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Schwannoma v0.13 PRKAR1A Zornitza Stark Gene: prkar1a has been classified as Green List (High Evidence).
Schwannoma v0.13 NF2 Zornitza Stark Marked gene: NF2 as ready
Schwannoma v0.13 NF2 Zornitza Stark Gene: nf2 has been classified as Green List (High Evidence).
Schwannoma v0.13 NF1 Zornitza Stark Marked gene: NF1 as ready
Schwannoma v0.13 NF1 Zornitza Stark Gene: nf1 has been classified as Green List (High Evidence).
Schwannoma v0.13 LZTR1 Zornitza Stark Marked gene: LZTR1 as ready
Schwannoma v0.13 LZTR1 Zornitza Stark Gene: lztr1 has been classified as Green List (High Evidence).
Schwannoma v0.13 LZTR1 Zornitza Stark Publications for gene: LZTR1 were set to PMID: 24362817, 29517885
Thyroid Cancer v1.0 Zornitza Stark promoted panel to version 1.0
Thyroid Cancer v0.15 Zornitza Stark Panel status changed from internal to public
Wilms Tumour v1.0 Zornitza Stark promoted panel to version 1.0
Wilms Tumour v0.41 Zornitza Stark Panel status changed from internal to public
Wilms Tumour v0.40 TP53 Zornitza Stark Marked gene: TP53 as ready
Wilms Tumour v0.40 TP53 Zornitza Stark Gene: tp53 has been classified as Red List (Low Evidence).
Wilms Tumour v0.40 PIK3CA Zornitza Stark Marked gene: PIK3CA as ready
Wilms Tumour v0.40 PIK3CA Zornitza Stark Gene: pik3ca has been classified as Red List (Low Evidence).
Wilms Tumour v0.40 CTCF Zornitza Stark Marked gene: CTCF as ready
Wilms Tumour v0.40 CTCF Zornitza Stark Gene: ctcf has been classified as Red List (Low Evidence).
Wilms Tumour v0.40 CDC73 Zornitza Stark Marked gene: CDC73 as ready
Wilms Tumour v0.40 CDC73 Zornitza Stark Gene: cdc73 has been classified as Red List (Low Evidence).
Wilms Tumour v0.40 ASXL1 Zornitza Stark Marked gene: ASXL1 as ready
Wilms Tumour v0.40 ASXL1 Zornitza Stark Gene: asxl1 has been classified as Red List (Low Evidence).
Wilms Tumour v0.40 AMER1 Zornitza Stark Marked gene: AMER1 as ready
Wilms Tumour v0.40 AMER1 Zornitza Stark Gene: amer1 has been classified as Red List (Low Evidence).
Wilms Tumour v0.40 NYNRIN Zornitza Stark Marked gene: NYNRIN as ready
Wilms Tumour v0.40 NYNRIN Zornitza Stark Gene: nynrin has been classified as Amber List (Moderate Evidence).
Wilms Tumour v0.40 FBXW7 Zornitza Stark Marked gene: FBXW7 as ready
Wilms Tumour v0.40 FBXW7 Zornitza Stark Gene: fbxw7 has been classified as Amber List (Moderate Evidence).
Wilms Tumour v0.40 DICER1 Zornitza Stark Marked gene: DICER1 as ready
Wilms Tumour v0.40 DICER1 Zornitza Stark Gene: dicer1 has been classified as Amber List (Moderate Evidence).
Wilms Tumour v0.40 WT1 Zornitza Stark Marked gene: WT1 as ready
Wilms Tumour v0.40 WT1 Zornitza Stark Gene: wt1 has been classified as Green List (High Evidence).
Wilms Tumour v0.40 TRIP13 Zornitza Stark Marked gene: TRIP13 as ready
Wilms Tumour v0.40 TRIP13 Zornitza Stark Gene: trip13 has been classified as Green List (High Evidence).
Wilms Tumour v0.40 TRIM37 Zornitza Stark Marked gene: TRIM37 as ready
Wilms Tumour v0.40 TRIM37 Zornitza Stark Gene: trim37 has been classified as Green List (High Evidence).
Wilms Tumour v0.40 TRIM28 Zornitza Stark Marked gene: TRIM28 as ready
Wilms Tumour v0.40 TRIM28 Zornitza Stark Gene: trim28 has been classified as Green List (High Evidence).
Wilms Tumour v0.40 REST Zornitza Stark Marked gene: REST as ready
Wilms Tumour v0.40 REST Zornitza Stark Gene: rest has been classified as Green List (High Evidence).
Wilms Tumour v0.40 PALB2 Zornitza Stark Marked gene: PALB2 as ready
Wilms Tumour v0.40 PALB2 Zornitza Stark Gene: palb2 has been classified as Green List (High Evidence).
Wilms Tumour v0.40 GPC3 Zornitza Stark Marked gene: GPC3 as ready
Wilms Tumour v0.40 GPC3 Zornitza Stark Gene: gpc3 has been classified as Green List (High Evidence).
Wilms Tumour v0.40 DIS3L2 Zornitza Stark Marked gene: DIS3L2 as ready
Wilms Tumour v0.40 DIS3L2 Zornitza Stark Gene: dis3l2 has been classified as Green List (High Evidence).
Wilms Tumour v0.40 CTR9 Zornitza Stark Marked gene: CTR9 as ready
Wilms Tumour v0.40 CTR9 Zornitza Stark Gene: ctr9 has been classified as Green List (High Evidence).
Wilms Tumour v0.40 CTR9 Zornitza Stark Publications for gene: CTR9 were set to PMID: 25099282, 39293508, 29292210
Wilms Tumour v0.39 CDKN1C Zornitza Stark Marked gene: CDKN1C as ready
Wilms Tumour v0.39 CDKN1C Zornitza Stark Gene: cdkn1c has been classified as Green List (High Evidence).
Wilms Tumour v0.39 BUB1B Zornitza Stark Marked gene: BUB1B as ready
Wilms Tumour v0.39 BUB1B Zornitza Stark Gene: bub1b has been classified as Green List (High Evidence).
Wilms Tumour v0.39 BRCA2 Zornitza Stark Marked gene: BRCA2 as ready
Wilms Tumour v0.39 BRCA2 Zornitza Stark Gene: brca2 has been classified as Green List (High Evidence).
Wilms Tumour v0.39 BLM Zornitza Stark Marked gene: BLM as ready
Wilms Tumour v0.39 BLM Zornitza Stark Gene: blm has been classified as Green List (High Evidence).
Paraganglioma_phaeochromocytoma v1.0 Zornitza Stark promoted panel to version 1.0
Paraganglioma_phaeochromocytoma v0.33 Zornitza Stark Panel status changed from internal to public
Paraganglioma_phaeochromocytoma v0.32 SLC25A11 Zornitza Stark Marked gene: SLC25A11 as ready
Paraganglioma_phaeochromocytoma v0.32 SLC25A11 Zornitza Stark Gene: slc25a11 has been classified as Red List (Low Evidence).
Paraganglioma_phaeochromocytoma v0.32 PRKAR1A Zornitza Stark Marked gene: PRKAR1A as ready
Paraganglioma_phaeochromocytoma v0.32 PRKAR1A Zornitza Stark Gene: prkar1a has been classified as Red List (Low Evidence).
Paraganglioma_phaeochromocytoma v0.32 MDH2 Zornitza Stark Marked gene: MDH2 as ready
Paraganglioma_phaeochromocytoma v0.32 MDH2 Zornitza Stark Gene: mdh2 has been classified as Red List (Low Evidence).
Paraganglioma_phaeochromocytoma v0.32 MDH2 Zornitza Stark Publications for gene: MDH2 were set to PMID: 25766404, 30008476
Paraganglioma_phaeochromocytoma v0.31 EPAS1 Zornitza Stark Marked gene: EPAS1 as ready
Paraganglioma_phaeochromocytoma v0.31 EPAS1 Zornitza Stark Gene: epas1 has been classified as Red List (Low Evidence).
Paraganglioma_phaeochromocytoma v0.31 EPAS1 Zornitza Stark Publications for gene: EPAS1 were set to PMID: 22931260, 23418310, 33300499
Paraganglioma_phaeochromocytoma v0.30 EGLN1 Zornitza Stark Marked gene: EGLN1 as ready
Paraganglioma_phaeochromocytoma v0.30 EGLN1 Zornitza Stark Gene: egln1 has been classified as Red List (Low Evidence).
Paraganglioma_phaeochromocytoma v0.30 DLST Zornitza Stark Marked gene: DLST as ready
Paraganglioma_phaeochromocytoma v0.30 DLST Zornitza Stark Gene: dlst has been classified as Red List (Low Evidence).
Paraganglioma_phaeochromocytoma v0.30 VHL Zornitza Stark Marked gene: VHL as ready
Paraganglioma_phaeochromocytoma v0.30 VHL Zornitza Stark Gene: vhl has been classified as Green List (High Evidence).
Paraganglioma_phaeochromocytoma v0.30 TMEM127 Zornitza Stark Marked gene: TMEM127 as ready
Paraganglioma_phaeochromocytoma v0.30 TMEM127 Zornitza Stark Gene: tmem127 has been classified as Green List (High Evidence).
Paraganglioma_phaeochromocytoma v0.30 SDHD Zornitza Stark Marked gene: SDHD as ready
Paraganglioma_phaeochromocytoma v0.30 SDHD Zornitza Stark Gene: sdhd has been classified as Green List (High Evidence).
Paraganglioma_phaeochromocytoma v0.30 SDHC Zornitza Stark Marked gene: SDHC as ready
Paraganglioma_phaeochromocytoma v0.30 SDHC Zornitza Stark Gene: sdhc has been classified as Green List (High Evidence).
Paraganglioma_phaeochromocytoma v0.30 SDHB Zornitza Stark Marked gene: SDHB as ready
Paraganglioma_phaeochromocytoma v0.30 SDHB Zornitza Stark Gene: sdhb has been classified as Green List (High Evidence).
Paraganglioma_phaeochromocytoma v0.30 SDHAF2 Zornitza Stark Marked gene: SDHAF2 as ready
Paraganglioma_phaeochromocytoma v0.30 SDHAF2 Zornitza Stark Gene: sdhaf2 has been classified as Green List (High Evidence).
Paraganglioma_phaeochromocytoma v0.30 SDHA Zornitza Stark Marked gene: SDHA as ready
Paraganglioma_phaeochromocytoma v0.30 SDHA Zornitza Stark Gene: sdha has been classified as Green List (High Evidence).
Paraganglioma_phaeochromocytoma v0.30 RET Zornitza Stark Marked gene: RET as ready
Paraganglioma_phaeochromocytoma v0.30 RET Zornitza Stark Gene: ret has been classified as Green List (High Evidence).
Paraganglioma_phaeochromocytoma v0.30 NF1 Zornitza Stark Marked gene: NF1 as ready
Paraganglioma_phaeochromocytoma v0.30 NF1 Zornitza Stark Gene: nf1 has been classified as Green List (High Evidence).
Paraganglioma_phaeochromocytoma v0.30 MEN1 Zornitza Stark Marked gene: MEN1 as ready
Paraganglioma_phaeochromocytoma v0.30 MEN1 Zornitza Stark Gene: men1 has been classified as Green List (High Evidence).
Paraganglioma_phaeochromocytoma v0.30 MAX Zornitza Stark Marked gene: MAX as ready
Paraganglioma_phaeochromocytoma v0.30 MAX Zornitza Stark Gene: max has been classified as Green List (High Evidence).
Paraganglioma_phaeochromocytoma v0.30 FH Zornitza Stark Marked gene: FH as ready
Paraganglioma_phaeochromocytoma v0.30 FH Zornitza Stark Gene: fh has been classified as Green List (High Evidence).
Pancreatic Cancer v1.0 Zornitza Stark promoted panel to version 1.0
Pancreatic Cancer v0.25 Zornitza Stark Panel status changed from internal to public
Ovarian Cancer v1.0 Zornitza Stark promoted panel to version 1.0
Ovarian Cancer v0.25 Zornitza Stark Panel status changed from internal to public
Ovarian Cancer v0.24 TP53 Zornitza Stark Marked gene: TP53 as ready
Ovarian Cancer v0.24 TP53 Zornitza Stark Gene: tp53 has been classified as Green List (High Evidence).
Ovarian Cancer v0.24 RAD51D Zornitza Stark Marked gene: RAD51D as ready
Ovarian Cancer v0.24 RAD51D Zornitza Stark Gene: rad51d has been classified as Green List (High Evidence).
Ovarian Cancer v0.24 RAD51C Zornitza Stark Marked gene: RAD51C as ready
Ovarian Cancer v0.24 RAD51C Zornitza Stark Gene: rad51c has been classified as Green List (High Evidence).
Ovarian Cancer v0.24 PMS2 Zornitza Stark Marked gene: PMS2 as ready
Ovarian Cancer v0.24 PMS2 Zornitza Stark Gene: pms2 has been classified as Green List (High Evidence).
Ovarian Cancer v0.24 PALB2 Zornitza Stark Marked gene: PALB2 as ready
Ovarian Cancer v0.24 PALB2 Zornitza Stark Gene: palb2 has been classified as Green List (High Evidence).
Ovarian Cancer v0.24 MSH6 Zornitza Stark Marked gene: MSH6 as ready
Ovarian Cancer v0.24 MSH6 Zornitza Stark Gene: msh6 has been classified as Green List (High Evidence).
Ovarian Cancer v0.24 MSH2 Zornitza Stark Marked gene: MSH2 as ready
Ovarian Cancer v0.24 MSH2 Zornitza Stark Gene: msh2 has been classified as Green List (High Evidence).
Ovarian Cancer v0.24 MLH1 Zornitza Stark Marked gene: MLH1 as ready
Ovarian Cancer v0.24 MLH1 Zornitza Stark Gene: mlh1 has been classified as Green List (High Evidence).
Ovarian Cancer v0.24 EPCAM Zornitza Stark Marked gene: EPCAM as ready
Ovarian Cancer v0.24 EPCAM Zornitza Stark Gene: epcam has been classified as Green List (High Evidence).
Ovarian Cancer v0.24 BRIP1 Zornitza Stark Marked gene: BRIP1 as ready
Ovarian Cancer v0.24 BRIP1 Zornitza Stark Gene: brip1 has been classified as Green List (High Evidence).
Ovarian Cancer v0.24 BRCA2 Zornitza Stark Marked gene: BRCA2 as ready
Ovarian Cancer v0.24 BRCA2 Zornitza Stark Gene: brca2 has been classified as Green List (High Evidence).
Ovarian Cancer v0.24 BRCA1 Zornitza Stark Marked gene: BRCA1 as ready
Ovarian Cancer v0.24 BRCA1 Zornitza Stark Gene: brca1 has been classified as Green List (High Evidence).
Neuroblastoma v1.0 Zornitza Stark promoted panel to version 1.0
Neuroblastoma v0.7 Zornitza Stark Panel status changed from internal to public
Neuroblastoma v0.6 SMARCA4 Zornitza Stark Marked gene: SMARCA4 as ready
Neuroblastoma v0.6 SMARCA4 Zornitza Stark Gene: smarca4 has been classified as Amber List (Moderate Evidence).
Neuroblastoma v0.6 PHOX2B Zornitza Stark Marked gene: PHOX2B as ready
Neuroblastoma v0.6 PHOX2B Zornitza Stark Gene: phox2b has been classified as Green List (High Evidence).
Neuroblastoma v0.6 ALK Zornitza Stark Marked gene: ALK as ready
Neuroblastoma v0.6 ALK Zornitza Stark Gene: alk has been classified as Green List (High Evidence).
Meningioma v1.0 Zornitza Stark promoted panel to version 1.0
Meningioma v0.11 Zornitza Stark Panel status changed from internal to public
Meningioma v0.10 SUFU Zornitza Stark Marked gene: SUFU as ready
Meningioma v0.10 SUFU Zornitza Stark Gene: sufu has been classified as Green List (High Evidence).
Meningioma v0.10 SMARCE1 Zornitza Stark Marked gene: SMARCE1 as ready
Meningioma v0.10 SMARCE1 Zornitza Stark Gene: smarce1 has been classified as Green List (High Evidence).
Meningioma v0.10 SMARCB1 Zornitza Stark Marked gene: SMARCB1 as ready
Meningioma v0.10 SMARCB1 Zornitza Stark Gene: smarcb1 has been classified as Green List (High Evidence).
Meningioma v0.10 NF2 Zornitza Stark Marked gene: NF2 as ready
Meningioma v0.10 NF2 Zornitza Stark Gene: nf2 has been classified as Green List (High Evidence).
Meningioma v0.10 BAP1 Zornitza Stark Marked gene: BAP1 as ready
Meningioma v0.10 BAP1 Zornitza Stark Gene: bap1 has been classified as Green List (High Evidence).
Melanoma v1.0 Zornitza Stark promoted panel to version 1.0
Melanoma v0.21 Zornitza Stark Panel status changed from internal to public
Melanoma v0.20 POT1 Zornitza Stark Marked gene: POT1 as ready
Melanoma v0.20 POT1 Zornitza Stark Gene: pot1 has been classified as Green List (High Evidence).
Melanoma v0.20 POT1 Zornitza Stark Publications for gene: POT1 were set to PMID: 24686849, 30586141, 24686846, 38724174
Melanoma v0.19 POT1 Zornitza Stark Classified gene: POT1 as Green List (high evidence)
Melanoma v0.19 POT1 Zornitza Stark Gene: pot1 has been classified as Green List (High Evidence).
Melanoma v0.18 CDKN2A Zornitza Stark Marked gene: CDKN2A as ready
Melanoma v0.18 CDKN2A Zornitza Stark Gene: cdkn2a has been classified as Green List (High Evidence).
Melanoma v0.18 CDKN2A Zornitza Stark Phenotypes for gene: CDKN2A were changed from to Melanoma, MONDO:0005105; Melanoma cutaneous malignant susceptibility to 2, MONDO:0007964; Melanoma-pancreatic cancer syndrome, MONDO:0011713; Melanoma and neural system tumor syndrome, MONDO:0007967; Melanoma, cutaneous malignant, 2, MIM#155601; Melanoma-pancreatic cancer syndrome, MIM#606719; Melanoma and neural system tumor syndrome, MIM#155755
Melanoma v0.17 CDK4 Zornitza Stark Marked gene: CDK4 as ready
Melanoma v0.17 CDK4 Zornitza Stark Gene: cdk4 has been classified as Green List (High Evidence).
Melanoma v0.17 CDK4 Zornitza Stark Phenotypes for gene: CDK4 were changed from to Melanoma, MONDO:0005105; CDK4 linked melanoma, MONDO:0022623; Melanoma cutaneous malignant susceptibility to 3, MONDO:0012183; Melanoma, cutaneous malignant, 3, MIM#609048
Melanoma v0.16 BAP1 Zornitza Stark Marked gene: BAP1 as ready
Melanoma v0.16 BAP1 Zornitza Stark Gene: bap1 has been classified as Green List (High Evidence).
Melanoma v0.16 BAP1 Zornitza Stark Phenotypes for gene: BAP1 were changed from to Melanoma, MONDO:0005105; BAP1-related tumor predisposition syndrome, MONDO:0013692; BAP1-tumour predisposition syndrome, MIM#614327
Medulloblastoma v1.0 Zornitza Stark promoted panel to version 1.0
Medulloblastoma v0.36 Zornitza Stark Panel status changed from internal to public
Medulloblastoma v0.35 TP53 Zornitza Stark Marked gene: TP53 as ready
Medulloblastoma v0.35 TP53 Zornitza Stark Gene: tp53 has been classified as Green List (High Evidence).
Medulloblastoma v0.35 TP53 Zornitza Stark Phenotypes for gene: TP53 were changed from to Medulloblastoma, MONDO:0007959; Li-Fraumeni syndrome, MONDO:0018875; Li-Fraumeni syndrome, MIM#151623
Medulloblastoma v0.34 SUFU Zornitza Stark Marked gene: SUFU as ready
Medulloblastoma v0.34 SUFU Zornitza Stark Gene: sufu has been classified as Green List (High Evidence).
Medulloblastoma v0.34 SUFU Zornitza Stark Phenotypes for gene: SUFU were changed from to Medulloblastoma, MONDO:0007959; Basal cell nevus syndrome 2, MONDO:0958189; Basal cell nevus syndrome 2, MIM#620343; Meningioma, familial, susceptibility to, MIM#607174; Medulloblastoma predisposition syndrome, MIM#155255
Medulloblastoma v0.33 PTCH1 Zornitza Stark Marked gene: PTCH1 as ready
Medulloblastoma v0.33 PTCH1 Zornitza Stark Gene: ptch1 has been classified as Green List (High Evidence).
Medulloblastoma v0.33 PTCH1 Zornitza Stark Phenotypes for gene: PTCH1 were changed from to Medulloblastoma, MONDO:0007959; Basal cell nevus syndrome 1, MONDO:0958174; Basal cell nevus syndrome 1, MIM#109400
Medulloblastoma v0.32 PMS2 Zornitza Stark Marked gene: PMS2 as ready
Medulloblastoma v0.32 PMS2 Zornitza Stark Gene: pms2 has been classified as Green List (High Evidence).
Medulloblastoma v0.32 MSH6 Zornitza Stark Marked gene: MSH6 as ready
Medulloblastoma v0.32 MSH6 Zornitza Stark Gene: msh6 has been classified as Green List (High Evidence).
Medulloblastoma v0.32 MSH2 Zornitza Stark Marked gene: MSH2 as ready
Medulloblastoma v0.32 MSH2 Zornitza Stark Gene: msh2 has been classified as Green List (High Evidence).
Medulloblastoma v0.32 MLH1 Zornitza Stark Marked gene: MLH1 as ready
Medulloblastoma v0.32 MLH1 Zornitza Stark Gene: mlh1 has been classified as Green List (High Evidence).
Medulloblastoma v0.32 GPR161 Zornitza Stark Marked gene: GPR161 as ready
Medulloblastoma v0.32 GPR161 Zornitza Stark Gene: gpr161 has been classified as Green List (High Evidence).
Medulloblastoma v0.32 GPR161 Zornitza Stark Phenotypes for gene: GPR161 were changed from {Medulloblastoma predisposition syndrome} 155255 to Medulloblastoma, MONDO:0007959; Medulloblastoma predisposition syndrome, MIM#155255
Medulloblastoma v0.31 GPR161 Zornitza Stark Publications for gene: GPR161 were set to
Medulloblastoma v0.30 GPR161 Zornitza Stark Mode of inheritance for gene: GPR161 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Medulloblastoma v0.29 EPCAM Zornitza Stark Marked gene: EPCAM as ready
Medulloblastoma v0.29 EPCAM Zornitza Stark Gene: epcam has been classified as Green List (High Evidence).
Medulloblastoma v0.29 ELP1 Zornitza Stark Marked gene: ELP1 as ready
Medulloblastoma v0.29 ELP1 Zornitza Stark Gene: elp1 has been classified as Green List (High Evidence).
Medulloblastoma v0.29 ELP1 Zornitza Stark Phenotypes for gene: ELP1 were changed from {Medulloblastoma} 155255 to Medulloblastoma, MONDO:0007959; Medulloblastoma predisposition syndrome, MIM#155255
Medulloblastoma v0.28 ELP1 Zornitza Stark Publications for gene: ELP1 were set to
Medulloblastoma v0.27 ELP1 Zornitza Stark Mode of inheritance for gene: ELP1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Medulloblastoma v0.26 BRCA2 Zornitza Stark Marked gene: BRCA2 as ready
Medulloblastoma v0.26 BRCA2 Zornitza Stark Gene: brca2 has been classified as Green List (High Evidence).
Medulloblastoma v0.26 APC Zornitza Stark Marked gene: APC as ready
Medulloblastoma v0.26 APC Zornitza Stark Gene: apc has been classified as Green List (High Evidence).
Medulloblastoma v0.26 APC Zornitza Stark Phenotypes for gene: APC were changed from to Medulloblastoma, MONDO:0007959; Familial adenomatous polyposis 1, MONDO:0021056; Adenomatous polyposis coli, MIM#175100
Kidney Cancer v1.0 Zornitza Stark promoted panel to version 1.0
Kidney Cancer v0.27 Zornitza Stark Panel status changed from internal to public
Gastrointestinal Stromal Tumour v1.0 Zornitza Stark promoted panel to version 1.0
Gastrointestinal Stromal Tumour v0.17 Zornitza Stark Panel status changed from internal to public
Gastrointestinal Stromal Tumour v0.16 SDHD Zornitza Stark Marked gene: SDHD as ready
Gastrointestinal Stromal Tumour v0.16 SDHD Zornitza Stark Gene: sdhd has been classified as Green List (High Evidence).
Gastrointestinal Stromal Tumour v0.16 SDHC Zornitza Stark Marked gene: SDHC as ready
Gastrointestinal Stromal Tumour v0.16 SDHC Zornitza Stark Gene: sdhc has been classified as Green List (High Evidence).
Gastrointestinal Stromal Tumour v0.16 SDHB Zornitza Stark Marked gene: SDHB as ready
Gastrointestinal Stromal Tumour v0.16 SDHB Zornitza Stark Gene: sdhb has been classified as Green List (High Evidence).
Gastrointestinal Stromal Tumour v0.16 SDHAF2 Zornitza Stark Marked gene: SDHAF2 as ready
Gastrointestinal Stromal Tumour v0.16 SDHAF2 Zornitza Stark Gene: sdhaf2 has been classified as Green List (High Evidence).
Gastrointestinal Stromal Tumour v0.16 SDHA Zornitza Stark Marked gene: SDHA as ready
Gastrointestinal Stromal Tumour v0.16 SDHA Zornitza Stark Gene: sdha has been classified as Green List (High Evidence).
Gastrointestinal Stromal Tumour v0.16 PDGFRA Zornitza Stark Marked gene: PDGFRA as ready
Gastrointestinal Stromal Tumour v0.16 PDGFRA Zornitza Stark Gene: pdgfra has been classified as Green List (High Evidence).
Gastrointestinal Stromal Tumour v0.16 NF1 Zornitza Stark Marked gene: NF1 as ready
Gastrointestinal Stromal Tumour v0.16 NF1 Zornitza Stark Gene: nf1 has been classified as Green List (High Evidence).
Gastrointestinal Stromal Tumour v0.16 KIT Zornitza Stark Marked gene: KIT as ready
Gastrointestinal Stromal Tumour v0.16 KIT Zornitza Stark Gene: kit has been classified as Green List (High Evidence).
Endometrial Cancer v1.0 Zornitza Stark promoted panel to version 1.0
Endometrial Cancer v0.21 Zornitza Stark Panel status changed from internal to public
Endometrial Cancer v0.20 TP53 Zornitza Stark Marked gene: TP53 as ready
Endometrial Cancer v0.20 TP53 Zornitza Stark Gene: tp53 has been classified as Green List (High Evidence).
Endometrial Cancer v0.20 PTEN Zornitza Stark Marked gene: PTEN as ready
Endometrial Cancer v0.20 PTEN Zornitza Stark Gene: pten has been classified as Green List (High Evidence).
Endometrial Cancer v0.20 POLE Zornitza Stark Marked gene: POLE as ready
Endometrial Cancer v0.20 POLE Zornitza Stark Gene: pole has been classified as Green List (High Evidence).
Endometrial Cancer v0.20 POLD1 Zornitza Stark Marked gene: POLD1 as ready
Endometrial Cancer v0.20 POLD1 Zornitza Stark Gene: pold1 has been classified as Green List (High Evidence).
Endometrial Cancer v0.20 PMS2 Zornitza Stark Marked gene: PMS2 as ready
Endometrial Cancer v0.20 PMS2 Zornitza Stark Gene: pms2 has been classified as Green List (High Evidence).
Endometrial Cancer v0.20 MSH6 Zornitza Stark Marked gene: MSH6 as ready
Endometrial Cancer v0.20 MSH6 Zornitza Stark Gene: msh6 has been classified as Green List (High Evidence).
Endometrial Cancer v0.20 MSH2 Zornitza Stark Marked gene: MSH2 as ready
Endometrial Cancer v0.20 MSH2 Zornitza Stark Gene: msh2 has been classified as Green List (High Evidence).
Endometrial Cancer v0.20 MLH1 Zornitza Stark Marked gene: MLH1 as ready
Endometrial Cancer v0.20 MLH1 Zornitza Stark Gene: mlh1 has been classified as Green List (High Evidence).
Endometrial Cancer v0.20 EPCAM Zornitza Stark Marked gene: EPCAM as ready
Endometrial Cancer v0.20 EPCAM Zornitza Stark Gene: epcam has been classified as Green List (High Evidence).
Endometrial Cancer v0.20 BRCA1 Zornitza Stark Marked gene: BRCA1 as ready
Endometrial Cancer v0.20 BRCA1 Zornitza Stark Gene: brca1 has been classified as Green List (High Evidence).
Diffuse Gastric Cancer v1.0 Zornitza Stark promoted panel to version 1.0
Diffuse Gastric Cancer v0.5 Zornitza Stark Panel status changed from internal to public
Diffuse Gastric Cancer v0.4 CTNNA1 Zornitza Stark Marked gene: CTNNA1 as ready
Diffuse Gastric Cancer v0.4 CTNNA1 Zornitza Stark Gene: ctnna1 has been classified as Green List (High Evidence).
Diffuse Gastric Cancer v0.4 CDH1 Zornitza Stark Marked gene: CDH1 as ready
Diffuse Gastric Cancer v0.4 CDH1 Zornitza Stark Gene: cdh1 has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v1.0 Zornitza Stark promoted panel to version 1.0
Colorectal Cancer and Polyposis v0.41 Zornitza Stark Panel status changed from internal to public
Colorectal Cancer and Polyposis v0.40 TP53 Zornitza Stark Marked gene: TP53 as ready
Colorectal Cancer and Polyposis v0.40 TP53 Zornitza Stark Gene: tp53 has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.40 STK11 Zornitza Stark Marked gene: STK11 as ready
Colorectal Cancer and Polyposis v0.40 STK11 Zornitza Stark Gene: stk11 has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.40 SMAD4 Zornitza Stark Marked gene: SMAD4 as ready
Colorectal Cancer and Polyposis v0.40 SMAD4 Zornitza Stark Gene: smad4 has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.40 RNF43 Zornitza Stark Marked gene: RNF43 as ready
Colorectal Cancer and Polyposis v0.40 RNF43 Zornitza Stark Gene: rnf43 has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.40 PTEN Zornitza Stark Marked gene: PTEN as ready
Colorectal Cancer and Polyposis v0.40 PTEN Zornitza Stark Gene: pten has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.40 POLE Zornitza Stark Marked gene: POLE as ready
Colorectal Cancer and Polyposis v0.40 POLE Zornitza Stark Gene: pole has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.40 POLD1 Zornitza Stark Marked gene: POLD1 as ready
Colorectal Cancer and Polyposis v0.40 POLD1 Zornitza Stark Gene: pold1 has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.40 PMS2 Zornitza Stark Marked gene: PMS2 as ready
Colorectal Cancer and Polyposis v0.40 PMS2 Zornitza Stark Gene: pms2 has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.40 NTHL1 Zornitza Stark Marked gene: NTHL1 as ready
Colorectal Cancer and Polyposis v0.40 NTHL1 Zornitza Stark Gene: nthl1 has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.40 MUTYH Zornitza Stark Marked gene: MUTYH as ready
Colorectal Cancer and Polyposis v0.40 MUTYH Zornitza Stark Gene: mutyh has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.40 MSH6 Zornitza Stark Marked gene: MSH6 as ready
Colorectal Cancer and Polyposis v0.40 MSH6 Zornitza Stark Gene: msh6 has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.40 MSH3 Zornitza Stark Marked gene: MSH3 as ready
Colorectal Cancer and Polyposis v0.40 MSH3 Zornitza Stark Gene: msh3 has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.40 MSH2 Zornitza Stark Marked gene: MSH2 as ready
Colorectal Cancer and Polyposis v0.40 MSH2 Zornitza Stark Gene: msh2 has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.40 MLH1 Zornitza Stark Marked gene: MLH1 as ready
Colorectal Cancer and Polyposis v0.40 MLH1 Zornitza Stark Gene: mlh1 has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.40 GREM1 Zornitza Stark Marked gene: GREM1 as ready
Colorectal Cancer and Polyposis v0.40 GREM1 Zornitza Stark Gene: grem1 has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.40 GREM1 Zornitza Stark Phenotypes for gene: GREM1 were changed from to Colorectal cancer, MONDO:0005575; Polyposis, MONDO:0000147; Hereditary mixed polyposis syndrome, MONDO:0011023; GREM1-associated polyposis, no MIM#
Colorectal Cancer and Polyposis v0.39 EPCAM Zornitza Stark Marked gene: EPCAM as ready
Colorectal Cancer and Polyposis v0.39 EPCAM Zornitza Stark Gene: epcam has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.39 BMPR1A Zornitza Stark Marked gene: BMPR1A as ready
Colorectal Cancer and Polyposis v0.39 BMPR1A Zornitza Stark Gene: bmpr1a has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.39 AXIN2 Zornitza Stark Marked gene: AXIN2 as ready
Colorectal Cancer and Polyposis v0.39 AXIN2 Zornitza Stark Gene: axin2 has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.39 APC Zornitza Stark Marked gene: APC as ready
Colorectal Cancer and Polyposis v0.39 APC Zornitza Stark Gene: apc has been classified as Green List (High Evidence).
Breast Cancer v1.0 Zornitza Stark promoted panel to version 1.0
Breast Cancer v0.27 Zornitza Stark Panel status changed from internal to public
Breast Cancer v0.26 TP53 Zornitza Stark Marked gene: TP53 as ready
Breast Cancer v0.26 TP53 Zornitza Stark Gene: tp53 has been classified as Green List (High Evidence).
Breast Cancer v0.26 STK11 Zornitza Stark Marked gene: STK11 as ready
Breast Cancer v0.26 STK11 Zornitza Stark Gene: stk11 has been classified as Green List (High Evidence).
Breast Cancer v0.26 RAD51D Zornitza Stark Marked gene: RAD51D as ready
Breast Cancer v0.26 RAD51D Zornitza Stark Gene: rad51d has been classified as Green List (High Evidence).
Breast Cancer v0.26 RAD51C Zornitza Stark Marked gene: RAD51C as ready
Breast Cancer v0.26 RAD51C Zornitza Stark Gene: rad51c has been classified as Green List (High Evidence).
Breast Cancer v0.26 PTEN Zornitza Stark Marked gene: PTEN as ready
Breast Cancer v0.26 PTEN Zornitza Stark Gene: pten has been classified as Green List (High Evidence).
Breast Cancer v0.26 PALB2 Zornitza Stark Marked gene: PALB2 as ready
Breast Cancer v0.26 PALB2 Zornitza Stark Gene: palb2 has been classified as Green List (High Evidence).
Breast Cancer v0.26 NF1 Zornitza Stark Marked gene: NF1 as ready
Breast Cancer v0.26 NF1 Zornitza Stark Gene: nf1 has been classified as Green List (High Evidence).
Breast Cancer v0.26 CHEK2 Zornitza Stark Marked gene: CHEK2 as ready
Breast Cancer v0.26 CHEK2 Zornitza Stark Gene: chek2 has been classified as Green List (High Evidence).
Breast Cancer v0.26 CDH1 Zornitza Stark Marked gene: CDH1 as ready
Breast Cancer v0.26 CDH1 Zornitza Stark Gene: cdh1 has been classified as Green List (High Evidence).
Breast Cancer v0.26 BRCA2 Zornitza Stark Marked gene: BRCA2 as ready
Breast Cancer v0.26 BRCA2 Zornitza Stark Gene: brca2 has been classified as Green List (High Evidence).
Breast Cancer v0.26 BRCA1 Zornitza Stark Marked gene: BRCA1 as ready
Breast Cancer v0.26 BRCA1 Zornitza Stark Gene: brca1 has been classified as Green List (High Evidence).
Breast Cancer v0.26 BARD1 Zornitza Stark Marked gene: BARD1 as ready
Breast Cancer v0.26 BARD1 Zornitza Stark Gene: bard1 has been classified as Green List (High Evidence).
Breast Cancer v0.26 ATM Zornitza Stark Marked gene: ATM as ready
Breast Cancer v0.26 ATM Zornitza Stark Gene: atm has been classified as Green List (High Evidence).
Basal Cell Cancer v1.0 Zornitza Stark promoted panel to version 1.0
Basal Cell Cancer v0.7 Zornitza Stark Panel status changed from internal to public
Basal Cell Cancer v0.6 PTCH2 Zornitza Stark Marked gene: PTCH2 as ready
Basal Cell Cancer v0.6 PTCH2 Zornitza Stark Gene: ptch2 has been classified as Red List (Low Evidence).
Basal Cell Cancer v0.6 SUFU Zornitza Stark Marked gene: SUFU as ready
Basal Cell Cancer v0.6 SUFU Zornitza Stark Gene: sufu has been classified as Green List (High Evidence).
Basal Cell Cancer v0.6 PTCH1 Zornitza Stark Marked gene: PTCH1 as ready
Basal Cell Cancer v0.6 PTCH1 Zornitza Stark Gene: ptch1 has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v0.148 CHD1 Boris Keren changed review comment from: Two of the 5 patients in the Pilarowski paper have macrocephaly associated with their neurodevelopmental disorder.
All the variants in the Pilarowski paper are missenses, and the assumed mechanism is a dominant negative effect, although there are now a few pathogenic/likely pathogenic LoFs in ClinVar.
Sources: Literature; to: Two of the 5 patients in the Pilarowski paper have macrocephaly associated with their neurodevelopmental disorder.
All the variants in the Pilarowski paper are missenses, and the assumed mechanism is a dominant negative effect, although there are now a few pathogenic/likely pathogenic LoFs in ClinVar.
Sources: Literature
Macrocephaly_Megalencephaly v0.148 CHD1 Boris Keren gene: CHD1 was added
gene: CHD1 was added to Macrocephaly_Megalencephaly. Sources: Literature
Mode of inheritance for gene: CHD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD1 were set to 28866611
Phenotypes for gene: CHD1 were set to intellectual disability; macrocephaly
Penetrance for gene: CHD1 were set to Incomplete
Mode of pathogenicity for gene: CHD1 was set to Other
Review for gene: CHD1 was set to AMBER
gene: CHD1 was marked as current diagnostic
Added comment: Two of the 5 patients in the Pilarowski paper have macrocephaly associated with their neurodevelopmental disorder.
All the variants in the Pilarowski paper are missenses, and the assumed mechanism is a dominant negative effect, although there are now a few pathogenic/likely pathogenic LoFs in ClinVar.
Sources: Literature
Prepair 1000+ v1.390 TPM3 Andrew Coventry reviewed gene: TPM3: Rating: GREEN; Mode of pathogenicity: None; Publications: 26418456 7704029 17376686 18382475 19487656 12196661 10619715; Phenotypes: Congenital myopathy 4B, autosomal recessive MIM#609284; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.390 TPI1 Andrew Coventry reviewed gene: TPI1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9338582 32873690 8503454; Phenotypes: Hemolytic anemia due to triosephosphate isomerase deficiency MIM#615512; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.390 TNFRSF11B Andrew Coventry reviewed gene: TNFRSF11B: Rating: GREEN; Mode of pathogenicity: None; Publications: 25108083 34166796 29080812 14672344; Phenotypes: Paget disease of bone 5, juvenile-onset MIM#239000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.390 THOC2 Andrew Coventry reviewed gene: THOC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26166480 32116545 29851191 32960281 34976470 37945483; Phenotypes: Intellectual developmental disorder, X-linked 12 MIM#300957; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Kidneyome_SuperPanel v8.79 Zornitza Stark Changed child panels to: Renal Ciliopathies and Nephronophthisis; Renal Tubulopathies and related disorders; Hypertension and Aldosterone disorders; Renal Tubulointerstitial Disease; Haematuria_Alport; Proteinuria; Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic; Congenital anomalies of the kidney and urinary tract (CAKUT) Nonsyndromic; Renal Macrocystic Disease; Atypical Haemolytic Uraemic Syndrome_MPGN; Amyloidosis
Intellectual disability syndromic and non-syndromic v0.6465 IPO8 Zornitza Stark Marked gene: IPO8 as ready
Intellectual disability syndromic and non-syndromic v0.6465 IPO8 Zornitza Stark Gene: ipo8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6465 IPO8 Zornitza Stark Classified gene: IPO8 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6465 IPO8 Zornitza Stark Gene: ipo8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6464 IPO8 Zornitza Stark gene: IPO8 was added
gene: IPO8 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: IPO8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IPO8 were set to 34010604; 33875846; 34010605
Phenotypes for gene: IPO8 were set to Vascular aneurysm, immune dysregulation, skeletal anomalies, and skin and joint laxity, MIM# 619472; Loeys-Dietz syndrome-like; cardiovascular, neurologic, skeletal and immunologic abnormalities
Review for gene: IPO8 was set to GREEN
Added comment: There are 35 unrelated cases with a IPO8 variant, 4/35 with mild ID, 1/35 with severe ID and 7 global developmental delay. There is a further case with severe ID, but the patient also has a 1.779Mb deletion in 19q13.4, which could be responsible for the ID (PMID: 34010605).
Sources: Literature
Mendeliome v1.2063 WFDC2 Zornitza Stark Marked gene: WFDC2 as ready
Mendeliome v1.2063 WFDC2 Zornitza Stark Gene: wfdc2 has been classified as Green List (High Evidence).
Mendeliome v1.2063 WFDC2 Zornitza Stark Classified gene: WFDC2 as Green List (high evidence)
Mendeliome v1.2063 WFDC2 Zornitza Stark Gene: wfdc2 has been classified as Green List (High Evidence).
Mendeliome v1.2062 WFDC2 Zornitza Stark gene: WFDC2 was added
gene: WFDC2 was added to Mendeliome. Sources: Literature
founder tags were added to gene: WFDC2.
Mode of inheritance for gene: WFDC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WFDC2 were set to 38626355
Phenotypes for gene: WFDC2 were set to bronchiectasis, MONDO:0004822, WFDC2-related
Review for gene: WFDC2 was set to GREEN
Added comment: 11 individuals from 10 families reported with bi-allelic variants in this gene and bronchiectasis and nasal polyps. p.Cys49Arg is recurrent and may be a founder variant.
Sources: Literature
Pulmonary Fibrosis_Interstitial Lung Disease v0.79 WFDC2 Zornitza Stark Marked gene: WFDC2 as ready
Pulmonary Fibrosis_Interstitial Lung Disease v0.79 WFDC2 Zornitza Stark Gene: wfdc2 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.79 WFDC2 Zornitza Stark Tag founder tag was added to gene: WFDC2.
Severe Combined Immunodeficiency (absent T present B cells) v1.9 TP63 Zornitza Stark Marked gene: TP63 as ready
Severe Combined Immunodeficiency (absent T present B cells) v1.9 TP63 Zornitza Stark Gene: tp63 has been classified as Green List (High Evidence).
Severe Combined Immunodeficiency (absent T present B cells) v1.9 TP63 Zornitza Stark Phenotypes for gene: TP63 were changed from lymphopaenia to Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3, MIM# 604292; lymphopaenia
Pulmonary Fibrosis_Interstitial Lung Disease v0.79 WFDC2 Zornitza Stark Classified gene: WFDC2 as Green List (high evidence)
Pulmonary Fibrosis_Interstitial Lung Disease v0.79 WFDC2 Zornitza Stark Gene: wfdc2 has been classified as Green List (High Evidence).
Pulmonary Fibrosis_Interstitial Lung Disease v0.78 WFDC2 Zornitza Stark gene: WFDC2 was added
gene: WFDC2 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Literature
Mode of inheritance for gene: WFDC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WFDC2 were set to 38626355
Phenotypes for gene: WFDC2 were set to bronchiectasis, MONDO:0004822, WFDC2-related
Review for gene: WFDC2 was set to GREEN
Added comment: 11 individuals from 10 families reported with bi-allelic variants in this gene and bronchiectasis and nasal polyps. p.Cys49Arg is recurrent and may be a founder variant.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6463 PRKACB Zornitza Stark Publications for gene: PRKACB were set to 33058759
Intellectual disability syndromic and non-syndromic v0.6462 PRKACB Zornitza Stark Classified gene: PRKACB as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6462 PRKACB Zornitza Stark Gene: prkacb has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6461 PRKACB Zornitza Stark edited their review of gene: PRKACB: Added comment: Additional individual reported with ID and de novo missense variant.; Changed rating: GREEN; Changed publications: 39095811
Severe Combined Immunodeficiency (absent T present B cells) v1.8 TP63 Zornitza Stark Classified gene: TP63 as Green List (high evidence)
Severe Combined Immunodeficiency (absent T present B cells) v1.8 TP63 Zornitza Stark Gene: tp63 has been classified as Green List (High Evidence).
Severe Combined Immunodeficiency (absent T present B cells) v1.7 TP63 Zornitza Stark reviewed gene: TP63: Rating: GREEN; Mode of pathogenicity: None; Publications: 39364398; Phenotypes: Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3, MIM# 604292; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Syndromic Retinopathy v0.216 MAN2B1 Zornitza Stark Marked gene: MAN2B1 as ready
Syndromic Retinopathy v0.216 MAN2B1 Zornitza Stark Gene: man2b1 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.216 MAN2B1 Zornitza Stark Classified gene: MAN2B1 as Green List (high evidence)
Syndromic Retinopathy v0.216 MAN2B1 Zornitza Stark Gene: man2b1 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.215 MAN2B1 Zornitza Stark gene: MAN2B1 was added
gene: MAN2B1 was added to Syndromic Retinopathy. Sources: Expert list
Mode of inheritance for gene: MAN2B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAN2B1 were set to 29859105
Phenotypes for gene: MAN2B1 were set to Mannosidosis, alpha-, types I and II, MIM# 248500
Review for gene: MAN2B1 was set to GREEN
Added comment: Retinal dystrophy can be a feature of the systemic alpha-mannosidosis phenotype, and can rarely be the presenting feature in apparent non-syndromic retinal dystrophy
Sources: Expert list
Prepair 1000+ v1.390 CLDN10 Crystle Lee reviewed gene: CLDN10: Rating: AMBER; Mode of pathogenicity: None; Publications: 37984702, 31671507, 28674042; Phenotypes: HELIX syndrome (MIM#617671); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.282 FLVCR1 Zornitza Stark Phenotypes for gene: FLVCR1 were changed from Ataxia, posterior column, with retinitis pigmentosa, MIM#609033 to neurodevelopmental disorder MONDO:0700092, FLVCR1-related; Ataxia, posterior column, with retinitis pigmentosa, MIM#609033
Fetal anomalies v1.281 FLVCR1 Zornitza Stark Publications for gene: FLVCR1 were set to
Fetal anomalies v1.280 FLVCR1 Zornitza Stark Classified gene: FLVCR1 as Green List (high evidence)
Fetal anomalies v1.280 FLVCR1 Zornitza Stark Gene: flvcr1 has been classified as Green List (High Evidence).
Fetal anomalies v1.279 FLVCR1 Zornitza Stark edited their review of gene: FLVCR1: Added comment: PMID 39306721: A new study with 30 patients from 23 unrelated families with biallelic ultra-rare missense and predicted loss-of-function variants in FLVCR1 with a novel FLVCR1-related phenotype characterised by severe developmental disorders with profound developmental delay, microcephaly, brain malformations, epilepsy, spasticity, and premature death. Optic disk atrophy, limb and digital malformations, and macrocytic anaemia can be present.

Included here as brain, limb and digital malformations can present antenatally.; Changed rating: GREEN; Changed publications: 39306721; Changed phenotypes: neurodevelopmental disorder MONDO:0700092, FLVCR1-related, Ataxia, posterior column, with retinitis pigmentosa, MIM#609033
Prepair 1000+ v1.390 CFP Crystle Lee reviewed gene: CFP: Rating: GREEN; Mode of pathogenicity: None; Publications: 22229731, 10909851; Phenotypes: Properdin deficiency, X-linked (MIM#312060); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Differences of Sex Development v0.297 RNF216 Zornitza Stark Marked gene: RNF216 as ready
Differences of Sex Development v0.297 RNF216 Zornitza Stark Gene: rnf216 has been classified as Green List (High Evidence).
Differences of Sex Development v0.297 RNF216 Zornitza Stark Classified gene: RNF216 as Green List (high evidence)
Differences of Sex Development v0.297 RNF216 Zornitza Stark Gene: rnf216 has been classified as Green List (High Evidence).
Differences of Sex Development v0.296 RNF216 Zornitza Stark gene: RNF216 was added
gene: RNF216 was added to Differences of Sex Development. Sources: Expert list
Mode of inheritance for gene: RNF216 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNF216 were set to 25841028; 23656588
Phenotypes for gene: RNF216 were set to Cerebellar ataxia and hypogonadotropic hypogonadism, MIM# 212840
Review for gene: RNF216 was set to GREEN
Added comment: Gordon Holmes syndrome is an autosomal recessive adult-onset neurodegenerative disorder characterized by progressive cognitive decline, dementia, and variable movement disorders, such as ataxia and chorea. The neurologic phenotype is associated with hypogonadotropic hypogonadism, which can present with amenorrhoea in females.
Sources: Expert list
Prepair 1000+ v1.390 CDH23 Crystle Lee reviewed gene: CDH23: Rating: GREEN; Mode of pathogenicity: None; Publications: 33316915; Phenotypes: Usher syndrome, type 1D (MIM#601067), Deafness, autosomal recessive 12 (MIM#601386); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Callosome v0.530 RAB18 Zornitza Stark Marked gene: RAB18 as ready
Callosome v0.530 RAB18 Zornitza Stark Gene: rab18 has been classified as Green List (High Evidence).
Callosome v0.530 RAB18 Zornitza Stark Phenotypes for gene: RAB18 were changed from to Warburg micro syndrome 3, MIM# 614222
Callosome v0.529 RAB18 Zornitza Stark Publications for gene: RAB18 were set to
Intellectual disability syndromic and non-syndromic v0.6461 RAF1 Zornitza Stark Marked gene: RAF1 as ready
Intellectual disability syndromic and non-syndromic v0.6461 RAF1 Zornitza Stark Gene: raf1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6461 RAF1 Zornitza Stark Phenotypes for gene: RAF1 were changed from Noonan syndrome 5, MIM# 611553 to Noonan syndrome 5, MIM# 611553
Intellectual disability syndromic and non-syndromic v0.6460 RAF1 Zornitza Stark Phenotypes for gene: RAF1 were changed from to Noonan syndrome 5, MIM# 611553
Intellectual disability syndromic and non-syndromic v0.6459 RAF1 Zornitza Stark Publications for gene: RAF1 were set to
Intellectual disability syndromic and non-syndromic v0.6458 RAF1 Zornitza Stark Mode of pathogenicity for gene: RAF1 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability syndromic and non-syndromic v0.6457 RAF1 Zornitza Stark Mode of inheritance for gene: RAF1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Callosome v0.528 RAB18 Zornitza Stark Mode of inheritance for gene: RAB18 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6456 RAB18 Zornitza Stark changed review comment from: Autosomal recessive syndrome characterised by microcephaly, microphthalmia, microcornea, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe mental retardation, spastic diplegia, and hypogonadism. At least 7 families reported, including 4 Pakistani families with a founder variant, p.Leu24Gln; to: Autosomal recessive syndrome characterised by microcephaly, microphthalmia, microcornea, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe ID, spastic diplegia, and hypogonadism. At least 7 families reported, including 4 Pakistani families with a founder variant, p.Leu24Gln
Callosome v0.527 RAB18 Zornitza Stark reviewed gene: RAB18: Rating: GREEN; Mode of pathogenicity: None; Publications: 11237903, 23420520; Phenotypes: Warburg micro syndrome 3, MIM# 614222; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6456 RAB18 Zornitza Stark Marked gene: RAB18 as ready
Intellectual disability syndromic and non-syndromic v0.6456 RAB18 Zornitza Stark Gene: rab18 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6456 RAB18 Zornitza Stark Phenotypes for gene: RAB18 were changed from to Warburg micro syndrome 3, MIM# 614222
Intellectual disability syndromic and non-syndromic v0.6455 RAB18 Zornitza Stark Publications for gene: RAB18 were set to
Intellectual disability syndromic and non-syndromic v0.6454 RAB18 Zornitza Stark Mode of inheritance for gene: RAB18 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6453 RAB18 Zornitza Stark Tag founder tag was added to gene: RAB18.
Intellectual disability syndromic and non-syndromic v0.6453 RAB18 Zornitza Stark reviewed gene: RAB18: Rating: GREEN; Mode of pathogenicity: None; Publications: 11237903, 23420520; Phenotypes: Warburg micro syndrome 3, MIM# 614222; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6453 PYCR1 Zornitza Stark Marked gene: PYCR1 as ready
Intellectual disability syndromic and non-syndromic v0.6453 PYCR1 Zornitza Stark Gene: pycr1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6453 PYCR1 Zornitza Stark Phenotypes for gene: PYCR1 were changed from to Cutis laxa, autosomal recessive, type IIB, MIM# 612940; Cutis laxa, autosomal recessive, type IIIB, MIM# 614438
Intellectual disability syndromic and non-syndromic v0.6452 PYCR1 Zornitza Stark Publications for gene: PYCR1 were set to
Intellectual disability syndromic and non-syndromic v0.6451 PYCR1 Zornitza Stark Mode of inheritance for gene: PYCR1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6450 PYCR1 Zornitza Stark reviewed gene: PYCR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19648921, 4076251, 22052856, 19576563, 19648921, 9648921, 22052856, 28294978, 27756598; Phenotypes: Cutis laxa, autosomal recessive, type IIB, MIM# 612940, Cutis laxa, autosomal recessive, type IIIB, MIM# 614438; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
IBMDx study v0.30 PUS1 Zornitza Stark Marked gene: PUS1 as ready
IBMDx study v0.30 PUS1 Zornitza Stark Gene: pus1 has been classified as Green List (High Evidence).
IBMDx study v0.30 PUS1 Zornitza Stark Publications for gene: PUS1 were set to
IBMDx study v0.29 PUS1 Zornitza Stark Mode of inheritance for gene: PUS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.940 PUS1 Zornitza Stark Phenotypes for gene: PUS1 were changed from Myopathy, lactic acidosis, and sideroblastic anaemia 1, MIM# 600462 to Myopathy, lactic acidosis, and sideroblastic anaemia 1, MIM# 600462
Mitochondrial disease v0.939 PUS1 Zornitza Stark Marked gene: PUS1 as ready
Mitochondrial disease v0.939 PUS1 Zornitza Stark Gene: pus1 has been classified as Green List (High Evidence).
Mitochondrial disease v0.939 PUS1 Zornitza Stark Phenotypes for gene: PUS1 were changed from to Myopathy, lactic acidosis, and sideroblastic anaemia 1, MIM# 600462
Intellectual disability syndromic and non-syndromic v0.6450 PUS1 Zornitza Stark Marked gene: PUS1 as ready
Intellectual disability syndromic and non-syndromic v0.6450 PUS1 Zornitza Stark Gene: pus1 has been classified as Green List (High Evidence).
Mitochondrial disease v0.938 PUS1 Zornitza Stark Publications for gene: PUS1 were set to
Intellectual disability syndromic and non-syndromic v0.6450 PUS1 Zornitza Stark Phenotypes for gene: PUS1 were changed from to Myopathy, lactic acidosis, and sideroblastic anaemia 1, MIM# 600462
Intellectual disability syndromic and non-syndromic v0.6449 PUS1 Zornitza Stark Publications for gene: PUS1 were set to
Intellectual disability syndromic and non-syndromic v0.6448 PUS1 Zornitza Stark Mode of inheritance for gene: PUS1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6448 PUS1 Zornitza Stark Mode of inheritance for gene: PUS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.937 PUS1 Zornitza Stark Mode of inheritance for gene: PUS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disease v0.936 PUS1 Zornitza Stark edited their review of gene: PUS1: Changed phenotypes: Myopathy, lactic acidosis, and sideroblastic anaemia 1, MIM# 600462
Intellectual disability syndromic and non-syndromic v0.6447 PUS1 Zornitza Stark edited their review of gene: PUS1: Changed phenotypes: Myopathy, lactic acidosis, and sideroblastic anaemia 1, MIM# 600462
Intellectual disability syndromic and non-syndromic v0.6447 PUS1 Zornitza Stark reviewed gene: PUS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25227147, 17056637, 15108122, 32287105, 31641589, 28832011; Phenotypes: Myopathy, lactic acidosis, and sideroblastic anemia 1, MIM# 600462; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6447 PTS Zornitza Stark Marked gene: PTS as ready
Intellectual disability syndromic and non-syndromic v0.6447 PTS Zornitza Stark Gene: pts has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6447 PTS Zornitza Stark Phenotypes for gene: PTS were changed from Hyperphenylalaninemia, BH4-deficient, A, MIM# 261640 to Hyperphenylalaninaemia, BH4-deficient, A, MIM# 261640
Intellectual disability syndromic and non-syndromic v0.6446 PTS Zornitza Stark Phenotypes for gene: PTS were changed from to Hyperphenylalaninemia, BH4-deficient, A, MIM# 261640
Intellectual disability syndromic and non-syndromic v0.6445 PTS Zornitza Stark Mode of inheritance for gene: PTS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6444 PTS Zornitza Stark reviewed gene: PTS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hyperphenylalaninemia, BH4-deficient, A, MIM# 261640; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6444 PTPN11 Zornitza Stark Marked gene: PTPN11 as ready
Intellectual disability syndromic and non-syndromic v0.6444 PTPN11 Zornitza Stark Gene: ptpn11 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6444 PTPN11 Zornitza Stark Phenotypes for gene: PTPN11 were changed from to Noonan syndrome 1, MIM#163950 AD; LEOPARD syndrome 1, 151100 AD (for reporting use Noonan syndrome with multiple lentigines)
Intellectual disability syndromic and non-syndromic v0.6443 PTPN11 Zornitza Stark Publications for gene: PTPN11 were set to
Intellectual disability syndromic and non-syndromic v0.6442 PTPN11 Zornitza Stark Mode of pathogenicity for gene: PTPN11 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability syndromic and non-syndromic v0.6441 PTPN11 Zornitza Stark Mode of inheritance for gene: PTPN11 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6440 PTF1A Zornitza Stark Marked gene: PTF1A as ready
Intellectual disability syndromic and non-syndromic v0.6440 PTF1A Zornitza Stark Gene: ptf1a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6440 PTF1A Zornitza Stark Phenotypes for gene: PTF1A were changed from to Pancreatic and cerebellar agenesis, MIM# 609069
Intellectual disability syndromic and non-syndromic v0.6439 PTF1A Zornitza Stark Publications for gene: PTF1A were set to
Intellectual disability syndromic and non-syndromic v0.6438 PTF1A Zornitza Stark Mode of inheritance for gene: PTF1A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6437 PTF1A Zornitza Stark reviewed gene: PTF1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 21749365, 10507728, 15543146, 19650412; Phenotypes: Pancreatic and cerebellar agenesis, MIM# 609069; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6437 PTDSS1 Zornitza Stark Marked gene: PTDSS1 as ready
Intellectual disability syndromic and non-syndromic v0.6437 PTDSS1 Zornitza Stark Gene: ptdss1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6437 PTDSS1 Zornitza Stark Phenotypes for gene: PTDSS1 were changed from Lenz-Majewski hyperostotic dwarfism MIM#151050 to Lenz-Majewski hyperostotic dwarfism MIM#151050
Intellectual disability syndromic and non-syndromic v0.6436 PTDSS1 Zornitza Stark Phenotypes for gene: PTDSS1 were changed from to Lenz-Majewski hyperostotic dwarfism MIM#151050
Intellectual disability syndromic and non-syndromic v0.6435 PTDSS1 Zornitza Stark Publications for gene: PTDSS1 were set to
Intellectual disability syndromic and non-syndromic v0.6434 PTDSS1 Zornitza Stark Mode of inheritance for gene: PTDSS1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6433 PTDSS1 Zornitza Stark commented on gene: PTDSS1: Lenz-Majewski hyperostotic dwarfism is a rare condition characterized by intellectual disability, sclerosing bone dysplasia, distinct craniofacial and dental anomalies, loose skin, and distal limb anomalies, particularly brachydactyly and symphalangism. Patients have multiple radiographic abnormalities due to progressive generalized hyperostosis that affects the cranium, vertebrae, and diaphyses of tubular bones, leading to severe growth retardation.

Multiple families. Gain-of-function is the established or expected mechanism of disease for these variants.
Intellectual disability syndromic and non-syndromic v0.6433 PTDSS1 Zornitza Stark edited their review of gene: PTDSS1: Changed publications: 24241535, 29341480, 31403251
Intellectual disability syndromic and non-syndromic v0.6433 PTDSS1 Zornitza Stark reviewed gene: PTDSS1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lenz-Majewski hyperostotic dwarfism MIM#151050; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6433 PTCH1 Zornitza Stark Marked gene: PTCH1 as ready
Intellectual disability syndromic and non-syndromic v0.6433 PTCH1 Zornitza Stark Gene: ptch1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6433 PTCH1 Zornitza Stark Phenotypes for gene: PTCH1 were changed from to Holoprosencephaly 7, MIM# 610828
Intellectual disability syndromic and non-syndromic v0.6432 PTCH1 Zornitza Stark Mode of inheritance for gene: PTCH1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6431 PTCH1 Zornitza Stark Mode of inheritance for gene: PTCH1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6430 PTCH1 Zornitza Stark reviewed gene: PTCH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Holoprosencephaly 7, MIM# 610828; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.2061 PTCH1 Zornitza Stark Phenotypes for gene: PTCH1 were changed from Holoprosencephaly 7, MIM# 610828 to Holoprosencephaly 7, MIM# 610828; Bladder exstrophy and epispadias complex (BEEC)
Intellectual disability syndromic and non-syndromic v0.6430 KBTBD2 Zornitza Stark Marked gene: KBTBD2 as ready
Intellectual disability syndromic and non-syndromic v0.6430 KBTBD2 Zornitza Stark Gene: kbtbd2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6430 KBTBD2 Zornitza Stark Classified gene: KBTBD2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6430 KBTBD2 Zornitza Stark Gene: kbtbd2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6429 KBTBD2 Zornitza Stark gene: KBTBD2 was added
gene: KBTBD2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: KBTBD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KBTBD2 were set to 39313616
Phenotypes for gene: KBTBD2 were set to neurodevelopmental disorder MONDO:0700092, KBTBD2-related
Review for gene: KBTBD2 was set to GREEN
Added comment: 3 families - 2 compound hets and 1 hom

phenotypes include:
Microcephaly, hypotonia, failure to thrive, IUGR, delayed gross motor development, dysmorphism
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6428 MAP2K1 Zornitza Stark Marked gene: MAP2K1 as ready
Intellectual disability syndromic and non-syndromic v0.6428 MAP2K1 Zornitza Stark Gene: map2k1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6428 MAP2K1 Zornitza Stark Phenotypes for gene: MAP2K1 were changed from to Cardiofaciocutaneous syndrome 3, MIM# 615279
Intellectual disability syndromic and non-syndromic v0.6427 MAP2K1 Zornitza Stark Publications for gene: MAP2K1 were set to 16439621; 17551924; 18042262; 20301365
Intellectual disability syndromic and non-syndromic v0.6426 MAP2K1 Zornitza Stark Publications for gene: MAP2K1 were set to
Intellectual disability syndromic and non-syndromic v0.6425 MAP2K1 Zornitza Stark Mode of pathogenicity for gene: MAP2K1 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability syndromic and non-syndromic v0.6424 MAP2K1 Zornitza Stark Mode of inheritance for gene: MAP2K1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6423 MAP2K1 Zornitza Stark Mode of inheritance for gene: MAP2K1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6422 MAP2K2 Zornitza Stark Marked gene: MAP2K2 as ready
Intellectual disability syndromic and non-syndromic v0.6422 MAP2K2 Zornitza Stark Gene: map2k2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6422 MAP2K2 Zornitza Stark Phenotypes for gene: MAP2K2 were changed from to Cardiofaciocutaneous syndrome 3, MIM# 615279
Intellectual disability syndromic and non-syndromic v0.6421 MAP2K2 Zornitza Stark Mode of pathogenicity for gene: MAP2K2 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability syndromic and non-syndromic v0.6420 MAP2K2 Zornitza Stark Publications for gene: MAP2K2 were set to
Intellectual disability syndromic and non-syndromic v0.6419 MAP2K2 Zornitza Stark Mode of inheritance for gene: MAP2K2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6418 MAT1A Zornitza Stark Marked gene: MAT1A as ready
Intellectual disability syndromic and non-syndromic v0.6418 MAT1A Zornitza Stark Gene: mat1a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6418 MAT1A Zornitza Stark Phenotypes for gene: MAT1A were changed from to Hypermethioninemia, persistent, autosomal dominant, due to methionine adenosyltransferase I/III deficiency MIM#250850; Methionine adenosyltransferase deficiency, autosomal recessive MIM#250850; Disorders of the metabolism of sulphur amino acids
Intellectual disability syndromic and non-syndromic v0.6417 MAT1A Zornitza Stark Publications for gene: MAT1A were set to
Intellectual disability syndromic and non-syndromic v0.6416 MAT1A Zornitza Stark Mode of inheritance for gene: MAT1A was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6415 MBOAT7 Zornitza Stark Marked gene: MBOAT7 as ready
Intellectual disability syndromic and non-syndromic v0.6415 MBOAT7 Zornitza Stark Gene: mboat7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6415 MBOAT7 Zornitza Stark Phenotypes for gene: MBOAT7 were changed from to Intellectual disability MIM#617188
Intellectual disability syndromic and non-syndromic v0.6414 MBOAT7 Zornitza Stark Publications for gene: MBOAT7 were set to
Intellectual disability syndromic and non-syndromic v0.6413 MBOAT7 Zornitza Stark Mode of inheritance for gene: MBOAT7 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6412 MKKS Zornitza Stark Marked gene: MKKS as ready
Intellectual disability syndromic and non-syndromic v0.6412 MKKS Zornitza Stark Gene: mkks has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6412 MKKS Zornitza Stark Phenotypes for gene: MKKS were changed from to McKusick-Kaufman syndrome, MIM# 236700; Bardet-Biedl syndrome 6, MIM# 605231; Retinitis pigmentosa
Intellectual disability syndromic and non-syndromic v0.6411 MKKS Zornitza Stark Publications for gene: MKKS were set to
Intellectual disability syndromic and non-syndromic v0.6410 MKKS Zornitza Stark Mode of inheritance for gene: MKKS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6409 MKS1 Zornitza Stark Marked gene: MKS1 as ready
Intellectual disability syndromic and non-syndromic v0.6409 MKS1 Zornitza Stark Gene: mks1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6409 MKS1 Zornitza Stark Phenotypes for gene: MKS1 were changed from to Joubert syndrome 28, MIM# 617121; MONDO:0014928; Meckel syndrome 1, MIM# 249000; MONDO:0009571; Bardet-Biedl syndrome 13, MIM# 615990; MONDO:0014441
Intellectual disability syndromic and non-syndromic v0.6408 MKS1 Zornitza Stark Publications for gene: MKS1 were set to
Intellectual disability syndromic and non-syndromic v0.6407 MKS1 Zornitza Stark Mode of inheritance for gene: MKS1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6406 MLC1 Zornitza Stark Marked gene: MLC1 as ready
Intellectual disability syndromic and non-syndromic v0.6406 MLC1 Zornitza Stark Gene: mlc1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6406 MLC1 Zornitza Stark Phenotypes for gene: MLC1 were changed from to Megalencephalic leukoencephalopathy with subcortical cysts (MIM#604004)
Intellectual disability syndromic and non-syndromic v0.6405 MLC1 Zornitza Stark Publications for gene: MLC1 were set to
Intellectual disability syndromic and non-syndromic v0.6404 MLC1 Zornitza Stark Mode of inheritance for gene: MLC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6403 MMAA Zornitza Stark Marked gene: MMAA as ready
Intellectual disability syndromic and non-syndromic v0.6403 MMAA Zornitza Stark Gene: mmaa has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6403 MMAA Zornitza Stark Phenotypes for gene: MMAA were changed from to Methylmalonic aciduria, vitamin B12-responsive, cblA type, MIM# 251100
Intellectual disability syndromic and non-syndromic v0.6402 MMAA Zornitza Stark Publications for gene: MMAA were set to
Intellectual disability syndromic and non-syndromic v0.6401 MMAA Zornitza Stark Mode of inheritance for gene: MMAA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6400 MMAB Zornitza Stark Marked gene: MMAB as ready
Intellectual disability syndromic and non-syndromic v0.6400 MMAB Zornitza Stark Gene: mmab has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6400 MMAB Zornitza Stark Phenotypes for gene: MMAB were changed from to Methylmalonic aciduria, vitamin B12-responsive, cblB type, MIM# 251110
Intellectual disability syndromic and non-syndromic v0.6399 MMAB Zornitza Stark Publications for gene: MMAB were set to
Intellectual disability syndromic and non-syndromic v0.6398 MMAB Zornitza Stark Mode of inheritance for gene: MMAB was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6397 MMADHC Zornitza Stark Marked gene: MMADHC as ready
Intellectual disability syndromic and non-syndromic v0.6397 MMADHC Zornitza Stark Gene: mmadhc has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6397 MMADHC Zornitza Stark Phenotypes for gene: MMADHC were changed from to Homocystinuria, cblD type, variant 1 MIM#277410; Methylmalonic aciduria and homocystinuria, cblD type MIM#277410; Methylmalonic aciduria, cblD type, variant 2 MIM#277410; Disorders of cobalamin absorption, transport and metabolism
Intellectual disability syndromic and non-syndromic v0.6396 MMADHC Zornitza Stark Publications for gene: MMADHC were set to
Intellectual disability syndromic and non-syndromic v0.6395 MMADHC Zornitza Stark Mode of inheritance for gene: MMADHC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6394 MUT Zornitza Stark Marked gene: MUT as ready
Intellectual disability syndromic and non-syndromic v0.6394 MUT Zornitza Stark Gene: mut has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6394 MUT Zornitza Stark Phenotypes for gene: MUT were changed from to Methylmalonic aciduria, mut(0) type, MIM# 251000
Intellectual disability syndromic and non-syndromic v0.6393 MUT Zornitza Stark Publications for gene: MUT were set to
Intellectual disability syndromic and non-syndromic v0.6392 MUT Zornitza Stark Mode of inheritance for gene: MUT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6391 MOCS2 Zornitza Stark Marked gene: MOCS2 as ready
Intellectual disability syndromic and non-syndromic v0.6391 MOCS2 Zornitza Stark Gene: mocs2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6391 MOCS2 Zornitza Stark Phenotypes for gene: MOCS2 were changed from to Molybdenum cofactor deficiency B MIM#252160; Disorders of molybdenum cofactor metabolism
Intellectual disability syndromic and non-syndromic v0.6390 MOCS2 Zornitza Stark Publications for gene: MOCS2 were set to
Intellectual disability syndromic and non-syndromic v0.6389 MOCS2 Zornitza Stark Mode of inheritance for gene: MOCS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v0.288 BMP5 Zornitza Stark Marked gene: BMP5 as ready
Skeletal dysplasia v0.288 BMP5 Zornitza Stark Gene: bmp5 has been classified as Red List (Low Evidence).
Skeletal dysplasia v0.288 BMP5 Zornitza Stark Phenotypes for gene: BMP5 were changed from Skeletal dysostosis and atrioventricular septal defect to Skeletal dysplasia, MONDO:0018230, BMP5-related; Skeletal dysostosis and atrioventricular septal defect
Skeletal dysplasia v0.287 BMP5 Zornitza Stark reviewed gene: BMP5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Skeletal dysplasia, MONDO:0018230, BMP5-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2060 BMP5 Zornitza Stark Marked gene: BMP5 as ready
Mendeliome v1.2060 BMP5 Zornitza Stark Gene: bmp5 has been classified as Red List (Low Evidence).
Mendeliome v1.2060 BMP5 Zornitza Stark Phenotypes for gene: BMP5 were changed from Skeletal dysostosis and atrioventricular septal defect, no OMIM# to Skeletal dysplasia, MONDO:0018230, BMP5-related; Skeletal dysostosis and atrioventricular septal defect, no OMIM#
Mendeliome v1.2059 BMP5 Zornitza Stark Publications for gene: BMP5 were set to
Combined Immunodeficiency v1.75 RELB Zornitza Stark Publications for gene: RELB were set to 7834753; 26385063
Mendeliome v1.2058 RELB Zornitza Stark Publications for gene: RELB were set to 7834753; 26385063
Regression v0.565 POLR3K Zornitza Stark changed review comment from: PMID 30584594: Additional compound het case (c.322G>T; p.D108Y and large deletion, spanning approximately 17.8 kb from chr16:30,362-48,162) reported a phenotype consistent with POLR3-related leukodystrophy. Reduced POLR3K RNA expressed in the patient compared to controls. Now 3 cases with paediatric onset have been reported with supporting functional evidence and similar phenotypes to the orthologous POLR3 genes.; to: https://doi.org/10.1155/2024/8807171: Additional compound het case (c.322G>T; p.D108Y and large deletion, spanning approximately 17.8 kb from chr16:30,362-48,162) reported a phenotype consistent with POLR3-related leukodystrophy. Reduced POLR3K RNA expressed in the patient compared to controls. Now 3 cases with paediatric onset have been reported with supporting functional evidence and similar phenotypes to the orthologous POLR3 genes.
Regression v0.565 POLR3K Zornitza Stark Publications for gene: POLR3K were set to 30584594; 33659930
Regression v0.564 POLR3K Zornitza Stark Classified gene: POLR3K as Green List (high evidence)
Regression v0.564 POLR3K Zornitza Stark Gene: polr3k has been classified as Green List (High Evidence).
Regression v0.563 POLR3K Zornitza Stark Classified gene: POLR3K as Green List (high evidence)
Regression v0.563 POLR3K Zornitza Stark Gene: polr3k has been classified as Green List (High Evidence).
Regression v0.562 POLR3K Zornitza Stark edited their review of gene: POLR3K: Added comment: PMID 30584594: Additional compound het case (c.322G>T; p.D108Y and large deletion, spanning approximately 17.8 kb from chr16:30,362-48,162) reported a phenotype consistent with POLR3-related leukodystrophy. Reduced POLR3K RNA expressed in the patient compared to controls. Now 3 cases with paediatric onset have been reported with supporting functional evidence and similar phenotypes to the orthologous POLR3 genes.; Changed rating: GREEN; Changed publications: 30584594, 33659930, 30584594
IBMDx study v0.28 KLF1 Zornitza Stark Marked gene: KLF1 as ready
IBMDx study v0.28 KLF1 Zornitza Stark Gene: klf1 has been classified as Green List (High Evidence).
IBMDx study v0.28 KLF1 Zornitza Stark Phenotypes for gene: KLF1 were changed from MONDO:0013355; Dyserythropoietic anaemia, congenital, type IV, MIM# 613673 to Dyserythropoietic anaemia, congenital, type IV, MIM# 613673; MONDO:0013355; Anaemia, congenital dyserythropoietic, type IVb, MIM#620969
IBMDx study v0.27 KLF1 Zornitza Stark Publications for gene: KLF1 were set to
IBMDx study v0.26 KLF1 Zornitza Stark Mode of inheritance for gene: KLF1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
IBMDx study v0.25 KLF1 Zornitza Stark edited their review of gene: KLF1: Added comment: Ten individuals reported with bi-allelic variants and congenital dyserythropoietic anaemia.; Changed publications: 21055716, 33339573, 32815883, 32221653, 32032242, 31818881, 24443441, 25724378, 28361594, 34554218; Changed phenotypes: Dyserythropoietic anaemia, congenital, type IV, MIM# 613673, MONDO:0013355, Anaemia, congenital dyserythropoietic, type IVb, MIM#620969; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.279 KLF1 Zornitza Stark Phenotypes for gene: KLF1 were changed from Dyserythropoietic anaemia, congenital, type IV MIM#613673 to Dyserythropoietic anaemia, congenital, type IV MIM#613673; Anaemia, congenital dyserythropoietic, type IVb, MIM#620969
Fetal anomalies v1.278 KLF1 Zornitza Stark Publications for gene: KLF1 were set to 28361594; 25724378
Fetal anomalies v1.277 KLF1 Zornitza Stark Mode of inheritance for gene: KLF1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v1.276 KLF1 Zornitza Stark reviewed gene: KLF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24443441, 25724378, 28361594, 34554218; Phenotypes: Anaemia, congenital dyserythropoietic, type IVb, MIM#620969; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Red cell disorders v1.29 KLF1 Zornitza Stark Phenotypes for gene: KLF1 were changed from Dyserythropoietic anaemia, congenital, type IV, MIM# 613673; MONDO:0013355 to Dyserythropoietic anaemia, congenital, type IV, MIM# 613673; MONDO:0013355; Anaemia, congenital dyserythropoietic, type IVb, MIM#620969
Red cell disorders v1.28 KLF1 Zornitza Stark Publications for gene: KLF1 were set to 21055716; 33339573; 32815883; 32221653; 32032242; 31818881
Red cell disorders v1.27 KLF1 Zornitza Stark Mode of inheritance for gene: KLF1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Red cell disorders v1.26 KLF1 Zornitza Stark edited their review of gene: KLF1: Added comment: Ten individuals reported with bi-allelic variants and congenital dyserythropoietic anaemia.; Changed publications: 21055716, 33339573, 32815883, 32221653, 32032242, 31818881, 24443441, 25724378, 28361594, 34554218; Changed phenotypes: Dyserythropoietic anaemia, congenital, type IV, MIM# 613673, MONDO:0013355, Anaemia, congenital dyserythropoietic, type IVb, MIM#620969; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.2057 KLF1 Zornitza Stark Phenotypes for gene: KLF1 were changed from Dyserythropoietic anaemia, congenital, type IV, MIM# 613673; MONDO:0013355 to Dyserythropoietic anaemia, congenital, type IV, MIM# 613673; MONDO:0013355; Anaemia, congenital dyserythropoietic, type IVb, MIM#620969
Mendeliome v1.2056 KLF1 Zornitza Stark Publications for gene: KLF1 were set to 21055716; 33339573; 32815883; 32221653; 32032242; 31818881
Mendeliome v1.2055 KLF1 Zornitza Stark Mode of inheritance for gene: KLF1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.2054 KLF1 Zornitza Stark edited their review of gene: KLF1: Added comment: Ten individuals reported with bi-allelic variants and congenital dyserythropoietic anaemia.; Changed publications: 21055716, 33339573, 32815883, 32221653, 32032242, 31818881, 24443441, 25724378, 28361594, 34554218; Changed phenotypes: Dyserythropoietic anaemia, congenital, type IV, MIM# 613673, MONDO:0013355, Anaemia, congenital dyserythropoietic, type IVb, MIM#620969; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hydrops fetalis v0.324 KLF1 Zornitza Stark Phenotypes for gene: KLF1 were changed from Congenital Dyserythropoietic Anemia Type IV, MIM#613673; severe nonspherocytic hemolytic anemia to Congenital Dyserythropoietic Anemia Type IV, MIM#613673; Anaemia, congenital dyserythropoietic, type IVb, MIM#620969
Hydrops fetalis v0.323 KLF1 Zornitza Stark Publications for gene: KLF1 were set to 29300242; 25724378; 28265383
Hydrops fetalis v0.322 KLF1 Zornitza Stark Mode of inheritance for gene: KLF1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hydrops fetalis v0.321 KLF1 Zornitza Stark reviewed gene: KLF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24443441, 25724378, 28361594, 34554218; Phenotypes: Anaemia, congenital dyserythropoietic, type IVb, MIM#620969; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bone Marrow Failure v1.101 KLF1 Zornitza Stark Phenotypes for gene: KLF1 were changed from Dyserythropoietic anaemia, congenital, type IV, MIM# 613673; MONDO:0013355 to Dyserythropoietic anaemia, congenital, type IVa, MIM# 613673; MONDO:0013355; Anaemia, congenital dyserythropoietic, type IVb, MIM#620969
Bone Marrow Failure v1.100 KLF1 Zornitza Stark Publications for gene: KLF1 were set to 21055716; 33339573; 32815883; 32221653; 32032242; 31818881
Bone Marrow Failure v1.99 KLF1 Zornitza Stark Mode of inheritance for gene: KLF1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Bone Marrow Failure v1.98 KLF1 Zornitza Stark edited their review of gene: KLF1: Added comment: Ten individuals reported with bi-allelic variants and congenital dyserythropoietic anaemia.; Changed publications: 21055716, 33339573, 32815883, 32221653, 32032242, 31818881, 24443441, 25724378, 28361594, 34554218; Changed phenotypes: Dyserythropoietic anaemia, congenital, type IVa, MIM# 613673, MONDO:0013355, Anaemia, congenital dyserythropoietic, type IVb, MIM#620969; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Prepair 1000+ v1.390 BBS10 Lilian Downie Marked gene: BBS10 as ready
Prepair 1000+ v1.390 BBS10 Lilian Downie Gene: bbs10 has been classified as Green List (High Evidence).
Prepair 1000+ v1.390 BBS10 Lilian Downie Publications for gene: BBS10 were set to
Prepair 1000+ v1.389 BSCL2 Lilian Downie Marked gene: BSCL2 as ready
Prepair 1000+ v1.389 BSCL2 Lilian Downie Gene: bscl2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.389 BSCL2 Lilian Downie Phenotypes for gene: BSCL2 were changed from Encephalopathy, progressive, with or without lipodystrophy, 615924 (3) to Encephalopathy, progressive, with or without lipodystrophy (MIM#615924); Lipodystrophy, congenital generalized, type 2 (MIM#269700)
Prepair 1000+ v1.388 BSCL2 Lilian Downie Publications for gene: BSCL2 were set to
Prepair 1000+ v1.387 C5 Lilian Downie Marked gene: C5 as ready
Prepair 1000+ v1.387 C5 Lilian Downie Gene: c5 has been classified as Green List (High Evidence).
Prepair 1000+ v1.387 C5 Lilian Downie Publications for gene: C5 were set to
Prepair 1000+ v1.386 CARS2 Lilian Downie Marked gene: CARS2 as ready
Prepair 1000+ v1.386 CARS2 Lilian Downie Gene: cars2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.386 CARS2 Lilian Downie Publications for gene: CARS2 were set to
Prepair 1000+ v1.385 SGPL1 Lilian Downie Marked gene: SGPL1 as ready
Prepair 1000+ v1.385 SGPL1 Lilian Downie Gene: sgpl1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.385 SGPL1 Lilian Downie Publications for gene: SGPL1 were set to
Prepair 1000+ v1.384 SGPL1 Lilian Downie reviewed gene: SGPL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 36050428, 30517686, 35748945; Phenotypes: RENI syndrome MIM#617575; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.384 TSPYL1 Lilian Downie Marked gene: TSPYL1 as ready
Prepair 1000+ v1.384 TSPYL1 Lilian Downie Added comment: Comment when marking as ready: Originally reported only in Amish community, founder variant
subsequently reported in 3 unrelated families, non amish - GREEN AT UPGRADE
2 cohort studies looking for variants in this gene in SIDS cohorts but it's very rare and presents with more of a progressive neurological phenotype in the non Amish families
Prepair 1000+ v1.384 TSPYL1 Lilian Downie Gene: tspyl1 has been classified as Red List (Low Evidence).
Prepair 1000+ v1.384 TSPYL1 Lilian Downie Publications for gene: TSPYL1 were set to
Prepair 1000+ v1.383 SLC38A8 Lilian Downie Marked gene: SLC38A8 as ready
Prepair 1000+ v1.383 SLC38A8 Lilian Downie Gene: slc38a8 has been classified as Green List (High Evidence).
Prepair 1000+ v1.383 SLC38A8 Lilian Downie Publications for gene: SLC38A8 were set to
Prepair 1000+ v1.382 NDUFS8 Lilian Downie Marked gene: NDUFS8 as ready
Prepair 1000+ v1.382 NDUFS8 Lilian Downie Gene: ndufs8 has been classified as Green List (High Evidence).
Prepair 1000+ v1.382 NDUFS8 Lilian Downie Phenotypes for gene: NDUFS8 were changed from Leigh syndrome due to mitochondrial complex I deficiency, 256000 (3) to Mitochondrial complex I deficiency, nuclear type 2 (MIM#618222)
Prepair 1000+ v1.381 NDUFS8 Lilian Downie Publications for gene: NDUFS8 were set to
Prepair 1000+ v1.380 NGF Lilian Downie Marked gene: NGF as ready
Prepair 1000+ v1.380 NGF Lilian Downie Gene: ngf has been classified as Green List (High Evidence).
Prepair 1000+ v1.380 NGF Lilian Downie Publications for gene: NGF were set to
Prepair 1000+ v1.379 NECTIN1 Lilian Downie Marked gene: NECTIN1 as ready
Prepair 1000+ v1.379 NECTIN1 Lilian Downie Gene: nectin1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.379 NECTIN1 Lilian Downie Publications for gene: NECTIN1 were set to
Prepair 1000+ v1.378 FGA Lilian Downie Marked gene: FGA as ready
Prepair 1000+ v1.378 FGA Lilian Downie Gene: fga has been classified as Green List (High Evidence).
Prepair 1000+ v1.378 FGB Lilian Downie Marked gene: FGB as ready
Prepair 1000+ v1.378 FGB Lilian Downie Gene: fgb has been classified as Green List (High Evidence).
Prepair 1000+ v1.378 FGG Lilian Downie Marked gene: FGG as ready
Prepair 1000+ v1.378 FGG Lilian Downie Gene: fgg has been classified as Green List (High Evidence).
Prepair 1000+ v1.378 FGG Lilian Downie Publications for gene: FGG were set to
Prepair 1000+ v1.377 GNPTAB Lilian Downie Marked gene: GNPTAB as ready
Prepair 1000+ v1.377 GNPTAB Lilian Downie Gene: gnptab has been classified as Green List (High Evidence).
Prepair 1000+ v1.377 GNPTAB Lilian Downie Phenotypes for gene: GNPTAB were changed from Mucolipidosis III alpha/beta, 252600 (3) to Mucolipidosis III alpha/beta MIM#252600; Mucolipidosis II alpha/beta MIM#252500
Prepair 1000+ v1.376 GNPTAB Lilian Downie Publications for gene: GNPTAB were set to
Prepair 1000+ v1.375 GSS Lilian Downie Marked gene: GSS as ready
Prepair 1000+ v1.375 GSS Lilian Downie Gene: gss has been classified as Green List (High Evidence).
Prepair 1000+ v1.375 HADHB Lilian Downie Marked gene: HADHB as ready
Prepair 1000+ v1.375 HADHB Lilian Downie Gene: hadhb has been classified as Green List (High Evidence).
Prepair 1000+ v1.375 HADHB Lilian Downie Phenotypes for gene: HADHB were changed from Trifunctional protein deficiency, 609015 (3) to Mitochondrial trifunctional protein deficiency 2 MIM#620300
Prepair 1000+ v1.374 HLCS Lilian Downie Marked gene: HLCS as ready
Prepair 1000+ v1.374 HLCS Lilian Downie Gene: hlcs has been classified as Green List (High Evidence).
Prepair 1000+ v1.374 HLCS Lilian Downie Publications for gene: HLCS were set to
Prepair 1000+ v1.373 HPS5 Lilian Downie Marked gene: HPS5 as ready
Prepair 1000+ v1.373 HPS5 Lilian Downie Gene: hps5 has been classified as Green List (High Evidence).
Prepair 1000+ v1.373 KCTD7 Lilian Downie Marked gene: KCTD7 as ready
Prepair 1000+ v1.373 KCTD7 Lilian Downie Gene: kctd7 has been classified as Green List (High Evidence).
Prepair 1000+ v1.373 KCTD7 Lilian Downie Publications for gene: KCTD7 were set to
Prepair 1000+ v1.372 LARS Lilian Downie Marked gene: LARS as ready
Prepair 1000+ v1.372 LARS Lilian Downie Gene: lars has been classified as Green List (High Evidence).
Prepair 1000+ v1.372 LARS Lilian Downie Publications for gene: LARS were set to
Prepair 1000+ v1.371 PNKP Lilian Downie Marked gene: PNKP as ready
Prepair 1000+ v1.371 PNKP Lilian Downie Gene: pnkp has been classified as Green List (High Evidence).
Prepair 1000+ v1.371 PNKP Lilian Downie Added comment: Comment on phenotypes: CMT phenotype is usually onset in 30's but childhood onset has been reported.
Prepair 1000+ v1.371 PNKP Lilian Downie Phenotypes for gene: PNKP were changed from Microcephaly, seizures, and developmental delay, 613402 (3) to Charcot-Marie-Tooth disease, type 2B2 MIM#605589; Ataxia-oculomotor apraxia 4 MIM#616267; Microcephaly, seizures, and developmental delay MIM#613402
Prepair 1000+ v1.370 PNKP Lilian Downie Publications for gene: PNKP were set to
Prepair 1000+ v1.369 CYP27A1 Lilian Downie Marked gene: CYP27A1 as ready
Prepair 1000+ v1.369 CYP27A1 Lilian Downie Added comment: Comment when marking as ready: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive lipid-storage disease characterized clinically by progressive neurologic dysfunction (cerebellar ataxia beginning after puberty, systemic spinal cord involvement and a pseudobulbar phase leading to death), premature atherosclerosis, and cataracts. Large deposits of cholesterol and cholestanol are found in virtually every tissue, particularly the Achilles tendons, brain, and lungs. Cholestanol, the 5-alpha-dihydro derivative of cholesterol, is enriched relative to cholesterol in all tissues. The diagnosis can be made by demonstrating cholestanol in abnormal amounts in the serum and tendon of persons suspected of being affected. Plasma cholesterol concentrations are low normal in CTX patients. (OMIM)
Prepair 1000+ v1.369 CYP27A1 Lilian Downie Gene: cyp27a1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.369 CYP27A1 Lilian Downie Publications for gene: CYP27A1 were set to
Prepair 1000+ v1.368 CYP7B1 Lilian Downie Marked gene: CYP7B1 as ready
Prepair 1000+ v1.368 CYP7B1 Lilian Downie Gene: cyp7b1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.368 CYP7B1 Lilian Downie Phenotypes for gene: CYP7B1 were changed from Bile acid synthesis defect, congenital, 3, 613812 (3) to Bile acid synthesis defect, congenital, 3, 613812 (3); Spastic paraplegia 5A, 270800 (3)
Prepair 1000+ v1.367 CYP7B1 Lilian Downie Publications for gene: CYP7B1 were set to
Prepair 1000+ v1.366 OCRL Lilian Downie Marked gene: OCRL as ready
Prepair 1000+ v1.366 OCRL Lilian Downie Gene: ocrl has been classified as Green List (High Evidence).
Prepair 1000+ v1.366 OCRL Lilian Downie Phenotypes for gene: OCRL were changed from Lowe syndrome, 309000 (3) to Dent disease 2 MIM#300555; Lowe syndrome MIM#309000
Prepair 1000+ v1.365 OCRL Lilian Downie Publications for gene: OCRL were set to
Prepair 1000+ v1.364 PKHD1 Lilian Downie Marked gene: PKHD1 as ready
Prepair 1000+ v1.364 PKHD1 Lilian Downie Gene: pkhd1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.364 PKHD1 Lilian Downie Phenotypes for gene: PKHD1 were changed from Polycystic kidney and hepatic disease, 263200 (3) to Polycystic kidney disease 4, with or without hepatic disease MIM#263200
Prepair 1000+ v1.363 PKHD1 Lilian Downie Publications for gene: PKHD1 were set to
Prepair 1000+ v1.362 DHCR7 Lilian Downie Marked gene: DHCR7 as ready
Prepair 1000+ v1.362 DHCR7 Lilian Downie Gene: dhcr7 has been classified as Green List (High Evidence).
Prepair 1000+ v1.362 DHCR7 Lilian Downie Publications for gene: DHCR7 were set to
Prepair 1000+ v1.361 ALPL Lilian Downie Marked gene: ALPL as ready
Prepair 1000+ v1.361 ALPL Lilian Downie Gene: alpl has been classified as Green List (High Evidence).
Prepair 1000+ v1.361 ALPL Lilian Downie Phenotypes for gene: ALPL were changed from Hypophosphatasia, infantile, 241500 (3) to Hypophosphatasia, childhood (MIM#241510); Hypophosphatasia, infantile (MIM#241500)
Prepair 1000+ v1.360 ALPL Lilian Downie Publications for gene: ALPL were set to
Intellectual disability syndromic and non-syndromic v0.6388 ATAD2B Zornitza Stark Marked gene: ATAD2B as ready
Intellectual disability syndromic and non-syndromic v0.6388 ATAD2B Zornitza Stark Gene: atad2b has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6388 ATAD2B Zornitza Stark Classified gene: ATAD2B as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6388 ATAD2B Zornitza Stark Gene: atad2b has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6387 POLR3K Bryony Thompson Classified gene: POLR3K as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6387 POLR3K Bryony Thompson Gene: polr3k has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6386 POLR3K Bryony Thompson gene: POLR3K was added
gene: POLR3K was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: POLR3K was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3K were set to https://doi.org/10.1155/2024/8807171; 30584594
Phenotypes for gene: POLR3K were set to POLR3-related leukodystrophy MONDO:0700282
Review for gene: POLR3K was set to GREEN
Added comment: 3 apparently unrelated cases (1 compound het & 2 homozygous for the same missense & supporting functional assays) with phenotypes consistent with POLR3-related leukodystrophy which includes ID and DD as part of the phenotype.
Sources: Literature
Leukodystrophy - paediatric v0.313 POLR3K Bryony Thompson Publications for gene: POLR3K were set to 30584594; 33659930
Leukodystrophy - paediatric v0.312 POLR3K Bryony Thompson Phenotypes for gene: POLR3K were changed from Hypomyelinating leukodystrophy-21, MIM#619310 to POLR3-related leukodystrophy MONDO:0700282
Leukodystrophy - paediatric v0.311 POLR3K Bryony Thompson Classified gene: POLR3K as Green List (high evidence)
Leukodystrophy - paediatric v0.311 POLR3K Bryony Thompson Gene: polr3k has been classified as Green List (High Evidence).
Leukodystrophy - paediatric v0.310 POLR3K Bryony Thompson reviewed gene: POLR3K: Rating: GREEN; Mode of pathogenicity: None; Publications: https://doi.org/10.1155/2024/8807171, 30584594; Phenotypes: POLR3-related leukodystrophy MONDO:0700282; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2054 POLR3K Bryony Thompson Phenotypes for gene: POLR3K were changed from Hypomyelinating leukodystrophy-21, MIM#619310 to POLR3-related leukodystrophy MONDO:0700282
Mendeliome v1.2053 POLR3K Bryony Thompson Publications for gene: POLR3K were set to 30584594; 33659930
Mendeliome v1.2052 POLR3K Bryony Thompson Classified gene: POLR3K as Green List (high evidence)
Mendeliome v1.2052 POLR3K Bryony Thompson Gene: polr3k has been classified as Green List (High Evidence).
Mendeliome v1.2051 POLR3K Bryony Thompson reviewed gene: POLR3K: Rating: GREEN; Mode of pathogenicity: None; Publications: https://doi.org/10.1155/2024/8807171, 30584594; Phenotypes: POLR3-related leukodystrophy MONDO:0700282; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2051 RELB Chirag Patel Classified gene: RELB as Green List (high evidence)
Mendeliome v1.2051 RELB Chirag Patel Gene: relb has been classified as Green List (High Evidence).
Mendeliome v1.2050 RELB Chirag Patel reviewed gene: RELB: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 39231201; Phenotypes: T-cell and B cell immunodeficiency, Immunodeficiency 53, OMIM #617585; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Combined Immunodeficiency v1.74 RELB Chirag Patel Classified gene: RELB as Green List (high evidence)
Combined Immunodeficiency v1.74 RELB Chirag Patel Gene: relb has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.73 RELB Chirag Patel reviewed gene: RELB: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 39231201; Phenotypes: T-cell and B cell immunodeficiency, Immunodeficiency 53, OMIM #617585,; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2049 BMP5 Chirag Patel edited their review of gene: BMP5: Changed publications: PMID: 39239663
Mendeliome v1.2048 BMP5 Chirag Patel gene: BMP5 was added
gene: BMP5 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: BMP5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BMP5 were set to Skeletal dysostosis and atrioventricular septal defect, no OMIM#
Phenotypes for gene: BMP5 were set to Skeletal dysostosis and atrioventricular septal defect, no OMIM#
Review for gene: BMP5 was set to RED
Added comment: 1 patient with skeletal dysostosis, atrioventricular septal defect, hypermobility, laryngo-tracheo-bronchomalacia and dysmorphic features (malar hypoplasia, short palpebral fissures, short nose, low nasal bridge, anteverted nares, long philtrum, small ears with abnormally folded antihelix). Skeletal survey showed mild thoracolumbar scoliosis, four sacral segments, absent ossification of the inferior pubic rami, and patellar aplasia. Trio WGS identified compound heterozygous loss of function variants in BMP5 (c.88_89del, p.(Gly30Argfs*11) and c.1104+2del, p.(?). Abnormal splicing was proven on the suspected splice variant using maternal fibroblasts. BMP5 expression is confined to specific parts of the skeleton and cartilage in mice and is tightly regulated by different enhancers. Previous studies of chicken embryonic heart development showed BMP5 expression in the endoderm underlying the precardiac mesoderm, the myocardium of the atrioventricular canal and outflow tract regions. Other bone morphogenetic proteins are linked to several genetic skeletal disorders.
Sources: Literature
Skeletal dysplasia v0.287 BMP5 Chirag Patel changed review comment from: 1 patient with skeletal dysostosis, atrioventricular septal defect, hypermobility, laryngo-tracheo-bronchomalacia and dysmorphic features (malar hypoplasia, short palpebral fissures, short nose, low nasal bridge, anteverted nares, long philtrum, small ears with abnormally folded antihelix). Skeletal survey showed mild thoracolumbar scoliosis, four sacral segments, absent ossification of the inferior pubic rami, and patellar aplasia. Trio WGS identified compound heterozygous loss of function variants in BMP5 (c.88_89del, p.(Gly30Argfs*11) and c.1104+2del, p.(?). Abnormal splicing was proven on the suspected splice variant using maternal fibroblasts. BMP5 expression is confined to specific parts of the skeleton and cartilage in mice and is tightly regulated by different enhancers. Previous studies of chicken embryonic heart development showed BMP5 expression in the endoderm underlying the precardiac mesoderm, the myocardium of the atrioventricular canal and outflow tract regions. Other bone morphogenetic proteins are linked to several genetic skeletal disorders.
Sources: Literature; to: 1 patient with skeletal dysostosis, atrioventricular septal defect, hypermobility, laryngo-tracheo-bronchomalacia and dysmorphic features (malar hypoplasia, short palpebral fissures, short nose, low nasal bridge, anteverted nares, long philtrum, small ears with abnormally folded antihelix). Skeletal survey showed mild thoracolumbar scoliosis, four sacral segments, absent ossification of the inferior pubic rami, and patellar aplasia. Trio WGS identified compound heterozygous loss of function variants in BMP5 (c.88_89del, p.(Gly30Argfs*11) and c.1104+2del, p.(?). Abnormal splicing was proven on the suspected splice variant using maternal fibroblasts. BMP5 expression is confined to specific parts of the skeleton and cartilage in mice and is tightly regulated by different enhancers. Previous studies of chicken embryonic heart development showed BMP5 expression in the endoderm underlying the precardiac mesoderm, the myocardium of the atrioventricular canal and outflow tract regions. Other bone morphogenetic proteins are linked to several genetic skeletal disorders.
Sources: Literature
Skeletal dysplasia v0.287 BMP5 Chirag Patel gene: BMP5 was added
gene: BMP5 was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: BMP5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BMP5 were set to PMID: 39239663
Phenotypes for gene: BMP5 were set to Skeletal dysostosis and atrioventricular septal defect
Review for gene: BMP5 was set to RED
Added comment: 1 patient with skeletal dysostosis, atrioventricular septal defect, hypermobility, laryngo-tracheo-bronchomalacia and dysmorphic features (malar hypoplasia, short palpebral fissures, short nose, low nasal bridge, anteverted nares, long philtrum, small ears with abnormally folded antihelix). Skeletal survey showed mild thoracolumbar scoliosis, four sacral segments, absent ossification of the inferior pubic rami, and patellar aplasia. Trio WGS identified compound heterozygous loss of function variants in BMP5 (c.88_89del, p.(Gly30Argfs*11) and c.1104+2del, p.(?). Abnormal splicing was proven on the suspected splice variant using maternal fibroblasts. BMP5 expression is confined to specific parts of the skeleton and cartilage in mice and is tightly regulated by different enhancers. Previous studies of chicken embryonic heart development showed BMP5 expression in the endoderm underlying the precardiac mesoderm, the myocardium of the atrioventricular canal and outflow tract regions. Other bone morphogenetic proteins are linked to several genetic skeletal disorders.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6385 GFAP Bryony Thompson Marked gene: GFAP as ready
Intellectual disability syndromic and non-syndromic v0.6385 GFAP Bryony Thompson Gene: gfap has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6385 GFAP Bryony Thompson Phenotypes for gene: GFAP were changed from to Alexander disease MONDO:0008752
Intellectual disability syndromic and non-syndromic v0.6384 GFAP Bryony Thompson Publications for gene: GFAP were set to
Intellectual disability syndromic and non-syndromic v0.6383 GFAP Bryony Thompson Mode of inheritance for gene: GFAP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6382 GFAP Bryony Thompson reviewed gene: GFAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301351; Phenotypes: Alexander disease MONDO:0008752; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hand and foot malformations v0.76 FLVCR1 Bryony Thompson Marked gene: FLVCR1 as ready
Hand and foot malformations v0.76 FLVCR1 Bryony Thompson Gene: flvcr1 has been classified as Green List (High Evidence).
Hand and foot malformations v0.76 FLVCR1 Bryony Thompson Classified gene: FLVCR1 as Green List (high evidence)
Hand and foot malformations v0.76 FLVCR1 Bryony Thompson Gene: flvcr1 has been classified as Green List (High Evidence).
Hand and foot malformations v0.75 FLVCR1 Bryony Thompson gene: FLVCR1 was added
gene: FLVCR1 was added to Hand and foot malformations. Sources: Literature
Mode of inheritance for gene: FLVCR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FLVCR1 were set to 39306721
Phenotypes for gene: FLVCR1 were set to neurodevelopmental disorder MONDO:0700092, FLVCR1-related
Review for gene: FLVCR1 was set to GREEN
gene: FLVCR1 was marked as current diagnostic
Added comment: A study with 30 patients from 23 unrelated families with biallelic ultra-rare missense and predicted loss-of-function variants in FLVCR1 with a novel FLVCR1-related phenotype characterised by severe developmental disorders with profound developmental delay, microcephaly, brain malformations, epilepsy, spasticity, and premature death. Optic disk atrophy, limb and digital malformations, and macrocytic anaemia can be present.
Sources: Literature
Optic Atrophy v1.42 FLVCR1 Bryony Thompson Marked gene: FLVCR1 as ready
Optic Atrophy v1.42 FLVCR1 Bryony Thompson Gene: flvcr1 has been classified as Green List (High Evidence).
Optic Atrophy v1.42 FLVCR1 Bryony Thompson Classified gene: FLVCR1 as Green List (high evidence)
Optic Atrophy v1.42 FLVCR1 Bryony Thompson Gene: flvcr1 has been classified as Green List (High Evidence).
Optic Atrophy v1.41 FLVCR1 Bryony Thompson gene: FLVCR1 was added
gene: FLVCR1 was added to Optic Atrophy. Sources: Literature
Mode of inheritance for gene: FLVCR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FLVCR1 were set to 39306721
Phenotypes for gene: FLVCR1 were set to neurodevelopmental disorder MONDO:0700092, FLVCR1-related
Review for gene: FLVCR1 was set to GREEN
Added comment: A study with 30 patients from 23 unrelated families with biallelic ultra-rare missense and predicted loss-of-function variants in FLVCR1 with a novel FLVCR1-related phenotype characterised by severe developmental disorders with profound developmental delay, microcephaly, brain malformations, epilepsy, spasticity, and premature death. Optic disk atrophy, limb and digital malformations, and macrocytic anaemia can be present.
Sources: Literature
Genetic Epilepsy v1.63 FLVCR1 Bryony Thompson Marked gene: FLVCR1 as ready
Genetic Epilepsy v1.63 FLVCR1 Bryony Thompson Gene: flvcr1 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.63 FLVCR1 Bryony Thompson Classified gene: FLVCR1 as Green List (high evidence)
Genetic Epilepsy v1.63 FLVCR1 Bryony Thompson Gene: flvcr1 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.62 FLVCR1 Bryony Thompson gene: FLVCR1 was added
gene: FLVCR1 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: FLVCR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FLVCR1 were set to 39306721
Phenotypes for gene: FLVCR1 were set to neurodevelopmental disorder MONDO:0700092, FLVCR1-related
Review for gene: FLVCR1 was set to GREEN
gene: FLVCR1 was marked as current diagnostic
Added comment: A study with 30 patients from 23 unrelated families with biallelic ultra-rare missense and predicted loss-of-function variants in FLVCR1 with a novel FLVCR1-related phenotype characterised by severe developmental disorders with profound developmental delay, microcephaly, brain malformations, epilepsy, spasticity, and premature death. Optic disk atrophy, limb and digital malformations, and macrocytic anaemia can be present.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6382 ATAD2B Zornitza Stark gene: ATAD2B was added
gene: ATAD2B was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ATAD2B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATAD2B were set to 39313616
Phenotypes for gene: ATAD2B were set to neurodevelopmental disorder MONDO:0700092, ATAD2B-related
Review for gene: ATAD2B was set to AMBER
Added comment: 3 families including 2 siblings
1 fam is hom for a highly conserved missense

Amber because of the lack of specific phenotypes:
Abnormality of the nervous system and Abnormality of the eye
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6381 MRPS22 Zornitza Stark Marked gene: MRPS22 as ready
Intellectual disability syndromic and non-syndromic v0.6381 MRPS22 Zornitza Stark Gene: mrps22 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6381 MRPS22 Zornitza Stark Phenotypes for gene: MRPS22 were changed from to Combined oxidative phosphorylation deficiency 5 MIM#611719
Intellectual disability syndromic and non-syndromic v0.6380 MRPS22 Zornitza Stark Publications for gene: MRPS22 were set to
Intellectual disability syndromic and non-syndromic v0.6379 MRPS22 Zornitza Stark Mode of inheritance for gene: MRPS22 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6378 MTFMT Zornitza Stark Marked gene: MTFMT as ready
Intellectual disability syndromic and non-syndromic v0.6378 MTFMT Zornitza Stark Gene: mtfmt has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6378 MTFMT Zornitza Stark Phenotypes for gene: MTFMT were changed from to Combined oxidative phosphorylation deficiency 15, MIM# 614947; Mitochondrial complex I deficiency, nuclear type 27, MIM# 618248
Intellectual disability syndromic and non-syndromic v0.6377 MTFMT Zornitza Stark Publications for gene: MTFMT were set to 21907147; 23499752; 24461907; 22499348
Intellectual disability syndromic and non-syndromic v0.6376 MTFMT Zornitza Stark Publications for gene: MTFMT were set to
Intellectual disability syndromic and non-syndromic v0.6375 MTFMT Zornitza Stark Mode of inheritance for gene: MTFMT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6374 MVK Zornitza Stark Marked gene: MVK as ready
Intellectual disability syndromic and non-syndromic v0.6374 MVK Zornitza Stark Gene: mvk has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6374 MVK Zornitza Stark Phenotypes for gene: MVK were changed from to Hyper-IgD syndrome (MIM#260920); Mevalonic aciduria (MIM#610377)
Intellectual disability syndromic and non-syndromic v0.6374 MVK Zornitza Stark Publications for gene: MVK were set to 29047407; 26409462
Intellectual disability syndromic and non-syndromic v0.6373 MVK Zornitza Stark Publications for gene: MVK were set to 29047407; 26409462
Intellectual disability syndromic and non-syndromic v0.6373 MVK Zornitza Stark Publications for gene: MVK were set to
Intellectual disability syndromic and non-syndromic v0.6373 MVK Zornitza Stark Mode of inheritance for gene: MVK was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6372 MVK Zornitza Stark Mode of inheritance for gene: MVK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6371 MYO5A Zornitza Stark Marked gene: MYO5A as ready
Intellectual disability syndromic and non-syndromic v0.6371 MYO5A Zornitza Stark Gene: myo5a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6371 MYO5A Zornitza Stark Phenotypes for gene: MYO5A were changed from to Griscelli syndrome, type 1 MIM#214450
Intellectual disability syndromic and non-syndromic v0.6370 MYO5A Zornitza Stark Publications for gene: MYO5A were set to
Intellectual disability syndromic and non-syndromic v0.6369 MYO5A Zornitza Stark Mode of inheritance for gene: MYO5A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6368 MTHFR Zornitza Stark Marked gene: MTHFR as ready
Intellectual disability syndromic and non-syndromic v0.6368 MTHFR Zornitza Stark Gene: mthfr has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6368 MTHFR Zornitza Stark Phenotypes for gene: MTHFR were changed from to Homocystinuria due to MTHFR deficiency MIM#236250; Disorders of folate metabolism and transport
Intellectual disability syndromic and non-syndromic v0.6367 MTHFR Zornitza Stark Publications for gene: MTHFR were set to
Intellectual disability syndromic and non-syndromic v0.6366 MTHFR Zornitza Stark Mode of inheritance for gene: MTHFR was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6365 NPC2 Zornitza Stark Marked gene: NPC2 as ready
Intellectual disability syndromic and non-syndromic v0.6365 NPC2 Zornitza Stark Gene: npc2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6365 NPC2 Zornitza Stark Phenotypes for gene: NPC2 were changed from to Niemann-pick disease, type C2, MIM# 607625; MONDO:0011873
Intellectual disability syndromic and non-syndromic v0.6364 NPC2 Zornitza Stark Publications for gene: NPC2 were set to 11125141; 17470133
Intellectual disability syndromic and non-syndromic v0.6363 NPC2 Zornitza Stark Publications for gene: NPC2 were set to
Intellectual disability syndromic and non-syndromic v0.6362 NPC2 Zornitza Stark Mode of inheritance for gene: NPC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6361 NPC1 Zornitza Stark Marked gene: NPC1 as ready
Intellectual disability syndromic and non-syndromic v0.6361 NPC1 Zornitza Stark Gene: npc1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6361 NPC1 Zornitza Stark Phenotypes for gene: NPC1 were changed from to Niemann-Pick disease, type C1 and type D, MIM# 257220; MONDO:0009757
Intellectual disability syndromic and non-syndromic v0.6360 NPC1 Zornitza Stark Publications for gene: NPC1 were set to
Intellectual disability syndromic and non-syndromic v0.6359 NPC1 Zornitza Stark Mode of inheritance for gene: NPC1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6358 NKX2-1 Zornitza Stark Marked gene: NKX2-1 as ready
Intellectual disability syndromic and non-syndromic v0.6358 NKX2-1 Zornitza Stark Gene: nkx2-1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6358 NKX2-1 Zornitza Stark Phenotypes for gene: NKX2-1 were changed from Choreoathetosis, hypothyroidism, and neonatal respiratory distress MIM#610978 to Choreoathetosis, hypothyroidism, and neonatal respiratory distress MIM#610978
Intellectual disability syndromic and non-syndromic v0.6357 NKX2-1 Zornitza Stark Phenotypes for gene: NKX2-1 were changed from to Choreoathetosis, hypothyroidism, and neonatal respiratory distress MIM#610978
Intellectual disability syndromic and non-syndromic v0.6356 NKX2-1 Zornitza Stark Publications for gene: NKX2-1 were set to 10931427; 27066577; 26839702; 26103969; 23911641; 11854319; 24714694
Intellectual disability syndromic and non-syndromic v0.6355 NKX2-1 Zornitza Stark Publications for gene: NKX2-1 were set to
Intellectual disability syndromic and non-syndromic v0.6354 NKX2-1 Zornitza Stark Mode of inheritance for gene: NKX2-1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6353 NGLY1 Zornitza Stark Marked gene: NGLY1 as ready
Intellectual disability syndromic and non-syndromic v0.6353 NGLY1 Zornitza Stark Gene: ngly1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6353 NGLY1 Zornitza Stark Phenotypes for gene: NGLY1 were changed from to Congenital disorder of deglycosylation (OMIM 615273)
Intellectual disability syndromic and non-syndromic v0.6352 NGLY1 Zornitza Stark reviewed gene: NGLY1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24651605, 27388694, 32259258; Phenotypes: Congenital disorder of deglycosylation (OMIM 615273); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6352 NGLY1 Zornitza Stark Publications for gene: NGLY1 were set to
Intellectual disability syndromic and non-syndromic v0.6351 NGLY1 Zornitza Stark Mode of inheritance for gene: NGLY1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6350 NFIX Zornitza Stark Marked gene: NFIX as ready
Intellectual disability syndromic and non-syndromic v0.6350 NFIX Zornitza Stark Gene: nfix has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6350 NFIX Zornitza Stark Phenotypes for gene: NFIX were changed from to Sotos syndrome 2 (MIM#614753); Marshall-Smith syndrome, MIM# 602535
Intellectual disability syndromic and non-syndromic v0.6349 NFIX Zornitza Stark Publications for gene: NFIX were set to 33034087; 29897170; 30548146; 25118028
Intellectual disability syndromic and non-syndromic v0.6348 NFIX Zornitza Stark Publications for gene: NFIX were set to
Intellectual disability syndromic and non-syndromic v0.6347 NFIX Zornitza Stark Mode of inheritance for gene: NFIX was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6346 NEU1 Zornitza Stark Marked gene: NEU1 as ready
Intellectual disability syndromic and non-syndromic v0.6346 NEU1 Zornitza Stark Gene: neu1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6346 NEU1 Zornitza Stark Phenotypes for gene: NEU1 were changed from to Sialidosis, type I and type II, MIM# 256550; MONDO:0009738
Intellectual disability syndromic and non-syndromic v0.6345 NEU1 Zornitza Stark Publications for gene: NEU1 were set to
Intellectual disability syndromic and non-syndromic v0.6344 NEU1 Zornitza Stark Mode of inheritance for gene: NEU1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6343 NDUFV1 Zornitza Stark Marked gene: NDUFV1 as ready
Intellectual disability syndromic and non-syndromic v0.6343 NDUFV1 Zornitza Stark Gene: ndufv1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6343 NDUFV1 Zornitza Stark Phenotypes for gene: NDUFV1 were changed from to Mitochondrial complex I deficiency, nuclear type 4 MIM#618225
Intellectual disability syndromic and non-syndromic v0.6342 NDUFV1 Zornitza Stark Publications for gene: NDUFV1 were set to
Intellectual disability syndromic and non-syndromic v0.6341 NDUFV1 Zornitza Stark Mode of inheritance for gene: NDUFV1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6340 NDUFS7 Zornitza Stark Marked gene: NDUFS7 as ready
Intellectual disability syndromic and non-syndromic v0.6340 NDUFS7 Zornitza Stark Gene: ndufs7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6340 NDUFS7 Zornitza Stark Phenotypes for gene: NDUFS7 were changed from to Mitochondrial complex I deficiency, nuclear type 3 (MIM# 618224)
Intellectual disability syndromic and non-syndromic v0.6339 NDUFS7 Zornitza Stark Publications for gene: NDUFS7 were set to
Intellectual disability syndromic and non-syndromic v0.6338 NDUFS7 Zornitza Stark Mode of inheritance for gene: NDUFS7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6337 NDUFA1 Zornitza Stark Marked gene: NDUFA1 as ready
Intellectual disability syndromic and non-syndromic v0.6337 NDUFA1 Zornitza Stark Gene: ndufa1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6337 NDUFA1 Zornitza Stark Phenotypes for gene: NDUFA1 were changed from Mitochondrial complex I deficiency, nuclear type 12 MIM#301020 to Mitochondrial complex I deficiency, nuclear type 12 MIM#301020
Intellectual disability syndromic and non-syndromic v0.6336 NDUFA1 Zornitza Stark Phenotypes for gene: NDUFA1 were changed from to Mitochondrial complex I deficiency, nuclear type 12 MIM#301020
Intellectual disability syndromic and non-syndromic v0.6335 NDUFA1 Zornitza Stark Publications for gene: NDUFA1 were set to
Intellectual disability syndromic and non-syndromic v0.6334 NDUFA1 Zornitza Stark Mode of inheritance for gene: NDUFA1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.6333 NALCN Zornitza Stark Marked gene: NALCN as ready
Intellectual disability syndromic and non-syndromic v0.6333 NALCN Zornitza Stark Gene: nalcn has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6333 NALCN Zornitza Stark Phenotypes for gene: NALCN were changed from to Congenital contractures of the limbs and face, hypotonia, and developmental delay, MIM# 616266; Hypotonia, infantile, with psychomotor retardation and characteristic facies 1, MIM # 615419
Intellectual disability syndromic and non-syndromic v0.6332 NALCN Zornitza Stark Publications for gene: NALCN were set to
Intellectual disability syndromic and non-syndromic v0.6331 NALCN Zornitza Stark Mode of inheritance for gene: NALCN was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6330 NAGLU Zornitza Stark Marked gene: NAGLU as ready
Intellectual disability syndromic and non-syndromic v0.6330 NAGLU Zornitza Stark Gene: naglu has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6330 NAGLU Zornitza Stark Phenotypes for gene: NAGLU were changed from to Mucopolysaccharidosis type IIIB (Sanfilippo B), MIM# 252920
Intellectual disability syndromic and non-syndromic v0.6329 NAGLU Zornitza Stark Publications for gene: NAGLU were set to
Intellectual disability syndromic and non-syndromic v0.6328 NAGLU Zornitza Stark Mode of inheritance for gene: NAGLU was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6327 NAGA Zornitza Stark Marked gene: NAGA as ready
Intellectual disability syndromic and non-syndromic v0.6327 NAGA Zornitza Stark Gene: naga has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6327 NAGA Zornitza Stark Phenotypes for gene: NAGA were changed from Kanzaki disease, MIM# 609242; Schindler disease, type I and type II 609241; alpha-N-acetylgalactosaminidase deficiency MONDO:0017779 to Kanzaki disease, MIM# 609242; Schindler disease, type I and type II 609241; alpha-N-acetylgalactosaminidase deficiency MONDO:0017779
Intellectual disability syndromic and non-syndromic v0.6327 NAGA Zornitza Stark Phenotypes for gene: NAGA were changed from to Kanzaki disease, MIM# 609242; Schindler disease, type I and type II 609241; alpha-N-acetylgalactosaminidase deficiency MONDO:0017779
Intellectual disability syndromic and non-syndromic v0.6326 NAGA Zornitza Stark Publications for gene: NAGA were set to
Intellectual disability syndromic and non-syndromic v0.6325 NAGA Zornitza Stark Mode of inheritance for gene: NAGA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6324 SCO2 Zornitza Stark Marked gene: SCO2 as ready
Intellectual disability syndromic and non-syndromic v0.6324 SCO2 Zornitza Stark Gene: sco2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6324 SCO2 Zornitza Stark Phenotypes for gene: SCO2 were changed from to Mitochondrial complex IV deficiency, nuclear type 2, MIM# 604377
Intellectual disability syndromic and non-syndromic v0.6323 SCO2 Zornitza Stark Publications for gene: SCO2 were set to
Intellectual disability syndromic and non-syndromic v0.6322 SCO2 Zornitza Stark Mode of inheritance for gene: SCO2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6321 SKI Zornitza Stark Marked gene: SKI as ready
Intellectual disability syndromic and non-syndromic v0.6321 SKI Zornitza Stark Gene: ski has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6321 SKI Zornitza Stark Phenotypes for gene: SKI were changed from to Shprintzen-Goldberg syndrome, MIM# 182212; Neurodevelopmental disorder, MONDO:0700092, SKI-related
Intellectual disability syndromic and non-syndromic v0.6320 SKI Zornitza Stark Publications for gene: SKI were set to
Intellectual disability syndromic and non-syndromic v0.6319 SKI Zornitza Stark Mode of inheritance for gene: SKI was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6318 SKI Zornitza Stark reviewed gene: SKI: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, SKI-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6318 SHH Zornitza Stark Marked gene: SHH as ready
Intellectual disability syndromic and non-syndromic v0.6318 SHH Zornitza Stark Gene: shh has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6318 SHH Zornitza Stark Phenotypes for gene: SHH were changed from to Holoprosencephaly 3 (MIM#142945)
Intellectual disability syndromic and non-syndromic v0.6317 SHH Zornitza Stark Publications for gene: SHH were set to
Intellectual disability syndromic and non-syndromic v0.6316 SHH Zornitza Stark Mode of inheritance for gene: SHH was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.2047 IL7 Zornitza Stark Marked gene: IL7 as ready
Mendeliome v1.2047 IL7 Zornitza Stark Gene: il7 has been classified as Green List (High Evidence).
Mendeliome v1.2047 IL7 Zornitza Stark Classified gene: IL7 as Green List (high evidence)
Mendeliome v1.2047 IL7 Zornitza Stark Gene: il7 has been classified as Green List (High Evidence).
Mendeliome v1.2046 IL7 Zornitza Stark gene: IL7 was added
gene: IL7 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: IL7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL7 were set to 39352394
Phenotypes for gene: IL7 were set to Combined immunodeficiency, MONDO:0015131, IL7-related
Review for gene: IL7 was set to GREEN
Added comment: 6 indviduals from 4 kindreds with combined immune deficiency and recurrent infections. Extensive immunophenotyping revealing IL7 dependent and independent development of T cells.
Sources: Literature
Combined Immunodeficiency v1.73 IL7 Zornitza Stark Marked gene: IL7 as ready
Combined Immunodeficiency v1.73 IL7 Zornitza Stark Gene: il7 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.73 IL7 Zornitza Stark Phenotypes for gene: IL7 were changed from Combined Immune deficiency to Combined immunodeficiency, MONDO:0015131, IL7-related
Combined Immunodeficiency v1.72 IL7 Zornitza Stark Classified gene: IL7 as Green List (high evidence)
Combined Immunodeficiency v1.72 IL7 Zornitza Stark Gene: il7 has been classified as Green List (High Evidence).
Combined Immunodeficiency v1.71 IL7 Zornitza Stark reviewed gene: IL7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Combined immunodeficiency, MONDO:0015131, IL7-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe early-onset obesity v1.12 LRRC7 Zornitza Stark Marked gene: LRRC7 as ready
Severe early-onset obesity v1.12 LRRC7 Zornitza Stark Gene: lrrc7 has been classified as Green List (High Evidence).
Severe early-onset obesity v1.12 LRRC7 Zornitza Stark Classified gene: LRRC7 as Green List (high evidence)
Severe early-onset obesity v1.12 LRRC7 Zornitza Stark Gene: lrrc7 has been classified as Green List (High Evidence).
Severe early-onset obesity v1.11 LRRC7 Zornitza Stark gene: LRRC7 was added
gene: LRRC7 was added to Severe early-onset obesity. Sources: Literature
Mode of inheritance for gene: LRRC7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LRRC7 were set to 39256359
Phenotypes for gene: LRRC7 were set to neurodevelopmental disorder (MONDO:0700092), LRRC7-related
Review for gene: LRRC7 was set to GREEN
Added comment: Over 30 individuals reported with a neurodevelopmental disorder and variants in this gene. Hyperphagia and early-onset obesity is a common feature.
Sources: Literature
Mendeliome v1.2045 LRRC7 Zornitza Stark Marked gene: LRRC7 as ready
Mendeliome v1.2045 LRRC7 Zornitza Stark Gene: lrrc7 has been classified as Green List (High Evidence).
Microcephaly v1.286 FLVCR1 Bryony Thompson Marked gene: FLVCR1 as ready
Microcephaly v1.286 FLVCR1 Bryony Thompson Gene: flvcr1 has been classified as Green List (High Evidence).
Mendeliome v1.2045 LRRC7 Zornitza Stark Phenotypes for gene: LRRC7 were changed from neurodevelopmental disorder (MONDO:0700092) to neurodevelopmental disorder (MONDO:0700092), LRRC7-related
Mendeliome v1.2044 LRRC7 Zornitza Stark Classified gene: LRRC7 as Green List (high evidence)
Mendeliome v1.2044 LRRC7 Zornitza Stark Gene: lrrc7 has been classified as Green List (High Evidence).
Mendeliome v1.2043 LRRC7 Zornitza Stark reviewed gene: LRRC7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: neurodevelopmental disorder (MONDO:0700092), LRRC7-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6315 LRRC7 Zornitza Stark Marked gene: LRRC7 as ready
Intellectual disability syndromic and non-syndromic v0.6315 LRRC7 Zornitza Stark Gene: lrrc7 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6315 LRRC7 Zornitza Stark Phenotypes for gene: LRRC7 were changed from neurodevelopmental disorder (MONDO:0700092) to neurodevelopmental disorder (MONDO:0700092), LRRC7-related
Intellectual disability syndromic and non-syndromic v0.6314 LRRC7 Zornitza Stark reviewed gene: LRRC7: Rating: GREEN; Mode of pathogenicity: None; Publications: 39256359; Phenotypes: neurodevelopmental disorder (MONDO:0700092), LRRC7-related; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.6314 LRRC7 Zornitza Stark Classified gene: LRRC7 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6314 LRRC7 Zornitza Stark Gene: lrrc7 has been classified as Green List (High Evidence).
Fetal anomalies v1.276 RPL26 Zornitza Stark Marked gene: RPL26 as ready
Fetal anomalies v1.276 RPL26 Zornitza Stark Gene: rpl26 has been classified as Green List (High Evidence).
Fetal anomalies v1.276 RPL26 Zornitza Stark Classified gene: RPL26 as Green List (high evidence)
Fetal anomalies v1.276 RPL26 Zornitza Stark Gene: rpl26 has been classified as Green List (High Evidence).
Fetal anomalies v1.275 RPL26 Zornitza Stark gene: RPL26 was added
gene: RPL26 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: RPL26 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPL26 were set to 22431104; 39268718
Phenotypes for gene: RPL26 were set to Diamond-Blackfan anaemia 11, MIM# 614900
Review for gene: RPL26 was set to GREEN
Added comment: Four unrelated families reported, radial ray defects are part of the phenotype.
Sources: Literature
Radial Ray Abnormalities v1.13 RPL26 Zornitza Stark Phenotypes for gene: RPL26 were changed from Diamond-Blackfan anemia 11, MIM# 614900 to Diamond-Blackfan anaemia 11, MIM# 614900
Radial Ray Abnormalities v1.12 RPL26 Zornitza Stark Publications for gene: RPL26 were set to 22431104
Radial Ray Abnormalities v1.11 RPL26 Zornitza Stark Classified gene: RPL26 as Green List (high evidence)
Radial Ray Abnormalities v1.11 RPL26 Zornitza Stark Gene: rpl26 has been classified as Green List (High Evidence).
Mendeliome v1.2043 RPL26 Zornitza Stark Phenotypes for gene: RPL26 were changed from Diamond-Blackfan anemia 11, MIM# 614900 to Diamond-Blackfan anaemia 11, MIM# 614900
Mendeliome v1.2042 RPL26 Zornitza Stark Publications for gene: RPL26 were set to 22431104
Mendeliome v1.2041 RPL26 Zornitza Stark Classified gene: RPL26 as Green List (high evidence)
Mendeliome v1.2041 RPL26 Zornitza Stark Gene: rpl26 has been classified as Green List (High Evidence).
Diamond Blackfan anaemia v1.8 RPL26 Zornitza Stark Classified gene: RPL26 as Green List (high evidence)
Diamond Blackfan anaemia v1.8 RPL26 Zornitza Stark Gene: rpl26 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.98 RPL26 Zornitza Stark Publications for gene: RPL26 were set to 22431104
Bone Marrow Failure v1.97 RPL26 Zornitza Stark Classified gene: RPL26 as Green List (high evidence)
Bone Marrow Failure v1.97 RPL26 Zornitza Stark Gene: rpl26 has been classified as Green List (High Evidence).
Bone Marrow Failure v1.96 RPL26 Zornitza Stark edited their review of gene: RPL26: Added comment: PMID 39268718: Additional reported cases with multiple congenital anomalies - predominantly radial ray defects Article reports five individuals from one family with an intronic variant (c.-6+3_-6+25del). The variant was shown to segregate with AD pattern across 3 generations in similarly affected individuals. Reported two other unrelated individuals with de novo variants (p.Met30Cysfs*9 and c.-5-2A>G).; Changed rating: GREEN; Changed publications: 22431104, 39268718; Changed phenotypes: Diamond-Blackfan anemia 11, MIM# 614900
Red cell disorders v1.26 RPL26 Zornitza Stark Publications for gene: RPL26 were set to 22431104
Red cell disorders v1.25 RPL26 Zornitza Stark Classified gene: RPL26 as Green List (high evidence)
Red cell disorders v1.25 RPL26 Zornitza Stark Gene: rpl26 has been classified as Green List (High Evidence).
Mendeliome v1.2040 FLVCR1 Zornitza Stark Phenotypes for gene: FLVCR1 were changed from posterior column ataxia-retinitis pigmentosa syndrome MONDO:0012177 to posterior column ataxia-retinitis pigmentosa syndrome MONDO:0012177; neurodevelopmental disorder MONDO:0700092, FLVCR1-related
Microcephaly v1.286 FLVCR1 Zornitza Stark Marked gene: FLVCR1 as ready
Microcephaly v1.286 FLVCR1 Zornitza Stark Gene: flvcr1 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.61 SECISBP2 Zornitza Stark Marked gene: SECISBP2 as ready
Genetic Epilepsy v1.61 SECISBP2 Zornitza Stark Gene: secisbp2 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.61 SECISBP2 Zornitza Stark Classified gene: SECISBP2 as Green List (high evidence)
Genetic Epilepsy v1.61 SECISBP2 Zornitza Stark Gene: secisbp2 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.60 SECISBP2 Zornitza Stark gene: SECISBP2 was added
gene: SECISBP2 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: SECISBP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SECISBP2 were set to 39315526
Phenotypes for gene: SECISBP2 were set to Thyroid hormone metabolism, abnormal, 1, MIM# 609698
Review for gene: SECISBP2 was set to GREEN
Added comment: Four individuals reported with bi-allelic variants and ID/seizures/autism phenotype.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6313 SECISBP2 Zornitza Stark Phenotypes for gene: SECISBP2 were changed from #609698 THYROID HORMONE METABOLISM, ABNORMAL to Thyroid hormone metabolism, abnormal, 1, MIM# 609698
Microcephaly v1.286 FLVCR1 Bryony Thompson Classified gene: FLVCR1 as Green List (high evidence)
Microcephaly v1.286 FLVCR1 Bryony Thompson Gene: flvcr1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6312 SECISBP2 Zornitza Stark Publications for gene: SECISBP2 were set to 16228000; 19602558; 21084748; 22247018
Intellectual disability syndromic and non-syndromic v0.6311 SECISBP2 Zornitza Stark Classified gene: SECISBP2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6311 SECISBP2 Zornitza Stark Gene: secisbp2 has been classified as Green List (High Evidence).
Microcephaly v1.285 FLVCR1 Bryony Thompson gene: FLVCR1 was added
gene: FLVCR1 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: FLVCR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FLVCR1 were set to 39306721
Phenotypes for gene: FLVCR1 were set to neurodevelopmental disorder MONDO:0700092, FLVCR1-related
Review for gene: FLVCR1 was set to GREEN
gene: FLVCR1 was marked as current diagnostic
Added comment: A study with 30 patients from 23 unrelated families with biallelic ultra-rare missense and predicted loss-of-function variants in FLVCR1 with a novel FLVCR1-related phenotype characterised by severe developmental disorders with profound developmental delay, microcephaly, brain malformations, epilepsy, spasticity, and premature death. Optic disk atrophy, limb and digital malformations, and macrocytic anaemia can be present.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6310 SECISBP2 Zornitza Stark reviewed gene: SECISBP2: Rating: GREEN; Mode of pathogenicity: None; Publications: 39315526; Phenotypes: Thyroid hormone metabolism, abnormal, 1, MIM# 609698; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Anophthalmia_Microphthalmia_Coloboma v1.40 NHEJ1 Zornitza Stark Marked gene: NHEJ1 as ready
Anophthalmia_Microphthalmia_Coloboma v1.40 NHEJ1 Zornitza Stark Gene: nhej1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.6310 FLVCR1 Bryony Thompson Phenotypes for gene: FLVCR1 were changed from Ataxia, posterior column, with retinitis pigmentosa, MIM#609033 to neurodevelopmental disorder MONDO:0700092, FLVCR1-related
Intellectual disability syndromic and non-syndromic v0.6309 FLVCR1 Bryony Thompson Publications for gene: FLVCR1 were set to
Mendeliome v1.2039 NHEJ1 Zornitza Stark Phenotypes for gene: NHEJ1 were changed from Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, MIM# 611291; Cernunnos-XLF deficiency MONDO:0012650 to Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, MIM# 611291; Cernunnos-XLF deficiency MONDO:0012650; Microphthalmia/coloboma, MIM# 13 620968
Mendeliome v1.2038 NHEJ1 Zornitza Stark Publications for gene: NHEJ1 were set to 30898087; 30666249; 28741180; 25288157; 24511403; 21721379; 21535335
Intellectual disability syndromic and non-syndromic v0.6308 FLVCR1 Bryony Thompson Classified gene: FLVCR1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6308 FLVCR1 Bryony Thompson Gene: flvcr1 has been classified as Green List (High Evidence).
Mendeliome v1.2037 NHEJ1 Zornitza Stark changed review comment from: PMID 37580330: Seven individuals from 2 consanguineous families identified with a deep intronic homozygous variant affecting the IHH enhancer within NHEJ1.; to: PMID 37580330: Seven individuals from 2 consanguineous families identified with a deep intronic homozygous variant affecting the IHH enhancer within NHEJ1 -- RED for this association.
Intellectual disability syndromic and non-syndromic v0.6307 FLVCR1 Bryony Thompson reviewed gene: FLVCR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 39306721; Phenotypes: neurodevelopmental disorder MONDO:0700092, FLVCR1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.2037 NHEJ1 Zornitza Stark edited their review of gene: NHEJ1: Added comment: PMID 37580330: Seven individuals from 2 consanguineous families identified with a deep intronic homozygous variant affecting the IHH enhancer within NHEJ1.; Changed publications: 30898087, 30666249, 28741180, 25288157, 24511403, 21721379, 21535335, 37580330; Changed phenotypes: Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, MIM# 611291, Cernunnos-XLF deficiency MONDO:0012650, Microphthalmia/coloboma, MIM# 13 620968
Anophthalmia_Microphthalmia_Coloboma v1.40 NHEJ1 Zornitza Stark gene: NHEJ1 was added
gene: NHEJ1 was added to Anophthalmia_Microphthalmia_Coloboma. Sources: Literature
deep intronic tags were added to gene: NHEJ1.
Mode of inheritance for gene: NHEJ1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NHEJ1 were set to 37580330
Phenotypes for gene: NHEJ1 were set to Microphthalmia/coloboma, MIM# 13 620968
Review for gene: NHEJ1 was set to RED
Added comment: Seven individuals from 2 consanguineous families identified with a deep intronic homozygous variant affecting the IHH enhancer within NHEJ1.
Sources: Literature
Prepair 1000+ v1.359 NECTIN1 Lauren Rogers reviewed gene: NECTIN1: Rating: ; Mode of pathogenicity: None; Publications: 25913853, 10932188, 26953873; Phenotypes: Cleft lip/palate-ectodermal dysplasia syndrome MIM#225060; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.359 NGF Lauren Rogers reviewed gene: NGF: Rating: GREEN; Mode of pathogenicity: None; Publications: 14976160, 20978020, 33884296, 32693191, 31685654, 30296891; Phenotypes: Neuropathy, hereditary sensory and autonomic, type V (MIM#608654); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2037 FLVCR1 Bryony Thompson edited their review of gene: FLVCR1: Added comment: A study with 30 patients from 23 unrelated families with biallelic ultra-rare missense and predicted loss-of-function variants in FLVCR1 with a novel FLVCR1-related phenotype characterised by severe developmental disorders with profound developmental delay, microcephaly, brain malformations, epilepsy, spasticity, and premature death. Optic disk atrophy, limb and digital malformations, and macrocytic anaemia can be present.; Changed publications: 21070897, 22279524, 21267618, 39306721; Changed phenotypes: posterior column ataxia-retinitis pigmentosa syndrome MONDO:0012177, neurodevelopmental disorder MONDO:0700092, FLVCR1-related
Red cell disorders v1.24 RPL26 Sangavi Sivagnanasundram reviewed gene: RPL26: Rating: GREEN; Mode of pathogenicity: None; Publications: 39268718; Phenotypes: Diamond-Blackfan anemia MONDO:0015253; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Diamond Blackfan anaemia v1.7 RPL26 Sangavi Sivagnanasundram reviewed gene: RPL26: Rating: GREEN; Mode of pathogenicity: None; Publications: 39268718; Phenotypes: Diamond-Blackfan anemia MONDO:0015253; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v1.359 NDUFS8 Lauren Rogers reviewed gene: NDUFS8: Rating: GREEN; Mode of pathogenicity: None; Publications: 23430795, 36101822; Phenotypes: Mitochondrial complex I deficiency, nuclear type 2 (MIM#618222); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Radial Ray Abnormalities v1.10 RPL26 Sangavi Sivagnanasundram reviewed gene: RPL26: Rating: GREEN; Mode of pathogenicity: None; Publications: 39268718; Phenotypes: Diamond-Blackfan anemia MONDO:0015253; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.2037 RPL26 Sangavi Sivagnanasundram reviewed gene: RPL26: Rating: GREEN; Mode of pathogenicity: None; Publications: 39268718; Phenotypes: Diamond-Blackfan anemia MONDO:0015253; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v1.359 SLC38A8 Lauren Rogers reviewed gene: SLC38A8: Rating: GREEN; Mode of pathogenicity: None; Publications: 24290379, 32744312; Phenotypes: Foveal hypoplasia 2, with or without optic nerve misrouting and/or anterior segment dysgenesis (MIM#609218); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.359 TSPYL1 Lauren Rogers reviewed gene: TSPYL1: Rating: AMBER; Mode of pathogenicity: None; Publications: 15273283, 32885560, 33075815, 36082874; Phenotypes: Sudden infant death with dysgenesis of the testes syndrome (MIM#608800); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6307 LRRC7 Sangavi Sivagnanasundram gene: LRRC7 was added
gene: LRRC7 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: LRRC7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LRRC7 were set to 39256359
Phenotypes for gene: LRRC7 were set to neurodevelopmental disorder (MONDO:0700092)
Review for gene: LRRC7 was set to GREEN
Added comment: Well established gene-disease association.
Neurodevelopmental disorder with a clinical spectrum - symptoms include ID, ADHD, aggression and in many cases, hyperphagia associate obesity.
Heterozygous missense and LoF variants have been reported and functional assays were conducted on missense and truncating variants that support LoF mechanism of disease.
Sources: Literature
Mendeliome v1.2037 LRRC7 Sangavi Sivagnanasundram gene: LRRC7 was added
gene: LRRC7 was added to Mendeliome. Sources: Other,Literature
Mode of inheritance for gene: LRRC7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LRRC7 were set to 39256359
Phenotypes for gene: LRRC7 were set to neurodevelopmental disorder (MONDO:0700092)
Review for gene: LRRC7 was set to GREEN
Added comment: Well established gene-disease association.
Neurodevelopmental disorder with a clinical spectrum - symptoms include ID, ADHD, aggression and in many cases, hyperphagia associate obesity.
Heterozygous missense and LoF variants have been reported and functional assays were conducted on missense and truncating variants that support LoF mechanism of disease.
Sources: Other, Literature
Combined Immunodeficiency v1.71 IL7 Peter McNaughton gene: IL7 was added
gene: IL7 was added to Combined Immunodeficiency. Sources: Literature
Mode of inheritance for gene: IL7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL7 were set to PMID: 39352394
Phenotypes for gene: IL7 were set to Combined Immune deficiency
Review for gene: IL7 was set to GREEN
Added comment: 6 patients from 4 kindreds with combined immune deficiency and recurrent infections. Extensive immunophenotyping revealing IL7 dependent and independent development of T cells.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6307 SHH Chirag Patel reviewed gene: SHH: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22791840, 19057928; Phenotypes: Holoprosencephaly 3 (MIM#142945); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6307 SKI Chirag Patel reviewed gene: SKI: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23023332, 23103230, 24736733, 30071989; Phenotypes: Shprintzen-Goldberg syndrome, MIM# 182212; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6307 SCO2 Chirag Patel reviewed gene: SCO2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 10545952, 10749987, 18924171; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 2, MIM# 604377; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Brain Calcification v1.97 AP1S2 Ain Roesley Phenotypes for gene: AP1S2 were changed from Pettigrew syndrome, MIM# 304340 to Pettigrew syndrome, MIM# 304340
Arthrogryposis v0.414 AP1S2 Ain Roesley Phenotypes for gene: AP1S2 were changed from Pettigrew syndrome, MIM# 304340 to Pettigrew syndrome, MIM# 304340
Brain Calcification v1.97 AP1S2 Ain Roesley Phenotypes for gene: AP1S2 were changed from Pettigrew syndrome, MIM# 304340 to Pettigrew syndrome, MIM# 304340
Arthrogryposis v0.414 AP1S2 Ain Roesley Phenotypes for gene: AP1S2 were changed from Pettigrew syndrome, MIM# 304340 to Pettigrew syndrome, MIM# 304340
Brain Calcification v1.97 AP1S2 Ain Roesley Phenotypes for gene: AP1S2 were changed from Mental retardation, X-linked syndromic 5, MIM#304340 to Pettigrew syndrome, MIM# 304340
Arthrogryposis v0.414 AP1S2 Ain Roesley Phenotypes for gene: AP1S2 were changed from Mental retardation, X-linked syndromic 5, MIM# 304340 to Pettigrew syndrome, MIM# 304340
Prepair 500+ v1.4 AP1S2 Ain Roesley Phenotypes for gene: AP1S2 were changed from Mental retardation, X-linked syndromic 5, 304340 (3) to Pettigrew syndrome, MIM# 304340
Ataxia - paediatric v1.28 AP1S2 Ain Roesley Phenotypes for gene: AP1S2 were changed from Mental retardation, X-linked syndromic 5, MIM#304340 to Pettigrew syndrome, MIM# 304340
Prepair 1000+ v1.359 AP1S2 Ain Roesley Phenotypes for gene: AP1S2 were changed from Mental retardation, X-linked syndromic 5, 304340 (3) to Pettigrew syndrome, MIM# 304340
Cerebellar and Pontocerebellar Hypoplasia v1.71 GMPPB Ain Roesley Phenotypes for gene: GMPPB were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 (MIM# 615350); Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 14 (MIM# 615351); Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 (MIM# 615352) to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 (MIM# 615350); Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 14 (MIM# 615351); Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 (MIM# 615352)
Lissencephaly and Band Heterotopia v1.20 GMPPB Ain Roesley Phenotypes for gene: GMPPB were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 (MIM# 615350); Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 14 (MIM# 615351); Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 (MIM# 615352) to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 (MIM# 615350); Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 14 (MIM# 615351); Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 (MIM# 615352)
Intellectual disability syndromic and non-syndromic v0.6307 NAGA Chirag Patel reviewed gene: NAGA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 11313741, 31468281, 15619430, 8782044; Phenotypes: Kanzaki disease, MIM# 609242, Schindler disease, type I and type II 609241, alpha-N-acetylgalactosaminidase deficiency MONDO:0017779; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6307 NAGLU Chirag Patel reviewed gene: NAGLU: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 8650226; Phenotypes: Mucopolysaccharidosis type IIIB (Sanfilippo B), MIM# 252920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Lissencephaly and Band Heterotopia v1.20 GMPPB Ain Roesley Phenotypes for gene: GMPPB were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 (MIM# 615350); Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 14 (MIM# 615351); Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 (MIM# 615352) to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 (MIM# 615350); Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 14 (MIM# 615351); Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 (MIM# 615352)
Cerebellar and Pontocerebellar Hypoplasia v1.71 GMPPB Ain Roesley Phenotypes for gene: GMPPB were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 615350; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 14 615351; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 615352 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 (MIM# 615350); Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 14 (MIM# 615351); Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 (MIM# 615352)
Congenital Disorders of Glycosylation v1.47 GMPPB Ain Roesley Phenotypes for gene: GMPPB were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 615350; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 14 615351; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 615352 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 (MIM# 615350); Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 14 (MIM# 615351); Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 (MIM# 615352)
Intellectual disability syndromic and non-syndromic v0.6307 NALCN Chirag Patel reviewed gene: NALCN: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25683120, 30167850, 23749988, 24075186; Phenotypes: Congenital contractures of the limbs and face, hypotonia, and developmental delay, MIM# 616266, Hypotonia, infantile, with psychomotor retardation and characteristic facies 1, MIM # 615419; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.2037 GMPPB Ain Roesley Phenotypes for gene: GMPPB were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 615350; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 14 615351; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 615352 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 (MIM# 615350); Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 14 (MIM# 615351); Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 (MIM# 615352)
Lissencephaly and Band Heterotopia v1.20 GMPPB Ain Roesley Phenotypes for gene: GMPPB were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 (MIM# 615350); Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 14 (MIM# 615351); Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 (MIM# 615352) to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 (MIM# 615350); Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 14 (MIM# 615351); Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 (MIM# 615352)
Congenital Disorders of Glycosylation v1.46 GMPPA Ain Roesley Phenotypes for gene: GMPPA were changed from Alacrima, achalasia, and impaired intellectual development syndrome (MIM# 615510) to Alacrima, achalasia, and impaired intellectual development syndrome (MIM# 615510)
Genetic Epilepsy v1.59 GMPPA Ain Roesley Phenotypes for gene: GMPPA were changed from Alacrima, achalasia, and impaired intellectual development syndrome (MIM# 615510) to Alacrima, achalasia, and impaired intellectual development syndrome (MIM# 615510)
Congenital Disorders of Glycosylation v1.46 GMPPA Ain Roesley Phenotypes for gene: GMPPA were changed from Alacrima, achalasia, and impaired intellectual development syndrome (MIM# 615510) to Alacrima, achalasia, and impaired intellectual development syndrome (MIM# 615510)
Genetic Epilepsy v1.59 GMPPA Ain Roesley Phenotypes for gene: GMPPA were changed from Alacrima, achalasia, and mental retardation syndrome (MIM# 615510) to Alacrima, achalasia, and impaired intellectual development syndrome (MIM# 615510)
Congenital Disorders of Glycosylation v1.46 GMPPA Ain Roesley Phenotypes for gene: GMPPA were changed from Alacrima, achalasia, and mental retardation syndrome (MIM# 615510) to Alacrima, achalasia, and impaired intellectual development syndrome (MIM# 615510)
Fetal anomalies v1.274 GMPPA Ain Roesley Phenotypes for gene: GMPPA were changed from Alacrima, achalasia, and mental retardation syndrome (MIM# 615510) to Alacrima, achalasia, and impaired intellectual development syndrome (MIM# 615510)
Autonomic neuropathy v0.51 GMPPA Ain Roesley Phenotypes for gene: GMPPA were changed from # 615510 ALACRIMA, ACHALASIA, AND MENTAL RETARDATION SYNDROME; AAMR to Alacrima, achalasia, and impaired intellectual development syndrome (MIM# 615510)
Mendeliome v1.2036 GMPPA Ain Roesley Phenotypes for gene: GMPPA were changed from Alacrima, achalasia, and mental retardation syndrome, MIM# 615510 to Alacrima, achalasia, and impaired intellectual development syndrome (MIM# 615510)
Polydactyly v0.277 USP9X Ain Roesley Phenotypes for gene: USP9X were changed from Intellectual developmental disorder 99 MIM#300919; syndromic, female-restricted Intellectual developmental disorder 99 MIM#300968 to Intellectual developmental disorder 99 MIM#300919; syndromic, female-restricted Intellectual developmental disorder 99 MIM#300968
Skeletal dysplasia v0.286 USP9X Ain Roesley Phenotypes for gene: USP9X were changed from intellectual disability, X-linked 99 MONDO:0010487 to Intellectual developmental disorder 99 MIM#300919; syndromic, female-restricted Intellectual developmental disorder 99 MIM#300968
Polydactyly v0.277 USP9X Ain Roesley Phenotypes for gene: USP9X were changed from Mental retardation, X-linked 99, syndromic, female-restricted, MIM# 300968 to Intellectual developmental disorder 99 MIM#300919; syndromic, female-restricted Intellectual developmental disorder 99 MIM#300968
Fetal anomalies v1.273 USP9X Ain Roesley Phenotypes for gene: USP9X were changed from Mental retardation, X-linked 99, XLR (MIM#300919) and XLD (MIM#300968) to Intellectual developmental disorder 99 MIM#300919; syndromic, female-restricted Intellectual developmental disorder 99 MIM#300968
Intellectual disability syndromic and non-syndromic v0.6307 USP9X Ain Roesley Phenotypes for gene: USP9X were changed from Mental retardation, X-linked 99, XLR (MIM#300919) and XLD (MIM#300968) to Intellectual developmental disorder 99 MIM#300919; syndromic, female-restricted Intellectual developmental disorder 99 MIM#300968
Prepair 1000+ v1.358 USP9X Ain Roesley Phenotypes for gene: USP9X were changed from Intellectual developmental disorder, X-linked 99, MIM#300919 to Intellectual developmental disorder 99 MIM#300919; syndromic, female-restricted Intellectual developmental disorder 99 MIM#300968
Prepair 500+ v1.3 USP9X Ain Roesley Phenotypes for gene: USP9X were changed from Mental retardation, X-linked 99, 300919 (3) to Intellectual developmental disorder 99 MIM#300919; syndromic, female-restricted Intellectual developmental disorder 99 MIM#300968
Choanal atresia v1.6 USP9X Ain Roesley Phenotypes for gene: USP9X were changed from Mental retardation, X-linked 99, syndromic, female-restricted MIM#300968; MONDO:0010502 to Intellectual developmental disorder 99 MIM#300919; syndromic, female-restricted Intellectual developmental disorder 99 MIM#300968
Clefting disorders v0.257 USP9X Ain Roesley Phenotypes for gene: USP9X were changed from Mental retardation, X-linked 99 300919 XLR; Mental retardation, X-linked 99, syndromic, female-restricted 300968 to Intellectual developmental disorder 99 MIM#300919; syndromic, female-restricted Intellectual developmental disorder 99 MIM#300968
Mendeliome v1.2035 USP9X Ain Roesley Phenotypes for gene: USP9X were changed from Mental retardation, X-linked 99, XLR (MIM#300919) and XLD (MIM#300968) to Intellectual developmental disorder 99 MIM#300919; syndromic, female-restricted Intellectual developmental disorder 99 MIM#300968
Severe Combined Immunodeficiency (absent T present B cells) v1.7 IL7R Ain Roesley Phenotypes for gene: IL7R were changed from severe combined immunodeficiency 104 MIM#608971 to severe combined immunodeficiency 104 MIM#608971
Severe Combined Immunodeficiency (absent T present B cells) v1.7 IL7R Ain Roesley Phenotypes for gene: IL7R were changed from Severe combined immunodeficiency, T-cell negative, B-cell/natural killer cell-positive type MIM# 608971; low T-cell numbers; normal-high B and NK-cell numbers; fever; rash; failure to thrive; recurrent respiratory and gastric infections; Hepatomegaly; Splenomegaly; diarrhoea; lymphadenopathy; pneumonitis; Pancytopaenia; decreased immunoglobulins to severe combined immunodeficiency 104 MIM#608971
Combined Immunodeficiency v1.71 IL7R Ain Roesley Phenotypes for gene: IL7R were changed from Severe combined immunodeficiency, T-cell negative, B-cell/natural killer cell-positive type MIM# 608971; fever; rash; failure to thrive; recurrent respiratory and gastric infections; diarrhoea; lymphadenopathy; pneumonitis; Pancytopaenia; low T-cell numbers; decreased immunoglobulins; normal-high B/NK-cell numbers. to severe combined immunodeficiency 104 MIM#608971
Prepair 500+ v1.2 IL7R Ain Roesley Phenotypes for gene: IL7R were changed from Severe combined immunodeficiency, T-cell negative, B-cell/natural killer cell-positive type, 608971 (3) to severe combined immunodeficiency 104 MIM#608971
Prepair 1000+ v1.357 IL7R Ain Roesley Phenotypes for gene: IL7R were changed from Severe combined immunodeficiency, T-cell negative, B-cell/natural killer cell-positive type, 608971 (3) to severe combined immunodeficiency 104 MIM#608971
Mendeliome v1.2034 IL7R Ain Roesley Phenotypes for gene: IL7R were changed from Severe combined immunodeficiency, T-cell negative, B-cell/natural killer cell-positive type MIM# 608971; fever; rash; failure to thrive; recurrent respiratory and gastric infections; diarrhoea; lymphadenopathy; pneumonitis; Pancytopaenia; low T-cell numbers; decreased immunoglobulins; normal-high B/NK-cell numbers. to severe combined immunodeficiency 104 MIM#608971
Intellectual disability syndromic and non-syndromic v0.6306 SGPL1 Ain Roesley Phenotypes for gene: SGPL1 were changed from Sphingosine Phosphate Lyase Insufficiency Syndrome; RENI syndrome (MIM#617575) to Sphingosine Phosphate Lyase Insufficiency Syndrome; RENI syndrome (MIM#617575)
Proteinuria v0.228 SGPL1 Ain Roesley Phenotypes for gene: SGPL1 were changed from RENI syndrome (MIM#617575) to RENI syndrome (MIM#617575)
Combined Immunodeficiency v1.70 SGPL1 Ain Roesley Phenotypes for gene: SGPL1 were changed from Sphingosine Phosphate Lyase Insufficiency Syndrome; RENI syndrome (MIM#617575) to Sphingosine Phosphate Lyase Insufficiency Syndrome; RENI syndrome (MIM#617575)
Hydrops fetalis v0.321 SGPL1 Ain Roesley Phenotypes for gene: SGPL1 were changed from Sphingosine Phosphate Lyase Insufficiency Syndrome; RENI syndrome (MIM#617575) to Sphingosine Phosphate Lyase Insufficiency Syndrome; RENI syndrome (MIM#617575)
Combined Immunodeficiency v1.70 SGPL1 Ain Roesley Phenotypes for gene: SGPL1 were changed from Sphingosine Phosphate Lyase Insufficiency Syndrome; Nephrotic syndrome, type 14, MIM#617575 to Sphingosine Phosphate Lyase Insufficiency Syndrome; RENI syndrome (MIM#617575)
Proteinuria v0.228 SGPL1 Ain Roesley Phenotypes for gene: SGPL1 were changed from Nephrotic syndrome, type 14, MIM# 617575 to RENI syndrome (MIM#617575)
Intellectual disability syndromic and non-syndromic v0.6305 SGPL1 Ain Roesley Phenotypes for gene: SGPL1 were changed from Sphingosine Phosphate Lyase Insufficiency Syndrome; Nephrotic syndrome, type 14, MIM#617575 to Sphingosine Phosphate Lyase Insufficiency Syndrome; RENI syndrome (MIM#617575)
Intellectual disability syndromic and non-syndromic v0.6304 NDUFA1 Chirag Patel reviewed gene: NDUFA1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29506883, 19185523, 17262856, 21596602; Phenotypes: Mitochondrial complex I deficiency, nuclear type 12 MIM#301020; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Hydrops fetalis v0.321 SGPL1 Ain Roesley Phenotypes for gene: SGPL1 were changed from Sphingosine Phosphate Lyase Insufficiency Syndrome; Nephrotic syndrome, type 14, MIM#617575 to Sphingosine Phosphate Lyase Insufficiency Syndrome; RENI syndrome (MIM#617575)
Hereditary Neuropathy - complex v1.17 SGPL1 Ain Roesley Phenotypes for gene: SGPL1 were changed from Nephrotic syndrome, type 14 (MIM#617575) to RENI syndrome (MIM#617575)
Deafness_IsolatedAndComplex v1.199 SGPL1 Ain Roesley Phenotypes for gene: SGPL1 were changed from Nephrotic syndrome, type 14, MIM# 617575 to RENI syndrome (MIM#617575)
Prepair 1000+ v1.356 SGPL1 Ain Roesley Phenotypes for gene: SGPL1 were changed from Nephrotic syndrome 14, 617575 (3), Autosomal recessive to RENI syndrome (MIM#617575)
Fetal anomalies v1.272 SGPL1 Ain Roesley Phenotypes for gene: SGPL1 were changed from Sphingosine Phosphate Lyase Insufficiency Syndrome; Nephrotic syndrome, type 14, MIM#617575 to Sphingosine Phosphate Lyase Insufficiency Syndrome; RENI syndrome (MIM#617575)
Differences of Sex Development v0.295 SGPL1 Ain Roesley Phenotypes for gene: SGPL1 were changed from Nephrotic syndrome, type 14 (MIM#617575) to RENI syndrome (MIM#617575)
Mendeliome v1.2033 SGPL1 Ain Roesley Phenotypes for gene: SGPL1 were changed from to RENI syndrome (MIM#617575)
Intellectual disability syndromic and non-syndromic v0.6304 NDUFS7 Chirag Patel reviewed gene: NDUFS7: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22644603; Phenotypes: Mitochondrial complex I deficiency, nuclear type 3 (MIM# 618224); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6304 NDUFS8 Chirag Patel reviewed gene: NDUFS8: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23430795, 9837812, 15159508, 22499348, 20818383, 20819849; Phenotypes: Mitochondrial complex I deficiency, nuclear type 2 MIM#618222; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6304 NDUFV1 Chirag Patel reviewed gene: NDUFV1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34807224; Phenotypes: Mitochondrial complex I deficiency, nuclear type 4 MIM#618225; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6304 NEU1 Chirag Patel reviewed gene: NEU1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 8985184, 9054950, 11063730; Phenotypes: Sialidosis, type I and type II, MIM# 256550, MONDO:0009738; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6304 NFIX Chirag Patel reviewed gene: NFIX: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33034087, 29897170, 30548146, 25118028; Phenotypes: Sotos syndrome 2 (MIM#614753), Marshall-Smith syndrome, MIM# 602535; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6304 NGLY1 Chirag Patel reviewed gene: NGLY1: Rating: GREEN; Mode of pathogenicity: None; Publications: Congenital disorder of deglycosylation (OMIM 615273); Phenotypes: PMID: 24651605, 27388694, 32259258; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6304 NKX2-1 Chirag Patel reviewed gene: NKX2-1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 10931427, 27066577, 26839702, 26103969, 23911641, 11854319, 24714694; Phenotypes: Choreoathetosis, hypothyroidism, and neonatal respiratory distress MIM#610978, Chorea, hereditary benign MIM#118700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Overgrowth v1.14 PPP2R5D Ain Roesley Phenotypes for gene: PPP2R5D were changed from Houge-Janssens syndrome 1, MIM#616355 to Houge-Janssens syndrome 1, MIM#616355
Macrocephaly_Megalencephaly v0.148 PPP2R5D Ain Roesley Phenotypes for gene: PPP2R5D were changed from Houge-Janssens syndrome 1, MIM#616355 to Houge-Janssens syndrome 1, MIM#616355
Early-onset Parkinson disease v2.10 PPP2R5D Ain Roesley Phenotypes for gene: PPP2R5D were changed from Early onset Parkinsonism; Houge-Janssens syndrome 1, MIM#616355 to Early onset Parkinsonism; Houge-Janssens syndrome 1, MIM#616355
Overgrowth v1.13 PPP2R5D Ain Roesley Phenotypes for gene: PPP2R5D were changed from Mental retardation, autosomal dominant 35, MIM# 616355 to Houge-Janssens syndrome 1, MIM#616355
Early-onset Parkinson disease v2.10 PPP2R5D Ain Roesley Phenotypes for gene: PPP2R5D were changed from Early onset Parkinsonism; Mental retardation, autosomal dominant 35, MIM# 616355 to Early onset Parkinsonism; Houge-Janssens syndrome 1, MIM#616355
Intellectual disability syndromic and non-syndromic v0.6304 PPP2R5D Ain Roesley Phenotypes for gene: PPP2R5D were changed from Mental retardation, autosomal dominant 35, MIM#616355 to Houge-Janssens syndrome 1, MIM#616355
Macrocephaly_Megalencephaly v0.147 PPP2R5D Ain Roesley Phenotypes for gene: PPP2R5D were changed from Mental retardation, autosomal dominant 35, MIM# 616355 to Houge-Janssens syndrome 1, MIM#616355
Fetal anomalies v1.271 PPP2R5D Ain Roesley Phenotypes for gene: PPP2R5D were changed from Mental retardation, autosomal dominant 35, MIM#616355 to Houge-Janssens syndrome 1, MIM#616355
Intellectual disability syndromic and non-syndromic v0.6303 NPC1 Chirag Patel reviewed gene: NPC1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 9211849, 11333381; Phenotypes: Niemann-Pick disease, type C1 and type D, MIM# 257220, MONDO:0009757; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2032 PPP2R5D Ain Roesley Phenotypes for gene: PPP2R5D were changed from Mental retardation, autosomal dominant 35, MIM#616355 to Houge-Janssens syndrome 1, MIM#616355
Intellectual disability syndromic and non-syndromic v0.6303 NPC2 Chirag Patel reviewed gene: NPC2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 11125141, 17470133; Phenotypes: Niemann-pick disease, type C2, MIM# 607625, MONDO:0011873; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6303 MTHFR Chirag Patel commented on gene: MTHFR: Well-established gene-disease association (see OMIM entry). Homocystinuria due to MTHFR deficiency is classified as a metabolic disorder by NIH GARD (https://rarediseases.info.nih.gov/diseases/diseases-by-category/14/metabolic-disorders) and is an inborn error of folate metabolism. DD/ID can be seen in condition.
Intellectual disability syndromic and non-syndromic v0.6303 MTHFR Chirag Patel reviewed gene: MTHFR: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27604308, 7920641; Phenotypes: Homocystinuria due to MTHFR deficiency MIM#236250, Disorders of folate metabolism and transport; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6303 MYO5A Chirag Patel reviewed gene: MYO5A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32275080, 22711375, 25283056; Phenotypes: Griscelli syndrome, type 1 MIM#214450; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6303 RAB27A Chirag Patel reviewed gene: RAB27A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.6303 MVK Chirag Patel reviewed gene: MVK: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29047407, 26409462; Phenotypes: Hyper-IgD syndrome (MIM#260920), Mevalonic aciduria (MIM#610377); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6303 MTFMT Chirag Patel reviewed gene: MTFMT: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 21907147, 23499752, 24461907, 22499348; Phenotypes: Combined oxidative phosphorylation deficiency 15, MIM# 614947, Mitochondrial complex I deficiency, nuclear type 27, MIM# 618248; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6303 MRPS22 Chirag Patel reviewed gene: MRPS22: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29566152,17873122, 25663021, 28752220; Phenotypes: Combined oxidative phosphorylation deficiency 5 MIM#611719, Ovarian dysgenesis 7 MIM#618117; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2031 ATAD2B Ain Roesley Marked gene: ATAD2B as ready
Mendeliome v1.2031 ATAD2B Ain Roesley Gene: atad2b has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2031 ATAD2B Ain Roesley Classified gene: ATAD2B as Amber List (moderate evidence)
Mendeliome v1.2031 ATAD2B Ain Roesley Gene: atad2b has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6303 MOCS2 Chirag Patel reviewed gene: MOCS2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27604308, 10053004; Phenotypes: Molybdenum cofactor deficiency B MIM#252160, Disorders of molybdenum cofactor metabolism; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2030 ATAD2B Ain Roesley gene: ATAD2B was added
gene: ATAD2B was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ATAD2B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATAD2B were set to 39313616
Phenotypes for gene: ATAD2B were set to neurodevelopmental disorder MONDO:0700092, ATAD2B-related
Review for gene: ATAD2B was set to AMBER
gene: ATAD2B was marked as current diagnostic
Added comment: 3 families including 2 siblings
1 fam is hom for a highly conserved missense

Amber because of the lack of specific phenotypes:
Abnormality of the nervous system and Abnormality of the eye
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6303 MUT Chirag Patel reviewed gene: MUT: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301409, 37420116, 1977311, 11528502, 12948746; Phenotypes: Methylmalonic aciduria, mut(0) type, MIM# 251000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6303 MMADHC Chirag Patel reviewed gene: MMADHC: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301409, 37420116,27604308, 18385497; Phenotypes: Homocystinuria, cblD type, variant 1 MIM#277410, Methylmalonic aciduria and homocystinuria, cblD type MIM#277410, Methylmalonic aciduria, cblD type, variant 2 MIM#277410, Disorders of cobalamin absorption, transport and metabolism; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6303 MMAB Chirag Patel reviewed gene: MMAB: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301409, 37420116; Phenotypes: Methylmalonic aciduria, vitamin B12-responsive, cblB type, MIM# 251110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6303 MMAA Chirag Patel reviewed gene: MMAA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301409, 37420116; Phenotypes: Methylmalonic aciduria, vitamin B12-responsive, cblA type, MIM# 251100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2029 ZDHHC16 Ain Roesley Classified gene: ZDHHC16 as Amber List (moderate evidence)
Mendeliome v1.2029 ZDHHC16 Ain Roesley Gene: zdhhc16 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6303 MLC1 Chirag Patel reviewed gene: MLC1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 11254442, 18757878, 16652334; Phenotypes: Megalencephalic leukoencephalopathy with subcortical cysts (MIM#604004); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6303 MKS1 Chirag Patel reviewed gene: MKS1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 17377820, 24886560, 19776033, 33193692, 27570071, 27377014, 18327255, 24608809; Phenotypes: Joubert syndrome 28, MIM# 617121, MONDO:0014928, Meckel syndrome 1, MIM# 249000, MONDO:0009571, Bardet-Biedl syndrome 13, MIM# 615990, MONDO:0014441; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6303 MKKS Chirag Patel reviewed gene: MKKS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 10973251, 10802661, 26900326; Phenotypes: McKusick-Kaufman syndrome, MIM# 236700, Bardet-Biedl syndrome 6, MIM# 605231, Retinitis pigmentosa; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6303 MBOAT7 Chirag Patel reviewed gene: MBOAT7: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33335874, 32645526, 32744787, 31852446, 31282596, 30701556; Phenotypes: Intellectual disability MIM#617188; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6303 MAT1A Chirag Patel reviewed gene: MAT1A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27604308, 7560086; Phenotypes: Hypermethioninemia, persistent, autosomal dominant, due to methionine adenosyltransferase I/III deficiency MIM#250850, Methionine adenosyltransferase deficiency, autosomal recessive MIM#250850, Disorders of the metabolism of sulphur amino acids; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6303 MAP2K2 Chirag Patel reviewed gene: MAP2K2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20358587, 16439621, 18042262; Phenotypes: Cardiofaciocutaneous syndrome 3, MIM# 615279; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6303 MAP2K1 Chirag Patel reviewed gene: MAP2K1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 16439621, 17551924, 18042262, 20301365; Phenotypes: Cardiofaciocutaneous syndrome 3, MIM# 615279; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Optic Atrophy v1.40 ZDHHC16 Ain Roesley Classified gene: ZDHHC16 as Amber List (moderate evidence)
Optic Atrophy v1.40 ZDHHC16 Ain Roesley Gene: zdhhc16 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6303 ZDHHC16 Ain Roesley Classified gene: ZDHHC16 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6303 ZDHHC16 Ain Roesley Gene: zdhhc16 has been classified as Amber List (Moderate Evidence).
Optic Atrophy v1.39 ZDHHC16 Ain Roesley Marked gene: ZDHHC16 as ready
Optic Atrophy v1.39 ZDHHC16 Ain Roesley Gene: zdhhc16 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6303 ZDHHC16 Ain Roesley Marked gene: ZDHHC16 as ready
Intellectual disability syndromic and non-syndromic v0.6303 ZDHHC16 Ain Roesley Gene: zdhhc16 has been classified as Amber List (Moderate Evidence).
Optic Atrophy v1.39 ZDHHC16 Ain Roesley Classified gene: ZDHHC16 as Amber List (moderate evidence)
Optic Atrophy v1.39 ZDHHC16 Ain Roesley Gene: zdhhc16 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6303 ZDHHC16 Ain Roesley Classified gene: ZDHHC16 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6303 ZDHHC16 Ain Roesley Gene: zdhhc16 has been classified as Amber List (Moderate Evidence).
Regression v0.562 ZDHHC16 Ain Roesley Marked gene: ZDHHC16 as ready
Regression v0.562 ZDHHC16 Ain Roesley Gene: zdhhc16 has been classified as Amber List (Moderate Evidence).
Regression v0.562 ZDHHC16 Ain Roesley Classified gene: ZDHHC16 as Amber List (moderate evidence)
Regression v0.562 ZDHHC16 Ain Roesley Gene: zdhhc16 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6302 ZDHHC16 Ain Roesley gene: ZDHHC16 was added
gene: ZDHHC16 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ZDHHC16 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZDHHC16 were set to 39313616
Phenotypes for gene: ZDHHC16 were set to neurodevelopmental disorder MONDO:0700092, ZDHHC16-related
Review for gene: ZDHHC16 was set to AMBER
gene: ZDHHC16 was marked as current diagnostic
Added comment: 6 families including a pair of siblings

Amber because 5 of the families had non specific phenotypes listed
Abnormality of:
the nervous system, metabolism/homeostasis, head/neck, immune system, the integument, the digestive system, the respiratory system, the endocrine system, Growth abnormality the skeletal system, the musculature, the eye

Specific HPOs were provided for one individual (homoyzygous for a canonical splice)

Abnormality of the face; Cerebellar hypoplasia; Developmental regression; Encephalopathy; Hyperreflexia; Hypertonia; Hypotonia; Inguinal hernia; Laryngomalacia; Microcephaly; Motor delay; Optic atrophy; Seizure; Spastic paraparesis; Spasticity; Talipes equinovarus; Umbilical hernia
Sources: Literature
Optic Atrophy v1.38 ZDHHC16 Ain Roesley gene: ZDHHC16 was added
gene: ZDHHC16 was added to Optic Atrophy. Sources: Literature
Mode of inheritance for gene: ZDHHC16 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZDHHC16 were set to 39313616
Phenotypes for gene: ZDHHC16 were set to neurodevelopmental disorder MONDO:0700092, ZDHHC16-related
Review for gene: ZDHHC16 was set to AMBER
gene: ZDHHC16 was marked as current diagnostic
Added comment: 6 families including a pair of siblings

Amber because 5 of the families had non specific phenotypes listed
Abnormality of:
the nervous system, metabolism/homeostasis, head/neck, immune system, the integument, the digestive system, the respiratory system, the endocrine system, Growth abnormality the skeletal system, the musculature, the eye

Specific HPOs were provided for one individual (homoyzygous for a canonical splice)

Abnormality of the face; Cerebellar hypoplasia; Developmental regression; Encephalopathy; Hyperreflexia; Hypertonia; Hypotonia; Inguinal hernia; Laryngomalacia; Microcephaly; Motor delay; Optic atrophy; Seizure; Spastic paraparesis; Spasticity; Talipes equinovarus; Umbilical hernia
Sources: Literature
Regression v0.561 ZDHHC16 Ain Roesley gene: ZDHHC16 was added
gene: ZDHHC16 was added to Regression. Sources: Literature
Mode of inheritance for gene: ZDHHC16 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZDHHC16 were set to 39313616
Phenotypes for gene: ZDHHC16 were set to neurodevelopmental disorder MONDO:0700092, ZDHHC16-related
Review for gene: ZDHHC16 was set to AMBER
gene: ZDHHC16 was marked as current diagnostic
Added comment: 6 families including a pair of siblings

Amber because 5 of the families had non specific phenotypes listed
Abnormality of:
the nervous system, metabolism/homeostasis, head/neck, immune system, the integument, the digestive system, the respiratory system, the endocrine system, Growth abnormality the skeletal system, the musculature, the eye

Specific HPOs were provided for one individual (homoyzygous for a canonical splice)

Abnormality of the face; Cerebellar hypoplasia; Developmental regression; Encephalopathy; Hyperreflexia; Hypertonia; Hypotonia; Inguinal hernia; Laryngomalacia; Microcephaly; Motor delay; Optic atrophy; Seizure; Spastic paraparesis; Spasticity; Talipes equinovarus; Umbilical hernia
Sources: Literature
Mendeliome v1.2028 ZDHHC16 Ain Roesley Marked gene: ZDHHC16 as ready
Mendeliome v1.2028 ZDHHC16 Ain Roesley Gene: zdhhc16 has been classified as Red List (Low Evidence).
Mendeliome v1.2028 ZDHHC16 Ain Roesley gene: ZDHHC16 was added
gene: ZDHHC16 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZDHHC16 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZDHHC16 were set to 39313616
Phenotypes for gene: ZDHHC16 were set to neurodevelopmental disorder MONDO:0700092, ZDHHC16-related
Review for gene: ZDHHC16 was set to AMBER
gene: ZDHHC16 was marked as current diagnostic
Added comment: 6 families including a pair of siblings

Amber because 5 of the families had non specific phenotypes listed
Abnormality of:
the nervous system, metabolism/homeostasis, head/neck, immune system, the integument, the digestive system, the respiratory system, the endocrine system, Growth abnormality the skeletal system, the musculature, the eye

Specific HPOs were provided for one individual (homoyzygous for a canonical splice)

Abnormality of the face; Cerebellar hypoplasia; Developmental regression; Encephalopathy; Hyperreflexia; Hypertonia; Hypotonia; Inguinal hernia; Laryngomalacia; Microcephaly; Motor delay; Optic atrophy; Seizure; Spastic paraparesis; Spasticity; Talipes equinovarus; Umbilical hernia
Sources: Literature
Fetal anomalies v1.270 KBTBD2 Ain Roesley Marked gene: KBTBD2 as ready
Microcephaly v1.284 KBTBD2 Ain Roesley Marked gene: KBTBD2 as ready
Fetal anomalies v1.270 KBTBD2 Ain Roesley Gene: kbtbd2 has been classified as Green List (High Evidence).
Microcephaly v1.284 KBTBD2 Ain Roesley Gene: kbtbd2 has been classified as Green List (High Evidence).
Microcephaly v1.284 KBTBD2 Ain Roesley Classified gene: KBTBD2 as Green List (high evidence)
Microcephaly v1.284 KBTBD2 Ain Roesley Gene: kbtbd2 has been classified as Green List (High Evidence).
Fetal anomalies v1.270 KBTBD2 Ain Roesley Classified gene: KBTBD2 as Green List (high evidence)
Fetal anomalies v1.270 KBTBD2 Ain Roesley Gene: kbtbd2 has been classified as Green List (High Evidence).
Mendeliome v1.2027 KBTBD2 Ain Roesley Marked gene: KBTBD2 as ready
Mendeliome v1.2027 KBTBD2 Ain Roesley Gene: kbtbd2 has been classified as Green List (High Evidence).
Mendeliome v1.2027 KBTBD2 Ain Roesley Classified gene: KBTBD2 as Green List (high evidence)
Mendeliome v1.2027 KBTBD2 Ain Roesley Gene: kbtbd2 has been classified as Green List (High Evidence).
Mendeliome v1.2026 KBTBD2 Ain Roesley gene: KBTBD2 was added
gene: KBTBD2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KBTBD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KBTBD2 were set to 39313616
Phenotypes for gene: KBTBD2 were set to neurodevelopmental disorder MONDO:0700092, KBTBD2-related
Review for gene: KBTBD2 was set to GREEN
gene: KBTBD2 was marked as current diagnostic
Added comment: 3 families - 2 compound hets and 1 hom

phenotypes include:
Microcephaly, hypotonia, failure to thrive, IUGR, delayed gross motor development, dysmorphism
Sources: Literature
Microcephaly v1.283 KBTBD2 Ain Roesley gene: KBTBD2 was added
gene: KBTBD2 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: KBTBD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KBTBD2 were set to 39313616
Phenotypes for gene: KBTBD2 were set to neurodevelopmental disorder MONDO:0700092, KBTBD2-related
Review for gene: KBTBD2 was set to GREEN
gene: KBTBD2 was marked as current diagnostic
Added comment: 3 families - 2 compound hets and 1 hom

phenotypes include:
Microcephaly, hypotonia, failure to thrive, IUGR, delayed gross motor development, dysmorphism
Sources: Literature
Fetal anomalies v1.269 KBTBD2 Ain Roesley gene: KBTBD2 was added
gene: KBTBD2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: KBTBD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KBTBD2 were set to 39313616
Phenotypes for gene: KBTBD2 were set to neurodevelopmental disorder MONDO:0700092, KBTBD2-related
Review for gene: KBTBD2 was set to GREEN
gene: KBTBD2 was marked as current diagnostic
Added comment: 3 families - 2 compound hets and 1 hom

phenotypes include:
Microcephaly, hypotonia, failure to thrive, IUGR, delayed gross motor development, dysmorphism
Sources: Literature
Clefting disorders v0.256 CRELD1 Ain Roesley Marked gene: CRELD1 as ready
Clefting disorders v0.256 CRELD1 Ain Roesley Gene: creld1 has been classified as Amber List (Moderate Evidence).
Clefting disorders v0.256 CRELD1 Ain Roesley Classified gene: CRELD1 as Amber List (moderate evidence)
Clefting disorders v0.256 CRELD1 Ain Roesley Gene: creld1 has been classified as Amber List (Moderate Evidence).
Clefting disorders v0.255 CRELD1 Ain Roesley gene: CRELD1 was added
gene: CRELD1 was added to Clefting disorders. Sources: Literature
Mode of inheritance for gene: CRELD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRELD1 were set to 37947183
Phenotypes for gene: CRELD1 were set to Jeffries-Lakhani neurodevelopmental syndrome, MIM# 620771
Review for gene: CRELD1 was set to AMBER
gene: CRELD1 was marked as current diagnostic
Added comment: 2 families with cleft palate, intra-familial variability noted
Sources: Literature
Genetic Epilepsy v1.58 EPB41L3 Bryony Thompson Marked gene: EPB41L3 as ready
Genetic Epilepsy v1.58 EPB41L3 Bryony Thompson Gene: epb41l3 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.58 EPB41L3 Bryony Thompson Classified gene: EPB41L3 as Green List (high evidence)
Genetic Epilepsy v1.58 EPB41L3 Bryony Thompson Gene: epb41l3 has been classified as Green List (High Evidence).
Genetic Epilepsy v1.57 EPB41L3 Bryony Thompson gene: EPB41L3 was added
gene: EPB41L3 was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: EPB41L3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EPB41L3 were set to 39292993
Phenotypes for gene: EPB41L3 were set to neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities MONDO:0030063
Review for gene: EPB41L3 was set to GREEN
Added comment: 6 cases from 5 unrelated consanguineous families (2nd & 3rd degree) with homozygous LoF variants and a neurodevelopmental condition, including ID and seizures. Epb41l3 shRNA-mediated downregulation in mouse oligodendroglia demonstrated impaired oligodendrocyte function.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6301 EPB41L3 Bryony Thompson Marked gene: EPB41L3 as ready
Intellectual disability syndromic and non-syndromic v0.6301 EPB41L3 Bryony Thompson Gene: epb41l3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6301 EPB41L3 Bryony Thompson Classified gene: EPB41L3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6301 EPB41L3 Bryony Thompson Gene: epb41l3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6300 EPB41L3 Bryony Thompson gene: EPB41L3 was added
gene: EPB41L3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: EPB41L3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EPB41L3 were set to 39292993
Phenotypes for gene: EPB41L3 were set to neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities MONDO:0030063
Review for gene: EPB41L3 was set to GREEN
Added comment: 6 cases from 5 unrelated consanguineous families (2nd & 3rd degree) with homozygous LoF variants and a neurodevelopmental condition, including ID and seizures. Epb41l3 shRNA-mediated downregulation in mouse oligodendroglia demonstrated impaired oligodendrocyte function.
Sources: Literature
Mendeliome v1.2025 EPB41L3 Bryony Thompson Marked gene: EPB41L3 as ready
Mendeliome v1.2025 EPB41L3 Bryony Thompson Gene: epb41l3 has been classified as Green List (High Evidence).
Mendeliome v1.2025 EPB41L3 Bryony Thompson Classified gene: EPB41L3 as Green List (high evidence)
Mendeliome v1.2025 EPB41L3 Bryony Thompson Gene: epb41l3 has been classified as Green List (High Evidence).
Mendeliome v1.2024 EPB41L3 Bryony Thompson gene: EPB41L3 was added
gene: EPB41L3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EPB41L3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EPB41L3 were set to 39292993
Phenotypes for gene: EPB41L3 were set to neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities MONDO:0030063
Review for gene: EPB41L3 was set to GREEN
Added comment: 6 cases from 5 unrelated consanguineous families (2nd & 3rd degree) with homozygous LoF variants and a neurodevelopmental condition, including ID and seizures. Epb41l3 shRNA-mediated downregulation in mouse oligodendroglia demonstrated impaired oligodendrocyte function.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6299 GCH1 Bryony Thompson Marked gene: GCH1 as ready
Intellectual disability syndromic and non-syndromic v0.6299 GCH1 Bryony Thompson Gene: gch1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6299 GCH1 Bryony Thompson Phenotypes for gene: GCH1 were changed from to GTP cyclohydrolase I deficiency with hyperphenylalaninemia MONDO:0100186
Intellectual disability syndromic and non-syndromic v0.6298 GCH1 Bryony Thompson Publications for gene: GCH1 were set to 22473768; 7869202
Intellectual disability syndromic and non-syndromic v0.6297 GCH1 Bryony Thompson Publications for gene: GCH1 were set to
Intellectual disability syndromic and non-syndromic v0.6296 GCH1 Bryony Thompson Mode of inheritance for gene: GCH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6295 GCH1 Bryony Thompson reviewed gene: GCH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22473768, 7869202; Phenotypes: GTP cyclohydrolase I deficiency with hyperphenylalaninemia MONDO:0100186; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Aminoacidopathy v1.133 GCH1 Bryony Thompson Mode of inheritance for gene: GCH1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6295 GAMT Bryony Thompson Marked gene: GAMT as ready
Intellectual disability syndromic and non-syndromic v0.6295 GAMT Bryony Thompson Gene: gamt has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6295 GAMT Bryony Thompson Phenotypes for gene: GAMT were changed from to guanidinoacetate methyltransferase deficiency MONDO:0012999
Intellectual disability syndromic and non-syndromic v0.6294 GAMT Bryony Thompson Publications for gene: GAMT were set to
Intellectual disability syndromic and non-syndromic v0.6293 GAMT Bryony Thompson Mode of inheritance for gene: GAMT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6292 GAMT Bryony Thompson reviewed gene: GAMT: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301745; Phenotypes: guanidinoacetate methyltransferase deficiency MONDO:0012999; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6292 GALE Bryony Thompson Marked gene: GALE as ready
Intellectual disability syndromic and non-syndromic v0.6292 GALE Bryony Thompson Gene: gale has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6292 GALE Bryony Thompson Phenotypes for gene: GALE were changed from to galactose epimerase deficiency MONDO:0009257
Intellectual disability syndromic and non-syndromic v0.6291 GALE Bryony Thompson Publications for gene: GALE were set to
Intellectual disability syndromic and non-syndromic v0.6290 GALE Bryony Thompson Mode of inheritance for gene: GALE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6289 GALE Bryony Thompson reviewed gene: GALE: Rating: GREEN; Mode of pathogenicity: None; Publications: 21290786; Phenotypes: galactose epimerase deficiency MONDO:0009257; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6289 GALC Bryony Thompson Marked gene: GALC as ready
Intellectual disability syndromic and non-syndromic v0.6289 GALC Bryony Thompson Gene: galc has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6289 GALC Bryony Thompson Phenotypes for gene: GALC were changed from to Krabbe disease MONDO:000949
Intellectual disability syndromic and non-syndromic v0.6288 GALC Bryony Thompson Publications for gene: GALC were set to
Intellectual disability syndromic and non-syndromic v0.6287 GALC Bryony Thompson Mode of inheritance for gene: GALC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6286 GALC Bryony Thompson reviewed gene: GALC: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301416; Phenotypes: Krabbe disease MONDO:000949; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Dystonia - complex v0.240 GABRB2 Bryony Thompson Marked gene: GABRB2 as ready
Dystonia - complex v0.240 GABRB2 Bryony Thompson Gene: gabrb2 has been classified as Green List (High Evidence).
Dystonia - complex v0.240 GABRB2 Bryony Thompson Classified gene: GABRB2 as Green List (high evidence)
Dystonia - complex v0.240 GABRB2 Bryony Thompson Gene: gabrb2 has been classified as Green List (High Evidence).
Dystonia - complex v0.239 GABRB2 Bryony Thompson gene: GABRB2 was added
gene: GABRB2 was added to Dystonia - complex. Sources: Literature
Mode of inheritance for gene: GABRB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABRB2 were set to 38996765
Phenotypes for gene: GABRB2 were set to epileptic encephalopathy, infantile or early childhood, 2 MONDO:0020631
Mode of pathogenicity for gene: GABRB2 was set to Other
Review for gene: GABRB2 was set to GREEN
gene: GABRB2 was marked as current diagnostic
Added comment: At least 7 cases reported with dystonia as a feature of phenotype associated with gain-of-function variants.
Sources: Literature
Microcephaly v1.282 GABRB2 Bryony Thompson Marked gene: GABRB2 as ready
Microcephaly v1.282 GABRB2 Bryony Thompson Gene: gabrb2 has been classified as Green List (High Evidence).
Microcephaly v1.282 GABRB2 Bryony Thompson Classified gene: GABRB2 as Green List (high evidence)
Microcephaly v1.282 GABRB2 Bryony Thompson Gene: gabrb2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.355 CARS2 Crystle Lee reviewed gene: CARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30139652, 34704010; Phenotypes: Combined oxidative phosphorylation deficiency 27 (MIM#616672); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.355 C5 Crystle Lee reviewed gene: C5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23743184, 23371790; Phenotypes: C5 deficiency (MIM#609536); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2023 PSKH1 Zornitza Stark Marked gene: PSKH1 as ready
Mendeliome v1.2023 PSKH1 Zornitza Stark Gene: pskh1 has been classified as Green List (High Evidence).
Mendeliome v1.2023 PSKH1 Zornitza Stark Classified gene: PSKH1 as Green List (high evidence)
Mendeliome v1.2023 PSKH1 Zornitza Stark Gene: pskh1 has been classified as Green List (High Evidence).
Mendeliome v1.2022 PSKH1 Zornitza Stark gene: PSKH1 was added
gene: PSKH1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PSKH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSKH1 were set to 39132680
Phenotypes for gene: PSKH1 were set to Cholestasis, progressive familial intrahepatic, 13, MIM# 620962
Review for gene: PSKH1 was set to GREEN
Added comment: 4 consanguineous families (out of 279 families) with intrahepatic cholestasis:
-1 patient died at 10mths with cholestasis/liver impairment and kidney impairment
-3 cousins with cholestasis (2 with liver failure needing transplant) and kidney features (2 with kidney failure, 1 with renal echogenicity)
-2 siblings with hepatic fibrosis (1 with unilateral renal agenesis)
-2 siblings with unexplained liver cirrhosis (1 needing transplant) but normal kidney function

WES identified 3 different homozygous variants in PSKH1 (Arg121Trp, Ile126Val, Arg183Cys). Patient fibroblasts displayed abnormal cilia that are long and show abnormal transport. A homozygous Pskh1 mutant mouse faithfully recapitulated the human phenotype and displayed abnormally long cilia. The phenotype could be rationalized by the loss of catalytic activity observed for each recombinant PSKH1 variant using in vitro kinase assays. Human PSKH1 is a poorly understood gene that may play important role in intracellular trafficking, is sensitive to intracellular Ca2+ concentration, and is localized to centrosomes, suggesting a link to cystogenesis.
Sources: Literature
Renal Ciliopathies and Nephronophthisis v1.26 PSKH1 Zornitza Stark Marked gene: PSKH1 as ready
Renal Ciliopathies and Nephronophthisis v1.26 PSKH1 Zornitza Stark Gene: pskh1 has been classified as Green List (High Evidence).
Renal Ciliopathies and Nephronophthisis v1.26 PSKH1 Zornitza Stark Phenotypes for gene: PSKH1 were changed from Hepatorenal syndrome, MONDO:0001382 to Cholestasis, progressive familial intrahepatic, 13, MIM# 620962
Ciliopathies v1.62 PSKH1 Zornitza Stark Marked gene: PSKH1 as ready
Ciliopathies v1.62 PSKH1 Zornitza Stark Gene: pskh1 has been classified as Green List (High Evidence).
Ciliopathies v1.62 PSKH1 Zornitza Stark Phenotypes for gene: PSKH1 were changed from Hepatorenal syndrome, MONDO:0001382 to Cholestasis, progressive familial intrahepatic, 13, MIM# 620962
Cholestasis v0.245 PSKH1 Zornitza Stark Marked gene: PSKH1 as ready
Cholestasis v0.245 PSKH1 Zornitza Stark Gene: pskh1 has been classified as Green List (High Evidence).
Cholestasis v0.245 PSKH1 Zornitza Stark Phenotypes for gene: PSKH1 were changed from Hepatorenal syndrome, MONDO:0001382 to Cholestasis, progressive familial intrahepatic, 13, MIM# 620962
Cholestasis v0.244 PSKH1 Zornitza Stark reviewed gene: PSKH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cholestasis, progressive familial intrahepatic, 13, MIM# 620962; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.355 BSCL2 Crystle Lee reviewed gene: BSCL2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23564749, 23659685, 26815532; Phenotypes: Encephalopathy, progressive, with or without lipodystrophy (MIM#615924), Lipodystrophy, congenital generalized, type 2 (MIM#269700); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.355 BBS10 Crystle Lee reviewed gene: BBS10: Rating: GREEN; Mode of pathogenicity: None; Publications: 36340607; Phenotypes: Bardet-Biedl syndrome 10 (MIM#615987); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.355 ALAD Lilian Downie Marked gene: ALAD as ready
Prepair 1000+ v1.355 ALAD Lilian Downie Gene: alad has been classified as Green List (High Evidence).
Prepair 1000+ v1.355 ALAD Lilian Downie Publications for gene: ALAD were set to
Prepair 1000+ v1.354 GAN Lilian Downie Marked gene: GAN as ready
Prepair 1000+ v1.354 GAN Lilian Downie Gene: gan has been classified as Green List (High Evidence).
Prepair 1000+ v1.354 GAN Lilian Downie Publications for gene: GAN were set to
Prepair 1000+ v1.353 ABAT Lilian Downie Marked gene: ABAT as ready
Prepair 1000+ v1.353 ABAT Lilian Downie Gene: abat has been classified as Green List (High Evidence).
Prepair 1000+ v1.353 ABAT Lilian Downie Publications for gene: ABAT were set to
Prepair 1000+ v1.352 GATM Lilian Downie Marked gene: GATM as ready
Prepair 1000+ v1.352 GATM Lilian Downie Gene: gatm has been classified as Green List (High Evidence).
Prepair 1000+ v1.352 GATM Lilian Downie Publications for gene: GATM were set to
Prepair 1000+ v1.351 AMPD2 Lilian Downie Marked gene: AMPD2 as ready
Prepair 1000+ v1.351 AMPD2 Lilian Downie Gene: ampd2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.351 AMPD2 Lilian Downie Publications for gene: AMPD2 were set to 23911318
Prepair 1000+ v1.350 AMPD2 Lilian Downie Publications for gene: AMPD2 were set to
Prepair 1000+ v1.349 ASPA Lilian Downie Marked gene: ASPA as ready
Prepair 1000+ v1.349 ASPA Lilian Downie Gene: aspa has been classified as Green List (High Evidence).
Prepair 1000+ v1.349 ASPA Lilian Downie Publications for gene: ASPA were set to
Prepair 1000+ v1.348 ALPL Crystle Lee reviewed gene: ALPL: Rating: GREEN; Mode of pathogenicity: None; Publications: 19500388, 23688511, 32029969, 24569605; Phenotypes: Hypophosphatasia, childhood (MIM#241510), Hypophosphatasia, infantile (MIM#241500); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.41 JAG2 Bryony Thompson Marked gene: JAG2 as ready
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.41 JAG2 Bryony Thompson Gene: jag2 has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.41 JAG2 Bryony Thompson Publications for gene: JAG2 were set to
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.40 JAG2 Bryony Thompson Classified gene: JAG2 as Green List (high evidence)
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.40 JAG2 Bryony Thompson Gene: jag2 has been classified as Green List (High Evidence).
Microcephaly v1.281 GABRB2 Bryony Thompson gene: GABRB2 was added
gene: GABRB2 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: GABRB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABRB2 were set to 38996765
Phenotypes for gene: GABRB2 were set to epileptic encephalopathy, infantile or early childhood, 2 MONDO:0020631
Mode of pathogenicity for gene: GABRB2 was set to Other
Review for gene: GABRB2 was set to GREEN
gene: GABRB2 was marked as current diagnostic
Added comment: Microcephaly has been reported in at least 13 individuals with gain of function variants.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6286 GABRB2 Bryony Thompson Marked gene: GABRB2 as ready
Intellectual disability syndromic and non-syndromic v0.6286 GABRB2 Bryony Thompson Gene: gabrb2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6286 GABRB2 Bryony Thompson Phenotypes for gene: GABRB2 were changed from to epileptic encephalopathy, infantile or early childhood, 2 MONDO:0020631
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.38 JAG2 Bryony Thompson gene: JAG2 was added
gene: JAG2 was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Other
Mode of inheritance for gene: JAG2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: JAG2 were set to muscular dystrophy, limb-girdle, autosomal recessive 27 MONDO:0030456
Mitochondrial disease v0.936 CIAO1 Zornitza Stark Marked gene: CIAO1 as ready
Mitochondrial disease v0.936 CIAO1 Zornitza Stark Gene: ciao1 has been classified as Green List (High Evidence).
Mitochondrial disease v0.936 CIAO1 Zornitza Stark Classified gene: CIAO1 as Green List (high evidence)
Mitochondrial disease v0.936 CIAO1 Zornitza Stark Gene: ciao1 has been classified as Green List (High Evidence).
Mitochondrial disease v0.935 CIAO1 Zornitza Stark gene: CIAO1 was added
gene: CIAO1 was added to Mitochondrial disease. Sources: Literature
Mode of inheritance for gene: CIAO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CIAO1 were set to 38411040; 38196629
Phenotypes for gene: CIAO1 were set to Multiple mitochondrial dysfunctions syndrome 10, MIM#620960
Review for gene: CIAO1 was set to GREEN
Added comment: PMID:38196629 (note pre-print) describes 4 unrelated patients with core features of progressive muscle weakness, respiratory insufficiency, joint hyperlaxity, ankle tightness, calf pseudohypertrophy, elevated CK, and larning disabilities/difficulties. 2 patients presented with increased iron deposition in the brain. Age of recognition of myopathic symptoms varied from early childhood to adolescence. Muscle biopsy showed variation in fiber size and an increase in internalized nuclei, as well as scattered degenerating/regenerating fibers and a mild to minimal increase in endomysial fibrosis. Electron microscopy revealed morphologically abnormal mitochondria.

PMID: 38411040 reports 2 unrelated patients. Patient 1 was born with microcephaly and borderline hypertonia, and died at 18 months of respiratory failure from bronchiolitis. Patient 2 presented with failure to thrive, a hyperkinetic movement disorder, and autism before deteriorating in late teens with muscle weakness, recurrent pneuomonia with respiratory insufficiency, and eventually death due to multi-organ failure with carnificating pneumonia, septic cardiomyopathy, and intracranial hemorrhages. Immune deficiency was ruled out.

All variants reported were homozygous or compound heterozygous missense variants, with the exception of one large in-frame deletion of exon 7. Cell line studies showed the variants resulted in reduced protein stability and downstream cellular defects which could be rescued by wild-type CIAO1. Electron microscopy of skeletal muscle demonstrated abnormal assembly of mitochondrial respiratory chain complexes.
Sources: Literature
Regression v0.560 CIAO1 Zornitza Stark Phenotypes for gene: CIAO1 were changed from Neurodegenerative disease, MONDO:0005559, CIAO1-related to Multiple mitochondrial dysfunctions syndrome 10, MIM#620960
Regression v0.559 CIAO1 Zornitza Stark edited their review of gene: CIAO1: Changed phenotypes: Multiple mitochondrial dysfunctions syndrome 10, MIM#620960
Muscular dystrophy and myopathy_Paediatric v1.75 CIAO1 Zornitza Stark Phenotypes for gene: CIAO1 were changed from Neurodegenerative disease, MONDO:0005559, CIAO1-related to Multiple mitochondrial dysfunctions syndrome 10, MIM#620960
Muscular dystrophy and myopathy_Paediatric v1.74 CIAO1 Zornitza Stark reviewed gene: CIAO1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Multiple mitochondrial dysfunctions syndrome 10, MIM#620960; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2021 CIAO1 Zornitza Stark Phenotypes for gene: CIAO1 were changed from Neurodegenerative disease, MONDO:0005559, CIAO1-related to Multiple mitochondrial dysfunctions syndrome 10, MIM#620960
Mendeliome v1.2020 CIAO1 Zornitza Stark reviewed gene: CIAO1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Multiple mitochondrial dysfunctions syndrome 10, MIM#620960; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2020 TREM2 Zornitza Stark Phenotypes for gene: TREM2 were changed from Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2, MIM# 618193 to Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2, MIM# 618193; {Alzhieimer disease 17, susceptibility to}, MIM# 615080
Mendeliome v1.2019 TREM2 Zornitza Stark edited their review of gene: TREM2: Changed phenotypes: Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2, MIM# 618193, {Alzhieimer disease 17, susceptibility to}, MIM# 615080
Early-onset Dementia v1.25 TREM2 Zornitza Stark Phenotypes for gene: TREM2 were changed from Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2, MIM# 618193 to Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2, MIM# 618193; {Alzhieimer disease 17, susceptibility to}, MIM# 615080
Early-onset Dementia v1.24 TREM2 Zornitza Stark edited their review of gene: TREM2: Changed phenotypes: Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2, MIM# 618193, {Alzhieimer disease 17, susceptibility to}, MIM# 615080
Muscular dystrophy and myopathy_Paediatric v1.74 JPH1 Zornitza Stark Phenotypes for gene: JPH1 were changed from Congenital myopathy MONDO:0019952 to Congenital myopathy 25, MIM# 620964
Muscular dystrophy and myopathy_Paediatric v1.73 JPH1 Zornitza Stark reviewed gene: JPH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital myopathy 25, MIM# 620964; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2019 JPH1 Zornitza Stark Phenotypes for gene: JPH1 were changed from Congenital myopathy MONDO:0019952 to Congenital myopathy 25, MIM# 620964
Mendeliome v1.2018 JPH1 Zornitza Stark reviewed gene: JPH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Congenital myopathy 25, MIM# 620964; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6285 GABRB2 Bryony Thompson Publications for gene: GABRB2 were set to
Intellectual disability syndromic and non-syndromic v0.6284 GABRB2 Bryony Thompson Mode of inheritance for gene: GABRB2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6283 GABRB2 Bryony Thompson reviewed gene: GABRB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38996765; Phenotypes: epileptic encephalopathy, infantile or early childhood, 2 MONDO:0020631; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Prepair 1000+ v1.348 HK1 Lilian Downie Marked gene: HK1 as ready
Prepair 1000+ v1.348 HK1 Lilian Downie Added comment: Comment when marking as ready: Caution mutliple phenotypes:

AD phenotype Neurodevelopmental disorder with visual defects and brain anomalies MIM#618547 caused by recurrent variants likely causing gain-of-function c.1370C>T, c.1334C>T, c.1240G>A
(PMID: 38617198)

AR HMSNR Founder variant in the Roma, -3818-195G-C, AltT2 EXON in 5'UTR identified in multiple families.
Prepair 1000+ v1.348 HK1 Lilian Downie Gene: hk1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.348 HK1 Lilian Downie Phenotypes for gene: HK1 were changed from Neuropathy, hereditary motor and sensory, Russe type, 605285 (3) to Hemolytic anemia due to hexokinase deficiency MIM#235700; Neuropathy, hereditary motor and sensory, Russe type, MIM#605285
Prepair 1000+ v1.347 HK1 Lilian Downie Publications for gene: HK1 were set to
Prepair 1000+ v1.346 ATP6V0A2 Lilian Downie Marked gene: ATP6V0A2 as ready
Prepair 1000+ v1.346 ATP6V0A2 Lilian Downie Gene: atp6v0a2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.346 ATP6V0A2 Lilian Downie Publications for gene: ATP6V0A2 were set to
Prepair 1000+ v1.345 PNPO Lilian Downie Marked gene: PNPO as ready
Prepair 1000+ v1.345 PNPO Lilian Downie Gene: pnpo has been classified as Green List (High Evidence).
Prepair 1000+ v1.345 PNPO Lilian Downie Publications for gene: PNPO were set to
Prepair 1000+ v1.344 POMGNT1 Lilian Downie Marked gene: POMGNT1 as ready
Prepair 1000+ v1.344 POMGNT1 Lilian Downie Added comment: Comment when marking as ready: Isolated RP presentation can start with night blindness in childhood.
Prepair 1000+ v1.344 POMGNT1 Lilian Downie Gene: pomgnt1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.344 POMGNT1 Lilian Downie Phenotypes for gene: POMGNT1 were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3, 253280 (3) to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3, MIM#253280; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B3, MIM#613151; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 3 MIM#613157
Prepair 1000+ v1.343 POMGNT1 Lilian Downie Publications for gene: POMGNT1 were set to
Prepair 1000+ v1.342 PQBP1 Lilian Downie Marked gene: PQBP1 as ready
Prepair 1000+ v1.342 PQBP1 Lilian Downie Gene: pqbp1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.342 PQBP1 Lilian Downie Publications for gene: PQBP1 were set to
Prepair 1000+ v1.341 PRG4 Lilian Downie Marked gene: PRG4 as ready
Prepair 1000+ v1.341 PRG4 Lilian Downie Gene: prg4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.341 PRG4 Lilian Downie Publications for gene: PRG4 were set to 10545950; 29397575
Prepair 1000+ v1.340 PRG4 Lilian Downie Publications for gene: PRG4 were set to
Intellectual disability syndromic and non-syndromic v0.6283 FUCA1 Bryony Thompson Marked gene: FUCA1 as ready
Intellectual disability syndromic and non-syndromic v0.6283 FUCA1 Bryony Thompson Gene: fuca1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6283 FUCA1 Bryony Thompson Phenotypes for gene: FUCA1 were changed from to Fucosidosis MONDO:0009254
Intellectual disability syndromic and non-syndromic v0.6282 FUCA1 Bryony Thompson Publications for gene: FUCA1 were set to
Intellectual disability syndromic and non-syndromic v0.6281 FUCA1 Bryony Thompson Mode of inheritance for gene: FUCA1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6280 FUCA1 Bryony Thompson reviewed gene: FUCA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33266441; Phenotypes: Fucosidosis MONDO:0009254; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6280 FOXRED1 Bryony Thompson Marked gene: FOXRED1 as ready
Intellectual disability syndromic and non-syndromic v0.6280 FOXRED1 Bryony Thompson Gene: foxred1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6280 FOXRED1 Bryony Thompson Phenotypes for gene: FOXRED1 were changed from to Mitochondrial disease MONDO:0044970
Intellectual disability syndromic and non-syndromic v0.6279 FOXRED1 Bryony Thompson Publications for gene: FOXRED1 were set to
Intellectual disability syndromic and non-syndromic v0.6278 FOXRED1 Bryony Thompson Mode of inheritance for gene: FOXRED1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6277 FOXRED1 Bryony Thompson reviewed gene: FOXRED1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31434271, 20818383, 20858599; Phenotypes: Mitochondrial disease MONDO:0044970; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6277 FOXG1 Bryony Thompson Marked gene: FOXG1 as ready
Intellectual disability syndromic and non-syndromic v0.6277 FOXG1 Bryony Thompson Gene: foxg1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6277 FOXG1 Bryony Thompson Phenotypes for gene: FOXG1 were changed from to FOXG1 disorder MONDO:0100040
Intellectual disability syndromic and non-syndromic v0.6276 FOXG1 Bryony Thompson Publications for gene: FOXG1 were set to
Intellectual disability syndromic and non-syndromic v0.6275 FOXG1 Bryony Thompson Mode of inheritance for gene: FOXG1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6274 FOXG1 Bryony Thompson reviewed gene: FOXG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 18571142, 19578037, 19564653, 28661489; Phenotypes: FOXG1 disorder MONDO:0100040; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6274 FKTN Bryony Thompson Marked gene: FKTN as ready
Intellectual disability syndromic and non-syndromic v0.6274 FKTN Bryony Thompson Gene: fktn has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6274 FKTN Bryony Thompson Phenotypes for gene: FKTN were changed from to Myopathy caused by variation in FKTN MONDO:0700067
Intellectual disability syndromic and non-syndromic v0.6273 FKTN Bryony Thompson Publications for gene: FKTN were set to
Intellectual disability syndromic and non-syndromic v0.6272 FKTN Bryony Thompson Mode of inheritance for gene: FKTN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6271 FKTN Bryony Thompson reviewed gene: FKTN: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301385; Phenotypes: Myopathy caused by variation in FKTN MONDO:0700067; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Muscular dystrophy and myopathy_Paediatric v1.73 FKRP Bryony Thompson Publications for gene: FKRP were set to
Muscular dystrophy and myopathy_Paediatric v1.72 FKRP Bryony Thompson Marked gene: FKRP as ready
Muscular dystrophy and myopathy_Paediatric v1.72 FKRP Bryony Thompson Gene: fkrp has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.72 FKRP Bryony Thompson Phenotypes for gene: FKRP were changed from to myopathy caused by variation in FKRP MONDO:0700066
Intellectual disability syndromic and non-syndromic v0.6271 FKRP Bryony Thompson Marked gene: FKRP as ready
Intellectual disability syndromic and non-syndromic v0.6271 FKRP Bryony Thompson Gene: fkrp has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6271 FKRP Bryony Thompson Phenotypes for gene: FKRP were changed from myopathy caused by variation in FKRP MONDO:0700066 to myopathy caused by variation in FKRP MONDO:0700066
Intellectual disability syndromic and non-syndromic v0.6270 FKRP Bryony Thompson Phenotypes for gene: FKRP were changed from to myopathy caused by variation in FKRP MONDO:0700066
Muscular dystrophy and myopathy_Paediatric v1.71 FKRP Bryony Thompson Mode of inheritance for gene: FKRP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6269 FKRP Bryony Thompson Publications for gene: FKRP were set to
Intellectual disability syndromic and non-syndromic v0.6268 FKRP Bryony Thompson Mode of inheritance for gene: FKRP was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6267 FKRP Bryony Thompson reviewed gene: FKRP: Rating: GREEN; Mode of pathogenicity: None; Publications: 33200426, 11053680, 12654965, 14652796, 15121789; Phenotypes: myopathy caused by variation in FKRP MONDO:0700066; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6267 FIG4 Bryony Thompson Marked gene: FIG4 as ready
Intellectual disability syndromic and non-syndromic v0.6267 FIG4 Bryony Thompson Gene: fig4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6267 FIG4 Bryony Thompson Phenotypes for gene: FIG4 were changed from to Charcot-Marie-Tooth disease MONDO:0015626
Intellectual disability syndromic and non-syndromic v0.6266 FIG4 Bryony Thompson Publications for gene: FIG4 were set to
Intellectual disability syndromic and non-syndromic v0.6265 FIG4 Bryony Thompson Mode of inheritance for gene: FIG4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6264 FIG4 Bryony Thompson reviewed gene: FIG4: Rating: GREEN; Mode of pathogenicity: None; Publications: 32385905, 34122524, 36529678; Phenotypes: Charcot-Marie-Tooth disease MONDO:0015626; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mitochondrial disease v0.934 FBXL4 Bryony Thompson Marked gene: FBXL4 as ready
Mitochondrial disease v0.934 FBXL4 Bryony Thompson Gene: fbxl4 has been classified as Green List (High Evidence).
Mitochondrial disease v0.934 FBXL4 Bryony Thompson Publications for gene: FBXL4 were set to
Mitochondrial disease v0.933 FBXL4 Bryony Thompson Phenotypes for gene: FBXL4 were changed from to Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type) MIM#615471
Intellectual disability syndromic and non-syndromic v0.6264 FBXL4 Bryony Thompson Marked gene: FBXL4 as ready
Intellectual disability syndromic and non-syndromic v0.6264 FBXL4 Bryony Thompson Gene: fbxl4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6264 FBXL4 Bryony Thompson Phenotypes for gene: FBXL4 were changed from to Leigh syndrome MONDO:0009723
Mitochondrial disease v0.932 FBXL4 Bryony Thompson Mode of inheritance for gene: FBXL4 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6263 FBXL4 Bryony Thompson Publications for gene: FBXL4 were set to
Mitochondrial disease v0.931 FBXL4 Bryony Thompson Mode of inheritance for gene: FBXL4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6262 FBXL4 Bryony Thompson reviewed gene: FBXL4: Rating: GREEN; Mode of pathogenicity: None; Publications: 28383868; Phenotypes: Leigh syndrome MONDO:0009723; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6262 FBXL4 Bryony Thompson Mode of inheritance for gene: FBXL4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6261 FAT4 Bryony Thompson Marked gene: FAT4 as ready
Intellectual disability syndromic and non-syndromic v0.6261 FAT4 Bryony Thompson Gene: fat4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6261 FAT4 Bryony Thompson Phenotypes for gene: FAT4 were changed from to Hennekam syndrome MONDO:0016256; van Maldergem syndrome MONDO:0017813
Intellectual disability syndromic and non-syndromic v0.6260 FAT4 Bryony Thompson Publications for gene: FAT4 were set to
Intellectual disability syndromic and non-syndromic v0.6259 FAT4 Bryony Thompson Mode of inheritance for gene: FAT4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6258 FAT4 Bryony Thompson reviewed gene: FAT4: Rating: GREEN; Mode of pathogenicity: None; Publications: 29681106; Phenotypes: Hennekam syndrome MONDO:0016256, van Maldergem syndrome MONDO:0017813; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Microcephaly v1.280 FAM20C Bryony Thompson Marked gene: FAM20C as ready
Microcephaly v1.280 FAM20C Bryony Thompson Gene: fam20c has been classified as Green List (High Evidence).
Microcephaly v1.280 FAM20C Bryony Thompson Classified gene: FAM20C as Green List (high evidence)
Microcephaly v1.280 FAM20C Bryony Thompson Gene: fam20c has been classified as Green List (High Evidence).
Microcephaly v1.279 FAM20C Bryony Thompson gene: FAM20C was added
gene: FAM20C was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: FAM20C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM20C were set to 34360805
Phenotypes for gene: FAM20C were set to lethal osteosclerotic bone dysplasia MONDO:0009821
Review for gene: FAM20C was set to GREEN
gene: FAM20C was marked as current diagnostic
Added comment: Microcephaly is present in ~36% of reported cases.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6258 FAM20C Bryony Thompson Marked gene: FAM20C as ready
Intellectual disability syndromic and non-syndromic v0.6258 FAM20C Bryony Thompson Gene: fam20c has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6258 FAM20C Bryony Thompson Phenotypes for gene: FAM20C were changed from to lethal osteosclerotic bone dysplasia MONDO:0009821
Macrocephaly_Megalencephaly v0.146 FAM20C Bryony Thompson Marked gene: FAM20C as ready
Macrocephaly_Megalencephaly v0.146 FAM20C Bryony Thompson Gene: fam20c has been classified as Red List (Low Evidence).
Macrocephaly_Megalencephaly v0.146 FAM20C Bryony Thompson Classified gene: FAM20C as Red List (low evidence)
Macrocephaly_Megalencephaly v0.146 FAM20C Bryony Thompson Added comment: Comment on list classification: Microcephaly rather than macrocephaly/megalencephaly is a feature of the condition
Macrocephaly_Megalencephaly v0.146 FAM20C Bryony Thompson Gene: fam20c has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.6257 FAM20C Bryony Thompson Publications for gene: FAM20C were set to
Intellectual disability syndromic and non-syndromic v0.6256 FAM20C Bryony Thompson Mode of inheritance for gene: FAM20C was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6255 FAM20C Bryony Thompson reviewed gene: FAM20C: Rating: GREEN; Mode of pathogenicity: None; Publications: 34360805; Phenotypes: lethal osteosclerotic bone dysplasia MONDO:0009821; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6255 FAM126A Bryony Thompson Marked gene: FAM126A as ready
Intellectual disability syndromic and non-syndromic v0.6255 FAM126A Bryony Thompson Gene: fam126a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6255 FAM126A Bryony Thompson Phenotypes for gene: FAM126A were changed from to hypomyelinating leukodystrophy 5 MONDO:0012514
Intellectual disability syndromic and non-syndromic v0.6254 FAM126A Bryony Thompson Publications for gene: FAM126A were set to
Intellectual disability syndromic and non-syndromic v0.6253 FAM126A Bryony Thompson Mode of inheritance for gene: FAM126A was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6252 FAM126A Bryony Thompson reviewed gene: FAM126A: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301737; Phenotypes: hypomyelinating leukodystrophy 5 MONDO:0012514; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6252 ESCO2 Bryony Thompson Marked gene: ESCO2 as ready
Intellectual disability syndromic and non-syndromic v0.6252 ESCO2 Bryony Thompson Gene: esco2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6252 ESCO2 Bryony Thompson Phenotypes for gene: ESCO2 were changed from to Roberts-SC phocomelia syndrome MONDO:0100253
Intellectual disability syndromic and non-syndromic v0.6251 ESCO2 Bryony Thompson Publications for gene: ESCO2 were set to
Intellectual disability syndromic and non-syndromic v0.6250 ESCO2 Bryony Thompson Mode of inheritance for gene: ESCO2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6249 ESCO2 Bryony Thompson reviewed gene: ESCO2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301332; Phenotypes: Roberts-SC phocomelia syndrome MONDO:0100253; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6249 INPP5K Sangavi Sivagnanasundram reviewed gene: INPP5K: Rating: GREEN; Mode of pathogenicity: None; Publications: 28190456, 28190459; Phenotypes: congenital muscular dystrophy with cataracts and intellectual disability MONDO:0024607; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6249 IKBKG Sangavi Sivagnanasundram reviewed gene: IKBKG: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301645; Phenotypes: Incontinentia pigmenti MONDO:0010631; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.339 PRUNE1 Lilian Downie Marked gene: PRUNE1 as ready
Prepair 1000+ v1.339 PRUNE1 Lilian Downie Gene: prune1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.339 PRUNE1 Lilian Downie Phenotypes for gene: PRUNE1 were changed from Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies, 617481 (3), Autosomal recessive to Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies MIM#617481
Prepair 1000+ v1.338 PRUNE1 Lilian Downie Publications for gene: PRUNE1 were set to
Prepair 1000+ v1.337 RBM10 Lilian Downie Marked gene: RBM10 as ready
Prepair 1000+ v1.337 RBM10 Lilian Downie Gene: rbm10 has been classified as Green List (High Evidence).
Prepair 1000+ v1.337 RBM10 Lilian Downie Publications for gene: RBM10 were set to
Prepair 1000+ v1.336 RFXAP Lilian Downie Marked gene: RFXAP as ready
Prepair 1000+ v1.336 RFXAP Lilian Downie Gene: rfxap has been classified as Green List (High Evidence).
Prepair 1000+ v1.336 RFXAP Lilian Downie Phenotypes for gene: RFXAP were changed from Bare lymphocyte syndrome, type II, complementation group D, 209920 (3) to MHC class II deficiency 4 MIM#620817
Prepair 1000+ v1.335 RFXAP Lilian Downie Publications for gene: RFXAP were set to
Prepair 1000+ v1.334 SARS2 Lilian Downie Marked gene: SARS2 as ready
Prepair 1000+ v1.334 SARS2 Lilian Downie Gene: sars2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.334 SARS2 Lilian Downie Publications for gene: SARS2 were set to
Prepair 1000+ v1.333 SLC13A5 Lilian Downie Marked gene: SLC13A5 as ready
Prepair 1000+ v1.333 SLC13A5 Lilian Downie Gene: slc13a5 has been classified as Green List (High Evidence).
Prepair 1000+ v1.333 SLC13A5 Lilian Downie Phenotypes for gene: SLC13A5 were changed from Epileptic encephalopathy, early infantile, 25, 615905 (3) to Developmental and epileptic encephalopathy 25, with amelogenesis imperfecta MIM#615905
Prepair 1000+ v1.332 SLC13A5 Lilian Downie Publications for gene: SLC13A5 were set to
Prepair 1000+ v1.331 SLC2A10 Lilian Downie Marked gene: SLC2A10 as ready
Prepair 1000+ v1.331 SLC2A10 Lilian Downie Gene: slc2a10 has been classified as Green List (High Evidence).
Prepair 1000+ v1.331 SLC2A10 Lilian Downie Publications for gene: SLC2A10 were set to
Prepair 1000+ v1.330 SLC45A2 Lilian Downie Marked gene: SLC45A2 as ready
Prepair 1000+ v1.330 SLC45A2 Lilian Downie Added comment: Comment when marking as ready: Gene also known as MATP
Prepair 1000+ v1.330 SLC45A2 Lilian Downie Gene: slc45a2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.330 SLC45A2 Lilian Downie Publications for gene: SLC45A2 were set to 11574907; 14722913; 14961451
Prepair 1000+ v1.329 SLC45A2 Lilian Downie Publications for gene: SLC45A2 were set to
Prepair 1000+ v1.328 SLC6A3 Lilian Downie Marked gene: SLC6A3 as ready
Prepair 1000+ v1.328 SLC6A3 Lilian Downie Gene: slc6a3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.328 SLC6A3 Lilian Downie Publications for gene: SLC6A3 were set to
Prepair 1000+ v1.327 SPAG1 Lilian Downie Marked gene: SPAG1 as ready
Prepair 1000+ v1.327 SPAG1 Lilian Downie Gene: spag1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.327 SPAG1 Lilian Downie Publications for gene: SPAG1 were set to
Prepair 1000+ v1.326 SPEG Lilian Downie Marked gene: SPEG as ready
Prepair 1000+ v1.326 SPEG Lilian Downie Gene: speg has been classified as Green List (High Evidence).
Prepair 1000+ v1.326 SPEG Lilian Downie Publications for gene: SPEG were set to 29614691; 30157964; 25087613; 29474540; 31625632; 28624463; 26578207; 30412272
Intellectual disability syndromic and non-syndromic v0.6249 RAF1 Chirag Patel reviewed gene: RAF1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 17603483, 17603482, 31145547, 31030682, 29271604; Phenotypes: Noonan syndrome 5, MIM# 611553; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6249 RIT1 Chirag Patel reviewed gene: RIT1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 23791108, 25124994, 24939608, 27101134; Phenotypes: Noonan syndrome 8, MIM# 615355; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6249 RRAS2 Chirag Patel Classified gene: RRAS2 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6249 RRAS2 Chirag Patel Gene: rras2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6248 RRAS2 Chirag Patel reviewed gene: RRAS2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.6248 PTPN11 Chirag Patel reviewed gene: PTPN11: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 11992261,21533187, 24935154; Phenotypes: LEOPARD syndrome 1, 151100 AD (for reporting use Noonan syndrome with multiple lentigines), Metachondromatosis, 156250 AD, Noonan syndrome 1, 163950 AD, Leukemia, juvenile myelomonocytic, somatic, 607785; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6248 KRAS Chirag Patel reviewed gene: KRAS: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 21797849, 16474404, 16474405, 16773572, 17056636; Phenotypes: Noonan syndrome 3, MIM# 609942, Cardiofaciocutaneous syndrome 2, MIM# 615278; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rasopathy v0.105 KRAS Chirag Patel reviewed gene: KRAS: Rating: ; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.6248 NRAS Chirag Patel reviewed gene: NRAS: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 19966803, 26467218, 28594414; Phenotypes: Noonan syndrome 6, MIM# 613224; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6248 NPHP1 Chirag Patel reviewed gene: NPHP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 15138899, 32139166, 28347285, 8852662, 9856524; Phenotypes: Joubert syndrome 4, MIM# 609583, Nephronophthisis 1, juvenile, MIM# 256100, Senior-Loken syndrome-1, MIM# 266900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.6248 OTX2 Chirag Patel reviewed gene: OTX2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 24167467, 25589041, 31969185,; Phenotypes: Microphthalmia, syndromic 5, MIM# 610125, Pituitary hormone deficiency, combined, 6, MIM# 613986, Retinal dystrophy, early-onset, with or without pituitary dysfunction, MIM# 610125, Otocephaly-dysgnathia complex; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6248 OPA3 Chirag Patel reviewed gene: OPA3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25159689, 31119193, 31928268; Phenotypes: 3-methylglutaconic aciduria, type III (MGA3) (MIM#258501), AR, Optic atrophy 3 with cataract (MIM#165300), AD; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6248 OCLN Chirag Patel reviewed gene: OCLN: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20727516, 32240828, 29192239, 28386946; Phenotypes: Pseudo-TORCH syndrome 1, MIM#251290; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.325 STAMBP Lilian Downie Marked gene: STAMBP as ready
Prepair 1000+ v1.325 STAMBP Lilian Downie Gene: stambp has been classified as Green List (High Evidence).
Prepair 1000+ v1.325 STAMBP Lilian Downie Publications for gene: STAMBP were set to
Prepair 1000+ v1.324 STAR Lilian Downie Marked gene: STAR as ready
Prepair 1000+ v1.324 STAR Lilian Downie Gene: star has been classified as Green List (High Evidence).
Prepair 1000+ v1.324 STAR Lilian Downie Publications for gene: STAR were set to
Prepair 1000+ v1.323 TBCE Lilian Downie Marked gene: TBCE as ready
Prepair 1000+ v1.323 TBCE Lilian Downie Gene: tbce has been classified as Green List (High Evidence).
Prepair 1000+ v1.323 TBCE Lilian Downie Phenotypes for gene: TBCE were changed from Kenny-Caffey syndrome-1, 244460 (3) to Encephalopathy, progressive, with amyotrophy and optic atrophy MIM#617207; Hypoparathyroidism-retardation-dysmorphism syndrome MIM#241410; Kenny-Caffey syndrome, type 1 MIM#244460
Pituitary Tumour v0.19 SDHD Chirag Patel Classified gene: SDHD as Green List (high evidence)
Pituitary Tumour v0.19 SDHD Chirag Patel Gene: sdhd has been classified as Green List (High Evidence).
Pituitary Tumour v0.18 SDHC Chirag Patel Classified gene: SDHC as Green List (high evidence)
Pituitary Tumour v0.18 SDHC Chirag Patel Gene: sdhc has been classified as Green List (High Evidence).
Pituitary Tumour v0.17 SDHB Chirag Patel Classified gene: SDHB as Green List (high evidence)
Pituitary Tumour v0.17 SDHB Chirag Patel Gene: sdhb has been classified as Green List (High Evidence).
Pituitary Tumour v0.16 SDHA Chirag Patel Classified gene: SDHA as Green List (high evidence)
Pituitary Tumour v0.16 SDHA Chirag Patel Gene: sdha has been classified as Green List (High Evidence).
Pituitary Tumour v0.15 PRKAR1A Chirag Patel Classified gene: PRKAR1A as Green List (high evidence)
Pituitary Tumour v0.15 PRKAR1A Chirag Patel Gene: prkar1a has been classified as Green List (High Evidence).
Pituitary Tumour v0.14 MEN1 Chirag Patel Classified gene: MEN1 as Green List (high evidence)
Pituitary Tumour v0.14 MEN1 Chirag Patel Gene: men1 has been classified as Green List (High Evidence).
Pituitary Tumour v0.13 CDKN1B Chirag Patel Classified gene: CDKN1B as Green List (high evidence)
Pituitary Tumour v0.13 CDKN1B Chirag Patel Gene: cdkn1b has been classified as Green List (High Evidence).
Pituitary Tumour v0.12 CDKN1B Chirag Patel Classified gene: CDKN1B as Green List (high evidence)
Pituitary Tumour v0.12 CDKN1B Chirag Patel Gene: cdkn1b has been classified as Green List (High Evidence).
Pituitary Tumour v0.11 AIP Chirag Patel Classified gene: AIP as Green List (high evidence)
Pituitary Tumour v0.11 AIP Chirag Patel Gene: aip has been classified as Green List (High Evidence).
Pituitary Tumour v0.10 SDHD Chirag Patel gene: SDHD was added
gene: SDHD was added to Pituitary Tumour. Sources: Expert list,Expert Review
Mode of inheritance for gene: SDHD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SDHD were set to Pituitary tumor, MONDO:0017611; Pituitary gland adenoma, MONDO:0006373; Hereditary pheochromocytoma-paraganglioma, MONDO:0017366; Pheochromocytoma/paraganglioma syndrome 1, MIM#168000
Review for gene: SDHD was set to GREEN
Added comment: ClinGen definitive. Pituitary tumour/adenomas reported in condition.
Sources: Expert list, Expert Review
Pituitary Tumour v0.9 SDHC Chirag Patel gene: SDHC was added
gene: SDHC was added to Pituitary Tumour. Sources: Expert list,Expert Review
Mode of inheritance for gene: SDHC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SDHC were set to Pituitary tumor, MONDO:0017611; Pituitary gland adenoma, MONDO:0006373; Hereditary pheochromocytoma-paraganglioma, MONDO:0017366; Pheochromocytoma/paraganglioma syndrome 3, MIM#605373
Review for gene: SDHC was set to GREEN
Added comment: ClinGen definitive. Pituitary tumour/adenomas reported in condition.
Sources: Expert list, Expert Review
Pituitary Tumour v0.8 SDHB Chirag Patel gene: SDHB was added
gene: SDHB was added to Pituitary Tumour. Sources: Expert list,Expert Review
Mode of inheritance for gene: SDHB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SDHB were set to Pituitary tumor, MONDO:0017611; Pituitary gland adenoma, MONDO:0006373; Hereditary pheochromocytoma-paraganglioma, MONDO:0017366; Pheochromocytoma/paraganglioma syndrome 4, MIM#115310
Review for gene: SDHB was set to GREEN
Added comment: ClinGen definitive. Pituitary tumour/adenomas reported in condition.
Sources: Expert list, Expert Review
Pituitary Tumour v0.7 SDHA Chirag Patel gene: SDHA was added
gene: SDHA was added to Pituitary Tumour. Sources: Expert list,Expert Review
Mode of inheritance for gene: SDHA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SDHA were set to Pituitary tumor, MONDO:0017611; Pituitary gland adenoma, MONDO:0006373; Hereditary pheochromocytoma-paraganglioma, MONDO:0017366; Pheochromocytoma/paraganglioma syndrome 5, MIM#614165
Review for gene: SDHA was set to GREEN
Added comment: ClinGen definitive. Pituitary tumour/adenomas reported in condition.
Sources: Expert list, Expert Review
Pituitary Tumour v0.6 PRKAR1A Chirag Patel gene: PRKAR1A was added
gene: PRKAR1A was added to Pituitary Tumour. Sources: Expert list,Expert Review
Mode of inheritance for gene: PRKAR1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PRKAR1A were set to Pituitary tumor, MONDO:0017611; Pituitary gland adenoma, MONDO:0006373; Carney complex type 1, MONDO:0008057; Carney complex, type 1, MIM#160980
Review for gene: PRKAR1A was set to GREEN
Added comment: ClinGen definitive. Pituitary tumour/adenomas reported in condition.
Sources: Expert list, Expert Review
Pituitary Tumour v0.5 MEN1 Chirag Patel gene: MEN1 was added
gene: MEN1 was added to Pituitary Tumour. Sources: Expert list,Expert Review
Mode of inheritance for gene: MEN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MEN1 were set to Pituitary tumor, MONDO:0017611; Pituitary gland adenoma, MONDO:0006373; Multiple endocrine neoplasia type 1, MONDO:0007540; Multiple endocrine neoplasia, type 1, MIM#131100
Review for gene: MEN1 was set to GREEN
Added comment: ClinGen definitive. Pituitary tumour/adenomas reported in condition.
Sources: Expert list, Expert Review
Pituitary Tumour v0.4 CDKN1B Chirag Patel gene: CDKN1B was added
gene: CDKN1B was added to Pituitary Tumour. Sources: Expert list,Expert Review
Mode of inheritance for gene: CDKN1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CDKN1B were set to Pituitary tumor, MONDO:0017611; Pituitary gland adenoma, MONDO:0006373; Multiple endocrine neoplasia type 4, MONDO:0012552; Multiple endocrine neoplasia, type 4, MIM#610755
Review for gene: CDKN1B was set to GREEN
Added comment: ClinGen definitive. Pituitary tumour/adenomas reported in condition.
Sources: Expert list, Expert Review
Pituitary Tumour v0.3 AIP Chirag Patel gene: AIP was added
gene: AIP was added to Pituitary Tumour. Sources: Expert list,Expert Review
Mode of inheritance for gene: AIP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: AIP were set to Pituitary tumor, MONDO:0017611; Pituitary gland adenoma, MONDO:0006373; Pituitary adenoma predisposition, MIM#102200
Review for gene: AIP was set to GREEN
Added comment: Established gene-disease association for pituitary tumour/adenoma..
Sources: Expert list, Expert Review
Pituitary Tumour v0.2 Chirag Patel Panel name changed from Pituitary Adenoma to Pituitary Tumour
Pituitary Tumour v0.1 Chirag Patel Panel name changed from Pituitary Tumour to Pituitary Adenoma
Wilms Tumour v0.39 DICER1 Chirag Patel changed review comment from: ClinGen definitive. Wilms tumour may rarely be associated with a germline DICER1 pathogenic variant.
Sources: Expert list, Expert Review; to: ClinGen definitive. Some evidence for presentation with Wilms tumour in disease.
Sources: Expert list, Expert Review
Wilms Tumour v0.39 PIK3CA Chirag Patel gene: PIK3CA was added
gene: PIK3CA was added to Wilms Tumour. Sources: Expert list,Expert Review
Mode of inheritance for gene: PIK3CA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PIK3CA were set to Wilms tumor, MONDO:0006058; PIK3CA-related overgrowth spectrum, MONDO:1040002; PIK3CA-related overgrowth syndrome, multiple MIM#
Mode of pathogenicity for gene: PIK3CA was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: PIK3CA was set to RED
Added comment: ClinGen definitive. Limited evidence for presentation with Wilms tumour in disease. GOF and mosaic variants.
Sources: Expert list, Expert Review
Wilms Tumour v0.38 TP53 Chirag Patel gene: TP53 was added
gene: TP53 was added to Wilms Tumour. Sources: Expert list,Expert Review
Mode of inheritance for gene: TP53 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TP53 were set to Wilms tumor, MONDO:0006058; Li-Fraumeni syndrome, MONDO:0018875; Li-Fraumeni syndrome, MIM#151623
Review for gene: TP53 was set to RED
Added comment: ClinGen definitive. Limited evidence for presentation with Wilms tumour in disease.
Sources: Expert list, Expert Review
Wilms Tumour v0.37 CDC73 Chirag Patel gene: CDC73 was added
gene: CDC73 was added to Wilms Tumour. Sources: Expert list,Expert Review,Literature
Mode of inheritance for gene: CDC73 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDC73 were set to PMID: 37339334, 7912571, 7717405
Phenotypes for gene: CDC73 were set to Wilms tumor, MONDO:0006058; Hyperparathyroidism 2 with jaw tumors, MONDO:0007768; Hyperparathyroidism-jaw tumor syndrome, MIM#145001; Hyperparathyroidism, familial primary, MIM#145000
Review for gene: CDC73 was set to RED
Added comment: ClinGen definitive. Limited evidence for presentation with Wilms tumour in disease. Three cases of Wilms tumour in unrelated individuals with HPT-JT syndrome.
Sources: Expert list, Expert Review, Literature
Wilms Tumour v0.36 CTCF Chirag Patel gene: CTCF was added
gene: CTCF was added to Wilms Tumour. Sources: Expert list,Expert Review,Literature
Mode of inheritance for gene: CTCF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTCF were set to PMID: 31239556, 35459888, 36454652
Phenotypes for gene: CTCF were set to Wilms tumor, MONDO:0006058; Intellectual developmental disorder, autosomal dominant 21, MIM#615502
Review for gene: CTCF was set to RED
Added comment: Limited evidence for presentation with Wilms tumour in disease. Four cases of Wilms tumour in unrelated individuals with CTCF-related disorder.
Sources: Expert list, Expert Review, Literature
Wilms Tumour v0.35 ASXL1 Chirag Patel gene: ASXL1 was added
gene: ASXL1 was added to Wilms Tumour. Sources: Expert list,Expert Review
Mode of inheritance for gene: ASXL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ASXL1 were set to Wilms tumor, MONDO:0006058; Bohring-Opitz syndrome, MONDO:0011510; Bohring-Opitz syndrome, MIM#605039
Review for gene: ASXL1 was set to RED
Added comment: Limited evidence for presentation with Wilms tumour in disease.
Sources: Expert list, Expert Review
Wilms Tumour v0.34 AMER1 Chirag Patel changed review comment from: Limited evidence for gene-disease association for Wilms tumour. Four cases of Wilms tumour in unrelated individuals with OSCS.
Sources: Expert list, Expert Review, Literature; to: Limited evidence for presentation with Wilms tumour in disease. Four cases of Wilms tumour in unrelated individuals with OSCS.
Sources: Expert list, Expert Review, Literature
Wilms Tumour v0.34 AMER1 Chirag Patel gene: AMER1 was added
gene: AMER1 was added to Wilms Tumour. Sources: Expert list,Expert Review,Literature
Mode of inheritance for gene: AMER1 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: AMER1 were set to PMID: 32879452
Phenotypes for gene: AMER1 were set to Wilms tumor, MONDO:0006058; Osteopathia striata with cranial sclerosis, MONDO:0010310; Osteopathia striata with cranial sclerosis. MIM#300373
Review for gene: AMER1 was set to RED
Added comment: Limited evidence for gene-disease association for Wilms tumour. Four cases of Wilms tumour in unrelated individuals with OSCS.
Sources: Expert list, Expert Review, Literature
Wilms Tumour v0.33 NYNRIN Chirag Patel Classified gene: NYNRIN as Amber List (moderate evidence)
Wilms Tumour v0.33 NYNRIN Chirag Patel Gene: nynrin has been classified as Amber List (Moderate Evidence).
Wilms Tumour v0.32 NYNRIN Chirag Patel gene: NYNRIN was added
gene: NYNRIN was added to Wilms Tumour. Sources: Expert list,Expert Review,Literature
Mode of inheritance for gene: NYNRIN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NYNRIN were set to PMID: 30885698
Phenotypes for gene: NYNRIN were set to Wilms tumor, MONDO:0006058; Wilms tumour, no MIM#
Review for gene: NYNRIN was set to AMBER
Added comment: Some evidence for gene-disease association for Wilms tumour. Three cases of biallelic truncating variants associated with sporadic Wilms tumour.
Sources: Expert list, Expert Review, Literature
Wilms Tumour v0.31 FBXW7 Chirag Patel changed review comment from: Some evidence for gene-disease association for Wilms tumour. Few cases of monoallelic truncating variants associated with sporadic Wilms tumour (possible incomplete penetrance).
Sources: Expert list, Expert Review, Literature; to: Some evidence for gene-disease association for Wilms tumour. Four cases of monoallelic truncating variants associated with sporadic Wilms tumour (possible incomplete penetrance).
Sources: Expert list, Expert Review, Literature
Wilms Tumour v0.31 FBXW7 Chirag Patel Classified gene: FBXW7 as Amber List (moderate evidence)
Wilms Tumour v0.31 FBXW7 Chirag Patel Gene: fbxw7 has been classified as Amber List (Moderate Evidence).
Wilms Tumour v0.30 CTR9 Chirag Patel changed review comment from: Evidence for gene-disease association for Wilms tumour. Truncating variants are a rare cause of familial Wilms tumour.

PMID: 25099282
Inactivating CTR9 mutations found in 3 of 35 Wilms tumour families, through exome and Sanger sequencing. All variants were absent in 1,000 population controls and segregated with Wilms tumour in the family with second mutational event present in available tumours. CTR9 is a key component of the polymerase-associated factor 1 complex which has multiple roles in RNA polymerase II regulation and is implicated in embryonic organogenesis and maintenance of embryonic stem cell pluripotency.

PMID: 39293508
1 individual with bilateral Wilms tumour and a pathogenic splice site variant in the CTR9 gene, leading to deletion of exon 9, and inherited from her asymptomatic father. The loss of heterozygosity in the tumour was confirmed.

PMID: 29292210
3 affected siblings from 1 family with Wilms tumour (one presenting an aggressive bilateral tumour). They identified a novel CTR9 germline variant, located in a consensus splice acceptor site, which was found to segregate with Wilms tumour in this family. The variant leads to the skipping of the entire exon 9 in the mRNA, which is predicted to encode a truncated CTR9 protein, strongly suggesting that it is pathogenic. They also detected loss of heterozygosity in the index case tumour, which is consistent with CTR9 being a tumour suppressor gene.
Sources: Expert list, Expert Review, Literature; to: Evidence for gene-disease association for Wilms tumour. Truncating variants are a rare cause of familial Wilms tumour.

PMID: 25099282
Inactivating CTR9 mutations found in 3 of 35 Wilms tumour families, through exome and Sanger sequencing. All variants were absent in 1,000 population controls and segregated with Wilms tumour in the family with second mutational event present in available tumours. CTR9 is a key component of the polymerase-associated factor 1 complex which has multiple roles in RNA polymerase II regulation and is implicated in embryonic organogenesis and maintenance of embryonic stem cell pluripotency.

PMID: 39293508
2 female siblings with Wilms tumour (1 with bilateral Wilms tumour) and a pathogenic splice site variant in the CTR9 gene, leading to deletion of exon 9, and inherited from her asymptomatic father. The loss of heterozygosity in the tumour was confirmed.

PMID: 29292210
3 affected siblings from 1 family with Wilms tumour (one presenting an aggressive bilateral tumour). They identified a novel CTR9 germline variant, located in a consensus splice acceptor site, which was found to segregate with Wilms tumour in this family. The variant leads to the skipping of the entire exon 9 in the mRNA, which is predicted to encode a truncated CTR9 protein, strongly suggesting that it is pathogenic. They also detected loss of heterozygosity in the index case tumour, which is consistent with CTR9 being a tumour suppressor gene.
Sources: Expert list, Expert Review, Literature
Wilms Tumour v0.30 FBXW7 Chirag Patel gene: FBXW7 was added
gene: FBXW7 was added to Wilms Tumour. Sources: Expert list,Expert Review,Literature
Mode of inheritance for gene: FBXW7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FBXW7 were set to PMID: 30885698
Phenotypes for gene: FBXW7 were set to Wilms tumor, MONDO:0006058; Wilms tumour, no MIM#
Review for gene: FBXW7 was set to AMBER
Added comment: Some evidence for gene-disease association for Wilms tumour. Few cases of monoallelic truncating variants associated with sporadic Wilms tumour (possible incomplete penetrance).
Sources: Expert list, Expert Review, Literature
Wilms Tumour v0.29 DICER1 Chirag Patel Classified gene: DICER1 as Amber List (moderate evidence)
Wilms Tumour v0.29 DICER1 Chirag Patel Gene: dicer1 has been classified as Amber List (Moderate Evidence).
Wilms Tumour v0.28 DICER1 Chirag Patel gene: DICER1 was added
gene: DICER1 was added to Wilms Tumour. Sources: Expert list,Expert Review
Mode of inheritance for gene: DICER1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: DICER1 were set to Wilms tumor, MONDO:0006058; DICER1-related tumor predisposition, MONDO:0100216; DICER1 syndrome, MIM#601200
Review for gene: DICER1 was set to AMBER
Added comment: ClinGen definitive. Wilms tumour may rarely be associated with a germline DICER1 pathogenic variant.
Sources: Expert list, Expert Review
Wilms Tumour v0.27 CTR9 Chirag Patel Classified gene: CTR9 as Green List (high evidence)
Wilms Tumour v0.27 CTR9 Chirag Patel Gene: ctr9 has been classified as Green List (High Evidence).
Wilms Tumour v0.26 CTR9 Chirag Patel gene: CTR9 was added
gene: CTR9 was added to Wilms Tumour. Sources: Expert list,Expert Review,Literature
Mode of inheritance for gene: CTR9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTR9 were set to PMID: 25099282, 39293508, 29292210
Phenotypes for gene: CTR9 were set to Wilms tumor, MONDO:0006058; Wilms tumor predisposition, no MIM#
Review for gene: CTR9 was set to GREEN
Added comment: Evidence for gene-disease association for Wilms tumour. Truncating variants are a rare cause of familial Wilms tumour.

PMID: 25099282
Inactivating CTR9 mutations found in 3 of 35 Wilms tumour families, through exome and Sanger sequencing. All variants were absent in 1,000 population controls and segregated with Wilms tumour in the family with second mutational event present in available tumours. CTR9 is a key component of the polymerase-associated factor 1 complex which has multiple roles in RNA polymerase II regulation and is implicated in embryonic organogenesis and maintenance of embryonic stem cell pluripotency.

PMID: 39293508
1 individual with bilateral Wilms tumour and a pathogenic splice site variant in the CTR9 gene, leading to deletion of exon 9, and inherited from her asymptomatic father. The loss of heterozygosity in the tumour was confirmed.

PMID: 29292210
3 affected siblings from 1 family with Wilms tumour (one presenting an aggressive bilateral tumour). They identified a novel CTR9 germline variant, located in a consensus splice acceptor site, which was found to segregate with Wilms tumour in this family. The variant leads to the skipping of the entire exon 9 in the mRNA, which is predicted to encode a truncated CTR9 protein, strongly suggesting that it is pathogenic. They also detected loss of heterozygosity in the index case tumour, which is consistent with CTR9 being a tumour suppressor gene.
Sources: Expert list, Expert Review, Literature
Wilms Tumour v0.25 TRIM28 Chirag Patel Classified gene: TRIM28 as Green List (high evidence)
Wilms Tumour v0.25 TRIM28 Chirag Patel Gene: trim28 has been classified as Green List (High Evidence).
Wilms Tumour v0.24 TRIM28 Chirag Patel gene: TRIM28 was added
gene: TRIM28 was added to Wilms Tumour. Sources: Expert list,Expert Review,Literature
Mode of inheritance for gene: TRIM28 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRIM28 were set to PMID: 29912901, 30694527, 30885698, 33565090
Phenotypes for gene: TRIM28 were set to Wilms tumor, MONDO:0006058; Wilms tumor predisposition, no MIM#
Review for gene: TRIM28 was set to GREEN
Added comment: Evidence for gene-disease association for Wilms tumour.

Among 890 individuals with Wilms tumour, a germline TRIM28 pathogenic variant was identified in 21 affected individuals. Age of onset ranged from 5 months to 9 years. TRIM28-related Wilms tumours can be either unilateral or bilateral, predominantly have epithelial-type histology, and are frequently accompanied by nephrogenic rests. Immunohistochemistry studies show negative staining for TRIM28. With few exceptions, the reported germline variants are truncating or splice site variants located throughout the protein coding regions with evidence suggestive of a maternal parent-of-origin effect. Germline TRIM28 pathogenic variants do not appear to be associated with any phenotype other than Wilms tumour.
Sources: Expert list, Expert Review, Literature
Wilms Tumour v0.23 REST Chirag Patel Classified gene: REST as Green List (high evidence)
Wilms Tumour v0.23 REST Chirag Patel Gene: rest has been classified as Green List (High Evidence).
Wilms Tumour v0.22 REST Chirag Patel gene: REST was added
gene: REST was added to Wilms Tumour. Sources: Expert list,Expert Review,Literature
Mode of inheritance for gene: REST was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: REST were set to PMID: 26551668
Phenotypes for gene: REST were set to Wilms tumor, MONDO:0006058; Wilms tumor 6, MONDO:0014779; Wilms tumor 6, susceptibility to, MIM#616806
Review for gene: REST was set to GREEN
Added comment: Evidence for gene-disease association for Wilms tumour.

11 different inactivating mutations in the REST gene in 4 familial Wilms tumor pedigrees and 9 non-familial cases. All variants were absent from ICR1000 control series and ExAC series. A second mutational event was found in two tumors, suggesting that REST may act as a tumor-suppressor gene in Wilms tumor pathogenesis. Ten of 11 mutations clustered within the portion of REST encoding the DNA-binding domain, and functional analyses showed that these mutations compromise REST transcriptional repression.
Sources: Expert list, Expert Review, Literature
Wilms Tumour v0.21 TRIP13 Chirag Patel Classified gene: TRIP13 as Green List (high evidence)
Wilms Tumour v0.21 TRIP13 Chirag Patel Gene: trip13 has been classified as Green List (High Evidence).
Wilms Tumour v0.20 TRIP13 Chirag Patel gene: TRIP13 was added
gene: TRIP13 was added to Wilms Tumour. Sources: Expert list,Expert Review,Literature
Mode of inheritance for gene: TRIP13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIP13 were set to PMID: 28553959
Phenotypes for gene: TRIP13 were set to Wilms tumor, MONDO:0006058; Mosaic variegated aneuploidy syndrome 3, MONDO:0054736; Mosaic variegated aneuploidy syndrome 3, MIM#617598
Review for gene: TRIP13 was set to GREEN
Added comment: Wilms tumour reported in condition.

6 unrelated patients with MVA3 with early-onset Wilms tumour, and homozygous truncating mutations in the TRIP13 gene. Cells derived from patients with the R354X mutation showed chromosomal instability, including aneuploidy, premature chromatid separation, lagging chromosomes, and chromosome bridges. Mutant cells showed increased mitotic exit and impaired recruitment of MAD2 to unattached kinetochores, indicating severe disruption of the spindle assembly checkpoint. These defects could be restored with wildtype TRIP13. The mutant protein was unable to rescue spindle assembly checkpoint defects in a cell line with CRISPR-Cas9-mediated knockdown of TRIP13, consistent with a loss of function.
Sources: Expert list, Expert Review, Literature
Mendeliome v1.2018 AHR Zornitza Stark Phenotypes for gene: AHR were changed from ?Retinitis pigmentosa 85 MIM#618345; foveal hypoplasia and infantile nystagmus to Retinitis pigmentosa 85 MIM#618345; Foveal hypoplasia 3, MIM# 620958
Mendeliome v1.2017 AHR Zornitza Stark edited their review of gene: AHR: Changed phenotypes: Foveal hypoplasia 3, MIM# 620958
Congenital nystagmus v1.22 AHR Zornitza Stark Phenotypes for gene: AHR were changed from Foveal hypoplasia without albinism; Infantile nystagmus to Foveal hypoplasia 3, MIM# 620958
Congenital nystagmus v1.21 AHR Zornitza Stark edited their review of gene: AHR: Changed phenotypes: Foveal hypoplasia 3, MIM# 620958
Wilms Tumour v0.19 BLM Chirag Patel Classified gene: BLM as Green List (high evidence)
Wilms Tumour v0.19 BLM Chirag Patel Gene: blm has been classified as Green List (High Evidence).
Wilms Tumour v0.18 BRCA2 Chirag Patel Classified gene: BRCA2 as Green List (high evidence)
Wilms Tumour v0.18 BRCA2 Chirag Patel Gene: brca2 has been classified as Green List (High Evidence).
Wilms Tumour v0.17 BUB1B Chirag Patel Classified gene: BUB1B as Green List (high evidence)
Wilms Tumour v0.17 BUB1B Chirag Patel Gene: bub1b has been classified as Green List (High Evidence).
Wilms Tumour v0.16 CDKN1C Chirag Patel Classified gene: CDKN1C as Green List (high evidence)
Wilms Tumour v0.16 CDKN1C Chirag Patel Gene: cdkn1c has been classified as Green List (High Evidence).
Wilms Tumour v0.15 DIS3L2 Chirag Patel Classified gene: DIS3L2 as Green List (high evidence)
Wilms Tumour v0.15 DIS3L2 Chirag Patel Gene: dis3l2 has been classified as Green List (High Evidence).
Wilms Tumour v0.14 GPC3 Chirag Patel Classified gene: GPC3 as Green List (high evidence)
Wilms Tumour v0.14 GPC3 Chirag Patel Gene: gpc3 has been classified as Green List (High Evidence).
Wilms Tumour v0.13 PALB2 Chirag Patel Classified gene: PALB2 as Green List (high evidence)
Wilms Tumour v0.13 PALB2 Chirag Patel Gene: palb2 has been classified as Green List (High Evidence).
Wilms Tumour v0.12 TRIM37 Chirag Patel Classified gene: TRIM37 as Green List (high evidence)
Wilms Tumour v0.12 TRIM37 Chirag Patel Gene: trim37 has been classified as Green List (High Evidence).
Genomic newborn screening: BabyScreen+ v1.116 PSTPIP1 Zornitza Stark Phenotypes for gene: PSTPIP1 were changed from Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, MIM# 604416 to Autoinflammatory syndrome with cytopenia, hyperzincemia, and hypercalprotectinemia, MIMM# 601979; Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, MIM# 604416
Wilms Tumour v0.11 WT1 Chirag Patel Classified gene: WT1 as Green List (high evidence)
Wilms Tumour v0.11 WT1 Chirag Patel Gene: wt1 has been classified as Green List (High Evidence).
Wilms Tumour v0.10 WT1 Chirag Patel gene: WT1 was added
gene: WT1 was added to Wilms Tumour. Sources: Expert list,Expert Review
Mode of inheritance for gene: WT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: WT1 were set to Wilms tumor, MONDO:0006058; Wilms tumor 1, MONDO:0008679; Wilms tumor, type 1, MIM#194070; Denys-Drash syndrome, MIM#194080; Frasier syndrome, MIM#136680
Review for gene: WT1 was set to GREEN
Added comment: ClinGen definitive. Wilms tumour reported in condition.
Sources: Expert list, Expert Review
Genomic newborn screening: BabyScreen+ v1.115 PSTPIP1 Zornitza Stark edited their review of gene: PSTPIP1: Changed phenotypes: Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, MIM# 604416, Autoinflammatory syndrome with cytopenia, hyperzincemia, and hypercalprotectinemia, MIMM# 601979
Wilms Tumour v0.9 TRIM37 Chirag Patel gene: TRIM37 was added
gene: TRIM37 was added to Wilms Tumour. Sources: Expert list,Expert Review
Mode of inheritance for gene: TRIM37 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRIM37 were set to Wilms tumor, MONDO:0006058; Mulibrey nanism, MONDO:0009664; Mulibrey nanism, MIM#253250
Review for gene: TRIM37 was set to GREEN
Added comment: ClinGen definitive. Wilms tumour reported in condition.
Sources: Expert list, Expert Review
Autoinflammatory Disorders v1.52 PSTPIP1 Zornitza Stark Phenotypes for gene: PSTPIP1 were changed from Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, MIM# 604416; PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome to Autoinflammatory syndrome with cytopenia, hyperzincemia, and hypercalprotectinemia, MIMM# 601979; Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, MIM# 604416; PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome
Wilms Tumour v0.8 PALB2 Chirag Patel gene: PALB2 was added
gene: PALB2 was added to Wilms Tumour. Sources: Expert list,Expert Review
Mode of inheritance for gene: PALB2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PALB2 were set to Wilms tumor, MONDO:0006058; Fanconi anemia complementation group N, MONDO:0012565; Fanconi anemia, complementation group N, MIM#610832
Review for gene: PALB2 was set to GREEN
Added comment: ClinGen definitive. Wilms tumour reported in condition.
Sources: Expert list, Expert Review
Autoinflammatory Disorders v1.51 PSTPIP1 Zornitza Stark edited their review of gene: PSTPIP1: Changed phenotypes: Autoinflammatory syndrome with cytopenia, hyperzincemia, and hypercalprotectinemia, MIMM# 601979, Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, MIM# 604416, PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome
Wilms Tumour v0.7 GPC3 Chirag Patel gene: GPC3 was added
gene: GPC3 was added to Wilms Tumour. Sources: Expert list,Expert Review
Mode of inheritance for gene: GPC3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: GPC3 were set to Wilms tumor, MONDO:0006058; Simpson-Golabi-Behmel syndrome type 1, MONDO:0020602; Simpson-Golabi-Behmel syndrome, type 1, MIM#312870
Review for gene: GPC3 was set to GREEN
Added comment: ClinGen definitive. Wilms tumour reported in condition.
Sources: Expert list, Expert Review
Mendeliome v1.2017 PSTPIP1 Zornitza Stark Phenotypes for gene: PSTPIP1 were changed from Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, MIM# 604416; PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome to Autoinflammatory syndrome with cytopenia, hyperzincemia, and hypercalprotectinemia, MIMM# 601979; Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, MIM# 604416; PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome
Wilms Tumour v0.6 DIS3L2 Chirag Patel gene: DIS3L2 was added
gene: DIS3L2 was added to Wilms Tumour. Sources: Expert list,Expert Review
Mode of inheritance for gene: DIS3L2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DIS3L2 were set to Wilms tumor, MONDO:0006058; Perlman syndrome, MONDO:0009965; Perlman syndrome, MIM#267000
Review for gene: DIS3L2 was set to GREEN
Added comment: ClinGen definitive. Wilms tumour reported in condition.
Sources: Expert list, Expert Review
Wilms Tumour v0.5 CDKN1C Chirag Patel gene: CDKN1C was added
gene: CDKN1C was added to Wilms Tumour. Sources: Expert list,Expert Review
Mode of inheritance for gene: CDKN1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CDKN1C were set to Wilms tumor, MONDO:0006058; Beckwith-Wiedemann syndrome due to CDKN1C mutation, MONDO:0016476; Beckwith-Wiedemann syndrome, MIM#130650
Review for gene: CDKN1C was set to GREEN
Added comment: Established gene-disease association. Wilms tumour reported in condition.
Sources: Expert list, Expert Review
Mendeliome v1.2016 PSTPIP1 Zornitza Stark edited their review of gene: PSTPIP1: Changed phenotypes: Autoinflammatory syndrome with cytopenia, hyperzincemia, and hypercalprotectinemia, MIMM# 601979, Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, MIM# 604416, PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome
Bone Marrow Failure v1.96 PSTPIP1 Zornitza Stark Phenotypes for gene: PSTPIP1 were changed from Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, MIM# 604416 to Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, MIM# 604416; Autoinflammatory syndrome with cytopenia, hyperzincemia, and hypercalprotectinemia, MIMM# 601979
Wilms Tumour v0.4 BUB1B Chirag Patel gene: BUB1B was added
gene: BUB1B was added to Wilms Tumour. Sources: Expert list,Expert Review
Mode of inheritance for gene: BUB1B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: BUB1B were set to Wilms tumor, MONDO:0006058; Mosaic variegated aneuploidy syndrome 1, MONDO:0009759; Mosaic variegated aneuploidy syndrome 1, MIM#257300
Review for gene: BUB1B was set to GREEN
Added comment: ClinGen definitive. Wilms tumour reported in condition.
Sources: Expert list, Expert Review
Wilms Tumour v0.3 BRCA2 Chirag Patel gene: BRCA2 was added
gene: BRCA2 was added to Wilms Tumour. Sources: Expert list,Expert Review
Mode of inheritance for gene: BRCA2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: BRCA2 were set to Wilms tumor, MONDO:0006058; Fanconi anemia complementation group D1,MONDO:0011584; Fanconi anemia, complementation group D1, MIM#605724
Review for gene: BRCA2 was set to GREEN
Added comment: ClinGen definitive. Wilms tumour reported in condition.
Sources: Expert list, Expert Review
Wilms Tumour v0.2 BLM Chirag Patel gene: BLM was added
gene: BLM was added to Wilms Tumour. Sources: Expert list,Expert Review
Mode of inheritance for gene: BLM was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: BLM were set to Wilms tumor, MONDO:0006058; Bloom syndrome, MONDO:0008876; Bloom syndrome, MIM#210900
Review for gene: BLM was set to GREEN
Added comment: ClinGen definitive. Wilms tumour reported in condition.
Sources: Expert list, Expert Review
Bone Marrow Failure v1.95 PSTPIP1 Zornitza Stark edited their review of gene: PSTPIP1: Changed phenotypes: Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, MIM# 604416, Autoinflammatory syndrome with cytopenia, hyperzincemia, and hypercalprotectinemia, MIMM# 601979
Vasculitis v0.86 PSTPIP1 Zornitza Stark Marked gene: PSTPIP1 as ready
Vasculitis v0.86 PSTPIP1 Zornitza Stark Gene: pstpip1 has been classified as Green List (High Evidence).
Vasculitis v0.86 PSTPIP1 Zornitza Stark Phenotypes for gene: PSTPIP1 were changed from Autoinflammatory syndrome with cytopenia, hyperzincemia, and hypercalprotectinemia, MIMM# 601979 to Autoinflammatory syndrome with cytopenia, hyperzincemia, and hypercalprotectinemia, MIMM# 601979
Vasculitis v0.85 PSTPIP1 Zornitza Stark Phenotypes for gene: PSTPIP1 were changed from to Autoinflammatory syndrome with cytopenia, hyperzincemia, and hypercalprotectinemia, MIMM# 601979
Vasculitis v0.84 PSTPIP1 Zornitza Stark Mode of inheritance for gene: PSTPIP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Vasculitis v0.83 PSTPIP1 Zornitza Stark Mode of inheritance for gene: PSTPIP1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Vasculitis v0.82 PSTPIP1 Zornitza Stark commented on gene: PSTPIP1: Well established gene-disease association.
Vasculitis v0.82 PSTPIP1 Zornitza Stark reviewed gene: PSTPIP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Autoinflammatory syndrome with cytopenia, hyperzincemia, and hypercalprotectinemia, MIMM# 601979; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Severe Combined Immunodeficiency (absent T present B cells) v1.6 TP63 Peter McNaughton gene: TP63 was added
gene: TP63 was added to Severe Combined Immunodeficiency (absent T present B cells). Sources: Literature
Mode of inheritance for gene: TP63 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TP63 were set to doi: 10.3389/fimmu.2024.1438383
Phenotypes for gene: TP63 were set to lymphopaenia
Review for gene: TP63 was set to GREEN
Added comment: Multiple patients presenting with T cell lymphopaenia, potentially identified on SCID new born screening. T cell lymphopaenia due to thymic defect rather than intrinsic T cell defect so treatment is with thymic transplant rather than HSCT. Should be included in SCID panel as identification of this gene defect in lymphopaenic patients identified on SCID NBS will change treatment pathway dramatically.
Sources: Literature
Sarcoma soft tissue v0.34 POT1 Chirag Patel Classified gene: POT1 as Amber List (moderate evidence)
Sarcoma soft tissue v0.34 POT1 Chirag Patel Gene: pot1 has been classified as Amber List (Moderate Evidence).
Sarcoma soft tissue v0.33 POT1 Chirag Patel gene: POT1 was added
gene: POT1 was added to Sarcoma soft tissue. Sources: Expert Review,Literature
Mode of inheritance for gene: POT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POT1 were set to PMID: 36656928, 37466057
Phenotypes for gene: POT1 were set to Soft tissue sarcoma, MONDO:0018078; Sarcoma, MONDO:0005089; Tumor predisposition syndrome 3, MONDO:0014368; Melanoma, cutaneous malignant, MIM#606478
Review for gene: POT1 was set to AMBER
Added comment: Tumor predisposition syndrome-3 (TPDS3) is characterised by an increased risk for the development of various types of benign and malignant neoplasms throughout life, with age-dependent penetrance (e.g. neoplasms involving epithelial, mesenchymal, and neuronal tissues, as well as clonal hematopoietic syndromes, including lymphoid and myeloid cancers).
Sources: Expert Review, Literature
Breast Cancer v0.26 CHEK2 Chirag Patel Classified gene: CHEK2 as Green List (high evidence)
Breast Cancer v0.26 CHEK2 Chirag Patel Gene: chek2 has been classified as Green List (High Evidence).
Breast Cancer v0.25 ATM Chirag Patel Classified gene: ATM as Green List (high evidence)
Breast Cancer v0.25 ATM Chirag Patel Gene: atm has been classified as Green List (High Evidence).
Breast Cancer v0.24 BARD1 Chirag Patel Classified gene: BARD1 as Green List (high evidence)
Breast Cancer v0.24 BARD1 Chirag Patel Gene: bard1 has been classified as Green List (High Evidence).
Breast Cancer v0.23 BARD1 Chirag Patel gene: BARD1 was added
gene: BARD1 was added to Breast Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: BARD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: BARD1 were set to Breast cancer, MONDO:0007254; BARD1-related cancer predisposition, MONDO:0700267; Breast cancer, susceptibility to, MIM#114480
Review for gene: BARD1 was set to GREEN
Added comment: ClinGen definitive. Breast cancers reported in condition.
Sources: Expert list, Expert Review
Breast Cancer v0.22 BRCA1 Chirag Patel Classified gene: BRCA1 as Green List (high evidence)
Breast Cancer v0.22 BRCA1 Chirag Patel Gene: brca1 has been classified as Green List (High Evidence).
Breast Cancer v0.21 BRCA2 Chirag Patel Classified gene: BRCA2 as Green List (high evidence)
Breast Cancer v0.21 BRCA2 Chirag Patel Gene: brca2 has been classified as Green List (High Evidence).
Breast Cancer v0.20 CDH1 Chirag Patel Classified gene: CDH1 as Green List (high evidence)
Breast Cancer v0.20 CDH1 Chirag Patel Gene: cdh1 has been classified as Green List (High Evidence).
Breast Cancer v0.19 NF1 Chirag Patel Classified gene: NF1 as Green List (high evidence)
Breast Cancer v0.19 NF1 Chirag Patel Gene: nf1 has been classified as Green List (High Evidence).
Breast Cancer v0.18 PALB2 Chirag Patel Classified gene: PALB2 as Green List (high evidence)
Breast Cancer v0.18 PALB2 Chirag Patel Gene: palb2 has been classified as Green List (High Evidence).
Breast Cancer v0.17 PTEN Chirag Patel Classified gene: PTEN as Green List (high evidence)
Breast Cancer v0.17 PTEN Chirag Patel Gene: pten has been classified as Green List (High Evidence).
Breast Cancer v0.16 RAD51C Chirag Patel Classified gene: RAD51C as Green List (high evidence)
Breast Cancer v0.16 RAD51C Chirag Patel Gene: rad51c has been classified as Green List (High Evidence).
Breast Cancer v0.15 RAD51D Chirag Patel Classified gene: RAD51D as Green List (high evidence)
Breast Cancer v0.15 RAD51D Chirag Patel Gene: rad51d has been classified as Green List (High Evidence).
Breast Cancer v0.14 STK11 Chirag Patel Classified gene: STK11 as Green List (high evidence)
Breast Cancer v0.14 STK11 Chirag Patel Gene: stk11 has been classified as Green List (High Evidence).
Breast Cancer v0.13 TP53 Chirag Patel Classified gene: TP53 as Green List (high evidence)
Breast Cancer v0.13 TP53 Chirag Patel Gene: tp53 has been classified as Green List (High Evidence).
Breast Cancer v0.12 TP53 Chirag Patel gene: TP53 was added
gene: TP53 was added to Breast Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: TP53 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TP53 were set to Breast cancer, MONDO:0007254; Li-Fraumeni syndrome, MONDO:0018875; Li-Fraumeni syndrome, MIM#151623
Review for gene: TP53 was set to GREEN
Added comment: ClinGen definitive. Breast cancers reported in condition.

Consider possibility that an identified variant could represent ACE (aberrant clonal expansion), which can be due to clonal haematopoiesis of indeterminate potential (CHIP) or an occult hematologic malignancy, especially in older patients who have undergone prior chemotherapy (PMID: 36040522).
Sources: Expert list, Expert Review
Breast Cancer v0.11 STK11 Chirag Patel gene: STK11 was added
gene: STK11 was added to Breast Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: STK11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: STK11 were set to Breast cancer, MONDO:0007254; Peutz-Jeghers syndrome, MONDO:0008280; Peutz-Jeghers syndrome, MIM#175200
Review for gene: STK11 was set to GREEN
Added comment: ClinGen definitive. Breast cancers reported in condition.

Single gene testing may be more appropriate if clinical features of JPS.
Sources: Expert list, Expert Review
Breast Cancer v0.10 RAD51D Chirag Patel gene: RAD51D was added
gene: RAD51D was added to Breast Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: RAD51D was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RAD51D were set to Breast cancer, MONDO:0007254; RAD51D-related cancer predisposition, MONDO:0700274; Breast-ovarian cancer, familial, susceptibility to, 4, MONDO:0013669; Breast-ovarian cancer, familial, susceptibility to, 4, MIM#614291
Review for gene: RAD51D was set to GREEN
Added comment: ClinGen definitive. Breast cancers reported in condition.
Sources: Expert list, Expert Review
Breast Cancer v0.9 RAD51C Chirag Patel gene: RAD51C was added
gene: RAD51C was added to Breast Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: RAD51C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RAD51C were set to Breast cancer, MONDO:0007254; RAD51C-related cancer predisposition, MONDO:0700273; Breast-ovarian cancer, familial, susceptibility to, 3, MONDO:0013253; Breast-ovarian cancer, familial, susceptibility to, 3, MIM#613399
Review for gene: RAD51C was set to GREEN
Added comment: ClinGen definitive. Breast cancers reported in condition.
Sources: Expert list, Expert Review
Breast Cancer v0.8 PTEN Chirag Patel gene: PTEN was added
gene: PTEN was added to Breast Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: PTEN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PTEN were set to Breast cancer, MONDO:0007254; PTEN hamartoma tumor syndrome, MONDO:0017623; PTEN hamartoma tumour syndromes, MIM#158350
Review for gene: PTEN was set to GREEN
Added comment: ClinGen definitive. Breast cancers reported in condition.
Sources: Expert list, Expert Review
Breast Cancer v0.7 PALB2 Chirag Patel gene: PALB2 was added
gene: PALB2 was added to Breast Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: PALB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PALB2 were set to Breast cancer, MONDO:0007254; PALB2-related cancer predisposition, MONDO:0700272; Breast-ovarian cancer, familial, susceptibility to, 5, MIM#620442; Pancreatic cancer, susceptibility to, 3, MIM#613348
Review for gene: PALB2 was set to GREEN
Added comment: ClinGen definitive. Breast cancers reported in condition.
Sources: Expert list, Expert Review
Breast Cancer v0.6 NF1 Chirag Patel gene: NF1 was added
gene: NF1 was added to Breast Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: NF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: NF1 were set to Breast cancer, MONDO:0007254; Neurofibromatosis type 1, MONDO:0018975; Neurofibromatosis, type 1, MIM#162200
Review for gene: NF1 was set to GREEN
Added comment: ClinGen definitive. Breast cancers reported in condition.

Single gene testing may be more appropriate if clinical features of NF1.
Sources: Expert list, Expert Review
Breast Cancer v0.5 CDH1 Chirag Patel gene: CDH1 was added
gene: CDH1 was added to Breast Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: CDH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CDH1 were set to Breast cancer, MONDO:0007254; CDH1-related diffuse gastric and lobular breast cancer syndrome, MONDO:0100488; Diffuse gastric and lobular breast cancer syndrome with or without cleft lip and/or palate, MIM#137215
Review for gene: CDH1 was set to GREEN
Added comment: ClinGen definitive. Breast cancers reported in condition.
Sources: Expert list, Expert Review
Breast Cancer v0.4 BRCA2 Chirag Patel gene: BRCA2 was added
gene: BRCA2 was added to Breast Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: BRCA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: BRCA2 were set to Breast cancer, MONDO:0007254; BRCA2-related cancer predisposition, MONDO:0700269; Breast-ovarian cancer, familial, 2, MIM#612555
Review for gene: BRCA2 was set to GREEN
Added comment: ClinGen definitive. Breast cancers reported in condition.
Sources: Expert list, Expert Review
Breast Cancer v0.3 BRCA1 Chirag Patel gene: BRCA1 was added
gene: BRCA1 was added to Breast Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: BRCA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: BRCA1 were set to Breast cancer, MONDO:0007254; BRCA1-related cancer predisposition, MONDO:0700268; Breast-ovarian cancer, familial, 1, MIM#604370
Review for gene: BRCA1 was set to GREEN
Added comment: ClinGen definitive. Breast cancers reported in condition.
Sources: Expert list, Expert Review
Breast Cancer v0.2 ATM Chirag Patel gene: ATM was added
gene: ATM was added to Breast Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: ATM was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ATM were set to Breast cancer, MONDO:0007254; ATM-related cancer predisposition, MONDO:0700270; Breast cancer, susceptibility to, MIM#114480
Review for gene: ATM was set to GREEN
Added comment: ClinGen definitive. Breast cancers reported in condition.

Consider possibility that an identified variant could represent ACE (aberrant clonal expansion), which can be due to clonal haematopoiesis of indeterminate potential (CHIP) or an occult hematologic malignancy, especially in older patients who have undergone prior chemotherapy (PMID: 36040522).
Sources: Expert list, Expert Review
Breast Cancer v0.1 CHEK2 Chirag Patel gene: CHEK2 was added
gene: CHEK2 was added to Breast Cancer. Sources: Expert list,Expert Review,Literature
Mode of inheritance for gene: CHEK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHEK2 were set to PMID: 33322746, 36529447
Phenotypes for gene: CHEK2 were set to Breast cancer, MONDO:0007254; CHEK2-related cancer predisposition, MONDO:0700271; Breast/prostate cancer, susceptibility to, MIM#609265
Review for gene: CHEK2 was set to GREEN
Added comment: Established gene-disease association. Breast cancers reported in condition.

Consider possibility that an identified variant could represent ACE (aberrant clonal expansion), which can be due to clonal haematopoiesis of indeterminate potential (CHIP) or an occult hematologic malignancy, especially in older patients who have undergone prior chemotherapy (PMID: 36040522).
Sources: Expert list, Expert Review, Literature
Colorectal Cancer and Polyposis v0.39 MLH1 Chirag Patel Classified gene: MLH1 as Green List (high evidence)
Colorectal Cancer and Polyposis v0.39 MLH1 Chirag Patel Gene: mlh1 has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.38 MSH2 Chirag Patel Classified gene: MSH2 as Green List (high evidence)
Colorectal Cancer and Polyposis v0.38 MSH2 Chirag Patel Gene: msh2 has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.37 MSH6 Chirag Patel Classified gene: MSH6 as Green List (high evidence)
Colorectal Cancer and Polyposis v0.37 MSH6 Chirag Patel Gene: msh6 has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.36 PMS2 Chirag Patel Classified gene: PMS2 as Green List (high evidence)
Colorectal Cancer and Polyposis v0.36 PMS2 Chirag Patel Gene: pms2 has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.35 MUTYH Chirag Patel Classified gene: MUTYH as Green List (high evidence)
Colorectal Cancer and Polyposis v0.35 MUTYH Chirag Patel Gene: mutyh has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.34 NTHL1 Chirag Patel Classified gene: NTHL1 as Green List (high evidence)
Colorectal Cancer and Polyposis v0.34 NTHL1 Chirag Patel Gene: nthl1 has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.33 MSH3 Chirag Patel Classified gene: MSH3 as Green List (high evidence)
Colorectal Cancer and Polyposis v0.33 MSH3 Chirag Patel Gene: msh3 has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.32 GREM1 Chirag Patel Classified gene: GREM1 as Green List (high evidence)
Colorectal Cancer and Polyposis v0.32 GREM1 Chirag Patel Gene: grem1 has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.31 RNF43 Chirag Patel Classified gene: RNF43 as Green List (high evidence)
Colorectal Cancer and Polyposis v0.31 RNF43 Chirag Patel Gene: rnf43 has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.30 RNF43 Chirag Patel gene: RNF43 was added
gene: RNF43 was added to Colorectal Cancer and Polyposis. Sources: Expert list,Expert Review,Literature
Mode of inheritance for gene: RNF43 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RNF43 were set to PMID: 24512911, 34541672, 27329244, 27081527, 29330307
Phenotypes for gene: RNF43 were set to Colorectal cancer, MONDO:0005575; Polyposis, MONDO:0000147; Sessile serrated polyposis cancer syndrome, MONDO:0014919; Sessile serrated polyposis cancer syndrome, MIM#617108
Review for gene: RNF43 was set to GREEN
Added comment: ClinGen definitive. Colorectal cancers and/or polyposis reported in condition.
Sources: Expert list, Expert Review, Literature
Colorectal Cancer and Polyposis v0.29 GREM1 Chirag Patel edited their review of gene: GREM1: Changed phenotypes: Colorectal cancer, MONDO:0005575, Polyposis, MONDO:0000147, Hereditary mixed polyposis syndrome, MONDO:0011023, GREM1-associated polyposis, no MIM#
Colorectal Cancer and Polyposis v0.29 GREM1 Chirag Patel gene: GREM1 was added
gene: GREM1 was added to Colorectal Cancer and Polyposis. Sources: Expert list,Expert Review,Literature
Mode of inheritance for gene: GREM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GREM1 were set to PMID: 22561515, 25419707
Mode of pathogenicity for gene: GREM1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: GREM1 was set to GREEN
Added comment: ClinGen definitive. Colorectal cancers and/or polyposis reported in condition. GOF variants.

Four variants leading to partial or complete duplication of GREM1 regulatory regions or coding sequences have been reported, resulting in increased allele-specific GREM1 expression. Most are carriers of the Ashkenazi founder variant, a 40kb duplication upstream of GREM1 (SCG5-GREM1 dup).
Sources: Expert list, Expert Review, Literature
Colorectal Cancer and Polyposis v0.28 MSH3 Chirag Patel gene: MSH3 was added
gene: MSH3 was added to Colorectal Cancer and Polyposis. Sources: Expert list,Expert Review
Mode of inheritance for gene: MSH3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MSH3 were set to Colorectal cancer, MONDO:0005575; Polyposis, MONDO:0000147; Familial adenomatous polyposis 4, MONDO:0044300; Familial adenomatous polyposis 4, MIM#617100
Review for gene: MSH3 was set to GREEN
Added comment: ClinGen definitive. Colorectal cancers and/or polyposis reported in condition.
Sources: Expert list, Expert Review
Colorectal Cancer and Polyposis v0.27 NTHL1 Chirag Patel gene: NTHL1 was added
gene: NTHL1 was added to Colorectal Cancer and Polyposis. Sources: Expert list,Expert Review
Mode of inheritance for gene: NTHL1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NTHL1 were set to Colorectal cancer, MONDO:0005575; Polyposis, MONDO:0000147; NTHL1-deficiency tumor predisposition syndrome, MONDO:0100502; Familial adenomatous polyposis 3, MIM#616415
Review for gene: NTHL1 was set to GREEN
Added comment: ClinGen definitive. Colorectal cancers and/or polyposis reported in condition.
Sources: Expert list, Expert Review
Colorectal Cancer and Polyposis v0.26 MUTYH Chirag Patel gene: MUTYH was added
gene: MUTYH was added to Colorectal Cancer and Polyposis. Sources: Expert list,Expert Review
Mode of inheritance for gene: MUTYH was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MUTYH were set to Colorectal cancer, MONDO:0005575; Polyposis, MONDO:0000147; Familial adenomatous polyposis 2, MONDO:0012041; Adenomas, multiple colorectal, MIM#608456
Review for gene: MUTYH was set to GREEN
Added comment: ClinGen definitive. Colorectal cancers and/or polyposis reported in condition.
Sources: Expert list, Expert Review
Colorectal Cancer and Polyposis v0.25 PMS2 Chirag Patel gene: PMS2 was added
gene: PMS2 was added to Colorectal Cancer and Polyposis. Sources: Expert list,Expert Review
Mode of inheritance for gene: PMS2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: PMS2 were set to Colorectal cancer, MONDO:0005575; Polyposis, MONDO:0000147; Lynch syndrome 4, MONDO:0013699; Mismatch repair cancer syndrome 4, MONDO:0030843; Lynch syndrome 4, MIM#614337; Mismatch repair cancer syndrome 4, MIM#619101
Review for gene: PMS2 was set to GREEN
Added comment: ClinGen definitive. Colorectal cancers and/or polyposis reported in condition.

Note: there is a high level of homology between PMS2 and pseudogenes
Sources: Expert list, Expert Review
Colorectal Cancer and Polyposis v0.24 MSH6 Chirag Patel gene: MSH6 was added
gene: MSH6 was added to Colorectal Cancer and Polyposis. Sources: Expert list,Expert Review
Mode of inheritance for gene: MSH6 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: MSH6 were set to Colorectal cancer, MONDO:0005575; Polyposis, MONDO:0000147; Lynch syndrome 5, MONDO:0013710; Mismatch repair cancer syndrome 3, MONDO:0030841; Lynch syndrome 5, MIM#614350; Mismatch repair cancer syndrome 3, MIM#619097
Review for gene: MSH6 was set to GREEN
Added comment: ClinGen definitive. Colorectal cancers and/or polyposis reported in condition.
Sources: Expert list, Expert Review
Colorectal Cancer and Polyposis v0.23 MSH2 Chirag Patel gene: MSH2 was added
gene: MSH2 was added to Colorectal Cancer and Polyposis. Sources: Expert list,Expert Review
Mode of inheritance for gene: MSH2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: MSH2 were set to Colorectal cancer, MONDO:0005575; Polyposis, MONDO:0000147; Lynch syndrome 1, MONDO:0007356; Mismatch repair cancer syndrome 2, MONDO:0030840; Lynch syndrome 1, MIM#120435; Mismatch repair cancer syndrome 2, MIM#619096
Review for gene: MSH2 was set to GREEN
Added comment: ClinGen definitive. Colorectal cancers and/or polyposis reported in condition.
Sources: Expert list, Expert Review
Colorectal Cancer and Polyposis v0.22 MLH1 Chirag Patel gene: MLH1 was added
gene: MLH1 was added to Colorectal Cancer and Polyposis. Sources: Expert list,Expert Review
Mode of inheritance for gene: MLH1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: MLH1 were set to Colorectal cancer, MONDO:0005575; Polyposis, MONDO:0000147; Lynch syndrome 2, MONDO:0012249; Mismatch repair cancer syndrome 1, MONDO:0010159; Lynch syndrome 2, MIM#609310; Mismatch repair cancer syndrome 1, MIM#276300
Review for gene: MLH1 was set to GREEN
Added comment: ClinGen definitive. Colorectal cancers and/or polyposis reported in condition.
Sources: Expert list, Expert Review
Colorectal Cancer and Polyposis v0.21 TP53 Chirag Patel Classified gene: TP53 as Green List (high evidence)
Colorectal Cancer and Polyposis v0.21 TP53 Chirag Patel Gene: tp53 has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.20 STK11 Chirag Patel Classified gene: STK11 as Green List (high evidence)
Colorectal Cancer and Polyposis v0.20 STK11 Chirag Patel Gene: stk11 has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.19 APC Chirag Patel Classified gene: APC as Green List (high evidence)
Colorectal Cancer and Polyposis v0.19 APC Chirag Patel Gene: apc has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.18 APC Chirag Patel Classified gene: APC as Green List (high evidence)
Colorectal Cancer and Polyposis v0.18 APC Chirag Patel Gene: apc has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.17 AXIN2 Chirag Patel Classified gene: AXIN2 as Green List (high evidence)
Colorectal Cancer and Polyposis v0.17 AXIN2 Chirag Patel Gene: axin2 has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.16 BMPR1A Chirag Patel Classified gene: BMPR1A as Green List (high evidence)
Colorectal Cancer and Polyposis v0.16 BMPR1A Chirag Patel Gene: bmpr1a has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.15 EPCAM Chirag Patel Classified gene: EPCAM as Green List (high evidence)
Colorectal Cancer and Polyposis v0.15 EPCAM Chirag Patel Gene: epcam has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.14 POLD1 Chirag Patel Classified gene: POLD1 as Green List (high evidence)
Colorectal Cancer and Polyposis v0.14 POLD1 Chirag Patel Gene: pold1 has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.13 POLE Chirag Patel Classified gene: POLE as Green List (high evidence)
Colorectal Cancer and Polyposis v0.13 POLE Chirag Patel Gene: pole has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.12 PTEN Chirag Patel Classified gene: PTEN as Green List (high evidence)
Colorectal Cancer and Polyposis v0.12 PTEN Chirag Patel Gene: pten has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.11 SMAD4 Chirag Patel Classified gene: SMAD4 as Green List (high evidence)
Colorectal Cancer and Polyposis v0.11 SMAD4 Chirag Patel Gene: smad4 has been classified as Green List (High Evidence).
Colorectal Cancer and Polyposis v0.10 SMAD4 Chirag Patel edited their review of gene: SMAD4: Changed phenotypes: Colorectal cancer, MONDO:0005575, Polyposis, MONDO:0000147, Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, MONDO:0008278, Polyposis, juvenile intestinal, MIM#174900, Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, MIM#175050
Colorectal Cancer and Polyposis v0.10 PTEN Chirag Patel edited their review of gene: PTEN: Changed phenotypes: Colorectal cancer, MONDO:0005575, Polyposis, MONDO:0000147, PTEN hamartoma tumor syndrome, MONDO:0017623, PTEN hamartoma tumour syndromes, MIM#158350
Colorectal Cancer and Polyposis v0.10 POLE Chirag Patel edited their review of gene: POLE: Changed phenotypes: Colorectal cancer, MONDO:0005575, Polyposis, MONDO:0000147, POLE-related polyposis and colorectal cancer syndrome, MONDO:0100287, POLE-associated polyposis, MIM#615083
Colorectal Cancer and Polyposis v0.10 POLD1 Chirag Patel edited their review of gene: POLD1: Changed phenotypes: Colorectal cancer, MONDO:0005575, Polyposis, MONDO:0000147, POLD1-related polyposis and colorectal cancer syndrome, MONDO:0100351, POLD1-associated polyposis, MIM#612591
Colorectal Cancer and Polyposis v0.10 EPCAM Chirag Patel edited their review of gene: EPCAM: Changed phenotypes: Colorectal cancer, MONDO:0005575, Polyposis, MONDO:0000147, Lynch syndrome 8, MONDO:0013196, Lynch syndrome 8, MIM#613244
Colorectal Cancer and Polyposis v0.10 BMPR1A Chirag Patel edited their review of gene: BMPR1A: Changed phenotypes: Colorectal cancer, MONDO:0005575, Polyposis, MONDO:0000147, Polyposis syndrome, hereditary mixed, 2, MONDO:0012405, Polyposis, juvenile intestinal, MIM#174900
Colorectal Cancer and Polyposis v0.10 AXIN2 Chirag Patel edited their review of gene: AXIN2: Changed phenotypes: Colorectal cancer, MONDO:0005575, Polyposis, MONDO:0000147, AXIN2-related attenuated familial adenomatous polyposis, MONDO:0018426, Oligodontia-cancer predisposition syndrome, MONDO:0012075, Oligodontia-colorectal cancer syndrome, MIM#608615
Colorectal Cancer and Polyposis v0.10 APC Chirag Patel edited their review of gene: APC: Changed phenotypes: Colorectal cancer, MONDO:0005575, Polyposis, MONDO:0000147, APC-related attenuated familial adenomatous polyposis, MONDO:0016613, Classic familial adenomatous polyposis, MONDO:0021055, Familial adenomatous polyposis 1, MONDO:0021056, Adenomatous polyposis coli, MIM#175100
Colorectal Cancer and Polyposis v0.10 STK11 Chirag Patel edited their review of gene: STK11: Changed phenotypes: Colorectal cancer, MONDO:0005575, Polyposis, MONDO:0000147, Peutz-Jeghers syndrome, MONDO:0008280, Peutz-Jeghers syndrome, MIM#175200
Colorectal Cancer and Polyposis v0.10 TP53 Chirag Patel gene: TP53 was added
gene: TP53 was added to Colorectal Cancer and Polyposis. Sources: Expert list,Expert Review
Mode of inheritance for gene: TP53 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TP53 were set to Colorectal cancer, MONDO:0005575; Polyposis, MONDO:0000147; Li-Fraumeni syndrome, MONDO:0018875; Li-Fraumeni syndrome, MIM#151623
Review for gene: TP53 was set to GREEN
Added comment: ClinGen definitive. Colorectal cancers and/or polyposis reported in condition.

Consider possibility that an identified variant could represent ACE (aberrant clonal expansion), which can be due to clonal haematopoiesis of indeterminate potential (CHIP) or an occult hematologic malignancy, especially in older patients who have undergone prior chemotherapy (PMID: 36040522).
Sources: Expert list, Expert Review
Colorectal Cancer and Polyposis v0.9 STK11 Chirag Patel gene: STK11 was added
gene: STK11 was added to Colorectal Cancer and Polyposis. Sources: Expert list,Expert Review
Mode of inheritance for gene: STK11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: STK11 were set to Peutz-Jeghers syndrome, MONDO:0008280; Peutz-Jeghers syndrome, MIM#175200
Review for gene: STK11 was set to GREEN
Added comment: ClinGen definitive. Colorectal cancers and/or polyposis reported in condition.

Single gene testing may be more appropriate if clinical features of JPS.
Sources: Expert list, Expert Review
Colorectal Cancer and Polyposis v0.8 SMAD4 Chirag Patel gene: SMAD4 was added
gene: SMAD4 was added to Colorectal Cancer and Polyposis. Sources: Expert list,Expert Review
Mode of inheritance for gene: SMAD4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SMAD4 were set to Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, MONDO:0008278; Polyposis, juvenile intestinal, MIM#174900; Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, MIM#175050
Review for gene: SMAD4 was set to GREEN
Added comment: ClinGen definitive. Colorectal cancers and/or polyposis reported in condition.
Sources: Expert list, Expert Review
Colorectal Cancer and Polyposis v0.7 PTEN Chirag Patel gene: PTEN was added
gene: PTEN was added to Colorectal Cancer and Polyposis. Sources: Expert list,Expert Review
Mode of inheritance for gene: PTEN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PTEN were set to PTEN hamartoma tumor syndrome, MONDO:0017623; PTEN hamartoma tumour syndromes, MIM#158350
Review for gene: PTEN was set to GREEN
Added comment: ClinGen definitive. Colorectal cancers and/or polyposis reported in condition.
Sources: Expert list, Expert Review
Colorectal Cancer and Polyposis v0.6 POLE Chirag Patel gene: POLE was added
gene: POLE was added to Colorectal Cancer and Polyposis. Sources: Expert list,Expert Review
Mode of inheritance for gene: POLE was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: POLE were set to POLE-related polyposis and colorectal cancer syndrome, MONDO:0100287; POLE-associated polyposis, MIM#615083
Review for gene: POLE was set to GREEN
Added comment: ClinGen definitive. Colorectal cancers and/or polyposis reported in condition. GOF variants.
Sources: Expert list, Expert Review
Colorectal Cancer and Polyposis v0.5 POLD1 Chirag Patel gene: POLD1 was added
gene: POLD1 was added to Colorectal Cancer and Polyposis. Sources: Expert list,Expert Review
Mode of inheritance for gene: POLD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: POLD1 were set to POLD1-related polyposis and colorectal cancer syndrome, MONDO:0100351; POLD1-associated polyposis, MIM#612591
Mode of pathogenicity for gene: POLD1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: POLD1 was set to GREEN
Added comment: ClinGen definitive. Colorectal cancers and/or polyposis reported in condition. GOF variants.
Sources: Expert list, Expert Review
Colorectal Cancer and Polyposis v0.4 EPCAM Chirag Patel gene: EPCAM was added
gene: EPCAM was added to Colorectal Cancer and Polyposis. Sources: Expert list,Expert Review
Mode of inheritance for gene: EPCAM was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: EPCAM were set to Lynch syndrome 8, MONDO:0013196; Lynch syndrome 8, MIM#613244
Review for gene: EPCAM was set to GREEN
Added comment: ClinGen definitive. Colorectal cancers and/or polyposis reported in condition.

Deletion of 3’end of EPCAM gene leading to epigenetic silencing of adjacent downstream MSH2 gene.
Sources: Expert list, Expert Review
Colorectal Cancer and Polyposis v0.3 BMPR1A Chirag Patel gene: BMPR1A was added
gene: BMPR1A was added to Colorectal Cancer and Polyposis. Sources: Expert list,Expert Review
Mode of inheritance for gene: BMPR1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: BMPR1A were set to Polyposis syndrome, hereditary mixed, 2, MONDO:0012405; Polyposis, juvenile intestinal, MIM#174900
Review for gene: BMPR1A was set to GREEN
Added comment: ClinGen definitive. Colorectal cancers and/or polyposis reported in condition.
Sources: Expert list, Expert Review
Colorectal Cancer and Polyposis v0.2 AXIN2 Chirag Patel gene: AXIN2 was added
gene: AXIN2 was added to Colorectal Cancer and Polyposis. Sources: Expert list,Expert Review
Mode of inheritance for gene: AXIN2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: AXIN2 were set to AXIN2-related attenuated familial adenomatous polyposis, MONDO:0018426; Oligodontia-cancer predisposition syndrome, MONDO:0012075; Oligodontia-colorectal cancer syndrome, MIM#608615
Review for gene: AXIN2 was set to GREEN
Added comment: ClinGen definitive. Colorectal cancers and/or polyposis reported in condition.
Sources: Expert list, Expert Review
Colorectal Cancer and Polyposis v0.1 APC Chirag Patel gene: APC was added
gene: APC was added to Colorectal Cancer and Polyposis. Sources: Expert list,Expert Review
Mode of inheritance for gene: APC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: APC were set to APC-related attenuated familial adenomatous polyposis, MONDO:0016613; Classic familial adenomatous polyposis, MONDO:0021055; Familial adenomatous polyposis 1, MONDO:0021056; Adenomatous polyposis coli, MIM#175100
Review for gene: APC was set to GREEN
Added comment: ClinGen definitive. Colorectal cancers and/or polyposis reported in condition.
Sources: Expert list, Expert Review
Sarcoma soft tissue v0.32 BUB1B Chirag Patel Classified gene: BUB1B as Green List (high evidence)
Sarcoma soft tissue v0.32 BUB1B Chirag Patel Gene: bub1b has been classified as Green List (High Evidence).
Sarcoma soft tissue v0.31 BUB1B Chirag Patel gene: BUB1B was added
gene: BUB1B was added to Sarcoma soft tissue. Sources: Expert list,Expert Review
Mode of inheritance for gene: BUB1B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: BUB1B were set to Soft tissue sarcoma, MONDO:0018078; Sarcoma, MONDO:0005089; Mosaic variegated aneuploidy syndrome 1, MONDO:0009759; Mosaic variegated aneuploidy syndrome 1, MIM#257300
Review for gene: BUB1B was set to GREEN
Added comment: ClinGen definitive. Soft-tissue sarcomas reported in condition.
Sources: Expert list, Expert Review
Prepair 1000+ v1.322 TBCE Andrew Coventry reviewed gene: TBCE: Rating: GREEN; Mode of pathogenicity: None; Publications: 27666369 34134906 17699660 34356170 12389028; Phenotypes: Encephalopathy, progressive, with amyotrophy and optic atrophy MIM#617207, Hypoparathyroidism-retardation-dysmorphism syndrome MIM#241410, Kenny-Caffey syndrome, type 1 MIM#244460; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.322 STAR Andrew Coventry reviewed gene: STAR: Rating: GREEN; Mode of pathogenicity: None; Publications: 7892608 8634702 9326645 8948562 9097960 11061515 11297612 14764819 16968793; Phenotypes: Lipoid adrenal hyperplasia MIM#201710; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.322 STAMBP Andrew Coventry reviewed gene: STAMBP: Rating: GREEN; Mode of pathogenicity: None; Publications: 23542699 31638258 29907875 27531570 25692795 25266620 11713295; Phenotypes: Microcephaly-capillary malformation syndrome MIM#614261; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.322 SPEG Andrew Coventry reviewed gene: SPEG: Rating: GREEN; Mode of pathogenicity: None; Publications: 25087613 31625632 30412272 30157964 29614691 29474540 28624463 26578207 25087613 32925938 33794647 19118250 25087613; Phenotypes: Centronuclear myopathy 5 MIM615959; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.322 SPAG1 Andrew Coventry reviewed gene: SPAG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24055112 32502479; Phenotypes: Ciliary dyskinesia, primary, 28 MIM#615505; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.322 SLC6A3 Andrew Coventry reviewed gene: SLC6A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 21112253 19478460; Phenotypes: Parkinsonism-dystonia, infantile, 1 MIM#613135; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.322 SLC45A2 Andrew Coventry reviewed gene: SLC45A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 11574907 14722913 14961451; Phenotypes: Albinism, oculocutaneous, type IV MIM#606574; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.322 SLC2A10 Andrew Coventry reviewed gene: SLC2A10: Rating: GREEN; Mode of pathogenicity: None; Publications: 30071989 16550171 17935213 22116938; Phenotypes: Arterial tortuosity syndrome MIM#208050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.322 SLC13A5 Andrew Coventry reviewed gene: SLC13A5: Rating: GREEN; Mode of pathogenicity: None; Publications: 24995870 26384929 27600704 38113697; Phenotypes: Developmental and epileptic encephalopathy 25, with amelogenesis imperfecta MIM#615905; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.322 SARS2 Andrew Coventry reviewed gene: SARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24034276 21255763 33751860 34407605 38326069 38264205; Phenotypes: Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis MIM#613845; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.322 RFXAP Andrew Coventry reviewed gene: RFXAP: Rating: GREEN; Mode of pathogenicity: None; Publications: 9118943 32875002 11258423; Phenotypes: MHC class II deficiency 4 MIM#620817; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.322 RBM10 Andrew Coventry reviewed gene: RBM10: Rating: GREEN; Mode of pathogenicity: None; Publications: 20451169 24259342 30450804 30189253 33340101; Phenotypes: TARP syndrome MIM#311900; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.322 PRUNE1 Andrew Coventry reviewed gene: PRUNE1: Rating: GREEN; Mode of pathogenicity: None; Publications: 26539891 28334956 33105479 29797509; Phenotypes: Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies MIM#617481; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.322 PRG4 Andrew Coventry reviewed gene: PRG4: Rating: GREEN; Mode of pathogenicity: None; Publications: 10545950 29397575; Phenotypes: Camptodactyly-arthropathy-coxa vara-pericarditis syndrome MIM#208250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.322 PQBP1 Andrew Coventry reviewed gene: PQBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31840929 14634649 20410308 19661183; Phenotypes: Renpenning syndrome MIM#309500; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.322 POMGNT1 Andrew Coventry reviewed gene: POMGNT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27391550 26908613 30961548 30937090; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3, MIM#253280, Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B3, MIM#613151, Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 3 MIM#613157; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.322 PNPO Andrew Coventry reviewed gene: PNPO: Rating: GREEN; Mode of pathogenicity: None; Publications: 34769443 33981986 33748042 32888189 24658933 15772097 31261385 31616300 31759955; Phenotypes: Pyridoxamine 5'-phosphate oxidase deficiency MIM#610090; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.322 ATP6V0A2 Clare Hunt reviewed gene: ATP6V0A2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19401719, 22773132; Phenotypes: Cutis laxa, autosomal recessive, type IIA MIM#219200, Wrinkly skin syndrome, MIM#278250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.322 HK1 Marta Cifuentes Ochoa reviewed gene: HK1: Rating: ; Mode of pathogenicity: None; Publications: 33361148, 12393545; Phenotypes: Hemolytic anemia due to hexokinase deficiency MIM#235700, Nonspherocytic hemolytic anemia due to hexokinase deficiency (NSHA due to HK1 deficiency) MONDO:0009340 and Neuropathy, hereditary motor and sensory, Russe type MIM#605285, Charcot-Marie-Tooth disease type 4G (CMT4G) MONDO:0011534; Mode of inheritance: None
Prepair 1000+ v1.322 ASPA Clare Hunt reviewed gene: ASPA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22750302, 20301412; Phenotypes: Canavan disease MIM#271900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.322 AMPD2 Clare Hunt reviewed gene: AMPD2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 23911318; Phenotypes: Pontocerebellar hypoplasia type 9 (PCH9); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.322 GATM Marta Cifuentes Ochoa reviewed gene: GATM: Rating: GREEN; Mode of pathogenicity: None; Publications: 11555793, 27604308; Phenotypes: Cerebral creatine deficiency syndrome 3 MIM#612718, AGAT deficiency MONDO:0012996; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.322 ABAT Clare Hunt reviewed gene: ABAT: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25738457; Phenotypes: GABA-transaminase deficiency, MIM# 613163, mtDNA depletion syndrome (MDS); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.322 GAN Marta Cifuentes Ochoa reviewed gene: GAN: Rating: GREEN; Mode of pathogenicity: None; Publications: 30532362, 11062483; Phenotypes: Giant axonal neuropathy-1, MIM# 256850, MONDO:0009749; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.322 AARS2 Clare Hunt edited their review of gene: AARS2: Added comment: At least 6 families presenting with a severe COXPD phenotype in infancy, primarily with cardiac, muscle and neurological features in addition to lactic acidosis. Further 6 reported with a progressive neurodegenerative disorder characterised by loss of motor and cognitive skills, usually with onset in young adulthood. Some had a history of delayed motor development or learning difficulties in early childhood. Neurologic decline was severe, usually resulting in gait difficulties, ataxia, spasticity, and cognitive decline and dementia. Most individuals lost speech and become wheelchair-bound or bedridden. Brain MRI showed progressive white matter signal abnormalities in the deep white matter. Affected females developed premature ovarian failure. These likely represent a spectrum of severity of a single mitochondrial disorder.
Created: 29 Aug 2020, 4:55 a.m. | Last Modified: 29 Aug 2020, 4:55 a.m.
Panel Version: 0.3999; Changed publications: 27839525
Prepair 1000+ v1.322 ALAD Lauren Thomas reviewed gene: ALAD: Rating: GREEN; Mode of pathogenicity: None; Publications: 16343966, 30724374, 2063868, 1569184, 15303011; Phenotypes: Porphyria, acute hepatic, MIM#612740; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.322 DHCR7 Cassandra Muller reviewed gene: DHCR7: Rating: GREEN; Mode of pathogenicity: None; Publications: 16906538, 10602371, 10677299; Phenotypes: Smith-Lemli-Opitz syndrome (MIM#270400); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early-onset Parkinson disease v2.9 PNPLA6 Bryony Thompson Marked gene: PNPLA6 as ready
Early-onset Parkinson disease v2.9 PNPLA6 Bryony Thompson Gene: pnpla6 has been classified as Amber List (Moderate Evidence).
Early-onset Parkinson disease v2.9 PNPLA6 Bryony Thompson Classified gene: PNPLA6 as Amber List (moderate evidence)
Early-onset Parkinson disease v2.9 PNPLA6 Bryony Thompson Gene: pnpla6 has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.322 PKHD1 Andrew Coventry reviewed gene: PKHD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28375157 21945273; Phenotypes: Polycystic kidney disease 4, with or without hepatic disease MIM#263200; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early-onset Parkinson disease v2.8 PNPLA6 Bryony Thompson gene: PNPLA6 was added
gene: PNPLA6 was added to Early-onset Parkinson disease. Sources: Literature
Mode of inheritance for gene: PNPLA6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNPLA6 were set to 32623594; 36825042
Phenotypes for gene: PNPLA6 were set to PNPLA6-related spastic paraplegia with or without ataxia MONDO:0100149
Review for gene: PNPLA6 was set to AMBER
Added comment: Parkinsonism is a part of the phenotype in at least 2 families, both compound hets including the same missense variant (PNPLA6 c.4003C>T p.Pro1335Ser).
Sources: Literature
Prepair 1000+ v1.322 OCRL Andrew Coventry reviewed gene: OCRL: Rating: GREEN; Mode of pathogenicity: None; Publications: 9199559 15627218 27625797; Phenotypes: Dent disease 2 MIM#300555, Lowe syndrome MIM#309000; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.322 CYP7B1 Cassandra Muller reviewed gene: CYP7B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9802883, 18252231, 31337596, 18252231; Phenotypes: Bile acid synthesis defect, congenital, 3, 613812 (3), Spastic paraplegia 5A, 270800 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.322 CYP27A1 Cassandra Muller reviewed gene: CYP27A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebrotendinous xanthomatosis, 213700 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6248 ERCC8 Bryony Thompson Marked gene: ERCC8 as ready
Intellectual disability syndromic and non-syndromic v0.6248 ERCC8 Bryony Thompson Gene: ercc8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6248 ERCC8 Bryony Thompson Phenotypes for gene: ERCC8 were changed from to Cockayne syndrome type 1 MONDO:0019569
Intellectual disability syndromic and non-syndromic v0.6247 ERCC8 Bryony Thompson Publications for gene: ERCC8 were set to
Intellectual disability syndromic and non-syndromic v0.6246 ERCC8 Bryony Thompson Mode of inheritance for gene: ERCC8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6245 ERCC8 Bryony Thompson reviewed gene: ERCC8: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301516; Phenotypes: Cockayne syndrome type 1 MONDO:0019569; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6245 ERCC6L2 Bryony Thompson Marked gene: ERCC6L2 as ready
Intellectual disability syndromic and non-syndromic v0.6245 ERCC6L2 Bryony Thompson Gene: ercc6l2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6245 ERCC6L2 Bryony Thompson Phenotypes for gene: ERCC6L2 were changed from to pancytopenia-developmental delay syndrome MONDO:0014317
Intellectual disability syndromic and non-syndromic v0.6244 ERCC6L2 Bryony Thompson Publications for gene: ERCC6L2 were set to
Intellectual disability syndromic and non-syndromic v0.6243 ERCC6L2 Bryony Thompson Mode of inheritance for gene: ERCC6L2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6242 ERCC6L2 Bryony Thompson reviewed gene: ERCC6L2: Rating: GREEN; Mode of pathogenicity: None; Publications: 36790458; Phenotypes: pancytopenia-developmental delay syndrome MONDO:0014317; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6242 ERCC6 Bryony Thompson Marked gene: ERCC6 as ready
Intellectual disability syndromic and non-syndromic v0.6242 ERCC6 Bryony Thompson Gene: ercc6 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6242 ERCC6 Bryony Thompson Phenotypes for gene: ERCC6 were changed from to Cockayne spectrum with or without cerebrooculofacioskeletal syndrome MONDO:0100506
Intellectual disability syndromic and non-syndromic v0.6241 ERCC6 Bryony Thompson Publications for gene: ERCC6 were set to
Intellectual disability syndromic and non-syndromic v0.6240 ERCC6 Bryony Thompson Mode of inheritance for gene: ERCC6 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6239 ERCC3 Bryony Thompson Marked gene: ERCC3 as ready
Intellectual disability syndromic and non-syndromic v0.6239 ERCC3 Bryony Thompson Gene: ercc3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6239 ERCC3 Bryony Thompson Phenotypes for gene: ERCC3 were changed from to xeroderma pigmentosum group B MONDO:0012531
Intellectual disability syndromic and non-syndromic v0.6238 ERCC3 Bryony Thompson Publications for gene: ERCC3 were set to
Intellectual disability syndromic and non-syndromic v0.6237 ERCC3 Bryony Thompson Mode of inheritance for gene: ERCC3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6236 ERCC2 Bryony Thompson Phenotypes for gene: ERCC2 were changed from xeroderma pigmentosum group D MONDO:0010212 to xeroderma pigmentosum group D MONDO:0010212; trichothiodystrophy 1, photosensitive MONDO:0011125; cerebrooculofacioskeletal syndrome 2 MONDO:0012553
Intellectual disability syndromic and non-syndromic v0.6235 ERCC2 Bryony Thompson Marked gene: ERCC2 as ready
Intellectual disability syndromic and non-syndromic v0.6235 ERCC2 Bryony Thompson Gene: ercc2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6235 ERCC2 Bryony Thompson Phenotypes for gene: ERCC2 were changed from to xeroderma pigmentosum group D MONDO:0010212
Intellectual disability syndromic and non-syndromic v0.6234 ERCC2 Bryony Thompson Publications for gene: ERCC2 were set to
Intellectual disability syndromic and non-syndromic v0.6233 ERCC2 Bryony Thompson Mode of inheritance for gene: ERCC2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6232 EP300 Bryony Thompson Marked gene: EP300 as ready
Intellectual disability syndromic and non-syndromic v0.6232 EP300 Bryony Thompson Gene: ep300 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6232 EP300 Bryony Thompson Phenotypes for gene: EP300 were changed from to Rubinstein-Taybi syndrome MONDO:0019188
Intellectual disability syndromic and non-syndromic v0.6231 EP300 Bryony Thompson Publications for gene: EP300 were set to https://search.clinicalgenome.org/CCID:004751
Intellectual disability syndromic and non-syndromic v0.6230 EP300 Bryony Thompson Publications for gene: EP300 were set to
Intellectual disability syndromic and non-syndromic v0.6229 EP300 Bryony Thompson Mode of inheritance for gene: EP300 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6228 ELOVL4 Bryony Thompson Marked gene: ELOVL4 as ready
Intellectual disability syndromic and non-syndromic v0.6228 ELOVL4 Bryony Thompson Gene: elovl4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6228 ELOVL4 Bryony Thompson Phenotypes for gene: ELOVL4 were changed from to congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome MONDO:0013760
Intellectual disability syndromic and non-syndromic v0.6227 ELOVL4 Bryony Thompson Publications for gene: ELOVL4 were set to
Intellectual disability syndromic and non-syndromic v0.6226 ELOVL4 Bryony Thompson Mode of inheritance for gene: ELOVL4 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6225 EIF2AK3 Bryony Thompson Marked gene: EIF2AK3 as ready
Intellectual disability syndromic and non-syndromic v0.6225 EIF2AK3 Bryony Thompson Gene: eif2ak3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6225 EIF2AK3 Bryony Thompson Mode of inheritance for gene: EIF2AK3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6224 EIF2AK3 Bryony Thompson Publications for gene: EIF2AK3 were set to
Intellectual disability syndromic and non-syndromic v0.6223 DIAPH1 Bryony Thompson Publications for gene: DIAPH1 were set to 24781755; 26463574
Intellectual disability syndromic and non-syndromic v0.6222 DIAPH1 Bryony Thompson reviewed gene: DIAPH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 39076976, 24781755, 26463574, 33662367; Phenotypes: progressive microcephaly-seizures-cortical blindness-developmental delay syndrome MONDO:0014714; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.322 PNKP Shakira Heerah reviewed gene: PNKP: Rating: GREEN; Mode of pathogenicity: None; Publications: 31436889, 31707899, 20118933, 23224214, 29243230, 2578773, 27066567; Phenotypes: Ataxia-oculomotor apraxia 4, Microcephaly, seizures, and developmental delay, Charcot-Marie-Tooth disease, type 2B2; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2016 PNKP Shakira Heerah Deleted their review
Mendeliome v1.2016 RPS6KB1 Bryony Thompson Classified gene: RPS6KB1 as Amber List (moderate evidence)
Mendeliome v1.2016 RPS6KB1 Bryony Thompson Added comment: Comment on list classification: Comment on list classification: ClinGen HCVD GCEP has classified this gene as Limited for HCM on 13/09/2023 - https://search.clinicalgenome.org/CCID:006034
Mendeliome v1.2016 RPS6KB1 Bryony Thompson Gene: rps6kb1 has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.322 LARS Lucy Spencer reviewed gene: LARS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Infantile liver failure syndrome 1, MIM# 615438; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.322 KCTD7 Lucy Spencer reviewed gene: KCTD7: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Epilepsy, progressive myoclonic 3, with or without intracellular inclusions MIM#611726; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.322 HPS5 Lucy Spencer reviewed gene: HPS5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hermansky-Pudlak syndrome 5 MIM#614074; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.322 HLCS Lucy Spencer reviewed gene: HLCS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Holocarboxylase synthetase deficiency MIM#253270; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.322 HADHB Lucy Spencer reviewed gene: HADHB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial trifunctional protein deficiency 2 MIM#620300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.322 GSS Lucy Spencer reviewed gene: GSS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Glutathione synthetase deficiency MIM#266130; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.322 GNPTAB Lucy Spencer reviewed gene: GNPTAB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mucolipidosis III alpha/beta MIM#252600, Mucolipidosis II alpha/beta MIM#252500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.322 FGG Lucy Spencer reviewed gene: FGG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Afibrinogenemia, congenital MIM#202400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.322 FGB Lucy Spencer reviewed gene: FGB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Afibrinogenemia, congenital MIM#202400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.322 FGA Lucy Spencer reviewed gene: FGA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Afibrinogenemia, congenital (MIM#202400); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.322 FGA Lucy Spencer Deleted their review
Prepair 1000+ v1.322 FGA Lucy Spencer reviewed gene: FGA: Rating: GREEN; Mode of pathogenicity: None; Publications: Afibrinogenemia, congenital (MIM#202400); Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 ERCC6L2 Ken Lee Wan reviewed gene: ERCC6L2: Rating: AMBER; Mode of pathogenicity: None; Publications: 24507776, 27185855, 28815563, 29633571; Phenotypes: pancytopenia-developmental delay syndrome MONDO:0014317; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6222 ERCC3 Ken Lee Wan reviewed gene: ERCC3: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301571; Phenotypes: xeroderma pigmentosum group B MONDO:0012531; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6222 ERCC2 Ken Lee Wan reviewed gene: ERCC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301571; Phenotypes: xeroderma pigmentosum group D MONDO:0010212, trichothiodystrophy 1, photosensitive MONDO:0011125, cerebrooculofacioskeletal syndrome 2 MONDO:0012553; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6222 EP300 Ken Lee Wan changed review comment from: EP300 is definitively associated with autosomal dominant Rubinstein-Taybi syndrome. Rubinstein-Taybi syndrome is characterized by distinctive facial features, broad and angulated thumbs and halluces, short stature, and intellectual disability (https://search.clinicalgenome.org/CCID:004751).

Mechanism of disease: loss of function; to: EP300 is definitively associated with autosomal dominant Rubinstein-Taybi syndrome. Rubinstein-Taybi syndrome is characterized by distinctive facial features, broad and angulated thumbs and halluces, short stature and intellectual disability (https://search.clinicalgenome.org/CCID:004751).

Mechanism of disease: loss of function
Intellectual disability syndromic and non-syndromic v0.6222 EP300 Ken Lee Wan reviewed gene: EP300: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Rubinstein-Taybi syndrome MONDO:0019188; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6222 ELOVL4 Ken Lee Wan reviewed gene: ELOVL4: Rating: GREEN; Mode of pathogenicity: None; Publications: 37592902; Phenotypes: congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome MONDO:0013760; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Ectodermal Dysplasia v0.86 RSPO4 Paul De Fazio gene: RSPO4 was added
gene: RSPO4 was added to Ectodermal Dysplasia. Sources: Literature
Mode of inheritance for gene: RSPO4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RSPO4 were set to 17041604; 17914448; 18070203
Phenotypes for gene: RSPO4 were set to Anonychia congenita MIM# 206800
Review for gene: RSPO4 was set to GREEN
gene: RSPO4 was marked as current diagnostic
Added comment: Congenital anonychia is defined as the absence of fingernails and toenails. Anonychia and its milder phenotypic variant, hyponychia, usually occur as a feature of genetic syndromes, in association with significant skeletal and limb anomalies. Isolated nonsyndromic congenital anonychia/hyponychia is a rare entity that usually follows autosomal recessive inheritance with variable expression, even within a given family. The nail phenotypes observed range from no nail field to a nail field of reduced size with an absent or rudimentary nail (summary by Bruchle et al., 2008). This form of nail disorder is referred to here as nonsyndromic congenital nail disorder-4 (NDNC4).

Multiple families with homozygous or compound heterozygous variants, in consanguineous and non-consanguineous families.
Sources: Literature
Ovarian Cancer v0.24 TP53 Chirag Patel changed review comment from: ClinGen definitive. Ovarian cancers reported in condition.
Sources: Expert list, Expert Review; to: ClinGen definitive. Ovarian cancers reported in condition.

Consider possibility that an identified variant could represent ACE (aberrant clonal expansion), which can be due to clonal haematopoiesis of indeterminate potential (CHIP) or an occult hematologic malignancy, especially in older patients who have undergone prior chemotherapy (PMID: 36040522).

Sources: Expert list, Expert Review
Ovarian Cancer v0.24 TP53 Chirag Patel Classified gene: TP53 as Green List (high evidence)
Ovarian Cancer v0.24 TP53 Chirag Patel Gene: tp53 has been classified as Green List (High Evidence).
Ovarian Cancer v0.23 RAD51D Chirag Patel Classified gene: RAD51D as Green List (high evidence)
Ovarian Cancer v0.23 RAD51D Chirag Patel Gene: rad51d has been classified as Green List (High Evidence).
Ovarian Cancer v0.22 RAD51C Chirag Patel Classified gene: RAD51C as Green List (high evidence)
Ovarian Cancer v0.22 RAD51C Chirag Patel Gene: rad51c has been classified as Green List (High Evidence).
Ovarian Cancer v0.21 PALB2 Chirag Patel Classified gene: PALB2 as Green List (high evidence)
Ovarian Cancer v0.21 PALB2 Chirag Patel Gene: palb2 has been classified as Green List (High Evidence).
Ovarian Cancer v0.20 EPCAM Chirag Patel Classified gene: EPCAM as Green List (high evidence)
Ovarian Cancer v0.20 EPCAM Chirag Patel Gene: epcam has been classified as Green List (High Evidence).
Ovarian Cancer v0.19 BRIP1 Chirag Patel Classified gene: BRIP1 as Green List (high evidence)
Ovarian Cancer v0.19 BRIP1 Chirag Patel Gene: brip1 has been classified as Green List (High Evidence).
Ovarian Cancer v0.18 BRCA2 Chirag Patel Classified gene: BRCA2 as Green List (high evidence)
Ovarian Cancer v0.18 BRCA2 Chirag Patel Gene: brca2 has been classified as Green List (High Evidence).
Ovarian Cancer v0.17 BRCA1 Chirag Patel Classified gene: BRCA1 as Green List (high evidence)
Ovarian Cancer v0.17 BRCA1 Chirag Patel Gene: brca1 has been classified as Green List (High Evidence).
Ovarian Cancer v0.16 TP53 Chirag Patel gene: TP53 was added
gene: TP53 was added to Ovarian Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: TP53 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TP53 were set to Ovarian cancer, MONDO:0008170; Li-Fraumeni syndrome, MONDO:0018875; Li-Fraumeni syndrome, MIM#151623
Review for gene: TP53 was set to GREEN
Added comment: ClinGen definitive. Ovarian cancers reported in condition.
Sources: Expert list, Expert Review
Ovarian Cancer v0.15 RAD51D Chirag Patel gene: RAD51D was added
gene: RAD51D was added to Ovarian Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: RAD51D was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RAD51D were set to Ovarian cancer, MONDO:0008170; RAD51D-related cancer predisposition, MONDO:0700274; Breast-ovarian cancer, familial, susceptibility to, 4, MONDO:0013669; Breast-ovarian cancer, familial, susceptibility to, 4, MIM#614291
Review for gene: RAD51D was set to GREEN
Added comment: ClinGen definitive. Ovarian cancers reported in condition.
Sources: Expert list, Expert Review
Ovarian Cancer v0.14 RAD51C Chirag Patel gene: RAD51C was added
gene: RAD51C was added to Ovarian Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: RAD51C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RAD51C were set to Ovarian cancer, MONDO:0008170; RAD51C-related cancer predisposition, MONDO:0700273; Breast-ovarian cancer, familial, susceptibility to, 3, MONDO:0013253; Breast-ovarian cancer, familial, susceptibility to, 3, MIM#613399
Review for gene: RAD51C was set to GREEN
Added comment: ClinGen definitive. Ovarian cancers reported in condition.
Sources: Expert list, Expert Review
Ovarian Cancer v0.13 PALB2 Chirag Patel gene: PALB2 was added
gene: PALB2 was added to Ovarian Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: PALB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PALB2 were set to Ovarian cancer, MONDO:0008170; PALB2-related cancer predisposition, MONDO:0700272; Breast-ovarian cancer, familial, susceptibility to, 5, MIM#620442; Pancreatic cancer, susceptibility to, 3, MIM#613348
Review for gene: PALB2 was set to GREEN
Added comment: ClinGen definitive. Ovarian cancers reported in condition.
Sources: Expert list, Expert Review
Ovarian Cancer v0.12 EPCAM Chirag Patel gene: EPCAM was added
gene: EPCAM was added to Ovarian Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: EPCAM was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: EPCAM were set to Ovarian cancer, MONDO:0008170; Lynch syndrome 8, MONDO:0013196; Lynch syndrome 8, MIM#613244
Review for gene: EPCAM was set to GREEN
Added comment: ClinGen definitive. Ovarian cancers reported in condition.

Deletion of 3’end of EPCAM gene leading to epigenetic silencing of adjacent downstream MSH2 gene.
Sources: Expert list, Expert Review
Ovarian Cancer v0.11 BRIP1 Chirag Patel gene: BRIP1 was added
gene: BRIP1 was added to Ovarian Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: BRIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: BRIP1 were set to Ovarian cancer, MONDO:0008170
Review for gene: BRIP1 was set to GREEN
Added comment: ClinGen definitive. Ovarian cancers reported in condition.
Sources: Expert list, Expert Review
Ovarian Cancer v0.10 BRCA2 Chirag Patel gene: BRCA2 was added
gene: BRCA2 was added to Ovarian Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: BRCA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: BRCA2 were set to Ovarian cancer, MONDO:0008170; BRCA2-related cancer predisposition, MONDO:0700269; Breast-ovarian cancer, familial, 2, MIM#612555
Review for gene: BRCA2 was set to GREEN
Added comment: ClinGen definitive. Ovarian cancers reported in condition.
Sources: Expert list, Expert Review
Ovarian Cancer v0.9 BRCA1 Chirag Patel gene: BRCA1 was added
gene: BRCA1 was added to Ovarian Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: BRCA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: BRCA1 were set to Ovarian cancer, MONDO:0008170; BRCA1-related cancer predisposition, MONDO:0700268; Breast-ovarian cancer, familial, 1, MIM#604370
Review for gene: BRCA1 was set to GREEN
Added comment: ClinGen definitive. Ovarian cancers reported in condition.
Sources: Expert list, Expert Review
Ovarian Cancer v0.8 PMS2 Chirag Patel Classified gene: PMS2 as Green List (high evidence)
Ovarian Cancer v0.8 PMS2 Chirag Patel Gene: pms2 has been classified as Green List (High Evidence).
Ovarian Cancer v0.7 MSH6 Chirag Patel Classified gene: MSH6 as Green List (high evidence)
Ovarian Cancer v0.7 MSH6 Chirag Patel Gene: msh6 has been classified as Green List (High Evidence).
Ovarian Cancer v0.6 MSH2 Chirag Patel Classified gene: MSH2 as Green List (high evidence)
Ovarian Cancer v0.6 MSH2 Chirag Patel Gene: msh2 has been classified as Green List (High Evidence).
Ovarian Cancer v0.5 MLH1 Chirag Patel Classified gene: MLH1 as Green List (high evidence)
Ovarian Cancer v0.5 MLH1 Chirag Patel Gene: mlh1 has been classified as Green List (High Evidence).
Ovarian Cancer v0.4 PMS2 Chirag Patel gene: PMS2 was added
gene: PMS2 was added to Ovarian Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: PMS2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: PMS2 were set to Ovarian cancer, MONDO:0008170; Lynch syndrome 4, MONDO:0013699; Mismatch repair cancer syndrome 4, MONDO:0030843; Lynch syndrome 4, MIM#614337; Mismatch repair cancer syndrome 4, MIM#619101
Review for gene: PMS2 was set to GREEN
Added comment: ClinGen definitive. Ovarian cancers reported in condition.

Note: there is a high level of homology between PMS2 and pseudogenes
Sources: Expert list, Expert Review
Ovarian Cancer v0.3 MSH6 Chirag Patel gene: MSH6 was added
gene: MSH6 was added to Ovarian Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: MSH6 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: MSH6 were set to Ovarian cancer, MONDO:0008170; Lynch syndrome 5, MONDO:0013710; Mismatch repair cancer syndrome 3, MONDO:0030841; Lynch syndrome 5, MIM#614350; Mismatch repair cancer syndrome 3, MIM#619097
Review for gene: MSH6 was set to GREEN
Added comment: ClinGen definitive. Ovarian cancers reported in condition.
Sources: Expert list, Expert Review
Ovarian Cancer v0.2 MSH2 Chirag Patel gene: MSH2 was added
gene: MSH2 was added to Ovarian Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: MSH2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: MSH2 were set to Ovarian cancer, MONDO:0008170; Lynch syndrome 1, MONDO:0007356; Mismatch repair cancer syndrome 2, MONDO:0030840; Lynch syndrome 1, MIM#120435; Mismatch repair cancer syndrome 2, MIM#619096
Review for gene: MSH2 was set to GREEN
Added comment: ClinGen definitive. Ovarian cancers reported in condition.
Sources: Expert list, Expert Review
Ovarian Cancer v0.1 MLH1 Chirag Patel gene: MLH1 was added
gene: MLH1 was added to Ovarian Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: MLH1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: MLH1 were set to Ovarian cancer, MONDO:0008170; Lynch syndrome 2, MONDO:0012249; Mismatch repair cancer syndrome 1, MONDO:0010159; Lynch syndrome 2, MIM#609310; Mismatch repair cancer syndrome 1, MIM#276300
Review for gene: MLH1 was set to GREEN
Added comment: ClinGen definitive. Ovarian cancers reported in condition.
Sources: Expert list, Expert Review
Endometrial Cancer v0.20 POLE Chirag Patel Classified gene: POLE as Green List (high evidence)
Endometrial Cancer v0.20 POLE Chirag Patel Gene: pole has been classified as Green List (High Evidence).
Endometrial Cancer v0.19 POLD1 Chirag Patel Classified gene: POLD1 as Green List (high evidence)
Endometrial Cancer v0.19 POLD1 Chirag Patel Gene: pold1 has been classified as Green List (High Evidence).
Endometrial Cancer v0.18 TP53 Chirag Patel Classified gene: TP53 as Green List (high evidence)
Endometrial Cancer v0.18 TP53 Chirag Patel Gene: tp53 has been classified as Green List (High Evidence).
Endometrial Cancer v0.17 PTEN Chirag Patel Classified gene: PTEN as Green List (high evidence)
Endometrial Cancer v0.17 PTEN Chirag Patel Gene: pten has been classified as Green List (High Evidence).
Endometrial Cancer v0.16 EPCAM Chirag Patel Classified gene: EPCAM as Green List (high evidence)
Endometrial Cancer v0.16 EPCAM Chirag Patel Gene: epcam has been classified as Green List (High Evidence).
Endometrial Cancer v0.15 BRCA1 Chirag Patel Classified gene: BRCA1 as Green List (high evidence)
Endometrial Cancer v0.15 BRCA1 Chirag Patel Gene: brca1 has been classified as Green List (High Evidence).
Endometrial Cancer v0.14 PMS2 Chirag Patel Classified gene: PMS2 as Green List (high evidence)
Endometrial Cancer v0.14 PMS2 Chirag Patel Gene: pms2 has been classified as Green List (High Evidence).
Endometrial Cancer v0.13 MSH6 Chirag Patel Classified gene: MSH6 as Green List (high evidence)
Endometrial Cancer v0.13 MSH6 Chirag Patel Gene: msh6 has been classified as Green List (High Evidence).
Endometrial Cancer v0.12 MSH2 Chirag Patel Classified gene: MSH2 as Green List (high evidence)
Endometrial Cancer v0.12 MSH2 Chirag Patel Gene: msh2 has been classified as Green List (High Evidence).
Endometrial Cancer v0.11 MLH1 Chirag Patel Classified gene: MLH1 as Green List (high evidence)
Endometrial Cancer v0.11 MLH1 Chirag Patel Gene: mlh1 has been classified as Green List (High Evidence).
Endometrial Cancer v0.10 POLE Chirag Patel gene: POLE was added
gene: POLE was added to Endometrial Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: POLE was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: POLE were set to Endometrial cancer, MONDO:0011962; POLE-related polyposis and colorectal cancer syndrome, MONDO:0100287; POLE-associated polyposis, MIM#615083
Mode of pathogenicity for gene: POLE was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: POLE was set to GREEN
Added comment: ClinGen definitive. Endometrial cancers reported in condition. GOF variants.
Sources: Expert list, Expert Review
Endometrial Cancer v0.9 POLD1 Chirag Patel gene: POLD1 was added
gene: POLD1 was added to Endometrial Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: POLD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: POLD1 were set to Endometrial cancer, MONDO:0011962; POLD1-related polyposis and colorectal cancer syndrome, MONDO:0100351; POLD1-associated polyposis, MIM#612591
Mode of pathogenicity for gene: POLD1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: POLD1 was set to GREEN
Added comment: ClinGen definitive. Endometrial cancers reported in condition. GOF variants.
Sources: Expert list, Expert Review
Endometrial Cancer v0.8 TP53 Chirag Patel gene: TP53 was added
gene: TP53 was added to Endometrial Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: TP53 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TP53 were set to Endometrial cancer, MONDO:0011962; Li-Fraumeni syndrome, MONDO:0018875; Li-Fraumeni syndrome, MIM#151623
Review for gene: TP53 was set to GREEN
Added comment: ClinGen definitive. Endometrial cancers reported in condition.

Consider possibility that an identified variant could represent ACE (aberrant clonal expansion), which can be due to clonal haematopoiesis of indeterminate potential (CHIP) or an occult hematologic malignancy, especially in older patients who have undergone prior chemotherapy (PMID: 36040522).
Sources: Expert list, Expert Review
Endometrial Cancer v0.7 PTEN Chirag Patel gene: PTEN was added
gene: PTEN was added to Endometrial Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: PTEN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PTEN were set to Endometrial cancer, MONDO:0011962; PTEN hamartoma tumor syndrome, MONDO:0017623; PTEN hamartoma tumour syndromes, MIM#158350
Review for gene: PTEN was set to GREEN
Added comment: ClinGen definitive. Endometrial cancers reported in condition.
Sources: Expert list, Expert Review
Endometrial Cancer v0.6 EPCAM Chirag Patel gene: EPCAM was added
gene: EPCAM was added to Endometrial Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: EPCAM was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: EPCAM were set to Endometrial cancer, MONDO:0011962; Lynch syndrome 8, MONDO:0013196; Lynch syndrome 8, MIM#613244
Review for gene: EPCAM was set to GREEN
Added comment: ClinGen definitive. Endometrial cancers reported in condition.

Deletion of 3’end of EPCAM gene leading to epigenetic silencing of adjacent downstream MSH2 gene.
Sources: Expert list, Expert Review
Endometrial Cancer v0.5 BRCA1 Chirag Patel gene: BRCA1 was added
gene: BRCA1 was added to Endometrial Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: BRCA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: BRCA1 were set to Endometrial cancer, MONDO:0011962; BRCA1-related cancer predisposition, MONDO:0700268; Breast-ovarian cancer, familial, 1, MIM#604370
Review for gene: BRCA1 was set to GREEN
Added comment: ClinGen definitive. Endometrial cancers reported in condition.
Sources: Expert list, Expert Review
Endometrial Cancer v0.4 PMS2 Chirag Patel gene: PMS2 was added
gene: PMS2 was added to Endometrial Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: PMS2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: PMS2 were set to Endometrial cancer, MONDO:0011962; Lynch syndrome 4, MONDO:0013699; Mismatch repair cancer syndrome 4, MONDO:0030843; Lynch syndrome 4, MIM#614337; Mismatch repair cancer syndrome 4, MIM#619101
Review for gene: PMS2 was set to GREEN
Added comment: ClinGen definitive. Endometrial cancers reported in condition.

Note: there is a high level of homology between PMS2 and pseudogenes
Sources: Expert list, Expert Review
Endometrial Cancer v0.3 MSH6 Chirag Patel gene: MSH6 was added
gene: MSH6 was added to Endometrial Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: MSH6 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: MSH6 were set to Endometrial cancer, MONDO:0011962; Lynch syndrome 5, MONDO:0013710; Mismatch repair cancer syndrome 3, MONDO:0030841; Lynch syndrome 5, MIM#614350; Mismatch repair cancer syndrome 3, MIM#619097
Review for gene: MSH6 was set to GREEN
Added comment: ClinGen definitive. Endometrial cancers reported in condition.
Sources: Expert list, Expert Review
Endometrial Cancer v0.2 MSH2 Chirag Patel gene: MSH2 was added
gene: MSH2 was added to Endometrial Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: MSH2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: MSH2 were set to Endometrial cancer, MONDO:0011962; Lynch syndrome 1, MONDO:0007356; Mismatch repair cancer syndrome 2, MONDO:0030840; Lynch syndrome 1, MIM#120435; Mismatch repair cancer syndrome 2, MIM#619096
Review for gene: MSH2 was set to GREEN
Added comment: ClinGen definitive. Endometrial cancers reported in condition.
Sources: Expert list, Expert Review
Endometrial Cancer v0.1 MLH1 Chirag Patel gene: MLH1 was added
gene: MLH1 was added to Endometrial Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: MLH1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: MLH1 were set to Endometrial cancer, MONDO:0011962; Lynch syndrome 2, MONDO:0012249; Mismatch repair cancer syndrome 1, MONDO:0010159; Lynch syndrome 2, MIM#609310; Mismatch repair cancer syndrome 1, MIM#276300
Review for gene: MLH1 was set to GREEN
Added comment: ClinGen definitive. Endometrial cancers reported in condition.
Sources: Expert list, Expert Review
Prostate Cancer v0.24 HOXB13 Chirag Patel Classified gene: HOXB13 as Green List (high evidence)
Prostate Cancer v0.24 HOXB13 Chirag Patel Gene: hoxb13 has been classified as Green List (High Evidence).
Prostate Cancer v0.23 HOXB13 Chirag Patel gene: HOXB13 was added
gene: HOXB13 was added to Prostate Cancer. Sources: Expert list,Expert Review,Literature
Mode of inheritance for gene: HOXB13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HOXB13 were set to PMID: 22236224, 30730552, 38766261
Phenotypes for gene: HOXB13 were set to Prostate cancer, MONDO:0008315; Prostate cancer, susceptibility to, MIM#610997
Review for gene: HOXB13 was set to GREEN
Added comment: Established gene-disease association (particularly G84E variant).

Several studies demonstrating the association of the HOXB13 G84E variant with prostate cancer, including a European study that showed an increased frequency of the HOXB13 G84E variant in patients with prostate cancer at 1.4% compared to those without prostate cancer at 0.1%.
Sources: Expert list, Expert Review, Literature
Prostate Cancer v0.22 CHEK2 Chirag Patel Classified gene: CHEK2 as Green List (high evidence)
Prostate Cancer v0.22 CHEK2 Chirag Patel Gene: chek2 has been classified as Green List (High Evidence).
Prostate Cancer v0.21 TP53 Chirag Patel Classified gene: TP53 as Green List (high evidence)
Prostate Cancer v0.21 TP53 Chirag Patel Gene: tp53 has been classified as Green List (High Evidence).
Prostate Cancer v0.20 PALB2 Chirag Patel Classified gene: PALB2 as Green List (high evidence)
Prostate Cancer v0.20 PALB2 Chirag Patel Gene: palb2 has been classified as Green List (High Evidence).
Prostate Cancer v0.19 EPCAM Chirag Patel Classified gene: EPCAM as Green List (high evidence)
Prostate Cancer v0.19 EPCAM Chirag Patel Gene: epcam has been classified as Green List (High Evidence).
Prostate Cancer v0.18 BRCA2 Chirag Patel Classified gene: BRCA2 as Green List (high evidence)
Prostate Cancer v0.18 BRCA2 Chirag Patel Gene: brca2 has been classified as Green List (High Evidence).
Prostate Cancer v0.17 BRCA1 Chirag Patel Classified gene: BRCA1 as Green List (high evidence)
Prostate Cancer v0.17 BRCA1 Chirag Patel Gene: brca1 has been classified as Green List (High Evidence).
Prostate Cancer v0.16 ATM Chirag Patel Classified gene: ATM as Green List (high evidence)
Prostate Cancer v0.16 ATM Chirag Patel Gene: atm has been classified as Green List (High Evidence).
Prostate Cancer v0.15 CHEK2 Chirag Patel gene: CHEK2 was added
gene: CHEK2 was added to Prostate Cancer. Sources: Expert list,Expert Review,Literature
Mode of inheritance for gene: CHEK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHEK2 were set to PMID: 33322746, 36529447
Phenotypes for gene: CHEK2 were set to Prostate cancer, MONDO:0008315; CHEK2-related cancer predisposition, MONDO:0700271; Breast/prostate cancer, susceptibility to, MIM#609265
Review for gene: CHEK2 was set to GREEN
Added comment: Established gene-disease association. Prostate cancers reported in condition.

Consider possibility that an identified variant could represent ACE (aberrant clonal expansion), which can be due to clonal haematopoiesis of indeterminate potential (CHIP) or an occult hematologic malignancy, especially in older patients who have undergone prior chemotherapy (PMID: 36040522).
Sources: Expert list, Expert Review, Literature
Prostate Cancer v0.14 TP53 Chirag Patel gene: TP53 was added
gene: TP53 was added to Prostate Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: TP53 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TP53 were set to Prostate cancer, MONDO:0008315; Li-Fraumeni syndrome, MONDO:0018875; Li-Fraumeni syndrome, MIM#151623
Review for gene: TP53 was set to GREEN
Added comment: ClinGen definitive. Prostate cancers reported in condition.

Consider possibility that an identified variant could represent ACE (aberrant clonal expansion), which can be due to clonal haematopoiesis of indeterminate potential (CHIP) or an occult hematologic malignancy, especially in older patients who have undergone prior chemotherapy (PMID: 36040522).
Sources: Expert list, Expert Review
Prostate Cancer v0.13 PALB2 Chirag Patel gene: PALB2 was added
gene: PALB2 was added to Prostate Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: PALB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PALB2 were set to Prostate cancer, MONDO:0008315; PALB2-related cancer predisposition, MONDO:0700272; Breast-ovarian cancer, familial, susceptibility to, 5, MIM#620442; Pancreatic cancer, susceptibility to, 3, MIM#613348
Review for gene: PALB2 was set to GREEN
Added comment: ClinGen definitive. Prostate cancers reported in condition.
Sources: Expert list, Expert Review
Prostate Cancer v0.12 EPCAM Chirag Patel gene: EPCAM was added
gene: EPCAM was added to Prostate Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: EPCAM was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: EPCAM were set to Prostate cancer, MONDO:0008315; Lynch syndrome 8, MONDO:0013196; Lynch syndrome 8, MIM#613244
Review for gene: EPCAM was set to GREEN
Added comment: ClinGen definitive. Prostate cancers reported in condition.

Deletion of 3’end of EPCAM gene leading to epigenetic silencing of adjacent downstream MSH2 gene.
Sources: Expert list, Expert Review
Prostate Cancer v0.11 BRCA2 Chirag Patel gene: BRCA2 was added
gene: BRCA2 was added to Prostate Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: BRCA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: BRCA2 were set to Prostate cancer, MONDO:0008315; BRCA2-related cancer predisposition, MONDO:0700269; Breast-ovarian cancer, familial, 2, MIM#612555
Review for gene: BRCA2 was set to GREEN
Added comment: ClinGen definitive. Prostate cancers reported in condition.
Sources: Expert list, Expert Review
Prostate Cancer v0.10 BRCA1 Chirag Patel gene: BRCA1 was added
gene: BRCA1 was added to Prostate Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: BRCA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: BRCA1 were set to Prostate cancer, MONDO:0008315; BRCA1-related cancer predisposition, MONDO:0700268; Breast-ovarian cancer, familial, 1, MIM#604370
Review for gene: BRCA1 was set to GREEN
Added comment: ClinGen definitive. Prostate cancers reported in condition.
Sources: Expert list, Expert Review
Prostate Cancer v0.9 ATM Chirag Patel gene: ATM was added
gene: ATM was added to Prostate Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: ATM was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ATM were set to Prostate cancer, MONDO:0008315; ATM-related cancer predisposition, MONDO:0700270; Breast cancer, susceptibility to, MIM#114480
Review for gene: ATM was set to GREEN
Added comment: ClinGen definitive. Prostate cancers reported in condition.

Consider possibility that an identified variant could represent ACE (aberrant clonal expansion), which can be due to clonal haematopoiesis of indeterminate potential (CHIP) or an occult hematologic malignancy, especially in older patients who have undergone prior chemotherapy (PMID: 36040522).
Sources: Expert list, Expert Review
Prostate Cancer v0.8 MLH1 Chirag Patel Classified gene: MLH1 as Green List (high evidence)
Prostate Cancer v0.8 MLH1 Chirag Patel Gene: mlh1 has been classified as Green List (High Evidence).
Prostate Cancer v0.7 MSH2 Chirag Patel Classified gene: MSH2 as Green List (high evidence)
Prostate Cancer v0.7 MSH2 Chirag Patel Gene: msh2 has been classified as Green List (High Evidence).
Prostate Cancer v0.6 MSH6 Chirag Patel Classified gene: MSH6 as Green List (high evidence)
Prostate Cancer v0.6 MSH6 Chirag Patel Gene: msh6 has been classified as Green List (High Evidence).
Prostate Cancer v0.5 PMS2 Chirag Patel Classified gene: PMS2 as Green List (high evidence)
Prostate Cancer v0.5 PMS2 Chirag Patel Gene: pms2 has been classified as Green List (High Evidence).
Prostate Cancer v0.4 PMS2 Chirag Patel gene: PMS2 was added
gene: PMS2 was added to Prostate Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: PMS2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: PMS2 were set to Prostate cancer, MONDO:0008315; Lynch syndrome 4, MONDO:0013699; Mismatch repair cancer syndrome 4, MONDO:0030843; Lynch syndrome 4, MIM#614337; Mismatch repair cancer syndrome 4, MIM#619101
Review for gene: PMS2 was set to GREEN
Added comment: ClinGen definitive. Prostate cancers reported in condition.

Note: there is a high level of homology between PMS2 and pseudogenes.
Sources: Expert list, Expert Review
Prostate Cancer v0.3 MSH6 Chirag Patel gene: MSH6 was added
gene: MSH6 was added to Prostate Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: MSH6 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: MSH6 were set to Prostate cancer, MONDO:0008315; Lynch syndrome 5, MONDO:0013710; Mismatch repair cancer syndrome 3, MONDO:0030841; Lynch syndrome 5, MIM#614350; Mismatch repair cancer syndrome 3, MIM#619097
Review for gene: MSH6 was set to GREEN
Added comment: ClinGen definitive. Prostate cancers reported in condition.
Sources: Expert list, Expert Review
Prostate Cancer v0.2 MSH2 Chirag Patel gene: MSH2 was added
gene: MSH2 was added to Prostate Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: MSH2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: MSH2 were set to Prostate cancer, MONDO:0008315; Lynch syndrome 1, MONDO:0007356; Mismatch repair cancer syndrome 2, MONDO:0030840; Lynch syndrome 1, MIM#120435; Mismatch repair cancer syndrome 2, MIM#619096
Review for gene: MSH2 was set to GREEN
Added comment: ClinGen definitive. Prostate cancers reported in condition.
Sources: Expert list, Expert Review
Prostate Cancer v0.1 MLH1 Chirag Patel gene: MLH1 was added
gene: MLH1 was added to Prostate Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: MLH1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: MLH1 were set to Prostate cancer, MONDO:0008315; Lynch syndrome 2, MONDO:0012249; Mismatch repair cancer syndrome 1, MONDO:0010159; Lynch syndrome 2, MIM#609310; Mismatch repair cancer syndrome 1, MIM#276300
Review for gene: MLH1 was set to GREEN
Added comment: ClinGen definitive. Prostate cancers reported in condition.
Sources: Expert list, Expert Review
Paraganglioma_phaeochromocytoma v0.30 EGLN1 Chirag Patel gene: EGLN1 was added
gene: EGLN1 was added to Paraganglioma_phaeochromocytoma. Sources: Expert list,Literature,Expert Review
Mode of inheritance for gene: EGLN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EGLN1 were set to PMID: 19092153, 36013579
Phenotypes for gene: EGLN1 were set to Paraganglioma, MONDO:0000448; Pheochromocytoma, MONDO:0008233; Pheochromocytoma/paraganglioma, susceptibility to, no MIM#; Erythrocytosis, familial, 3, MIM#609820
Review for gene: EGLN1 was set to RED
Added comment: PMID: 19092153
1 patient with erythrocytosis and recurrent paraganglioma with a novel de novo germline EGLN1 gene (PHD2) variant (H374R). There was loss of heterozygosity of PHD2 in the tumour. Wild-type PHD2 caused the dose-related suppression of HIF-α–mediated induction of the reporter gene, whereas the response to the H374R PHD2 mutant was impaired.

PMID: 36013579
1 patient with metastatic pheochromocytoma and chronic myeloid leukaemia (CML) without polycythaemia, and a novel germline EGLN1 gene variant (c.153G>A, p.W51*) inherited from unaffected father. The patient had lower expression of PHD2 and higher levels of HIF2α compared to the healthy adrenal tissues, confirming that PHD2 down-regulation results in HIF2α stabilization.
Sources: Expert list, Literature, Expert Review
Paraganglioma_phaeochromocytoma v0.29 EPAS1 Chirag Patel gene: EPAS1 was added
gene: EPAS1 was added to Paraganglioma_phaeochromocytoma. Sources: Expert list,Expert Review,Literature
Mode of inheritance for gene: EPAS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EPAS1 were set to PMID: 22931260, 23418310, 33300499
Phenotypes for gene: EPAS1 were set to Paraganglioma, MONDO:0000448; Pheochromocytoma, MONDO:0008233; Pheochromocytoma/paraganglioma, susceptibility to, no MIM#; Erythrocytosis, familial, 4, MIM#611783
Review for gene: EPAS1 was set to RED
Added comment: PMID: 22931260
2 somatic gain-of-function variants in EPAS1 gene encoding hypoxia-inducible factor 2α (HIF2A) in two patients (1 x paraganglioma, 1 x paraganglioma + somatostatinoma). Both patients had polycythemia (congenital erythrocytosis). The two variants were associated with increased HIF-2α activity and increased protein half-life.

PMID: 23418310
7 patients with somatic variants in EPAS1 gene (4 x multiple PGLs, 3 x single sporadic PCC/PGL). Gene expression analysis of EPAS1-mutated tumours revealed similar mRNA EPAS1 levels to those found in SDH-gene- and VHL-mutated cases and a significant up-regulation of two hypoxia-induced genes (PCSK6 and GNA14). Multiplex-PCR screening for small rearrangements detected a specific EPAS1 gain in another EPAS1-mutated tumour and in 3 non-EPAS1-mutated cases.

PMID: 33300499
6 germline missense variants in EPAS1 gene in patients with PPGL (Arg247Ser, Phe374Tyr, His194Arg, Pro785Thr, Ile789Val, Thr766Pro). In transient transfection studies, EPAS1/HIF-2α Arg247Ser, Phe374Tyr and Pro785Thr were all stable in normoxia. In co-immunoprecipitation assays, only the Arg247Ser variant showed diminished interaction with pVHL. A direct interaction between HIF-2α Arg247 and pVHL was confirmed in structural models. Transactivation was assessed by means of a HRE-containing reporter gene in transiently transfected cells, and significantly higher reporter activity was only observed with EPAS1/HIF-2α Phe374Tyr and Pro785Thr. In conclusion, three germline EPAS1 variants (c.739C>A (p.Arg247Ser), c.1121T>A (p.Phe374Tyr) and c.2353C>A (p.Pro785Thr)) all have some functional features in common with somatic activating mutations. Their findings suggest that these three germline variants are hypermorphic alleles that may act as modifiers to the expression of PPGLs.
Sources: Expert list, Expert Review, Literature
Paraganglioma_phaeochromocytoma v0.28 MDH2 Chirag Patel gene: MDH2 was added
gene: MDH2 was added to Paraganglioma_phaeochromocytoma. Sources: Expert list,Expert Review,Literature
Mode of inheritance for gene: MDH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MDH2 were set to PMID: 25766404, 30008476
Phenotypes for gene: MDH2 were set to Paraganglioma, MONDO:0000448; Pheochromocytoma, MONDO:0008233; Pheochromocytoma/paraganglioma, susceptibility to, no MIM#; Developmental and epileptic encephalopathy 51, MIM#617339
Review for gene: MDH2 was set to RED
Added comment: PMID: 25766404
WES of tumour in 1 patient with multiple malignant paragangliomas identified a germline splice variant in MDH2 (c.429+1G>T)(variant confirmed in blood). Sanger sequencing of the 4 available primary tumours from the patient revealed loss of the MDH2 wild-type allele in two tumours, indicating loss of heterozygosity. MDH2 mRNA expression analysis revealed 6-14 fold lower levels of MDH2 expression in the four tumors carrying the variant compared with control patients. Substantially lower levels of MDH2 protein were detected in the MDH2-related tumours compared with control patients. Knockdown (KD) of MDH2 in HeLa cells by shRNA triggered the accumulation of both malate and fumarate, which was reversed by transient introduction of WT MDH2 cDNA. Segregation testing found the variant in 2 out of 5 asymptomatic relatives. MDH2 mRNA and protein expression in blood cells were statistically significantly lower in the two carriers compared with control patients. Subsequent clinical testing detected high levels of normetanephrine for one of the carriers, thus confirming the presence of the disease.

PMID: 30008476
Sequencing of MDH2 in 830 patients with PPGLs (negative for the main PPGL driver genes), identified 5 germline variants with potential involvement in pathogenicity (3 x missense, 1 x in-frame deletion, 1 x splice-site). None of the variants was associated with an altered MDH2 localization, or mitochondrial quantity and morphology. LOH was not detected in any of the tumours carrying the missense variants, but was seen in the patient with the inframe deletion.
Sources: Expert list, Expert Review, Literature
Paraganglioma_phaeochromocytoma v0.27 PRKAR1A Chirag Patel gene: PRKAR1A was added
gene: PRKAR1A was added to Paraganglioma_phaeochromocytoma. Sources: Expert list,Expert Review,Literature
Mode of inheritance for gene: PRKAR1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PRKAR1A were set to Paraganglioma, MONDO:0000448; Pheochromocytoma, MONDO:0008233; Carney complex, type 1, MIM#160980
Review for gene: PRKAR1A was set to RED
Added comment: ClinGen definitive. BUT paragangliomas and phaeochromocytomas not classically reported in condition.
Sources: Expert list, Expert Review, Literature
Paraganglioma_phaeochromocytoma v0.26 SLC25A11 Chirag Patel gene: SLC25A11 was added
gene: SLC25A11 was added to Paraganglioma_phaeochromocytoma. Sources: Expert list,Expert Review,Literature
Mode of inheritance for gene: SLC25A11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC25A11 were set to PMID: 29431636
Phenotypes for gene: SLC25A11 were set to Paragangliomas 6, MONDO:0032767; Pheochromocytoma, MONDO:0008233; Hereditary pheochromocytoma-paraganglioma, MONDO:0017366; Pheochromocytoma/paraganglioma syndrome 6, MIM#618464
Review for gene: SLC25A11 was set to RED
Added comment: 7 patients with paraganglioma with germline variants in the SLC25A11 gene. The variants were missense, splice site, frameshift, and silent change. The variants were not found in dbSNP or ExAC databases. The missense variants affected highly conserved residues in the signature protein sequence or alpha matrix helix. The variants were associated with loss of heterozygosity, suggesting that SLC25A11 acts as a tumour suppressor gene. Immunohistochemical studies on the tumour tissue showed absence of the SLC25A11 protein and hypermethylation of DNA and histones compared to controls. Pseudohypoxic and hypermethylator phenotypes comparable with those described in SDHx- and FH-related tumours were observed both in tumours with mutated SLC25A11 and in Slc25a11Δ/Δ immortalized mouse chromaffin knockout cells generated by CRISPR-Cas9 technology.
Sources: Expert list, Expert Review, Literature
Paraganglioma_phaeochromocytoma v0.25 DLST Chirag Patel gene: DLST was added
gene: DLST was added to Paraganglioma_phaeochromocytoma. Sources: Expert list,Expert Review,Literature
Mode of inheritance for gene: DLST was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DLST were set to PMID: 30929736, 33180916
Phenotypes for gene: DLST were set to Paragangliomas 7, MONDO:0032771; Pheochromocytoma, MONDO:0008233; Hereditary pheochromocytoma-paraganglioma, MONDO:0017366; Pheochromocytoma/paraganglioma syndrome 7, MIM#618475
Review for gene: DLST was set to RED
Added comment: PMID: 30929736
4 unrelated patients with pheochromocytomas and paragangliomas with the same germline heterozygous missense variant in DLST gene (G374E). Analysis of tumour tissue available from 3 of the patients showed loss of heterozygosity (LOH) for DLST due to uniparental disomy (UPD) of the paternal chromosome. None of the patients had a family history of the disorder, although 3 probands had asymptomatic family members who carried the mutation, consistent with incomplete penetrance. Knockdown of the DLST gene in human H838 cells resulted in a significant block in carbon flow in the tricarboxylic acid (TCA) cycle, which was rescued by wildtype DLST, but not by the G374E mutant. Many PPGL genes encode proteins involved in the tricarboxylic acid (TCA) cycle. In vitro functional expression studies showed that the G374E mutant had compromised catalytic activity compared to wildtype, resulting in a high alpha-KG/fumarate ratio and accumulation of the oncometabolite 2-hydroxyglutaric acid (2HG), particularly the L-2HG enantiomer. Analysis of patient tumours showed strong immunostaining for DLST as well as a hypermethylated phenotype, categorized in the non-CIMP (CpG island methylator phenotype) cluster, and a pseudohypoxic state with increased expression of HIF3A. The findings indicated that DLST can act as a tumour suppression gene. Heterozygous missense variants in DLST (R231Q, D304N, and Y422C) were found in 3 additional probands, but in vitro functional studies of these 3 other missense variants indicated that they behaved similar to wildtype DLST in the assay used. None of the patients besides those with the G374E variant showed LOH in tumour tissue.

PMID: 30929736
2 unrelated patients with pheochromocytomas and paragangliomas with 2 different germline heterozygous missense variants in DLST gene (Pro384Leu, Gly374Glu). Tumour testing in 1 patient identified a second somatic missense variant in DLST (Thr383Ala). They showed the p.(Pro384Leu) variant, located in the catalytic site of DLST, leads to a dramatic but not complete loss of catalytic activity.
Sources: Expert list, Expert Review, Literature
Paraganglioma_phaeochromocytoma v0.24 FH Chirag Patel Classified gene: FH as Green List (high evidence)
Paraganglioma_phaeochromocytoma v0.24 FH Chirag Patel Gene: fh has been classified as Green List (High Evidence).
Paraganglioma_phaeochromocytoma v0.23 MEN1 Chirag Patel Classified gene: MEN1 as Green List (high evidence)
Paraganglioma_phaeochromocytoma v0.23 MEN1 Chirag Patel Gene: men1 has been classified as Green List (High Evidence).
Paraganglioma_phaeochromocytoma v0.22 NF1 Chirag Patel Classified gene: NF1 as Green List (high evidence)
Paraganglioma_phaeochromocytoma v0.22 NF1 Chirag Patel Gene: nf1 has been classified as Green List (High Evidence).
Paraganglioma_phaeochromocytoma v0.21 RET Chirag Patel Classified gene: RET as Green List (high evidence)
Paraganglioma_phaeochromocytoma v0.21 RET Chirag Patel Gene: ret has been classified as Green List (High Evidence).
Paraganglioma_phaeochromocytoma v0.20 RET Chirag Patel gene: RET was added
gene: RET was added to Paraganglioma_phaeochromocytoma. Sources: Expert list,Expert Review
Mode of inheritance for gene: RET was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RET were set to Paraganglioma, MONDO:0000448; Pheochromocytoma, MONDO:0008233; Multiple endocrine neoplasia type 2A, MONDO:0008234; Multiple endocrine neoplasia type 2B, MONDO:0008082; Multiple endocrine neoplasia, type 2A, MIM#171400; Multiple endocrine neoplasia, type 2B, MIM#162300; Pheochromocytoma, MIM#171300; Medullary thyroid carcinoma, MIM#155240; Pheochromocytoma, susceptibility to, MIM#171300
Mode of pathogenicity for gene: RET was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: RET was set to GREEN
Added comment: ClinGen definitive. Paragangliomas and phaeochromocytomas reported in condition. GOF variants.
Sources: Expert list, Expert Review
Paraganglioma_phaeochromocytoma v0.19 NF1 Chirag Patel gene: NF1 was added
gene: NF1 was added to Paraganglioma_phaeochromocytoma. Sources: Expert list,Expert Review
Mode of inheritance for gene: NF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: NF1 were set to Paraganglioma, MONDO:0000448; Pheochromocytoma, MONDO:0008233; Neurofibromatosis type 1, MONDO:0018975; Neurofibromatosis, type 1, MIM#162200
Review for gene: NF1 was set to GREEN
Added comment: ClinGen definitive. Paragangliomas and phaeochromocytomas reported in condition.

Single gene testing may be more appropriate if clinical features of NF1.
Sources: Expert list, Expert Review
Paraganglioma_phaeochromocytoma v0.18 MEN1 Chirag Patel gene: MEN1 was added
gene: MEN1 was added to Paraganglioma_phaeochromocytoma. Sources: Expert list,Expert Review
Mode of inheritance for gene: MEN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MEN1 were set to Paraganglioma, MONDO:0000448; Pheochromocytoma, MONDO:0008233; Multiple endocrine neoplasia type 1, MONDO:0007540; Multiple endocrine neoplasia, type 1, MIM#131100
Review for gene: MEN1 was set to GREEN
Added comment: ClinGen definitive. Paragangliomas and phaeochromocytomas reported in condition.
Sources: Expert list, Expert Review
Paraganglioma_phaeochromocytoma v0.17 FH Chirag Patel gene: FH was added
gene: FH was added to Paraganglioma_phaeochromocytoma. Sources: Expert list,Expert Review
Mode of inheritance for gene: FH was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FH were set to Paraganglioma, MONDO:0000448; Pheochromocytoma, MONDO:0008233; Hereditary leiomyomatosis and renal cell cancer, MONDO:0007888; Leiomyomatosis and renal cell cancer, MIM#150800
Review for gene: FH was set to GREEN
Added comment: ClinGen definitive. Paragangliomas and phaeochromocytomas reported in condition.
Sources: Expert list, Expert Review
Paraganglioma_phaeochromocytoma v0.16 MAX Chirag Patel Classified gene: MAX as Green List (high evidence)
Paraganglioma_phaeochromocytoma v0.16 MAX Chirag Patel Gene: max has been classified as Green List (High Evidence).
Paraganglioma_phaeochromocytoma v0.15 SDHA Chirag Patel Classified gene: SDHA as Green List (high evidence)
Paraganglioma_phaeochromocytoma v0.15 SDHA Chirag Patel Gene: sdha has been classified as Green List (High Evidence).
Paraganglioma_phaeochromocytoma v0.14 SDHAF2 Chirag Patel Classified gene: SDHAF2 as Green List (high evidence)
Paraganglioma_phaeochromocytoma v0.14 SDHAF2 Chirag Patel Gene: sdhaf2 has been classified as Green List (High Evidence).
Paraganglioma_phaeochromocytoma v0.13 SDHB Chirag Patel Classified gene: SDHB as Green List (high evidence)
Paraganglioma_phaeochromocytoma v0.13 SDHB Chirag Patel Gene: sdhb has been classified as Green List (High Evidence).
Paraganglioma_phaeochromocytoma v0.12 SDHC Chirag Patel Classified gene: SDHC as Green List (high evidence)
Paraganglioma_phaeochromocytoma v0.12 SDHC Chirag Patel Gene: sdhc has been classified as Green List (High Evidence).
Paraganglioma_phaeochromocytoma v0.11 SDHD Chirag Patel Classified gene: SDHD as Green List (high evidence)
Paraganglioma_phaeochromocytoma v0.11 SDHD Chirag Patel Gene: sdhd has been classified as Green List (High Evidence).
Paraganglioma_phaeochromocytoma v0.10 TMEM127 Chirag Patel Classified gene: TMEM127 as Green List (high evidence)
Paraganglioma_phaeochromocytoma v0.10 TMEM127 Chirag Patel Gene: tmem127 has been classified as Green List (High Evidence).
Paraganglioma_phaeochromocytoma v0.9 VHL Chirag Patel Classified gene: VHL as Green List (high evidence)
Paraganglioma_phaeochromocytoma v0.9 VHL Chirag Patel Gene: vhl has been classified as Green List (High Evidence).
Paraganglioma_phaeochromocytoma v0.8 VHL Chirag Patel gene: VHL was added
gene: VHL was added to Paraganglioma_phaeochromocytoma. Sources: Expert list,Expert Review
Mode of inheritance for gene: VHL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: VHL were set to Paraganglioma, MONDO:0000448; Pheochromocytoma, MONDO:0008233; Von Hippel-Lindau disease, MONDO:0008667; von Hippel-Lindau syndrome, MIM#193300; Pheochromocytoma, susceptibility to, MIM#171300
Review for gene: VHL was set to GREEN
Added comment: ClinGen definitive. Paragangliomas and phaeochromocytomas reported in condition.
Sources: Expert list, Expert Review
Paraganglioma_phaeochromocytoma v0.7 TMEM127 Chirag Patel gene: TMEM127 was added
gene: TMEM127 was added to Paraganglioma_phaeochromocytoma. Sources: Expert list,Expert Review
Mode of inheritance for gene: TMEM127 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TMEM127 were set to Paraganglioma, MONDO:0000448; Pheochromocytoma, MONDO:0008233; Hereditary pheochromocytoma-paraganglioma, MONDO:0017366; Pheochromocytoma, susceptibility to, MIM#171300
Review for gene: TMEM127 was set to GREEN
Added comment: ClinGen definitive.
Sources: Expert list, Expert Review
Paraganglioma_phaeochromocytoma v0.6 SDHD Chirag Patel gene: SDHD was added
gene: SDHD was added to Paraganglioma_phaeochromocytoma. Sources: Expert list,Expert Review
Mode of inheritance for gene: SDHD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SDHD were set to Paragangliomas 1, MONDO:0008192; Pheochromocytoma, MONDO:0008233; Hereditary pheochromocytoma-paraganglioma, MONDO:0017366; Pheochromocytoma/paraganglioma syndrome 1, MIM#168000
Review for gene: SDHD was set to GREEN
Added comment: ClinGen definitive.
Sources: Expert list, Expert Review
Paraganglioma_phaeochromocytoma v0.5 SDHC Chirag Patel gene: SDHC was added
gene: SDHC was added to Paraganglioma_phaeochromocytoma. Sources: Expert list,Expert Review
Mode of inheritance for gene: SDHC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SDHC were set to Paragangliomas 3, MONDO:0011544; Pheochromocytoma, MONDO:0008233; Hereditary pheochromocytoma-paraganglioma, MONDO:0017366; Pheochromocytoma/paraganglioma syndrome 3, MIM#605373
Review for gene: SDHC was set to GREEN
Added comment: ClinGen definitive.
Sources: Expert list, Expert Review
Paraganglioma_phaeochromocytoma v0.4 SDHB Chirag Patel gene: SDHB was added
gene: SDHB was added to Paraganglioma_phaeochromocytoma. Sources: Expert list,Expert Review
Mode of inheritance for gene: SDHB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SDHB were set to Paragangliomas 4, MONDO:0007273; Pheochromocytoma, MONDO:0008233; Hereditary pheochromocytoma-paraganglioma, MONDO:0017366; Pheochromocytoma/paraganglioma syndrome 4, MIM#115310
Review for gene: SDHB was set to GREEN
Added comment: ClinGen definitive.
Sources: Expert list, Expert Review
Paraganglioma_phaeochromocytoma v0.3 SDHAF2 Chirag Patel gene: SDHAF2 was added
gene: SDHAF2 was added to Paraganglioma_phaeochromocytoma. Sources: Expert list,Expert Review
Mode of inheritance for gene: SDHAF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SDHAF2 were set to Paragangliomas 2, MONDO:0011121; Pheochromocytoma, MONDO:0008233; Hereditary pheochromocytoma-paraganglioma, MONDO:0017366; Pheochromocytoma/paraganglioma syndrome 2, MIM#601650
Review for gene: SDHAF2 was set to GREEN
Added comment: ClinGen definitive.
Sources: Expert list, Expert Review
Paraganglioma_phaeochromocytoma v0.2 SDHA Chirag Patel gene: SDHA was added
gene: SDHA was added to Paraganglioma_phaeochromocytoma. Sources: Expert list,Expert Review
Mode of inheritance for gene: SDHA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SDHA were set to Paragangliomas 5, MONDO:0013602; Pheochromocytoma, MONDO:0008233; Hereditary pheochromocytoma-paraganglioma, MONDO:0017366; Pheochromocytoma/paraganglioma syndrome 5, MIM#614165
Review for gene: SDHA was set to GREEN
Added comment: ClinGen definitive.
Sources: Expert list, Expert Review
Paraganglioma_phaeochromocytoma v0.1 MAX Chirag Patel gene: MAX was added
gene: MAX was added to Paraganglioma_phaeochromocytoma. Sources: Expert list,Expert Review
Mode of inheritance for gene: MAX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MAX were set to Paraganglioma, MONDO:0000448; Pheochromocytoma, MONDO:0008233; Hereditary pheochromocytoma-paraganglioma, MONDO:0017366; Pheochromocytoma, susceptibility to, MIM#171300
Review for gene: MAX was set to GREEN
Added comment: ClinGen definitive.
Sources: Expert list, Expert Review
Prepair 1000+ v1.322 DYNC2LI1 Lilian Downie Marked gene: DYNC2LI1 as ready
Prepair 1000+ v1.322 DYNC2LI1 Lilian Downie Gene: dync2li1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.322 DYNC2LI1 Lilian Downie Publications for gene: DYNC2LI1 were set to
Prepair 1000+ v1.321 EPCAM Lilian Downie Marked gene: EPCAM as ready
Prepair 1000+ v1.321 EPCAM Lilian Downie Gene: epcam has been classified as Green List (High Evidence).
Prepair 1000+ v1.321 EPCAM Lilian Downie Publications for gene: EPCAM were set to
Prepair 1000+ v1.320 EVC Lilian Downie Marked gene: EVC as ready
Prepair 1000+ v1.320 EVC Lilian Downie Gene: evc has been classified as Green List (High Evidence).
Prepair 1000+ v1.320 EVC Lilian Downie Publications for gene: EVC were set to
Prepair 1000+ v1.319 ERCC2 Lilian Downie Marked gene: ERCC2 as ready
Prepair 1000+ v1.319 ERCC2 Lilian Downie Gene: ercc2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.319 ERCC2 Lilian Downie Phenotypes for gene: ERCC2 were changed from Cerebrooculofacioskeletal syndrome 2, 610756 (3) to Cerebrooculofacioskeletal syndrome 2, MIM# 610756; Trichothiodystrophy 1, photosensitive, MIM# 601675; Xeroderma pigmentosum, group D, MIM# 278730
Prepair 1000+ v1.318 ERCC2 Lilian Downie Publications for gene: ERCC2 were set to
Prepair 1000+ v1.317 ABCD1 Lilian Downie Marked gene: ABCD1 as ready
Prepair 1000+ v1.317 ABCD1 Lilian Downie Gene: abcd1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.317 ABCD1 Lilian Downie Publications for gene: ABCD1 were set to
Prepair 1000+ v1.316 ACOX1 Lilian Downie Marked gene: ACOX1 as ready
Prepair 1000+ v1.316 ACOX1 Lilian Downie Gene: acox1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.316 ACOX1 Lilian Downie Publications for gene: ACOX1 were set to
Prepair 1000+ v1.315 ADAMTS13 Lilian Downie Marked gene: ADAMTS13 as ready
Prepair 1000+ v1.315 ADAMTS13 Lilian Downie Gene: adamts13 has been classified as Green List (High Evidence).
Prepair 1000+ v1.315 ADAMTS13 Lilian Downie Phenotypes for gene: ADAMTS13 were changed from Thrombotic thrombocytopenic purpura, familial, 274150 (3) to Thrombotic thrombocytopenic purpura, hereditary, MIM#274150
Prepair 1000+ v1.314 ADAMTS13 Lilian Downie Publications for gene: ADAMTS13 were set to 16796708; 34702267
Prepair 1000+ v1.313 ADAMTS13 Lilian Downie Publications for gene: ADAMTS13 were set to
Prepair 1000+ v1.312 AIPL1 Lilian Downie Marked gene: AIPL1 as ready
Prepair 1000+ v1.312 AIPL1 Lilian Downie Gene: aipl1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.312 AIPL1 Lilian Downie Phenotypes for gene: AIPL1 were changed from Cone-rod dystrophy, 604393 (3) to Leber congenital amaurosis 4, 604393; Cone-rod dystrophy, 604393; Retinitis pigmentosa, juvenile, 604393
Prepair 1000+ v1.311 AIPL1 Lilian Downie Publications for gene: AIPL1 were set to
Intellectual disability syndromic and non-syndromic v0.6222 IFT172 Sangavi Sivagnanasundram reviewed gene: IFT172: Rating: AMBER; Mode of pathogenicity: None; Publications: 24290075, 26763875; Phenotypes: Bardet-Biedl syndrome MONDO:0015229; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 IFIH1 Sangavi Sivagnanasundram changed review comment from: ID is a prominent feature of this condition in most cases and those affected will likely have severe intellectual and physical disability.

GoF is the mechanism of disease.; to: ID is a prominent feature of this condition in most cases and those affected will likely have severe intellectual and physical disability.

GoF is the mechanism of disease.

Classified as DEFINITIVE by ClinGen's Leukodystrophy and Leukoencephalopathy GCEP on 23/08/2024 - https://search.clinicalgenome.org/CCID:008354
Intellectual disability syndromic and non-syndromic v0.6222 IFIH1 Sangavi Sivagnanasundram reviewed gene: IFIH1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 20301648, 25620204; Phenotypes: IFIH1-related type 1 interferonopathy MONDO:0700262; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6222 ERCC6 Mark Cleghorn reviewed gene: ERCC6: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301516; Phenotypes: Cockayne syndrome type B, Cerebrooculofacioskeletal syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 IDUA Sangavi Sivagnanasundram reviewed gene: IDUA: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301341; Phenotypes: mucopolysaccharidosis type 1 MONDO:0001586; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 IDH2 Sangavi Sivagnanasundram reviewed gene: IDH2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20847235, 35359529; Phenotypes: mitochondrial disease MONDO:0044970; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability syndromic and non-syndromic v0.6222 HTRA2 Sangavi Sivagnanasundram reviewed gene: HTRA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27208207, 27696117, 30114719, 32445293; Phenotypes: 3-methylglutaconic aciduria type 8 MONDO:0044723; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 HSPD1 Sangavi Sivagnanasundram reviewed gene: HSPD1: Rating: AMBER; Mode of pathogenicity: None; Publications: 18571143, 27405012; Phenotypes: Leukodystrophy, hypomyelinating, 4, MIM #612233; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 HSD17B10 Sangavi Sivagnanasundram reviewed gene: HSD17B10: Rating: GREEN; Mode of pathogenicity: None; Publications: 22132097, 17618155; Phenotypes: HSD10 mitochondrial disease MONDO:0010327; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Prepair 1000+ v1.310 ALG11 Lilian Downie Marked gene: ALG11 as ready
Prepair 1000+ v1.310 ALG11 Lilian Downie Gene: alg11 has been classified as Green List (High Evidence).
Prepair 1000+ v1.310 ALG11 Lilian Downie Publications for gene: ALG11 were set to
Prepair 1000+ v1.309 ALG8 Lilian Downie Marked gene: ALG8 as ready
Prepair 1000+ v1.309 ALG8 Lilian Downie Gene: alg8 has been classified as Green List (High Evidence).
Prepair 1000+ v1.309 ALG8 Lilian Downie Publications for gene: ALG8 were set to
Prepair 1000+ v1.308 AP3B2 Lilian Downie Marked gene: AP3B2 as ready
Prepair 1000+ v1.308 AP3B2 Lilian Downie Gene: ap3b2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.308 AP3B2 Lilian Downie Phenotypes for gene: AP3B2 were changed from Epileptic encephalopathy, early infantile, 48, 617276 (3), Autosomal recessive to Developmental and epileptic encephalopathy 48 MIM#617276
Prepair 1000+ v1.307 AP3B2 Lilian Downie Publications for gene: AP3B2 were set to
Prepair 1000+ v1.306 ARPC1B Lilian Downie Marked gene: ARPC1B as ready
Prepair 1000+ v1.306 ARPC1B Lilian Downie Gene: arpc1b has been classified as Green List (High Evidence).
Prepair 1000+ v1.306 ARPC1B Lilian Downie Phenotypes for gene: ARPC1B were changed from Platelet abnormalities with eosinophilia and immune-mediated inflammatory disease, 617718 (3), Autosomal recessive to Immunodeficiency 71 with inflammatory disease and congenital thrombocytopenia MIM#617718
Intellectual disability syndromic and non-syndromic v0.6222 HPD Sangavi Sivagnanasundram reviewed gene: HPD: Rating: AMBER; Mode of pathogenicity: None; Publications: 31537781; Phenotypes: tyrosinemia type III MONDO:0010162; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 HMGCL Sangavi Sivagnanasundram reviewed gene: HMGCL: Rating: AMBER; Mode of pathogenicity: None; Publications: 36771238, 35646072; Phenotypes: 3-hydroxy-3-methylglutaric aciduria MONDO:0009520; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 HLCS Sangavi Sivagnanasundram reviewed gene: HLCS: Rating: GREEN; Mode of pathogenicity: None; Publications: 18974016, 18429047, 12124727; Phenotypes: holocarboxylase synthetase deficiency MONDO:0009666; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 HIBCH Sangavi Sivagnanasundram reviewed gene: HIBCH: Rating: GREEN; Mode of pathogenicity: None; Publications: 24299452, 30847210, 17160907, 26163321, 26026795, 31523596, 32022391, 24299452, 32677093; Phenotypes: 3-hydroxyisobutyryl-CoA hydrolase deficiency MONDO:0009603, Leigh syndrome MONDO:0009723; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 HEXB Sangavi Sivagnanasundram reviewed gene: HEXB: Rating: GREEN; Mode of pathogenicity: None; Publications: 35420740; Phenotypes: Sandhoff disease MONDO:0010006; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 HEXA Sangavi Sivagnanasundram reviewed gene: HEXA: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301397; Phenotypes: Tay-Sachs disease MONDO:0010100; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.305 ARPC1B Lilian Downie Publications for gene: ARPC1B were set to
Heterotaxy v1.32 DNAH6 Seb Lunke reviewed gene: DNAH6: Rating: AMBER; Mode of pathogenicity: None; Publications: 34215651; Phenotypes: situs inversus, MONDO:0010029, transposition of the great arteries, MONDO:0000153; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.2015 DNAH6 Seb Lunke reviewed gene: DNAH6: Rating: AMBER; Mode of pathogenicity: None; Publications: 34215651; Phenotypes: situs inversus, MONDO:0010029, transposition of the great arteries, MONDO:0000153; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6222 HESX1 Sangavi Sivagnanasundram reviewed gene: HESX1: Rating: AMBER; Mode of pathogenicity: None; Publications: 19623216, 30888394; Phenotypes: septooptic dysplasia MONDO:0008428, Pituitary hormone deficiency, combined, 5 MONDO:0013099; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 HEPACAM Sangavi Sivagnanasundram reviewed gene: HEPACAM: Rating: GREEN; Mode of pathogenicity: None; Publications: 21419380, 24202401, 27389245, 31372844, 21419380, 24202401, 27322623; Phenotypes: Megalencephalic leukoencephalopathy with subcortical cysts 2A MONDO:0013490, Megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without intellectual disability MONDO:0013491; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 HCCS Sangavi Sivagnanasundram reviewed gene: HCCS: Rating: AMBER; Mode of pathogenicity: None; Publications: 18950397; Phenotypes: linear skin defects with multiple congenital anomalies 1 (MONDO:0024552); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.6222 HADHA Sangavi Sivagnanasundram reviewed gene: HADHA: Rating: AMBER; Mode of pathogenicity: None; Publications: 36063482; Phenotypes: long chain 3-hydroxyacyl-CoA dehydrogenase deficiency MONDO:0012173; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Repeat Disorders v0.168 SCA_THAP11_CAG Zornitza Stark Phenotypes for STR: SCA_THAP11_CAG were changed from autosomal dominant cerebellar ataxia MONDO:0020380 to Spinocerebellar ataxia 51, MIM# 620947
Repeat Disorders v0.167 SCA_THAP11_CAG Zornitza Stark reviewed STR: SCA_THAP11_CAG: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinocerebellar ataxia 51, MIM# 620947; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v1.268 EXOC3L2 Zornitza Stark Phenotypes for gene: EXOC3L2 were changed from Dandy-Walker malformation, MONDO:0009072; Meckel-Gruber-like syndrome to Brain malformation renal syndrome, MIM# 620943
Fetal anomalies v1.267 EXOC3L2 Zornitza Stark reviewed gene: EXOC3L2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Brain malformation renal syndrome, MIM# 620943; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2015 EXOC3L2 Zornitza Stark Phenotypes for gene: EXOC3L2 were changed from Dandy-Walker malformation, MONDO:0009072; renal dysplasia; bone marrow failure to Brain malformation renal syndrome, MIM# 620943
Mendeliome v1.2014 EXOC3L2 Zornitza Stark edited their review of gene: EXOC3L2: Changed phenotypes: Brain malformation renal syndrome, MIM# 620943
Ciliopathies v1.61 EXOC3L2 Zornitza Stark Phenotypes for gene: EXOC3L2 were changed from Dandy-Walker malformation; renal dysplasia; bone marrow failure to Brain malformation renal syndrome, MIM# 620943
Ciliopathies v1.60 EXOC3L2 Zornitza Stark edited their review of gene: EXOC3L2: Changed phenotypes: Brain malformation renal syndrome, MIM# 620943
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.139 EXOC3L2 Zornitza Stark Phenotypes for gene: EXOC3L2 were changed from Dandy-Walker malformation; renal dysplasia; bone marrow failure to Brain malformation renal syndrome, MIM# 620943
Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic v0.138 EXOC3L2 Zornitza Stark edited their review of gene: EXOC3L2: Changed phenotypes: Brain malformation renal syndrome, MIM# 620943
Mendeliome v1.2014 THAP11 Zornitza Stark Phenotypes for gene: THAP11 were changed from Inborn disorder of cobalamin metabolism and transport, MONDO:0019220, THAP11-related to Methylmalonic aciduria, cblC type-like, MIM# 620940; Inborn disorder of cobalamin metabolism and transport, MONDO:0019220, THAP11-related
Mendeliome v1.2013 THAP11 Zornitza Stark edited their review of gene: THAP11: Changed phenotypes: Methylmalonic aciduria, cblC type-like, MIM# 620940, Inborn disorder of cobalamin metabolism and transport, MONDO:0019220, THAP11-related
Genomic newborn screening: BabyScreen+ v1.115 THAP11 Zornitza Stark Phenotypes for gene: THAP11 were changed from Inborn disorder of cobalamin metabolism and transport, MONDO:0019220, THAP11-related to Methylmalonic aciduria, cblC type-like, MIM# 620940; Inborn disorder of cobalamin metabolism and transport, MONDO:0019220, THAP11-related
Genomic newborn screening: BabyScreen+ v1.114 THAP11 Zornitza Stark reviewed gene: THAP11: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Methylmalonic aciduria, cblC type-like, MIM# 620940, Inborn disorder of cobalamin metabolism and transport, MONDO:0019220, THAP11-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Vitamin metabolism disorders v1.7 THAP11 Zornitza Stark Phenotypes for gene: THAP11 were changed from Methylmalonic aciduria and homocystinuria MONDO:0016826 to Methylmalonic aciduria, cblC type-like, MIM# 620940; Inborn disorder of cobalamin metabolism and transport, MONDO:0019220, THAP11-related
Vitamin metabolism disorders v1.6 THAP11 Zornitza Stark edited their review of gene: THAP11: Changed phenotypes: Methylmalonic aciduria, cblC type-like, MIM# 620940, Inborn disorder of cobalamin metabolism and transport, MONDO:0019220, THAP11-related
Sarcoma soft tissue v0.30 BRCA1 Chirag Patel Classified gene: BRCA1 as Green List (high evidence)
Sarcoma soft tissue v0.30 BRCA1 Chirag Patel Gene: brca1 has been classified as Green List (High Evidence).
Sarcoma soft tissue v0.29 BRCA2 Chirag Patel Classified gene: BRCA2 as Green List (high evidence)
Sarcoma soft tissue v0.29 BRCA2 Chirag Patel Gene: brca2 has been classified as Green List (High Evidence).
Sarcoma soft tissue v0.28 DICER1 Chirag Patel Classified gene: DICER1 as Green List (high evidence)
Sarcoma soft tissue v0.28 DICER1 Chirag Patel Gene: dicer1 has been classified as Green List (High Evidence).
Sarcoma soft tissue v0.27 HRAS Chirag Patel Classified gene: HRAS as Green List (high evidence)
Sarcoma soft tissue v0.27 HRAS Chirag Patel Gene: hras has been classified as Green List (High Evidence).
Sarcoma soft tissue v0.26 NF1 Chirag Patel Classified gene: NF1 as Green List (high evidence)
Sarcoma soft tissue v0.26 NF1 Chirag Patel Gene: nf1 has been classified as Green List (High Evidence).
Sarcoma soft tissue v0.25 RB1 Chirag Patel Classified gene: RB1 as Green List (high evidence)
Sarcoma soft tissue v0.25 RB1 Chirag Patel Gene: rb1 has been classified as Green List (High Evidence).
Sarcoma soft tissue v0.24 SMARCA4 Chirag Patel Classified gene: SMARCA4 as Green List (high evidence)
Sarcoma soft tissue v0.24 SMARCA4 Chirag Patel Gene: smarca4 has been classified as Green List (High Evidence).
Sarcoma soft tissue v0.23 SMARCB1 Chirag Patel Classified gene: SMARCB1 as Green List (high evidence)
Sarcoma soft tissue v0.23 SMARCB1 Chirag Patel Gene: smarcb1 has been classified as Green List (High Evidence).
Sarcoma soft tissue v0.22 TP53 Chirag Patel Classified gene: TP53 as Green List (high evidence)
Sarcoma soft tissue v0.22 TP53 Chirag Patel Gene: tp53 has been classified as Green List (High Evidence).
Sarcoma soft tissue v0.21 TP53 Chirag Patel gene: TP53 was added
gene: TP53 was added to Sarcoma soft tissue. Sources: Expert list,Expert Review
Mode of inheritance for gene: TP53 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TP53 were set to Soft tissue sarcoma, MONDO:0018078; Sarcoma, MONDO:0005089; Li-Fraumeni syndrome, MONDO:0018875; Li-Fraumeni syndrome, MIM#151623
Review for gene: TP53 was set to GREEN
Added comment: ClinGen definitive. Soft-tissue sarcomas reported in condition.

Consider possibility that an identified variant could represent ACE (aberrant clonal expansion), which can be due to clonal haematopoiesis of indeterminate potential (CHIP) or an occult hematologic malignancy, especially in older patients who have undergone prior chemotherapy (PMID: 36040522).
Sources: Expert list, Expert Review
Sarcoma soft tissue v0.20 SMARCB1 Chirag Patel gene: SMARCB1 was added
gene: SMARCB1 was added to Sarcoma soft tissue. Sources: Expert list,Expert Review
Mode of inheritance for gene: SMARCB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SMARCB1 were set to Soft tissue sarcoma, MONDO:0018078; Sarcoma, MONDO:0005089; Rhabdoid tumor predisposition syndrome 1, MONDO:0012252; Rhabdoid tumor predisposition syndrome 1, MIM#609322
Review for gene: SMARCB1 was set to GREEN
Added comment: ClinGen definitive. Soft-tissue sarcomas reported in condition.
Sources: Expert list, Expert Review
Sarcoma soft tissue v0.19 SMARCA4 Chirag Patel gene: SMARCA4 was added
gene: SMARCA4 was added to Sarcoma soft tissue. Sources: Expert list,Expert Review
Mode of inheritance for gene: SMARCA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SMARCA4 were set to Soft tissue sarcoma, MONDO:0018078; Sarcoma, MONDO:0005089; Rhabdoid tumor predisposition syndrome 2, MONDO:0013224; Rhabdoid tumor predisposition syndrome 2, MIM#613325
Review for gene: SMARCA4 was set to GREEN
Added comment: ClinGen definitive. Soft-tissue sarcomas reported in condition.
Sources: Expert list, Expert Review
Sarcoma soft tissue v0.18 RB1 Chirag Patel gene: RB1 was added
gene: RB1 was added to Sarcoma soft tissue. Sources: Expert list,Expert Review
Mode of inheritance for gene: RB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RB1 were set to Soft tissue sarcoma, MONDO:0018078; Sarcoma, MONDO:0005089; Retinoblastoma, MONDO:0008380; Retinoblastoma, MIM#180200
Review for gene: RB1 was set to GREEN
Added comment: ClinGen definitive. Soft-tissue sarcomas reported in condition.
Sources: Expert list, Expert Review
Sarcoma soft tissue v0.17 NF1 Chirag Patel gene: NF1 was added
gene: NF1 was added to Sarcoma soft tissue. Sources: Expert list,Expert Review
Mode of inheritance for gene: NF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: NF1 were set to Soft tissue sarcoma, MONDO:0018078; Sarcoma, MONDO:0005089; Neurofibromatosis type 1, MONDO:0018975; Neurofibromatosis, type 1, MIM#162200
Review for gene: NF1 was set to GREEN
Added comment: ClinGen definitive. Soft-tissue sarcomas reported in condition.

Single gene testing may be more appropriate if clinical features of NF1.
Sources: Expert list, Expert Review
Sarcoma soft tissue v0.16 HRAS Chirag Patel gene: HRAS was added
gene: HRAS was added to Sarcoma soft tissue. Sources: Expert list,Expert Review
Mode of inheritance for gene: HRAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: HRAS were set to Soft tissue sarcoma, MONDO:0018078; Sarcoma, MONDO:0005089; Costello syndrome, MONDO:0009026; Costello syndrome, MIM#218040
Mode of pathogenicity for gene: HRAS was set to Other
Review for gene: HRAS was set to GREEN
Added comment: ClinGen definitive. Soft-tissue sarcomas reported in condition. GOF variants.
Sources: Expert list, Expert Review
Sarcoma soft tissue v0.15 DICER1 Chirag Patel gene: DICER1 was added
gene: DICER1 was added to Sarcoma soft tissue. Sources: Expert list,Expert Review
Mode of inheritance for gene: DICER1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: DICER1 were set to Soft tissue sarcoma, MONDO:0018078; Sarcoma, MONDO:0005089; DICER1-related tumor predisposition, MONDO:0100216; DICER1 syndrome, MIM#601200
Review for gene: DICER1 was set to GREEN
Added comment: ClinGen definitive. Soft-tissue sarcomas reported in condition.
Sources: Expert list, Expert Review
Sarcoma soft tissue v0.14 BRCA2 Chirag Patel gene: BRCA2 was added
gene: BRCA2 was added to Sarcoma soft tissue. Sources: Expert list,Expert Review
Mode of inheritance for gene: BRCA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: BRCA2 were set to Soft tissue sarcoma, MONDO:0018078; Sarcoma, MONDO:0005089; BRCA2-related cancer predisposition, MONDO:0700269; Breast-ovarian cancer, familial, 2, MIM#612555
Review for gene: BRCA2 was set to GREEN
Added comment: ClinGen definitive. Soft-tissue sarcomas reported in condition.
Sources: Expert list, Expert Review
Sarcoma soft tissue v0.13 BRCA1 Chirag Patel gene: BRCA1 was added
gene: BRCA1 was added to Sarcoma soft tissue. Sources: Expert list,Expert Review
Mode of inheritance for gene: BRCA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: BRCA1 were set to Soft tissue sarcoma, MONDO:0018078; Sarcoma, MONDO:0005089; BRCA1-related cancer predisposition, MONDO:0700268; Breast-ovarian cancer, familial, 1, MIM#604370
Review for gene: BRCA1 was set to GREEN
Added comment: ClinGen definitive. Soft-tissue sarcomas reported in condition.
Sources: Expert list, Expert Review
Sarcoma soft tissue v0.12 MLH1 Chirag Patel Classified gene: MLH1 as Green List (high evidence)
Sarcoma soft tissue v0.12 MLH1 Chirag Patel Gene: mlh1 has been classified as Green List (High Evidence).
Sarcoma soft tissue v0.11 MSH2 Chirag Patel Classified gene: MSH2 as Green List (high evidence)
Sarcoma soft tissue v0.11 MSH2 Chirag Patel Gene: msh2 has been classified as Green List (High Evidence).
Sarcoma soft tissue v0.10 MSH6 Chirag Patel Classified gene: MSH6 as Green List (high evidence)
Sarcoma soft tissue v0.10 MSH6 Chirag Patel Gene: msh6 has been classified as Green List (High Evidence).
Sarcoma soft tissue v0.9 NBN Chirag Patel Classified gene: NBN as Green List (high evidence)
Sarcoma soft tissue v0.9 NBN Chirag Patel Gene: nbn has been classified as Green List (High Evidence).
Sarcoma soft tissue v0.8 PMS2 Chirag Patel Classified gene: PMS2 as Green List (high evidence)
Sarcoma soft tissue v0.8 PMS2 Chirag Patel Gene: pms2 has been classified as Green List (High Evidence).
Sarcoma soft tissue v0.7 WRN Chirag Patel Classified gene: WRN as Green List (high evidence)
Sarcoma soft tissue v0.7 WRN Chirag Patel Gene: wrn has been classified as Green List (High Evidence).
Sarcoma soft tissue v0.6 MLH1 Chirag Patel gene: MLH1 was added
gene: MLH1 was added to Sarcoma soft tissue. Sources: Expert list,Expert Review
Mode of inheritance for gene: MLH1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MLH1 were set to Soft tissue sarcoma, MONDO:0018078; Sarcoma, MONDO:0005089; Mismatch repair cancer syndrome 1, MONDO:0010159; Mismatch repair cancer syndrome 1, MIM#276300
Review for gene: MLH1 was set to GREEN
Added comment: ClinGen definitive. Soft-tissue sarcomas reported in condition.
Sources: Expert list, Expert Review
Sarcoma soft tissue v0.5 MSH2 Chirag Patel gene: MSH2 was added
gene: MSH2 was added to Sarcoma soft tissue. Sources: Expert list,Expert Review
Mode of inheritance for gene: MSH2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MSH2 were set to Soft tissue sarcoma, MONDO:0018078; Sarcoma, MONDO:0005089; Mismatch repair cancer syndrome 2, MONDO:0030840; Mismatch repair cancer syndrome 2, MIM#619096
Review for gene: MSH2 was set to GREEN
Added comment: ClinGen definitive. Soft-tissue sarcomas reported in condition.
Sources: Expert list, Expert Review
Sarcoma soft tissue v0.4 MSH6 Chirag Patel gene: MSH6 was added
gene: MSH6 was added to Sarcoma soft tissue. Sources: Expert list,Expert Review
Mode of inheritance for gene: MSH6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MSH6 were set to Soft tissue sarcoma, MONDO:0018078; Sarcoma, MONDO:0005089; Mismatch repair cancer syndrome 3, MONDO:0030841; Mismatch repair cancer syndrome 3, MIM#619097
Review for gene: MSH6 was set to GREEN
Added comment: ClinGen definitive. Soft-tissue sarcomas reported in condition.
Sources: Expert list, Expert Review
Sarcoma soft tissue v0.3 NBN Chirag Patel gene: NBN was added
gene: NBN was added to Sarcoma soft tissue. Sources: Expert list,Expert Review
Mode of inheritance for gene: NBN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NBN were set to Soft tissue sarcoma, MONDO:0018078; Sarcoma, MONDO:0005089; Nijmegen breakage syndrome, MONDO:0009623; Nijmegen breakage syndrome, MIM#251260
Review for gene: NBN was set to GREEN
Added comment: ClinGen definitive. Soft-tissue sarcomas reported in condition.
Sources: Expert list, Expert Review
Sarcoma soft tissue v0.2 PMS2 Chirag Patel gene: PMS2 was added
gene: PMS2 was added to Sarcoma soft tissue. Sources: Expert list,Expert Review
Mode of inheritance for gene: PMS2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PMS2 were set to Soft tissue sarcoma, MONDO:0018078; Sarcoma, MONDO:0005089; Mismatch repair cancer syndrome 4, MONDO:0030843; Mismatch repair cancer syndrome 4, MIM#619101
Review for gene: PMS2 was set to GREEN
Added comment: ClinGen definitive. Soft-tissue sarcomas reported in condition.

Note: there is a high level of homology between PMS2 and pseudogenes
Sources: Expert list, Expert Review
Sarcoma soft tissue v0.1 WRN Chirag Patel gene: WRN was added
gene: WRN was added to Sarcoma soft tissue. Sources: Expert list,Expert Review
Mode of inheritance for gene: WRN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WRN were set to Soft tissue sarcoma, MONDO:0018078; Sarcoma, MONDO:0005089; Werner syndrome, MONDO:0010196; Werner syndrome, MIM#277700
Review for gene: WRN was set to GREEN
Added comment: ClinGen definitive. Soft-tissue sarcomas reported in condition.
Sources: Expert list, Expert Review
Sarcoma non-soft tissue v0.15 TP53 Chirag Patel Classified gene: TP53 as Green List (high evidence)
Sarcoma non-soft tissue v0.15 TP53 Chirag Patel Gene: tp53 has been classified as Green List (High Evidence).
Sarcoma non-soft tissue v0.14 RB1 Chirag Patel Classified gene: RB1 as Green List (high evidence)
Sarcoma non-soft tissue v0.14 RB1 Chirag Patel Gene: rb1 has been classified as Green List (High Evidence).
Sarcoma non-soft tissue v0.13 EXT2 Chirag Patel Classified gene: EXT2 as Green List (high evidence)
Sarcoma non-soft tissue v0.13 EXT2 Chirag Patel Gene: ext2 has been classified as Green List (High Evidence).
Sarcoma non-soft tissue v0.12 EXT1 Chirag Patel Classified gene: EXT1 as Green List (high evidence)
Sarcoma non-soft tissue v0.12 EXT1 Chirag Patel Gene: ext1 has been classified as Green List (High Evidence).
Sarcoma non-soft tissue v0.11 WRN Chirag Patel Classified gene: WRN as Green List (high evidence)
Sarcoma non-soft tissue v0.11 WRN Chirag Patel Gene: wrn has been classified as Green List (High Evidence).
Sarcoma non-soft tissue v0.10 RECQL4 Chirag Patel Classified gene: RECQL4 as Green List (high evidence)
Sarcoma non-soft tissue v0.10 RECQL4 Chirag Patel Gene: recql4 has been classified as Green List (High Evidence).
Sarcoma non-soft tissue v0.9 BLM Chirag Patel Classified gene: BLM as Green List (high evidence)
Sarcoma non-soft tissue v0.9 BLM Chirag Patel Gene: blm has been classified as Green List (High Evidence).
Sarcoma non-soft tissue v0.8 TP53 Chirag Patel gene: TP53 was added
gene: TP53 was added to Sarcoma non-soft tissue. Sources: Expert list,Expert Review
Mode of inheritance for gene: TP53 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TP53 were set to Sarcoma, MONDO:0005089; Li-Fraumeni syndrome, MONDO:0018875; Li-Fraumeni syndrome, MIM#151623
Review for gene: TP53 was set to GREEN
Added comment: ClinGen definitive. Non-soft-tissue sarcomas reported in condition.

Consider possibility that an identified variant could represent ACE (aberrant clonal expansion), which can be due to clonal haematopoiesis of indeterminate potential (CHIP) or an occult hematologic malignancy, especially in older patients who have undergone prior chemotherapy (PMID: 36040522).
Sources: Expert list, Expert Review
Sarcoma non-soft tissue v0.7 RB1 Chirag Patel gene: RB1 was added
gene: RB1 was added to Sarcoma non-soft tissue. Sources: Expert list,Expert Review
Mode of inheritance for gene: RB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RB1 were set to Sarcoma, MONDO:0005089; Retinoblastoma, MONDO:0008380; Retinoblastoma, MIM#180200
Review for gene: RB1 was set to GREEN
Added comment: ClinGen definitive. Non-soft-tissue sarcomas reported in condition.
Sources: Expert list, Expert Review
Sarcoma non-soft tissue v0.6 EXT2 Chirag Patel gene: EXT2 was added
gene: EXT2 was added to Sarcoma non-soft tissue. Sources: Expert list,Expert Review
Mode of inheritance for gene: EXT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: EXT2 were set to Sarcoma, MONDO:0005089; Exostoses, multiple, type 2, MONDO:0007586; Exostoses, multiple, type 2, MIM#133701
Review for gene: EXT2 was set to GREEN
Added comment: ClinGen definitive. Non-soft-tissue sarcomas reported in condition.
Sources: Expert list, Expert Review
Sarcoma non-soft tissue v0.5 EXT1 Chirag Patel gene: EXT1 was added
gene: EXT1 was added to Sarcoma non-soft tissue. Sources: Expert list,Expert Review
Mode of inheritance for gene: EXT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: EXT1 were set to Sarcoma, MONDO:0005089; Exostoses, multiple, type 1, MONDO:0007585; Exostoses, multiple, type 1, MIM#133700
Review for gene: EXT1 was set to GREEN
Added comment: ClinGen definitive. Non-soft-tissue sarcomas reported in condition.
Sources: Expert list, Expert Review
Sarcoma non-soft tissue v0.4 WRN Chirag Patel gene: WRN was added
gene: WRN was added to Sarcoma non-soft tissue. Sources: Expert list,Expert Review
Mode of inheritance for gene: WRN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WRN were set to Sarcoma, MONDO:0005089; Werner syndrome, MONDO:0010196; Werner syndrome, MIM#277700
Review for gene: WRN was set to GREEN
Added comment: ClinGen definitive. Non-soft-tissue sarcomas reported in condition.
Sources: Expert list, Expert Review
Sarcoma non-soft tissue v0.3 RECQL4 Chirag Patel gene: RECQL4 was added
gene: RECQL4 was added to Sarcoma non-soft tissue. Sources: Expert list,Expert Review
Mode of inheritance for gene: RECQL4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RECQL4 were set to Sarcoma, MONDO:0005089; Rothmund-Thomson syndrome type 2, MONDO:0016369; Rothmund-Thomson syndrome, type 2, MIM#268400
Review for gene: RECQL4 was set to GREEN
Added comment: ClinGen definitive. Non-soft-tissue sarcomas reported in condition.
Sources: Expert list, Expert Review
Sarcoma non-soft tissue v0.2 BLM Chirag Patel gene: BLM was added
gene: BLM was added to Sarcoma non-soft tissue. Sources: Expert list,Expert Review
Mode of inheritance for gene: BLM was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: BLM were set to Sarcoma, MONDO:0005089; Bloom syndrome, MONDO:0008876; Bloom syndrome, MIM#210900
Review for gene: BLM was set to GREEN
Added comment: ClinGen definitive. Non-soft-tissue sarcomas reported in condition.
Sources: Expert list, Expert Review
Prepair 1000+ v1.304 ARPC1B Crystle Lee edited their review of gene: ARPC1B: Changed publications: 36708766, 33679784
Prepair 1000+ v1.304 ARPC1B Crystle Lee reviewed gene: ARPC1B: Rating: GREEN; Mode of pathogenicity: None; Publications: 36708766; Phenotypes: Immunodeficiency 71 with inflammatory disease and congenital thrombocytopenia, MIM#617718; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 GTF2H5 Sangavi Sivagnanasundram reviewed gene: GTF2H5: Rating: AMBER; Mode of pathogenicity: None; Publications: 30359777, 24986372; Phenotypes: Trichothiodystrophy 3, photosensitive MIM#616395; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.304 AP3B2 Crystle Lee reviewed gene: AP3B2: Rating: GREEN; Mode of pathogenicity: None; Publications: 27889060; Phenotypes: Developmental and epileptic encephalopathy 48, MIM#617276; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 GRM1 Sangavi Sivagnanasundram reviewed gene: GRM1: Rating: AMBER; Mode of pathogenicity: None; Publications: 26308914, 22901947, 31319223, 36675067; Phenotypes: autosomal recessive spinocerebellar ataxia 13 MONDO:0013905; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 GNS Sangavi Sivagnanasundram reviewed gene: GNS: Rating: GREEN; Mode of pathogenicity: None; Publications: 31536183, 25851924, 17998446, 6450420; Phenotypes: mucopolysaccharidosis type 3D MONDO:0009658; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 GNPTAB Sangavi Sivagnanasundram reviewed gene: GNPTAB: Rating: ; Mode of pathogenicity: None; Publications: 20301728; Phenotypes: GNPTAB-mucolipidosis MONDO:0100122; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 GNPAT Sangavi Sivagnanasundram reviewed gene: GNPAT: Rating: GREEN; Mode of pathogenicity: None; Publications: 9843043, 19270340, 21990100; Phenotypes: glyceronephosphate O-acyltransferase deficiency MONDO:0100273; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.304 ALG8 Crystle Lee reviewed gene: ALG8: Rating: GREEN; Mode of pathogenicity: None; Publications: 35716054, 36574950; Phenotypes: Congenital disorder of glycosylation, type Ih, MIM#608104; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 GMPPB Sangavi Sivagnanasundram reviewed gene: GMPPB: Rating: GREEN; Mode of pathogenicity: None; Publications: 23768512, 26133662, 27147698; Phenotypes: myopathy caused by variation in GMPPB MONDO:0700084; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 GMPPA Sangavi Sivagnanasundram reviewed gene: GMPPA: Rating: GREEN; Mode of pathogenicity: None; Publications: 31898852, 35607266; Phenotypes: alacrima, achalasia, and intellectual disability syndrome MONDO:0014219; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.304 ALG11 Crystle Lee reviewed gene: ALG11: Rating: GREEN; Mode of pathogenicity: None; Publications: 36843332, 30676690; Phenotypes: Congenital disorder of glycosylation, type Ip, MIM#613661; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6222 GM2A Sangavi Sivagnanasundram reviewed gene: GM2A: Rating: GREEN; Mode of pathogenicity: None; Publications: 33819415, 20301397; Phenotypes: Tay-Sachs disease AB variant MONDO:0010099; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.304 AIPL1 Crystle Lee changed review comment from: Biallelic AIPL1 variants are associated with a spectrum of inherited retinal disease, ranging from severe Leber congenital amaurosis (LCA) to later onset retinitis pigmentosa (RP). Heterozygotes present with a milder, later onset cone rod dystrophy and RP.

LCA is a congenital-onset, rapid and progressive disease leading to severe vision impariment and/or loss of vision.; to: Biallelic AIPL1 variants are associated with a spectrum of inherited retinal disease, ranging from severe Leber congenital amaurosis (LCA) to later onset retinitis pigmentosa (RP). Heterozygotes present with a milder, later onset cone rod dystrophy and RP.

LCA is a congenital-onset, rapid and progressive disease leading to severe vision impairment and/or loss of vision.
Prepair 1000+ v1.304 AIPL1 Crystle Lee reviewed gene: AIPL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33067476; Phenotypes: Leber congenital amaurosis 4, 604393, Cone-rod dystrophy, 604393, Retinitis pigmentosa, juvenile, 604393; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.304 ADAMTS13 Crystle Lee reviewed gene: ADAMTS13: Rating: GREEN; Mode of pathogenicity: None; Publications: 16796708, 34702267; Phenotypes: Thrombotic thrombocytopenic purpura, hereditary, MIM#274150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.304 ACOX1 Crystle Lee reviewed gene: ACOX1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32169171, 17458872; Phenotypes: Peroxisomal acyl-CoA oxidase deficiency, MIM#264470; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.304 ABCD1 Crystle Lee reviewed gene: ABCD1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35983253; Phenotypes: Adrenoleukodystrophy, MIM#300100; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.304 ERCC2 Ee Ming Wong changed review comment from: - Bi-allelic inactivation of XPD protein, a nucleotide excision repair (NER) signaling pathway component encoded by ERCC2 gene, has been associated with several defective DNA repair phenotypes, including xeroderma pigmentosum, photosensitive trichothiodystrophy, and cerebro-oculo-facio-skeletal syndrome.
- Severe, early onset of all three phenotypes have been reported
- Variable expressivity has been reported for Xeroderma pigmentosum, group D, MIM# 278730 where individuals can present with or without mild or severe neurologic abnormalities (GeneReviews)
- OMIM: The location of variants (mutagenic pattern) is consistent in determining the phenotype. Variants shared by both phenotypes are functionally null alleles, and the second / compound heterozygous variant then determines the phenotype. Changes at p.Arg683 are clearly associated with XP, whereas p.Arg112His, p.Arg722Trp, and changes at p.Arg658 are associated with TTD.; to: - Bi-allelic inactivation of XPD protein, a nucleotide excision repair (NER) signaling pathway component encoded by ERCC2 gene, has been associated with several defective DNA repair phenotypes, including xeroderma pigmentosum, photosensitive trichothiodystrophy, and cerebro-oculo-facio-skeletal syndrome.
- Severe, early onset of all three phenotypes have been reported
- Variable expressivity has been reported for Xeroderma pigmentosum, group D, MIM# 278730 where individuals can present with or without mild or severe neurologic abnormalities (GeneReviews)
- OMIM: The location of variants (mutagenic pattern) is consistent in determining the phenotype. Variants shared by both phenotypes are functionally null alleles, and the second / compound heterozygous variant then determines the phenotype. Changes at p.Arg683 are clearly associated with XP, whereas p.Arg112His, p.Arg722Trp, and changes at p.Arg658 are associated with TTD.
Prepair 1000+ v1.304 EVC Ee Ming Wong reviewed gene: EVC: Rating: GREEN; Mode of pathogenicity: None; Publications: 23220543; Phenotypes: Ellis-van Creveld syndrome, MIM# 225500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.304 ERCC2 Ee Ming Wong reviewed gene: ERCC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 20301571, 32047639, 33369099; Phenotypes: Cerebrooculofacioskeletal syndrome 2, MIM# 610756, Trichothiodystrophy 1, photosensitive, MIM# 601675, Xeroderma pigmentosum, group D, MIM# 278730; Mode of inheritance: None; Current diagnostic: yes
Prepair 1000+ v1.304 EPCAM Ee Ming Wong reviewed gene: EPCAM: Rating: GREEN; Mode of pathogenicity: None; Publications: 24142340; Phenotypes: Diarrhea 5, with tufting enteropathy, congenital, MIM# 613217; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.304 DYNC2LI1 Ee Ming Wong reviewed gene: DYNC2LI1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33030252; Phenotypes: Short-rib thoracic dysplasia 15 with polydactyly (MIM#617088); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v1.267 NME8 Achchuthan Shanmugasundram changed review comment from: The phenotype listed in the review below, namely, CINCA syndrome, OMIM:607115 is associated with NLRP3 gene rather than NME8 in OMIM. The publications listed below (PMIDs: 12032915, 12483741, 12928894) also reports cases with NLRP3 variants (gene alias: CIAS1) rather than NME8 variants. Hence, this gene should be demoted from green rating and NLRP3 should be added to this panel.; to: The phenotype listed in the review below, namely, CINCA syndrome, OMIM:607115 is associated with NLRP3 gene rather than NME8 in OMIM. The publications listed below (PMIDs: 12032915, 12483741, 12928894) also report cases with NLRP3 variants (gene alias: CIAS1) rather than NME8 variants. Hence, this gene should be demoted from green rating and NLRP3 should be added to this panel.
Mendeliome v1.2013 PHKG2 Sangavi Sivagnanasundram reviewed gene: PHKG2: Rating: GREEN; Mode of pathogenicity: None; Publications: 6962066, 8896567, 9384616, 35549678, 24389071, 25266922, 21646031; Phenotypes: glycogen storage disease IXc MONDO:0013091; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2013 PIH1D3 Sangavi Sivagnanasundram reviewed gene: PIH1D3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28041644, 28176794, 32170493, 38051289, 33106461, 38408845, 33635866; Phenotypes: ciliary dyskinesia, primary, 36, X-linked MONDO:0010517; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v1.2013 IFIH1 Sangavi Sivagnanasundram reviewed gene: IFIH1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 24686847, 24995871, 25620204, 30219631, 31898846; Phenotypes: IFIH1-related type 1 interferonopathy MONDO:0700262; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.2013 IRF4 Sangavi Sivagnanasundram reviewed gene: IRF4: Rating: GREEN; Mode of pathogenicity: None; Publications: 36662884, 36917008, 29537367, 29408330; Phenotypes: combined immunodeficiency MONDO:0015131; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.2013 AICDA Sangavi Sivagnanasundram reviewed gene: AICDA: Rating: GREEN; Mode of pathogenicity: None; Publications: 22992148, 12910268, 14564357, 15893695, 32423680, 35570134, 17560278; Phenotypes: hyper-IgM syndrome type 2 MONDO:0011528; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Prepair 1000+ v1.304 PSAT1 Zornitza Stark Marked gene: PSAT1 as ready
Prepair 1000+ v1.304 PSAT1 Zornitza Stark Gene: psat1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.304 PSAT1 Zornitza Stark Phenotypes for gene: PSAT1 were changed from Neu-Laxova syndrome 2, 616038 (3) to Phosphoserine aminotransferase deficiency MIM#610992; Neu-Laxova syndrome 2 MIM#616038
Prepair 1000+ v1.303 PSAT1 Zornitza Stark Publications for gene: PSAT1 were set to
Cerebral Palsy v1.369 TSEN54 Zornitza Stark Marked gene: TSEN54 as ready
Cerebral Palsy v1.369 TSEN54 Zornitza Stark Gene: tsen54 has been classified as Red List (Low Evidence).
Cerebral Palsy v1.369 TSEN54 Zornitza Stark Classified gene: TSEN54 as Red List (low evidence)
Cerebral Palsy v1.369 TSEN54 Zornitza Stark Gene: tsen54 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.6222 DIAPH1 Zornitza Stark Marked gene: DIAPH1 as ready
Intellectual disability syndromic and non-syndromic v0.6222 DIAPH1 Zornitza Stark Gene: diaph1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6222 DIAPH1 Zornitza Stark Phenotypes for gene: DIAPH1 were changed from to progressive microcephaly-seizures-cortical blindness-developmental delay syndrome MONDO:0014714
Intellectual disability syndromic and non-syndromic v0.6221 DIAPH1 Zornitza Stark Publications for gene: DIAPH1 were set to 24781755; 26463574
Intellectual disability syndromic and non-syndromic v0.6220 DIAPH1 Zornitza Stark Publications for gene: DIAPH1 were set to
Intellectual disability syndromic and non-syndromic v0.6220 DIAPH1 Zornitza Stark Mode of inheritance for gene: DIAPH1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6219 DIAPH1 Zornitza Stark reviewed gene: DIAPH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: progressive microcephaly-seizures-cortical blindness-developmental delay syndrome MONDO:0014714; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6219 EIF2AK3 Ken Lee Wan reviewed gene: EIF2AK3: Rating: GREEN; Mode of pathogenicity: None; Publications: 20202148; Phenotypes: Wolcott-Rallison syndrome MONDO:0009192; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6219 DYNC1H1 Zornitza Stark Marked gene: DYNC1H1 as ready
Intellectual disability syndromic and non-syndromic v0.6219 DYNC1H1 Zornitza Stark Gene: dync1h1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6219 DYNC1H1 Zornitza Stark Phenotypes for gene: DYNC1H1 were changed from to dyneinopathy MONDO:1040031
Intellectual disability syndromic and non-syndromic v0.6218 DYNC1H1 Zornitza Stark Mode of inheritance for gene: DYNC1H1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pancreatic Cancer v0.24 TP53 Zornitza Stark Marked gene: TP53 as ready
Pancreatic Cancer v0.24 TP53 Zornitza Stark Gene: tp53 has been classified as Green List (High Evidence).
Pancreatic Cancer v0.24 STK11 Zornitza Stark Marked gene: STK11 as ready
Pancreatic Cancer v0.24 STK11 Zornitza Stark Gene: stk11 has been classified as Green List (High Evidence).
Pancreatic Cancer v0.24 PMS2 Zornitza Stark Marked gene: PMS2 as ready
Pancreatic Cancer v0.24 PMS2 Zornitza Stark Gene: pms2 has been classified as Green List (High Evidence).
Pancreatic Cancer v0.24 PALB2 Zornitza Stark Marked gene: PALB2 as ready
Pancreatic Cancer v0.24 PALB2 Zornitza Stark Gene: palb2 has been classified as Green List (High Evidence).
Pancreatic Cancer v0.24 MSH6 Zornitza Stark Marked gene: MSH6 as ready
Pancreatic Cancer v0.24 MSH6 Zornitza Stark Gene: msh6 has been classified as Green List (High Evidence).
Pancreatic Cancer v0.24 MSH2 Zornitza Stark Marked gene: MSH2 as ready
Pancreatic Cancer v0.24 MSH2 Zornitza Stark Gene: msh2 has been classified as Green List (High Evidence).
Pancreatic Cancer v0.24 MLH1 Zornitza Stark Marked gene: MLH1 as ready
Pancreatic Cancer v0.24 MLH1 Zornitza Stark Gene: mlh1 has been classified as Green List (High Evidence).
Pancreatic Cancer v0.24 EPCAM Zornitza Stark Marked gene: EPCAM as ready
Pancreatic Cancer v0.24 EPCAM Zornitza Stark Gene: epcam has been classified as Green List (High Evidence).
Pancreatic Cancer v0.24 CDKN2A Zornitza Stark Marked gene: CDKN2A as ready
Pancreatic Cancer v0.24 CDKN2A Zornitza Stark Gene: cdkn2a has been classified as Green List (High Evidence).
Pancreatic Cancer v0.24 BRCA2 Zornitza Stark Marked gene: BRCA2 as ready
Pancreatic Cancer v0.24 BRCA2 Zornitza Stark Gene: brca2 has been classified as Green List (High Evidence).
Pancreatic Cancer v0.24 BRCA1 Zornitza Stark Marked gene: BRCA1 as ready
Pancreatic Cancer v0.24 BRCA1 Zornitza Stark Gene: brca1 has been classified as Green List (High Evidence).
Pancreatic Cancer v0.24 ATM Zornitza Stark Marked gene: ATM as ready
Pancreatic Cancer v0.24 ATM Zornitza Stark Gene: atm has been classified as Green List (High Evidence).
Prepair 1000+ v1.302 GMPPA Zornitza Stark Marked gene: GMPPA as ready
Prepair 1000+ v1.302 GMPPA Zornitza Stark Gene: gmppa has been classified as Green List (High Evidence).
Prepair 1000+ v1.302 GMPPA Zornitza Stark Phenotypes for gene: GMPPA were changed from Alacrima, achalasia, and mental retardation syndrome, 615510 (3) to Alacrima, achalasia, and impaired intellectual development syndrome (MIM#615510)
Prepair 1000+ v1.301 GMPPA Zornitza Stark Publications for gene: GMPPA were set to
Prepair 1000+ v1.300 GMPPB Zornitza Stark Marked gene: GMPPB as ready
Prepair 1000+ v1.300 GMPPB Zornitza Stark Gene: gmppb has been classified as Green List (High Evidence).
Prepair 1000+ v1.300 GMPPB Zornitza Stark Phenotypes for gene: GMPPB were changed from Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14, 615352 (3) to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 615350; Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 14 615351; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 615352
Prepair 1000+ v1.299 GMPPB Zornitza Stark Publications for gene: GMPPB were set to
Prepair 1000+ v1.298 GMPPB Zornitza Stark reviewed gene: GMPPB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 615350, Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 14 615351, Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 615352; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.298 LCAT Zornitza Stark Marked gene: LCAT as ready
Prepair 1000+ v1.298 LCAT Zornitza Stark Gene: lcat has been classified as Green List (High Evidence).
Prepair 1000+ v1.298 LCAT Zornitza Stark Phenotypes for gene: LCAT were changed from Norum disease, 245900 (3) to Norum disease, MIM#245900; Fish-eye disease, MIM# 136120
Prepair 1000+ v1.297 LCAT Zornitza Stark Publications for gene: LCAT were set to
Prepair 1000+ v1.296 LCAT Zornitza Stark Tag for review tag was added to gene: LCAT.
Prepair 1000+ v1.296 LCAT Zornitza Stark reviewed gene: LCAT: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Fish-eye disease, MIM# 136120; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6217 DYNC1H1 Ken Lee Wan changed review comment from: DYNC1H1 is definitively associated with autosomal dominant dyneinopathy.

A spectrum of diseases related to monoallelic variants in DYNC1H1 and characterized by variable neuromuscular and/or neurodevelopmental presentations.

DYNC1H1 have been reported with a predominantly neuromuscular presentation, including congenital myopathy, spinal muscular atrophy, Charcot-Marie-Tooth (CMT) and less frequently, intellectual disability and autism.

(https://search.clinicalgenome.org/CCID:004713) (http://purl.obolibrary.org/obo/MONDO_1040031) (OMIM: 600112); to: DYNC1H1 is definitively associated with autosomal dominant dyneinopathy.

A spectrum of diseases related to monoallelic variants in DYNC1H1 and characterized by variable neuromuscular and/or neurodevelopmental presentations.

DYNC1H1 have been reported with a predominantly neuromuscular presentation, including congenital myopathy, spinal muscular atrophy, Charcot-Marie-Tooth (CMT) and less frequently, intellectual disability and autism.

Mechanism of disease: gain of function
(https://search.clinicalgenome.org/CCID:004713) (http://purl.obolibrary.org/obo/MONDO_1040031) (OMIM: 600112)
Prepair 1000+ v1.296 ZMYND10 Zornitza Stark Marked gene: ZMYND10 as ready
Prepair 1000+ v1.296 ZMYND10 Zornitza Stark Gene: zmynd10 has been classified as Green List (High Evidence).
Prepair 1000+ v1.296 ZMYND10 Zornitza Stark Phenotypes for gene: ZMYND10 were changed from Ciliary dyskinesia, primary, 22, 615444 (3) to Ciliary dyskinesia, primary, 22 (MIM#615444)
Prepair 1000+ v1.295 ZMYND10 Zornitza Stark Publications for gene: ZMYND10 were set to
Prepair 1000+ v1.294 MRE11 Zornitza Stark Marked gene: MRE11 as ready
Prepair 1000+ v1.294 MRE11 Zornitza Stark Gene: mre11 has been classified as Green List (High Evidence).
Prepair 1000+ v1.294 MRE11 Zornitza Stark Publications for gene: MRE11 were set to
Prepair 1000+ v1.293 ALDH18A1 Zornitza Stark Marked gene: ALDH18A1 as ready
Prepair 1000+ v1.293 ALDH18A1 Zornitza Stark Gene: aldh18a1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.293 ALDH18A1 Zornitza Stark Phenotypes for gene: ALDH18A1 were changed from Spastic paraplegia 9B, autosomal recessive, 616586 (3) to Cutis laxa, autosomal recessive, type IIIA (MIM#219150); Spastic paraplegia 9B, autosomal recessive (MIM#616586)
Prepair 1000+ v1.292 ALDH18A1 Zornitza Stark Publications for gene: ALDH18A1 were set to
Prepair 1000+ v1.291 ALDH1A3 Zornitza Stark Marked gene: ALDH1A3 as ready
Prepair 1000+ v1.291 ALDH1A3 Zornitza Stark Gene: aldh1a3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.291 ALDH1A3 Zornitza Stark Publications for gene: ALDH1A3 were set to
Prepair 1000+ v1.290 AP1S2 Zornitza Stark Marked gene: AP1S2 as ready
Prepair 1000+ v1.290 AP1S2 Zornitza Stark Gene: ap1s2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.290 AP1S2 Zornitza Stark Publications for gene: AP1S2 were set to
Intellectual disability syndromic and non-syndromic v0.6217 DIS3L2 Zornitza Stark Marked gene: DIS3L2 as ready
Intellectual disability syndromic and non-syndromic v0.6217 DIS3L2 Zornitza Stark Gene: dis3l2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6217 DIS3L2 Zornitza Stark Phenotypes for gene: DIS3L2 were changed from to Perlman syndrome MONDO:0009965
Intellectual disability syndromic and non-syndromic v0.6216 DIS3L2 Zornitza Stark Publications for gene: DIS3L2 were set to
Intellectual disability syndromic and non-syndromic v0.6215 DIAPH1 Ken Lee Wan changed review comment from: Seizures, cortical blindness, and microcephaly syndrome (SCBMS) is an autosomal recessive neurodevelopmental disorder characterized by microcephaly, early-onset seizures, severely delayed psychomotor development, and cortical blindness. Affected individuals also tend to show poor overall growth with short stature (MIM: 616632).

Biallelic loss-of-function DIAPH1 variants have been reported in 3 Middle Eastern consanguineous families with a unique syndrome of early onset seizures, progressive microcephaly, intellectual disability and severe visual impairment (PMIDs: 24781755; 26463574). Western blot analysis showed lack of the mDia1 protein for affected individuals (PMID: 24781755).; to: Seizures, cortical blindness, and microcephaly syndrome (SCBMS) is an autosomal recessive neurodevelopmental disorder characterized by microcephaly, early-onset seizures, severely delayed psychomotor development and cortical blindness. Affected individuals also tend to show poor overall growth with short stature (MIM: 616632).

Biallelic loss-of-function DIAPH1 variants have been reported in 3 Middle Eastern consanguineous families with a unique syndrome of early onset seizures, progressive microcephaly, intellectual disability and severe visual impairment (PMIDs: 24781755; 26463574). Western blot analysis showed lack of the mDia1 protein for affected individuals (PMID: 24781755).
Intellectual disability syndromic and non-syndromic v0.6215 DIS3L2 Zornitza Stark Mode of inheritance for gene: DIS3L2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6214 DNMT3B Ken Lee Wan changed review comment from: DNMT3B is a well-established gene disease association with autosomal recessive immunodeficiency-centromeric instability-facial anomalies syndrome 1 (https://search.clinicalgenome.org/CCID:004692).

Immunodeficiency, centromeric instability, and facial dysmorphism (ICF) syndrome is a rare autosomal recessive disease characterized by facial dysmorphism, immunoglobulin deficiency and branching of chromosomes 1, 9, and 16 after phytohemagglutinin (PHA) stimulation of lymphocytes. The most frequent symptoms of the syndrome are facial dysmorphism, intellectual disability, recurrent and prolonged respiratory infections, infections of the skin and digestive system and variable immune deficiency with a constant decrease of IgA (MIM: 242860).

Mechanism of disease: loss of function; to: DNMT3B is a well-established gene disease association with autosomal recessive immunodeficiency-centromeric instability-facial anomalies syndrome 1 (https://search.clinicalgenome.org/CCID:004692).

Immunodeficiency, centromeric instability and facial dysmorphism (ICF) syndrome is a rare autosomal recessive disease characterized by facial dysmorphism, immunoglobulin deficiency and branching of chromosomes 1, 9 and 16 after phytohemagglutinin (PHA) stimulation of lymphocytes. The most frequent symptoms of the syndrome are facial dysmorphism, intellectual disability, recurrent and prolonged respiratory infections, infections of the skin and digestive system and variable immune deficiency with a constant decrease of IgA (MIM: 242860).

Mechanism of disease: loss of function
Intellectual disability syndromic and non-syndromic v0.6214 DYNC1H1 Ken Lee Wan changed review comment from: DYNC1H1 is definitively associated with autosomal dominant dyneinopathy.

A spectrum of diseases related to monoallelic variants in DYNC1H1 and characterized by variable neuromuscular and/or neurodevelopmental presentations.

DYNC1H1 have been reported with a predominantly neuromuscular presentation, including congenital myopathy, spinal muscular atrophy, Charcot-Marie-Tooth (CMT), and less frequently, intellectual disability and autism.

(https://search.clinicalgenome.org/CCID:004713) (http://purl.obolibrary.org/obo/MONDO_1040031) (OMIM: 600112); to: DYNC1H1 is definitively associated with autosomal dominant dyneinopathy.

A spectrum of diseases related to monoallelic variants in DYNC1H1 and characterized by variable neuromuscular and/or neurodevelopmental presentations.

DYNC1H1 have been reported with a predominantly neuromuscular presentation, including congenital myopathy, spinal muscular atrophy, Charcot-Marie-Tooth (CMT) and less frequently, intellectual disability and autism.

(https://search.clinicalgenome.org/CCID:004713) (http://purl.obolibrary.org/obo/MONDO_1040031) (OMIM: 600112)
Intellectual disability syndromic and non-syndromic v0.6214 DYNC1H1 Ken Lee Wan changed review comment from: DYNC1H1 is definitively associated with autosomal dominant dyneinopathy.

A spectrum of diseases related to monoallelic variants in DYNC1H1 and characterized by variable neuromuscular and/or neurodevelopmental presentations.

DYNC1H1 have been reported with a predominantly neuromuscular presentation, including congenital myopathy, spinal muscular atrophy, Charcot-Marie-Tooth (CMT), and less frequently, intellectual disability and autism.

(https://search.clinicalgenome.org/CCID:004713) (http://purl.obolibrary.org/obo/MONDO_1040031) (OMIM#600112); to: DYNC1H1 is definitively associated with autosomal dominant dyneinopathy.

A spectrum of diseases related to monoallelic variants in DYNC1H1 and characterized by variable neuromuscular and/or neurodevelopmental presentations.

DYNC1H1 have been reported with a predominantly neuromuscular presentation, including congenital myopathy, spinal muscular atrophy, Charcot-Marie-Tooth (CMT), and less frequently, intellectual disability and autism.

(https://search.clinicalgenome.org/CCID:004713) (http://purl.obolibrary.org/obo/MONDO_1040031) (OMIM: 600112)
Intellectual disability syndromic and non-syndromic v0.6214 DYNC1H1 Ken Lee Wan reviewed gene: DYNC1H1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: dyneinopathy MONDO:1040031; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6214 DIS3L2 Zornitza Stark Mode of inheritance for gene: DIS3L2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6213 DNAJC19 Zornitza Stark Marked gene: DNAJC19 as ready
Intellectual disability syndromic and non-syndromic v0.6213 DNAJC19 Zornitza Stark Gene: dnajc19 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6213 DNAJC19 Zornitza Stark Phenotypes for gene: DNAJC19 were changed from 3-methylglutaconic aciduria type 5 MONDO:0012435 to 3-methylglutaconic aciduria type 5 MONDO:0012435
Intellectual disability syndromic and non-syndromic v0.6212 DNAJC19 Zornitza Stark Phenotypes for gene: DNAJC19 were changed from to 3-methylglutaconic aciduria type 5 MONDO:0012435
Intellectual disability syndromic and non-syndromic v0.6211 DNAJC19 Zornitza Stark Mode of inheritance for gene: DNAJC19 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6210 DNAJC19 Zornitza Stark Mode of inheritance for gene: DNAJC19 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.289 PSAT1 Lauren Rogers reviewed gene: PSAT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32077105, 17436247, 25152457; Phenotypes: Phosphoserine aminotransferase deficiency MIM#610992, Neu-Laxova syndrome 2 MIM#616038; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.289 PIP5K1C Zornitza Stark Marked gene: PIP5K1C as ready
Prepair 1000+ v1.289 PIP5K1C Zornitza Stark Gene: pip5k1c has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.289 PIP5K1C Zornitza Stark Publications for gene: PIP5K1C were set to
Prepair 1000+ v1.288 PIP5K1C Zornitza Stark Classified gene: PIP5K1C as Amber List (moderate evidence)
Prepair 1000+ v1.288 PIP5K1C Zornitza Stark Gene: pip5k1c has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.287 PIP5K1C Zornitza Stark reviewed gene: PIP5K1C: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Lethal congenital contractural syndrome 3 (MIM#611369); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6209 DNMT3B Zornitza Stark Marked gene: DNMT3B as ready
Intellectual disability syndromic and non-syndromic v0.6209 DNMT3B Zornitza Stark Gene: dnmt3b has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6209 DNMT3B Zornitza Stark Phenotypes for gene: DNMT3B were changed from to immunodeficiency-centromeric instability-facial anomalies syndrome 1 MONDO:0009454
Intellectual disability syndromic and non-syndromic v0.6208 DNMT3B Zornitza Stark Mode of inheritance for gene: DNMT3B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6207 DNMT3B Ken Lee Wan reviewed gene: DNMT3B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: immunodeficiency-centromeric instability-facial anomalies syndrome 1 MONDO:0009454; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.287 PIP5K1C Lauren Rogers reviewed gene: PIP5K1C: Rating: RED; Mode of pathogenicity: None; Publications: 17701898, 38491417; Phenotypes: Lethal congenital contractural syndrome 3 (MIM#611369); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6207 DNAJC19 Ken Lee Wan reviewed gene: DNAJC19: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: 3-methylglutaconic aciduria type 5 MONDO:0012435; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6207 DIS3L2 Ken Lee Wan changed review comment from: Perlman syndrome is a well-established gene-disease association with autosomal recessive Perlman syndrome (https://search.clinicalgenome.org/CCID:004649)

Perlman syndrome (PRLMNS) is an autosomal recessive congenital overgrowth syndrome with similarities to Beckwith-Wiedemann syndrome (BWS; 130650). Affected children are large at birth, are hypotonic and show organomegaly, characteristic facial dysmorphisms, renal anomalies, frequent neurodevelopmental delay and high neonatal mortality. Perlman syndrome is associated with a high risk of Wilms tumour (OMIM: 267000).

PMID 16278893: 6 out of 22 patients have developmental delay

PMID 22306653: 5 surviving patients with at least one loss-of-function variant identified have developmental delay.

PMID 28328139: 1 surviving patient with compound heterozygous (splice site and missense variants) has developmental delay

Mechanism of disease causation: loss of function; to: DIS3L2 is a well-established gene-disease association with autosomal recessive Perlman syndrome (https://search.clinicalgenome.org/CCID:004649)

Perlman syndrome (PRLMNS) is an autosomal recessive congenital overgrowth syndrome with similarities to Beckwith-Wiedemann syndrome (BWS; 130650). Affected children are large at birth, are hypotonic and show organomegaly, characteristic facial dysmorphisms, renal anomalies, frequent neurodevelopmental delay and high neonatal mortality. Perlman syndrome is associated with a high risk of Wilms tumour (OMIM: 267000).

PMID 16278893: 6 out of 22 patients have developmental delay

PMID 22306653: 5 surviving patients with at least one loss-of-function variant identified have developmental delay.

PMID 28328139: 1 surviving patient with compound heterozygous (splice site and missense variants) has developmental delay

Mechanism of disease causation: loss of function
Intellectual disability syndromic and non-syndromic v0.6207 DIS3L2 Ken Lee Wan reviewed gene: DIS3L2: Rating: GREEN; Mode of pathogenicity: None; Publications: 16278893, 22306653, 28328139; Phenotypes: Perlman syndrome MONDO:0009965; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.287 AP1S2 Lauren Rogers reviewed gene: AP1S2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30714330, 23756445, 17186471; Phenotypes: Pettigrew syndrome, MIM# 304340; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.287 ALDH1A3 Lauren Rogers reviewed gene: ALDH1A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 23312594, 30200890; Phenotypes: Microphthalmia, isolated 8 (MIM#615113); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.287 ALDH18A1 Lauren Rogers reviewed gene: ALDH18A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24913064, 18478038, 26026163; Phenotypes: Cutis laxa, autosomal recessive, type IIIA (MIM#219150), Spastic paraplegia 9B, autosomal recessive (MIM#616586); Mode of inheritance: None
Prepair 1000+ v1.287 MRE11 Lauren Rogers reviewed gene: MRE11: Rating: GREEN; Mode of pathogenicity: None; Publications: 10612394, 11371508, 15269180, 22863007, 24332946, 21227757; Phenotypes: Ataxia-telangiectasia-like disorder 1 (MIM#604391); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Speech apraxia v1.27 DIP2C Zornitza Stark Classified gene: DIP2C as Amber List (moderate evidence)
Speech apraxia v1.27 DIP2C Zornitza Stark Gene: dip2c has been classified as Amber List (Moderate Evidence).
Speech apraxia v1.26 Zornitza Stark removed gene:TRIM8 from the panel
Speech apraxia v1.25 Zornitza Stark removed gene:TAB2 from the panel
Speech apraxia v1.24 Zornitza Stark removed gene:SPTBN1 from the panel
Speech apraxia v1.23 Zornitza Stark removed gene:SMARCA2 from the panel
Speech apraxia v1.22 Zornitza Stark removed gene:SLC6A1 from the panel
Speech apraxia v1.21 Zornitza Stark removed gene:SETD5 from the panel
Speech apraxia v1.20 Zornitza Stark removed gene:SETD2 from the panel
Speech apraxia v1.19 Zornitza Stark removed gene:SET from the panel
Speech apraxia v1.18 Zornitza Stark removed gene:SCN8A from the panel
Speech apraxia v1.17 Zornitza Stark removed gene:RAF1 from the panel
Speech apraxia v1.16 Zornitza Stark removed gene:PPP2R5D from the panel
Speech apraxia v1.15 Zornitza Stark removed gene:NSD1 from the panel
Speech apraxia v1.14 Zornitza Stark removed gene:KCND3 from the panel
Speech apraxia v1.13 Zornitza Stark removed gene:GNAI1 from the panel
Speech apraxia v1.12 Zornitza Stark removed gene:FOXP1 from the panel
Speech apraxia v1.11 Zornitza Stark removed gene:FBXW7 from the panel
Speech apraxia v1.10 Zornitza Stark removed gene:EHMT1 from the panel
Speech apraxia v1.9 Zornitza Stark removed gene:CAMTA1 from the panel
Speech apraxia v1.8 Zornitza Stark removed gene:CAMK2A from the panel
Speech apraxia v1.7 Zornitza Stark removed gene:CACNA1A from the panel
Prepair 1000+ v1.287 ZMYND10 Lauren Rogers reviewed gene: ZMYND10: Rating: GREEN; Mode of pathogenicity: None; Publications: 23891471, 23891469; Phenotypes: Ciliary dyskinesia, primary, 22 (MIM#615444); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.287 LCAT Lauren Rogers changed review comment from: Well established gene-disease association.

A disorder of lipoprotein metabolism that causes a typical triad of diffuse corneal opacities, target cell hemolytic anemia, and proteinuria with renal failure.

Onset is generally in adulthood; to: Well established gene-disease association.

A disorder of lipoprotein metabolism that causes a typical triad of diffuse corneal opacities, target cell hemolytic anemia, and proteinuria with renal failure.

Onset/diagnosis is generally in adulthood
Prepair 1000+ v1.287 LCAT Lauren Rogers reviewed gene: LCAT: Rating: AMBER; Mode of pathogenicity: None; Publications: 30720493, 6624548, 34256778; Phenotypes: Norum disease (MIM#245900); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.287 LCAT Lauren Rogers Deleted their review
Prepair 1000+ v1.287 LCAT Lauren Rogers reviewed gene: LCAT: Rating: GREEN; Mode of pathogenicity: None; Publications: 30720493, 6624548; Phenotypes: Norum disease (MIM#245900); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.287 GMPPB Lauren Rogers reviewed gene: GMPPB: Rating: ; Mode of pathogenicity: None; Publications: 36833299; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 615350, Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 14 615351, Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 615352; Mode of inheritance: None
Prepair 1000+ v1.287 GMPPA Lauren Rogers reviewed gene: GMPPA: Rating: GREEN; Mode of pathogenicity: None; Publications: 24035193, 28574218; Phenotypes: Alacrima, achalasia, and impaired intellectual development syndrome (MIM#615510); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pancreatic Cancer v0.24 ATM Chirag Patel changed review comment from: ClinGen definitive. Pancreatic cancer reported in condition.
Sources: Expert list, Expert Review; to: ClinGen definitive. Pancreatic cancer reported in condition.

Consider possibility that an identified variant could represent ACE (aberrant clonal expansion), which can be due to clonal haematopoiesis of indeterminate potential (CHIP) or an occult hematologic malignancy, especially in older patients who have undergone prior chemotherapy (PMID: 36040522).

Sources: Expert list, Expert Review
Pancreatic Cancer v0.24 TP53 Chirag Patel changed review comment from: ClinGen definitive. Pancreatic cancer reported in condition.

Consider possibility that an identified variant could represent ACE (aberrant clonal expansion), which can be due to clonal haematopoiesis of indeterminate potential (CHIP) or an occult hematologic malignancy, especially in older patients who have undergone prior chemotherapy. Genes most commonly associated with ACE include ATM, CHEK2, and TP53 (PMID: 36040522).

Sources: Expert list, Expert Review; to: ClinGen definitive. Pancreatic cancer reported in condition.

Consider possibility that an identified variant could represent ACE (aberrant clonal expansion), which can be due to clonal haematopoiesis of indeterminate potential (CHIP) or an occult hematologic malignancy, especially in older patients who have undergone prior chemotherapy (PMID: 36040522).

Sources: Expert list, Expert Review
Medulloblastoma v0.25 TP53 Chirag Patel changed review comment from: ClinGen definitive. Medulloblastoma reported in condition.

Consider possibility that an identified variant could represent ACE (aberrant clonal expansion), which can be due to clonal haematopoiesis of indeterminate potential (CHIP) or an occult hematologic malignancy, especially in older patients who have undergone prior chemotherapy. Genes most commonly associated with ACE include ATM, CHEK2, and TP53 (PMID: 36040522).; to: ClinGen definitive. Medulloblastoma reported in condition.

Consider possibility that an identified variant could represent ACE (aberrant clonal expansion), which can be due to clonal haematopoiesis of indeterminate potential (CHIP) or an occult hematologic malignancy, especially in older patients who have undergone prior chemotherapy (PMID: 36040522).
Intellectual disability syndromic and non-syndromic v0.6207 DIAPH1 Ken Lee Wan reviewed gene: DIAPH1: Rating: AMBER; Mode of pathogenicity: None; Publications: 24781755, 26463574; Phenotypes: progressive microcephaly-seizures-cortical blindness-developmental delay syndrome MONDO:0014714; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Prepair 1000+ v1.287 GAS8 Lauren Rogers reviewed gene: GAS8: Rating: GREEN; Mode of pathogenicity: None; Publications: 38873586, 26387594, 27120127; Phenotypes: Ciliary dyskinesia, primary, 33 MIM#616726; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pancreatic Cancer v0.24 TP53 Chirag Patel changed review comment from: ClinGen definitive. Pancreatic cancer reported in condition.
Sources: Expert list, Expert Review; to: ClinGen definitive. Pancreatic cancer reported in condition.

Consider possibility that an identified variant could represent ACE (aberrant clonal expansion), which can be due to clonal haematopoiesis of indeterminate potential (CHIP) or an occult hematologic malignancy, especially in older patients who have undergone prior chemotherapy. Genes most commonly associated with ACE include ATM, CHEK2, and TP53 (PMID: 36040522).

Sources: Expert list, Expert Review
Medulloblastoma v0.25 TP53 Chirag Patel changed review comment from: ClinGen definitive. Medulloblastoma reported in condition.; to: ClinGen definitive. Medulloblastoma reported in condition.

Consider possibility that an identified variant could represent ACE (aberrant clonal expansion), which can be due to clonal haematopoiesis of indeterminate potential (CHIP) or an occult hematologic malignancy, especially in older patients who have undergone prior chemotherapy. Genes most commonly associated with ACE include ATM, CHEK2, and TP53 (PMID: 36040522).
Medulloblastoma v0.25 ELP1 Chirag Patel reviewed gene: ELP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32296180, 39184053; Phenotypes: Medulloblastoma, MONDO:0007959, Medulloblastoma predisposition syndrome, MIM#155255; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Medulloblastoma v0.25 GPR161 Chirag Patel reviewed gene: GPR161: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31609649, 39184053; Phenotypes: Medulloblastoma, MONDO:0007959, Medulloblastoma predisposition syndrome, MIM#155255; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Melanoma v0.15 Chirag Patel Panel status changed from public to internal
Medulloblastoma v0.25 Chirag Patel Panel status changed from public to internal
Medulloblastoma v0.24 BRCA2 Chirag Patel Classified gene: BRCA2 as Green List (high evidence)
Medulloblastoma v0.24 BRCA2 Chirag Patel Gene: brca2 has been classified as Green List (High Evidence).
Medulloblastoma v0.23 EPCAM Chirag Patel Classified gene: EPCAM as Green List (high evidence)
Medulloblastoma v0.23 EPCAM Chirag Patel Gene: epcam has been classified as Green List (High Evidence).
Medulloblastoma v0.22 MLH1 Chirag Patel Classified gene: MLH1 as Green List (high evidence)
Medulloblastoma v0.22 MLH1 Chirag Patel Gene: mlh1 has been classified as Green List (High Evidence).
Medulloblastoma v0.21 MSH2 Chirag Patel Classified gene: MSH2 as Green List (high evidence)
Medulloblastoma v0.21 MSH2 Chirag Patel Gene: msh2 has been classified as Green List (High Evidence).
Medulloblastoma v0.20 MSH6 Chirag Patel Classified gene: MSH6 as Green List (high evidence)
Medulloblastoma v0.20 MSH6 Chirag Patel Gene: msh6 has been classified as Green List (High Evidence).
Medulloblastoma v0.19 PMS2 Chirag Patel Classified gene: PMS2 as Green List (high evidence)
Medulloblastoma v0.19 PMS2 Chirag Patel Gene: pms2 has been classified as Green List (High Evidence).
Medulloblastoma v0.18 PMS2 Chirag Patel gene: PMS2 was added
gene: PMS2 was added to Medulloblastoma. Sources: Expert list,Expert Review
Mode of inheritance for gene: PMS2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: PMS2 were set to Medulloblastoma, MONDO:0007959; Lynch syndrome 4, MONDO:0013699; Mismatch repair cancer syndrome 4, MONDO:0030843; Lynch syndrome 4, MIM#614337; Mismatch repair cancer syndrome 4, MIM#619101
Review for gene: PMS2 was set to GREEN
Added comment: ClinGen definitive. Medulloblastoma reported in condition.

Note: there is a high level of homology between PMS2 and pseudogenes.
Sources: Expert list, Expert Review
Medulloblastoma v0.17 MSH6 Chirag Patel gene: MSH6 was added
gene: MSH6 was added to Medulloblastoma. Sources: Expert list,Expert Review
Mode of inheritance for gene: MSH6 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: MSH6 were set to Medulloblastoma, MONDO:0007959; Lynch syndrome 5, MONDO:0013710; Mismatch repair cancer syndrome 3, MONDO:0030841; Lynch syndrome 5, MIM#614350; Mismatch repair cancer syndrome 3, MIM#619097
Review for gene: MSH6 was set to GREEN
Added comment: ClinGen definitive. Medulloblastoma reported in condition.
Sources: Expert list, Expert Review
Medulloblastoma v0.16 MSH2 Chirag Patel gene: MSH2 was added
gene: MSH2 was added to Medulloblastoma. Sources: Expert list,Expert Review
Mode of inheritance for gene: MSH2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: MSH2 were set to Medulloblastoma, MONDO:0007959; Lynch syndrome 1, MONDO:0007356; Mismatch repair cancer syndrome 2, MONDO:0030840; Lynch syndrome 1, MIM#120435; Mismatch repair cancer syndrome 2, MIM#619096
Review for gene: MSH2 was set to GREEN
Added comment: ClinGen definitive. Medulloblastoma reported in condition.
Sources: Expert list, Expert Review
Medulloblastoma v0.15 MLH1 Chirag Patel gene: MLH1 was added
gene: MLH1 was added to Medulloblastoma. Sources: Expert list,Expert Review
Mode of inheritance for gene: MLH1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: MLH1 were set to Medulloblastoma, MONDO:0007959; Lynch syndrome 2, MONDO:0012249; Mismatch repair cancer syndrome 1, MONDO:0010159; Lynch syndrome 2, MIM#609310; Mismatch repair cancer syndrome 1, MIM#276300
Review for gene: MLH1 was set to GREEN
Added comment: ClinGen definitive. Medulloblastoma reported in condition.
Sources: Expert list, Expert Review
Medulloblastoma v0.14 EPCAM Chirag Patel gene: EPCAM was added
gene: EPCAM was added to Medulloblastoma. Sources: Expert list,Expert Review
Mode of inheritance for gene: EPCAM was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: EPCAM were set to Medulloblastoma, MONDO:0007959; Lynch syndrome 8, MONDO:0013196; Lynch syndrome 8, MIM#613244
Review for gene: EPCAM was set to GREEN
Added comment: ClinGen definitive. Medulloblastoma reported in condition.

Deletion of 3’end of EPCAM gene leading to epigenetic silencing of adjacent downstream MSH2 gene.
Sources: Expert list, Expert Review
Medulloblastoma v0.13 BRCA2 Chirag Patel gene: BRCA2 was added
gene: BRCA2 was added to Medulloblastoma. Sources: Expert list,Expert Review
Mode of inheritance for gene: BRCA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: BRCA2 were set to Medulloblastoma, MONDO:0007959; BRCA2-related cancer predisposition, MONDO:0700269; Breast-ovarian cancer, familial, 2, MIM#612555
Review for gene: BRCA2 was set to GREEN
Added comment: ClinGen definitive. Medulloblastoma reported in condition.
Sources: Expert list, Expert Review
Medulloblastoma v0.12 TP53 Chirag Patel reviewed gene: TP53: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Medulloblastoma, MONDO:0007959, Li-Fraumeni syndrome, MONDO:0018875, Li-Fraumeni syndrome, MIM#151623; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Medulloblastoma v0.12 SUFU Chirag Patel reviewed gene: SUFU: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Medulloblastoma, MONDO:0007959, Basal cell nevus syndrome 2, MONDO:0958189, Basal cell nevus syndrome 2, MIM#620343, Meningioma, familial, susceptibility to, MIM#607174, Medulloblastoma predisposition syndrome, MIM#155255; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Medulloblastoma v0.12 PTCH1 Chirag Patel reviewed gene: PTCH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Medulloblastoma, MONDO:0007959, Basal cell nevus syndrome 1, MONDO:0958174, Basal cell nevus syndrome 1, MIM#109400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Medulloblastoma v0.12 APC Chirag Patel reviewed gene: APC: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Medulloblastoma, MONDO:0007959, Familial adenomatous polyposis 1, MONDO:0021056, Adenomatous polyposis coli, MIM#175100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Medulloblastoma v0.12 Chirag Patel Panel status changed from retired to public
Pancreatic Cancer v0.24 ATM Chirag Patel Classified gene: ATM as Green List (high evidence)
Pancreatic Cancer v0.24 ATM Chirag Patel Gene: atm has been classified as Green List (High Evidence).
Pancreatic Cancer v0.23 STK11 Chirag Patel Classified gene: STK11 as Green List (high evidence)
Pancreatic Cancer v0.23 STK11 Chirag Patel Gene: stk11 has been classified as Green List (High Evidence).
Pancreatic Cancer v0.22 TP53 Chirag Patel Classified gene: TP53 as Green List (high evidence)
Pancreatic Cancer v0.22 TP53 Chirag Patel Gene: tp53 has been classified as Green List (High Evidence).
Pancreatic Cancer v0.21 PALB2 Chirag Patel Classified gene: PALB2 as Green List (high evidence)
Pancreatic Cancer v0.21 PALB2 Chirag Patel Gene: palb2 has been classified as Green List (High Evidence).
Pancreatic Cancer v0.20 BRCA1 Chirag Patel Classified gene: BRCA1 as Green List (high evidence)
Pancreatic Cancer v0.20 BRCA1 Chirag Patel Gene: brca1 has been classified as Green List (High Evidence).
Pancreatic Cancer v0.19 BRCA2 Chirag Patel Classified gene: BRCA2 as Green List (high evidence)
Pancreatic Cancer v0.19 BRCA2 Chirag Patel Gene: brca2 has been classified as Green List (High Evidence).
Pancreatic Cancer v0.18 CDKN2A Chirag Patel Classified gene: CDKN2A as Green List (high evidence)
Pancreatic Cancer v0.18 CDKN2A Chirag Patel Gene: cdkn2a has been classified as Green List (High Evidence).
Pancreatic Cancer v0.17 CDKN2A Chirag Patel gene: CDKN2A was added
gene: CDKN2A was added to Pancreatic Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: CDKN2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CDKN2A were set to Malignant pancreatic neoplasm, MONDO:0009831; Melanoma-pancreatic cancer syndrome, MONDO:0011713; Melanoma and neural system tumor syndrome, MONDO:0007967; Melanoma cutaneous malignant susceptibility to 2, MONDO:0007964; Melanoma, cutaneous malignant, 2, MIM#155601; Melanoma-pancreatic cancer syndrome, MIM#606719; Melanoma and neural system tumor syndrome, MIM#155755
Review for gene: CDKN2A was set to GREEN
Added comment: ClinGen definitive. Pancreatic cancer reported in condition
Sources: Expert list, Expert Review
Pancreatic Cancer v0.16 BRCA1 Chirag Patel gene: BRCA1 was added
gene: BRCA1 was added to Pancreatic Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: BRCA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: BRCA1 were set to Malignant pancreatic neoplasm, MONDO:0009831; BRCA1-related cancer predisposition, MONDO:0700268; Breast-ovarian cancer, familial, 1, MIM#604370
Review for gene: BRCA1 was set to GREEN
Added comment: ClinGen definitive. Pancreatic cancer reported in condition.
Sources: Expert list, Expert Review
Pancreatic Cancer v0.15 BRCA2 Chirag Patel gene: BRCA2 was added
gene: BRCA2 was added to Pancreatic Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: BRCA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: BRCA2 were set to Malignant pancreatic neoplasm, MONDO:0009831; BRCA2-related cancer predisposition, MONDO:0700269; Breast-ovarian cancer, familial, 2, MIM#612555
Review for gene: BRCA2 was set to GREEN
Added comment: ClinGen definitive. Pancreatic cancer reported in condition.
Sources: Expert list, Expert Review
Pancreatic Cancer v0.14 PALB2 Chirag Patel gene: PALB2 was added
gene: PALB2 was added to Pancreatic Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: PALB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PALB2 were set to Malignant pancreatic neoplasm, MONDO:0009831; PALB2-related cancer predisposition, MONDO:0700272; Breast-ovarian cancer, familial, susceptibility to, 5, MIM#620442; Pancreatic cancer, susceptibility to, 3, MIM#613348
Review for gene: PALB2 was set to GREEN
Added comment: ClinGen definitive. Pancreatic cancer reported in condition.
Sources: Expert list, Expert Review
Pancreatic Cancer v0.13 TP53 Chirag Patel gene: TP53 was added
gene: TP53 was added to Pancreatic Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: TP53 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TP53 were set to Malignant pancreatic neoplasm, MONDO:0009831; Li-Fraumeni syndrome, MONDO:0018875; Li-Fraumeni syndrome, MIM#151623
Review for gene: TP53 was set to GREEN
Added comment: ClinGen definitive. Pancreatic cancer reported in condition.
Sources: Expert list, Expert Review
Pancreatic Cancer v0.12 STK11 Chirag Patel gene: STK11 was added
gene: STK11 was added to Pancreatic Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: STK11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: STK11 were set to Malignant pancreatic neoplasm, MONDO:0009831; Peutz-Jeghers syndrome, MONDO:0008280; Peutz-Jeghers syndrome, MIM#175200
Review for gene: STK11 was set to GREEN
Added comment: ClinGen definitive. Pancreatic cancer reported in condition.
Single gene testing may be more appropriate if clinical features of JPS.
Sources: Expert list, Expert Review
Pancreatic Cancer v0.11 ATM Chirag Patel gene: ATM was added
gene: ATM was added to Pancreatic Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: ATM was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ATM were set to Malignant pancreatic neoplasm, MONDO:0009831; ATM-related cancer predisposition, MONDO:0700270; Breast cancer, susceptibility to, MIM#114480
Review for gene: ATM was set to GREEN
Added comment: ClinGen definitive. Pancreatic cancer reported in condition.
Sources: Expert list, Expert Review
Pancreatic Cancer v0.10 EPCAM Chirag Patel Classified gene: EPCAM as Green List (high evidence)
Pancreatic Cancer v0.10 EPCAM Chirag Patel Gene: epcam has been classified as Green List (High Evidence).
Pancreatic Cancer v0.9 PMS2 Chirag Patel Classified gene: PMS2 as Green List (high evidence)
Pancreatic Cancer v0.9 PMS2 Chirag Patel Gene: pms2 has been classified as Green List (High Evidence).
Pancreatic Cancer v0.8 MSH6 Chirag Patel Classified gene: MSH6 as Green List (high evidence)
Pancreatic Cancer v0.8 MSH6 Chirag Patel Gene: msh6 has been classified as Green List (High Evidence).
Pancreatic Cancer v0.7 MSH2 Chirag Patel Classified gene: MSH2 as Green List (high evidence)
Pancreatic Cancer v0.7 MSH2 Chirag Patel Gene: msh2 has been classified as Green List (High Evidence).
Pancreatic Cancer v0.6 MLH1 Chirag Patel Classified gene: MLH1 as Green List (high evidence)
Pancreatic Cancer v0.6 MLH1 Chirag Patel Gene: mlh1 has been classified as Green List (High Evidence).
Pancreatic Cancer v0.5 PMS2 Chirag Patel gene: PMS2 was added
gene: PMS2 was added to Pancreatic Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: PMS2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: PMS2 were set to Malignant pancreatic neoplasm, MONDO:0009831; Lynch syndrome 4, MONDO:0013699; Mismatch repair cancer syndrome 4, MONDO:0030843; Lynch syndrome 4, MIM#614337; Mismatch repair cancer syndrome 4, MIM#619101
Review for gene: PMS2 was set to GREEN
Added comment: ClinGen definitive. Pancreatic cancer reported in condition.

Note: there is a high level of homology between PMS2 and pseudogenes.
Sources: Expert list, Expert Review
Pancreatic Cancer v0.4 MSH6 Chirag Patel gene: MSH6 was added
gene: MSH6 was added to Pancreatic Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: MSH6 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: MSH6 were set to Malignant pancreatic neoplasm, MONDO:0009831; Lynch syndrome 5, MONDO:0013710; Mismatch repair cancer syndrome 3, MONDO:0030841; Lynch syndrome 5, MIM#614350; Mismatch repair cancer syndrome 3, MIM#619097
Review for gene: MSH6 was set to GREEN
Added comment: ClinGen definitive. Pancreatic cancer reported in condition.
Sources: Expert list, Expert Review
Pancreatic Cancer v0.3 MSH2 Chirag Patel gene: MSH2 was added
gene: MSH2 was added to Pancreatic Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: MSH2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: MSH2 were set to Malignant pancreatic neoplasm, MONDO:0009831; Lynch syndrome 1, MONDO:0007356; Mismatch repair cancer syndrome 2, MONDO:0030840; Lynch syndrome 1, MIM#120435; Mismatch repair cancer syndrome 2, MIM#619096
Review for gene: MSH2 was set to GREEN
Added comment: ClinGen definitive. Pancreatic cancer reported in condition.
Sources: Expert list, Expert Review
Pancreatic Cancer v0.2 MLH1 Chirag Patel gene: MLH1 was added
gene: MLH1 was added to Pancreatic Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: MLH1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: MLH1 were set to Malignant pancreatic neoplasm, MONDO:0009831; Lynch syndrome 2, MONDO:0012249; Mismatch repair cancer syndrome 1, MONDO:0010159; Lynch syndrome 2, MIM#609310; Mismatch repair cancer syndrome 1, MIM#276300
Review for gene: MLH1 was set to GREEN
Added comment: ClinGen definitive. Pancreatic cancer reported in condition.
Sources: Expert list, Expert Review
Pancreatic Cancer v0.1 EPCAM Chirag Patel gene: EPCAM was added
gene: EPCAM was added to Pancreatic Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: EPCAM was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: EPCAM were set to Malignant pancreatic neoplasm, MONDO:0009831; Lynch syndrome 8, MONDO:0013196; Lynch syndrome 8, MIM#613244
Review for gene: EPCAM was set to GREEN
Added comment: ClinGen definitive. Pancreatic cancer reported in condition.

Deletion of 3’end of EPCAM gene leading to epigenetic silencing of adjacent downstream MSH2 gene.
Sources: Expert list, Expert Review
Parathyroid Tumour v0.13 Chirag Patel Panel name changed from Parathyroid Neoplasm to Parathyroid Cancer
Speech apraxia v1.6 CACNA1A Thomas Scerri Deleted their review
Speech apraxia v1.6 CAMK2A Thomas Scerri Deleted their review
Speech apraxia v1.6 CAMTA1 Thomas Scerri Deleted their review
Speech apraxia v1.6 EHMT1 Thomas Scerri Deleted their review
Speech apraxia v1.6 FBXW7 Thomas Scerri Deleted their review
Speech apraxia v1.6 FOXP1 Thomas Scerri Deleted their review
Speech apraxia v1.6 GNAI1 Thomas Scerri Deleted their review
Speech apraxia v1.6 KCND3 Thomas Scerri Deleted their review
Speech apraxia v1.6 NSD1 Thomas Scerri Deleted their review
Speech apraxia v1.6 PPP2R5D Thomas Scerri Deleted their review
Speech apraxia v1.6 RAF1 Thomas Scerri Deleted their review
Speech apraxia v1.6 SCN8A Thomas Scerri Deleted their review
Speech apraxia v1.6 SET Thomas Scerri Deleted their review
Speech apraxia v1.6 SETD2 Thomas Scerri Deleted their review
Speech apraxia v1.6 SETD5 Thomas Scerri Deleted their review
Speech apraxia v1.6 SLC6A1 Thomas Scerri Deleted their review
Speech apraxia v1.6 SMARCA2 Thomas Scerri Deleted their review
Speech apraxia v1.6 SPTBN1 Thomas Scerri Deleted their review
Speech apraxia v1.6 TAB2 Thomas Scerri Deleted their review
Speech apraxia v1.6 TRIM8 Thomas Scerri Deleted their review
Speech apraxia v1.6 FOXP1 Thomas Scerri changed review comment from: An in-house (as yet unpublished) CAS proband with a pathogenic variant. The proband shows mild CAS.

Another in-house (unpublished) CAS proband with a de novo splice variant that is listed as pathogenic in ClinVar.

Braden et al., (2021; 34109629) examined 29 probands with pathogenic FOXP1 variants, and reported that "All verbal patients had dysarthric and apraxic features, with phonologicaldeficits in most (14 out of 16)."
Sources: Expert list, Expert Review; to: An in-house (as yet unpublished) CAS proband with a pathogenic variant. The proband shows mild CAS.

Another in-house (unpublished) CAS proband with a de novo splice variant that is listed as pathogenic in ClinVar.

Braden et al., (2021; PMID: 34109629) examined 29 probands with pathogenic FOXP1 variants, and reported that "All verbal patients had dysarthric and apraxic features, with phonologicaldeficits in most (14 out of 16)."
Sources: Expert list, Expert Review
Speech apraxia v1.6 FOXP1 Thomas Scerri gene: FOXP1 was added
gene: FOXP1 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: FOXP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXP1 were set to 34109629
Phenotypes for gene: FOXP1 were set to Intellectual developmental disorder with language impairment with or without autistic features, MIM# 613670
Review for gene: FOXP1 was set to GREEN
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant. The proband shows mild CAS.

Another in-house (unpublished) CAS proband with a de novo splice variant that is listed as pathogenic in ClinVar.

Braden et al., (2021; 34109629) examined 29 probands with pathogenic FOXP1 variants, and reported that "All verbal patients had dysarthric and apraxic features, with phonologicaldeficits in most (14 out of 16)."
Sources: Expert list, Expert Review
Speech apraxia v1.6 TRIM8 Thomas Scerri gene: TRIM8 was added
gene: TRIM8 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: TRIM8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TRIM8 were set to Focal segmental glomerulosclerosis and neurodevelopmental syndrome, MIM# 619428
Review for gene: TRIM8 was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.6 TAB2 Thomas Scerri gene: TAB2 was added
gene: TAB2 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: TAB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TAB2 were set to Congenital heart defects, nonsyndromic, 2, MIM# 614980
Review for gene: TAB2 was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.6 SPTBN1 Thomas Scerri gene: SPTBN1 was added
gene: SPTBN1 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: SPTBN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SPTBN1 were set to Developmental delay, impaired speech, and behavioral abnormalities, MIM# 619475
Review for gene: SPTBN1 was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.6 SMARCA2 Thomas Scerri gene: SMARCA2 was added
gene: SMARCA2 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: SMARCA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SMARCA2 were set to Blepharophimosis-impaired intellectual development syndrome, MIM# 619293; Nicolaides-Baraitser syndrome, MIM# 601358
Review for gene: SMARCA2 was set to RED
Added comment: Two in-house (as yet unpublished) CAS probands with pathogenic variants.
Sources: Expert list, Expert Review
Speech apraxia v1.6 SLC6A1 Thomas Scerri gene: SLC6A1 was added
gene: SLC6A1 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: SLC6A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SLC6A1 were set to Myoclonic-atonic epilepsy, MIM# 616421
Review for gene: SLC6A1 was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.6 SETD5 Thomas Scerri gene: SETD5 was added
gene: SETD5 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: SETD5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SETD5 were set to Intellectual developmental disorder, autosomal dominant 23, MIM# 615761
Review for gene: SETD5 was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.6 SETD2 Thomas Scerri gene: SETD2 was added
gene: SETD2 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: SETD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SETD2 were set to Intellectual developmental disorder, autosomal dominant 70, MIM# 620157; Luscan-Lumish syndrome, MIM# 616831; Rabin-Pappas syndrome, MIM# 620155
Review for gene: SETD2 was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.6 SET Thomas Scerri gene: SET was added
gene: SET was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: SET was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SET were set to Intellectual developmental disorder, autosomal dominant 58, MIM# 618106
Review for gene: SET was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.6 SCN8A Thomas Scerri gene: SCN8A was added
gene: SCN8A was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: SCN8A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SCN8A were set to Cognitive impairment with or without cerebellar ataxia, MIM# 614306; Developmental and epileptic encephalopathy 13, MIM# 614558; Seizures, benign familial infantile, 5, MIM# 617080
Review for gene: SCN8A was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.6 RAF1 Thomas Scerri gene: RAF1 was added
gene: RAF1 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: RAF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RAF1 were set to Cardiomyopathy, dilated, 1NN, MIM# 615916; LEOPARD syndrome 2, MIM# 611554; Noonan syndrome 5, MIM# 611553
Review for gene: RAF1 was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.6 PPP2R5D Thomas Scerri gene: PPP2R5D was added
gene: PPP2R5D was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: PPP2R5D was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PPP2R5D were set to Houge-Janssens syndrome 1, MIM# 616355
Review for gene: PPP2R5D was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.6 NSD1 Thomas Scerri gene: NSD1 was added
gene: NSD1 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: NSD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: NSD1 were set to Sotos syndrome, MIM# 117550
Review for gene: NSD1 was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.6 KDM5C Thomas Scerri commented on gene: KDM5C: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Speech apraxia v1.6 KCND3 Thomas Scerri gene: KCND3 was added
gene: KCND3 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: KCND3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: KCND3 were set to Brugada syndrome 9, MIM# 616399; Spinocerebellar ataxia 19, MIM# 607346
Review for gene: KCND3 was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.6 GNAI1 Thomas Scerri gene: GNAI1 was added
gene: GNAI1 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: GNAI1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: GNAI1 were set to Neurodevelopmental disorder with hypotonia, impaired speech, and behavioral abnormalities, MIM# 619854
Review for gene: GNAI1 was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.6 FBXW7 Thomas Scerri gene: FBXW7 was added
gene: FBXW7 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: FBXW7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FBXW7 were set to Developmental delay, hypotonia, and impaired language, MIM# 620012
Review for gene: FBXW7 was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.6 EHMT1 Thomas Scerri gene: EHMT1 was added
gene: EHMT1 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: EHMT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: EHMT1 were set to Kleefstra syndrome 1, MIM# 610253
Review for gene: EHMT1 was set to RED
Added comment: Two in-house (as yet unpublished) CAS probands with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.6 CAMTA1 Thomas Scerri gene: CAMTA1 was added
gene: CAMTA1 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: CAMTA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CAMTA1 were set to Cerebellar dysfunction with variable cognitive and behavioral abnormalities, MIM# 614756
Review for gene: CAMTA1 was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.6 CAMK2A Thomas Scerri gene: CAMK2A was added
gene: CAMK2A was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: CAMK2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CAMK2A were set to Intellectual developmental disorder, autosomal dominant 53, MIM# 617798
Review for gene: CAMK2A was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.6 CACNA1A Thomas Scerri gene: CACNA1A was added
gene: CACNA1A was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: CACNA1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CACNA1A were set to 38712155
Phenotypes for gene: CACNA1A were set to Developmental and epileptic encephalopathy 42, MIM# 617106; Episodic ataxia, type 2, MIM# 108500; Migraine, familial hemiplegic, 1, MIM# 141500; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia, MIM# 141500; Spinocerebellar ataxia 6, MIM# 183086
Review for gene: CACNA1A was set to GREEN
Added comment: Three in-house (as yet unpublished) CAS probands with pathogenic variants.

Magielski et al. (2024; PMID: 38712155) report 1 individual with speech apraxia and a CACNA1C genetic diagnosis.
Sources: Expert list, Expert Review
Parathyroid Tumour v0.12 RET Zornitza Stark Marked gene: RET as ready
Parathyroid Tumour v0.12 RET Zornitza Stark Gene: ret has been classified as Green List (High Evidence).
Parathyroid Tumour v0.12 MEN1 Zornitza Stark Marked gene: MEN1 as ready
Parathyroid Tumour v0.12 MEN1 Zornitza Stark Gene: men1 has been classified as Green List (High Evidence).
Parathyroid Tumour v0.12 GCM2 Zornitza Stark Marked gene: GCM2 as ready
Parathyroid Tumour v0.12 GCM2 Zornitza Stark Gene: gcm2 has been classified as Green List (High Evidence).
Parathyroid Tumour v0.12 CDKN1B Zornitza Stark Marked gene: CDKN1B as ready
Parathyroid Tumour v0.12 CDKN1B Zornitza Stark Gene: cdkn1b has been classified as Green List (High Evidence).
Parathyroid Tumour v0.12 CDC73 Zornitza Stark Marked gene: CDC73 as ready
Parathyroid Tumour v0.12 CDC73 Zornitza Stark Gene: cdc73 has been classified as Green List (High Evidence).
Parathyroid Tumour v0.12 CASR Zornitza Stark Marked gene: CASR as ready
Parathyroid Tumour v0.12 CASR Zornitza Stark Gene: casr has been classified as Green List (High Evidence).
Thyroid Cancer v0.13 Zornitza Stark Panel name changed from Thyroid Neoplasm to Thyroid Cancer
Thyroid Cancer v0.12 RET Zornitza Stark Marked gene: RET as ready
Thyroid Cancer v0.12 RET Zornitza Stark Gene: ret has been classified as Green List (High Evidence).
Thyroid Cancer v0.12 PTEN Zornitza Stark Marked gene: PTEN as ready
Thyroid Cancer v0.12 PTEN Zornitza Stark Gene: pten has been classified as Green List (High Evidence).
Thyroid Cancer v0.12 PRKAR1A Zornitza Stark Marked gene: PRKAR1A as ready
Thyroid Cancer v0.12 PRKAR1A Zornitza Stark Gene: prkar1a has been classified as Green List (High Evidence).
Thyroid Cancer v0.12 DICER1 Zornitza Stark Marked gene: DICER1 as ready
Thyroid Cancer v0.12 DICER1 Zornitza Stark Gene: dicer1 has been classified as Green List (High Evidence).
Thyroid Cancer v0.12 CDKN1B Zornitza Stark Marked gene: CDKN1B as ready
Thyroid Cancer v0.12 CDKN1B Zornitza Stark Gene: cdkn1b has been classified as Green List (High Evidence).
Thyroid Cancer v0.12 APC Zornitza Stark Marked gene: APC as ready
Thyroid Cancer v0.12 APC Zornitza Stark Gene: apc has been classified as Green List (High Evidence).
Speech apraxia v1.6 ANK2 Zornitza Stark Marked gene: ANK2 as ready
Speech apraxia v1.6 ANK2 Zornitza Stark Gene: ank2 has been classified as Red List (Low Evidence).
Speech apraxia v1.6 ANK2 Zornitza Stark Phenotypes for gene: ANK2 were changed from Cardiac arrhythmia, ankyrin-B-relatedNeurodevelopmental disorder (MONDO:0700092), gene-related to Neurodevelopmental disorder (MONDO:0700092), gene-related
Speech apraxia v1.5 ANK2 Zornitza Stark Classified gene: ANK2 as Red List (low evidence)
Speech apraxia v1.5 ANK2 Zornitza Stark Gene: ank2 has been classified as Red List (Low Evidence).
Speech apraxia v1.4 BPTF Zornitza Stark Marked gene: BPTF as ready
Speech apraxia v1.4 BPTF Zornitza Stark Gene: bptf has been classified as Red List (Low Evidence).
Speech apraxia v1.4 BPTF Zornitza Stark Classified gene: BPTF as Red List (low evidence)
Speech apraxia v1.4 BPTF Zornitza Stark Gene: bptf has been classified as Red List (Low Evidence).
Kidney Cancer v0.26 VHL Zornitza Stark Marked gene: VHL as ready
Kidney Cancer v0.26 VHL Zornitza Stark Gene: vhl has been classified as Green List (High Evidence).
Kidney Cancer v0.26 TSC2 Zornitza Stark Marked gene: TSC2 as ready
Kidney Cancer v0.26 TSC2 Zornitza Stark Gene: tsc2 has been classified as Green List (High Evidence).
Kidney Cancer v0.26 TSC1 Zornitza Stark Marked gene: TSC1 as ready
Kidney Cancer v0.26 TSC1 Zornitza Stark Gene: tsc1 has been classified as Green List (High Evidence).
Kidney Cancer v0.26 SDHD Zornitza Stark Marked gene: SDHD as ready
Kidney Cancer v0.26 SDHD Zornitza Stark Gene: sdhd has been classified as Green List (High Evidence).
Kidney Cancer v0.26 SDHC Zornitza Stark Marked gene: SDHC as ready
Kidney Cancer v0.26 SDHC Zornitza Stark Gene: sdhc has been classified as Green List (High Evidence).
Kidney Cancer v0.26 SDHB Zornitza Stark Marked gene: SDHB as ready
Kidney Cancer v0.26 SDHB Zornitza Stark Gene: sdhb has been classified as Green List (High Evidence).
Kidney Cancer v0.26 SDHAF2 Zornitza Stark Marked gene: SDHAF2 as ready
Kidney Cancer v0.26 SDHAF2 Zornitza Stark Gene: sdhaf2 has been classified as Green List (High Evidence).
Kidney Cancer v0.26 SDHA Zornitza Stark Marked gene: SDHA as ready
Kidney Cancer v0.26 SDHA Zornitza Stark Gene: sdha has been classified as Green List (High Evidence).
Kidney Cancer v0.26 PTEN Zornitza Stark Marked gene: PTEN as ready
Kidney Cancer v0.26 PTEN Zornitza Stark Gene: pten has been classified as Green List (High Evidence).
Kidney Cancer v0.26 MET Zornitza Stark Marked gene: MET as ready
Kidney Cancer v0.26 MET Zornitza Stark Gene: met has been classified as Green List (High Evidence).
Kidney Cancer v0.26 FLCN Zornitza Stark Marked gene: FLCN as ready
Kidney Cancer v0.26 FLCN Zornitza Stark Gene: flcn has been classified as Green List (High Evidence).
Kidney Cancer v0.26 FH Zornitza Stark Marked gene: FH as ready
Kidney Cancer v0.26 FH Zornitza Stark Gene: fh has been classified as Green List (High Evidence).
Kidney Cancer v0.26 BAP1 Zornitza Stark Marked gene: BAP1 as ready
Kidney Cancer v0.26 BAP1 Zornitza Stark Gene: bap1 has been classified as Green List (High Evidence).
Speech apraxia v1.3 BPTF Thomas Scerri gene: BPTF was added
gene: BPTF was added to Speech apraxia. Sources: Expert Review,Expert list
Mode of inheritance for gene: BPTF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: BPTF were set to Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies, MIM# 617755
Review for gene: BPTF was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert Review, Expert list
Speech apraxia v1.3 ANK2 Thomas Scerri changed review comment from: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert Review; to: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.3 ANK2 Thomas Scerri edited their review of gene: ANK2: Changed phenotypes: Cardiac arrhythmia, ankyrin-B-related, MIM# 600919, Long QT syndrome 4, MIM# 600919, Neurodevelopmental disorder (MONDO:0700092), ANK2-related
Speech apraxia v1.3 ANK2 Thomas Scerri edited their review of gene: ANK2: Changed phenotypes: Cardiac arrhythmia, ankyrin-B-related, MIM# 600919, Long QT syndrome 4, MIM# 600919, Neurodevelopmental disorder (MONDO:0700092), gene-related
Speech apraxia v1.3 ANK2 Thomas Scerri gene: ANK2 was added
gene: ANK2 was added to Speech apraxia. Sources: Expert Review
Mode of inheritance for gene: ANK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANK2 were set to 37195288
Phenotypes for gene: ANK2 were set to Cardiac arrhythmia, ankyrin-B-relatedNeurodevelopmental disorder (MONDO:0700092), gene-related
Review for gene: ANK2 was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert Review
Speech apraxia v1.3 SETBP1 Thomas Scerri commented on gene: SETBP1: Two in-house (as yet unpublished) CAS probands with pathogenic variants.
Speech apraxia v1.3 FOXP2 Thomas Scerri changed review comment from: An unpublished CAS proband with a pathogenic variant.; to: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Speech apraxia v1.3 FOXP2 Thomas Scerri commented on gene: FOXP2: An unpublished CAS proband with a pathogenic variant.
Speech apraxia v1.3 SHANK3 Zornitza Stark Classified gene: SHANK3 as Amber List (moderate evidence)
Speech apraxia v1.3 SHANK3 Zornitza Stark Gene: shank3 has been classified as Amber List (Moderate Evidence).
Speech apraxia v1.2 WDR5 Zornitza Stark Classified gene: WDR5 as Amber List (moderate evidence)
Speech apraxia v1.2 WDR5 Zornitza Stark Gene: wdr5 has been classified as Amber List (Moderate Evidence).
Speech apraxia v1.1 SETD1A Zornitza Stark Classified gene: SETD1A as Green List (high evidence)
Speech apraxia v1.1 SETD1A Zornitza Stark Gene: setd1a has been classified as Green List (High Evidence).
Kidney Cancer v0.26 BAP1 Chirag Patel Classified gene: BAP1 as Green List (high evidence)
Kidney Cancer v0.26 BAP1 Chirag Patel Gene: bap1 has been classified as Green List (High Evidence).
Kidney Cancer v0.25 FH Chirag Patel Classified gene: FH as Green List (high evidence)
Kidney Cancer v0.25 FH Chirag Patel Gene: fh has been classified as Green List (High Evidence).
Kidney Cancer v0.24 FLCN Chirag Patel Classified gene: FLCN as Green List (high evidence)
Kidney Cancer v0.24 FLCN Chirag Patel Gene: flcn has been classified as Green List (High Evidence).
Kidney Cancer v0.23 PTEN Chirag Patel Classified gene: PTEN as Green List (high evidence)
Kidney Cancer v0.23 PTEN Chirag Patel Gene: pten has been classified as Green List (High Evidence).
Kidney Cancer v0.22 MET Chirag Patel Classified gene: MET as Green List (high evidence)
Kidney Cancer v0.22 MET Chirag Patel Gene: met has been classified as Green List (High Evidence).
Kidney Cancer v0.21 MET Chirag Patel gene: MET was added
gene: MET was added to Kidney Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: MET was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MET were set to Renal carcinoma, MONDO:0005206; Papillary renal cell carcinoma, MONDO:0017884; Renal cell carcinoma, papillary, 1, familial, MIM#605074
Mode of pathogenicity for gene: MET was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: MET was set to GREEN
Added comment: ClinGen definitive. GOF variants.
Sources: Expert list, Expert Review
Kidney Cancer v0.20 PTEN Chirag Patel gene: PTEN was added
gene: PTEN was added to Kidney Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: PTEN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PTEN were set to Renal carcinoma, MONDO:0005206; PTEN hamartoma tumor syndrome, MONDO:0017623; PTEN hamartoma tumour syndromes, MIM#158350
Review for gene: PTEN was set to GREEN
Added comment: ClinGen definitive. Renal carcinoma reported in condition.
Sources: Expert list, Expert Review
Kidney Cancer v0.19 FLCN Chirag Patel gene: FLCN was added
gene: FLCN was added to Kidney Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: FLCN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FLCN were set to Renal carcinoma, MONDO:0005206; Birt-Hogg-Dube syndrome 1, MONDO:0800445; Birt-Hogg-Dube syndrome, MIM#135150
Review for gene: FLCN was set to GREEN
Added comment: ClinGen definitive. Renal carcinoma reported in condition.
Sources: Expert list, Expert Review
Kidney Cancer v0.18 FH Chirag Patel gene: FH was added
gene: FH was added to Kidney Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: FH was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FH were set to Renal carcinoma, MONDO:0005206; Hereditary leiomyomatosis and renal cell cancer, MONDO:0007888; Leiomyomatosis and renal cell cancer, MIM#150800
Review for gene: FH was set to GREEN
Added comment: ClinGen definitive. Renal carcinoma reported in condition.
Sources: Expert list, Expert Review
Kidney Cancer v0.17 BAP1 Chirag Patel gene: BAP1 was added
gene: BAP1 was added to Kidney Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: BAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: BAP1 were set to Renal carcinoma, MONDO:0005206; BAP1-related tumor predisposition syndrome, MONDO:0013692; BAP1-tumour predisposition syndrome, MIM#614327
Review for gene: BAP1 was set to GREEN
Added comment: ClinGen definitive. Renal carcinoma reported in condition.
Sources: Expert list, Expert Review
Kidney Cancer v0.16 TSC1 Chirag Patel Classified gene: TSC1 as Green List (high evidence)
Kidney Cancer v0.16 TSC1 Chirag Patel Gene: tsc1 has been classified as Green List (High Evidence).
Kidney Cancer v0.15 TSC2 Chirag Patel Classified gene: TSC2 as Green List (high evidence)
Kidney Cancer v0.15 TSC2 Chirag Patel Gene: tsc2 has been classified as Green List (High Evidence).
Kidney Cancer v0.14 VHL Chirag Patel Classified gene: VHL as Green List (high evidence)
Kidney Cancer v0.14 VHL Chirag Patel Gene: vhl has been classified as Green List (High Evidence).
Kidney Cancer v0.13 VHL Chirag Patel gene: VHL was added
gene: VHL was added to Kidney Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: VHL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: VHL were set to Renal carcinoma, MONDO:0005206; Von Hippel-Lindau disease, MONDO:0008667; von Hippel-Lindau syndrome, MIM#193300; Pheochromocytoma, susceptibility to, MIM#171300
Review for gene: VHL was set to GREEN
Added comment: ClinGen definitive. Renal carcinoma reported in condition.
Sources: Expert list, Expert Review
Kidney Cancer v0.12 TSC2 Chirag Patel gene: TSC2 was added
gene: TSC2 was added to Kidney Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: TSC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TSC2 were set to Renal carcinoma, MONDO:0005206; Tuberous sclerosis 2, MONDO:0013199; Tuberous sclerosis-2, MIM#613254
Review for gene: TSC2 was set to GREEN
Added comment: ClinGen definitive. Renal carcinoma reported in condition.
Sources: Expert list, Expert Review
Kidney Cancer v0.11 TSC1 Chirag Patel gene: TSC1 was added
gene: TSC1 was added to Kidney Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: TSC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TSC1 were set to Renal carcinoma, MONDO:0005206; Tuberous sclerosis 1, MONDO:0008612; Tuberous sclerosis-1, MIM#191100
Review for gene: TSC1 was set to GREEN
Added comment: ClinGen definitive. Renal carcinoma reported in condition.
Sources: Expert list, Expert Review
Kidney Cancer v0.10 SDHD Chirag Patel Classified gene: SDHD as Green List (high evidence)
Kidney Cancer v0.10 SDHD Chirag Patel Gene: sdhd has been classified as Green List (High Evidence).
Kidney Cancer v0.9 SDHC Chirag Patel Classified gene: SDHC as Green List (high evidence)
Kidney Cancer v0.9 SDHC Chirag Patel Gene: sdhc has been classified as Green List (High Evidence).
Kidney Cancer v0.8 SDHB Chirag Patel Classified gene: SDHB as Green List (high evidence)
Kidney Cancer v0.8 SDHB Chirag Patel Gene: sdhb has been classified as Green List (High Evidence).
Kidney Cancer v0.7 SDHAF2 Chirag Patel Classified gene: SDHAF2 as Green List (high evidence)
Kidney Cancer v0.7 SDHAF2 Chirag Patel Gene: sdhaf2 has been classified as Green List (High Evidence).
Kidney Cancer v0.6 SDHA Chirag Patel Classified gene: SDHA as Green List (high evidence)
Kidney Cancer v0.6 SDHA Chirag Patel Gene: sdha has been classified as Green List (High Evidence).
Kidney Cancer v0.5 SDHA Chirag Patel gene: SDHA was added
gene: SDHA was added to Kidney Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: SDHA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SDHA were set to Renal carcinoma, MONDO:0005206; Hereditary pheochromocytoma-paraganglioma, MONDO:0017366; Pheochromocytoma/paraganglioma syndrome 5, MIM#614165
Review for gene: SDHA was set to GREEN
Added comment: ClinGen definitive. Renal carcinoma reported in condition.
Sources: Expert list, Expert Review
Kidney Cancer v0.4 SDHAF2 Chirag Patel gene: SDHAF2 was added
gene: SDHAF2 was added to Kidney Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: SDHAF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SDHAF2 were set to Renal carcinoma, MONDO:0005206; Hereditary pheochromocytoma-paraganglioma, MONDO:0017366; Pheochromocytoma/paraganglioma syndrome 2, MIM#601650
Review for gene: SDHAF2 was set to GREEN
Added comment: ClinGen definitive. Renal carcinoma reported in condition.
Sources: Expert list, Expert Review
Kidney Cancer v0.3 SDHB Chirag Patel gene: SDHB was added
gene: SDHB was added to Kidney Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: SDHB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SDHB were set to Renal carcinoma, MONDO:0005206; Hereditary pheochromocytoma-paraganglioma, MONDO:0017366; Pheochromocytoma/paraganglioma syndrome 4, MIM#115310
Review for gene: SDHB was set to GREEN
Added comment: ClinGen definitive. Renal carcinoma reported in condition.
Sources: Expert list, Expert Review
Kidney Cancer v0.2 SDHC Chirag Patel gene: SDHC was added
gene: SDHC was added to Kidney Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: SDHC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SDHC were set to Renal carcinoma, MONDO:0005206; Hereditary pheochromocytoma-paraganglioma, MONDO:0017366; Pheochromocytoma/paraganglioma syndrome 3, MIM#605373
Review for gene: SDHC was set to GREEN
Added comment: ClinGen definitive. Renal carcinoma reported in condition.
Sources: Expert list, Expert Review
Kidney Cancer v0.1 SDHD Chirag Patel gene: SDHD was added
gene: SDHD was added to Kidney Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: SDHD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SDHD were set to Renal carcinoma, MONDO:0005206; Hereditary pheochromocytoma-paraganglioma, MONDO:0017366; Pheochromocytoma/paraganglioma syndrome 1, MIM#168000
Review for gene: SDHD was set to GREEN
Added comment: ClinGen definitive. Renal carcinoma reported in condition.
Sources: Expert list, Expert Review
Thyroid Cancer v0.12 APC Chirag Patel Classified gene: APC as Green List (high evidence)
Thyroid Cancer v0.12 APC Chirag Patel Gene: apc has been classified as Green List (High Evidence).
Thyroid Cancer v0.11 CDKN1B Chirag Patel Classified gene: CDKN1B as Green List (high evidence)
Thyroid Cancer v0.11 CDKN1B Chirag Patel Gene: cdkn1b has been classified as Green List (High Evidence).
Thyroid Cancer v0.10 DICER1 Chirag Patel Classified gene: DICER1 as Green List (high evidence)
Thyroid Cancer v0.10 DICER1 Chirag Patel Gene: dicer1 has been classified as Green List (High Evidence).
Thyroid Cancer v0.9 PRKAR1A Chirag Patel Classified gene: PRKAR1A as Green List (high evidence)
Thyroid Cancer v0.9 PRKAR1A Chirag Patel Gene: prkar1a has been classified as Green List (High Evidence).
Thyroid Cancer v0.8 PTEN Chirag Patel Classified gene: PTEN as Green List (high evidence)
Thyroid Cancer v0.8 PTEN Chirag Patel Gene: pten has been classified as Green List (High Evidence).
Thyroid Cancer v0.7 RET Chirag Patel Classified gene: RET as Green List (high evidence)
Thyroid Cancer v0.7 RET Chirag Patel Gene: ret has been classified as Green List (High Evidence).
Thyroid Cancer v0.6 APC Chirag Patel gene: APC was added
gene: APC was added to Thyroid Neoplasm. Sources: Expert list,Expert Review
Mode of inheritance for gene: APC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: APC were set to Thyroid cancer, MONDO:0002108; Thyroid gland papillary carcinoma, MONDO:0005075; Familial adenomatous polyposis 1, MONDO:0021056; Adenomatous polyposis coli, MIM#175100
Review for gene: APC was set to GREEN
Added comment: ClinGen definitive. Papillary thyroid cancer reported in condition.
Sources: Expert list, Expert Review
Thyroid Cancer v0.5 CDKN1B Chirag Patel gene: CDKN1B was added
gene: CDKN1B was added to Thyroid Neoplasm. Sources: Expert list,Expert Review
Mode of inheritance for gene: CDKN1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CDKN1B were set to Thyroid cancer, MONDO:0002108; Thyroid gland papillary carcinoma, MONDO:0005075; Multiple endocrine neoplasia type 4, MONDO:0012552; Multiple endocrine neoplasia, type 4, MIM#610755
Review for gene: CDKN1B was set to GREEN
Added comment: ClinGen definitive. Papillary thyroid cancer reported in condition.
Sources: Expert list, Expert Review
Thyroid Cancer v0.4 DICER1 Chirag Patel gene: DICER1 was added
gene: DICER1 was added to Thyroid Neoplasm. Sources: Expert list,Expert Review
Mode of inheritance for gene: DICER1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: DICER1 were set to Thyroid cancer, MONDO:0002108; Thyroid gland papillary carcinoma, MONDO:0005075; DICER1-related tumor predisposition, MONDO:0100216; DICER1 syndrome, MIM#601200
Review for gene: DICER1 was set to GREEN
Added comment: ClinGen definitive. Papillary thyroid cancer reported in condition.
Sources: Expert list, Expert Review
Thyroid Cancer v0.3 RET Chirag Patel changed review comment from: ClinGen definitive. GOF variants.
Sources: Expert list, Expert Review; to: ClinGen definitive. Medullary thyroid cancer reported in condition. GOF variants.
Sources: Expert list, Expert Review
Thyroid Cancer v0.3 PRKAR1A Chirag Patel gene: PRKAR1A was added
gene: PRKAR1A was added to Thyroid Neoplasm. Sources: Expert list,Expert Review
Mode of inheritance for gene: PRKAR1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PRKAR1A were set to Thyroid cancer, MONDO:0002108; Thyroid gland follicular carcinoma, MONDO:0005034; Carney complex type 1, MONDO:0008057; Carney complex, type 1, MIM#160980
Review for gene: PRKAR1A was set to GREEN
Added comment: ClinGen definitive. Follicular thyroid cancer reported in condition.
Sources: Expert list, Expert Review
Thyroid Cancer v0.2 PTEN Chirag Patel gene: PTEN was added
gene: PTEN was added to Thyroid Neoplasm. Sources: Expert list,Expert Review
Mode of inheritance for gene: PTEN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PTEN were set to Thyroid cancer, MONDO:0002108; Thyroid gland follicular carcinoma, MONDO:0005034; PTEN hamartoma tumor syndrome, MONDO:0017623; PTEN hamartoma tumour syndromes, MIM#158350
Review for gene: PTEN was set to GREEN
Added comment: ClinGen definitive. Follicular thyroid cancer reported in condition.
Sources: Expert list, Expert Review
Thyroid Cancer v0.1 RET Chirag Patel changed review comment from: ClinGen definitive. Thyroid cancer reported in condition. GOF variants.
Sources: Expert list, Expert Review; to: ClinGen definitive. GOF variants.
Sources: Expert list, Expert Review
Thyroid Cancer v0.1 RET Chirag Patel gene: RET was added
gene: RET was added to Thyroid Neoplasm. Sources: Expert list,Expert Review
Mode of inheritance for gene: RET was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RET were set to Thyroid cancer, MONDO:0002108; Medullary thyroid gland carcinoma, MONDO:0015277; Multiple endocrine neoplasia type 2A, MONDO:0008234; Multiple endocrine neoplasia type 2B, MONDO:0008082; Multiple endocrine neoplasia, type 2A, MIM#171400; Multiple endocrine neoplasia, type 2B, MIM#162300; Pheochromocytoma, MIM#171300; Medullary thyroid carcinoma, MIM#155240; Pheochromocytoma, susceptibility to, MIM#171300
Mode of pathogenicity for gene: RET was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: RET was set to GREEN
Added comment: ClinGen definitive. Thyroid cancer reported in condition. GOF variants.
Sources: Expert list, Expert Review
Parathyroid Tumour v0.12 CASR Chirag Patel Classified gene: CASR as Green List (high evidence)
Parathyroid Tumour v0.12 CASR Chirag Patel Gene: casr has been classified as Green List (High Evidence).
Parathyroid Tumour v0.11 CDC73 Chirag Patel Classified gene: CDC73 as Green List (high evidence)
Parathyroid Tumour v0.11 CDC73 Chirag Patel Gene: cdc73 has been classified as Green List (High Evidence).
Parathyroid Tumour v0.10 CDKN1B Chirag Patel Classified gene: CDKN1B as Green List (high evidence)
Parathyroid Tumour v0.10 CDKN1B Chirag Patel Gene: cdkn1b has been classified as Green List (High Evidence).
Parathyroid Tumour v0.9 MEN1 Chirag Patel Classified gene: MEN1 as Green List (high evidence)
Parathyroid Tumour v0.9 MEN1 Chirag Patel Gene: men1 has been classified as Green List (High Evidence).
Parathyroid Tumour v0.8 RET Chirag Patel Classified gene: RET as Green List (high evidence)
Parathyroid Tumour v0.8 RET Chirag Patel Gene: ret has been classified as Green List (High Evidence).
Parathyroid Tumour v0.7 GCM2 Chirag Patel Classified gene: GCM2 as Green List (high evidence)
Parathyroid Tumour v0.7 GCM2 Chirag Patel Gene: gcm2 has been classified as Green List (High Evidence).
Parathyroid Tumour v0.6 CASR Chirag Patel gene: CASR was added
gene: CASR was added to Parathyroid Neoplasm. Sources: Expert list,Expert Review
Mode of inheritance for gene: CASR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CASR were set to Tumor of parathyroid gland, MONDO:0021360; Familial hypocalciuric hypercalcemia 1, MONDO:0007791; Hypocalciuric hypercalcemia, type I, MIM#145980; Hypocalcemia, autosomal dominant, MIM#601198
Review for gene: CASR was set to GREEN
Added comment: ClinGen definitive. Parathyroid neoplasm reported in condition.
Sources: Expert list, Expert Review
Parathyroid Tumour v0.5 CDC73 Chirag Patel gene: CDC73 was added
gene: CDC73 was added to Parathyroid Neoplasm. Sources: Expert list,Expert Review
Mode of inheritance for gene: CDC73 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CDC73 were set to Tumor of parathyroid gland, MONDO:0021360; Hyperparathyroidism 2 with jaw tumors, MONDO:0007768; Hyperparathyroidism-jaw tumor syndrome, MIM#145001; Hyperparathyroidism, familial primary, MIM#145000
Review for gene: CDC73 was set to GREEN
Added comment: ClinGen definitive. Parathyroid neoplasm reported in condition.
Sources: Expert list, Expert Review
Parathyroid Tumour v0.4 GCM2 Chirag Patel changed review comment from: Established gene-disease association. Numerous families reported. GOF variants.
Sources: Expert list, Expert Review, Literature; to: Established gene-disease association. Numerous families reported.
Parathyroid neoplasm reported in condition.
GOF variants.
Sources: Expert list, Expert Review, Literature
Parathyroid Tumour v0.4 CDKN1B Chirag Patel gene: CDKN1B was added
gene: CDKN1B was added to Parathyroid Neoplasm. Sources: Expert list,Expert Review
Mode of inheritance for gene: CDKN1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CDKN1B were set to Tumor of parathyroid gland, MONDO:0021360; Multiple endocrine neoplasia type 4, MONDO:0012552; Multiple endocrine neoplasia, type 4, MIM#610755
Review for gene: CDKN1B was set to GREEN
Added comment: ClinGen definitive.
Sources: Expert list, Expert Review
Parathyroid Tumour v0.3 MEN1 Chirag Patel gene: MEN1 was added
gene: MEN1 was added to Parathyroid Neoplasm. Sources: Expert list,Expert Review
Mode of inheritance for gene: MEN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MEN1 were set to Tumor of parathyroid gland, MONDO:0021360; Multiple endocrine neoplasia type 1, MONDO:0007540; Multiple endocrine neoplasia, type 1, MIM#131100
Review for gene: MEN1 was set to GREEN
Added comment: ClinGen definitive.
Sources: Expert list, Expert Review
Parathyroid Tumour v0.2 RET Chirag Patel gene: RET was added
gene: RET was added to Parathyroid Neoplasm. Sources: Expert list,Expert Review
Mode of inheritance for gene: RET was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RET were set to Tumor of parathyroid gland, MONDO:0021360; Multiple endocrine neoplasia type 2A, MONDO:0008234; Multiple endocrine neoplasia type 2B, MONDO:0008082; Multiple endocrine neoplasia, type 2A, MIM#171400; Multiple endocrine neoplasia, type 2B, MIM#162300; Pheochromocytoma, MIM#171300; Medullary thyroid carcinoma, MIM#155240; Pheochromocytoma, susceptibility to, MIM#171300
Mode of pathogenicity for gene: RET was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: RET was set to GREEN
Added comment: ClinGen definitive. GOF variants.
Sources: Expert list, Expert Review
Parathyroid Tumour v0.1 GCM2 Chirag Patel gene: GCM2 was added
gene: GCM2 was added to Parathyroid Neoplasm. Sources: Expert list,Expert Review,Literature
Mode of inheritance for gene: GCM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GCM2 were set to PMID: 27745835, 34967908, 33471711, 29108698
Phenotypes for gene: GCM2 were set to Tumor of parathyroid gland, MONDO:0021360; Hyperparathyroidism 4, MONDO:0024570; Hyperparathyroidism 4, MIM#617343
Mode of pathogenicity for gene: GCM2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: GCM2 was set to GREEN
Added comment: Established gene-disease association. Numerous families reported. GOF variants.
Sources: Expert list, Expert Review, Literature
Melanoma v0.14 CDK4 Chirag Patel Mode of pathogenicity for gene: CDK4 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Melanoma v0.13 POT1 Chirag Patel Classified gene: POT1 as Amber List (moderate evidence)
Melanoma v0.13 POT1 Chirag Patel Gene: pot1 has been classified as Amber List (Moderate Evidence).
Gastrointestinal Stromal Tumour v0.16 SDHD Chirag Patel Classified gene: SDHD as Green List (high evidence)
Gastrointestinal Stromal Tumour v0.16 SDHD Chirag Patel Gene: sdhd has been classified as Green List (High Evidence).
Gastrointestinal Stromal Tumour v0.15 SDHC Chirag Patel Classified gene: SDHC as Green List (high evidence)
Gastrointestinal Stromal Tumour v0.15 SDHC Chirag Patel Gene: sdhc has been classified as Green List (High Evidence).
Gastrointestinal Stromal Tumour v0.14 SDHB Chirag Patel Classified gene: SDHB as Green List (high evidence)
Gastrointestinal Stromal Tumour v0.14 SDHB Chirag Patel Gene: sdhb has been classified as Green List (High Evidence).
Gastrointestinal Stromal Tumour v0.13 SDHAF2 Chirag Patel Classified gene: SDHAF2 as Green List (high evidence)
Gastrointestinal Stromal Tumour v0.13 SDHAF2 Chirag Patel Gene: sdhaf2 has been classified as Green List (High Evidence).
Gastrointestinal Stromal Tumour v0.12 SDHA Chirag Patel Classified gene: SDHA as Green List (high evidence)
Gastrointestinal Stromal Tumour v0.12 SDHA Chirag Patel Gene: sdha has been classified as Green List (High Evidence).
Gastrointestinal Stromal Tumour v0.11 SDHD Chirag Patel gene: SDHD was added
gene: SDHD was added to Gastrointestinal Stromal Tumour. Sources: Expert list,Expert Review
Mode of inheritance for gene: SDHD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SDHD were set to Gastrointestinal stromal tumor, MONDO:0011719; Hereditary pheochromocytoma-paraganglioma, MONDO:0017366; Pheochromocytoma/paraganglioma syndrome 1, MIM#168000
Review for gene: SDHD was set to GREEN
Added comment: ClinGen definitive. GIST reported in condition.
Sources: Expert list, Expert Review
Gastrointestinal Stromal Tumour v0.10 SDHC Chirag Patel gene: SDHC was added
gene: SDHC was added to Gastrointestinal Stromal Tumour. Sources: Expert list,Expert Review
Mode of inheritance for gene: SDHC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SDHC were set to Gastrointestinal stromal tumor, MONDO:0011719; Hereditary pheochromocytoma-paraganglioma, MONDO:0017366; Pheochromocytoma/paraganglioma syndrome 3, MIM#605373
Review for gene: SDHC was set to GREEN
Added comment: ClinGen definitive. GIST reported in condition.
Sources: Expert list, Expert Review
Gastrointestinal Stromal Tumour v0.9 SDHB Chirag Patel gene: SDHB was added
gene: SDHB was added to Gastrointestinal Stromal Tumour. Sources: Expert list,Expert Review
Mode of inheritance for gene: SDHB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SDHB were set to Gastrointestinal stromal tumor, MONDO:0011719; Hereditary pheochromocytoma-paraganglioma, MONDO:0017366; Pheochromocytoma/paraganglioma syndrome 4, MIM#115310
Review for gene: SDHB was set to GREEN
Added comment: ClinGen definitive. GIST reported in condition.
Sources: Expert list, Expert Review
Gastrointestinal Stromal Tumour v0.8 SDHAF2 Chirag Patel gene: SDHAF2 was added
gene: SDHAF2 was added to Gastrointestinal Stromal Tumour. Sources: Expert list,Expert Review
Mode of inheritance for gene: SDHAF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SDHAF2 were set to Gastrointestinal stromal tumor, MONDO:0011719; Hereditary pheochromocytoma-paraganglioma, MONDO:0017366; Pheochromocytoma/paraganglioma syndrome 2, MIM#601650
Review for gene: SDHAF2 was set to GREEN
Added comment: ClinGen definitive. GIST reported in condition.
Sources: Expert list, Expert Review
Gastrointestinal Stromal Tumour v0.7 SDHA Chirag Patel gene: SDHA was added
gene: SDHA was added to Gastrointestinal Stromal Tumour. Sources: Expert list,Expert Review
Mode of inheritance for gene: SDHA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SDHA were set to Gastrointestinal stromal tumor, MONDO:0011719; Hereditary pheochromocytoma-paraganglioma, MONDO:0017366; Pheochromocytoma/paraganglioma syndrome 5, MIM#614165
Review for gene: SDHA was set to GREEN
Added comment: ClinGen definitive. GIST reported in condition.
Sources: Expert list, Expert Review
Gastrointestinal Stromal Tumour v0.6 NF1 Chirag Patel Classified gene: NF1 as Green List (high evidence)
Gastrointestinal Stromal Tumour v0.6 NF1 Chirag Patel Gene: nf1 has been classified as Green List (High Evidence).
Gastrointestinal Stromal Tumour v0.5 PDGFRA Chirag Patel Classified gene: PDGFRA as Green List (high evidence)
Gastrointestinal Stromal Tumour v0.5 PDGFRA Chirag Patel Gene: pdgfra has been classified as Green List (High Evidence).
Gastrointestinal Stromal Tumour v0.4 KIT Chirag Patel Classified gene: KIT as Green List (high evidence)
Gastrointestinal Stromal Tumour v0.4 KIT Chirag Patel Gene: kit has been classified as Green List (High Evidence).
Gastrointestinal Stromal Tumour v0.3 NF1 Chirag Patel gene: NF1 was added
gene: NF1 was added to Gastrointestinal Stromal Tumour. Sources: Expert list,Expert Review
Mode of inheritance for gene: NF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: NF1 were set to Gastrointestinal stromal tumor, MONDO:0011719; Neurofibromatosis type 1, MONDO:0018975; Neurofibromatosis, type 1, MIM#162200
Review for gene: NF1 was set to GREEN
Added comment: ClinGen definitive. GIST reported in condition.
Single gene testing may be more appropriate if clinical features of NF1.
Sources: Expert list, Expert Review
Gastrointestinal Stromal Tumour v0.2 PDGFRA Chirag Patel gene: PDGFRA was added
gene: PDGFRA was added to Gastrointestinal Stromal Tumour. Sources: Expert list,Expert Review
Mode of inheritance for gene: PDGFRA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PDGFRA were set to Gastrointestinal stromal tumor, MONDO:0011719; Gastrointestinal stromal tumor/GIST-plus syndrome, somatic or familial, MIM#175510
Mode of pathogenicity for gene: PDGFRA was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: PDGFRA was set to GREEN
Added comment: ClinGen definitive. GOF variants.
Sources: Expert list, Expert Review
Gastrointestinal Stromal Tumour v0.1 KIT Chirag Patel gene: KIT was added
gene: KIT was added to Gastrointestinal Stromal Tumour. Sources: Expert list,Expert Review
Mode of inheritance for gene: KIT was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: KIT were set to Gastrointestinal stromal tumor, MONDO:0011719; Gastrointestinal stromal tumor, familial, MIM#606764
Mode of pathogenicity for gene: KIT was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: KIT was set to GREEN
Added comment: ClinGen definitive. GOF variants.
Sources: Expert list, Expert Review
Diffuse Gastric Cancer v0.4 CDH1 Chirag Patel Classified gene: CDH1 as Green List (high evidence)
Diffuse Gastric Cancer v0.4 CDH1 Chirag Patel Gene: cdh1 has been classified as Green List (High Evidence).
Diffuse Gastric Cancer v0.3 CTNNA1 Chirag Patel Classified gene: CTNNA1 as Green List (high evidence)
Diffuse Gastric Cancer v0.3 CTNNA1 Chirag Patel Gene: ctnna1 has been classified as Green List (High Evidence).
Diffuse Gastric Cancer v0.2 CTNNA1 Chirag Patel gene: CTNNA1 was added
gene: CTNNA1 was added to Diffuse Gastric Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: CTNNA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CTNNA1 were set to Diffuse gastric cancer, MONDO:0957519; CTNNA1-related diffuse gastric and lobular breast cancer syndrome, MONDO:0100256; no MIM#
Review for gene: CTNNA1 was set to GREEN
Added comment: ClinGen definitive.
Sources: Expert list, Expert Review
Diffuse Gastric Cancer v0.1 CDH1 Chirag Patel gene: CDH1 was added
gene: CDH1 was added to Diffuse Gastric Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: CDH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CDH1 were set to Diffuse gastric cancer, MONDO:0957519; CDH1-related diffuse gastric and lobular breast cancer syndrome, MONDO:0100488; Diffuse gastric and lobular breast cancer syndrome with or without cleft lip and/or palate, MIM#137215
Review for gene: CDH1 was set to GREEN
Added comment: ClinGen definitive.
Sources: Expert list, Expert Review
Melanoma v0.12 POT1 Chirag Patel Classified gene: POT1 as Green List (high evidence)
Melanoma v0.12 POT1 Chirag Patel Gene: pot1 has been classified as Green List (High Evidence).
Melanoma v0.11 POT1 Chirag Patel gene: POT1 was added
gene: POT1 was added to Melanoma. Sources: Expert Review,Literature
Mode of inheritance for gene: POT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POT1 were set to PMID: 24686849, 30586141, 24686846, 38724174
Phenotypes for gene: POT1 were set to Melanoma, MONDO:0005105; Tumor predisposition syndrome 3, MONDO:0014368; Melanoma, cutaneous malignant, MIM#606478
Review for gene: POT1 was set to GREEN
Added comment: Tumor predisposition syndrome-3 (TPDS3) is characterised by an increased risk for the development of various types of benign and malignant neoplasms throughout life, with age-dependent penetrance (e.g. neoplasms involving epithelial, mesenchymal, and neuronal tissues, as well as clonal hematopoietic syndromes, including lymphoid and myeloid cancers).

Cutaneous melanoma is the most commonly reported malignancy in individuals with POT1-Tumor predisposition syndrome (increased risk for various benign and malignant neoplasms throughout life, with age-dependent penetrance - neoplasms involving epithelial, mesenchymal, and neuronal tissues, as well as clonal hematopoietic syndromes, including lymphoid and myeloid cancers). Multiple unrelated families reported with melanoma and POT1 variant.
Sources: Expert Review, Literature
Melanoma v0.9 CDKN2A Chirag Patel reviewed gene: CDKN2A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Melanoma, MONDO:0005105, Melanoma cutaneous malignant susceptibility to 2, MONDO:0007964, Melanoma-pancreatic cancer syndrome, MONDO:0011713, Melanoma and neural system tumor syndrome, MONDO:0007967, Melanoma, cutaneous malignant, 2, MIM#155601, Melanoma-pancreatic cancer syndrome, MIM#606719, Melanoma and neural system tumor syndrome, MIM#155755; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Melanoma v0.9 CDK4 Chirag Patel Deleted their comment
Melanoma v0.9 CDK4 Chirag Patel commented on gene: CDK4: ClinGen definitive. GOF variants.
Melanoma v0.9 CDK4 Chirag Patel changed review comment from: ClinGen definitive.; to: ClinGen definitive. GOF variants.
Melanoma v0.9 CDK4 Chirag Patel reviewed gene: CDK4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Melanoma, MONDO:0005105, CDK4 linked melanoma, MONDO:0022623, Melanoma cutaneous malignant susceptibility to 3, MONDO:0012183, Melanoma, cutaneous malignant, 3, MIM#609048; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Melanoma v0.9 BAP1 Chirag Patel reviewed gene: BAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Melanoma, MONDO:0005105, BAP1-related tumor predisposition syndrome, MONDO:0013692, BAP1-tumour predisposition syndrome, MIM#614327; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Melanoma v0.7 BAP1 Chirag Patel Deleted their review
Melanoma v0.6 BAP1 Chirag Patel reviewed gene: BAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Melanoma, MONDO:0005105, BAP1-related tumor predisposition syndrome, MONDO:0013692, BAP1-tumour predisposition syndrome, MIM#614327; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Melanoma v0.6 Chirag Patel Panel status changed from retired to public
Basal Cell Cancer v0.6 PTCH2 Chirag Patel gene: PTCH2 was added
gene: PTCH2 was added to Basal Cell Cancer. Sources: Literature,Expert Review
Mode of inheritance for gene: PTCH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTCH2 were set to PMID: 34170463, 18285427, 23479190, 30820324, 38354379
Phenotypes for gene: PTCH2 were set to Basal cell carcinoma, MONDO:0020804; Nevoid basal cell carcinoma syndrome, MONDO:0007187
Review for gene: PTCH2 was set to RED
Added comment: A number of case/family reports have proposed PTCH2 as a putative Gorlin Syndrome (GS) gene, but evidence to support this is lacking. PMID: 34170463 paper found no pathogenic or likely pathogenic PTCH2 variants in cohort of 21 PTCH1/SUFU negative GS families.
They assessed evidence from reported cases/families with PTCH2 variants, and determined that none of the previously published PTCH2 variants in GS families/cases could be considered pathogenic or likely pathogenic using current guidelines. There is also a high frequency of Loss-of-function (LoF) variants in the general population, including the presence of homozygous LoF variants without a clinical phenotype.
Sources: Literature, Expert Review
Schwannoma v0.12 SMARCB1 Chirag Patel changed review comment from: ClinGen definitive
Schwannomas reported in condition
Sources: Expert list, Expert Review; to: ClinGen definitive. Schwannomas reported in condition.
Sources: Expert list, Expert Review
Schwannoma v0.12 PRKAR1A Chirag Patel changed review comment from: ClinGen definitive
Schwannomas reported in condition
Sources: Expert list, Expert Review; to: ClinGen definitive. Schwannomas reported in condition.
Sources: Expert list, Expert Review
Schwannoma v0.12 NF2 Chirag Patel changed review comment from: ClinGen definitive
Schwannomas reported in condition
Sources: Expert list, Expert Review; to: ClinGen definitive. Schwannomas reported in condition.
Sources: Expert list, Expert Review
Schwannoma v0.12 NF1 Chirag Patel changed review comment from: ClinGen definitive
Schwannomas reported in condition
Sources: Expert list, Expert Review; to: ClinGen definitive. Schwannomas reported in condition.
Sources: Expert list, Expert Review
Meningioma v0.10 SUFU Chirag Patel changed review comment from: ClinGen definitive
Meningiomas reported in condition
Sources: Expert list, Expert Review; to: ClinGen definitive. Meningiomas reported in condition.
Sources: Expert list, Expert Review
Meningioma v0.10 SMARCB1 Chirag Patel changed review comment from: ClinGen definitive
Meningiomas reported in condition
Sources: Expert list, Expert Review; to: ClinGen definitive. Meningiomas reported in condition.
Sources: Expert list, Expert Review
Meningioma v0.10 NF2 Chirag Patel changed review comment from: ClinGen definitive
Meningiomas reported in condition
Sources: Expert list, Expert Review; to: ClinGen definitive. Meningiomas reported in condition.
Sources: Expert list, Expert Review
Meningioma v0.10 BAP1 Chirag Patel changed review comment from: ClinGen definitive
Meningiomas reported in condition
Sources: Expert list, Expert Review; to: ClinGen definitive. Meningiomas reported in condition.
Sources: Expert list, Expert Review
Basal Cell Cancer v0.5 SUFU Chirag Patel Classified gene: SUFU as Green List (high evidence)
Basal Cell Cancer v0.5 SUFU Chirag Patel Gene: sufu has been classified as Green List (High Evidence).
Basal Cell Cancer v0.4 SUFU Chirag Patel gene: SUFU was added
gene: SUFU was added to Basal Cell Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: SUFU was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SUFU were set to PMID: 20301330
Phenotypes for gene: SUFU were set to Basal cell carcinoma, MONDO:0020804; Basal cell nevus syndrome 2, MONDO:0958189; Basal cell nevus syndrome 2, MIM#620343; Meningioma, familial, susceptibility to, MIM#607174; Medulloblastoma predisposition syndrome, MIM#155255
Review for gene: SUFU was set to GREEN
Added comment: Established gene-disease association with basal cell nevus syndrome (also known as Gorlin syndrome). Basal cell cancers reported in condition. ClinGen definitive for medulloblastoma.
Sources: Expert list, Expert Review
Basal Cell Cancer v0.3 PTCH1 Chirag Patel changed review comment from: ClinGen definitive
Basal cell cancers reported in condition
Sources: Expert list, Expert Review; to: ClinGen definitive. Basal cell cancers reported in condition
Sources: Expert list, Expert Review
Basal Cell Cancer v0.3 PTCH1 Chirag Patel Classified gene: PTCH1 as Green List (high evidence)
Basal Cell Cancer v0.3 PTCH1 Chirag Patel Gene: ptch1 has been classified as Green List (High Evidence).
Basal Cell Cancer v0.2 PTCH1 Chirag Patel Classified gene: PTCH1 as Green List (high evidence)
Basal Cell Cancer v0.2 PTCH1 Chirag Patel Gene: ptch1 has been classified as Green List (High Evidence).
Basal Cell Cancer v0.1 PTCH1 Chirag Patel gene: PTCH1 was added
gene: PTCH1 was added to Basal Cell Cancer. Sources: Expert list,Expert Review
Mode of inheritance for gene: PTCH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PTCH1 were set to Basal cell carcinoma, MONDO:0020804; Basal cell nevus syndrome 1, MONDO:0958174; Basal cell nevus syndrome 1, MIM#109400
Review for gene: PTCH1 was set to GREEN
Added comment: ClinGen definitive
Basal cell cancers reported in condition
Sources: Expert list, Expert Review
Schwannoma v0.12 SMARCA4 Chirag Patel gene: SMARCA4 was added
gene: SMARCA4 was added to Schwannoma. Sources: Expert Review,Literature
Mode of inheritance for gene: SMARCA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMARCA4 were set to PMID: 36786840
Phenotypes for gene: SMARCA4 were set to Schwannoma, MONDO:0002546; Rhabdoid tumor predisposition syndrome 2, MONDO:0013224; Rhabdoid tumor predisposition syndrome 2, MIM#613325
Review for gene: SMARCA4 was set to RED
Added comment: ClinGen definitive for RTPS2

1 family with 3 affected individuals with adult-onset schwannomas (2/3), glioblastoma (1/3), and malignant peripheral nerve sheath tumour (1/3). Whole-genome sequencing in proband identified a variant in SMARCA4 gene ([c.1752_1755del, p.(Lys585Argfs*27).

In the schwannomas, immunohistochemical (IHC) staining showed loss of BRG1 (SMARCA4) expression in 80–90% of cells and loss of INI1 (SMARCB1) in the complementary 10–20% of cells in all 5 schwannomas but complete retention of BRG1 and INI1 in the glioblastoma.

Whole exome sequencing (WES) of DNA from proband's blood, mother’s normal skin, all 5
schwannomas and the glioblastoma, confirmed the presence of the truncating SMARCA4 LPV in all samples. LOH was observed at the SMARCA4 locus, extending to 12–23 Mb of Chromosome 19p (Chr19p) in all schwannomas, but not in the glioblastoma. No LOH of Chr22q was detected in the schwannomas. The germline SMARCA4 variant was also detected in proband's maternal grandfather’s MPNST in a heterozygous state.
Sources: Expert Review, Literature
Neuroblastoma v0.6 SMARCA4 Chirag Patel changed review comment from: ClinGen definitive for RTPS2

11 patients with neuroblastoma (age of diagnosis from 2 months-26 years) with heterozygous germline variants in SMARCA4. Eight of the germline variants were expected to result in loss of function of SMARCA4 (large deletion, truncating and canonical splice variants), while the remaining four were missense variants. Loss of heterozygosity of the wild-type SMARCA4 allele was found in all eight cases where somatic testing was performed, supporting the notion that SMARCA4 functions as a classic tumour suppressor.
Sources: Expert Review, Literature; to: ClinGen definitive for RTPS2

11 patients with neuroblastoma (age of diagnosis from 2 months-26 years) with heterozygous germline variants in SMARCA4. Eight of the germline variants were expected to result in loss of function of SMARCA4 (large deletion, truncating and canonical splice variants), while the remaining four were missense variants. Loss of heterozygosity of the wild-type SMARCA4 allele was found in all eight cases where somatic testing was performed, supporting the notion that SMARCA4 functions as a classic tumour suppressor.
Sources: Expert Review, Literature
Neuroblastoma v0.6 SMARCA4 Chirag Patel Classified gene: SMARCA4 as Amber List (moderate evidence)
Neuroblastoma v0.6 SMARCA4 Chirag Patel Gene: smarca4 has been classified as Amber List (Moderate Evidence).
Neuroblastoma v0.5 SMARCA4 Chirag Patel gene: SMARCA4 was added
gene: SMARCA4 was added to Neuroblastoma. Sources: Expert Review,Literature
Mode of inheritance for gene: SMARCA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SMARCA4 were set to Neuroblastoma, MONDO:0005072; Rhabdoid tumor predisposition syndrome 2, MONDO:0013224; Rhabdoid tumor predisposition syndrome 2, MIM#613325
Review for gene: SMARCA4 was set to AMBER
Added comment: ClinGen definitive for RTPS2

11 patients with neuroblastoma (age of diagnosis from 2 months-26 years) with heterozygous germline variants in SMARCA4. Eight of the germline variants were expected to result in loss of function of SMARCA4 (large deletion, truncating and canonical splice variants), while the remaining four were missense variants. Loss of heterozygosity of the wild-type SMARCA4 allele was found in all eight cases where somatic testing was performed, supporting the notion that SMARCA4 functions as a classic tumour suppressor.
Sources: Expert Review, Literature
Neuroblastoma v0.4 PHOX2B Chirag Patel Classified gene: PHOX2B as Green List (high evidence)
Neuroblastoma v0.4 PHOX2B Chirag Patel Gene: phox2b has been classified as Green List (High Evidence).
Neuroblastoma v0.3 PHOX2B Chirag Patel gene: PHOX2B was added
gene: PHOX2B was added to Neuroblastoma. Sources: Expert list,Expert Review
Mode of inheritance for gene: PHOX2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PHOX2B were set to PMID: 17637745
Phenotypes for gene: PHOX2B were set to Neuroblastoma, MONDO:0005072; Neuroblastoma susceptibility to 2, MONDO:0700041; Neuroblastoma, susceptibility to, 2, MIM#613013; Neuroblastoma with Hirschsprung disease, MIM #613013
Review for gene: PHOX2B was set to GREEN
Added comment: ClinGen definitive
Sources: Expert list, Expert Review
Neuroblastoma v0.2 ALK Chirag Patel Classified gene: ALK as Green List (high evidence)
Neuroblastoma v0.2 ALK Chirag Patel Gene: alk has been classified as Green List (High Evidence).
Neuroblastoma v0.1 ALK Chirag Patel gene: ALK was added
gene: ALK was added to Neuroblastoma. Sources: Expert list,Expert Review
Mode of inheritance for gene: ALK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ALK were set to PMID: 18724359
Phenotypes for gene: ALK were set to Neuroblastoma, MONDO:0005072; Neuroblastoma susceptibility to 3, MONDO:0013083; Neuroblastoma, susceptibility to, 3, MIM#613014
Review for gene: ALK was set to GREEN
Added comment: ClinGen definitive
Sources: Expert list, Expert Review
Schwannoma v0.11 DGCR8 Chirag Patel gene: DGCR8 was added
gene: DGCR8 was added to Schwannoma. Sources: Literature,Expert Review
Mode of inheritance for gene: DGCR8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DGCR8 were set to PMID: 31805011
Phenotypes for gene: DGCR8 were set to Schwannoma, MONDO:0002546; Early-onset multinodular goiter and schwannomatosis, no MIM#
Review for gene: DGCR8 was set to RED
Added comment: 1 family with 6 affected individuals with early-onset MNG (6/6) and adult-onset schwannomatosis (5/6). Whole-exome sequencing identified a variant in DGCR8 gene (c.1552G>A; p.E518K) which segregated with disease.

Copy number loss of chromosome 22q, leading to loss of heterozygosity at the DGCR8 locus, was found in all 13 tissue samples from familial and nonfamilial DGCR8-E518K-positive tumours. miRNA profiling of PTCs, MNG, schwannomas, and Wilms tumours revealed a common profile among E518K hemizygous tumours. In vitro cleavage demonstrated improper processing of pre-miRNA by DGCR8-E518K. MicroRNA and RNA profiling show that this variant disrupts precursor microRNA production, impacting populations of canonical microRNAs and mirtrons.
Sources: Literature, Expert Review
Bone Marrow Failure v1.95 RBSN Zornitza Stark Marked gene: RBSN as ready
Bone Marrow Failure v1.95 RBSN Zornitza Stark Gene: rbsn has been classified as Red List (Low Evidence).
Bone Marrow Failure v1.95 RBSN Zornitza Stark gene: RBSN was added
gene: RBSN was added to Bone Marrow Failure. Sources: Literature
Mode of inheritance for gene: RBSN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RBSN were set to 29784638
Phenotypes for gene: RBSN were set to Myelofibrosis, congenital, with anemia, neutropenia, developmental delay, and ocular abnormalities, MIM# 620939
Review for gene: RBSN was set to RED
Added comment: Single family reported, 3 affected sibs, homozygous splice site variant. However, also note biallelic variants in this gene have also been associated with a neurodevelopmental syndrome in the absence of bone marrow involvement, Kariminejad-Reversade neurodevelopmental syndrome, MIM#620937. Given the overall small number of families reported, it is currently unclear whether these are two distinct disorders or part of a spectrum.
Sources: Literature
Schwannoma v0.10 LZTR1 Chirag Patel Classified gene: LZTR1 as Green List (high evidence)
Schwannoma v0.10 LZTR1 Chirag Patel Gene: lztr1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6207 RBSN Zornitza Stark Phenotypes for gene: RBSN were changed from intellectual disability, MONDO:0001071 to Kariminejad-Reversade neurodevelopmental syndrome, MIM# 620937
Intellectual disability syndromic and non-syndromic v0.6206 RBSN Zornitza Stark reviewed gene: RBSN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Kariminejad-Reversade neurodevelopmental syndrome, MIM# 620937; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2013 RBSN Zornitza Stark Phenotypes for gene: RBSN were changed from intellectual disability, MONDO:0001071, RBSN-related to Kariminejad-Reversade neurodevelopmental syndrome, MIM# 620937
Schwannoma v0.9 LZTR1 Chirag Patel gene: LZTR1 was added
gene: LZTR1 was added to Schwannoma. Sources: Expert list,Expert Review
Mode of inheritance for gene: LZTR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LZTR1 were set to PMID: 24362817, 29517885
Phenotypes for gene: LZTR1 were set to Schwannoma, MONDO:0002546; Schwannomatosis 2, MONDO:0014299; Schwannomatosis, susceptibility to, 2, MIM#615670
Review for gene: LZTR1 was set to GREEN
gene: LZTR1 was marked as current diagnostic
Added comment: 15 different germline heterozygous mutations in the LZTR1 gene identified in 16/20 probands with schwannomatosis. There were 6 truncating mutations, 1 in-frame splice site mutation, 1 deletion affecting a splice site, and 7 missense mutations at highly conserved residues. Mutations segregated with disease in all available affected first-degree relatives, although four asymptomatic parents also carried an LZTR1 mutation.

All schwannomas studied also carried the heterozygous LZTR1 mutation, and all showed loss of heterozygosity (LOH) at chromosome 22q11, including the LZTR1, NF2, and SMARCB1 genes. In addition, all tumours carried a heterozygous somatic mutation in the NF2 gene. These findings were consistent with biallelic loss of function of both LZTR1 and NF2 in all tumours. Functional studies of the variants were not performed. Pathogenesis of tumour characterised as resulting from 3 mutational events: a germline LZTR1 mutation (E1), a deletion of 22q that includes the LZTR1 and NF2 genes (E2), and a somatic NF2 mutation (E3). Loss of LZTR1 function can predispose to the development of autosomal dominant multiple schwannomas, thus implicating LZTR1 as a tumor suppressor gene.
Sources: Expert list, Expert Review
Mendeliome v1.2012 RBSN Zornitza Stark edited their review of gene: RBSN: Changed phenotypes: Kariminejad-Reversade neurodevelopmental syndrome, MIM# 620937
Schwannoma v0.8 PRKAR1A Chirag Patel Classified gene: PRKAR1A as Green List (high evidence)
Schwannoma v0.8 PRKAR1A Chirag Patel Gene: prkar1a has been classified as Green List (High Evidence).
Schwannoma v0.7 NF1 Chirag Patel Classified gene: NF1 as Green List (high evidence)
Schwannoma v0.7 NF1 Chirag Patel Gene: nf1 has been classified as Green List (High Evidence).
Schwannoma v0.6 NF2 Chirag Patel Classified gene: NF2 as Green List (high evidence)
Schwannoma v0.6 NF2 Chirag Patel Gene: nf2 has been classified as Green List (High Evidence).
Schwannoma v0.5 PRKAR1A Chirag Patel gene: PRKAR1A was added
gene: PRKAR1A was added to Schwannoma. Sources: Expert list,Expert Review
Mode of inheritance for gene: PRKAR1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PRKAR1A were set to Schwannoma, MONDO:0002546; Carney complex type 1, MONDO:0008057; Carney complex, type 1, MIM#160980
Review for gene: PRKAR1A was set to GREEN
gene: PRKAR1A was marked as current diagnostic
Added comment: ClinGen definitive
Schwannomas reported in condition
Sources: Expert list, Expert Review
Schwannoma v0.4 SMARCB1 Chirag Patel Classified gene: SMARCB1 as Green List (high evidence)
Schwannoma v0.4 SMARCB1 Chirag Patel Gene: smarcb1 has been classified as Green List (High Evidence).
Schwannoma v0.3 SMARCB1 Chirag Patel gene: SMARCB1 was added
gene: SMARCB1 was added to Schwannoma. Sources: Expert list,Expert Review
Mode of inheritance for gene: SMARCB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SMARCB1 were set to Schwannoma, MONDO:0002546; Schwannomatosis 1, MONDO:0024517; Rhabdoid tumor predisposition syndrome 1, MONDO:0012252; Rhabdoid tumor predisposition syndrome 1, MIM#609322; Schwannomatosis, susceptibility to, 1, MIM#162091
Review for gene: SMARCB1 was set to GREEN
gene: SMARCB1 was marked as current diagnostic
Added comment: ClinGen definitive
Schwannomas reported in condition
Sources: Expert list, Expert Review
Schwannoma v0.2 NF2 Chirag Patel gene: NF2 was added
gene: NF2 was added to Schwannoma. Sources: Expert list,Expert Review
Mode of inheritance for gene: NF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: NF2 were set to Schwannoma, MONDO:0002546; Neurofibromatosis type 2, MONDO:0007039; Neurofibromatosis, type 2, MIM#607174
Review for gene: NF2 was set to GREEN
gene: NF2 was marked as current diagnostic
Added comment: ClinGen definitive
Schwannomas reported in condition
Sources: Expert list, Expert Review
Schwannoma v0.1 NF1 Chirag Patel gene: NF1 was added
gene: NF1 was added to Schwannoma. Sources: Expert list,Expert Review
Mode of inheritance for gene: NF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: NF1 were set to Schwannoma, MONDO:0002546; Neurofibromatosis type 1, MONDO:0018975; Neurofibromatosis, type 1, MIM#162200
Review for gene: NF1 was set to GREEN
gene: NF1 was marked as current diagnostic
Added comment: ClinGen definitive
Schwannomas reported in condition
Sources: Expert list, Expert Review
Meningioma v0.10 SUFU Chirag Patel Classified gene: SUFU as Green List (high evidence)
Meningioma v0.10 SUFU Chirag Patel Gene: sufu has been classified as Green List (High Evidence).
Meningioma v0.9 SMARCE1 Chirag Patel Classified gene: SMARCE1 as Green List (high evidence)
Meningioma v0.9 SMARCE1 Chirag Patel Gene: smarce1 has been classified as Green List (High Evidence).
Meningioma v0.8 SMARCB1 Chirag Patel Classified gene: SMARCB1 as Green List (high evidence)
Meningioma v0.8 SMARCB1 Chirag Patel Gene: smarcb1 has been classified as Green List (High Evidence).
Meningioma v0.7 NF2 Chirag Patel Classified gene: NF2 as Green List (high evidence)
Meningioma v0.7 NF2 Chirag Patel Gene: nf2 has been classified as Green List (High Evidence).
Meningioma v0.6 BAP1 Chirag Patel Classified gene: BAP1 as Green List (high evidence)
Meningioma v0.6 BAP1 Chirag Patel Gene: bap1 has been classified as Green List (High Evidence).
Meningioma v0.5 SUFU Chirag Patel gene: SUFU was added
gene: SUFU was added to Meningioma. Sources: Expert list,Expert Review
Mode of inheritance for gene: SUFU was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SUFU were set to Meningioma, MONDO:0016642; Basal cell nevus syndrome 2, MONDO:0958189; Basal cell nevus syndrome 2, MIM#620343; Meningioma, familial, susceptibility to, MIM#607174; Medulloblastoma predisposition syndrome, MIM#155255
Review for gene: SUFU was set to GREEN
gene: SUFU was marked as current diagnostic
Added comment: ClinGen definitive
Meningiomas reported in condition
Sources: Expert list, Expert Review
Meningioma v0.4 SMARCE1 Chirag Patel gene: SMARCE1 was added
gene: SMARCE1 was added to Meningioma. Sources: Expert list,Expert Review
Mode of inheritance for gene: SMARCE1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SMARCE1 were set to Meningioma, MONDO:0016642; Meningioma, familial, susceptibility to, MIM#607174
Review for gene: SMARCE1 was set to GREEN
gene: SMARCE1 was marked as current diagnostic
Added comment: ClinGen definitive
Sources: Expert list, Expert Review
Meningioma v0.3 SMARCB1 Chirag Patel gene: SMARCB1 was added
gene: SMARCB1 was added to Meningioma. Sources: Expert list,Expert Review
Mode of inheritance for gene: SMARCB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SMARCB1 were set to Meningioma, MONDO:0016642; Rhabdoid tumor predisposition syndrome 1, MONDO:0012252; Rhabdoid tumor predisposition syndrome 1, MIM#609322; Schwannomatosis, susceptibility to, 1, MIM#162091
Review for gene: SMARCB1 was set to GREEN
gene: SMARCB1 was marked as current diagnostic
Added comment: ClinGen definitive
Meningiomas reported in condition
Sources: Expert list, Expert Review
Meningioma v0.2 NF2 Chirag Patel gene: NF2 was added
gene: NF2 was added to Meningioma. Sources: Expert list,Expert Review
Mode of inheritance for gene: NF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: NF2 were set to Meningioma, MONDO:0016642; Neurofibromatosis type 2, MONDO:0007039; Neurofibromatosis, type 2, MIM#607174
Review for gene: NF2 was set to GREEN
gene: NF2 was marked as current diagnostic
Added comment: ClinGen definitive
Meningiomas reported in condition
Sources: Expert list, Expert Review
Meningioma v0.1 BAP1 Chirag Patel gene: BAP1 was added
gene: BAP1 was added to Meningioma. Sources: Expert list,Expert Review
Mode of inheritance for gene: BAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: BAP1 were set to Meningioma, MONDO:0016642; BAP1-related tumor predisposition syndrome, MONDO:0013692; BAP1-tumour predisposition syndrome, MIM#614327
Review for gene: BAP1 was set to GREEN
gene: BAP1 was marked as current diagnostic
Added comment: ClinGen definitive
Meningiomas reported in condition
Sources: Expert list, Expert Review
Breast Cancer v0.0 Chirag Patel Added Panel Breast Cancer
Set panel types to: Cancer Germline
Ovarian Cancer v0.0 Chirag Patel Added Panel Ovarian Cancer
Set panel types to: Cancer Germline
Endometrial Cancer v0.0 Chirag Patel Added Panel Endometrial Cancer
Set panel types to: Cancer Germline
Prostate Cancer v0.0 Chirag Patel Added Panel Prostate Cancer
Set panel types to: Cancer Germline
Colorectal Cancer and Polyposis v0.0 Chirag Patel Added Panel Colorectal Cancer and Polyposis
Set panel types to: Cancer Germline
Pancreatic Cancer v0.0 Chirag Patel Added Panel Pancreatic Cancer
Set panel types to: Cancer Germline
Gastrointestinal Stromal Tumour v0.0 Chirag Patel Added Panel Gastrointestinal Stromal Tumour
Set panel types to: Cancer Germline
Diffuse Gastric Cancer v0.0 Chirag Patel Added Panel Diffuse Gastric Cancer
Set panel types to: Cancer Germline
Kidney Cancer v0.0 Chirag Patel Added Panel Kidney Cancer
Set panel types to: Cancer Germline
Wilms Tumour v0.0 Chirag Patel Added Panel Wilms Tumour
Set panel types to: Cancer Germline
Paraganglioma_phaeochromocytoma v0.0 Chirag Patel Added Panel Paraganglioma_phaeochromocytoma
Set panel types to: Cancer Germline
Pituitary Tumour v0.0 Chirag Patel Added Panel Pituitary Tumour
Set panel types to: Cancer Germline
Parathyroid Tumour v0.0 Chirag Patel Added Panel Parathyroid Neoplasm
Set panel types to: Cancer Germline
Thyroid Cancer v0.0 Chirag Patel Added Panel Thyroid Neoplasm
Set panel types to: Cancer Germline
Melanoma v0.5 Chirag Patel Panel status changed from public to retired
Neuroblastoma v0.0 Chirag Patel Added Panel Neuroblastoma
Set panel types to: Cancer Germline
Basal Cell Cancer v0.0 Chirag Patel Added Panel Basal Cell Cancer
Set panel types to: Cancer Germline
Medulloblastoma v0.11 Chirag Patel Panel status changed from public to retired
Sarcoma non-soft tissue v0.0 Chirag Patel Added Panel Sarcoma non-soft tissue
Set panel types to: Cancer Germline
Sarcoma soft tissue v0.0 Chirag Patel Added Panel Sarcoma soft tissue
Set panel types to: Cancer Germline
Schwannoma v0.0 Chirag Patel Added Panel Schwannoma
Set panel types to: Cancer Germline
Meningioma v0.0 Chirag Patel Added Panel Meningioma
Set panel types to: Cancer Germline
Mendeliome v1.2012 B2M Bryony Thompson Mode of inheritance for gene: B2M was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.2011 B2M Bryony Thompson reviewed gene: B2M: Rating: GREEN; Mode of pathogenicity: None; Publications: 22693999, 37223323, 24014031, 35575118, 32875920; Phenotypes: variant ABeta2M amyloidosis MONDO:0017810; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Genetic Epilepsy v1.56 RNU2-2P Zornitza Stark Marked gene: RNU2-2P as ready
Genetic Epilepsy v1.56 RNU2-2P Zornitza Stark Gene: rnu2-2p has been classified as Green List (High Evidence).
Mendeliome v1.2011 RNU2-2P Zornitza Stark Marked gene: RNU2-2P as ready
Mendeliome v1.2011 RNU2-2P Zornitza Stark Gene: rnu2-2p has been classified as Green List (High Evidence).
Mendeliome v1.2011 RNU2-2P Zornitza Stark Classified gene: RNU2-2P as Green List (high evidence)
Mendeliome v1.2011 RNU2-2P Zornitza Stark Gene: rnu2-2p has been classified as Green List (High Evidence).
Mendeliome v1.2010 RNU2-2P Zornitza Stark gene: RNU2-2P was added
gene: RNU2-2P was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RNU2-2P was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RNU2-2P were set to https://www.medrxiv.org/content/10.1101/2024.09.03.24312863v1
Phenotypes for gene: RNU2-2P were set to Neurodevelopmental disorder, MONDO:0700092, RNU2-2P-related
Review for gene: RNU2-2P was set to GREEN
Added comment: 15 individuals reported with de novo, recurrent variants in this gene at nucleotide positions 4 and 35. The disorder is characterized by intellectual disability, neurodevelopmental delay, autistic behavior, microcephaly, hypotonia, epilepsy and hyperventilation. All cases display a severe and complex seizure phenotype.
Sources: Literature
Genetic Epilepsy v1.56 RNU2-2P Zornitza Stark Classified gene: RNU2-2P as Green List (high evidence)
Genetic Epilepsy v1.56 RNU2-2P Zornitza Stark Gene: rnu2-2p has been classified as Green List (High Evidence).
Genetic Epilepsy v1.55 RNU2-2P Zornitza Stark Classified gene: RNU2-2P as Green List (high evidence)
Genetic Epilepsy v1.55 RNU2-2P Zornitza Stark Gene: rnu2-2p has been classified as Green List (High Evidence).
Genetic Epilepsy v1.54 RNU2-2P Zornitza Stark gene: RNU2-2P was added
gene: RNU2-2P was added to Genetic Epilepsy. Sources: Literature
Mode of inheritance for gene: RNU2-2P was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RNU2-2P were set to https://www.medrxiv.org/content/10.1101/2024.09.03.24312863v1
Phenotypes for gene: RNU2-2P were set to Neurodevelopmental disorder, MONDO:0700092, RNU2-2P-related
Review for gene: RNU2-2P was set to GREEN
Added comment: 15 individuals reported with de novo, recurrent variants in this gene at nucleotide positions 4 and 35. The disorder is characterized by intellectual disability, neurodevelopmental delay, autistic behavior, microcephaly, hypotonia, epilepsy and hyperventilation. All cases display a severe and complex seizure phenotype.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6206 RNU2-2P Zornitza Stark Marked gene: RNU2-2P as ready
Intellectual disability syndromic and non-syndromic v0.6206 RNU2-2P Zornitza Stark Gene: rnu2-2p has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6206 RNU2-2P Zornitza Stark Classified gene: RNU2-2P as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6206 RNU2-2P Zornitza Stark Gene: rnu2-2p has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6205 RNU2-2P Zornitza Stark gene: RNU2-2P was added
gene: RNU2-2P was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: RNU2-2P was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RNU2-2P were set to https://www.medrxiv.org/content/10.1101/2024.09.03.24312863v1
Phenotypes for gene: RNU2-2P were set to Neurodevelopmental disorder, MONDO:0700092, RNU2-2P-related
Review for gene: RNU2-2P was set to GREEN
Added comment: 15 individuals reported with de novo, recurrent variants in this gene at nucleotide positions 4 and 35. The disorder is characterized by intellectual disability, neurodevelopmental delay, autistic behavior, microcephaly, hypotonia, epilepsy and hyperventilation. All cases display a severe and complex seizure phenotype.
Sources: Literature
Prepair 1000+ v1.287 NYX Andrew Coventry reviewed gene: NYX: Rating: GREEN; Mode of pathogenicity: None; Publications: 11062471 11062472 16670814 23714322 34064005 34165036 12506099 11062471 17004930; Phenotypes: Night blindness, congenital stationary (complete), 1A, X-linked MIM310500; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.287 NPHS2 Andrew Coventry reviewed gene: NPHS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32467597 30260545 24509478 10742096 23242530 24509478 12464671; Phenotypes: Nephrotic syndrome, type 2 MIM#600995; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2009 PNKP Shakira Heerah reviewed gene: PNKP: Rating: GREEN; Mode of pathogenicity: None; Publications: 31436889, 31707899, 20118933, 23224214, 29243230, 2578773, 27066567; Phenotypes: Ataxia-oculomotor apraxia 4, Microcephaly, seizures, and developmental delay, Charcot-Marie-Tooth disease, type 2B2; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.287 NIPAL4 Andrew Coventry reviewed gene: NIPAL4: Rating: GREEN; Mode of pathogenicity: None; Publications: 15317751 17557927 10712205; Phenotypes: Ichthyosis, congenital, autosomal recessive 6 MIM#612281; Mode of inheritance: None
Prepair 1000+ v1.287 MPLKIP Andrew Coventry reviewed gene: MPLKIP: Rating: GREEN; Mode of pathogenicity: None; Publications: 15645389 16977596; Phenotypes: Trichothiodystrophy 4, nonphotosensitive MIM#234050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.287 MGAT2 Andrew Coventry reviewed gene: MGAT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 8808595 11228641 22105986 33044030 31420886; Phenotypes: Congenital disorder of glycosylation, type IIa MIM#212066; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.287 CTSF Cassandra Muller reviewed gene: CTSF: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ceroid lipofuscinosis, neuronal, 13, Kufs type, 615362 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.287 MCFD2 Andrew Coventry reviewed gene: MCFD2: Rating: AMBER; Mode of pathogenicity: None; Publications: 12717434 17610559 18391077 15886209; Phenotypes: Factor V and factor VIII, combined deficiency of MIM#613625; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.2009 NFU1 Zornitza Stark Phenotypes for gene: NFU1 were changed from Multiple mitochondrial dysfunctions syndrome 1, MIM# 605711 to Multiple mitochondrial dysfunctions syndrome 1, MIM# 605711; Spastic paraplegia 93, autosomal recessive, MIM# 620938
Mendeliome v1.2008 NFU1 Zornitza Stark edited their review of gene: NFU1: Changed phenotypes: Multiple mitochondrial dysfunctions syndrome 1, MIM# 605711, Spastic paraplegia 93, autosomal recessive, MIM# 620938
Hereditary Spastic Paraplegia - paediatric v1.84 NFU1 Zornitza Stark Phenotypes for gene: NFU1 were changed from Multiple mitochondrial dysfunctions syndrome 1 (MIM#605711) to Multiple mitochondrial dysfunctions syndrome 1 (MIM#605711); Spastic paraplegia 93, autosomal recessive, MIM# 620938
Hereditary Spastic Paraplegia - paediatric v1.83 NFU1 Zornitza Stark reviewed gene: NFU1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 93, autosomal recessive, MIM# 620938; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.287 LRP5 Andrew Coventry reviewed gene: LRP5: Rating: GREEN; Mode of pathogenicity: None; Publications: 9056564 9831343 11719191 15346351 18602879; Phenotypes: Exudative vitreoretinopathy 4 MIM#601813, Osteoporosis-pseudoglioma syndrome MIM#259770; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Amyloidosis v0.27 Bryony Thompson Panel name changed from Renal Amyloidosis to Amyloidosis
HPO terms changed from Renal amyloidosis, HP:0001917 to Renal amyloidosis, HP:0001917; Amyloidosis, HP:0011034
List of related panels changed from Renal amyloidosis; HP:0001917 to Renal amyloidosis; HP:0001917; Amyloidosis; HP:0011034
Panel types changed to Victorian Clinical Genetics Services; KidGen; Royal Melbourne Hospital
Lysosomal Storage Disorder v1.13 SGMS1 Bryony Thompson Marked gene: SGMS1 as ready
Lysosomal Storage Disorder v1.13 SGMS1 Bryony Thompson Gene: sgms1 has been classified as Amber List (Moderate Evidence).
Lysosomal Storage Disorder v1.13 SGMS1 Bryony Thompson Classified gene: SGMS1 as Amber List (moderate evidence)
Lysosomal Storage Disorder v1.13 SGMS1 Bryony Thompson Gene: sgms1 has been classified as Amber List (Moderate Evidence).
Lysosomal Storage Disorder v1.12 SGMS1 Bryony Thompson Classified gene: SGMS1 as Amber List (moderate evidence)
Lysosomal Storage Disorder v1.12 SGMS1 Bryony Thompson Gene: sgms1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2008 SGMS1 Bryony Thompson Marked gene: SGMS1 as ready
Mendeliome v1.2008 SGMS1 Bryony Thompson Gene: sgms1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2008 SGMS1 Bryony Thompson Classified gene: SGMS1 as Amber List (moderate evidence)
Mendeliome v1.2008 SGMS1 Bryony Thompson Gene: sgms1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6204 REPS2 Bryony Thompson Marked gene: REPS2 as ready
Intellectual disability syndromic and non-syndromic v0.6204 REPS2 Bryony Thompson Gene: reps2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6204 REPS2 Bryony Thompson Classified gene: REPS2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6204 REPS2 Bryony Thompson Gene: reps2 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.368 REPS2 Bryony Thompson Marked gene: REPS2 as ready
Cerebral Palsy v1.368 REPS2 Bryony Thompson Gene: reps2 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.368 REPS2 Bryony Thompson Classified gene: REPS2 as Amber List (moderate evidence)
Cerebral Palsy v1.368 REPS2 Bryony Thompson Gene: reps2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6203 TTL Bryony Thompson Marked gene: TTL as ready
Intellectual disability syndromic and non-syndromic v0.6203 TTL Bryony Thompson Gene: ttl has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.368 REPS2 Bryony Thompson Classified gene: REPS2 as Amber List (moderate evidence)
Cerebral Palsy v1.368 REPS2 Bryony Thompson Gene: reps2 has been classified as Amber List (Moderate Evidence).
Tubulinopathies v1.2 TTL Bryony Thompson Marked gene: TTL as ready
Tubulinopathies v1.2 TTL Bryony Thompson Gene: ttl has been classified as Amber List (Moderate Evidence).
Tubulinopathies v1.2 TTL Bryony Thompson Classified gene: TTL as Amber List (moderate evidence)
Tubulinopathies v1.2 TTL Bryony Thompson Gene: ttl has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6203 TTL Bryony Thompson Classified gene: TTL as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6203 TTL Bryony Thompson Gene: ttl has been classified as Amber List (Moderate Evidence).
Tubulinopathies v1.2 TTL Bryony Thompson Classified gene: TTL as Amber List (moderate evidence)
Tubulinopathies v1.2 TTL Bryony Thompson Gene: ttl has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2007 REPS2 Bryony Thompson Marked gene: REPS2 as ready
Mendeliome v1.2007 REPS2 Bryony Thompson Gene: reps2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2007 TTL Bryony Thompson Marked gene: TTL as ready
Mendeliome v1.2007 TTL Bryony Thompson Gene: ttl has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2007 REPS2 Bryony Thompson Classified gene: REPS2 as Amber List (moderate evidence)
Mendeliome v1.2007 REPS2 Bryony Thompson Gene: reps2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2006 TTL Bryony Thompson Classified gene: TTL as Amber List (moderate evidence)
Mendeliome v1.2006 TTL Bryony Thompson Gene: ttl has been classified as Amber List (Moderate Evidence).
Mitochondrial disease v0.930 MRPL42 Bryony Thompson Marked gene: MRPL42 as ready
Mitochondrial disease v0.930 MRPL42 Bryony Thompson Gene: mrpl42 has been classified as Red List (Low Evidence).
Mitochondrial disease v0.930 MRPL42 Bryony Thompson Classified gene: MRPL42 as Red List (low evidence)
Mitochondrial disease v0.930 MRPL42 Bryony Thompson Gene: mrpl42 has been classified as Red List (Low Evidence).
Mendeliome v1.2005 MRPL42 Bryony Thompson Marked gene: MRPL42 as ready
Mendeliome v1.2005 MRPL42 Bryony Thompson Gene: mrpl42 has been classified as Red List (Low Evidence).
Mendeliome v1.2005 MRPL42 Bryony Thompson Classified gene: MRPL42 as Red List (low evidence)
Mendeliome v1.2005 MRPL42 Bryony Thompson Gene: mrpl42 has been classified as Red List (Low Evidence).
Mendeliome v1.2004 MED16 Bryony Thompson Marked gene: MED16 as ready
Mendeliome v1.2004 MED16 Bryony Thompson Gene: med16 has been classified as Green List (High Evidence).
Mendeliome v1.2004 MED16 Bryony Thompson Classified gene: MED16 as Green List (high evidence)
Mendeliome v1.2004 MED16 Bryony Thompson Gene: med16 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6202 GPN2 Bryony Thompson Marked gene: GPN2 as ready
Intellectual disability syndromic and non-syndromic v0.6202 GPN2 Bryony Thompson Gene: gpn2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6202 GPN2 Bryony Thompson Classified gene: GPN2 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6202 GPN2 Bryony Thompson Gene: gpn2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2003 GPN2 Bryony Thompson Marked gene: GPN2 as ready
Mendeliome v1.2003 GPN2 Bryony Thompson Gene: gpn2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2003 GPN2 Bryony Thompson Classified gene: GPN2 as Amber List (moderate evidence)
Mendeliome v1.2003 GPN2 Bryony Thompson Gene: gpn2 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6201 FKBP4 Bryony Thompson Marked gene: FKBP4 as ready
Intellectual disability syndromic and non-syndromic v0.6201 FKBP4 Bryony Thompson Gene: fkbp4 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6201 FKBP4 Bryony Thompson Classified gene: FKBP4 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6201 FKBP4 Bryony Thompson Gene: fkbp4 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.294 FKBP4 Bryony Thompson Marked gene: FKBP4 as ready
Differences of Sex Development v0.294 FKBP4 Bryony Thompson Gene: fkbp4 has been classified as Amber List (Moderate Evidence).
Differences of Sex Development v0.294 FKBP4 Bryony Thompson Classified gene: FKBP4 as Amber List (moderate evidence)
Differences of Sex Development v0.294 FKBP4 Bryony Thompson Gene: fkbp4 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2002 FKBP4 Bryony Thompson Marked gene: FKBP4 as ready
Mendeliome v1.2002 FKBP4 Bryony Thompson Gene: fkbp4 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2002 FKBP4 Bryony Thompson Classified gene: FKBP4 as Amber List (moderate evidence)
Mendeliome v1.2002 FKBP4 Bryony Thompson Gene: fkbp4 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6200 EIF3I Bryony Thompson Marked gene: EIF3I as ready
Intellectual disability syndromic and non-syndromic v0.6200 EIF3I Bryony Thompson Gene: eif3i has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6200 EIF3I Bryony Thompson Classified gene: EIF3I as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6200 EIF3I Bryony Thompson Gene: eif3i has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6199 EIF3I Bryony Thompson Classified gene: EIF3I as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6199 EIF3I Bryony Thompson Gene: eif3i has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2001 EIF3I Bryony Thompson Marked gene: EIF3I as ready
Mendeliome v1.2001 EIF3I Bryony Thompson Gene: eif3i has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2001 EIF3I Bryony Thompson Classified gene: EIF3I as Amber List (moderate evidence)
Mendeliome v1.2001 EIF3I Bryony Thompson Gene: eif3i has been classified as Amber List (Moderate Evidence).
Ciliary Dyskinesia v1.40 DNAH17 Bryony Thompson Marked gene: DNAH17 as ready
Ciliary Dyskinesia v1.40 DNAH17 Bryony Thompson Gene: dnah17 has been classified as Green List (High Evidence).
Ciliary Dyskinesia v1.40 DNAH17 Bryony Thompson Classified gene: DNAH17 as Green List (high evidence)
Ciliary Dyskinesia v1.40 DNAH17 Bryony Thompson Gene: dnah17 has been classified as Green List (High Evidence).
Mendeliome v1.2000 DNAH17 Bryony Thompson Marked gene: DNAH17 as ready
Mendeliome v1.2000 DNAH17 Bryony Thompson Gene: dnah17 has been classified as Green List (High Evidence).
Mendeliome v1.2000 DNAH17 Bryony Thompson Classified gene: DNAH17 as Green List (high evidence)
Mendeliome v1.2000 DNAH17 Bryony Thompson Gene: dnah17 has been classified as Green List (High Evidence).
Joubert syndrome and other neurological ciliopathies v1.28 CEP76 Bryony Thompson Marked gene: CEP76 as ready
Joubert syndrome and other neurological ciliopathies v1.28 CEP76 Bryony Thompson Gene: cep76 has been classified as Amber List (Moderate Evidence).
Joubert syndrome and other neurological ciliopathies v1.28 CEP76 Bryony Thompson Classified gene: CEP76 as Amber List (moderate evidence)
Joubert syndrome and other neurological ciliopathies v1.28 CEP76 Bryony Thompson Gene: cep76 has been classified as Amber List (Moderate Evidence).
Syndromic Retinopathy v0.214 CEP76 Bryony Thompson Marked gene: CEP76 as ready
Syndromic Retinopathy v0.214 CEP76 Bryony Thompson Gene: cep76 has been classified as Green List (High Evidence).
Syndromic Retinopathy v0.214 CEP76 Bryony Thompson Classified gene: CEP76 as Green List (high evidence)
Syndromic Retinopathy v0.214 CEP76 Bryony Thompson Gene: cep76 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6198 CEP76 Bryony Thompson Marked gene: CEP76 as ready
Intellectual disability syndromic and non-syndromic v0.6198 CEP76 Bryony Thompson Gene: cep76 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6198 CEP76 Bryony Thompson Classified gene: CEP76 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6198 CEP76 Bryony Thompson Gene: cep76 has been classified as Green List (High Evidence).
Ciliopathies v1.60 CEP76 Bryony Thompson Marked gene: CEP76 as ready
Ciliopathies v1.60 CEP76 Bryony Thompson Gene: cep76 has been classified as Green List (High Evidence).
Ciliopathies v1.60 CEP76 Bryony Thompson Classified gene: CEP76 as Green List (high evidence)
Ciliopathies v1.60 CEP76 Bryony Thompson Gene: cep76 has been classified as Green List (High Evidence).
Mendeliome v1.1999 CEP76 Bryony Thompson Marked gene: CEP76 as ready
Mendeliome v1.1999 CEP76 Bryony Thompson Gene: cep76 has been classified as Green List (High Evidence).
Mendeliome v1.1999 CEP76 Bryony Thompson Classified gene: CEP76 as Green List (high evidence)
Mendeliome v1.1999 CEP76 Bryony Thompson Gene: cep76 has been classified as Green List (High Evidence).
Amyloidosis v0.26 B2M Bryony Thompson Classified gene: B2M as Green List (high evidence)
Amyloidosis v0.26 B2M Bryony Thompson Gene: b2m has been classified as Green List (High Evidence).
Amyloidosis v0.25 B2M Bryony Thompson gene: B2M was added
gene: B2M was added to Renal Amyloidosis. Sources: Literature
Mode of inheritance for gene: B2M was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: B2M were set to 22693999; 37223323; 24014031; 35575118; 32875920
Phenotypes for gene: B2M were set to variant ABeta2M amyloidosis MONDO:0017810
Review for gene: B2M was set to GREEN
Added comment: 4 probands/families with amyloidosis and supporting in vitro functional studies.
Sources: Literature
Amyloidosis v0.24 TTR Bryony Thompson Marked gene: TTR as ready
Amyloidosis v0.24 TTR Bryony Thompson Gene: ttr has been classified as Green List (High Evidence).
Amyloidosis v0.24 TTR Bryony Thompson Classified gene: TTR as Green List (high evidence)
Amyloidosis v0.24 TTR Bryony Thompson Gene: ttr has been classified as Green List (High Evidence).
Amyloidosis v0.23 TTR Bryony Thompson gene: TTR was added
gene: TTR was added to Renal Amyloidosis. Sources: Literature
Mode of inheritance for gene: TTR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TTR were set to 20301373; 38484868
Phenotypes for gene: TTR were set to hereditary ATTR amyloidosis MONDO:0017132
Review for gene: TTR was set to GREEN
gene: TTR was marked as current diagnostic
Added comment: The kidney is one of the main organs affected by transthyretin amyloidosis.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6197 MRAS Krithika Murali Mode of inheritance for gene: MRAS was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6197 MRAS Krithika Murali Classified gene: MRAS as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6197 MRAS Krithika Murali Gene: mras has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6196 MRAS Krithika Murali Marked gene: MRAS as ready
Intellectual disability syndromic and non-syndromic v0.6196 MRAS Krithika Murali Gene: mras has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.6196 MRAS Krithika Murali gene: MRAS was added
gene: MRAS was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: MRAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MRAS were set to Noonan syndrome 11 - MIM#618499
Review for gene: MRAS was set to GREEN
Added comment: Developmental delay is a phenotypic feature
Sources: Literature
Spontaneous coronary artery dissection v0.53 FLNA Kunal Verma reviewed gene: FLNA: Rating: AMBER; Mode of pathogenicity: None; Publications: 34863227; Phenotypes: Spontaneous coronary artery dissection; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Renal Tubulopathies and related disorders v1.15 SLC36A2 Bryony Thompson Classified gene: SLC36A2 as Amber List (moderate evidence)
Renal Tubulopathies and related disorders v1.15 SLC36A2 Bryony Thompson Added comment: Comment on list classification: Biochemical phenotypes without adverse clinical consequences
Renal Tubulopathies and related disorders v1.15 SLC36A2 Bryony Thompson Gene: slc36a2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1998 CEP76 Mark Cleghorn gene: CEP76 was added
gene: CEP76 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: CEP76 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CEP76 were set to complex neurodevelopmental disorder MONDO:0100038; Joubert syndrome; Bardet-Biedl syndrome; retinitis pigmentosa
Penetrance for gene: CEP76 were set to unknown
Review for gene: CEP76 was set to GREEN
Added comment: Erica Davis, Stanley Manne Children’s research institute, Chicago
ESHG presentation 4/6/24, unpublished

CEP76 associated with syndromic ciliopathy

CEP76 localizes to centrioles and basal body primary cilia
Role in normal centriolar duplication

Index case
Bardet Biedl syndrome
Compound heterozygous pLoF variants in CEP76

Via Gene matcher
7 cases in 7 families- biallelic CEP76 and various clinical features within ciliopathy spectrum:
Obesity
Ocular phenotype
Structural brain anomalies
Renal?

3/7 families clinical Dx Joubert syndrome
1/7 BBS
1/7 GDD/ID NOS
2/7 retinitis pigmentosa (1 of these with learning difficulties)

Mixture of biallelic pLOF and missense variant

CEP76 knockout zebrafish model shows retinal phenotype w photoreceptor loss, similar to homozygous known BBS4 pathogenic variant

Cell based fx studies with missense variants above, consistent with centriolar duplication dysfunction
Sources: Other
Intellectual disability syndromic and non-syndromic v0.6195 CEP76 Mark Cleghorn gene: CEP76 was added
gene: CEP76 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: CEP76 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CEP76 were set to complex neurodevelopmental disorder MONDO:0100038; Joubert syndrome; Bardet-Biedl syndrome; retinitis pigmentosa
Penetrance for gene: CEP76 were set to unknown
Review for gene: CEP76 was set to GREEN
Added comment: Erica Davis, Stanley Manne Children’s research institute, Chicago
ESHG presentation 4/6/24, unpublished

CEP76 associated with syndromic ciliopathy

CEP76 localizes to centrioles and basal body primary cilia
Role in normal centriolar duplication

Index case
Bardet Biedl syndrome
Compound heterozygous pLoF variants in CEP76

Via Gene matcher
7 cases in 7 families- biallelic CEP76 and various clinical features within ciliopathy spectrum:
Obesity
Ocular phenotype
Structural brain anomalies
Renal?

3/7 families clinical Dx Joubert syndrome
1/7 BBS
1/7 GDD/ID NOS
2/7 retinitis pigmentosa (1 of these with learning difficulties)

Mixture of biallelic pLOF and missense variant

CEP76 knockout zebrafish model shows retinal phenotype w photoreceptor loss, similar to homozygous known BBS4 pathogenic variant

Cell based fx studies with missense variants above, consistent with centriolar duplication dysfunction
Sources: Other
Syndromic Retinopathy v0.213 CEP76 Mark Cleghorn gene: CEP76 was added
gene: CEP76 was added to Syndromic Retinopathy. Sources: Other
Mode of inheritance for gene: CEP76 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CEP76 were set to complex neurodevelopmental disorder MONDO:0100038; Joubert syndrome; Bardet-Biedl syndrome; retinitis pigmentosa
Penetrance for gene: CEP76 were set to unknown
Review for gene: CEP76 was set to GREEN
Added comment: Erica Davis, Stanley Manne Children’s research institute, Chicago
ESHG presentation 4/6/24, unpublished

CEP76 associated with syndromic ciliopathy

CEP76 localizes to centrioles and basal body primary cilia
Role in normal centriolar duplication

Index case
Bardet Biedl syndrome
Compound heterozygous pLoF variants in CEP76

Via Gene matcher
7 cases in 7 families- biallelic CEP76 and various clinical features within ciliopathy spectrum:
Obesity
Ocular phenotype
Structural brain anomalies
Renal?

3/7 families clinical Dx Joubert syndrome
1/7 BBS
1/7 GDD/ID NOS
2/7 retinitis pigmentosa (1 of these with learning difficulties)

Mixture of biallelic pLOF and missense variant

CEP76 knockout zebrafish model shows retinal phenotype w photoreceptor loss, similar to homozygous known BBS4 pathogenic variant

Cell based fx studies with missense variants above, consistent with centriolar duplication dysfunction
Sources: Other
Ciliopathies v1.59 CEP76 Mark Cleghorn gene: CEP76 was added
gene: CEP76 was added to Ciliopathies. Sources: Other
Mode of inheritance for gene: CEP76 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CEP76 were set to complex neurodevelopmental disorder MONDO:0100038; Joubert syndrome; Bardet-Biedl syndrome; retinitis pigmentosa
Penetrance for gene: CEP76 were set to unknown
Review for gene: CEP76 was set to GREEN
Added comment: Erica Davis, Stanley Manne Children’s research institute, Chicago
ESHG presentation 4/6/24, unpublished

CEP76 associated with syndromic ciliopathy

CEP76 localizes to centrioles and basal body primary cilia
Role in normal centriolar duplication

Index case
Bardet Biedl syndrome
Compound heterozygous pLoF variants in CEP76

Via Gene matcher
7 cases in 7 families- biallelic CEP76 and various clinical features within ciliopathy spectrum:
Obesity
Ocular phenotype
Structural brain anomalies
Renal?

3/7 families clinical Dx Joubert syndrome
1/7 BBS
1/7 GDD/ID NOS
2/7 retinitis pigmentosa (1 of these with learning difficulties)

Mixture of biallelic pLOF and missense variant

CEP76 knockout zebrafish model shows retinal phenotype w photoreceptor loss, similar to homozygous known BBS4 pathogenic variant

Cell based fx studies with missense variants above, consistent with centriolar duplication dysfunction
Sources: Other
Joubert syndrome and other neurological ciliopathies v1.27 CEP76 Mark Cleghorn gene: CEP76 was added
gene: CEP76 was added to Joubert syndrome and other neurological ciliopathies. Sources: Other
Mode of inheritance for gene: CEP76 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CEP76 were set to complex neurodevelopmental disorder MONDO:0100038; Joubert syndrome; Bardet-Biedl syndrome; retinitis pigmentosa
Penetrance for gene: CEP76 were set to unknown
Review for gene: CEP76 was set to GREEN
Added comment: Erica Davis, Stanley Manne Children’s research institute, Chicago
ESHG presentation 4/6/24, unpublished

CEP76 associated with syndromic ciliopathy

CEP76 localizes to centrioles and basal body primary cilia
Role in normal centriolar duplication

Index case
Bardet Biedl syndrome
Compound heterozygous pLoF variants in CEP76

Via Gene matcher
7 cases in 7 families- biallelic CEP76 and various clinical features within ciliopathy spectrum:
Obesity
Ocular phenotype
Structural brain anomalies
Renal?

3/7 families clinical Dx Joubert syndrome
1/7 BBS
1/7 GDD/ID NOS
2/7 retinitis pigmentosa (1 of these with learning difficulties)

Mixture of biallelic pLOF and missense variants

CEP76 knockout zebrafish model shows retinal phenotype w photoreceptor loss, similar to homozygous known BBS4 pathogenic variant

Cell based fx studies with missense variants above, consistent with centriolar duplication dysfunction
Sources: Other
Mendeliome v1.1998 EIF3I Mark Cleghorn gene: EIF3I was added
gene: EIF3I was added to Mendeliome. Sources: Other
Mode of inheritance for gene: EIF3I was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: EIF3I were set to complex neurodevelopmental disorder MONDO:0100038
Penetrance for gene: EIF3I were set to unknown
Review for gene: EIF3I was set to AMBER
Added comment: Marcello Scala, Genoa
ESHG presentation 4/6/24, unpublished

De novo EIF3I missense variants as a cause for novel NDD syndrome

EIF3 complex involved in regulating initiation of mRNA translation
Negative regulator of the TGF beta pathway

8 individuals from 8 families
Mod/severe GDD or ID
Short stature
Midline brain anomalies (hypoplasia/agenesis of corpus callosum and pituitary hypoplasia)
Frontal bossing, hypertelorism, long philtrum
All w rare de novo missense variants in EIF3I, clustering within highly conserved WD repeats

Functional studies
Transfected HEK293 cell studies suggested EIF3I protein from variant alleles (from patients above) had disrupted interaction with other EIF subunits, and cells had reduced protein synthesis overall
No animal models
Sources: Other
Intellectual disability syndromic and non-syndromic v0.6195 EIF3I Mark Cleghorn gene: EIF3I was added
gene: EIF3I was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: EIF3I was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: EIF3I were set to complex neurodevelopmental disorder MONDO:0100038
Penetrance for gene: EIF3I were set to unknown
Review for gene: EIF3I was set to AMBER
Added comment: Marcello Scala, Genoa
ESHG presentation 4/6/24, unpublished

De novo EIF3I missense variants as a cause for novel NDD syndrome

EIF3 complex involved in regulating initiation of mRNA translation
Negative regulator of the TGF beta pathway

8 individuals from 8 families
Mod/severe GDD or ID
Short stature
Midline brain anomalies (hypoplasia/agenesis of corpus callosum and pituitary hypoplasia)
Frontal bossing, hypertelorism, long philtrum
All w rare de novo missense variants om EIF3I, clustering within highly conserved WD repeats

Functional studies
Transfected HEK293 cell studies suggested EIF3I protein from variant alleles (from patients above) had disrupted interaction with other EIF subunits, and cells had reduced protein synthesis overall
No animal models
Sources: Other
Intellectual disability syndromic and non-syndromic v0.6195 DDHD2 Bryony Thompson Phenotypes for gene: DDHD2 were changed from hereditary spastic paraplegia 54 MONDO:0014018 to hereditary spastic paraplegia 54 MONDO:0014018
Intellectual disability syndromic and non-syndromic v0.6194 DDHD2 Bryony Thompson Marked gene: DDHD2 as ready
Intellectual disability syndromic and non-syndromic v0.6194 DDHD2 Bryony Thompson Gene: ddhd2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6194 DDHD2 Bryony Thompson Phenotypes for gene: DDHD2 were changed from to hereditary spastic paraplegia 54 MONDO:0014018
Intellectual disability syndromic and non-syndromic v0.6193 DDHD2 Bryony Thompson Publications for gene: DDHD2 were set to
Intellectual disability syndromic and non-syndromic v0.6192 DDHD2 Bryony Thompson Mode of inheritance for gene: DDHD2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6191 DDHD2 Bryony Thompson reviewed gene: DDHD2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23486545, 23176823, 36090575, 26113134, 25417924; Phenotypes: hereditary spastic paraplegia 54 MONDO:0014018; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6191 DDC Bryony Thompson Marked gene: DDC as ready
Intellectual disability syndromic and non-syndromic v0.6191 DDC Bryony Thompson Gene: ddc has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6191 DDC Bryony Thompson Publications for gene: DDC were set to
Intellectual disability syndromic and non-syndromic v0.6190 DDC Bryony Thompson Mode of inheritance for gene: DDC was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6189 DDC Bryony Thompson reviewed gene: DDC: Rating: GREEN; Mode of pathogenicity: None; Publications: 37824694; Phenotypes: Aromatic L-amino acid decarboxylase deficiency MONDO:0012084; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Mendeliome v1.1998 MRPL42 Mark Cleghorn gene: MRPL42 was added
gene: MRPL42 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: MRPL42 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MRPL42 were set to complex neurodevelopmental disorder MONDO:0100038
Penetrance for gene: MRPL42 were set to unknown
Review for gene: MRPL42 was set to RED
Added comment: Bjorn Fischer-Zirnsak, Charite Berlin
ESHG presentation 4/6/24, unpublished

++ supportive functional data (on patient-derived cells) presented, but only 1 case

Biallelic MRPL42 LoF with lethal mitochondrial disease

Index case, born to consanguineous parents
Small
Hypotonia
Seizures
Conductive hearing impairment
CV: hypertrophic RV, small VSD
Hepatomegaly
Lactic acidosis

Homozygous MRPL42: c.219+6T>A (spliceAI 0.83 donor loss)
RNASeq and RT-PCR supportive of aberrant splicing resulting in out of frame exon 4 skipping
Sources: Other
Mitochondrial disease v0.929 MRPL42 Mark Cleghorn gene: MRPL42 was added
gene: MRPL42 was added to Mitochondrial disease. Sources: Other
Mode of inheritance for gene: MRPL42 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MRPL42 were set to complex neurodevelopmental disorder MONDO:0100038
Penetrance for gene: MRPL42 were set to unknown
Review for gene: MRPL42 was set to RED
Added comment: Bjorn Fischer-Zirnsak, Charite Berlin
ESHG presentation 4/6/24, unpublished

++ supportive functional data (on patient-derived cells) presented, but only 1 case

Biallelic MRPL42 LoF with lethal mitochondrial disease

Index case, born to consanguineous parents
Small
Hypotonia
Seizures
Conductive hearing impairment
CV: hypertrophic RV, small VSD
Hepatomegaly
Lactic acidosis

Homozygous MRPL42: c.219+6T>A (spliceAI 0.83 donor loss)
RNASeq and RT-PCR supportive of aberrant splicing resulting in out of frame exon 4 skipping
Sources: Other
Mendeliome v1.1998 MED16 Mark Cleghorn gene: MED16 was added
gene: MED16 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: MED16 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MED16 were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: MED16 was set to GREEN
Added comment: Charlotte Guillouet, Imagine institute Paris
ESHG presentation 4/6/24, unpublished

MED16 is part of tail of ‘mediator complex’
Plays a role in enhancer/promotor regions

Disruptive variants in other genes encoding proteins within this mediator complex (MED11/12/12/17/20, CDK8) are assoc w neurodevelopmental/neurodegenerative disorders

Cases
index family
Sibs (M/F) to consanguineous parents w NDD/mod ID, tetralogy of Fallot or VSD, bilat deafness, micrognathia, malar hypoplasia, dental AbN, pre auricular tags, hypoplastic nails, brachydactly
WES: biallelic MED16 p.Asp217Asn

Via genematcher
16 families total, 22 individuals, homozygous or compound het rare MED16 variants
Mixture of pLoF and missense variants

Motor delay in 16/17
DD or ID in 17/17
Speech delay in 15/15
6/19 ToF
7/19 other septal/aortic defects
6/18 deafness
11/18 microretrognathia
6/17 cleft palate
8/19 preauricular tags
9/20 puffy eyelids
12/20 nasal dysplasia (most commonly short columella w bulbous nasal tip)
7/20 corpus callosum anomalies

Not clear that functional work recapitulated phenotype as yet?
Immunofluroescence on HeLa cells transfected with variants observed ?conclusion
MED16 knockout mouse > growth delay, pre weaning lethality
MED16 knockout zebrafish > reduced body length, early death, no obvious craniofacial phenotype
Sources: Other
Mendeliome v1.1998 GPN2 Mark Cleghorn gene: GPN2 was added
gene: GPN2 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: GPN2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GPN2 were set to complex neurodevelopmental disorder MONDO:0100038; Perrault syndrome
Penetrance for gene: GPN2 were set to unknown
Review for gene: GPN2 was set to AMBER
Added comment: GPN2
ESHG talk 2/6/24, unpublished
Thomas Smith, University of Manchester

Biallelic GPN2 proposed to cause Perrault syndrome (SNHL, ovarian dysfunction, NDD)
RNA polymerase assembly factor

4 families (14 affected individuals) w biallalic GPN2 rare missense variants
Segregated w phenotype
Fam 2 and 3 may be distantly related (leaving 3 distinct kindreds)

Clinical features
13/14 SNHL
3/4 families all females of adolescent age or older had primary ovarian insufficiency
4/4 GDD, ataxia (no data on family w 10 affected indiv.)

Some functional work, not conclusive
Sources: Other
Mendeliome v1.1998 FKBP4 Mark Cleghorn gene: FKBP4 was added
gene: FKBP4 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: FKBP4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FKBP4 were set to complex neurodevelopmental disorder MONDO:0100038
Penetrance for gene: FKBP4 were set to unknown
Review for gene: FKBP4 was set to AMBER
Added comment: Rebecca Yarwood, University of Manchester
ESHG presentation 4/6/24, unpublished

Bilalleic FKBP4 w NDD + DSD
Protein has functions in hormone receptor trafficking
FKPB4 highly expressed in stem cell and progenitor cells in gonad and neuronal degeneration

Index case
Severe GDD
abN external genitalia
CV AbN
FBBP4 p.E196*

Via GeneMatcher
7 families (12 individuals)

12/12 severe GDD/ID
9/10 microcephaly
11/12 external genital abnormalities (details not provided)

All w homozygous pLoF variants (mixture of canonical splice, frameshift, nonsense)
Sources: Other
Intellectual disability syndromic and non-syndromic v0.6189 FKBP4 Mark Cleghorn gene: FKBP4 was added
gene: FKBP4 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: FKBP4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FKBP4 were set to complex neurodevelopmental disorder MONDO:0100038
Penetrance for gene: FKBP4 were set to unknown
Review for gene: FKBP4 was set to AMBER
Added comment: Rebecca Yarwood, University of Manchester
ESHG presentation 4/6/24, unpublished

Bilalleic FKBP4 w NDD + DSD
Protein has functions in hormone receptor trafficking
FKPB4 highly expressed in stem cell and progenitor cells in gonad and neuronal degeneration

Index case
Severe GDD
abN external genitalia
CV AbN
FBBP4 p.E196*

Via GeneMatcher
7 families (12 individuals)

12/12 severe GDD/ID
9/10 microcephaly
11/12 external genital abnormalities (details not provided)

All w homozygous pLoF variants (mixture of canonical splice, frameshift, nonsense)
Sources: Other
Differences of Sex Development v0.293 FKBP4 Mark Cleghorn gene: FKBP4 was added
gene: FKBP4 was added to Differences of Sex Development. Sources: Other
Mode of inheritance for gene: FKBP4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FKBP4 were set to complex neurodevelopmental disorder MONDO:0100038
Penetrance for gene: FKBP4 were set to unknown
Review for gene: FKBP4 was set to AMBER
Added comment: Rebecca Yarwood, University of Manchester
ESHG presentation 4/6/24, unpublished

Bilalleic FKBP4 w NDD + DSD
Protein has functions in hormone receptor trafficking
FKPB4 highly expressed in stem cell and progenitor cells in gonad and neuronal degeneration

Index case
Severe GDD
abN external genitalia
CV AbN
FBBP4 p.E196*

Via GeneMatcher
7 families (12 individuals)

12/12 severe GDD/ID
9/10 microcephaly
11/12 external genital abnormalities (details not provided)

All w homozygous pLoF variants (mixture of canonical splice, frameshift, nonsense)
Sources: Other
Mendeliome v1.1998 SGMS1 Mark Cleghorn gene: SGMS1 was added
gene: SGMS1 was added to Mendeliome. Sources: Other
Mode of inheritance for gene: SGMS1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SGMS1 were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: SGMS1 was set to AMBER
Added comment: SGMS1
Johannes Kopp, Charite Berlin
ESHG presentation 4/6/24, unpublished

Biallelic SGMS1 with novel metabolic disorder

Only 2 families (3 cases) reported
NDD, AbN cerebral myelination, SNHL, ichthyosis

Homozygous or compound het SGMS1 missense

Functional work to support role of SGMS1 in sphingolipid metabolism
Sources: Other
Prepair 1000+ v1.287 ADGRV1 Lauren Thomas reviewed gene: ADGRV1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19357117; Phenotypes: Usher syndrome, type 2C, MIM# 605472 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6189 MED16 Bryony Thompson Classified gene: MED16 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6189 MED16 Bryony Thompson Gene: med16 has been classified as Green List (High Evidence).
Prepair 1000+ v1.287 ADGRG1 Lauren Thomas reviewed gene: ADGRG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 16240336, 33299078; Phenotypes: Polymicrogyria, bilateral frontoparietal, MIM#606854; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Lysosomal Storage Disorder v1.11 SGMS1 Mark Cleghorn gene: SGMS1 was added
gene: SGMS1 was added to Lysosomal Storage Disorder. Sources: Other
Mode of inheritance for gene: SGMS1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SGMS1 were set to complex neurodevelopmental disorder MONDO:0100038
Penetrance for gene: SGMS1 were set to unknown
Review for gene: SGMS1 was set to AMBER
Added comment: SGMS1
Johannes Kopp, Charite Berlin
ESHG presentation 4/6/24, unpublished

Biallelic SGMS1 with novel metabolic disorder

Only 2 families (3 cases) reported
NDD, AbN cerebral myelination, SNHL, ichthyosis

Homozygous or compound het SGMS1 missense

Functional work to support role of SGMS1 in sphingolipid metabolism
Sources: Other
Intellectual disability syndromic and non-syndromic v0.6188 MED16 Mark Cleghorn gene: MED16 was added
gene: MED16 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: MED16 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MED16 were set to complex neurodevelopmental disorder MONDO:0100038
Penetrance for gene: MED16 were set to unknown
Review for gene: MED16 was set to GREEN
Added comment: MED16
Charlotte Guillouet, Imagine institute Paris
ESHG presentation 4/6/24, unpublished

MED16 is part of tail of ‘mediator complex’
Plays a role in enhancer/promotor regions

Disruptive variants in other genes encoding proteins within this mediator complex (MED11/12/12/17/20, CDK8) are assoc w neurodevelopmental/neurodegenerative disorders

Cases
index family
Sibs (M/F) to consanguineous parents w NDD/mod ID, tetralogy of Fallot or VSD, bilat deafness, micrognathia, malar hypoplasia, dental AbN, pre auricular tags, hypoplastic nails, brachydactly
WES: biallelic MED16 p.Asp217Asn

Via genematcher
16 families total, 22 individuals, homozygous or compound het rare MED16 variants
Mixture of pLoF and missense variants

Motor delay in 16/17
DD or ID in 17/17
Speech delay in 15/15
6/19 ToF
7/19 other septal/aortic defects
6/18 deafness
11/18 microretognathia
6/17 cleft palate
8/19 preauricular tags
9/20 puffy eyelids
12/20 nasal dysplasia (most commonly short columella w bulbous nasal tip)
7/20 corpus callosum anomalies

Not clear that functional work recapitulated phenotype as yet?
Immunofluroescence on HeLa cells transfected with variants observed ?conclusion
MED16 knockout mouse > growth delay, pre weaning lethality
MED16 knockout zebrafish > reduced body length, early death, no obvious craniofacial phenotype
Sources: Other
Prepair 1000+ v1.287 ADA2 Lauren Thomas reviewed gene: ADA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24552284, 24552285, 33791889; Phenotypes: Vasculitis, autoinflammation, immunodeficiency, and hematologic defects syndrome, MIM# 615688; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.287 ABCC6 Lauren Thomas reviewed gene: ABCC6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Pseudoxanthoma elasticum MIM#264800, Arterial calcification, generalized, of infancy, 2 MIM#614473; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.287 COL2A1 Zornitza Stark Marked gene: COL2A1 as ready
Prepair 1000+ v1.287 COL2A1 Zornitza Stark Gene: col2a1 has been classified as Red List (Low Evidence).
Prepair 1000+ v1.287 COL2A1 Zornitza Stark Classified gene: COL2A1 as Red List (low evidence)
Prepair 1000+ v1.287 COL2A1 Zornitza Stark Gene: col2a1 has been classified as Red List (Low Evidence).
Prepair 1000+ v1.286 COL2A1 Zornitza Stark reviewed gene: COL2A1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spondyloperipheral dysplasia, MIM #271700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Prepair 1000+ v1.286 GNAT2 Zornitza Stark Marked gene: GNAT2 as ready
Prepair 1000+ v1.286 GNAT2 Zornitza Stark Gene: gnat2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.286 GNAT2 Zornitza Stark Phenotypes for gene: GNAT2 were changed from Achromatopsia-4, 613856 (3) to Achromatopsia 4 MIM#613856
Prepair 1000+ v1.285 GNAT2 Zornitza Stark Publications for gene: GNAT2 were set to
Prepair 1000+ v1.284 DLL3 Zornitza Stark Marked gene: DLL3 as ready
Prepair 1000+ v1.284 DLL3 Zornitza Stark Gene: dll3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.284 DLL3 Zornitza Stark Phenotypes for gene: DLL3 were changed from Spondylocostal dysostosis 1, autosomal recessive, 277300 (3) to Spondylocostal dysostosis 1, autosomal recessive, MIM# 277300; MONDO:0020692
Prepair 1000+ v1.283 DLL3 Zornitza Stark Publications for gene: DLL3 were set to
Intellectual disability syndromic and non-syndromic v0.6188 LARS2 Chirag Patel reviewed gene: LARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29205794, 32423379, 30737337, 26537577, 23541342; Phenotypes: Perrault syndrome 4, MIM# 615300, Hydrops, lactic acidosis, and sideroblastic anemia, MIM# 617021; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6188 LARGE1 Chirag Patel reviewed gene: LARGE1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 12966029, 19067344, 17436019, 21248746, 19299310; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 6, MIM# 613154, Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 6, MIM# 608840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6188 LAMP2 Chirag Patel reviewed gene: LAMP2: Rating: GREEN; Mode of pathogenicity: None; Publications: PubMed: 10972294; Phenotypes: Danon disease, MIM# 300257, MONDO:0010281; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6188 PARN Chirag Patel reviewed gene: PARN: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 25893599, 26342108; Phenotypes: Dyskeratosis congenita, autosomal recessive 6, MIM# 616353; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Regression v0.559 PAX6 Chirag Patel Classified gene: PAX6 as Red List (low evidence)
Regression v0.559 PAX6 Chirag Patel Gene: pax6 has been classified as Red List (Low Evidence).
Ataxia - paediatric v1.27 PAX6 Chirag Patel Classified gene: PAX6 as Red List (low evidence)
Ataxia - paediatric v1.27 PAX6 Chirag Patel Gene: pax6 has been classified as Red List (Low Evidence).
Ataxia - paediatric v1.26 PAX6 Chirag Patel reviewed gene: PAX6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Regression v0.558 PAX6 Chirag Patel Classified gene: PAX6 as Red List (low evidence)
Regression v0.558 PAX6 Chirag Patel Gene: pax6 has been classified as Red List (Low Evidence).
Regression v0.558 PAX6 Chirag Patel Classified gene: PAX6 as Red List (low evidence)
Regression v0.558 PAX6 Chirag Patel Gene: pax6 has been classified as Red List (Low Evidence).
Regression v0.557 PAX6 Chirag Patel reviewed gene: PAX6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability syndromic and non-syndromic v0.6188 PAX6 Chirag Patel reviewed gene: PAX6: Rating: GREEN; Mode of pathogenicity: None; Publications: PubMed: 26130484, 31700164; Phenotypes: Microphthalmia/coloboma 12, OMIM #120200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital hypothyroidism v0.43 PAX8 Chirag Patel reviewed gene: PAX8: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33272083, 9590296 11232006 15356023 15718293; Phenotypes: Hypothyroidism, congenital, due to thyroid dysgenesis or hypoplasia, MIM# 218700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6188 PAX8 Chirag Patel reviewed gene: PAX8: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33272083, 9590296 11232006 15356023 15718293; Phenotypes: Hypothyroidism, congenital, due to thyroid dysgenesis or hypoplasia, MIM# 218700; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability syndromic and non-syndromic v0.6188 PC Chirag Patel reviewed gene: PC: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 9585612, 12112657; Phenotypes: Pyruvate carboxylase deficiency - MIM#266150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Genomic newborn screening: BabyScreen+ v1.114 AHCY Carolyn Bursle reviewed gene: AHCY: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Prepair 1000+ v1.282 CSTB Lilian Downie Marked gene: CSTB as ready
Prepair 1000+ v1.282 CSTB Lilian Downie Added comment: Comment when marking as ready: downgrade to amber when updating, common variant not detected with WES
Prepair 1000+ v1.282 CSTB Lilian Downie Gene: cstb has been classified as Green List (High Evidence).
Prepair 1000+ v1.282 EIF2B4 Lilian Downie Marked gene: EIF2B4 as ready
Prepair 1000+ v1.282 EIF2B4 Lilian Downie Gene: eif2b4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.282 EIF2B4 Lilian Downie Publications for gene: EIF2B4 were set to
Prepair 1000+ v1.281 ERBB3 Lilian Downie Marked gene: ERBB3 as ready
Prepair 1000+ v1.281 ERBB3 Lilian Downie Added comment: Comment when marking as ready: Upgrade to green
Prepair 1000+ v1.281 ERBB3 Lilian Downie Gene: erbb3 has been classified as Amber List (Moderate Evidence).
Prepair 1000+ v1.281 ERBB3 Lilian Downie Tag for review tag was added to gene: ERBB3.
Prepair 1000+ v1.281 ERBB3 Lilian Downie Phenotypes for gene: ERBB3 were changed from Lethal congenital contractural syndrome 2, 607598 (3) to Visceral neuropathy, familial, 1, autosomal recessive MIM#243180
Prepair 1000+ v1.280 ERBB3 Lilian Downie Publications for gene: ERBB3 were set to
Intellectual disability syndromic and non-syndromic v0.6188 SLC6A3 Zornitza Stark Marked gene: SLC6A3 as ready
Intellectual disability syndromic and non-syndromic v0.6188 SLC6A3 Zornitza Stark Gene: slc6a3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6188 SLC6A3 Zornitza Stark Phenotypes for gene: SLC6A3 were changed from to Parkinsonism-dystonia, infantile, 1, MIM# 613135
Intellectual disability syndromic and non-syndromic v0.6187 SLC6A3 Zornitza Stark Publications for gene: SLC6A3 were set to
Intellectual disability syndromic and non-syndromic v0.6186 SLC6A3 Zornitza Stark Mode of inheritance for gene: SLC6A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6185 SLC6A3 Zornitza Stark reviewed gene: SLC6A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 21112253; Phenotypes: Parkinsonism-dystonia, infantile, 1, MIM# 613135; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6185 SRD5A3 Zornitza Stark Marked gene: SRD5A3 as ready
Intellectual disability syndromic and non-syndromic v0.6185 SRD5A3 Zornitza Stark Gene: srd5a3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6185 SRD5A3 Zornitza Stark Phenotypes for gene: SRD5A3 were changed from to Congenital disorder of glycosylation, type Iq, MIM#612379; Kahrizi syndrome, MIM# 612713
Intellectual disability syndromic and non-syndromic v0.6184 SRD5A3 Zornitza Stark Publications for gene: SRD5A3 were set to
Intellectual disability syndromic and non-syndromic v0.6183 SRD5A3 Zornitza Stark Mode of inheritance for gene: SRD5A3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6182 SRD5A3 Zornitza Stark reviewed gene: SRD5A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 32424323; Phenotypes: Congenital disorder of glycosylation, type Iq, MIM#612379, Kahrizi syndrome, MIM# 612713; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6182 SLC6A8 Zornitza Stark Marked gene: SLC6A8 as ready
Intellectual disability syndromic and non-syndromic v0.6182 SLC6A8 Zornitza Stark Gene: slc6a8 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6182 SLC6A8 Zornitza Stark Phenotypes for gene: SLC6A8 were changed from to Cerebral creatine deficiency syndrome 1, MIM# 300352
Intellectual disability syndromic and non-syndromic v0.6181 SLC6A8 Zornitza Stark Publications for gene: SLC6A8 were set to
Intellectual disability syndromic and non-syndromic v0.6180 SLC6A8 Zornitza Stark Mode of inheritance for gene: SLC6A8 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability syndromic and non-syndromic v0.6179 SLC6A8 Zornitza Stark reviewed gene: SLC6A8: Rating: GREEN; Mode of pathogenicity: None; Publications: 27604308, 16738945; Phenotypes: Cerebral creatine deficiency syndrome 1, MIM# 300352; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Prepair 1000+ v1.279 B3GALNT2 Lilian Downie Marked gene: B3GALNT2 as ready
Prepair 1000+ v1.279 B3GALNT2 Lilian Downie Added comment: Comment when marking as ready: Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A) is an autosomal recessive disorder with congenital muscular dystrophy resulting in muscle weakness early in life and brain and eye anomalies. It is usually associated with delayed psychomotor development and shortened life expectancy. The phenotype includes the alternative clinical designations Walker-Warburg syndrome (WWS) and muscle-eye-brain disease (MEB). The disorder represents the most severe end of a phenotypic spectrum of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as 'dystroglycanopathies'
Prepair 1000+ v1.279 B3GALNT2 Lilian Downie Gene: b3galnt2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.279 B3GALNT2 Lilian Downie Publications for gene: B3GALNT2 were set to
Prepair 1000+ v1.278 EVC2 Lilian Downie Marked gene: EVC2 as ready
Prepair 1000+ v1.278 EVC2 Lilian Downie Gene: evc2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.278 EVC2 Lilian Downie Publications for gene: EVC2 were set to
Prepair 1000+ v1.277 FAT4 Lilian Downie Marked gene: FAT4 as ready
Prepair 1000+ v1.277 FAT4 Lilian Downie Gene: fat4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.277 FAT4 Lilian Downie Phenotypes for gene: FAT4 were changed from Hennekam lymphangiectasia-lymphedema syndrome 2, 616006 (3) to Hennekam lymphangiectasia-lymphedema syndrome 2 MIM#616006; Van Maldergem syndrome 2 MIM#615546
Prepair 1000+ v1.276 FAT4 Lilian Downie Publications for gene: FAT4 were set to
Prepair 1000+ v1.275 FKTN Lilian Downie Marked gene: FKTN as ready
Prepair 1000+ v1.275 FKTN Lilian Downie Gene: fktn has been classified as Green List (High Evidence).
Prepair 1000+ v1.275 FKTN Lilian Downie Phenotypes for gene: FKTN were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4, 253800 (3) to Cardiomyopathy, dilated, 1X MIM#611615; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4MIM#253800; Muscular dystrophy-dystroglycanopathy (congenital without impaired intellectual development), type B, 4 MIM#613152; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 4 MIM# 611588
Prepair 1000+ v1.274 FKTN Lilian Downie Publications for gene: FKTN were set to
Prepair 1000+ v1.273 GDF5 Lilian Downie Marked gene: GDF5 as ready
Prepair 1000+ v1.273 GDF5 Lilian Downie Gene: gdf5 has been classified as Green List (High Evidence).
Prepair 1000+ v1.273 GDF5 Lilian Downie Publications for gene: GDF5 were set to
Intellectual disability syndromic and non-syndromic v0.6179 SPTBN2 Zornitza Stark Mode of inheritance for gene: SPTBN2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6178 SPTBN2 Zornitza Stark reviewed gene: SPTBN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23236289, 23838597, 22781464, 31617442, 31066025; Phenotypes: Spinocerebellar ataxia, autosomal recessive 14, MIM# 615386, Spinocerebellar ataxia 5, MIM# 600224; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hypercalcaemia v1.2 AP2S1 Chirag Patel reviewed gene: AP2S1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29325022; Phenotypes: Hypocalciuric hypercalcaemia, type III, MIM# 600740, MONDO:0010926; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6178 ST3GAL3 Zornitza Stark Marked gene: ST3GAL3 as ready
Intellectual disability syndromic and non-syndromic v0.6178 ST3GAL3 Zornitza Stark Gene: st3gal3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6178 ST3GAL3 Zornitza Stark Phenotypes for gene: ST3GAL3 were changed from to Intellectual disability, autosomal recessive 12 MIM# 611090
Intellectual disability syndromic and non-syndromic v0.6177 ST3GAL3 Zornitza Stark Publications for gene: ST3GAL3 were set to
Prepair 1000+ v1.272 FANCC Lilian Downie Marked gene: FANCC as ready
Prepair 1000+ v1.272 FANCC Lilian Downie Added comment: Comment when marking as ready: Characteristic clinical features include developmental abnormalities in major organ systems, early-onset bone marrow failure, and a high predisposition to cancer. The cellular hallmark of FA is hypersensitivity to DNA crosslinking agents and high frequency of chromosomal aberrations pointing to a defect in DNA repair
Prepair 1000+ v1.272 FANCC Lilian Downie Gene: fancc has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6176 ST3GAL3 Zornitza Stark Mode of inheritance for gene: ST3GAL3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.272 FANCC Lilian Downie Publications for gene: FANCC were set to
Intellectual disability syndromic and non-syndromic v0.6175 ST3GAL3 Zornitza Stark reviewed gene: ST3GAL3: Rating: GREEN; Mode of pathogenicity: None; Publications: 23252400, 21907012, 31584066, 37938134; Phenotypes: Intellectual disability, autosomal recessive 12 MIM# 611090; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital Disorders of Glycosylation v1.45 ST3GAL3 Zornitza Stark Phenotypes for gene: ST3GAL3 were changed from Mental retardation, autosomal recessive 12 MIM# 611090 to Intellectual disability, autosomal recessive 12 MIM# 611090
Prepair 1000+ v1.271 KCNJ11 Lilian Downie Marked gene: KCNJ11 as ready
Prepair 1000+ v1.271 KCNJ11 Lilian Downie Added comment: Comment when marking as ready: Permanent neonatal diabetes mellitus-2 (PNDM2) is characterized by onset of insulin-requiring hyperglycemia within the first months of life that requires insulin therapy throughout life. Some patients additionally have marked developmental delay, muscle weakness, and epilepsy
Prepair 1000+ v1.271 KCNJ11 Lilian Downie Gene: kcnj11 has been classified as Green List (High Evidence).
Prepair 1000+ v1.271 KCNJ11 Lilian Downie Publications for gene: KCNJ11 were set to
Congenital Disorders of Glycosylation v1.44 ST3GAL3 Zornitza Stark edited their review of gene: ST3GAL3: Changed phenotypes: Intellectual disability, autosomal recessive 12 MIM# 611090
Prepair 1000+ v1.270 COL4A4 Lilian Downie Marked gene: COL4A4 as ready
Prepair 1000+ v1.270 COL4A4 Lilian Downie Gene: col4a4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.270 COL4A4 Lilian Downie Publications for gene: COL4A4 were set to
Intellectual disability syndromic and non-syndromic v0.6175 SUCLG1 Zornitza Stark Marked gene: SUCLG1 as ready
Intellectual disability syndromic and non-syndromic v0.6175 SUCLG1 Zornitza Stark Gene: suclg1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6175 SUCLG1 Zornitza Stark Phenotypes for gene: SUCLG1 were changed from Mitochondrial DNA depletion syndrome 9 (encephalomyopathic type with methylmalonic aciduria) MIM#245400 to Mitochondrial DNA depletion syndrome 9 (encephalomyopathic type with methylmalonic aciduria) MIM#245400
Intellectual disability syndromic and non-syndromic v0.6174 SUCLG1 Zornitza Stark Phenotypes for gene: SUCLG1 were changed from to Mitochondrial DNA depletion syndrome 9 (encephalomyopathic type with methylmalonic aciduria) MIM#245400
Prepair 1000+ v1.269 ICOS Lilian Downie Marked gene: ICOS as ready
Prepair 1000+ v1.269 ICOS Lilian Downie Gene: icos has been classified as Green List (High Evidence).
Prepair 1000+ v1.269 ICOS Lilian Downie Publications for gene: ICOS were set to
Intellectual disability syndromic and non-syndromic v0.6173 SUCLG1 Zornitza Stark Publications for gene: SUCLG1 were set to
Prepair 1000+ v1.268 ICOS Lilian Downie Tag SV/CNV tag was added to gene: ICOS.
Intellectual disability syndromic and non-syndromic v0.6172 SUCLG1 Zornitza Stark Mode of inheritance for gene: SUCLG1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.268 ITGB2 Lilian Downie Marked gene: ITGB2 as ready
Prepair 1000+ v1.268 ITGB2 Lilian Downie Gene: itgb2 has been classified as Green List (High Evidence).
Prepair 1000+ v1.268 ITGB2 Lilian Downie Publications for gene: ITGB2 were set to
Intellectual disability syndromic and non-syndromic v0.6171 SUCLG1 Zornitza Stark Mode of inheritance for gene: SUCLG1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6170 SUCLG1 Zornitza Stark reviewed gene: SUCLG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33230783, 28358460; Phenotypes: Mitochondrial DNA depletion syndrome 9 (encephalomyopathic type with methylmalonic aciduria) MIM#245400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.267 JAK3 Lilian Downie Marked gene: JAK3 as ready
Prepair 1000+ v1.267 JAK3 Lilian Downie Gene: jak3 has been classified as Green List (High Evidence).
Prepair 1000+ v1.267 JAK3 Lilian Downie Publications for gene: JAK3 were set to
Intellectual disability syndromic and non-syndromic v0.6170 SURF1 Zornitza Stark Marked gene: SURF1 as ready
Intellectual disability syndromic and non-syndromic v0.6170 SURF1 Zornitza Stark Gene: surf1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6170 SURF1 Zornitza Stark Phenotypes for gene: SURF1 were changed from to Mitochondrial complex IV deficiency, nuclear type 1, MIM# 220110
Prepair 1000+ v1.266 LAMB1 Lilian Downie Marked gene: LAMB1 as ready
Prepair 1000+ v1.266 LAMB1 Lilian Downie Gene: lamb1 has been classified as Green List (High Evidence).
Prepair 1000+ v1.266 LAMB1 Lilian Downie Publications for gene: LAMB1 were set to
Intellectual disability syndromic and non-syndromic v0.6169 SURF1 Zornitza Stark Publications for gene: SURF1 were set to
Intellectual disability syndromic and non-syndromic v0.6168 SURF1 Zornitza Stark Mode of inheritance for gene: SURF1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.265 LGI4 Lilian Downie Marked gene: LGI4 as ready
Prepair 1000+ v1.265 LGI4 Lilian Downie Gene: lgi4 has been classified as Green List (High Evidence).
Prepair 1000+ v1.265 LGI4 Lilian Downie Publications for gene: LGI4 were set to
Intellectual disability syndromic and non-syndromic v0.6167 SURF1 Zornitza Stark reviewed gene: SURF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 9843204, 9837813; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 1, MIM# 220110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Prepair 1000+ v1.264 CPT1A Lilian Downie Marked gene: CPT1A as ready
Prepair 1000+ v1.264 CPT1A Lilian Downie Gene: cpt1a has been classified as Green List (High Evidence).
Prepair 1000+ v1.264 CPT1A Lilian Downie Publications for gene: CPT1A were set to
Prepair 1000+ v1.263 CSTB Lilian Downie Tag for review tag was added to gene: CSTB.
Prepair 1000+ v1.263 CSTB Lilian Downie Publications for gene: CSTB were set to
Prepair 1000+ v1.262 CFH Lilian Downie Marked gene: CFH as ready
Prepair 1000+ v1.262 CFH Lilian Downie Added comment: Comment when marking as ready: This deficiency, with biallelic form can cause atypical hemolytic uremic syndrome (HUS), type II or III membranoproliferative glomerulonephritis (MPGN) and increased susceptibility to meningicoccal infection. Can be early onset and severe requiring renal transplant. Variable expression

Gene also known as HF1
Prepair 1000+ v1.262 CFH Lilian Downie Gene: cfh has been classified as Green List (High Evidence).
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.37 CAPN3 Sangavi Sivagnanasundram reviewed gene: CAPN3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: muscular dystrophy, limb-girdle, autosomal dominant MONDO:0015151, autosomal recessive limb-girdle muscular dystrophy MONDO:0015152; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.1998 CAPN3 Sangavi Sivagnanasundram reviewed gene: CAPN3: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: muscular dystrophy, limb-girdle, autosomal dominant MONDO:0015151, autosomal recessive limb-girdle muscular dystrophy MONDO:0015152; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Limb-Girdle Muscular Dystrophy and Distal Myopathy v1.37 BVES Sangavi Sivagnanasundram reviewed gene: BVES: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: autosomal recessive limb-girdle muscular dystrophy MONDO:0015152; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1998 BVES Sangavi Sivagnanasundram reviewed gene: BVES: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: autosomal recessive limb-girdle muscular dystrophy MONDO:0015152; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary angioedema v1.5 F12 Sangavi Sivagnanasundram changed review comment from: Update to ClinGen ClinGen Hemostasis Thrombosis VCEP - classified as DEFINITIVE for this gene-disease association on 04/09/2024 - https://search.clinicalgenome.org/CCID:004793; to: Update to ClinGen Hemostasis Thrombosis VCEP - classified as DEFINITIVE for this gene-disease association on 04/09/2024 - https://search.clinicalgenome.org/CCID:004793
Hereditary angioedema v1.5 F12 Sangavi Sivagnanasundram reviewed gene: F12: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: hereditary angioedema type 3 MONDO:0012526; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Bleeding and Platelet Disorders v1.52 EPHB2 Sangavi Sivagnanasundram reviewed gene: EPHB2: Rating: AMBER; Mode of pathogenicity: None; Publications: 30213874; Phenotypes: bleeding disorder, platelet-type, 22 MONDO:0032765; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6167 TMEM5 Zornitza Stark Tag new gene name tag was added to gene: TMEM5.
Intellectual disability syndromic and non-syndromic v0.6167 TMEM5 Zornitza Stark Marked gene: TMEM5 as ready
Intellectual disability syndromic and non-syndromic v0.6167 TMEM5 Zornitza Stark Gene: tmem5 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6167 TMEM5 Zornitza Stark Phenotypes for gene: TMEM5 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 10, MIM# 615041
Intellectual disability syndromic and non-syndromic v0.6166 TMEM5 Zornitza Stark Publications for gene: TMEM5 were set to 23217329; 23519211
Intellectual disability syndromic and non-syndromic v0.6165 TMEM5 Zornitza Stark Publications for gene: TMEM5 were set to
Intellectual disability syndromic and non-syndromic v0.6164 TMEM5 Zornitza Stark Mode of inheritance for gene: TMEM5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6163 TMEM5 Zornitza Stark reviewed gene: TMEM5: Rating: GREEN; Mode of pathogenicity: None; Publications: 23217329, 23519211; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 10, MIM# 615041; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal Macrocystic Disease v0.70 ALG8 Chirag Patel edited their review of gene: ALG8: Added comment: 2023 Paper:
236 individuals identified with ALG8 protein-truncating variants. Patients were significantly at increased risk of having any kidney/liver cyst diagnosis (Odds Ratio 2.42), cystic kidney disease (OR 3.03), and nephrolithiasis (OR 1.89). ALG8 PTV heterozygotes were significantly more likely to have cystic kidney disease, defined as four or more kidney cysts (57.7% vs. 7.7%), or bilateral kidney cysts (69.2% vs. 15.4%), but not one or more liver cyst (11.5% vs. 7.7%).

ALG8 PTVs were not associated with chronic kidney disease or kidney failure in the MyCode study or the UK Biobank data. Thus, PTVs in ALG8 result in increased risk of a mild cystic kidney disease phenotype.; Changed publications: PMID: 36574950
Autoinflammatory Disorders v1.51 PTCRA Zornitza Stark Phenotypes for gene: PTCRA were changed from Autoinflammatory syndrome, MONDO:0019751, PTCRA-related to Immunodeficiency 126, MIM# 620931
Autoinflammatory Disorders v1.50 PTCRA Zornitza Stark edited their review of gene: PTCRA: Changed phenotypes: Immunodeficiency 126, MIM# 620931
Mendeliome v1.1998 PTCRA Zornitza Stark Phenotypes for gene: PTCRA were changed from Autoinflammatory syndrome, MONDO:0019751, PTCRA-related to Immunodeficiency 126, MIM# 620931
Mendeliome v1.1997 PTCRA Zornitza Stark edited their review of gene: PTCRA: Changed phenotypes: Immunodeficiency 126, MIM# 620931
Intellectual disability syndromic and non-syndromic v0.6163 TSEN2 Zornitza Stark Marked gene: TSEN2 as ready
Intellectual disability syndromic and non-syndromic v0.6163 TSEN2 Zornitza Stark Gene: tsen2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6163 TSEN2 Zornitza Stark Phenotypes for gene: TSEN2 were changed from to Pontocerebellar hypoplasia type 2B, MIM# 612389
Intellectual disability syndromic and non-syndromic v0.6162 TSEN2 Zornitza Stark Publications for gene: TSEN2 were set to 23562994; 20952379
Intellectual disability syndromic and non-syndromic v0.6161 TSEN2 Zornitza Stark Publications for gene: TSEN2 were set to
Intellectual disability syndromic and non-syndromic v0.6160 TSEN2 Zornitza Stark Mode of inheritance for gene: TSEN2 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6159 TSEN2 Zornitza Stark Mode of inheritance for gene: TSEN2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6158 TSEN2 Zornitza Stark reviewed gene: TSEN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23562994, 20952379; Phenotypes: Pontocerebellar hypoplasia type 2B, MIM# 612389; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6158 TTC19 Zornitza Stark Marked gene: TTC19 as ready
Intellectual disability syndromic and non-syndromic v0.6158 TTC19 Zornitza Stark Gene: ttc19 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6158 TTC19 Zornitza Stark Phenotypes for gene: TTC19 were changed from to Mitochondrial complex III deficiency, nuclear type 2, MIM#615157
Intellectual disability syndromic and non-syndromic v0.6157 TTC19 Zornitza Stark Publications for gene: TTC19 were set to
Intellectual disability syndromic and non-syndromic v0.6156 TTC19 Zornitza Stark Mode of inheritance for gene: TTC19 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6155 TTC19 Zornitza Stark changed review comment from: Mitochondrial complex III deficiency nuclear type 2 is an autosomal recessive severe neurodegenerative disorder that usually presents in childhood, but may show later onset, even in adulthood. Affected individuals have motor disability, with ataxia, apraxia, dystonia, and dysarthria, associated with necrotic lesions throughout the brain. Most patients also have cognitive impairment and axonal neuropathy and become severely disabled later in life. The disorder may present clinically as spinocerebellar ataxia or Leigh syndrome, or with psychiatric disturbances.

At least 4 unrelated families reported.; to: Mitochondrial complex III deficiency nuclear type 2 is an autosomal recessive severe neurodegenerative disorder that usually presents in childhood, but may show later onset, even in adulthood. Affected individuals have motor disability, with ataxia, apraxia, dystonia, and dysarthria, associated with necrotic lesions throughout the brain. Most patients also have cognitive impairment and axonal neuropathy and become severely disabled later in life. The disorder may present clinically as spinocerebellar ataxia or Leigh syndrome, or with psychiatric disturbances.

Included due to phenotypic overlap.

At least 4 unrelated families reported.
Intellectual disability syndromic and non-syndromic v0.6155 TTC19 Zornitza Stark reviewed gene: TTC19: Rating: GREEN; Mode of pathogenicity: None; Publications: 21278747, 23532514, 24368687, 24397319; Phenotypes: Mitochondrial complex III deficiency, nuclear type 2, MIM#615157; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6155 TUBA1A Zornitza Stark Marked gene: TUBA1A as ready
Intellectual disability syndromic and non-syndromic v0.6155 TUBA1A Zornitza Stark Gene: tuba1a has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6155 TUBA1A Zornitza Stark Phenotypes for gene: TUBA1A were changed from to Lissencephaly 3, MIM# 611603
Intellectual disability syndromic and non-syndromic v0.6154 TUBA1A Zornitza Stark Mode of inheritance for gene: TUBA1A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability syndromic and non-syndromic v0.6153 TUBA1A Zornitza Stark reviewed gene: TUBA1A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lissencephaly 3, MIM# 611603; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Microcephaly v1.278 ZNRF3 Bryony Thompson Marked gene: ZNRF3 as ready
Microcephaly v1.278 ZNRF3 Bryony Thompson Gene: znrf3 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.278 ZNRF3 Bryony Thompson Classified gene: ZNRF3 as Amber List (moderate evidence)
Microcephaly v1.278 ZNRF3 Bryony Thompson Gene: znrf3 has been classified as Amber List (Moderate Evidence).
Congenital Heart Defect v0.420 ZNRF3 Bryony Thompson Marked gene: ZNRF3 as ready
Congenital Heart Defect v0.420 ZNRF3 Bryony Thompson Gene: znrf3 has been classified as Amber List (Moderate Evidence).
Microcephaly v1.277 ZNRF3 Bryony Thompson gene: ZNRF3 was added
gene: ZNRF3 was added to Microcephaly. Sources: Literature
Mode of inheritance for gene: ZNRF3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZNRF3 were set to 39168120
Phenotypes for gene: ZNRF3 were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: ZNRF3 was set to AMBER
Added comment: 12 individuals with ZNRF3 variants and various phenotypes. 8 individuals with de novo missense and neurodevelopment disorders (NDD), including cluster of variants in the RING ligase domain with macrocephalic NDD. Plus 4 individuals from 3 families with de novo truncating or de novo/inherited large in-frame deletion variants with non-NDD phenotypes, including heart, adrenal, or nephrotic problems. Overall, 4 individuals had congenital heart defects and 2 had microcephaly. Also, supporting in vitro functional assays.
Sources: Literature
Macrocephaly_Megalencephaly v0.145 ZNRF3 Bryony Thompson Marked gene: ZNRF3 as ready
Macrocephaly_Megalencephaly v0.145 ZNRF3 Bryony Thompson Gene: znrf3 has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v0.145 ZNRF3 Bryony Thompson Classified gene: ZNRF3 as Green List (high evidence)
Macrocephaly_Megalencephaly v0.145 ZNRF3 Bryony Thompson Gene: znrf3 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.420 ZNRF3 Bryony Thompson Classified gene: ZNRF3 as Amber List (moderate evidence)
Congenital Heart Defect v0.420 ZNRF3 Bryony Thompson Gene: znrf3 has been classified as Amber List (Moderate Evidence).
Macrocephaly_Megalencephaly v0.144 ZNRF3 Bryony Thompson Classified gene: ZNRF3 as Green List (high evidence)
Macrocephaly_Megalencephaly v0.144 ZNRF3 Bryony Thompson Gene: znrf3 has been classified as Green List (High Evidence).
Congenital Heart Defect v0.419 ZNRF3 Bryony Thompson gene: ZNRF3 was added
gene: ZNRF3 was added to Congenital Heart Defect. Sources: Literature
Mode of inheritance for gene: ZNRF3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZNRF3 were set to 39168120
Phenotypes for gene: ZNRF3 were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: ZNRF3 was set to AMBER
Added comment: 12 individuals with ZNRF3 variants and various phenotypes. 8 individuals with de novo missense and neurodevelopment disorders (NDD), including cluster of variants in the RING ligase domain with macrocephalic NDD. Plus 4 individuals from 3 families with de novo truncating or de novo/inherited large in-frame deletion variants with non-NDD phenotypes, including heart, adrenal, or nephrotic problems. Overall, 4 individuals had congenital heart defects and 2 had microcephaly. Also, supporting in vitro functional assays.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6153 ZNRF3 Bryony Thompson Marked gene: ZNRF3 as ready
Intellectual disability syndromic and non-syndromic v0.6153 ZNRF3 Bryony Thompson Gene: znrf3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6153 ZNRF3 Bryony Thompson Classified gene: ZNRF3 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6153 ZNRF3 Bryony Thompson Gene: znrf3 has been classified as Green List (High Evidence).
Macrocephaly_Megalencephaly v0.143 ZNRF3 Bryony Thompson gene: ZNRF3 was added
gene: ZNRF3 was added to Macrocephaly_Megalencephaly. Sources: Literature
Mode of inheritance for gene: ZNRF3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZNRF3 were set to 39168120
Phenotypes for gene: ZNRF3 were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: ZNRF3 was set to GREEN
Added comment: 12 individuals with ZNRF3 variants and various phenotypes. 8 individuals with de novo missense and neurodevelopment disorders (NDD), including cluster of variants in the RING ligase domain with macrocephalic NDD. Plus 4 individuals from 3 families with de novo truncating or de novo/inherited large in-frame deletion variants with non-NDD phenotypes, including heart, adrenal, or nephrotic problems. Overall, 4 individuals had congenital heart defects and 2 had microcephaly. Also, supporting in vitro functional assays.
Sources: Literature
Mendeliome v1.1997 ZNRF3 Bryony Thompson Marked gene: ZNRF3 as ready
Mendeliome v1.1997 ZNRF3 Bryony Thompson Gene: znrf3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6152 ZNRF3 Bryony Thompson gene: ZNRF3 was added
gene: ZNRF3 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ZNRF3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZNRF3 were set to 39168120
Phenotypes for gene: ZNRF3 were set to Complex neurodevelopmental disorder MONDO:0100038
Review for gene: ZNRF3 was set to GREEN
Added comment: 12 individuals with ZNRF3 variants and various phenotypes. 8 individuals with de novo missense and neurodevelopment disorders (NDD), including cluster of variants in the RING ligase domain with macrocephalic NDD. Plus 4 individuals from 3 families with de novo truncating or de novo/inherited large in-frame deletion variants with non-NDD phenotypes, including heart, adrenal, or nephrotic problems. Overall, 4 individuals had congenital heart defects and 2 had microcephaly. Also, supporting in vitro functional assays.
Sources: Literature
Mendeliome v1.1997 ZNRF3 Bryony Thompson Classified gene: ZNRF3 as Green List (high evidence)
Mendeliome v1.1997 ZNRF3 Bryony Thompson Gene: znrf3 has been classified as Green List (High Evidence).
Mendeliome v1.1996 ZNRF3 Bryony Thompson gene: ZNRF3 was added
gene: ZNRF3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZNRF3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZNRF3 were set to 39168120
Phenotypes for gene: ZNRF3 were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: ZNRF3 was set to GREEN
Added comment: 12 individuals with ZNRF3 variants and various phenotypes. 8 individuals with de novo missense and neurodevelopment disorders (NDD), including cluster of variants in the RING ligase domain with macrocephalic NDD. Plus 4 individuals from 3 families with de novo truncating or de novo/inherited large in-frame deletion variants with non-NDD phenotypes, including heart, adrenal, or nephrotic problems. Overall, 4 individuals had congenital heart defects and 2 had microcephaly. Also, supporting in vitro functional assays.
Sources: Literature
Intellectual disability syndromic and non-syndromic v0.6151 NFIA Zornitza Stark Marked gene: NFIA as ready
Intellectual disability syndromic and non-syndromic v0.6151 NFIA Zornitza Stark Gene: nfia has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6151 DHTKD1 Zornitza Stark Marked gene: DHTKD1 as ready
Intellectual disability syndromic and non-syndromic v0.6151 DHTKD1 Zornitza Stark Gene: dhtkd1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6151 DHTKD1 Zornitza Stark Phenotypes for gene: DHTKD1 were changed from to 2-aminoadipic 2-oxoadipic aciduria MIM#204750; Disorders of histidine, tryptophan or lysine metabolism
Intellectual disability syndromic and non-syndromic v0.6150 DHTKD1 Zornitza Stark Publications for gene: DHTKD1 were set to
Intellectual disability syndromic and non-syndromic v0.6149 DHTKD1 Zornitza Stark Mode of inheritance for gene: DHTKD1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6148 DHTKD1 Zornitza Stark Classified gene: DHTKD1 as Amber List (moderate evidence)
Intellectual disability syndromic and non-syndromic v0.6148 DHTKD1 Zornitza Stark Gene: dhtkd1 has been classified as Amber List (Moderate Evidence).
Intellectual disability syndromic and non-syndromic v0.6147 DCX Zornitza Stark Marked gene: DCX as ready
Intellectual disability syndromic and non-syndromic v0.6147 DCX Zornitza Stark Gene: dcx has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6147 DCX Zornitza Stark Phenotypes for gene: DCX were changed from to Lissencephaly, X-linked, MIM# 300067; Subcortical laminal heterotopia, X-linked 300067
Intellectual disability syndromic and non-syndromic v0.6146 DCX Zornitza Stark Publications for gene: DCX were set to 26743950; 11468322; 20726879; 20301364; 12552055; 9489699
Intellectual disability syndromic and non-syndromic v0.6145 DCX Zornitza Stark Publications for gene: DCX were set to
Intellectual disability syndromic and non-syndromic v0.6144 DCX Zornitza Stark Mode of inheritance for gene: DCX was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability syndromic and non-syndromic v0.6143 DARS2 Zornitza Stark Marked gene: DARS2 as ready
Intellectual disability syndromic and non-syndromic v0.6143 DARS2 Zornitza Stark Gene: dars2 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6143 DARS2 Zornitza Stark Phenotypes for gene: DARS2 were changed from to Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, MIM# 611105
Intellectual disability syndromic and non-syndromic v0.6142 DARS2 Zornitza Stark Publications for gene: DARS2 were set to
Intellectual disability syndromic and non-syndromic v0.6141 DARS2 Zornitza Stark Mode of inheritance for gene: DARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6140 D2HGDH Zornitza Stark Marked gene: D2HGDH as ready
Intellectual disability syndromic and non-syndromic v0.6140 D2HGDH Zornitza Stark Gene: d2hgdh has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6140 D2HGDH Zornitza Stark Phenotypes for gene: D2HGDH were changed from to D-2-hydroxyglutaric aciduria MIM#600721
Intellectual disability syndromic and non-syndromic v0.6139 D2HGDH Zornitza Stark Publications for gene: D2HGDH were set to
Prepair 1000+ v1.262 CFH Cassandra Muller reviewed gene: CFH: Rating: AMBER; Mode of pathogenicity: None; Publications: 7742208, 9312129, 10803850, 14978182; Phenotypes: Complement factor H deficiency, 609814 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6138 D2HGDH Zornitza Stark Mode of inheritance for gene: D2HGDH was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6137 D2HGDH Zornitza Stark Mode of inheritance for gene: D2HGDH was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.6136 COX15 Zornitza Stark Phenotypes for gene: COX15 were changed from Mitochondrial complex IV deficiency, nuclear type 6, MIM# 615119 to Mitochondrial complex IV deficiency, nuclear type 6, MIM# 615119
Intellectual disability syndromic and non-syndromic v0.6136 COX15 Zornitza Stark Marked gene: COX15 as ready
Intellectual disability syndromic and non-syndromic v0.6136 COX15 Zornitza Stark Gene: cox15 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6136 COX15 Zornitza Stark Phenotypes for gene: COX15 were changed from Mitochondrial complex IV deficiency, nuclear type 6, MIM# 615119 to Mitochondrial complex IV deficiency, nuclear type 6, MIM# 615119
Intellectual disability syndromic and non-syndromic v0.6135 COX15 Zornitza Stark Phenotypes for gene: COX15 were changed from to Mitochondrial complex IV deficiency, nuclear type 6, MIM# 615119
Prepair 1000+ v1.262 CSTB Cassandra Muller reviewed gene: CSTB: Rating: AMBER; Mode of pathogenicity: None; Publications: 9012407; Phenotypes: Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), 254800 (3); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v1.1995 RFC4 Chirag Patel Classified gene: RFC4 as Green List (high evidence)
Mendeliome v1.1995 RFC4 Chirag Patel Gene: rfc4 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6134 GPN2 Mark Cleghorn gene: GPN2 was added
gene: GPN2 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: GPN2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GPN2 were set to complex neurodevelopmental disorder MONDO:0100038; Perrault syndrome
Review for gene: GPN2 was set to AMBER
Added comment: GPN2
ESHG talk 2/6/24, unpublished
Thomas Smith, University of Manchester

Biallelic GPN2 proposed to cause Perrault syndrome (SNHL, ovarian dysfunction, NDD)
RNA polymerase assembly factor

4 families (14 affected individuals) w biallalic GPN2 rare missense variants
Segregated w phenotype
Fam 2 and 3 may be distantly related (leaving 3 distinct kindreds)

Clinical features
13/14 SNHL
3/4 families all females of adolescent age or older had primary ovarian insufficiency
4/4 GDD, ataxia (no data on family w 10 affected indiv.)

Some functional work, not conclusive
Sources: Other
Mendeliome v1.1994 ATP6V1C1 Zornitza Stark Marked gene: ATP6V1C1 as ready
Mendeliome v1.1994 ATP6V1C1 Zornitza Stark Gene: atp6v1c1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.6134 ATP6V1C1 Zornitza Stark Marked gene: ATP6V1C1 as ready
Intellectual disability syndromic and non-syndromic v0.6134 ATP6V1C1 Zornitza Stark Gene: atp6v1c1 has been classified as Red List (Low Evidence).
Intellectual disability syndromic and non-syndromic v0.6134 ATP6V1C1 Zornitza Stark gene: ATP6V1C1 was added
gene: ATP6V1C1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature
Mode of inheritance for gene: ATP6V1C1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP6V1C1 were set to 39210597
Phenotypes for gene: ATP6V1C1 were set to neurodevelopmental disorder MONDO:0700092, ATP6V1C1-related
Review for gene: ATP6V1C1 was set to RED
Added comment: 1x de novo missense p.Glu289Lys (absent in v4 gnomad). Manual inspection of IGV found the dad was mosaic 7% VAF and he shared some of the clinical features (minor digit anomalies). Some functional studies using patient fibroblasts were performed, demonstrating similar effects as known pathogenic variants in ATP6V1B2. - lysosomal morphology - autophagic flux dysregulation - increased acidification of lysosome borderline red/amber
Sources: Literature
Mendeliome v1.1994 ATP6V1C1 Zornitza Stark Phenotypes for gene: ATP6V1C1 were changed from to neurodevelopmental disorder MONDO:0700092, ATP6V1C1-related
Intellectual disability syndromic and non-syndromic v0.6133 C12orf66 Zornitza Stark Marked gene: C12orf66 as ready
Intellectual disability syndromic and non-syndromic v0.6133 C12orf66 Zornitza Stark Gene: c12orf66 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6133 C12orf66 Zornitza Stark Classified gene: C12orf66 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6133 C12orf66 Zornitza Stark Gene: c12orf66 has been classified as Green List (High Evidence).
Mendeliome v1.1993 C12orf66 Zornitza Stark Marked gene: C12orf66 as ready
Mendeliome v1.1993 C12orf66 Zornitza Stark Gene: c12orf66 has been classified as Green List (High Evidence).
Mendeliome v1.1993 C12orf66 Zornitza Stark Classified gene: C12orf66 as Green List (high evidence)
Mendeliome v1.1993 C12orf66 Zornitza Stark Gene: c12orf66 has been classified as Green List (High Evidence).
Mendeliome v1.1992 RFC4 Chirag Patel gene: RFC4 was added
gene: RFC4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: RFC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RFC4 were set to PMID: 39106866
Phenotypes for gene: RFC4 were set to RFC4-related multisystem disorder
Review for gene: RFC4 was set to GREEN
gene: RFC4 was marked as current diagnostic
Added comment: 9 affected individuals (aged birth to 47yrs) from 8 unrelated families with a multisystem disorder. Clinical features included: muscle weakness/myopathy (9/9), motor incoordination/gait disturbance (8/8), delayed gross motor development (6/9), dysarthria (5/5), peripheral neuropathy (3/3 adults), bilateral sensorineural hearing impairment (6/9), decreased body weight (8/9), short stature (5/9), microcephaly (4/9), respiratory issues/insufficiency (6/9), cerebellar atrophy (4/9), pituitary hypoplasia (3/9).

WES or WGS identified biallelic loss-of-function variants in RFC4 (3 frameshift, 2 splice site, 1 single AA duplication, 2 single AA deletions, 2 missense), and almost all are likely to disrupt the C-terminal domain indispensable for Replication factor C (RFC) complex formation. All variants segregated with the disease.

The RFC complex (with 5 subunits) is central to process of regulation of DNA replication, and it loads proliferating cell nuclear antigen onto DNA to facilitate the recruitment of replication and repair proteins and enhance DNA polymerase processivity. RFC1 is associated with CANVAS but the contributions of RFC2-5 subunits on human Mendelian disorders is unknown.

Analysis of a previously determined cryo-EM structure of RFC bound to proliferating cell nuclear antigen suggested that the variants disrupt interactions within RFC4 and/or destabilize the RFC complex. Cellular studies using RFC4-deficient HeLa cells and primary fibroblasts demonstrated decreased RFC4 protein, compromised stability of the other RFC complex subunits, and perturbed RFC complex formation. Additionally, functional studies of the RFC4 variants affirmed diminished RFC complex formation, and cell cycle studies suggested perturbation of DNA replication and cell cycle progression.
Sources: Literature
Mendeliome v1.1991 COQ8B Zornitza Stark Phenotypes for gene: COQ8B were changed from Nephrotic syndrome, type 9 MIM#615573 to Nephrotic syndrome, type 9 MIM#615573; Retinitis pigmentosa MONDO:0019200
Mendeliome v1.1990 COQ8B Zornitza Stark Publications for gene: COQ8B were set to 24270420
Mendeliome v1.1989 SF3B1 Zornitza Stark Classified gene: SF3B1 as Green List (high evidence)
Mendeliome v1.1989 SF3B1 Zornitza Stark Gene: sf3b1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6132 SF3B1 Zornitza Stark Marked gene: SF3B1 as ready
Intellectual disability syndromic and non-syndromic v0.6132 SF3B1 Zornitza Stark Gene: sf3b1 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.6132 SF3B1 Zornitza Stark Classified gene: SF3B1 as Green List (high evidence)
Intellectual disability syndromic and non-syndromic v0.6132 SF3B1 Zornitza Stark Gene: sf3b1 has been classified as Green List (High Evidence).
Mendeliome v1.1988 SF3B1 Zornitza Stark Marked gene: SF3B1 as ready
Mendeliome v1.1988 SF3B1 Zornitza Stark Gene: sf3b1 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1988 SF3B1 Zornitza Stark Classified gene: SF3B1 as Amber List (moderate evidence)
Mendeliome v1.1988 SF3B1 Zornitza Stark Gene: sf3b1 has been classified as Amber List (Moderate Evidence).
Muscular dystrophy and myopathy_Paediatric v1.70 JPH1 Zornitza Stark Classified gene: JPH1 as Green List (high evidence)
Muscular dystrophy and myopathy_Paediatric v1.70 JPH1 Zornitza Stark Gene: jph1 has been classified as Green List (High Evidence).
Muscular dystrophy and myopathy_Paediatric v1.70 JPH1 Zornitza Stark Classified gene: JPH1 as Green List (high evidence)