CNOT3.
Intellectual disability v3.1509 ZNF335 Arina Puzriakova Source NHS GMS was added to ZNF335.
Intellectual disability v3.1509 MFSD2A Arina Puzriakova Source NHS GMS was added to MFSD2A.
Intellectual disability v3.1509 MAPRE2 Arina Puzriakova Source NHS GMS was added to MAPRE2.
Intellectual disability v3.1509 SCN1B Arina Puzriakova Source NHS GMS was added to SCN1B.
Intellectual disability v3.1509 SCAMP5 Arina Puzriakova Source NHS GMS was added to SCAMP5.
Intellectual disability v3.1509 KAT8 Arina Puzriakova Source NHS GMS was added to KAT8.
Intellectual disability v3.1509 GPC4 Arina Puzriakova Source NHS GMS was added to GPC4.
Intellectual disability v3.1509 KDM6B Arina Puzriakova Source NHS GMS was added to KDM6B.
Intellectual disability v3.1509 CDK19 Arina Puzriakova Source NHS GMS was added to CDK19.
Intellectual disability v3.1509 EXT2 Arina Puzriakova Source NHS GMS was added to EXT2.
Intellectual disability v3.1509 TOR1A Arina Puzriakova Source NHS GMS was added to TOR1A.
Intellectual disability v3.1227 HNMT Ivone Leong Tag watchlist was removed from gene: HNMT.
Tag Q3_21_rating tag was added to gene: HNMT.
Tag Q3_21_NHS_review tag was added to gene: HNMT.
Intellectual disability v3.1195 CEP85L Rachel Challis gene: CEP85L was added
gene: CEP85L was added to Intellectual disability. Sources: NHS GMS
Mode of inheritance for gene: CEP85L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CEP85L were set to 32097629; 32097630
Phenotypes for gene: CEP85L were set to Intellectual disability; epilepsy, lissencephaly
Penetrance for gene: CEP85L were set to unknown
Review for gene: CEP85L was set to GREEN
gene: CEP85L was marked as current diagnostic
Added comment: Recommend adding as Green gene to GMS - R29 Intellectual disability panel.

Monoallelic missense and loss of function variants in CEP85L are associated with Lissencephaly (OMIM 618873). Over 10 unrelated families have been described with de novo and inherited rare variants in CEP85L. Functional work in cell lines and knockdown of Cep85l in mice confirms the role of CEP85L in neuronal migration.
PMID: 32097629
PMID: 32097630
Sources: NHS GMS
Intellectual disability v3.1164 CUX2 Arina Puzriakova Tag Q3_21_NHS_review tag was added to gene: CUX2.
Intellectual disability v3.1117 SMARCA5 Arina Puzriakova Tag Q2_21_rating tag was added to gene: SMARCA5.
Tag Q2_21_NHS_review tag was added to gene: SMARCA5.
Intellectual disability v3.1117 SMARCA5 Arina Puzriakova Added comment: Comment on list classification: New gene added and reviewed Green by Julia Baptista (RD&E NHS FT). SMARCA5 should be promoted to Green at the next GMS panel update.

Variants have been associated with a variable neurodevelopmental phenotype including predominantly mild DD, short stature, and microcephaly (PMID:33980485). Regarding cognition, four probands had mild ID and one had severe ID. Although relatively mild in most patients, the number of unrelated families presenting ID is sufficient for a Green rating and inclusion on this panel should increase the likelihood of detecting cases.
Intellectual disability v3.963 ERBB4 Arina Puzriakova Tag Q2_21_NHS_review tag was added to gene: ERBB4.
Intellectual disability v3.483 PIGP Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).
Intellectual disability v3.482 PUM1 Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).
Intellectual disability v3.481 RALGAPA1 Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).
Intellectual disability v3.480 RARS Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).
Intellectual disability v3.479 RNF113A Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).
Intellectual disability v3.478 RNF13 Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).
Intellectual disability v3.477 GAD1 Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).
Intellectual disability v3.476 CEP55 Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).
Intellectual disability v3.475 CTU2 Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).
Intellectual disability v3.474 ALG9 Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).
Intellectual disability v3.473 EXT2 Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).
Intellectual disability v3.472 PTRHD1 Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).
Intellectual disability v3.471 TRAPPC4 Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).
Intellectual disability v3.470 UGP2 Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).
Intellectual disability v3.469 CXorf56 Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).
Intellectual disability v3.468 KAT8 Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).
Intellectual disability v3.467 SLC5A6 Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).
Intellectual disability v3.466 SNX27 Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).
Intellectual disability v3.465 WNT1 Arina Puzriakova Added comment: Comment on list classification: Changed rating to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).
Intellectual disability v3.464 PIGK Arina Puzriakova Added comment: Comment on list classification: Changed rating to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).
Intellectual disability v3.459 ALG14 Arina Puzriakova Added comment: Comment on list classification: Changed rating to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update.
Intellectual disability v3.114 SIX1 Sarah Leigh Publications for gene: SIX1 were set to 25529582; Version 12 ukgtn.nhs.uk
Intellectual disability v2.530 TUBA8 Rebecca Foulger Added comment: Comment on list classification: Demoted from Green to Amber based on re-review of evidence. Demotion agreed by Clinical Fellow Helen Brittain.

TUBA8 was originally rated Green on the panel because TUBA8 is a confirmed DD-G2P gene for 'POLYMICROGYRIA WITH OPTIC NERVE HYPOPLASIA' (the former name for Cortical dysplasia, complex, with other brain malformations 8, 613180) and TUBA8 is on the UKGTN 43 gene panel for brain malformations:
https://ukgtn.nhs.uk/find-a-test/search-by-disorder-gene/brain-malformation-disorders-cortical-43-gene-panel-886/.

However, the reported evidence comes from one 2009 paper (PMID:19896110) with 4 literature cases coming from 2 consaguineous families (1 variant); at least PMID:25008804 questions whether the families are related. A 2017 paper identifies an additional VUS (compound heterozygous) in a chinese EE patient (PMID:29588952).

Anna de Burca confirmed that there are lots of cases with CNVs involving TUBA8 in DECIPHER but there are only two cases with SNVs in the gene. One of them is classified as unknown pathogenicity, the other likely benign.

I contacted Usha Kini at Oxford, and also the Leeds and Cardiff genetic testing groups (as recommended by Usha) since they all offer cortical malformation panels. All three confirmed (pers. comm. via email) that they have no further cases for TUBA8.

The literature evidence and communications from Oxford, Leeds and Cardiff all support demotion of TUBA8 to Amber rating: The phenotype is still appropriate for the panel but insufficient cases for diagnostic rating.

Added 'watchlist' tag to look out for further cases.
Intellectual disability v2.468 NHS Louise Daugherty Source Victorian Clinical Genetics Services was added to NHS.
Intellectual disability v2.458 KDM1A Louise Daugherty edited their review of gene: KDM1A: Added comment: Recommendation that this gene should be Green. Three patients https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4902791/, there is functional characterisation of the three described mutations https://www.ncbi.nlm.nih.gov/pubmed/27094131?dopt=Abstract and the patients seem to share a similar phenotype, which recapitulates features of other deleterious mutations in better-characterised lysine demethylase and chromatin remodelling genes. There is also a recurrent de novo variant p.Tyr831Cys which has been reported in two separate "autism spectrum" patients in large cohort studies. The gene is also extensively constrained against both missense and LOF variation in humans http://exac.broadinstitute.org/gene/ENSG00000004487. I think what's been reported so far is probably robust enough to use the gene clinically.Pers comm. Ian Berry (NHS Leeds Genetics Laboratory); Changed rating: GREEN
Intellectual disability v2.455 PHIP Louise Daugherty edited their review of gene: PHIP: Added comment: Recommendation that this gene should be Green based on recent publication PMID:29209020, more than 20 unrelated cases Pers comm. Ian Berry (NHS Leeds Genetics Laboratory); Changed rating: GREEN; Changed publications: 29209020, 23033978, 27900362; Changed phenotypes: Developmental delay, intellectual disability, obesity, and dysmorphic features, 617991; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability NHS BRIDGE consortium edited their review of NHS
Intellectual disability NHS BRIDGE consortium edited their review of NHS
Intellectual disability NHS BRIDGE consortium reviewed NHS