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"count": 221416,
"next": "https://panelapp-aus.org/api/v1/activities/?format=api&page=494",
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"results": [
{
"created": "2024-02-01T11:54:30.836386+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1513",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: sp9 has been classified as Green List (High Evidence).",
"entity_name": "SP9",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:54:29.729175+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1513",
"user_name": "Suliman Khan",
"item_type": "entity",
"text": "commented on gene: SP9: PMID: 38288683: reported 5 unrelated patients with de novo heterozygous variants (missense and PTV) in SP9 gene. In silico and in vitro studies suggested a novel form of interneuronopathy with variable severity depending on the presence of loss or gain of function variants. Patients with loss-of-function variants had ID, ASD, and epilepsy, whereas missense variants in the second C2H2 binding domain result in hypomorphic and neomorphic DNA binding functions that cause severe epileptic encephalopathy. The author suggested a novel form of interneuronopathy with variable severity depending on the presence of loss or gain of function variants.",
"entity_name": "SP9",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:54:19.774865+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1513",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: SP9 were changed from neurodevelopmental disorder MONDO:0700092 to neurodevelopmental disorder MONDO:0700092, SP9-related",
"entity_name": "SP9",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:53:47.361433+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1512",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: SP9 as Green List (high evidence)",
"entity_name": "SP9",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:53:47.346601+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1512",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: sp9 has been classified as Green List (High Evidence).",
"entity_name": "SP9",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:53:13.485681+11:00",
"panel_name": "Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic",
"panel_id": 63,
"panel_version": "0.134",
"user_name": "Seb Lunke",
"item_type": "entity",
"text": "Marked gene: WDR44 as ready",
"entity_name": "WDR44",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:53:13.480978+11:00",
"panel_name": "Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic",
"panel_id": 63,
"panel_version": "0.134",
"user_name": "Seb Lunke",
"item_type": "entity",
"text": "Added comment: Comment when marking as ready: GoF mentioned but not well supported.",
"entity_name": "WDR44",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:53:13.446189+11:00",
"panel_name": "Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic",
"panel_id": 63,
"panel_version": "0.134",
"user_name": "Seb Lunke",
"item_type": "entity",
"text": "Gene: wdr44 has been classified as Green List (High Evidence).",
"entity_name": "WDR44",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:53:09.064781+11:00",
"panel_name": "Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic",
"panel_id": 63,
"panel_version": "0.134",
"user_name": "Seb Lunke",
"item_type": "entity",
"text": "Classified gene: WDR44 as Green List (high evidence)",
"entity_name": "WDR44",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:53:09.041249+11:00",
"panel_name": "Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic",
"panel_id": 63,
"panel_version": "0.134",
"user_name": "Seb Lunke",
"item_type": "entity",
"text": "Gene: wdr44 has been classified as Green List (High Evidence).",
"entity_name": "WDR44",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:52:47.529511+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1511",
"user_name": "Suliman Khan",
"item_type": "entity",
"text": "gene: SP9 was added\ngene: SP9 was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: SP9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: SP9 were set to PMID: 38288683\nPhenotypes for gene: SP9 were set to neurodevelopmental disorder MONDO:0700092\nReview for gene: SP9 was set to GREEN\nAdded comment: Sources: Literature",
"entity_name": "SP9",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:52:17.452414+11:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.2200",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: SP9 as ready",
"entity_name": "SP9",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:52:17.434233+11:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.2200",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: sp9 has been classified as Green List (High Evidence).",
"entity_name": "SP9",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:52:08.984708+11:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.2200",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: SP9 were changed from neurodevelopmental disorder MONDO:0700092 to neurodevelopmental disorder MONDO:0700092, SP9-related",
"entity_name": "SP9",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:51:42.674920+11:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.2199",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: SP9 as Green List (high evidence)",
"entity_name": "SP9",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:51:42.667125+11:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.2199",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: sp9 has been classified as Green List (High Evidence).",
"entity_name": "SP9",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:48:12.939054+11:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.2198",
"user_name": "Suliman Khan",
"item_type": "entity",
"text": "gene: SP9 was added\ngene: SP9 was added to Genetic Epilepsy. Sources: Literature\nMode of inheritance for gene: SP9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: SP9 were set to PMID: 38288683\nPhenotypes for gene: SP9 were set to neurodevelopmental disorder MONDO:0700092\nPenetrance for gene: SP9 were set to Incomplete\nReview for gene: SP9 was set to GREEN\nAdded comment: PMID: 38288683: reported 5 unrelated patients with de novo heterozygous variants (missense and PTV) in SP9 gene. In silico and in vitro studies suggested a novel form of interneuronopathy with variable severity depending on the presence of loss or gain of function variants. Patients with loss-of-function variants had ID, ASD, and epilepsy, whereas missense variants in the second C2H2 binding domain result in hypomorphic and neomorphic DNA binding functions that cause severe epileptic encephalopathy. The author suggested a novel form of interneuronopathy with variable severity depending on the presence of loss or gain of function variants. \nSources: Literature",
"entity_name": "SP9",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:45:22.830620+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1511",
"user_name": "Lisa Norbart",
"item_type": "entity",
"text": "edited their review of gene: MEI4: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "MEI4",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:45:03.402169+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1511",
"user_name": "Lisa Norbart",
"item_type": "entity",
"text": "changed review comment from: PMID: 38252283 - 5x compound heterozygous missense variants and 1x homozygous missense variant seen in five individuals across 4 unrelated families affected with female infertility characterised by preimplantation embryonic arrest. Includes one family with two affected sisters with the same compound heterozygous variants. 2/4 families showed inheritance, parental data not available for other two families. Homozygous variant in the consanguineous family appears with a more severe phenotype. \r\n\r\nIn vitro evidence shows variants reduced the interactions between MEI4 and DNA, but no effects on protein levels. In vivo knock-out mouse model showed female mice were infertile, characterised by developmental defects during oogenesis. \nSources: Literature; to: PMID: 38252283 - 5x compound heterozygous missense variants and 1x homozygous missense variant seen in five individuals across 4 unrelated families affected with female infertility characterised by preimplantation embryonic arrest. Includes one family with two affected sisters with the same compound heterozygous variants. 2/4 families showed inheritance, parental data not available for other two families. Homozygous variant in the consanguineous family appears with a more severe phenotype. \r\n\r\nIn vitro evidence shows variants reduced the interactions between MEI4 and DNA, but no effects on protein levels. In vivo knock-out mouse model showed female mice were infertile, characterised by developmental defects during oogenesis. \r\nSources: Literature",
"entity_name": "MEI4",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:45:00.180875+11:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.2198",
"user_name": "Rylee Peters",
"item_type": "entity",
"text": "reviewed gene: CCDC88C: Rating: AMBER; Mode of pathogenicity: None; Publications: 38173219; Phenotypes: monogenic epilepsy MONDO:0015653, CCDC88C-related; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal",
"entity_name": "CCDC88C",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:44:45.909865+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1511",
"user_name": "Rylee Peters",
"item_type": "entity",
"text": "reviewed gene: CCDC88C: Rating: AMBER; Mode of pathogenicity: None; Publications: 38173219; Phenotypes: monogenic epilepsy MONDO:0015653, CCDC88C-related; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal",
"entity_name": "CCDC88C",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:44:38.583654+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1511",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: RHOXF1 as ready",
"entity_name": "RHOXF1",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:44:38.574442+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1511",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: rhoxf1 has been classified as Amber List (Moderate Evidence).",
"entity_name": "RHOXF1",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:44:24.483890+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1511",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: RHOXF1 as Amber List (moderate evidence)",
"entity_name": "RHOXF1",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:44:24.471773+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1511",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: rhoxf1 has been classified as Amber List (Moderate Evidence).",
"entity_name": "RHOXF1",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:43:36.186591+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "1.184",
"user_name": "Chern Lim",
"item_type": "entity",
"text": "edited their review of gene: CELSR1: Changed rating: GREEN",
"entity_name": "CELSR1",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:43:28.354850+11:00",
"panel_name": "Hydrops fetalis",
"panel_id": 116,
"panel_version": "0.308",
"user_name": "Chern Lim",
"item_type": "entity",
"text": "edited their review of gene: CELSR1: Changed rating: GREEN",
"entity_name": "CELSR1",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:43:16.265068+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1510",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: MEI4 as ready",
"entity_name": "MEI4",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:43:16.231672+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1510",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: mei4 has been classified as Green List (High Evidence).",
"entity_name": "MEI4",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:43:15.788104+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1510",
"user_name": "Chris Ciotta",
"item_type": "entity",
"text": "gene: RHOXF1 was added\ngene: RHOXF1 was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: RHOXF1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females\nPublications for gene: RHOXF1 were set to PMID: 38258527\nPhenotypes for gene: RHOXF1 were set to Spermatogenic failure, MONDO:0004983, RHOXF1-related\nReview for gene: RHOXF1 was set to AMBER\nAdded comment: In a cohort of 1,201 men from China with oligozoospermia and azoospermia, hemizygous RHOXF1 variants were identified in 4 unrelated individuals. \r\n\r\nThree of these variants were missense variants (V130M, A91V & A156V), all were absent from gnomAD (including version 4) and had deleterious in silicos.\r\n\r\nThe one other variant was a nonsense variant (R160X) which is predicted to escape NMD and truncate the protein. This is seen in gnomAD version 4 in 1 heterozygote female, and absent in other versions.\r\n\r\nIn vitro functional evidence for these variants was provided, the V130M, A156V and R160X mutants demonstrated impaired protein localisation with an increase in the protein in the cytoplasm and impaired nuclear entry, the A91V mutant protein did not share these localisation defects. \r\n\r\nFurther, The V130M mutant protein decreased DMRT1 promotor activity, DMRT1 is considered essential for testicular development and spermatogenesis. However, the R160X variant demonstrated increased activation, three times higher than WT. The two other missense variants had no effect. \nSources: Literature",
"entity_name": "RHOXF1",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:43:07.009597+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1510",
"user_name": "Elena Savva",
"item_type": "entity",
"text": "Marked gene: PRDM6 as ready",
"entity_name": "PRDM6",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:43:06.997877+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1510",
"user_name": "Elena Savva",
"item_type": "entity",
"text": "Gene: prdm6 has been classified as Green List (High Evidence).",
"entity_name": "PRDM6",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:42:55.334068+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1510",
"user_name": "Elena Savva",
"item_type": "entity",
"text": "Classified gene: PRDM6 as Green List (high evidence)",
"entity_name": "PRDM6",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:42:55.322246+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1510",
"user_name": "Elena Savva",
"item_type": "entity",
"text": "Gene: prdm6 has been classified as Green List (High Evidence).",
"entity_name": "PRDM6",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:42:27.006912+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1509",
"user_name": "Elena Savva",
"item_type": "entity",
"text": "gene: PRDM6 was added\ngene: PRDM6 was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: PRDM6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown\nPublications for gene: PRDM6 were set to 38071433; 27716515; 27181681\nPhenotypes for gene: PRDM6 were set to Patent ductus arteriosus 3 MIM#617039\nReview for gene: PRDM6 was set to GREEN\nAdded comment: Gene is established for patent ductus arteriosus. Only missense reported but supported by functional studies suggesting LOF.\r\n\r\nPMID: 38071433 - Two families (3 affected, 6 affected) with patent ductus arteriosus with/without additional coarctation of the aorta. Family 1 had a missense, family 2 had a PTC - both regarded as VUSs\r\n\r\nAdditional papers PMID: 27716515;27181681 describe nonsyndromic patent ductus arteriosus for the first time \nSources: Literature",
"entity_name": "PRDM6",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:42:21.980550+11:00",
"panel_name": "Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic",
"panel_id": 63,
"panel_version": "0.133",
"user_name": "Andrew Fennell",
"item_type": "entity",
"text": "gene: WDR44 was added\ngene: WDR44 was added to Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic. Sources: Literature\nMode of inheritance for gene: WDR44 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females\nPublications for gene: WDR44 were set to PMID: 38191484\nPhenotypes for gene: WDR44 were set to Ciliopathy, MONDO:0005308, WDR44-related\nReview for gene: WDR44 was set to GREEN\nAdded comment: 11 male patients with 6 missense and 1 nonsense variant in WDR44 displaying a wide range of cognitive impairment and variable congenital anomalies associated with primary cilium dysfunction.\r\n3 patients had renal anomalies including 1 with unilateral cystic kidney disease; and nephritis, and kidney hypoplasia resulting in renal failure in two patients.\r\nAll patients had learning difficulties with 8 labelled as intellectually disabled (mild-moderate). Other clinical features included anomalies of craniofacial, musculoskeletal, brain, and cardiac development.\r\nWDR44 is a negative regulator of ciliogenesis. Increased binding is hypothesised to underlie the pathogenicity of WDR44 variants identified in this cohort. Functional data supported impaired ciliogenesis initiation in patient fibroblasts and a zebrafish model. A zebrafish model recapitulated the human phenotype when morphants expressed WDR44 L668S, D669N, S764F, G782C, H839R, and R733* variants. Of note, D648G or N840S did not recapitulate the phenotype in the zebrafish model.\r\nThe studies supported a GoF mechanism, but the authors could not rule out that LoF of WDR44 contributes to the ciliopathy-like phenotype observed, because protein expression data was only available for a limited number of patients. \nSources: Literature",
"entity_name": "WDR44",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:42:12.556268+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1508",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: MEI4 as Green List (high evidence)",
"entity_name": "MEI4",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:42:12.544141+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1508",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: mei4 has been classified as Green List (High Evidence).",
"entity_name": "MEI4",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:41:27.612328+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1507",
"user_name": "Lisa Norbart",
"item_type": "entity",
"text": "gene: MEI4 was added\ngene: MEI4 was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: MEI4 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal\nPublications for gene: MEI4 were set to 38252283\nPhenotypes for gene: MEI4 were set to Infertility disorder, MONDO:0005047, MEI4-related\nReview for gene: MEI4 was set to GREEN\nAdded comment: PMID: 38252283 - 5x compound heterozygous missense variants and 1x homozygous missense variant seen in five individuals across 4 unrelated families affected with female infertility characterised by preimplantation embryonic arrest. Includes one family with two affected sisters with the same compound heterozygous variants. 2/4 families showed inheritance, parental data not available for other two families. Homozygous variant in the consanguineous family appears with a more severe phenotype. \r\n\r\nIn vitro evidence shows variants reduced the interactions between MEI4 and DNA, but no effects on protein levels. In vivo knock-out mouse model showed female mice were infertile, characterised by developmental defects during oogenesis. \nSources: Literature",
"entity_name": "MEI4",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:39:27.709501+11:00",
"panel_name": "Hydrops fetalis",
"panel_id": 116,
"panel_version": "0.308",
"user_name": "Ain Roesley",
"item_type": "entity",
"text": "Phenotypes for gene: CELSR1 were changed from Lymphatic malformation 9, MIM# 619319 to Lymphatic malformation 9, MIM# 619319",
"entity_name": "CELSR1",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:38:32.813711+11:00",
"panel_name": "Hydrops fetalis",
"panel_id": 116,
"panel_version": "0.307",
"user_name": "Ain Roesley",
"item_type": "entity",
"text": "changed review comment from: Comment on phenotypes: Presentation of hydrod is a phenotypic expansion on Lymphatic malformation; to: Comment on phenotypes: Presentation of hydrops is a phenotypic expansion on Lymphatic malformation",
"entity_name": "CELSR1",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:38:16.672736+11:00",
"panel_name": "Hydrops fetalis",
"panel_id": 116,
"panel_version": "0.307",
"user_name": "Ain Roesley",
"item_type": "entity",
"text": "Marked gene: CELSR1 as ready",
"entity_name": "CELSR1",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:38:16.658358+11:00",
"panel_name": "Hydrops fetalis",
"panel_id": 116,
"panel_version": "0.307",
"user_name": "Ain Roesley",
"item_type": "entity",
"text": "Gene: celsr1 has been classified as Green List (High Evidence).",
"entity_name": "CELSR1",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:38:12.891015+11:00",
"panel_name": "Hydrops fetalis",
"panel_id": 116,
"panel_version": "0.307",
"user_name": "Ain Roesley",
"item_type": "entity",
"text": "Added comment: Comment on phenotypes: Presentation of hydrod is a phenotypic expansion on Lymphatic malformation",
"entity_name": "CELSR1",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:38:12.859321+11:00",
"panel_name": "Hydrops fetalis",
"panel_id": 116,
"panel_version": "0.307",
"user_name": "Ain Roesley",
"item_type": "entity",
"text": "Phenotypes for gene: CELSR1 were changed from hydrops fetalis (MONDO:0015193), CELSR1-related to Lymphatic malformation 9, MIM# 619319",
"entity_name": "CELSR1",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:37:34.317795+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1507",
"user_name": "Seb Lunke",
"item_type": "entity",
"text": "Marked gene: WDR44 as ready",
"entity_name": "WDR44",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:37:34.313805+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1507",
"user_name": "Seb Lunke",
"item_type": "entity",
"text": "Added comment: Comment when marking as ready: GoF mentioned but not well established.",
"entity_name": "WDR44",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:37:34.244134+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1507",
"user_name": "Seb Lunke",
"item_type": "entity",
"text": "Gene: wdr44 has been classified as Green List (High Evidence).",
"entity_name": "WDR44",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:37:24.081701+11:00",
"panel_name": "Hydrops fetalis",
"panel_id": 116,
"panel_version": "0.306",
"user_name": "Ain Roesley",
"item_type": "entity",
"text": "Classified gene: CELSR1 as Green List (high evidence)",
"entity_name": "CELSR1",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:37:24.068612+11:00",
"panel_name": "Hydrops fetalis",
"panel_id": 116,
"panel_version": "0.306",
"user_name": "Ain Roesley",
"item_type": "entity",
"text": "Gene: celsr1 has been classified as Green List (High Evidence).",
"entity_name": "CELSR1",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:37:12.060357+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1507",
"user_name": "Seb Lunke",
"item_type": "entity",
"text": "Classified gene: WDR44 as Green List (high evidence)",
"entity_name": "WDR44",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:37:12.035113+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1507",
"user_name": "Seb Lunke",
"item_type": "entity",
"text": "Gene: wdr44 has been classified as Green List (High Evidence).",
"entity_name": "WDR44",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:37:02.491080+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "1.184",
"user_name": "Naomi Baker",
"item_type": "entity",
"text": "reviewed gene: PIEZO1: Rating: RED; Mode of pathogenicity: None; Publications: PMID:38184690; Phenotypes: Prune belly syndrome (MONDO:0007032), PIEZO1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "PIEZO1",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:36:39.402910+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "1.184",
"user_name": "Seb Lunke",
"item_type": "entity",
"text": "Marked gene: WDR44 as ready",
"entity_name": "WDR44",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:36:39.398765+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "1.184",
"user_name": "Seb Lunke",
"item_type": "entity",
"text": "Added comment: Comment when marking as ready: GoF mentioned but not well established.",
"entity_name": "WDR44",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:36:39.361273+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "1.184",
"user_name": "Seb Lunke",
"item_type": "entity",
"text": "Gene: wdr44 has been classified as Green List (High Evidence).",
"entity_name": "WDR44",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:36:32.419217+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "1.184",
"user_name": "Ain Roesley",
"item_type": "entity",
"text": "Publications for gene: CELSR1 were set to 31215153; 31403174; 26855770",
"entity_name": "CELSR1",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:36:29.672692+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "1.184",
"user_name": "Seb Lunke",
"item_type": "entity",
"text": "Classified gene: WDR44 as Green List (high evidence)",
"entity_name": "WDR44",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:36:29.646811+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "1.184",
"user_name": "Seb Lunke",
"item_type": "entity",
"text": "Gene: wdr44 has been classified as Green List (High Evidence).",
"entity_name": "WDR44",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:36:22.890420+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "1.183",
"user_name": "Ain Roesley",
"item_type": "entity",
"text": "Classified gene: CELSR1 as Green List (high evidence)",
"entity_name": "CELSR1",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:36:22.882083+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "1.183",
"user_name": "Ain Roesley",
"item_type": "entity",
"text": "Gene: celsr1 has been classified as Green List (High Evidence).",
"entity_name": "CELSR1",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:36:19.065374+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1506",
"user_name": "Andrew Fennell",
"item_type": "entity",
"text": "gene: WDR44 was added\ngene: WDR44 was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: WDR44 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females\nPublications for gene: WDR44 were set to PMID: 38191484\nPhenotypes for gene: WDR44 were set to Ciliopathy, MONDO:0005308, WDR44-related\nReview for gene: WDR44 was set to GREEN\nAdded comment: 11 male patients with 6 missense and 1 nonsense variant in WDR44 displaying a wide range of cognitive impairment and variable congenital anomalies associated with primary cilium dysfunction. All patients had learning difficulties with 8 labelled as intellectually disabled (mild-moderate). Other clinical features included anomalies of craniofacial, musculoskeletal, brain, renal and cardiac development.\r\nWDR44 is a negative regulator of ciliogenesis. Increased binding is hypothesised to underlie the pathogenicity of WDR44 variants identified in this cohort. Functional data supported impaired ciliogenesis initiation in patient fibroblasts and a zebrafish model. A zebrafish model recapitulated the human phenotype when morphants expressed WDR44 L668S, D669N, S764F, G782C, H839R, and R733* variants. Of note, D648G or N840S did not recapitulate the phenotype in the zebrafish model.\r\nThe studies supported a GoF mechanism, but the authors could not rule out that LoF of WDR44 contributes to the ciliopathy-like phenotype observed, because protein expression data was only available for a limited number of patients. \nSources: Literature",
"entity_name": "WDR44",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:34:54.023666+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "1.182",
"user_name": "Andrew Fennell",
"item_type": "entity",
"text": "gene: WDR44 was added\ngene: WDR44 was added to Fetal anomalies. Sources: Literature\nMode of inheritance for gene: WDR44 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females\nPublications for gene: WDR44 were set to PMID: 38191484\nPhenotypes for gene: WDR44 were set to Ciliopathy, MONDO:0005308, WDR44-related\nReview for gene: WDR44 was set to GREEN\nAdded comment: 11 male patients with 6 missense and 1 nonsense variant in WDR44 displaying a wide range of cognitive impairment and variable congenital anomalies associated with primary cilium dysfunction. All patients had learning difficulties with 8 labelled as intellectually disabled (mild-moderate). Other clinical features included anomalies of craniofacial, musculoskeletal, brain, renal and cardiac development.\r\nWDR44 is a negative regulator of ciliogenesis. Increased binding is hypothesised to underlie the pathogenicity of WDR44 variants identified in this cohort. Functional data supported impaired ciliogenesis initiation in patient fibroblasts and a zebrafish model. A zebrafish model recapitulated the human phenotype when morphants expressed WDR44 L668S, D669N, S764F, G782C, H839R, and R733* variants. Of note, D648G or N840S did not recapitulate the phenotype in the zebrafish model.\r\nThe studies supported a GoF mechanism, but the authors could not rule out that LoF of WDR44 contributes to the ciliopathy-like phenotype observed, because protein expression data was only available for a limited number of patients. \nSources: Literature",
"entity_name": "WDR44",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:34:37.098587+11:00",
"panel_name": "Macular Dystrophy/Stargardt Disease",
"panel_id": 303,
"panel_version": "0.44",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: SAMD7 as ready",
"entity_name": "SAMD7",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:34:37.082227+11:00",
"panel_name": "Macular Dystrophy/Stargardt Disease",
"panel_id": 303,
"panel_version": "0.44",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: samd7 has been classified as Green List (High Evidence).",
"entity_name": "SAMD7",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:34:32.500717+11:00",
"panel_name": "Macular Dystrophy/Stargardt Disease",
"panel_id": 303,
"panel_version": "0.44",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: SAMD7 as Green List (high evidence)",
"entity_name": "SAMD7",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:34:32.488986+11:00",
"panel_name": "Macular Dystrophy/Stargardt Disease",
"panel_id": 303,
"panel_version": "0.44",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: samd7 has been classified as Green List (High Evidence).",
"entity_name": "SAMD7",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:34:21.918056+11:00",
"panel_name": "Bone Marrow Failure",
"panel_id": 56,
"panel_version": "1.86",
"user_name": "Ain Roesley",
"item_type": "entity",
"text": "Marked gene: SH2B3 as ready",
"entity_name": "SH2B3",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:34:21.905261+11:00",
"panel_name": "Bone Marrow Failure",
"panel_id": 56,
"panel_version": "1.86",
"user_name": "Ain Roesley",
"item_type": "entity",
"text": "Gene: sh2b3 has been classified as Green List (High Evidence).",
"entity_name": "SH2B3",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:34:17.136689+11:00",
"panel_name": "Bone Marrow Failure",
"panel_id": 56,
"panel_version": "1.86",
"user_name": "Ain Roesley",
"item_type": "entity",
"text": "Classified gene: SH2B3 as Green List (high evidence)",
"entity_name": "SH2B3",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:34:17.123826+11:00",
"panel_name": "Bone Marrow Failure",
"panel_id": 56,
"panel_version": "1.86",
"user_name": "Ain Roesley",
"item_type": "entity",
"text": "Gene: sh2b3 has been classified as Green List (High Evidence).",
"entity_name": "SH2B3",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:34:13.325785+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1506",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: SAMD7 as ready",
"entity_name": "SAMD7",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:34:13.301103+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1506",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: samd7 has been classified as Green List (High Evidence).",
"entity_name": "SAMD7",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:34:02.787546+11:00",
"panel_name": "Ciliopathies",
"panel_id": 84,
"panel_version": "1.47",
"user_name": "Seb Lunke",
"item_type": "entity",
"text": "Marked gene: WDR44 as ready",
"entity_name": "WDR44",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:34:02.782663+11:00",
"panel_name": "Ciliopathies",
"panel_id": 84,
"panel_version": "1.47",
"user_name": "Seb Lunke",
"item_type": "entity",
"text": "Added comment: Comment when marking as ready: GoF mentioned but not well supported.",
"entity_name": "WDR44",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:34:02.741351+11:00",
"panel_name": "Ciliopathies",
"panel_id": 84,
"panel_version": "1.47",
"user_name": "Seb Lunke",
"item_type": "entity",
"text": "Gene: wdr44 has been classified as Green List (High Evidence).",
"entity_name": "WDR44",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:33:53.471302+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1506",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: SAMD7 as Green List (high evidence)",
"entity_name": "SAMD7",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:33:53.460391+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1506",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: samd7 has been classified as Green List (High Evidence).",
"entity_name": "SAMD7",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:33:38.971677+11:00",
"panel_name": "Ciliopathies",
"panel_id": 84,
"panel_version": "1.47",
"user_name": "Seb Lunke",
"item_type": "entity",
"text": "Classified gene: WDR44 as Green List (high evidence)",
"entity_name": "WDR44",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:33:38.957598+11:00",
"panel_name": "Ciliopathies",
"panel_id": 84,
"panel_version": "1.47",
"user_name": "Seb Lunke",
"item_type": "entity",
"text": "Gene: wdr44 has been classified as Green List (High Evidence).",
"entity_name": "WDR44",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:33:37.436636+11:00",
"panel_name": "Bone Marrow Failure",
"panel_id": 56,
"panel_version": "1.85",
"user_name": "Ain Roesley",
"item_type": "entity",
"text": "gene: SH2B3 was added\ngene: SH2B3 was added to Bone Marrow Failure. Sources: Literature\nMode of inheritance for gene: SH2B3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal\nPublications for gene: SH2B3 were set to 37206266; 23908464; 38152053; 37206266; 38152053\nPhenotypes for gene: SH2B3 were set to Predisposition to haematological malignancies; Myeloproliferation and multi-organ autoimmunity; juvenile myelomonocytic leukemia MONDO:001190, SH2B3-related\nReview for gene: SH2B3 was set to GREEN\ngene: SH2B3 was marked as current diagnostic\nAdded comment: PMID:37206266\r\n2x families\r\n- hom missense variant Val402Met:\r\nfunctional performed on patient's fibroblasts demonstrated increased basal pSTAT5, pSTAT3 and increased pJAK2 + pSTAT5 after stimulation with IL-3, GH, GM-CSF and EPO\r\n\r\n- hom fs Arg148Profs*40\r\nfunctional performed in zebrafish demonstrated increased number of macrophages and thrombocytes\r\n\r\nPMID:23908464;\r\n1 fam with 2 affecteds with dev delay + autoimmunity + (1x) ALL, hom for Asp231Gly fs*3\r\n\r\nPMID:38152053;\r\nJMML cohort - 2x hom missense + 2x het PTCs \nSources: Literature",
"entity_name": "SH2B3",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:32:45.878836+11:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "1.182",
"user_name": "Chern Lim",
"item_type": "entity",
"text": "reviewed gene: CELSR1: Rating: AMBER; Mode of pathogenicity: None; Publications: 38272662; Phenotypes: hydrops fetalis (MONDO:0015193), CELSR1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes",
"entity_name": "CELSR1",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:32:40.537993+11:00",
"panel_name": "Hydrops fetalis",
"panel_id": 116,
"panel_version": "0.305",
"user_name": "Chern Lim",
"item_type": "entity",
"text": "gene: CELSR1 was added\ngene: CELSR1 was added to Hydrops fetalis. Sources: Literature\nMode of inheritance for gene: CELSR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: CELSR1 were set to 38272662\nPhenotypes for gene: CELSR1 were set to hydrops fetalis (MONDO:0015193), CELSR1-related\nReview for gene: CELSR1 was set to AMBER\ngene: CELSR1 was marked as current diagnostic\nAdded comment: PMID: 38272662:\r\n-\tHet de novo missense variants in two unrelated cases of fetal pleural effusions leading to severe fetal hydrops - Cys1318Tyr, Cys1349Arg.\r\n-\tBoth variants lie within the same protein domain.\r\n-\tFunctional studies performed for only one of the variants, p.(Cys1318Tyr): the variant affected CELSR1 protein cell membrane localisation compared with wild-type CELSR1 protein in both a plasmid-based overexpression system and the patient fibroblast cells. Bulk RNA-seq of RNA samples extracted from the proband and the mother’s fibroblast cells demonstrated that in the proband mRNA samples, the amount of CELSR1 mRNA was significantly decreased.\r\n-\tNo functional testing was performed on the p.(Cys1349Arg) variant. \nSources: Literature",
"entity_name": "CELSR1",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:31:54.393622+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1505",
"user_name": "Ain Roesley",
"item_type": "entity",
"text": "Phenotypes for gene: SH2B3 were changed from Predisposition to haematological malignancies to Predisposition to haematological malignancies; Myeloproliferation and multi-organ autoimmunity; juvenile myelomonocytic leukemia MONDO:001190, SH2B3-related",
"entity_name": "SH2B3",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:31:42.332940+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1504",
"user_name": "Ain Roesley",
"item_type": "entity",
"text": "Publications for gene: SH2B3 were set to 26457647; 23908464; 31102422; 31173385",
"entity_name": "SH2B3",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:31:23.174308+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1503",
"user_name": "Ain Roesley",
"item_type": "entity",
"text": "Mode of inheritance for gene: SH2B3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal",
"entity_name": "SH2B3",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:30:59.207405+11:00",
"panel_name": "Ciliopathies",
"panel_id": 84,
"panel_version": "1.46",
"user_name": "Andrew Fennell",
"item_type": "entity",
"text": "changed review comment from: 11 male patients with 6 missense and 1 nonsense variant in WDR44 displaying a wide range of cognitive impairment and variable congenital anomalies associated with primary cilium dysfunction. All patients had learning difficulties with 8 labelled as intellectually disabled (mild-moderate). Other clinical features included anomalies of craniofacial, musculoskeletal, brain, renal and cardiac development.\r\nWDR44 is a negative regulator of ciliogenesis. Increased binding is hypothesised to underlie the pathogenicity of WDR44 variants identified in this cohort. Functional data supported impaired ciliogenesis initiation in patient fibroblasts and a zebrafish model. A zebrafish model recaptulated the human phenotype when morphants expressed WDR44 L668S, D669N, S764F, G782C, H839R, and R733* variants. Of note, D648G or N840S did not recapitulate the phenotype in the zebrafish model.\r\nThe studies supported a GoF mechanism, but the authors could not rule out that LoF of WDR44 contributes to the ciliopathy-like phenotype observed, because protein expression data was only available for a limited number of patients. \nSources: Literature; to: 11 male patients with 6 missense and 1 nonsense variant in WDR44 displaying a wide range of cognitive impairment and variable congenital anomalies associated with primary cilium dysfunction. All patients had learning difficulties with 8 labelled as intellectually disabled (mild-moderate). Other clinical features included anomalies of craniofacial, musculoskeletal, brain, renal and cardiac development.\r\nWDR44 is a negative regulator of ciliogenesis. Increased binding is hypothesised to underlie the pathogenicity of WDR44 variants identified in this cohort. Functional data supported impaired ciliogenesis initiation in patient fibroblasts and a zebrafish model. A zebrafish model recapitulated the human phenotype when morphants expressed WDR44 L668S, D669N, S764F, G782C, H839R, and R733* variants. Of note, D648G or N840S did not recapitulate the phenotype in the zebrafish model.\r\nThe studies supported a GoF mechanism, but the authors could not rule out that LoF of WDR44 contributes to the ciliopathy-like phenotype observed, because protein expression data was only available for a limited number of patients. \r\nSources: Literature",
"entity_name": "WDR44",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:30:22.224615+11:00",
"panel_name": "Ciliopathies",
"panel_id": 84,
"panel_version": "1.46",
"user_name": "Andrew Fennell",
"item_type": "entity",
"text": "gene: WDR44 was added\ngene: WDR44 was added to Ciliopathies. Sources: Literature\nMode of inheritance for gene: WDR44 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females\nPublications for gene: WDR44 were set to PMID: 38191484\nPhenotypes for gene: WDR44 were set to Ciliopathy, MONDO:0005308, WDR44-related\nReview for gene: WDR44 was set to GREEN\nAdded comment: 11 male patients with 6 missense and 1 nonsense variant in WDR44 displaying a wide range of cognitive impairment and variable congenital anomalies associated with primary cilium dysfunction. All patients had learning difficulties with 8 labelled as intellectually disabled (mild-moderate). Other clinical features included anomalies of craniofacial, musculoskeletal, brain, renal and cardiac development.\r\nWDR44 is a negative regulator of ciliogenesis. Increased binding is hypothesised to underlie the pathogenicity of WDR44 variants identified in this cohort. Functional data supported impaired ciliogenesis initiation in patient fibroblasts and a zebrafish model. A zebrafish model recaptulated the human phenotype when morphants expressed WDR44 L668S, D669N, S764F, G782C, H839R, and R733* variants. Of note, D648G or N840S did not recapitulate the phenotype in the zebrafish model.\r\nThe studies supported a GoF mechanism, but the authors could not rule out that LoF of WDR44 contributes to the ciliopathy-like phenotype observed, because protein expression data was only available for a limited number of patients. \nSources: Literature",
"entity_name": "WDR44",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:30:00.398239+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1502",
"user_name": "Ain Roesley",
"item_type": "entity",
"text": "Deleted their comment",
"entity_name": "SH2B3",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:29:41.494506+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1502",
"user_name": "Ain Roesley",
"item_type": "entity",
"text": "commented on gene: SH2B3: PMID:37206266\r\n2x families \r\n- hom missense variant Val402Met:\r\nfunctional performed on patient's fibroblasts demonstrated increased basal pSTAT5, pSTAT3 and increased pJAK2 + pSTAT5 after stimulation with IL-3, GH, GM-CSF and EPO\r\n\r\n- hom fs Arg148Profs*40\r\nfunctional performed in zebrafish demonstrated increased number of macrophages and thrombocytes\r\n\r\nPMID:23908464;\r\n1 fam with 2 affecteds with dev delay + autoimmunity + (1x) ALL, hom for Asp231Gly fs*3\r\n\r\nPMID:38152053;\r\nJMML cohort - 2x hom missense + 2x het PTCs",
"entity_name": "SH2B3",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:29:40.705501+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1502",
"user_name": "Ain Roesley",
"item_type": "entity",
"text": "reviewed gene: SH2B3: Rating: GREEN; Mode of pathogenicity: None; Publications: 37206266, 23908464, 38152053; Phenotypes: Myeloproliferation and multi-organ autoimmunity, juvenile myelomonocytic leukemia MONDO:001190, SH2B3-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes",
"entity_name": "SH2B3",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:29:25.446165+11:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.1502",
"user_name": "Paul De Fazio",
"item_type": "entity",
"text": "gene: SAMD7 was added\ngene: SAMD7 was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: SAMD7 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: SAMD7 were set to 38272031\nPhenotypes for gene: SAMD7 were set to Macular dystrophy, retinal, SAMD7-related MONDO:0031166\nReview for gene: SAMD7 was set to GREEN\ngene: SAMD7 was marked as current diagnostic\nAdded comment: Five biallelic variants were identified in eight individuals from six families with macular dystrophy with or without cone dysfunction. Three families were consanguineous. Mean age at first presentation was 34.8 years, range 14 to 51.\r\n\r\nFour variants affected splicing, while one missense variant impaired the repressive activity of SAMD7. All functional work was performed using in vitro assays. \nSources: Literature",
"entity_name": "SAMD7",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:28:10.667502+11:00",
"panel_name": "Macular Dystrophy/Stargardt Disease",
"panel_id": 303,
"panel_version": "0.43",
"user_name": "Paul De Fazio",
"item_type": "entity",
"text": "gene: SAMD7 was added\ngene: SAMD7 was added to Macular Dystrophy/Stargardt Disease. Sources: Literature\nMode of inheritance for gene: SAMD7 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: SAMD7 were set to 38272031\nPhenotypes for gene: SAMD7 were set to Macular dystrophy, retinal, SAMD7-related MONDO:0031166\nReview for gene: SAMD7 was set to GREEN\ngene: SAMD7 was marked as current diagnostic\nAdded comment: Five biallelic variants were identified in eight individuals from six families with macular dystrophy with or without cone dysfunction. Three families were consanguineous. Mean age at first presentation was 34.8 years, range 14 to 51.\r\n\r\nFour variants affected splicing, while one missense variant impaired the repressive activity of SAMD7. All functional work was performed using in vitro assays. \nSources: Literature",
"entity_name": "SAMD7",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:27:07.703038+11:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.2198",
"user_name": "Elena Savva",
"item_type": "entity",
"text": "Classified gene: CAMK2D as Amber List (moderate evidence)",
"entity_name": "CAMK2D",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:27:07.690707+11:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.2198",
"user_name": "Elena Savva",
"item_type": "entity",
"text": "Gene: camk2d has been classified as Amber List (Moderate Evidence).",
"entity_name": "CAMK2D",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:26:44.938744+11:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.2198",
"user_name": "Elena Savva",
"item_type": "entity",
"text": "Classified gene: CAMK2D as Amber List (moderate evidence)",
"entity_name": "CAMK2D",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:26:44.929002+11:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.2198",
"user_name": "Elena Savva",
"item_type": "entity",
"text": "Gene: camk2d has been classified as Amber List (Moderate Evidence).",
"entity_name": "CAMK2D",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:26:36.115172+11:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.2197",
"user_name": "Elena Savva",
"item_type": "entity",
"text": "Marked gene: CAMK2D as ready",
"entity_name": "CAMK2D",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:26:36.102030+11:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.2197",
"user_name": "Elena Savva",
"item_type": "entity",
"text": "Gene: camk2d has been classified as Red List (Low Evidence).",
"entity_name": "CAMK2D",
"entity_type": "gene"
},
{
"created": "2024-02-01T11:26:13.517386+11:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.2197",
"user_name": "Elena Savva",
"item_type": "entity",
"text": "gene: CAMK2D was added\ngene: CAMK2D was added to Genetic Epilepsy. Sources: Literature\nMode of inheritance for gene: CAMK2D was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown\nPublications for gene: CAMK2D were set to 38272033\nPhenotypes for gene: CAMK2D were set to Neurodevelopmental disorder (MONDO#0700092), CAMK2D-related\nReview for gene: CAMK2D was set to AMBER\nAdded comment: PMID: 38272033 \r\n- 8 patients (5/8 de novo) with mostly missense and a single splice site variant, ages range from 5 weeks to 20 years old \r\n- Most variants functionally shown to have a GOF mechanism causing addition DCM phenotype, LOF is only neurological \r\n- Phenotypes include dev delay (mild-severe) (7/7 patients), skeletal anomalies (7/8, scoliosis, kyphosis, involving spine/hands/feet/palate), DCM (6/8), seizures (3/8), visual anomalies (astigmatism, cortical vision impairment, myopia, strabismus 5/5), enlarged brain ventricles (3/5) \nSources: Literature",
"entity_name": "CAMK2D",
"entity_type": "gene"
}
]
}