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{
"count": 221415,
"next": "https://panelapp-aus.org/api/v1/activities/?format=api&page=400",
"previous": "https://panelapp-aus.org/api/v1/activities/?format=api&page=398",
"results": [
{
"created": "2024-09-05T12:19:17.833606+10:00",
"panel_name": "Prepair 1000+",
"panel_id": 3861,
"panel_version": "1.259",
"user_name": "Lilian Downie",
"item_type": "entity",
"text": "Gene: b9d1 has been classified as Amber List (Moderate Evidence).",
"entity_name": "B9D1",
"entity_type": "gene"
},
{
"created": "2024-09-05T12:18:25.362768+10:00",
"panel_name": "Prepair 1000+",
"panel_id": 3861,
"panel_version": "1.259",
"user_name": "Lilian Downie",
"item_type": "entity",
"text": "Publications for gene: B9D1 were set to 21493627; 24886560; 25920555",
"entity_name": "B9D1",
"entity_type": "gene"
},
{
"created": "2024-09-05T12:18:03.649808+10:00",
"panel_name": "Prepair 1000+",
"panel_id": 3861,
"panel_version": "1.258",
"user_name": "Lilian Downie",
"item_type": "entity",
"text": "reviewed gene: B9D1: Rating: AMBER; Mode of pathogenicity: None; Publications: 21493627, 24886560, 25920555, 32622957; Phenotypes: Joubert syndrome 27, MIM# 617120, Meckel syndrome 9, MIM# 614209; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "B9D1",
"entity_type": "gene"
},
{
"created": "2024-09-05T12:16:48.508390+10:00",
"panel_name": "Optic Atrophy",
"panel_id": 149,
"panel_version": "1.32",
"user_name": "Mark Cleghorn",
"item_type": "entity",
"text": "gene: NDUFA7 was added\ngene: NDUFA7 was added to Optic Atrophy. Sources: Other\nMode of inheritance for gene: NDUFA7 was set to BIALLELIC, autosomal or pseudoautosomal\nPhenotypes for gene: NDUFA7 were set to Leber Hereditary Optic Neuropathy, MIM#619382\nPenetrance for gene: NDUFA7 were set to unknown\nReview for gene: NDUFA7 was set to AMBER\nAdded comment: NDUFA7\r\nESHG talk 2/6/24, unpublished\r\nChristine Michaela Neuhofer, Technische Universitat Munchen\r\n\r\nBiallelic LoF with Leber Hereditary optic neuropathy (LHON)\r\n\r\nOnly 1 case, with LHON and homozygous NDUFA7:c.51+1dup\r\nNDUFA7 protein interacts w DNAJC30 – known nuclear LHON gene\r\n\r\nAnalysis on patient fibroblasts supports disruption to complex I activity via DNAJC30 \nSources: Other",
"entity_name": "NDUFA7",
"entity_type": "gene"
},
{
"created": "2024-09-05T12:08:54.473691+10:00",
"panel_name": "Corneal Dystrophy",
"panel_id": 91,
"panel_version": "1.11",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "gene: SPARCL1 was added\ngene: SPARCL1 was added to Corneal Dystrophy. Sources: Literature\nMode of inheritance for gene: SPARCL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: SPARCL1 were set to PMID: 39169229\nPhenotypes for gene: SPARCL1 were set to Corneal dystrophy, MONDO:0018102\nReview for gene: SPARCL1 was set to RED\nAdded comment: 8 affected individuals with corneal dystrophy from 1 family (3 generations). Affected individuals had diffuse central stromal opacity, with reduced visual acuity in older family members. Histopathology of affected cornea tissue revealed mild stromal textural alterations with alcianophilic deposits. \r\n\r\nWGS from 4 affected individuals in family identified a novel heterozygous missense variant in exon 4 of SPARCL1 (c.334G > A; p.(Glu112Lys)) which segregated with disease.\r\n\r\nSPARC-like protein 1 (SPARCL1) is a secreted matricellular protein involved in cell migration, cell adhesion, tissue repair, and remodelling. SPARCL1 has been shown to regulate decorin. Heterozygous variants in DCN, encoding decorin, cause autosomal dominant congenital stromal corneal dystrophy, suggesting a common pathogenic pathway. Immunohistochemistry showed the level of decorin was significantly decreased in the corneal stroma of the affected tissue, and SPARCL1 appeared to be retained in the epithelium. \nSources: Literature",
"entity_name": "SPARCL1",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:59:30.303016+10:00",
"panel_name": "Dystonia - complex",
"panel_id": 290,
"panel_version": "0.237",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Classified gene: PNPLA8 as Green List (high evidence)",
"entity_name": "PNPLA8",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:59:30.290451+10:00",
"panel_name": "Dystonia - complex",
"panel_id": 290,
"panel_version": "0.237",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Gene: pnpla8 has been classified as Green List (High Evidence).",
"entity_name": "PNPLA8",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:58:51.189462+10:00",
"panel_name": "Dystonia - complex",
"panel_id": 290,
"panel_version": "0.236",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "gene: PNPLA8 was added\ngene: PNPLA8 was added to Dystonia - complex. Sources: Literature\nMode of inheritance for gene: PNPLA8 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: PNPLA8 were set to PMID: 39082157\nPhenotypes for gene: PNPLA8 were set to PNPLA8-related neurological diseases\nReview for gene: PNPLA8 was set to GREEN\ngene: PNPLA8 was marked as current diagnostic\nAdded comment: Cohort analysis of clinical features of new and previously reported individuals with biallelic PNPLA8 variants (25 affected individuals across 20 families). They showed that PNPLA8-related neurological diseases manifest as a continuum ranging from variable developmental and/or degenerative epileptic-dyskinetic encephalopathy to childhood-onset neurodegeneration. Complete loss of PNPLA8 was associated with the more profound end of the spectrum. 11/15 individuals (info available) had dystonia (onset in childhood).\r\n\r\nUsing cerebral organoids generated from human induced pluripotent stem cells, they found that loss of PNPLA8 led to developmental defects by reducing the number of basal radial glial cells and upper-layer neurons. Neural progenitor cells lacking PNPLA8 showed a reduced amount of lysophosphatidic acid, lysophosphatidylethanolamine and phosphatidic acid. They show that PNPLA8 is crucial to meet phospholipid synthetic needs and to produce abundant basal radial glial cells in human brain development. \nSources: Literature",
"entity_name": "PNPLA8",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:57:57.553456+10:00",
"panel_name": "Hereditary Spastic Paraplegia - paediatric",
"panel_id": 317,
"panel_version": "1.82",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Classified gene: PNPLA8 as Green List (high evidence)",
"entity_name": "PNPLA8",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:57:57.529122+10:00",
"panel_name": "Hereditary Spastic Paraplegia - paediatric",
"panel_id": 317,
"panel_version": "1.82",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Gene: pnpla8 has been classified as Green List (High Evidence).",
"entity_name": "PNPLA8",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:57:52.528106+10:00",
"panel_name": "Cerebellar and Pontocerebellar Hypoplasia",
"panel_id": 72,
"panel_version": "1.67",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Classified gene: PNPLA8 as Green List (high evidence)",
"entity_name": "PNPLA8",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:57:52.504649+10:00",
"panel_name": "Cerebellar and Pontocerebellar Hypoplasia",
"panel_id": 72,
"panel_version": "1.67",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Gene: pnpla8 has been classified as Green List (High Evidence).",
"entity_name": "PNPLA8",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:56:16.544536+10:00",
"panel_name": "Hereditary Spastic Paraplegia - paediatric",
"panel_id": 317,
"panel_version": "1.81",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "gene: PNPLA8 was added\ngene: PNPLA8 was added to Hereditary Spastic Paraplegia - paediatric. Sources: Literature\nMode of inheritance for gene: PNPLA8 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: PNPLA8 were set to PMID: 39082157\nPhenotypes for gene: PNPLA8 were set to PNPLA8-related neurological diseases\nReview for gene: PNPLA8 was set to GREEN\ngene: PNPLA8 was marked as current diagnostic\nAdded comment: Cohort analysis of clinical features of new and previously reported individuals with biallelic PNPLA8 variants (25 affected individuals across 20 families). They showed that PNPLA8-related neurological diseases manifest as a continuum ranging from variable developmental and/or degenerative epileptic-dyskinetic encephalopathy to childhood-onset neurodegeneration. Complete loss of PNPLA8 was associated with the more profound end of the spectrum. 15/23 individuals (info available) had spasticity (onset in early childhood).\r\n\r\nUsing cerebral organoids generated from human induced pluripotent stem cells, they found that loss of PNPLA8 led to developmental defects by reducing the number of basal radial glial cells and upper-layer neurons. Neural progenitor cells lacking PNPLA8 showed a reduced amount of lysophosphatidic acid, lysophosphatidylethanolamine and phosphatidic acid. They show that PNPLA8 is crucial to meet phospholipid synthetic needs and to produce abundant basal radial glial cells in human brain development. \nSources: Literature",
"entity_name": "PNPLA8",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:55:34.695295+10:00",
"panel_name": "Cerebellar and Pontocerebellar Hypoplasia",
"panel_id": 72,
"panel_version": "1.66",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "gene: PNPLA8 was added\ngene: PNPLA8 was added to Cerebellar and Pontocerebellar Hypoplasia. Sources: Literature\nMode of inheritance for gene: PNPLA8 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: PNPLA8 were set to PMID: 39082157\nPhenotypes for gene: PNPLA8 were set to PNPLA8-related neurological diseases\nReview for gene: PNPLA8 was set to GREEN\ngene: PNPLA8 was marked as current diagnostic\nAdded comment: Cohort analysis of clinical features of new and previously reported individuals with biallelic PNPLA8 variants (25 affected individuals across 20 families). They showed that PNPLA8-related neurological diseases manifest as a continuum ranging from variable developmental and/or degenerative epileptic-dyskinetic encephalopathy to childhood-onset neurodegeneration. Complete loss of PNPLA8 was associated with the more profound end of the spectrum. 20/21 individuals (info available) had cerebellar atrophy with/without pontocerebellar hypoplasia.\r\n\r\nUsing cerebral organoids generated from human induced pluripotent stem cells, they found that loss of PNPLA8 led to developmental defects by reducing the number of basal radial glial cells and upper-layer neurons. Neural progenitor cells lacking PNPLA8 showed a reduced amount of lysophosphatidic acid, lysophosphatidylethanolamine and phosphatidic acid. They show that PNPLA8 is crucial to meet phospholipid synthetic needs and to produce abundant basal radial glial cells in human brain development. \nSources: Literature",
"entity_name": "PNPLA8",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:54:21.188130+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "1.48",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Classified gene: PNPLA8 as Green List (high evidence)",
"entity_name": "PNPLA8",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:54:21.164758+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "1.48",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Gene: pnpla8 has been classified as Green List (High Evidence).",
"entity_name": "PNPLA8",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:54:10.569199+10:00",
"panel_name": "Autism",
"panel_id": 51,
"panel_version": "0.198",
"user_name": "Sangavi Sivagnanasundram",
"item_type": "entity",
"text": "gene: LARP1 was added\ngene: LARP1 was added to Autism. Sources: Other\nMode of inheritance for gene: LARP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: LARP1 were set to 39182167\nPhenotypes for gene: LARP1 were set to Neurodevelopmental disorder; MONDO:0700092\nReview for gene: LARP1 was set to GREEN\nAdded comment: Seven unrelated probands (6 males and 1 female) with ASD or another variable NDD phenotype (ID, hypotonia, motor delay and/or ASD). Variants were showed to be de novo null variants or missense variants that resulted in haploinsufficiency.\r\n\r\nEx vivo (knockout CRISPR-Cas9) functional assay using lymphoblasts that was collected and immortilised from one proband was conducted to assess the functional impact of the LARP1 variant. The results showed a reduction in protein compared to WT causing reduced rates of aerobic respiration and glycolysis. \nSources: Other",
"entity_name": "LARP1",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:53:19.817398+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.6126",
"user_name": "Sangavi Sivagnanasundram",
"item_type": "entity",
"text": "gene: LARP1 was added\ngene: LARP1 was added to Intellectual disability syndromic and non-syndromic. Sources: Other\nMode of inheritance for gene: LARP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: LARP1 were set to 39182167\nPhenotypes for gene: LARP1 were set to Neurodevelopmental disorder; MONDO:0700092\nReview for gene: LARP1 was set to GREEN\nAdded comment: Seven unrelated probands (6 males and 1 female) with ASD or another variable NDD phenotype (ID, hypotonia, motor delay and/or ASD). Variants were showed to be de novo null variants or missense variants that resulted in haploinsufficiency.\r\n\r\nEx vivo (knockout CRISPR-Cas9) functional assay using lymphoblasts that was collected and immortilised from one proband was conducted to assess the functional impact of the LARP1 variant. The results showed a reduction in protein compared to WT causing reduced rates of aerobic respiration and glycolysis \nSources: Other",
"entity_name": "LARP1",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:52:18.646487+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.6126",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Classified gene: PNPLA8 as Green List (high evidence)",
"entity_name": "PNPLA8",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:52:18.633163+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.6126",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Gene: pnpla8 has been classified as Green List (High Evidence).",
"entity_name": "PNPLA8",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:51:33.007657+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1980",
"user_name": "Sangavi Sivagnanasundram",
"item_type": "entity",
"text": "gene: LARP1 was added\ngene: LARP1 was added to Mendeliome. Sources: Other\nMode of inheritance for gene: LARP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: LARP1 were set to 39182167\nPhenotypes for gene: LARP1 were set to Neurodevelopmental disorder; MONDO:0700092\nReview for gene: LARP1 was set to GREEN\nAdded comment: Seven unrelated probands (6 males and 1 female) with ASD or another variable NDD phenotype (ID, hypotonia, motor delay and/or ASD). Variants were showed to be de novo null variants or missense variants that resulted in haploinsufficiency.\r\n\r\nEx vivo (knockout CRISPR-Cas9) functional assay using lymphoblasts that was collected and immortilised from one proband was conducted to assess the functional impact of the LARP1 variant. The results showed a reduction in protein compared to WT causing reduced rates of aerobic respiration and glycolysis. \nSources: Other",
"entity_name": "LARP1",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:51:11.222375+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "1.47",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "gene: PNPLA8 was added\ngene: PNPLA8 was added to Genetic Epilepsy. Sources: Literature\nMode of inheritance for gene: PNPLA8 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: PNPLA8 were set to PMID: 39082157\nPhenotypes for gene: PNPLA8 were set to PNPLA8-related neurological diseases\nReview for gene: PNPLA8 was set to GREEN\ngene: PNPLA8 was marked as current diagnostic\nAdded comment: Cohort analysis of clinical features of new and previously reported individuals with biallelic PNPLA8 variants (25 affected individuals across 20 families). They showed that PNPLA8-related neurological diseases manifest as a continuum ranging from variable developmental and/or degenerative epileptic-dyskinetic encephalopathy to childhood-onset neurodegeneration. Complete loss of PNPLA8 was associated with the more profound end of the spectrum. 19/25 individuals had seizures (onset 1 day to 31 years). \r\n\r\nUsing cerebral organoids generated from human induced pluripotent stem cells, they found that loss of PNPLA8 led to developmental defects by reducing the number of basal radial glial cells and upper-layer neurons. Neural progenitor cells lacking PNPLA8 showed a reduced amount of lysophosphatidic acid, lysophosphatidylethanolamine and phosphatidic acid. They show that PNPLA8 is crucial to meet phospholipid synthetic needs and to produce abundant basal radial glial cells in human brain development. \nSources: Literature",
"entity_name": "PNPLA8",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:50:07.501260+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.6125",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Classified gene: PNPLA8 as Green List (high evidence)",
"entity_name": "PNPLA8",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:50:07.484909+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.6125",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Gene: pnpla8 has been classified as Green List (High Evidence).",
"entity_name": "PNPLA8",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:49:30.314416+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1980",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "edited their review of gene: PNPLA8: Added comment: Cohort analysis of clinical features of new and previously reported individuals with biallelic PNPLA8 variants (25 affected individuals across 20 families). They showed that PNPLA8-related neurological diseases manifest as a continuum ranging from variable developmental and/or degenerative epileptic-dyskinetic encephalopathy to childhood-onset neurodegeneration. Complete loss of PNPLA8 was associated with the more profound end of the spectrum. \r\n\r\nUsing cerebral organoids generated from human induced pluripotent stem cells, they found that loss of PNPLA8 led to developmental defects by reducing the number of basal radial glial cells and upper-layer neurons. Neural progenitor cells lacking PNPLA8 showed a reduced amount of lysophosphatidic acid, lysophosphatidylethanolamine and phosphatidic acid. They show that PNPLA8 is crucial to meet phospholipid synthetic needs and to produce abundant basal radial glial cells in human brain development.; Set current diagnostic: yes",
"entity_name": "PNPLA8",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:49:27.884078+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1980",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "reviewed gene: PNPLA8: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 39082157; Phenotypes: PNPLA8-related neurological diseases; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "PNPLA8",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:48:40.154811+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.6124",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "gene: PNPLA8 was added\ngene: PNPLA8 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: PNPLA8 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: PNPLA8 were set to PMID: 39082157\nPhenotypes for gene: PNPLA8 were set to PNPLA8-related neurological diseases\nReview for gene: PNPLA8 was set to GREEN\ngene: PNPLA8 was marked as current diagnostic\nAdded comment: Cohort analysis of clinical features of new and previously reported individuals with biallelic PNPLA8 variants (25 affected individuals across 20 families). They showed that PNPLA8-related neurological diseases manifest as a continuum ranging from variable developmental and/or degenerative epileptic-dyskinetic encephalopathy to childhood-onset neurodegeneration. Complete loss of PNPLA8 was associated with the more profound end of the spectrum. 13/19 individuals (info available) had developmental delay and/or severe intellectual disability. \r\n\r\nUsing cerebral organoids generated from human induced pluripotent stem cells, they found that loss of PNPLA8 led to developmental defects by reducing the number of basal radial glial cells and upper-layer neurons. Neural progenitor cells lacking PNPLA8 showed a reduced amount of lysophosphatidic acid, lysophosphatidylethanolamine and phosphatidic acid. They show that PNPLA8 is crucial to meet phospholipid synthetic needs and to produce abundant basal radial glial cells in human brain development. \nSources: Literature",
"entity_name": "PNPLA8",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:48:07.477103+10:00",
"panel_name": "Microcephaly",
"panel_id": 138,
"panel_version": "1.275",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Phenotypes for gene: PNPLA8 were changed from PNPLA8-related neurological diseases; Mitochondrial myopathy with lactic acidosis, OMIM # 251950 to PNPLA8-related neurological diseases",
"entity_name": "PNPLA8",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:44:09.721231+10:00",
"panel_name": "Microcephaly",
"panel_id": 138,
"panel_version": "1.274",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Classified gene: PNPLA8 as Green List (high evidence)",
"entity_name": "PNPLA8",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:44:09.705163+10:00",
"panel_name": "Microcephaly",
"panel_id": 138,
"panel_version": "1.274",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Gene: pnpla8 has been classified as Green List (High Evidence).",
"entity_name": "PNPLA8",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:43:02.719415+10:00",
"panel_name": "Microcephaly",
"panel_id": 138,
"panel_version": "1.273",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "gene: PNPLA8 was added\ngene: PNPLA8 was added to Microcephaly. Sources: Literature\nMode of inheritance for gene: PNPLA8 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: PNPLA8 were set to PMID: 39082157\nPhenotypes for gene: PNPLA8 were set to PNPLA8-related neurological diseases; Mitochondrial myopathy with lactic acidosis, OMIM # 251950\nReview for gene: PNPLA8 was set to GREEN\ngene: PNPLA8 was marked as current diagnostic\nAdded comment: Cohort analysis of clinical features of new and previously reported individuals with biallelic PNPLA8 variants (25 affected individuals across 20 families). They showed that PNPLA8-related neurological diseases manifest as a continuum ranging from variable developmental and/or degenerative epileptic-dyskinetic encephalopathy to childhood-onset neurodegeneration. Complete loss of PNPLA8 was associated with the more profound end of the spectrum. 17/25 individuals had congenital and/or progressive microcephaly. \r\n\r\nUsing cerebral organoids generated from human induced pluripotent stem cells, they found that loss of PNPLA8 led to developmental defects by reducing the number of basal radial glial cells and upper-layer neurons. Neural progenitor cells lacking PNPLA8 showed a reduced amount of lysophosphatidic acid, lysophosphatidylethanolamine and phosphatidic acid. They show that PNPLA8 is crucial to meet phospholipid synthetic needs and to produce abundant basal radial glial cells in human brain development. \nSources: Literature",
"entity_name": "PNPLA8",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:31:21.418226+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1980",
"user_name": "Mark Cleghorn",
"item_type": "entity",
"text": "gene: MED22 was added\ngene: MED22 was added to Mendeliome. Sources: Other\nMode of inheritance for gene: MED22 was set to BIALLELIC, autosomal or pseudoautosomal\nPhenotypes for gene: MED22 were set to complex neurodevelopmental disorder MONDO:0100038\nPenetrance for gene: MED22 were set to unknown\nReview for gene: MED22 was set to AMBER\nAdded comment: ESHG talk 2/6/24, unpublished\r\nElisa Cali, UCL\r\n\r\nRecurrent homozygous MED22:c.397_399del (p.Glu133del) inframe variant in 8 individuals from 6 families w progressive NDD, microcepahly, cerebellar atrophy, dystonia, seizures\r\n\r\nRare in gnomad v4.1 (9 het alleles, no homozygotes)\r\n\r\nFunctional work on patient fibroblasts: quantity of protein comparable to controls, did not mentioned assays of protein function (?mechanism proposed)\r\nDrosophilia heterozygous model with equivalent of p.Glu133del variant: structural anomalies, less movements, all died prior to pupae stage\r\nZebrafish: MED22 mutants less mobile, died prior to adulthood, reduced brain size \nSources: Other",
"entity_name": "MED22",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:30:30.288472+10:00",
"panel_name": "Ciliopathies",
"panel_id": 84,
"panel_version": "1.59",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: TMEM216 were set to 20036350; 20512146",
"entity_name": "TMEM216",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:29:54.523359+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.6123",
"user_name": "Mark Cleghorn",
"item_type": "entity",
"text": "gene: MED22 was added\ngene: MED22 was added to Intellectual disability syndromic and non-syndromic. Sources: Other\nMode of inheritance for gene: MED22 was set to BIALLELIC, autosomal or pseudoautosomal\nPhenotypes for gene: MED22 were set to complex neurodevelopmental disorder MONDO:0100038\nPenetrance for gene: MED22 were set to unknown\nReview for gene: MED22 was set to AMBER\nAdded comment: ESHG talk 2/6/24, unpublished\r\nElisa Cali, UCL\r\n\r\nRecurrent homozygous MED22:c.397_399del (p.Glu133del) inframe variant in 8 individuals from 6 families w progressive NDD, microcepahly, cerebellar atrophy, dystonia, seizures\r\n\r\nRare in gnomad v4.1 (9 het alleles, no homozygotes)\r\n\r\nFunctional work on patient fibroblasts: quantity of protein comparable to controls, did not mentioned assays of protein function (?mechanism proposed)\r\nDrosophilia heterozygous model with equivalent of p.Glu133del variant: structural anomalies, less movements, all died prior to pupae stage\r\nZebrafish: MED22 mutants less mobile, died prior to adulthood, reduced brain size \nSources: Other",
"entity_name": "MED22",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:29:43.326343+10:00",
"panel_name": "Ciliopathies",
"panel_id": 84,
"panel_version": "1.58",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Tag UTR tag was added to gene: TMEM216.",
"entity_name": "TMEM216",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:29:32.447593+10:00",
"panel_name": "Ciliopathies",
"panel_id": 84,
"panel_version": "1.58",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "edited their review of gene: TMEM216: Added comment: PMID 39191256: Two rare nucleotide substitutions at the same genomic location on chromosome 11 (g.61392563 [GRCh38]), 69 base pairs upstream of the start codon of the ciliopathy gene TMEM216 (c.-69G>A, c.-69G>T [GenBank: NM_001173991.3]) found in individuals of South Asian and African ancestry, respectively.\r\n\r\nThis included 71 homozygotes and 3 mixed heterozygotes in trans with a predicted loss-of-function allele. Haplotype analysis showed single-nucleotide variants (SNVs) common across families, suggesting ancestral alleles within the two distinct ethnic populations.\r\n\r\nClinical phenotype analysis of 62 available individuals from 49 families indicated a similar clinical presentation with night blindness in the first decade and progressive peripheral field loss thereafter. No evident systemic ciliopathy features were noted.\r\n\r\nFunctional characterization of these variants by luciferase reporter gene assay showed reduced promotor activity.; Changed publications: 20036350, 20512146, 39191256; Changed phenotypes: Joubert syndrome 2, MIM# 608091, Meckel syndrome 2, MIM# 603194, Retinitis pigmentosa, MONDO:0019200, TMEM216-related",
"entity_name": "TMEM216",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:28:00.428323+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1980",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: TMEM216 were changed from Joubert syndrome 2, MIM# 608091; MONDO:0011963; Meckel syndrome 2, MIM# 603194; MONDO:0011296 to Joubert syndrome 2, MIM# 608091; MONDO:0011963; Meckel syndrome 2, MIM# 603194; MONDO:0011296; Retinitis pigmentosa, MONDO:0019200, TMEM216-related",
"entity_name": "TMEM216",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:27:40.145013+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1979",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: TMEM216 were set to 20036350; 20512146",
"entity_name": "TMEM216",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:27:12.619728+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1978",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Tag founder tag was added to gene: TMEM216.\nTag UTR tag was added to gene: TMEM216.",
"entity_name": "TMEM216",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:26:55.407742+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1978",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "edited their review of gene: TMEM216: Added comment: PMID 39191256: Two rare nucleotide substitutions at the same genomic location on chromosome 11 (g.61392563 [GRCh38]), 69 base pairs upstream of the start codon of the ciliopathy gene TMEM216 (c.-69G>A, c.-69G>T [GenBank: NM_001173991.3]) found in individuals of South Asian and African ancestry, respectively.\r\n\r\nThis included 71 homozygotes and 3 mixed heterozygotes in trans with a predicted loss-of-function allele. Haplotype analysis showed single-nucleotide variants (SNVs) common across families, suggesting ancestral alleles within the two distinct ethnic populations.\r\n\r\nClinical phenotype analysis of 62 available individuals from 49 families indicated a similar clinical presentation with night blindness in the first decade and progressive peripheral field loss thereafter. No evident systemic ciliopathy features were noted.\r\n\r\nFunctional characterization of these variants by luciferase reporter gene assay showed reduced promotor activity.; Changed publications: 20036350, 20512146, 39191256; Changed phenotypes: Joubert syndrome 2, MIM# 608091, MONDO:0011963, Meckel syndrome 2, MIM# 603194, MONDO:0011296, Retinitis pigmentosa, MONDO:0019200, TMEM216-related",
"entity_name": "TMEM216",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:26:06.161445+10:00",
"panel_name": "Retinitis pigmentosa_Autosomal Recessive/X-linked",
"panel_id": 277,
"panel_version": "0.152",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: TMEM216 were set to ",
"entity_name": "TMEM216",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:25:51.118290+10:00",
"panel_name": "Retinitis pigmentosa_Autosomal Recessive/X-linked",
"panel_id": 277,
"panel_version": "0.151",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "edited their review of gene: TMEM216: Changed publications: 39191256",
"entity_name": "TMEM216",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:24:37.982537+10:00",
"panel_name": "Congenital diaphragmatic hernia",
"panel_id": 69,
"panel_version": "1.16",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Classified gene: MED12 as Green List (high evidence)",
"entity_name": "MED12",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:24:37.961656+10:00",
"panel_name": "Congenital diaphragmatic hernia",
"panel_id": 69,
"panel_version": "1.16",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "Gene: med12 has been classified as Green List (High Evidence).",
"entity_name": "MED12",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:24:01.617622+10:00",
"panel_name": "Congenital diaphragmatic hernia",
"panel_id": 69,
"panel_version": "1.15",
"user_name": "Chirag Patel",
"item_type": "entity",
"text": "gene: MED12 was added\ngene: MED12 was added to Congenital diaphragmatic hernia. Sources: Literature\nMode of inheritance for gene: MED12 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)\nPublications for gene: MED12 were set to PMID: 39215511\nPhenotypes for gene: MED12 were set to MED12-related disorders; Hardikar syndrome, OMIM # 301068\nReview for gene: MED12 was set to GREEN\ngene: MED12 was marked as current diagnostic\nAdded comment: MED12-related disorders include: \r\n1) X-linked recessive Opitz-Kaveggia syndrome, Lujan-Fryns syndrome, Ohdo syndrome, and nonspecific intellectual disability in males predominantly carrying missense variants\r\n2) X-linked dominant Hardikar syndrome and nonspecific intellectual disability in females known to predominantly carry de novo nonsense/frameshift and nonsense/missense variants, respectively. \r\n\r\nPaper reviews occurrence of congenital diaphragmatic hernia in 18 individuals with molecularly confirmed MED12 mutation on WES/WGS. They report CDH in 3/7 females with Hardikar syndrome or nonspecific intellectual disability, but no CDH in 11 males with MED12-related disorders. \nSources: Literature",
"entity_name": "MED12",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:20:59.835413+10:00",
"panel_name": "Retinitis pigmentosa_Autosomal Recessive/X-linked",
"panel_id": 277,
"panel_version": "0.151",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: TMEM216 as ready",
"entity_name": "TMEM216",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:20:59.806776+10:00",
"panel_name": "Retinitis pigmentosa_Autosomal Recessive/X-linked",
"panel_id": 277,
"panel_version": "0.151",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: tmem216 has been classified as Green List (High Evidence).",
"entity_name": "TMEM216",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:20:55.220621+10:00",
"panel_name": "Retinitis pigmentosa_Autosomal Recessive/X-linked",
"panel_id": 277,
"panel_version": "0.151",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: TMEM216 as Green List (high evidence)",
"entity_name": "TMEM216",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:20:55.190993+10:00",
"panel_name": "Retinitis pigmentosa_Autosomal Recessive/X-linked",
"panel_id": 277,
"panel_version": "0.151",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: tmem216 has been classified as Green List (High Evidence).",
"entity_name": "TMEM216",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:20:44.467616+10:00",
"panel_name": "Retinitis pigmentosa_Autosomal Recessive/X-linked",
"panel_id": 277,
"panel_version": "0.150",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "gene: TMEM216 was added\ngene: TMEM216 was added to Retinitis pigmentosa_Autosomal Recessive/X-linked. Sources: Literature\nUTR tags were added to gene: TMEM216.\nMode of inheritance for gene: TMEM216 was set to BIALLELIC, autosomal or pseudoautosomal\nPhenotypes for gene: TMEM216 were set to Retinitis pigmentosa, MONDO:0019200, TMEM216-related\nReview for gene: TMEM216 was set to GREEN\nAdded comment: Two rare nucleotide substitutions at the same genomic location on chromosome 11 (g.61392563 [GRCh38]), 69 base pairs upstream of the start codon of the ciliopathy gene TMEM216 (c.-69G>A, c.-69G>T [GenBank: NM_001173991.3]) found in individuals of South Asian and African ancestry, respectively.\r\n\r\nThis included 71 homozygotes and 3 mixed heterozygotes in trans with a predicted loss-of-function allele. Haplotype analysis showed single-nucleotide variants (SNVs) common across families, suggesting ancestral alleles within the two distinct ethnic populations.\r\n\r\nClinical phenotype analysis of 62 available individuals from 49 families indicated a similar clinical presentation with night blindness in the first decade and progressive peripheral field loss thereafter. No evident systemic ciliopathy features were noted.\r\n\r\nFunctional characterization of these variants by luciferase reporter gene assay showed reduced promotor activity. \nSources: Literature",
"entity_name": "TMEM216",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:15:26.609116+10:00",
"panel_name": "Muscular dystrophy and myopathy_Paediatric",
"panel_id": 141,
"panel_version": "1.67",
"user_name": "Sangavi Sivagnanasundram",
"item_type": "entity",
"text": "gene: JPH1 was added\ngene: JPH1 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Other\nMode of inheritance for gene: JPH1 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: JPH1 were set to 39209426\nPhenotypes for gene: JPH1 were set to Congenital myopathy MONDO:0019952\nReview for gene: JPH1 was set to GREEN\nAdded comment: 4 unrelated probands presented with congenital myopathy with facial weakness and ocular involvement. All individuals had presence of 4 different LoF variants identified in JPH1. \r\n\r\np.(Asp125Thrfs*30), p.(Tyr118*), p.(Leu580Trpfs*16) and p.(Glu504Serfs*3) - all variants were absent from gnomADv4.1 \nSources: Other",
"entity_name": "JPH1",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:15:16.586286+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1978",
"user_name": "Sangavi Sivagnanasundram",
"item_type": "entity",
"text": "changed review comment from: 4 unrelated probands presented with congenital myopathy with prominent facial and ocular involvement. All individuals had presence of 4 different LoF variants identified in JPH1. \r\n\r\np.(Asp125Thrfs*30), p.(Tyr118*), p.(Leu580Trpfs*16) and p.(Glu504Serfs*3) - all variants were absent from gnomADv4.1 \nSources: Other; to: 4 unrelated probands presented with congenital myopathy with facial weakness and ocular involvement. All individuals had presence of 4 different LoF variants identified in JPH1. \r\n\r\np.(Asp125Thrfs*30), p.(Tyr118*), p.(Leu580Trpfs*16) and p.(Glu504Serfs*3) - all variants were absent from gnomADv4.1 \r\nSources: Other",
"entity_name": "JPH1",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:13:20.869061+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1978",
"user_name": "Sangavi Sivagnanasundram",
"item_type": "entity",
"text": "gene: JPH1 was added\ngene: JPH1 was added to Mendeliome. Sources: Other\nMode of inheritance for gene: JPH1 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: JPH1 were set to 39209426\nPhenotypes for gene: JPH1 were set to Congenital myopathy MONDO:0019952\nReview for gene: JPH1 was set to GREEN\nAdded comment: 4 unrelated probands presented with congenital myopathy with prominent facial and ocular involvement. All individuals had presence of 4 different LoF variants identified in JPH1. \r\n\r\np.(Asp125Thrfs*30), p.(Tyr118*), p.(Leu580Trpfs*16) and p.(Glu504Serfs*3) - all variants were absent from gnomADv4.1 \nSources: Other",
"entity_name": "JPH1",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:12:40.839707+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1978",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: PLEC were changed from ?Epidermolysis bullosa simplex with nail dystrophy, MIM#\t616487; Epidermolysis bullosa simplex with muscular dystrophy, MIM#\t226670; Epidermolysis bullosa simplex with pyloric atresia, MIM#\t612138; Epidermolysis bullosa simplex, Ogna type\tMIM#131950; Muscular dystrophy, limb-girdle, autosomal recessive 17, MIM#\t613723 to Epidermolysis bullosa simplex with nail dystrophy, MIM#\t616487; Epidermolysis bullosa simplex with muscular dystrophy, MIM#\t226670; Epidermolysis bullosa simplex with pyloric atresia, MIM#\t612138; Epidermolysis bullosa simplex, Ogna type\tMIM#131950; Muscular dystrophy, limb-girdle, autosomal recessive 17, MIM#\t613723; Progressive familial intrahepatic cholestasis, MONDO:0015762, PLEC-related",
"entity_name": "PLEC",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:11:43.921822+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1977",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: PLEC were set to 22144912",
"entity_name": "PLEC",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:11:08.751790+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1976",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: PLEC: Rating: AMBER; Mode of pathogenicity: None; Publications: 39168815; Phenotypes: Progressive familial intrahepatic cholestasis, MONDO:0015762, PLEC-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "PLEC",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:10:05.545426+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.244",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: PLEC as ready",
"entity_name": "PLEC",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:10:05.532433+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.244",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: plec has been classified as Amber List (Moderate Evidence).",
"entity_name": "PLEC",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:09:59.707330+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.244",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: PLEC as Amber List (moderate evidence)",
"entity_name": "PLEC",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:09:59.691566+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.244",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: plec has been classified as Amber List (Moderate Evidence).",
"entity_name": "PLEC",
"entity_type": "gene"
},
{
"created": "2024-09-05T11:09:23.171790+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.243",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "gene: PLEC was added\ngene: PLEC was added to Cholestasis. Sources: Literature\nMode of inheritance for gene: PLEC was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: PLEC were set to 39168815\nPhenotypes for gene: PLEC were set to Progressive familial intrahepatic cholestasis, MONDO:0015762, PLEC-related\nReview for gene: PLEC was set to AMBER\nAdded comment: Four individuals reported with PFIC and bi-allelic variants in PLEC (one pair of sibs, and two other unrelated infants). However, limited functional data and several of the variants are missense. \nSources: Literature",
"entity_name": "PLEC",
"entity_type": "gene"
},
{
"created": "2024-09-05T10:43:22.323795+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.6123",
"user_name": "Mark Cleghorn",
"item_type": "entity",
"text": "reviewed gene: BICRA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Coffin-Siris syndrome-12, MIM#619325; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "BICRA",
"entity_type": "gene"
},
{
"created": "2024-09-05T10:17:20.157881+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1976",
"user_name": "Mark Cleghorn",
"item_type": "entity",
"text": "gene: SF3B1 was added\ngene: SF3B1 was added to Mendeliome. Sources: Other\nMode of inheritance for gene: SF3B1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPhenotypes for gene: SF3B1 were set to complex neurodevelopmental disorder MONDO:0100038\nPenetrance for gene: SF3B1 were set to unknown\nReview for gene: SF3B1 was set to AMBER\nAdded comment: SF3B1\r\nDelphine Bernard, University of Brest\r\nESHG talk 2/6/24, unpublished\r\n\r\nDe novo germline SF3B1 variants, proposed spliceosomopathy/NDD gene\r\n\r\nSF3B1 is an RNA binding protein that stabilizes the U2 snRNP complex at branchpoint sequences\r\nSomatic SF3B1 missense commonly occur in haematological malignancy (K700E recurrent)\r\n\r\n25 patients with syndromic NDD + de novo heterozygous rare SF3B1 variants identified on WES, genematcher\r\n13 missense (incl recurrent xxx and xxx) within HEAT domain\r\n5 nonsense\r\n4 splicing\r\n1 frameshift\r\n\r\nPatients w missense variants may have more severe phenotype incl mircocepahly, palate anomalies, cerebral anomalies, GI/cardiac anomalies\r\n\r\nCellular models of missense variants: erythroleukaemia K562, HEK293T\r\nSuggest missense variants do not cause loss of function, but increase exon skipping and alternative 3’ splice site use \nSources: Other",
"entity_name": "SF3B1",
"entity_type": "gene"
},
{
"created": "2024-09-05T10:16:06.118632+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.6123",
"user_name": "Mark Cleghorn",
"item_type": "entity",
"text": "gene: SF3B1 was added\ngene: SF3B1 was added to Intellectual disability syndromic and non-syndromic. Sources: Other\nMode of inheritance for gene: SF3B1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPhenotypes for gene: SF3B1 were set to complex neurodevelopmental disorder MONDO:0100038\nPenetrance for gene: SF3B1 were set to unknown\nReview for gene: SF3B1 was set to AMBER\nAdded comment: SF3B1\r\nDelphine Bernard, University of Brest\r\nESHG talk 2/6/24, unpublished\r\n\r\nDe novo germline SF3B1 variants, proposed spliceosomopathy/NDD gene\r\n\r\nSF3B1 is an RNA binding protein that stabilizes the U2 snRNP complex at branchpoint sequences\r\nSomatic SF3B1 missense commonly occur in haematological malignancy (K700E recurrent)\r\n\r\n25 patients with syndromic NDD + de novo heterozygous rare SF3B1 variants identified on WES, genematcher\r\n13 missense (incl recurrent xxx and xxx) within HEAT domain\r\n5 nonsense\r\n4 splicing\r\n1 frameshift\r\n\r\nPatients w missense variants may have more severe phenotype incl mircocepahly, palate anomalies, cerebral anomalies, GI/cardiac anomalies\r\n\r\nCellular models of missense variants: erythroluekaemia K562, HEK293T\r\nSuggest missense variants do not cause loss of function, but increase exon skipping and alternative 3’ splice sites \nSources: Other",
"entity_name": "SF3B1",
"entity_type": "gene"
},
{
"created": "2024-09-05T08:46:43.941435+10:00",
"panel_name": "Cataract",
"panel_id": 66,
"panel_version": "0.369",
"user_name": "Ain Roesley",
"item_type": "entity",
"text": "Marked gene: GBF1 as ready",
"entity_name": "GBF1",
"entity_type": "gene"
},
{
"created": "2024-09-05T08:46:43.923838+10:00",
"panel_name": "Cataract",
"panel_id": 66,
"panel_version": "0.369",
"user_name": "Ain Roesley",
"item_type": "entity",
"text": "Gene: gbf1 has been classified as Red List (Low Evidence).",
"entity_name": "GBF1",
"entity_type": "gene"
},
{
"created": "2024-09-05T08:46:07.550530+10:00",
"panel_name": "Cataract",
"panel_id": 66,
"panel_version": "0.369",
"user_name": "Ain Roesley",
"item_type": "entity",
"text": "gene: GBF1 was added\ngene: GBF1 was added to Cataract. Sources: Literature\nMode of inheritance for gene: GBF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: GBF1 were set to 39110251\nPhenotypes for gene: GBF1 were set to autosomal dominant cataract MONDO:0022672, GBF1-related\nPenetrance for gene: GBF1 were set to Complete\nReview for gene: GBF1 was set to RED\ngene: GBF1 was marked as current diagnostic\nAdded comment: 1 missense in a multi-generational family.\r\n\r\nhowever, this variant has 98 hets on gnomad v4 and low conservation (changes in 2 mammals and reptiles).\r\n\r\nUsing the human lens epithelium (HLE) cell line, we found that the p.T1287I mutation reduced GBF1 protein levels. Knockdown of endogenous GBF1 activated the unfolded protein response and enhanced autophagy, as well as increasing XBP1s protein levels and decreasing p-JNK1 protein levels. Heterozygous Gbf1 knockout (Gbf1+/-) mice also exhibited cataract malformation, while their littermate wild-type (Gbf1+/+) mice did not. \nSources: Literature",
"entity_name": "GBF1",
"entity_type": "gene"
},
{
"created": "2024-09-05T08:45:39.809643+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1976",
"user_name": "Ain Roesley",
"item_type": "entity",
"text": "reviewed gene: GBF1: Rating: RED; Mode of pathogenicity: None; Publications: 39110251; Phenotypes: autosomal dominant cataract MONDO:0022672, GBF1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes",
"entity_name": "GBF1",
"entity_type": "gene"
},
{
"created": "2024-09-05T08:32:54.347848+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1976",
"user_name": "Ain Roesley",
"item_type": "entity",
"text": "reviewed gene: TLN1: Rating: AMBER; Mode of pathogenicity: None; Publications: 39163585; Phenotypes: idiopathic spontaneous coronary artery dissection MONDO:0007385; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes",
"entity_name": "TLN1",
"entity_type": "gene"
},
{
"created": "2024-09-04T22:02:25.104202+10:00",
"panel_name": "Prepair 1000+",
"panel_id": 3861,
"panel_version": "1.258",
"user_name": "Andrew Coventry",
"item_type": "entity",
"text": "reviewed gene: LGI4: Rating: GREEN; Mode of pathogenicity: None; Publications: 28318499 16341215 31513940; Phenotypes: Arthrogryposis multiplex congenita 1, neurogenic, with myelin defect MIM#617468; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "LGI4",
"entity_type": "gene"
},
{
"created": "2024-09-04T21:51:46.952055+10:00",
"panel_name": "Retinitis pigmentosa_Autosomal Recessive/X-linked",
"panel_id": 277,
"panel_version": "0.149",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Marked gene: COQ8B as ready",
"entity_name": "COQ8B",
"entity_type": "gene"
},
{
"created": "2024-09-04T21:51:46.937892+10:00",
"panel_name": "Retinitis pigmentosa_Autosomal Recessive/X-linked",
"panel_id": 277,
"panel_version": "0.149",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Gene: coq8b has been classified as Green List (High Evidence).",
"entity_name": "COQ8B",
"entity_type": "gene"
},
{
"created": "2024-09-04T21:51:43.013584+10:00",
"panel_name": "Retinitis pigmentosa_Autosomal Recessive/X-linked",
"panel_id": 277,
"panel_version": "0.149",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Classified gene: COQ8B as Green List (high evidence)",
"entity_name": "COQ8B",
"entity_type": "gene"
},
{
"created": "2024-09-04T21:51:42.980582+10:00",
"panel_name": "Retinitis pigmentosa_Autosomal Recessive/X-linked",
"panel_id": 277,
"panel_version": "0.149",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Gene: coq8b has been classified as Green List (High Evidence).",
"entity_name": "COQ8B",
"entity_type": "gene"
},
{
"created": "2024-09-04T21:51:31.930273+10:00",
"panel_name": "Retinitis pigmentosa_Autosomal Recessive/X-linked",
"panel_id": 277,
"panel_version": "0.148",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "gene: COQ8B was added\ngene: COQ8B was added to Retinitis pigmentosa_Autosomal Recessive/X-linked. Sources: Literature\nMode of inheritance for gene: COQ8B was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: COQ8B were set to 39226897; 25967120\nPhenotypes for gene: COQ8B were set to Retinitis pigmentosa MONDO:0019200\nReview for gene: COQ8B was set to GREEN\ngene: COQ8B was marked as current diagnostic\nAdded comment: PMID: 39226897 - 5 individuals from 4 unrelated families with non-syndromic RP (normal renal function) and COQ8B chet variants (5 different variants). In vitro functional assays of the variant demonstrated a significant decrease in ligand-protein interaction compared to the wild type.\r\nPMID: 25967120 - 1 case with a homozygous truncating variant reported with FSGS and RP \nSources: Literature",
"entity_name": "COQ8B",
"entity_type": "gene"
},
{
"created": "2024-09-04T21:49:35.421990+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1976",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "reviewed gene: COQ8B: Rating: GREEN; Mode of pathogenicity: None; Publications: 39226897, 25967120; Phenotypes: Retinitis pigmentosa MONDO:0019200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes",
"entity_name": "COQ8B",
"entity_type": "gene"
},
{
"created": "2024-09-04T21:42:16.214742+10:00",
"panel_name": "Prepair 1000+",
"panel_id": 3861,
"panel_version": "1.258",
"user_name": "Andrew Coventry",
"item_type": "entity",
"text": "reviewed gene: LAMB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23472759 25925986 29888467 25925986 32548278 34606115 32548278 34606115; Phenotypes: Lissencephaly 5 MIM#615191; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "LAMB1",
"entity_type": "gene"
},
{
"created": "2024-09-04T21:30:03.899175+10:00",
"panel_name": "Prepair 1000+",
"panel_id": 3861,
"panel_version": "1.258",
"user_name": "Andrew Coventry",
"item_type": "entity",
"text": "reviewed gene: KRT85: Rating: AMBER; Mode of pathogenicity: None; Publications: 16525032 19865094 31273852 37178037; Phenotypes: Ectodermal dysplasia 4, hair/nail type MIM#602032; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "KRT85",
"entity_type": "gene"
},
{
"created": "2024-09-04T21:05:19.785645+10:00",
"panel_name": "Prepair 1000+",
"panel_id": 3861,
"panel_version": "1.258",
"user_name": "Andrew Coventry",
"item_type": "entity",
"text": "reviewed gene: JAK3: Rating: GREEN; Mode of pathogenicity: None; Publications: 14615376 11668610 7481767 7481769 9354668 7659163 7481768 30032486 9753072; Phenotypes: Severe combined immunodeficiency, autosomal recessive, T-negative/B-positive type MIM#600802; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "JAK3",
"entity_type": "gene"
},
{
"created": "2024-09-04T20:56:39.056141+10:00",
"panel_name": "Prepair 1000+",
"panel_id": 3861,
"panel_version": "1.258",
"user_name": "Andrew Coventry",
"item_type": "entity",
"text": "reviewed gene: ITGB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 1968911 1694220 33957747 32279896 31374327; Phenotypes: Leukocyte adhesion deficiency MIM#116920; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "ITGB2",
"entity_type": "gene"
},
{
"created": "2024-09-04T20:45:07.450180+10:00",
"panel_name": "Prepair 1000+",
"panel_id": 3861,
"panel_version": "1.258",
"user_name": "Andrew Coventry",
"item_type": "entity",
"text": "reviewed gene: ICOS: Rating: GREEN; Mode of pathogenicity: None; Publications: 12577056 15507387 19380800 28861081 31858365 11343122 16982935 8438047; Phenotypes: Immunodeficiency, common variable, 1 MIM#607594; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "ICOS",
"entity_type": "gene"
},
{
"created": "2024-09-04T17:51:57.659692+10:00",
"panel_name": "Prepair 1000+",
"panel_id": 3861,
"panel_version": "1.258",
"user_name": "Kate Scarff",
"item_type": "entity",
"text": "reviewed gene: COL4A4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 20301386; Phenotypes: Alport syndrome 2, autosomal recessive MIM# 203780; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "COL4A4",
"entity_type": "gene"
},
{
"created": "2024-09-04T17:06:19.750909+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1976",
"user_name": "Mark Cleghorn",
"item_type": "entity",
"text": "gene: C12orf66 was added\ngene: C12orf66 was added to Mendeliome. Sources: Other\nMode of inheritance for gene: C12orf66 was set to BIALLELIC, autosomal or pseudoautosomal\nPhenotypes for gene: C12orf66 were set to complex neurodevelopmental disorder MONDO:0100038\nPenetrance for gene: C12orf66 were set to unknown\nReview for gene: C12orf66 was set to AMBER\nAdded comment: KICS2 (previously known as C12ORF66)\r\nRebecca Buchert, Universitatklinikum Tubingen\r\nESHG talk 2/6/24, unpublished\r\n\r\nProposed ID + epilepsy gene\r\n\r\n8 families w 11 affected individuals\r\nPhenotypes: 11/11 ID, 9/11 epilepsy, 3/11 hearing impairment\r\n3/8 homozygous missense variants (p.Asp296Glu, p.Tyr393Cys, p.Tyr393Cys), all highly conserved\r\n1/8 compound het PTC (p.Lys262*) with 1.1Mb deletion\r\n4/8 homozygous PTC (p.Glu3*, p.Gly79Valfs*18, p.Gly79Valfs*18, p.Lys260Asnfs*18)\r\n\r\nGene appears to be involved in mTOR pathway, and cilia function\r\nmTORC1 activity in CRISPR-HEK293T cells – reduced activity in cells w variants above\r\n\r\nZebrafish model: otolith defects, ciliary dysfunction\r\n?not clear that this truly mimics phenotype observed in patient cohort described \nSources: Other",
"entity_name": "C12orf66",
"entity_type": "gene"
},
{
"created": "2024-09-04T17:04:56.341172+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.6123",
"user_name": "Mark Cleghorn",
"item_type": "entity",
"text": "gene: C12orf66 was added\ngene: C12orf66 was added to Intellectual disability syndromic and non-syndromic. Sources: Other\nMode of inheritance for gene: C12orf66 was set to BIALLELIC, autosomal or pseudoautosomal\nPhenotypes for gene: C12orf66 were set to complex neurodevelopmental disorder MONDO:0100038\nPenetrance for gene: C12orf66 were set to unknown\nReview for gene: C12orf66 was set to AMBER\nAdded comment: KICS2 (previously known as C12ORF66)\r\nRebecca Buchert, Universitatklinikum Tubingen\r\nESHG talk 2/6/24, unpublished\r\n\r\nProposed ID + epilepsy gene\r\n\r\n8 families w 11 affected individuals\r\nPhenotypes: 11/11 ID, 9/11 epilepsy, 3/11 hearing impairment\r\n3/8 homozygous missense variants (p.Asp296Glu, p.Tyr393Cys, p.Tyr393Cys), all highly conserved\r\n1/8 compound het PTC (p.Lys262*) with 1.1Mb deletion\r\n4/8 homozygous PTC (p.Glu3*, p.Gly79Valfs*18, p.Gly79Valfs*18, p.Lys260Asnfs*18)\r\n\r\nGene appears to be involved in mTOR pathway, and cilia function\r\nmTORC1 activity in CRISPR-HEK293T cells – reduced activity in cells w variants above\r\n\r\nZebrafish model: otolith defects, ciliary dysfunction\r\n?not clear if truly mimics phenotype observed in patient cohort described \nSources: Other",
"entity_name": "C12orf66",
"entity_type": "gene"
},
{
"created": "2024-09-04T16:50:21.824721+10:00",
"panel_name": "Prepair 1000+",
"panel_id": 3861,
"panel_version": "1.258",
"user_name": "Lilian Downie",
"item_type": "entity",
"text": "Marked gene: EPM2A as ready",
"entity_name": "EPM2A",
"entity_type": "gene"
},
{
"created": "2024-09-04T16:50:21.804162+10:00",
"panel_name": "Prepair 1000+",
"panel_id": 3861,
"panel_version": "1.258",
"user_name": "Lilian Downie",
"item_type": "entity",
"text": "Gene: epm2a has been classified as Green List (High Evidence).",
"entity_name": "EPM2A",
"entity_type": "gene"
},
{
"created": "2024-09-04T16:49:54.455237+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1976",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: MYBBP1A as ready",
"entity_name": "MYBBP1A",
"entity_type": "gene"
},
{
"created": "2024-09-04T16:49:54.437114+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1976",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: mybbp1a has been classified as Green List (High Evidence).",
"entity_name": "MYBBP1A",
"entity_type": "gene"
},
{
"created": "2024-09-04T16:49:35.712070+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1976",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: MYBBP1A as Green List (high evidence)",
"entity_name": "MYBBP1A",
"entity_type": "gene"
},
{
"created": "2024-09-04T16:49:35.697114+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1976",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: mybbp1a has been classified as Green List (High Evidence).",
"entity_name": "MYBBP1A",
"entity_type": "gene"
},
{
"created": "2024-09-04T16:48:38.288664+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1975",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "gene: MYBBP1A was added\ngene: MYBBP1A was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: MYBBP1A was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: MYBBP1A were set to 39191491; 28425981\nPhenotypes for gene: MYBBP1A were set to Hydrops fetalis, MONDO:0015193, MYBBP1A-related\nReview for gene: MYBBP1A was set to GREEN\nAdded comment: Three unrelated fetuses with bi-allelic variants in this gene and severe hydrops. \nSources: Literature",
"entity_name": "MYBBP1A",
"entity_type": "gene"
},
{
"created": "2024-09-04T16:46:38.088207+10:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "1.267",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: MYBBP1A as ready",
"entity_name": "MYBBP1A",
"entity_type": "gene"
},
{
"created": "2024-09-04T16:46:38.072750+10:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "1.267",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: mybbp1a has been classified as Green List (High Evidence).",
"entity_name": "MYBBP1A",
"entity_type": "gene"
},
{
"created": "2024-09-04T16:46:32.700677+10:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "1.267",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: MYBBP1A as Green List (high evidence)",
"entity_name": "MYBBP1A",
"entity_type": "gene"
},
{
"created": "2024-09-04T16:46:32.681873+10:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "1.267",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: mybbp1a has been classified as Green List (High Evidence).",
"entity_name": "MYBBP1A",
"entity_type": "gene"
},
{
"created": "2024-09-04T16:46:14.059306+10:00",
"panel_name": "Prepair 1000+",
"panel_id": 3861,
"panel_version": "1.258",
"user_name": "Lilian Downie",
"item_type": "entity",
"text": "Publications for gene: EPM2A were set to 9771710 9931343 11175283 12019207 12560877 14722920; 30947044; 22036712; 16311711; 28818698",
"entity_name": "EPM2A",
"entity_type": "gene"
},
{
"created": "2024-09-04T16:46:06.018177+10:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "1.266",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "gene: MYBBP1A was added\ngene: MYBBP1A was added to Fetal anomalies. Sources: Literature\nMode of inheritance for gene: MYBBP1A was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: MYBBP1A were set to 39191491; 28425981\nPhenotypes for gene: MYBBP1A were set to Hydrops fetalis, MONDO:0015193, MYBBP1A-related\nReview for gene: MYBBP1A was set to GREEN\nAdded comment: Three unrelated fetuses with bi-allelic variants in this gene and severe hydrops. \nSources: Literature",
"entity_name": "MYBBP1A",
"entity_type": "gene"
},
{
"created": "2024-09-04T16:45:50.373875+10:00",
"panel_name": "Hydrops fetalis",
"panel_id": 116,
"panel_version": "0.320",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: MYBBP1A as ready",
"entity_name": "MYBBP1A",
"entity_type": "gene"
},
{
"created": "2024-09-04T16:45:50.351213+10:00",
"panel_name": "Hydrops fetalis",
"panel_id": 116,
"panel_version": "0.320",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: mybbp1a has been classified as Green List (High Evidence).",
"entity_name": "MYBBP1A",
"entity_type": "gene"
},
{
"created": "2024-09-04T16:45:46.125924+10:00",
"panel_name": "Hydrops fetalis",
"panel_id": 116,
"panel_version": "0.320",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: MYBBP1A as Green List (high evidence)",
"entity_name": "MYBBP1A",
"entity_type": "gene"
}
]
}