{"count":220790,"next":"https://panelapp-aus.org/api/v1/activities/?format=json&page=177","previous":"https://panelapp-aus.org/api/v1/activities/?format=json&page=175","results":[{"created":"2025-09-04T14:46:54.865267+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2980","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: REPS1 were set to 29395073","entity_name":"REPS1","entity_type":"gene"},{"created":"2025-09-04T14:46:38.993796+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2979","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: REPS1: Added comment: Additional family reported in PMID 40788509, but homozygous missense variant with no further supporting information.; Changed publications: 29395073, 40788509","entity_name":"REPS1","entity_type":"gene"},{"created":"2025-09-04T14:46:05.428975+10:00","panel_name":"Neurodegeneration with brain iron accumulation","panel_id":3438,"panel_version":"1.1","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: REPS1 were set to 29395073","entity_name":"REPS1","entity_type":"gene"},{"created":"2025-09-04T14:45:41.517665+10:00","panel_name":"Neurodegeneration with brain iron accumulation","panel_id":3438,"panel_version":"1.0","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: REPS1: Added comment: Additional family reported in PMID 40788509, but homozygous missense variant with no further supporting information.; Changed publications: 29395073, 40788509; Changed phenotypes: Neurodegeneration with brain iron accumulation 7 , MIM# 617916","entity_name":"REPS1","entity_type":"gene"},{"created":"2025-09-04T14:44:13.032070+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2979","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: MYOF were set to 32542751","entity_name":"MYOF","entity_type":"gene"},{"created":"2025-09-04T14:43:53.326640+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2978","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: MYOF: Added comment: Two further families reported but with missense variants, which did not completely segregate with disease. No other supportive information provided.; Changed publications: 32542751, 40797221","entity_name":"MYOF","entity_type":"gene"},{"created":"2025-09-04T14:42:59.263622+10:00","panel_name":"Hereditary angioedema","panel_id":226,"panel_version":"1.6","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: MYOF were set to 32542751","entity_name":"MYOF","entity_type":"gene"},{"created":"2025-09-04T14:42:31.653687+10:00","panel_name":"Hereditary angioedema","panel_id":226,"panel_version":"1.5","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: MYOF: Added comment: Two further families reported but with missense variants, which did not completely segregate with disease. No other supportive information provided.; Changed publications: 32542751, 40797221","entity_name":"MYOF","entity_type":"gene"},{"created":"2025-09-04T14:40:05.307318+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"1.273","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: CDK6 were set to 23918663","entity_name":"CDK6","entity_type":"gene"},{"created":"2025-09-04T14:39:36.411560+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"1.272","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: CDK6: Added comment: Second family reported, but same homozygous missense variant, likely founder.; Changed publications: 23918663, 40801391","entity_name":"CDK6","entity_type":"gene"},{"created":"2025-09-04T14:39:01.633131+10:00","panel_name":"Microcephaly","panel_id":138,"panel_version":"1.331","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: CDK6 were set to 23918663","entity_name":"CDK6","entity_type":"gene"},{"created":"2025-09-04T14:38:39.234823+10:00","panel_name":"Microcephaly","panel_id":138,"panel_version":"1.330","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: CDK6: Added comment: Report of a second family but same homozygous variant, likely founder.; Changed publications: 23918663, 40801391","entity_name":"CDK6","entity_type":"gene"},{"created":"2025-09-04T14:37:27.865996+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2978","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: CDK6 were set to 23918663","entity_name":"CDK6","entity_type":"gene"},{"created":"2025-09-04T14:37:07.374476+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2977","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: CDK6: Added comment: Report of a second family, but same homozygous missense variant, suggestive of founder effect.; Changed publications: 23918663, 40801391","entity_name":"CDK6","entity_type":"gene"},{"created":"2025-09-04T14:31:41.461702+10:00","panel_name":"Incidentalome","panel_id":126,"panel_version":"0.322","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: DNAJC7 were set to 31768050","entity_name":"DNAJC7","entity_type":"gene"},{"created":"2025-09-04T14:31:14.752971+10:00","panel_name":"Incidentalome","panel_id":126,"panel_version":"0.321","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: DNAJC7: Added comment: PMID 40802071: single family with three affected sibs and bi-allelic variants associated with ALS.; Changed publications: 31768050, 40802071","entity_name":"DNAJC7","entity_type":"gene"},{"created":"2025-09-04T14:30:31.298572+10:00","panel_name":"Motor Neurone Disease","panel_id":25,"panel_version":"1.34","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: DNAJC7 were set to 31768050","entity_name":"DNAJC7","entity_type":"gene"},{"created":"2025-09-04T14:29:42.929402+10:00","panel_name":"Motor Neurone Disease","panel_id":25,"panel_version":"1.33","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: DNAJC7: Added comment: PMID 40802071: report of bi-allelic LoF variants in three sibs with ALS.; Changed publications: 40802071","entity_name":"DNAJC7","entity_type":"gene"},{"created":"2025-09-04T10:28:12.093229+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"1.195","user_name":"Krithika Murali","item_type":"entity","text":"changed review comment from: PMID: 40632521 Li et al 2025 (Epilepsia) reported 6 unrelated individuals of Han Chinese descent with biallelic CSMD2 missense variants (NM_052896) and focal epilepsy. 5 individuals were compound heterozygous and one was homozygous. These individuals were ascertained through trio WES analysis of 420 unrelated individuals with focal epilepsy enrolled in the China Epilepsy Gene 1.0 project.\r\n\r\nPhenotypic features\r\n- age of onset 1.5-10 years old\r\n- complex partial seizures (4), secondary GTCS (2)\r\n- Normal MRI-B (3), focal cortical dysplasia (1)\r\n- mild ID (1).\r\n\r\nThe variants were noted to be rare in EXAC-East Asian cohort, most located in CUB/Sushi domains. The gene has some evidence of missense and LoF constraint in gnomAD v4. There was also enrichment of biallelic CSMD2 variants in affected individuals versus a control cohort of unaffected parents (5/420 compound hets affected individuals, 3/1942 compound hets in unaffected parents). Previous mouse Csmd2 knockdown models demonstrated reduction in dendritic spine density and complexity. LoF is the postulated disease mechanism.\r\n\r\nClosely related gene paralog CSMD1 has a definitive association with autosomal recessive complex neurodevelopmental disorder with a more severe phenotype.  Different expression profiles during developmental stages between CSMD1 and CSMD2 postulated for the comparatively milder phenotype associated with the latter.\r\n\r\nCSMD2 has 71 exons and 3631 amino acids. The true prevalence of biallelic missense variants in healthy individuals across diverse ancestries has not been ascertained. Review of the missense variants in this study highlighted issues in a number of them including poor-moderate conservation, conflicting or benign in silicos including REVEL, non-coding in an alternative transcript, Case 4 p.Val1547Ile homozygote – this variant has been noted in an East Asian male homozygote aged between 45-50 in gnomAD v4. In addition, no information about unaffected siblings and segregation testing has been provided.\r\n\r\nGiven prevalence of focal epilepsy, stronger case-control evidence from diverse ancestries and variant-specific functional evidence is required to support this proposed gene-disease association. \r\nSources: Literature; to: PMID: 40632521 Li et al 2025 (Epilepsia) reported 6 unrelated individuals of Han Chinese descent with biallelic CSMD2 missense variants (NM_052896) and focal epilepsy. 5 individuals were compound heterozygous and one was homozygous. These individuals were ascertained through trio WES analysis of 420 unrelated individuals with focal epilepsy enrolled in the China Epilepsy Gene 1.0 project.\r\n\r\nPhenotypic features\r\n- age of onset 1.5-10 years old\r\n- complex partial seizures (4), secondary GTCS (2)\r\n- Normal MRI-B (3), focal cortical dysplasia (1)\r\n- mild ID (1).\r\n\r\nThe variants were noted to be rare in EXAC-East Asian cohort, most located in CUB/Sushi domains. The gene has some evidence of missense and LoF constraint in gnomAD v4. There was also enrichment of biallelic CSMD2 variants in affected individuals versus a control cohort of unaffected parents (5/420 compound hets affected individuals, 3/1942 compound hets in unaffected parents). Previous mouse Csmd2 knockdown models demonstrated reduction in dendritic spine density and complexity. LoF is the postulated disease mechanism.\r\n\r\nClosely related gene paralog CSMD1 has a definitive association with autosomal recessive complex neurodevelopmental disorder with a more severe phenotype.  Different expression profiles during developmental stages between CSMD1 and CSMD2 postulated for the comparatively milder phenotype associated with the latter.\r\n\r\nCSMD2 has 71 exons and 3631 amino acids. The true prevalence of biallelic missense variants in healthy individuals across diverse ancestries has not been ascertained. Review of the missense variants in this study highlighted issues in a number of them including poor-moderate conservation, conflicting or benign in silicos including REVEL, non-coding in an alternative transcript, Case 4 p.Val1547Ile homozygote – this variant has been noted in an East Asian male homozygote aged between 45-50 in gnomAD v4. In addition, no information about unaffected/affected siblings and segregation testing has been provided.\r\n\r\nGiven prevalence of focal epilepsy, stronger case-control evidence from diverse ancestries and variant-specific functional evidence is required to support this proposed gene-disease association. \r\nSources: Literature","entity_name":"CSMD2","entity_type":"gene"},{"created":"2025-09-04T10:27:48.685826+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2977","user_name":"Krithika Murali","item_type":"entity","text":"changed review comment from: PMID: 40632521 Li et al 2025 (Epilepsia) reported 6 unrelated individuals of Han Chinese descent with biallelic CSMD2 missense variants (NM_052896) and focal epilepsy. 5 individuals were compound heterozygous and one was homozygous. These individuals were ascertained through trio WES analysis of 420 unrelated individuals with focal epilepsy enrolled in the China Epilepsy Gene 1.0 project.\r\n\r\nPhenotypic features\r\n- age of onset 1.5-10 years old\r\n- complex partial seizures (4), secondary GTCS (2)\r\n- Normal MRI-B (3), focal cortical dysplasia (1)\r\n- mild ID (1).\r\n\r\nThe variants were noted to be rare in EXAC-East Asian cohort, most located in CUB/Sushi domains. The gene has some evidence of missense and LoF constraint in gnomAD v4. There was also enrichment of biallelic CSMD2 variants in affected individuals versus a control cohort of unaffected parents (5/420 compound hets affected individuals, 3/1942 compound hets in unaffected parents). Previous mouse Csmd2 knockdown models demonstrated reduction in dendritic spine density and complexity. LoF is the postulated disease mechanism.\r\n\r\nClosely related gene paralog CSMD1 has a definitive association with autosomal recessive complex neurodevelopmental disorder with a more severe phenotype.  Different expression profiles during developmental stages between CSMD1 and CSMD2 postulated for the comparatively milder phenotype associated with the latter.\r\n\r\nCSMD2 has 71 exons and 3631 amino acids. The true prevalence of biallelic missense variants in healthy individuals across diverse ancestries has not been ascertained. Review of the missense variants in this study highlighted issues in a number of them including poor-moderate conservation, conflicting or benign in silicos including REVEL, non-coding in an alternative transcript, Case 4 p.Val1547Ile homozygote – this variant has been noted in an East Asian male homozygote aged between 45-50 in gnomAD v4.  In addition, no information about unaffected siblings and segregation testing has been provided.\r\n\r\nGiven prevalence of focal epilepsy, stronger case-control evidence from diverse ancestries and variant-specific functional evidence is required to support this proposed gene-disease association.; to: PMID: 40632521 Li et al 2025 (Epilepsia) reported 6 unrelated individuals of Han Chinese descent with biallelic CSMD2 missense variants (NM_052896) and focal epilepsy. 5 individuals were compound heterozygous and one was homozygous. These individuals were ascertained through trio WES analysis of 420 unrelated individuals with focal epilepsy enrolled in the China Epilepsy Gene 1.0 project.\r\n\r\nPhenotypic features\r\n- age of onset 1.5-10 years old\r\n- complex partial seizures (4), secondary GTCS (2)\r\n- Normal MRI-B (3), focal cortical dysplasia (1)\r\n- mild ID (1).\r\n\r\nThe variants were noted to be rare in EXAC-East Asian cohort, most located in CUB/Sushi domains. The gene has some evidence of missense and LoF constraint in gnomAD v4. There was also enrichment of biallelic CSMD2 variants in affected individuals versus a control cohort of unaffected parents (5/420 compound hets affected individuals, 3/1942 compound hets in unaffected parents). Previous mouse Csmd2 knockdown models demonstrated reduction in dendritic spine density and complexity. LoF is the postulated disease mechanism.\r\n\r\nClosely related gene paralog CSMD1 has a definitive association with autosomal recessive complex neurodevelopmental disorder with a more severe phenotype.  Different expression profiles during developmental stages between CSMD1 and CSMD2 postulated for the comparatively milder phenotype associated with the latter.\r\n\r\nCSMD2 has 71 exons and 3631 amino acids. The true prevalence of biallelic missense variants in healthy individuals across diverse ancestries has not been ascertained. Review of the missense variants in this study highlighted issues in a number of them including poor-moderate conservation, conflicting or benign in silicos including REVEL, non-coding in an alternative transcript, Case 4 p.Val1547Ile homozygote – this variant has been noted in an East Asian male homozygote aged between 45-50 in gnomAD v4.  In addition, no information about unaffected/affected siblings and segregation testing has been provided.\r\n\r\nGiven prevalence of focal epilepsy, stronger case-control evidence from diverse ancestries and variant-specific functional evidence is required to support this proposed gene-disease association.","entity_name":"CSMD2","entity_type":"gene"},{"created":"2025-09-04T10:24:48.699243+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"1.195","user_name":"Krithika Murali","item_type":"entity","text":"changed review comment from: PMID: 40632521 Li et al 2025 (Epilepsia) reported 6 unrelated individuals of Han Chinese descent with biallelic CSMD2 missense variants (NM_052896) and focal epilepsy. 5 individuals were compound heterozygous and one was homozygous. These individuals were ascertained through trio WES analysis of 420 unrelated individuals with focal epilepsy enrolled in the China Epilepsy Gene 1.0 project.\r\n\r\nPhenotypic features\r\n- age of onset 1.5-10 years old\r\n- complex partial seizures (4), secondary GTCS (2)\r\n- Normal MRI-B (3), focal cortical dysplasia (1)\r\n- mild ID (1).\r\n\r\nThe variants were noted to be rare in EXAC-East Asian cohort, most located in CUB/Sushi domains. The gene has some evidence of missense and LoF constraint in gnomAD v4. There was also enrichment of biallelic CSMD2 variants in affected individuals versus a control cohort of unaffected parents (5/420 compound hets affected individuals, 3/1942 compound hets in unaffected parents). Previous mouse Csmd2 knockdown models demonstrated reduction in dendritic spine density and complexity. LoF is the postulated disease mechanism.\r\n\r\nClosely related gene paralog CSMD1 has a definitive association with autosomal recessive complex neurodevelopmental disorder with a more severe phenotype.  Different expression profiles during developmental stages between CSMD1 and CSMD2 postulated for the comparatively milder phenotype associated with the latter.\r\n\r\nCSMD2 has 71 exons and 3631 amino acids. The true prevalence of biallelic missense variants in healthy individuals across diverse ancestries has not been ascertained. Review of the missense variants in this study highlighted issues in a number of them including poor-moderate conservation, conflicting or benign in silicos including REVEL, non-coding in an alternative transcript, Case 4 p.Val1547Ile homozygote – this variant has been noted in an East Asian male homozygote aged between 45-50 in gnomAD v4.\r\n\r\nGiven prevalence of focal epilepsy, stronger case-control evidence from diverse ancestries and variant-specific functional evidence is required to support this proposed gene-disease association. \nSources: Literature; to: PMID: 40632521 Li et al 2025 (Epilepsia) reported 6 unrelated individuals of Han Chinese descent with biallelic CSMD2 missense variants (NM_052896) and focal epilepsy. 5 individuals were compound heterozygous and one was homozygous. These individuals were ascertained through trio WES analysis of 420 unrelated individuals with focal epilepsy enrolled in the China Epilepsy Gene 1.0 project.\r\n\r\nPhenotypic features\r\n- age of onset 1.5-10 years old\r\n- complex partial seizures (4), secondary GTCS (2)\r\n- Normal MRI-B (3), focal cortical dysplasia (1)\r\n- mild ID (1).\r\n\r\nThe variants were noted to be rare in EXAC-East Asian cohort, most located in CUB/Sushi domains. The gene has some evidence of missense and LoF constraint in gnomAD v4. There was also enrichment of biallelic CSMD2 variants in affected individuals versus a control cohort of unaffected parents (5/420 compound hets affected individuals, 3/1942 compound hets in unaffected parents). Previous mouse Csmd2 knockdown models demonstrated reduction in dendritic spine density and complexity. LoF is the postulated disease mechanism.\r\n\r\nClosely related gene paralog CSMD1 has a definitive association with autosomal recessive complex neurodevelopmental disorder with a more severe phenotype.  Different expression profiles during developmental stages between CSMD1 and CSMD2 postulated for the comparatively milder phenotype associated with the latter.\r\n\r\nCSMD2 has 71 exons and 3631 amino acids. The true prevalence of biallelic missense variants in healthy individuals across diverse ancestries has not been ascertained. Review of the missense variants in this study highlighted issues in a number of them including poor-moderate conservation, conflicting or benign in silicos including REVEL, non-coding in an alternative transcript, Case 4 p.Val1547Ile homozygote – this variant has been noted in an East Asian male homozygote aged between 45-50 in gnomAD v4. In addition, no information about unaffected siblings and segregation testing has been provided.\r\n\r\nGiven prevalence of focal epilepsy, stronger case-control evidence from diverse ancestries and variant-specific functional evidence is required to support this proposed gene-disease association. \r\nSources: Literature","entity_name":"CSMD2","entity_type":"gene"},{"created":"2025-09-04T10:24:27.909912+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2977","user_name":"Krithika Murali","item_type":"entity","text":"changed review comment from: PMID: 40632521 Li et al 2025 (Epilepsia) reported 6 unrelated individuals of Han Chinese descent with biallelic CSMD2 missense variants (NM_052896) and focal epilepsy. 5 individuals were compound heterozygous and one was homozygous. These individuals were ascertained through trio WES analysis of 420 unrelated individuals with focal epilepsy enrolled in the China Epilepsy Gene 1.0 project.\r\n\r\nPhenotypic features\r\n- age of onset 1.5-10 years old\r\n- complex partial seizures (4), secondary GTCS (2)\r\n- Normal MRI-B (3), focal cortical dysplasia (1)\r\n- mild ID (1).\r\n\r\nThe variants were noted to be rare in EXAC-East Asian cohort, most located in CUB/Sushi domains. The gene has some evidence of missense and LoF constraint in gnomAD v4. There was also enrichment of biallelic CSMD2 variants in affected individuals versus a control cohort of unaffected parents (5/420 compound hets affected individuals, 3/1942 compound hets in unaffected parents). Previous mouse Csmd2 knockdown models demonstrated reduction in dendritic spine density and complexity. LoF is the postulated disease mechanism.\r\n\r\nClosely related gene paralog CSMD1 has a definitive association with autosomal recessive complex neurodevelopmental disorder with a more severe phenotype.  Different expression profiles during developmental stages between CSMD1 and CSMD2 postulated for the comparatively milder phenotype associated with the latter.\r\n\r\nCSMD2 has 71 exons and 3631 amino acids. The true prevalence of biallelic missense variants in healthy individuals across diverse ancestries has not been ascertained. Review of the missense variants in this study highlighted issues in a number of them including poor-moderate conservation, conflicting or benign in silicos including REVEL, non-coding in an alternative transcript, Case 4 p.Val1547Ile homozygote – this variant has been noted in an East Asian male homozygote aged between 45-50 in gnomAD v4.\r\n\r\nGiven prevalence of focal epilepsy, stronger case-control evidence from diverse ancestries and variant-specific functional evidence is required to support this proposed gene-disease association.; to: PMID: 40632521 Li et al 2025 (Epilepsia) reported 6 unrelated individuals of Han Chinese descent with biallelic CSMD2 missense variants (NM_052896) and focal epilepsy. 5 individuals were compound heterozygous and one was homozygous. These individuals were ascertained through trio WES analysis of 420 unrelated individuals with focal epilepsy enrolled in the China Epilepsy Gene 1.0 project.\r\n\r\nPhenotypic features\r\n- age of onset 1.5-10 years old\r\n- complex partial seizures (4), secondary GTCS (2)\r\n- Normal MRI-B (3), focal cortical dysplasia (1)\r\n- mild ID (1).\r\n\r\nThe variants were noted to be rare in EXAC-East Asian cohort, most located in CUB/Sushi domains. The gene has some evidence of missense and LoF constraint in gnomAD v4. There was also enrichment of biallelic CSMD2 variants in affected individuals versus a control cohort of unaffected parents (5/420 compound hets affected individuals, 3/1942 compound hets in unaffected parents). Previous mouse Csmd2 knockdown models demonstrated reduction in dendritic spine density and complexity. LoF is the postulated disease mechanism.\r\n\r\nClosely related gene paralog CSMD1 has a definitive association with autosomal recessive complex neurodevelopmental disorder with a more severe phenotype.  Different expression profiles during developmental stages between CSMD1 and CSMD2 postulated for the comparatively milder phenotype associated with the latter.\r\n\r\nCSMD2 has 71 exons and 3631 amino acids. The true prevalence of biallelic missense variants in healthy individuals across diverse ancestries has not been ascertained. Review of the missense variants in this study highlighted issues in a number of them including poor-moderate conservation, conflicting or benign in silicos including REVEL, non-coding in an alternative transcript, Case 4 p.Val1547Ile homozygote – this variant has been noted in an East Asian male homozygote aged between 45-50 in gnomAD v4.  In addition, no information about unaffected siblings and segregation testing has been provided.\r\n\r\nGiven prevalence of focal epilepsy, stronger case-control evidence from diverse ancestries and variant-specific functional evidence is required to support this proposed gene-disease association.","entity_name":"CSMD2","entity_type":"gene"},{"created":"2025-09-04T10:03:42.750284+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"1.272","user_name":"Krithika Murali","item_type":"entity","text":"gene: CSMD2 was added\ngene: CSMD2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: CSMD2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: CSMD2 were set to PMID: 40632521; 31068362; 38649688\nPhenotypes for gene: CSMD2 were set to Focal epilepsy - MONDO:0005384, CSMD2-related\nReview for gene: CSMD2 was set to RED\nAdded comment: PMID: 40632521 Li et al 2025 (Epilepsia) reported 6 unrelated individuals of Han Chinese descent with biallelic CSMD2 missense variants (NM_052896) and focal epilepsy. 5 individuals were compound heterozygous and one was homozygous. These individuals were ascertained through trio WES analysis of 420 unrelated individuals with focal epilepsy enrolled in the China Epilepsy Gene 1.0 project.\r\n\r\nPhenotypic features\r\n- age of onset 1.5-10 years old\r\n- complex partial seizures (4), secondary GTCS (2)\r\n- Normal MRI-B (3), focal cortical dysplasia (1)\r\n- mild ID (1).\r\n\r\nThe variants were noted to be rare in EXAC-East Asian cohort, most located in CUB/Sushi domains. The gene has some evidence of missense and LoF constraint in gnomAD v4. There was also enrichment of biallelic CSMD2 variants in affected individuals versus a control cohort of unaffected parents (5/420 compound hets affected individuals, 3/1942 compound hets in unaffected parents). Previous mouse Csmd2 knockdown models demonstrated reduction in dendritic spine density and complexity. LoF is the postulated disease mechanism.\r\n\r\nClosely related gene paralog CSMD1 has a definitive association with autosomal recessive complex neurodevelopmental disorder with a more severe phenotype.  Different expression profiles during developmental stages between CSMD1 and CSMD2 postulated for the comparatively milder phenotype associated with the latter.\r\n\r\nCSMD2 has 71 exons and 3631 amino acids. The true prevalence of biallelic missense variants in healthy individuals across diverse ancestries has not been ascertained. Review of the missense variants in this study highlighted issues in a number of them including poor-moderate conservation, conflicting or benign in silicos including REVEL, non-coding in an alternative transcript, Case 4 p.Val1547Ile homozygote – this variant has been noted in an East Asian male homozygote aged between 45-50 in gnomAD v4.\r\n\r\nGiven prevalence of focal epilepsy, stronger case-control evidence from diverse ancestries and variant-specific functional evidence is required to support this proposed gene-disease association. \nSources: Literature","entity_name":"CSMD2","entity_type":"gene"},{"created":"2025-09-04T10:03:42.195833+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"1.195","user_name":"Krithika Murali","item_type":"entity","text":"Marked gene: CSMD2 as ready","entity_name":"CSMD2","entity_type":"gene"},{"created":"2025-09-04T10:03:42.182080+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"1.195","user_name":"Krithika Murali","item_type":"entity","text":"Gene: csmd2 has been classified as Red List (Low Evidence).","entity_name":"CSMD2","entity_type":"gene"},{"created":"2025-09-04T10:03:31.278885+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"1.272","user_name":"Krithika Murali","item_type":"entity","text":"gene: CSMD2 was added\ngene: CSMD2 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: CSMD2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: CSMD2 were set to PMID: 40632521; 31068362; 38649688\nPhenotypes for gene: CSMD2 were set to Focal epilepsy - MONDO:0005384, CSMD2-related\nReview for gene: CSMD2 was set to RED\nAdded comment: PMID: 40632521 Li et al 2025 (Epilepsia) reported 6 unrelated individuals of Han Chinese descent with biallelic CSMD2 missense variants (NM_052896) and focal epilepsy. 5 individuals were compound heterozygous and one was homozygous. These individuals were ascertained through trio WES analysis of 420 unrelated individuals with focal epilepsy enrolled in the China Epilepsy Gene 1.0 project.\r\n\r\nPhenotypic features\r\n- age of onset 1.5-10 years old\r\n- complex partial seizures (4), secondary GTCS (2)\r\n- Normal MRI-B (3), focal cortical dysplasia (1)\r\n- mild ID (1).\r\n\r\nThe variants were noted to be rare in EXAC-East Asian cohort, most located in CUB/Sushi domains. The gene has some evidence of missense and LoF constraint in gnomAD v4. There was also enrichment of biallelic CSMD2 variants in affected individuals versus a control cohort of unaffected parents (5/420 compound hets affected individuals, 3/1942 compound hets in unaffected parents). Previous mouse Csmd2 knockdown models demonstrated reduction in dendritic spine density and complexity. LoF is the postulated disease mechanism.\r\n\r\nClosely related gene paralog CSMD1 has a definitive association with autosomal recessive complex neurodevelopmental disorder with a more severe phenotype.  Different expression profiles during developmental stages between CSMD1 and CSMD2 postulated for the comparatively milder phenotype associated with the latter.\r\n\r\nCSMD2 has 71 exons and 3631 amino acids. The true prevalence of biallelic missense variants in healthy individuals across diverse ancestries has not been ascertained. Review of the missense variants in this study highlighted issues in a number of them including poor-moderate conservation, conflicting or benign in silicos including REVEL, non-coding in an alternative transcript, Case 4 p.Val1547Ile homozygote – this variant has been noted in an East Asian male homozygote aged between 45-50 in gnomAD v4.\r\n\r\nGiven prevalence of focal epilepsy, stronger case-control evidence from diverse ancestries and variant-specific functional evidence is required to support this proposed gene-disease association. \nSources: Literature","entity_name":"CSMD2","entity_type":"gene"},{"created":"2025-09-04T10:01:56.856093+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2977","user_name":"Krithika Murali","item_type":"entity","text":"changed review comment from: PMID: 40632521 Li et al 2025 (Epilepsia) reported 6 unrelated individuals of Han Chinese descent with biallelic CSMD2 missense variants (NM_052896) and focal epilepsy. 5 individuals were compound heterozygous and one was homozygous. These individuals were ascertained through trio WES analysis of 420 unrelated individuals with focal epilepsy enrolled in the China Epilepsy Gene 1.0 project.\r\n\r\nPhenotypic features\r\n- age of onset 1.5-10 years old\r\n- complex partial seizures (4), secondary GTCS (2)\r\n- Normal MRI-B (3), focal cortical dysplasia (1)\r\n- mild ID (1).\r\n\r\nThe variants were noted to be rare in EXAC-East Asian cohort, most located in CUB/Sushi domains. The gene has some evidence of missense and LoF constraint in gnomAD v4. There was also enrichment of biallelic CSMD2 variants in affected individuals versus a control cohort of unaffected parents (5/420 compound hets affected individuals, 3/1942 compound hets in unaffected parents). Previous mouse Csmd2 knockdown models demonstrated reduction in dendritic spine density and complexity. LoF is the postulated disease mechanism.\r\n\r\nClosely related gene paralog CSMD1 has a definitive association with autosomal recessive complex neurodevelopmental disorder with a more severe phenotype.  Different expression profiles during developmental stages between CSMD1 and CSMD2 postulated for the comparatively milder phenotype associated with the latter.\r\n\r\nCSMD2 has 71 exons and 3631 amino acids. The true prevalence of biallelic missense variants in healthy individuals across diverse ancestries has not been ascertained. Review of the missense variants in this study highlighted issues in a number of them including poor-moderate conservation, conflicting or benign in silicos including REVEL, non-coding in an alternative transcript, Case 4 p.Val1547Ile homozygote – this variant has been noted in an East Asian male homozygote aged between 45-50.\r\n\r\nGiven prevalence of focal epilepsy, stronger case-control evidence from diverse ancestries and variant-specific functional evidence is required to support this proposed gene-disease association.; to: PMID: 40632521 Li et al 2025 (Epilepsia) reported 6 unrelated individuals of Han Chinese descent with biallelic CSMD2 missense variants (NM_052896) and focal epilepsy. 5 individuals were compound heterozygous and one was homozygous. These individuals were ascertained through trio WES analysis of 420 unrelated individuals with focal epilepsy enrolled in the China Epilepsy Gene 1.0 project.\r\n\r\nPhenotypic features\r\n- age of onset 1.5-10 years old\r\n- complex partial seizures (4), secondary GTCS (2)\r\n- Normal MRI-B (3), focal cortical dysplasia (1)\r\n- mild ID (1).\r\n\r\nThe variants were noted to be rare in EXAC-East Asian cohort, most located in CUB/Sushi domains. The gene has some evidence of missense and LoF constraint in gnomAD v4. There was also enrichment of biallelic CSMD2 variants in affected individuals versus a control cohort of unaffected parents (5/420 compound hets affected individuals, 3/1942 compound hets in unaffected parents). Previous mouse Csmd2 knockdown models demonstrated reduction in dendritic spine density and complexity. LoF is the postulated disease mechanism.\r\n\r\nClosely related gene paralog CSMD1 has a definitive association with autosomal recessive complex neurodevelopmental disorder with a more severe phenotype.  Different expression profiles during developmental stages between CSMD1 and CSMD2 postulated for the comparatively milder phenotype associated with the latter.\r\n\r\nCSMD2 has 71 exons and 3631 amino acids. The true prevalence of biallelic missense variants in healthy individuals across diverse ancestries has not been ascertained. Review of the missense variants in this study highlighted issues in a number of them including poor-moderate conservation, conflicting or benign in silicos including REVEL, non-coding in an alternative transcript, Case 4 p.Val1547Ile homozygote – this variant has been noted in an East Asian male homozygote aged between 45-50 in gnomAD v4.\r\n\r\nGiven prevalence of focal epilepsy, stronger case-control evidence from diverse ancestries and variant-specific functional evidence is required to support this proposed gene-disease association.","entity_name":"CSMD2","entity_type":"gene"},{"created":"2025-09-04T10:01:38.302087+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"1.195","user_name":"Krithika Murali","item_type":"entity","text":"gene: CSMD2 was added\ngene: CSMD2 was added to Genetic Epilepsy. Sources: Literature\nMode of inheritance for gene: CSMD2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: CSMD2 were set to PMID: 40632521; 31068362; 38649688\nPhenotypes for gene: CSMD2 were set to Focal epilepsy - MONDO:0005384, CSMD2-related\nReview for gene: CSMD2 was set to RED\nAdded comment: PMID: 40632521 Li et al 2025 (Epilepsia) reported 6 unrelated individuals of Han Chinese descent with biallelic CSMD2 missense variants (NM_052896) and focal epilepsy. 5 individuals were compound heterozygous and one was homozygous. These individuals were ascertained through trio WES analysis of 420 unrelated individuals with focal epilepsy enrolled in the China Epilepsy Gene 1.0 project.\r\n\r\nPhenotypic features\r\n- age of onset 1.5-10 years old\r\n- complex partial seizures (4), secondary GTCS (2)\r\n- Normal MRI-B (3), focal cortical dysplasia (1)\r\n- mild ID (1).\r\n\r\nThe variants were noted to be rare in EXAC-East Asian cohort, most located in CUB/Sushi domains. The gene has some evidence of missense and LoF constraint in gnomAD v4. There was also enrichment of biallelic CSMD2 variants in affected individuals versus a control cohort of unaffected parents (5/420 compound hets affected individuals, 3/1942 compound hets in unaffected parents). Previous mouse Csmd2 knockdown models demonstrated reduction in dendritic spine density and complexity. LoF is the postulated disease mechanism.\r\n\r\nClosely related gene paralog CSMD1 has a definitive association with autosomal recessive complex neurodevelopmental disorder with a more severe phenotype.  Different expression profiles during developmental stages between CSMD1 and CSMD2 postulated for the comparatively milder phenotype associated with the latter.\r\n\r\nCSMD2 has 71 exons and 3631 amino acids. The true prevalence of biallelic missense variants in healthy individuals across diverse ancestries has not been ascertained. Review of the missense variants in this study highlighted issues in a number of them including poor-moderate conservation, conflicting or benign in silicos including REVEL, non-coding in an alternative transcript, Case 4 p.Val1547Ile homozygote – this variant has been noted in an East Asian male homozygote aged between 45-50 in gnomAD v4.\r\n\r\nGiven prevalence of focal epilepsy, stronger case-control evidence from diverse ancestries and variant-specific functional evidence is required to support this proposed gene-disease association. \nSources: Literature","entity_name":"CSMD2","entity_type":"gene"},{"created":"2025-09-04T09:56:05.357851+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2977","user_name":"Krithika Murali","item_type":"entity","text":"Marked gene: CSMD2 as ready","entity_name":"CSMD2","entity_type":"gene"},{"created":"2025-09-04T09:56:05.350545+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2977","user_name":"Krithika Murali","item_type":"entity","text":"Gene: csmd2 has been classified as Red List (Low Evidence).","entity_name":"CSMD2","entity_type":"gene"},{"created":"2025-09-04T09:55:53.642773+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2977","user_name":"Krithika Murali","item_type":"entity","text":"reviewed gene: CSMD2: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 40632521, 31068362, 38649688; Phenotypes: Focal epilepsy - MONDO:0005384, CSMD2-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"CSMD2","entity_type":"gene"},{"created":"2025-09-04T09:55:22.884450+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"1.271","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: NSF as Green List (high evidence)","entity_name":"NSF","entity_type":"gene"},{"created":"2025-09-04T09:55:22.877097+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"1.271","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: nsf has been classified as Green List (High Evidence).","entity_name":"NSF","entity_type":"gene"},{"created":"2025-09-04T09:54:29.456716+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"1.270","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: NSF: Added comment: Personal communication of additional cases with de novo variants and epilepsy; internal case at VCGS.; Changed rating: GREEN","entity_name":"NSF","entity_type":"gene"},{"created":"2025-09-04T09:54:17.971024+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"1.194","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: NSF as Green List (high evidence)","entity_name":"NSF","entity_type":"gene"},{"created":"2025-09-04T09:54:17.956583+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"1.194","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: nsf has been classified as Green List (High Evidence).","entity_name":"NSF","entity_type":"gene"},{"created":"2025-09-04T09:54:02.096844+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"1.193","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: NSF as Green List (high evidence)","entity_name":"NSF","entity_type":"gene"},{"created":"2025-09-04T09:54:02.084458+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"1.193","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: nsf has been classified as Green List (High Evidence).","entity_name":"NSF","entity_type":"gene"},{"created":"2025-09-04T09:53:24.891576+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"1.192","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: NSF: Added comment: Personal communication of additional cases with de novo variants and epilepsy; internal case at VCGS.; Changed rating: GREEN","entity_name":"NSF","entity_type":"gene"},{"created":"2025-09-04T09:52:31.418969+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2977","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: NSF as Green List (high evidence)","entity_name":"NSF","entity_type":"gene"},{"created":"2025-09-04T09:52:31.406989+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2977","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: nsf has been classified as Green List (High Evidence).","entity_name":"NSF","entity_type":"gene"},{"created":"2025-09-04T09:52:13.582461+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2976","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: NSF: Added comment: Personal communication of additional cases with de novo variants and epilepsy; internal case at VCGS.; Changed rating: GREEN","entity_name":"NSF","entity_type":"gene"},{"created":"2025-09-04T09:51:23.659174+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2976","user_name":"Krithika Murali","item_type":"entity","text":"Deleted their review","entity_name":"CSMD2","entity_type":"gene"},{"created":"2025-09-04T09:46:52.889446+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"1.270","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: HIRA were changed from Neurodevelopmental disorder to Neurodevelopmental disorder, MONDO:0700092, HIRA-related","entity_name":"HIRA","entity_type":"gene"},{"created":"2025-09-04T08:41:45.318151+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2976","user_name":"Krithika Murali","item_type":"entity","text":"changed review comment from: PMID: 40632521 Li et al 2025 (Epilepsia) reported 6 unrelated individuals with biallelic CSMD2 missense variants (NM_052896) and focal epilepsy. 5 individuals were compound heterozygous and one was homozygous. These individuals were ascertained through trio WES analysis of 420 unrelated individuals of Han Chinese descent with focal epilepsy enrolled in the China Epilepsy Gene 1.0 project.\r\n\r\nThe age of onset was 1.5-10 years old, complex partial seizures (4 individuals), secondary GTCS (2 individuals), normal MRI (3), focal cortical dysplasia (1), mild ID (1).\r\n\r\nThe variants were noted to be rare, most located in CUB/Sushi domains, none reported in EXAC - East Asian population in homozygotes, and none predicted to have co-occurred as compound hets.  There was also a significant enrichment of biallelic CSMD2 variants in affected individuals versus a control cohort of unaffected parents (5/420 compound hets affected individuals, 3/1942 compound hets in unaffected parents).\r\n\r\nPrevious mouse Csmd2 knockdown models demonstrated reduction in dendritic spine density and complexity and LoF is the postulated mechanism.\r\n\r\nClosely related gene paralog CSMD1 has a definitive association with autosomal recessive complex neurodevelopmental disorder with a more severe phenotype.  Different expression profiles during developmental stages between CSMD1 and CSMD2 postulated for the comparatively milder phenotype with the latter.\r\n\r\nCSMD2 has 71 exons and true prevalence of biallelic missense variants in healthy individuals across diverse ancestries has not been ascertained. Closer review of the missense variants in this study showed some to be moderately conserved residues with conflicting or benign in silicos. \r\n\r\nGiven prevalence of focal epilepsy, stronger case-control evidence from diverse ancestries required to support gene-disease association in conjunction with variant-specific functional evidence. \r\nSources: Literature; to: PMID: 40632521 Li et al 2025 (Epilepsia) reported 6 unrelated individuals with biallelic CSMD2 missense variants (NM_052896) and focal epilepsy. 5 individuals were compound heterozygous and one was homozygous. These individuals were ascertained through trio WES analysis of 420 unrelated individuals of Han Chinese descent with focal epilepsy enrolled in the China Epilepsy Gene 1.0 project.\r\n\r\nThe age of onset was 1.5-10 years old, complex partial seizures (4 individuals), secondary GTCS (2 individuals), normal MRI (3), focal cortical dysplasia (1), mild ID (1).\r\n\r\nThe variants were noted to be rare, most located in CUB/Sushi domains, none reported in EXAC - East Asian population in homozygotes, and none predicted to have co-occurred as compound hets.  There was also a significant enrichment of biallelic CSMD2 variants in affected individuals versus a control cohort of unaffected parents (5/420 compound hets affected individuals, 3/1942 compound hets in unaffected parents).\r\n\r\nPrevious mouse Csmd2 knockdown models demonstrated reduction in dendritic spine density and complexity and LoF is the postulated mechanism.\r\n\r\nClosely related gene paralog CSMD1 has a definitive association with autosomal recessive complex neurodevelopmental disorder with a more severe phenotype.  Different expression profiles during developmental stages between CSMD1 and CSMD2 postulated for the comparatively milder phenotype with the latter.\r\n\r\nCSMD2 has 71 exons and 3631 amino acids. The true prevalence of biallelic missense variants in healthy individuals across diverse ancestries has not been ascertained. Closer review of the missense variants in this study showed some to be moderately conserved residues with conflicting or benign in silicos. \r\n\r\nGiven prevalence of focal epilepsy, stronger case-control evidence from diverse ancestries required to support gene-disease association in conjunction with variant-specific functional evidence. \r\nSources: Literature","entity_name":"CSMD2","entity_type":"gene"},{"created":"2025-09-04T08:40:35.599966+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2976","user_name":"Krithika Murali","item_type":"entity","text":"changed review comment from: PMID: 40632521 Li et al 2025 (Epilepsia) reported 6 unrelated individuals with biallelic CSMD2 missense variants (NM_052896) and focal epilepsy. 5 individuals were compound heterozygous and one was homozygous. These individuals were ascertained through trio WES analysis of 420 unrelated individuals of Han Chinese descent with focal epilepsy enrolled in the China Epilepsy Gene 1.0 project.\r\n\r\nThe age of onset was 1.5-10 years old, complex partial seizures (4 individuals), secondary GTCS (2 individuals), normal MRI (3), focal cortical dysplasia (1), mild ID (1).\r\n\r\nThe variants were noted to be rare, most located in CUB/Sushi domains, none reported in EXAC - East Asian population in homozygotes, and none predicted to have co-occurred as compound hets.  There was also a significant enrichment of biallelic CSMD2 variants in affected individuals versus a control cohort of unaffected parents (5/420 compound hets affected individuals, 3/1942 compound hets in unaffected parents).\r\n\r\nPrevious mouse Csmd2 knockdown models demonstrated reduction in dendritic spine density and complexity and LoF is the postulated mechanism.\r\n\r\nClosely related gene paralog CSMD1 has a definitive association with autosomal recessive complex neurodevelopmental disorder with a more severe phenotype.  Different expression profiles during developmental stages between CSMD1 and CSMD2 postulated for the comparatively milder phenotype with the latter.\r\n\r\nCSMD2 has 71 exons and true prevalence of biallelic missense variants in healthy individuals across diverse ancestries has not been ascertained. Closer review of the missense variants in this study showed a number of them to be moderately conserved residues with conflicting or benign in silicos. \r\n\r\nGiven prevalence of focal epilepsy, stronger case-control evidence required from diverse ancestries required to support gene-disease association in conjunction with variant-specific functional evidence. \nSources: Literature; to: PMID: 40632521 Li et al 2025 (Epilepsia) reported 6 unrelated individuals with biallelic CSMD2 missense variants (NM_052896) and focal epilepsy. 5 individuals were compound heterozygous and one was homozygous. These individuals were ascertained through trio WES analysis of 420 unrelated individuals of Han Chinese descent with focal epilepsy enrolled in the China Epilepsy Gene 1.0 project.\r\n\r\nThe age of onset was 1.5-10 years old, complex partial seizures (4 individuals), secondary GTCS (2 individuals), normal MRI (3), focal cortical dysplasia (1), mild ID (1).\r\n\r\nThe variants were noted to be rare, most located in CUB/Sushi domains, none reported in EXAC - East Asian population in homozygotes, and none predicted to have co-occurred as compound hets.  There was also a significant enrichment of biallelic CSMD2 variants in affected individuals versus a control cohort of unaffected parents (5/420 compound hets affected individuals, 3/1942 compound hets in unaffected parents).\r\n\r\nPrevious mouse Csmd2 knockdown models demonstrated reduction in dendritic spine density and complexity and LoF is the postulated mechanism.\r\n\r\nClosely related gene paralog CSMD1 has a definitive association with autosomal recessive complex neurodevelopmental disorder with a more severe phenotype.  Different expression profiles during developmental stages between CSMD1 and CSMD2 postulated for the comparatively milder phenotype with the latter.\r\n\r\nCSMD2 has 71 exons and true prevalence of biallelic missense variants in healthy individuals across diverse ancestries has not been ascertained. Closer review of the missense variants in this study showed some to be moderately conserved residues with conflicting or benign in silicos. \r\n\r\nGiven prevalence of focal epilepsy, stronger case-control evidence from diverse ancestries required to support gene-disease association in conjunction with variant-specific functional evidence. \r\nSources: Literature","entity_name":"CSMD2","entity_type":"gene"},{"created":"2025-09-04T08:38:53.014918+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2976","user_name":"Krithika Murali","item_type":"entity","text":"gene: CSMD2 was added\ngene: CSMD2 was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: CSMD2 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: CSMD2 were set to PMID: 40632521; 38649688; 31068362\nPhenotypes for gene: CSMD2 were set to Focal epilepsy - MONDO:0005384, CSMD1-related\nReview for gene: CSMD2 was set to AMBER\nAdded comment: PMID: 40632521 Li et al 2025 (Epilepsia) reported 6 unrelated individuals with biallelic CSMD2 missense variants (NM_052896) and focal epilepsy. 5 individuals were compound heterozygous and one was homozygous. These individuals were ascertained through trio WES analysis of 420 unrelated individuals of Han Chinese descent with focal epilepsy enrolled in the China Epilepsy Gene 1.0 project.\r\n\r\nThe age of onset was 1.5-10 years old, complex partial seizures (4 individuals), secondary GTCS (2 individuals), normal MRI (3), focal cortical dysplasia (1), mild ID (1).\r\n\r\nThe variants were noted to be rare, most located in CUB/Sushi domains, none reported in EXAC - East Asian population in homozygotes, and none predicted to have co-occurred as compound hets.  There was also a significant enrichment of biallelic CSMD2 variants in affected individuals versus a control cohort of unaffected parents (5/420 compound hets affected individuals, 3/1942 compound hets in unaffected parents).\r\n\r\nPrevious mouse Csmd2 knockdown models demonstrated reduction in dendritic spine density and complexity and LoF is the postulated mechanism.\r\n\r\nClosely related gene paralog CSMD1 has a definitive association with autosomal recessive complex neurodevelopmental disorder with a more severe phenotype.  Different expression profiles during developmental stages between CSMD1 and CSMD2 postulated for the comparatively milder phenotype with the latter.\r\n\r\nCSMD2 has 71 exons and true prevalence of biallelic missense variants in healthy individuals across diverse ancestries has not been ascertained. Closer review of the missense variants in this study showed a number of them to be moderately conserved residues with conflicting or benign in silicos. \r\n\r\nGiven prevalence of focal epilepsy, stronger case-control evidence required from diverse ancestries required to support gene-disease association in conjunction with variant-specific functional evidence. \nSources: Literature","entity_name":"CSMD2","entity_type":"gene"},{"created":"2025-09-03T18:40:19.265803+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2975","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: PTCH2 were changed from Basal cell carcinoma, somatic 605462; Basal cell nevus syndrome, 109400; Medulloblastoma, somatic to Duplication of pituitary gland; Basal cell carcinoma, somatic 605462; Basal cell nevus syndrome, 109400; Medulloblastoma, somatic","entity_name":"PTCH2","entity_type":"gene"},{"created":"2025-09-03T18:39:59.893827+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2974","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: PTCH2 were set to 30820324; 23479190; 18285427","entity_name":"PTCH2","entity_type":"gene"},{"created":"2025-09-03T18:39:33.605469+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2973","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: PTCH2: Added comment: PMID 40803816: novel splice site PTCH2 variant, c.1590+1G>A, leading to exon 12 skipping and an in-frame deletion of 44 amino acids identified in individual with duplication of the pituitary gland. Unclear how this relates to previously reported variants and phenotypes.; Changed publications: 30820324, 23479190, 18285427, 40803816; Changed phenotypes: Basal cell nevus syndrome, MIM#109400, Duplication of pituitary gland","entity_name":"PTCH2","entity_type":"gene"},{"created":"2025-09-03T18:31:16.808756+10:00","panel_name":"Haem degradation and bilirubin metabolism defects","panel_id":3077,"panel_version":"0.19","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: SLC10A2 as ready","entity_name":"SLC10A2","entity_type":"gene"},{"created":"2025-09-03T18:31:16.801745+10:00","panel_name":"Haem degradation and bilirubin metabolism defects","panel_id":3077,"panel_version":"0.19","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: slc10a2 has been classified as Amber List (Moderate Evidence).","entity_name":"SLC10A2","entity_type":"gene"},{"created":"2025-09-03T18:31:09.283403+10:00","panel_name":"Haem degradation and bilirubin metabolism defects","panel_id":3077,"panel_version":"0.19","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: SLC10A2 were set to 9109432","entity_name":"SLC10A2","entity_type":"gene"},{"created":"2025-09-03T18:30:54.276248+10:00","panel_name":"Haem degradation and bilirubin metabolism defects","panel_id":3077,"panel_version":"0.18","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: SLC10A2 as Amber List (moderate evidence)","entity_name":"SLC10A2","entity_type":"gene"},{"created":"2025-09-03T18:30:54.265187+10:00","panel_name":"Haem degradation and bilirubin metabolism defects","panel_id":3077,"panel_version":"0.18","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: slc10a2 has been classified as Amber List (Moderate Evidence).","entity_name":"SLC10A2","entity_type":"gene"},{"created":"2025-09-03T18:30:40.392412+10:00","panel_name":"Haem degradation and bilirubin metabolism defects","panel_id":3077,"panel_version":"0.17","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: SLC10A2: Rating: AMBER; Mode of pathogenicity: None; Publications: 9109432, 40814585; Phenotypes: Bile acid malabsorption, primary, MIM# 613291; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"SLC10A2","entity_type":"gene"},{"created":"2025-09-03T18:29:41.562199+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2973","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: SLC10A2 as Amber List (moderate evidence)","entity_name":"SLC10A2","entity_type":"gene"},{"created":"2025-09-03T18:29:41.548735+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2973","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: slc10a2 has been classified as Amber List (Moderate Evidence).","entity_name":"SLC10A2","entity_type":"gene"},{"created":"2025-09-03T18:29:19.946696+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2972","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: SLC10A2: Added comment: Second individual reported homozygous missense, but quite a specific phenotype so upgrade to Amber.; Changed rating: AMBER; Changed publications: 9109432, 40814585","entity_name":"SLC10A2","entity_type":"gene"},{"created":"2025-09-03T18:28:39.664752+10:00","panel_name":"Congenital Diarrhoea","panel_id":89,"panel_version":"1.21","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: SLC10A2 were set to 9109432","entity_name":"SLC10A2","entity_type":"gene"},{"created":"2025-09-03T18:28:16.429771+10:00","panel_name":"Congenital Diarrhoea","panel_id":89,"panel_version":"1.20","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: SLC10A2 as Amber List (moderate evidence)","entity_name":"SLC10A2","entity_type":"gene"},{"created":"2025-09-03T18:28:16.418879+10:00","panel_name":"Congenital Diarrhoea","panel_id":89,"panel_version":"1.20","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: slc10a2 has been classified as Amber List (Moderate Evidence).","entity_name":"SLC10A2","entity_type":"gene"},{"created":"2025-09-03T18:27:54.849292+10:00","panel_name":"Congenital Diarrhoea","panel_id":89,"panel_version":"1.19","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: SLC10A2: Added comment: Second individual reported homozygous missense, but quite a specific phenotype so upgrade to Amber.; Changed rating: AMBER; Changed publications: 9109432, 40814585","entity_name":"SLC10A2","entity_type":"gene"},{"created":"2025-09-03T12:54:27.521310+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2972","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: KLHL9 were set to 20554658","entity_name":"KLHL9","entity_type":"gene"},{"created":"2025-09-03T12:54:08.327697+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2971","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: KLHL9: Rating: AMBER; Mode of pathogenicity: None; Publications: 40818927; Phenotypes: distal myopathy MONDO:0018949; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"KLHL9","entity_type":"gene"},{"created":"2025-09-03T12:52:20.415976+10:00","panel_name":"Limb-Girdle Muscular Dystrophy and Distal Myopathy","panel_id":3071,"panel_version":"1.61","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: KLHL9 were set to 20554658","entity_name":"KLHL9","entity_type":"gene"},{"created":"2025-09-03T12:51:31.275636+10:00","panel_name":"Limb-Girdle Muscular Dystrophy and Distal Myopathy","panel_id":3071,"panel_version":"1.60","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: KLHL9: Rating: AMBER; Mode of pathogenicity: None; Publications: 40818927; Phenotypes: distal myopathy MONDO:0018949; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted","entity_name":"KLHL9","entity_type":"gene"},{"created":"2025-09-03T12:49:40.132158+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2971","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: UHRF1 were set to 29574422; 28976982; 36458887","entity_name":"UHRF1","entity_type":"gene"},{"created":"2025-09-03T12:48:48.733468+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2970","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: UHRF1 as Amber List (moderate evidence)","entity_name":"UHRF1","entity_type":"gene"},{"created":"2025-09-03T12:48:48.713531+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2970","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: uhrf1 has been classified as Amber List (Moderate Evidence).","entity_name":"UHRF1","entity_type":"gene"},{"created":"2025-09-03T12:48:29.368841+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2969","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: UHRF1: Added comment: Second family reported with homozygous missense variant.; Changed rating: AMBER; Changed publications: 29574422, 28976982, 40825131; Changed phenotypes: Imprinting disorder","entity_name":"UHRF1","entity_type":"gene"},{"created":"2025-09-03T12:48:19.052244+10:00","panel_name":"Imprinting disorders","panel_id":3663,"panel_version":"1.8","user_name":"Zornitza Stark","item_type":"entity","text":"commented on gene: UHRF1: Second family reported with homozygous missense variant.","entity_name":"UHRF1","entity_type":"gene"},{"created":"2025-09-03T12:47:30.802850+10:00","panel_name":"Imprinting disorders","panel_id":3663,"panel_version":"1.8","user_name":"Zornitza Stark","item_type":"entity","text":"Phenotypes for gene: UHRF1 were changed from Multi locus imprinting disturbance in offspring to Multi locus imprinting disturbance in offspring; Imprinting disorder","entity_name":"UHRF1","entity_type":"gene"},{"created":"2025-09-03T12:47:17.426217+10:00","panel_name":"Imprinting disorders","panel_id":3663,"panel_version":"1.7","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: UHRF1 were set to 29574422; 28976982","entity_name":"UHRF1","entity_type":"gene"},{"created":"2025-09-03T12:47:07.295040+10:00","panel_name":"Imprinting disorders","panel_id":3663,"panel_version":"1.6","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: UHRF1 as Amber List (moderate evidence)","entity_name":"UHRF1","entity_type":"gene"},{"created":"2025-09-03T12:47:07.284667+10:00","panel_name":"Imprinting disorders","panel_id":3663,"panel_version":"1.6","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: uhrf1 has been classified as Amber List (Moderate Evidence).","entity_name":"UHRF1","entity_type":"gene"},{"created":"2025-09-03T12:46:46.497390+10:00","panel_name":"Imprinting disorders","panel_id":3663,"panel_version":"1.5","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: UHRF1: Changed rating: AMBER; Changed publications: 40825131; Changed phenotypes: Imprinting disorder; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"UHRF1","entity_type":"gene"},{"created":"2025-09-03T12:40:06.163525+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"1.269","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: RNF2 as Green List (high evidence)","entity_name":"RNF2","entity_type":"gene"},{"created":"2025-09-03T12:40:06.155932+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"1.269","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: rnf2 has been classified as Green List (High Evidence).","entity_name":"RNF2","entity_type":"gene"},{"created":"2025-09-03T12:39:43.217083+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"1.268","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: RNF2: Added comment: PMID 40831499 is a preprint which identifies additional individuals with de novo variants. p.S82R is recurrent. Functional data to support gene-disease association.; Changed rating: GREEN; Changed publications: 33864376, 40831499","entity_name":"RNF2","entity_type":"gene"},{"created":"2025-09-03T12:39:16.528347+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"1.192","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: RNF2 were set to 33864376","entity_name":"RNF2","entity_type":"gene"},{"created":"2025-09-03T12:38:44.375471+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"1.191","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: RNF2 as Green List (high evidence)","entity_name":"RNF2","entity_type":"gene"},{"created":"2025-09-03T12:38:44.364446+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"1.191","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: rnf2 has been classified as Green List (High Evidence).","entity_name":"RNF2","entity_type":"gene"},{"created":"2025-09-03T12:38:10.683435+10:00","panel_name":"Genetic Epilepsy","panel_id":202,"panel_version":"1.190","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: RNF2: Added comment: PMID 40831499 is a preprint which identifies additional individuals with de novo variants. p.S82R is recurrent. Functional data to support gene-disease association.; Changed rating: GREEN; Changed publications: 33864376, 40831499","entity_name":"RNF2","entity_type":"gene"},{"created":"2025-09-03T12:37:14.658852+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2969","user_name":"Zornitza Stark","item_type":"entity","text":"Publications for gene: RNF2 were set to 33864376","entity_name":"RNF2","entity_type":"gene"},{"created":"2025-09-03T12:36:58.572348+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2968","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: RNF2 as Green List (high evidence)","entity_name":"RNF2","entity_type":"gene"},{"created":"2025-09-03T12:36:58.560273+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2968","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: rnf2 has been classified as Green List (High Evidence).","entity_name":"RNF2","entity_type":"gene"},{"created":"2025-09-03T12:36:17.490903+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2967","user_name":"Zornitza Stark","item_type":"entity","text":"edited their review of gene: RNF2: Added comment: PMID 40831499 is a preprint which identifies additional individuals with de novo variants. p.S82R is recurrent. Functional data to support gene-disease association.; Changed rating: GREEN; Changed publications: 40831499","entity_name":"RNF2","entity_type":"gene"},{"created":"2025-09-03T08:59:54.315715+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"1.268","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: CCDC93 as ready","entity_name":"CCDC93","entity_type":"gene"},{"created":"2025-09-03T08:59:54.300322+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"1.268","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: ccdc93 has been classified as Red List (Low Evidence).","entity_name":"CCDC93","entity_type":"gene"},{"created":"2025-09-03T08:59:43.762455+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"1.268","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: CCDC93 as Red List (low evidence)","entity_name":"CCDC93","entity_type":"gene"},{"created":"2025-09-03T08:59:43.752102+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"1.268","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: ccdc93 has been classified as Red List (Low Evidence).","entity_name":"CCDC93","entity_type":"gene"},{"created":"2025-09-03T08:59:16.873449+10:00","panel_name":"Intellectual disability syndromic and non-syndromic","panel_id":250,"panel_version":"1.267","user_name":"Zornitza Stark","item_type":"entity","text":"reviewed gene: CCDC93: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ritscher-Schinzel syndrome, MONDO:0019078, CCDC93-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal","entity_name":"CCDC93","entity_type":"gene"},{"created":"2025-09-03T08:58:41.156516+10:00","panel_name":"Callosome","panel_id":205,"panel_version":"0.554","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: CCDC93 as ready","entity_name":"CCDC93","entity_type":"gene"},{"created":"2025-09-03T08:58:41.145738+10:00","panel_name":"Callosome","panel_id":205,"panel_version":"0.554","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: ccdc93 has been classified as Red List (Low Evidence).","entity_name":"CCDC93","entity_type":"gene"},{"created":"2025-09-03T08:58:37.475234+10:00","panel_name":"Callosome","panel_id":205,"panel_version":"0.554","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: CCDC93 as Red List (low evidence)","entity_name":"CCDC93","entity_type":"gene"},{"created":"2025-09-03T08:58:37.463884+10:00","panel_name":"Callosome","panel_id":205,"panel_version":"0.554","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: ccdc93 has been classified as Red List (Low Evidence).","entity_name":"CCDC93","entity_type":"gene"},{"created":"2025-09-03T08:58:13.125166+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2967","user_name":"Zornitza Stark","item_type":"entity","text":"Marked gene: CCDC93 as ready","entity_name":"CCDC93","entity_type":"gene"},{"created":"2025-09-03T08:58:13.114581+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2967","user_name":"Zornitza Stark","item_type":"entity","text":"Gene: ccdc93 has been classified as Red List (Low Evidence).","entity_name":"CCDC93","entity_type":"gene"},{"created":"2025-09-03T08:58:05.967667+10:00","panel_name":"Mendeliome","panel_id":137,"panel_version":"1.2967","user_name":"Zornitza Stark","item_type":"entity","text":"Classified gene: CCDC93 as Red List (low evidence)","entity_name":"CCDC93","entity_type":"gene"}]}