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{
"count": 220725,
"next": "https://panelapp-aus.org/api/v1/activities/?format=api&page=772",
"previous": "https://panelapp-aus.org/api/v1/activities/?format=api&page=770",
"results": [
{
"created": "2022-09-09T07:59:11.471772+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.1661",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: TRAPPC10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with microcephaly, short stature, and speech delay, MIM# 620027; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "TRAPPC10",
"entity_type": "gene"
},
{
"created": "2022-09-09T07:58:51.770443+10:00",
"panel_name": "Microcephaly",
"panel_id": 138,
"panel_version": "1.152",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: TRAPPC10 were changed from neurodevelopmental disorder (MONDO:0700092), TRAPPC10-related to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, MIM# 620027",
"entity_name": "TRAPPC10",
"entity_type": "gene"
},
{
"created": "2022-09-09T07:58:17.283376+10:00",
"panel_name": "Microcephaly",
"panel_id": 138,
"panel_version": "1.151",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: TRAPPC10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with microcephaly, short stature, and speech delay, MIM# 620027; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "TRAPPC10",
"entity_type": "gene"
},
{
"created": "2022-09-09T07:54:54.928793+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.319",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: TRAPPC10 were changed from neurodevelopmental disorder (MONDO:0700092), TRAPPC10-related to Neurodevelopmental disorder with microcephaly, short stature, and speech delay, MIM# 620027",
"entity_name": "TRAPPC10",
"entity_type": "gene"
},
{
"created": "2022-09-09T07:54:25.122731+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.318",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: TRAPPC10: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with microcephaly, short stature, and speech delay, MIM# 620027; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "TRAPPC10",
"entity_type": "gene"
},
{
"created": "2022-09-08T06:41:08.799900+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.1661",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: CAPRIN1 were set to 35979925",
"entity_name": "CAPRIN1",
"entity_type": "gene"
},
{
"created": "2022-09-08T06:39:38.958951+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.4933",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: CAPRIN1 were set to 35979925",
"entity_name": "CAPRIN1",
"entity_type": "gene"
},
{
"created": "2022-09-08T06:38:18.732584+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.318",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "changed review comment from: Based on Jia et al (2022 - PMID: 35977029) speech, motor delay as well as ID are observed in individuals harboring de novo pLoF variants in UBAP2L. The gene encodes a regulator of the stress granule (SG) assembly. Extensive evidence is provided on the effect of variants as well as the role of UBAP2L and other genes for components and/or regulation of SG in pathogenesis of NDDs. Among others a Ubap2l htz deletion mouse model (behavioral and cognitive impairment, abnormal cortical development due to impaired SG assembly, etc). Data from 26 previous studies, aggregating 40,853 probands with NDDs (mostly DD/ID, also ASD) suggest enrichment for DNMs in UBAP2L or other genes previously known and further shown to be important for SG formation (incl. G3BP1/G3BP2, CAPRIN1). \nSources: Literature; to: Based on Jia et al (2022 - PMID: 35977029) speech, motor delay as well as ID are observed in 11 individuals harboring de novo pLoF variants in UBAP2L. The gene encodes a regulator of the stress granule (SG) assembly. Extensive evidence is provided on the effect of variants as well as the role of UBAP2L and other genes for components and/or regulation of SG in pathogenesis of NDDs. Among others a Ubap2l htz deletion mouse model (behavioral and cognitive impairment, abnormal cortical development due to impaired SG assembly, etc). Data from 26 previous studies, aggregating 40,853 probands with NDDs (mostly DD/ID, also ASD) suggest enrichment for DNMs in UBAP2L or other genes previously known and further shown to be important for SG formation (incl. G3BP1/G3BP2, CAPRIN1). \r\nSources: Literature",
"entity_name": "UBAP2L",
"entity_type": "gene"
},
{
"created": "2022-09-08T06:37:59.660496+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.318",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: UBAP2L as ready",
"entity_name": "UBAP2L",
"entity_type": "gene"
},
{
"created": "2022-09-08T06:37:59.629395+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.318",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: ubap2l has been classified as Green List (High Evidence).",
"entity_name": "UBAP2L",
"entity_type": "gene"
},
{
"created": "2022-09-08T06:37:47.792372+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.318",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: UBAP2L as Green List (high evidence)",
"entity_name": "UBAP2L",
"entity_type": "gene"
},
{
"created": "2022-09-08T06:37:47.784928+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.318",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: ubap2l has been classified as Green List (High Evidence).",
"entity_name": "UBAP2L",
"entity_type": "gene"
},
{
"created": "2022-09-08T06:36:58.564708+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.317",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "gene: UBAP2L was added\ngene: UBAP2L was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: UBAP2L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted\nPublications for gene: UBAP2L were set to 35977029\nPhenotypes for gene: UBAP2L were set to Neurodevelopmental disorder, MONDO:0700092, UBAP2L-related\nReview for gene: UBAP2L was set to GREEN\nAdded comment: Based on Jia et al (2022 - PMID: 35977029) speech, motor delay as well as ID are observed in individuals harboring de novo pLoF variants in UBAP2L. The gene encodes a regulator of the stress granule (SG) assembly. Extensive evidence is provided on the effect of variants as well as the role of UBAP2L and other genes for components and/or regulation of SG in pathogenesis of NDDs. Among others a Ubap2l htz deletion mouse model (behavioral and cognitive impairment, abnormal cortical development due to impaired SG assembly, etc). Data from 26 previous studies, aggregating 40,853 probands with NDDs (mostly DD/ID, also ASD) suggest enrichment for DNMs in UBAP2L or other genes previously known and further shown to be important for SG formation (incl. G3BP1/G3BP2, CAPRIN1). \nSources: Literature",
"entity_name": "UBAP2L",
"entity_type": "gene"
},
{
"created": "2022-09-08T06:36:20.869484+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.1660",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: UBAP2L were changed from Neurodevelopmental disorder, MONDO:0700092, UBAP2L-related; Delayed speech and language development; Motor delay; Intellectual disability; Autistic behavior; Seizures; Microcephaly; Abnormality of head or neck; Short stature; Abnormality of the skeletal system to Neurodevelopmental disorder, MONDO:0700092, UBAP2L-related; Delayed speech and language development; Motor delay; Intellectual disability; Autistic behavior; Seizures; Microcephaly; Abnormality of head or neck; Short stature; Abnormality of the skeletal system",
"entity_name": "UBAP2L",
"entity_type": "gene"
},
{
"created": "2022-09-08T06:36:10.857443+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.1660",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: UBAP2L as ready",
"entity_name": "UBAP2L",
"entity_type": "gene"
},
{
"created": "2022-09-08T06:36:10.848361+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.1660",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: ubap2l has been classified as Green List (High Evidence).",
"entity_name": "UBAP2L",
"entity_type": "gene"
},
{
"created": "2022-09-08T06:35:59.455827+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.1660",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: UBAP2L were changed from Delayed speech and language development; Motor delay; Intellectual disability; Autistic behavior; Seizures; Microcephaly; Abnormality of head or neck; Short stature; Abnormality of the skeletal system to Neurodevelopmental disorder, MONDO:0700092, UBAP2L-related; Delayed speech and language development; Motor delay; Intellectual disability; Autistic behavior; Seizures; Microcephaly; Abnormality of head or neck; Short stature; Abnormality of the skeletal system",
"entity_name": "UBAP2L",
"entity_type": "gene"
},
{
"created": "2022-09-08T06:33:22.671823+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.1659",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: UBAP2L as Green List (high evidence)",
"entity_name": "UBAP2L",
"entity_type": "gene"
},
{
"created": "2022-09-08T06:33:22.664393+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.1659",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: ubap2l has been classified as Green List (High Evidence).",
"entity_name": "UBAP2L",
"entity_type": "gene"
},
{
"created": "2022-09-08T06:33:04.097923+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.4932",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: UBAP2L as ready",
"entity_name": "UBAP2L",
"entity_type": "gene"
},
{
"created": "2022-09-08T06:33:04.085029+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.4932",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: ubap2l has been classified as Green List (High Evidence).",
"entity_name": "UBAP2L",
"entity_type": "gene"
},
{
"created": "2022-09-08T06:32:48.859583+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.4932",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: UBAP2L were changed from Delayed speech and language development; Motor delay; Intellectual disability; Autistic behavior; Seizures; Microcephaly; Abnormality of head or neck; Short stature; Abnormality of the skeletal system to Neurodevelopmental disorder, MONDO:0700092, UBAP2L-related; Delayed speech and language development; Motor delay; Intellectual disability; Autistic behavior; Seizures; Microcephaly; Abnormality of head or neck; Short stature; Abnormality of the skeletal system",
"entity_name": "UBAP2L",
"entity_type": "gene"
},
{
"created": "2022-09-08T06:32:39.376598+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.1658",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: UBAP2L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, UBAP2L-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "UBAP2L",
"entity_type": "gene"
},
{
"created": "2022-09-08T06:32:13.485920+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.4931",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: UBAP2L was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "UBAP2L",
"entity_type": "gene"
},
{
"created": "2022-09-08T06:31:35.886647+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.4930",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: UBAP2L as Green List (high evidence)",
"entity_name": "UBAP2L",
"entity_type": "gene"
},
{
"created": "2022-09-08T06:31:35.874957+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.4930",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: ubap2l has been classified as Green List (High Evidence).",
"entity_name": "UBAP2L",
"entity_type": "gene"
},
{
"created": "2022-09-08T06:30:58.262802+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.4929",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: UBAP2L: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, UBAP2L-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "UBAP2L",
"entity_type": "gene"
},
{
"created": "2022-09-07T09:39:03.460882+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.205",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Marked gene: SMARCB1 as ready",
"entity_name": "SMARCB1",
"entity_type": "gene"
},
{
"created": "2022-09-07T09:39:03.453381+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.205",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Gene: smarcb1 has been classified as Green List (High Evidence).",
"entity_name": "SMARCB1",
"entity_type": "gene"
},
{
"created": "2022-09-07T09:16:25.549304+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.205",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Phenotypes for gene: SMARCB1 were changed from Coffin Siris syndrome to Coffin-Siris syndrome 3, MIM# 614608",
"entity_name": "SMARCB1",
"entity_type": "gene"
},
{
"created": "2022-09-07T09:12:28.224796+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.204",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Mode of inheritance for gene: SMARCB1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "SMARCB1",
"entity_type": "gene"
},
{
"created": "2022-09-07T09:11:16.367924+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.203",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Publications for gene: SMARCB1 were set to ",
"entity_name": "SMARCB1",
"entity_type": "gene"
},
{
"created": "2022-09-07T09:10:03.765231+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.202",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Classified gene: SMARCB1 as Green List (high evidence)",
"entity_name": "SMARCB1",
"entity_type": "gene"
},
{
"created": "2022-09-07T09:10:03.756816+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.202",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Gene: smarcb1 has been classified as Green List (High Evidence).",
"entity_name": "SMARCB1",
"entity_type": "gene"
},
{
"created": "2022-09-07T08:59:43.219868+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.201",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Marked gene: SOX11 as ready",
"entity_name": "SOX11",
"entity_type": "gene"
},
{
"created": "2022-09-07T08:59:43.208475+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.201",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Gene: sox11 has been classified as Green List (High Evidence).",
"entity_name": "SOX11",
"entity_type": "gene"
},
{
"created": "2022-09-07T08:59:22.199013+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.201",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Mode of inheritance for gene: SOX11 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "SOX11",
"entity_type": "gene"
},
{
"created": "2022-09-07T08:57:39.984102+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.200",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Phenotypes for gene: SOX11 were changed from Coffin-Siris syndrome to Coffin-Siris syndrome MONDO:0015452",
"entity_name": "SOX11",
"entity_type": "gene"
},
{
"created": "2022-09-07T08:57:08.814657+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.199",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Classified gene: SOX11 as Green List (high evidence)",
"entity_name": "SOX11",
"entity_type": "gene"
},
{
"created": "2022-09-07T08:57:08.805551+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.199",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Gene: sox11 has been classified as Green List (High Evidence).",
"entity_name": "SOX11",
"entity_type": "gene"
},
{
"created": "2022-09-07T08:56:39.944147+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.198",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "reviewed gene: SOX11: Rating: GREEN; Mode of pathogenicity: None; Publications: 26543203; Phenotypes: Coffin-Siris syndrome MONDO:0015452; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "SOX11",
"entity_type": "gene"
},
{
"created": "2022-09-07T08:54:00.970674+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.198",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Publications for gene: SOX11 were set to ",
"entity_name": "SOX11",
"entity_type": "gene"
},
{
"created": "2022-09-07T08:50:45.610296+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.197",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Marked gene: USP9X as ready",
"entity_name": "USP9X",
"entity_type": "gene"
},
{
"created": "2022-09-07T08:50:45.597039+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.197",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Gene: usp9x has been classified as Green List (High Evidence).",
"entity_name": "USP9X",
"entity_type": "gene"
},
{
"created": "2022-09-07T08:50:35.712656+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.197",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Phenotypes for gene: USP9X were changed from New syndrom with skd to intellectual disability, X-linked 99 MONDO:0010487",
"entity_name": "USP9X",
"entity_type": "gene"
},
{
"created": "2022-09-07T08:49:38.810280+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.196",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Publications for gene: USP9X were set to ",
"entity_name": "USP9X",
"entity_type": "gene"
},
{
"created": "2022-09-07T08:49:02.929341+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.195",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Mode of inheritance for gene: USP9X was changed from to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)",
"entity_name": "USP9X",
"entity_type": "gene"
},
{
"created": "2022-09-07T08:47:28.661032+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.194",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Classified gene: USP9X as Green List (high evidence)",
"entity_name": "USP9X",
"entity_type": "gene"
},
{
"created": "2022-09-07T08:47:28.644172+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.194",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Gene: usp9x has been classified as Green List (High Evidence).",
"entity_name": "USP9X",
"entity_type": "gene"
},
{
"created": "2022-09-07T08:46:08.874057+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.193",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Marked gene: SMARCE1 as ready",
"entity_name": "SMARCE1",
"entity_type": "gene"
},
{
"created": "2022-09-07T08:46:08.865488+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.193",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Gene: smarce1 has been classified as Green List (High Evidence).",
"entity_name": "SMARCE1",
"entity_type": "gene"
},
{
"created": "2022-09-07T08:46:06.398636+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.193",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Phenotypes for gene: SMARCE1 were changed from Coffin-Siris syndrome 5, MIM# 616938 to Coffin-Siris syndrome 5, MIM# 616938",
"entity_name": "SMARCE1",
"entity_type": "gene"
},
{
"created": "2022-09-07T08:45:45.389040+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.192",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Phenotypes for gene: SMARCE1 were changed from Coffin-Siris syndrome to Coffin-Siris syndrome 5, MIM# 616938",
"entity_name": "SMARCE1",
"entity_type": "gene"
},
{
"created": "2022-09-07T08:45:23.628363+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.192",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Mode of inheritance for gene: SMARCE1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "SMARCE1",
"entity_type": "gene"
},
{
"created": "2022-09-07T08:44:41.639280+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.191",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Publications for gene: SMARCE1 were set to ",
"entity_name": "SMARCE1",
"entity_type": "gene"
},
{
"created": "2022-09-07T08:44:19.505899+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.190",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Classified gene: SMARCE1 as Green List (high evidence)",
"entity_name": "SMARCE1",
"entity_type": "gene"
},
{
"created": "2022-09-07T08:44:19.494314+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.190",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Gene: smarce1 has been classified as Green List (High Evidence).",
"entity_name": "SMARCE1",
"entity_type": "gene"
},
{
"created": "2022-09-07T08:38:22.822746+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.189",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Deleted their review",
"entity_name": "ZNF423",
"entity_type": "gene"
},
{
"created": "2022-09-05T08:17:24.856057+10:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "1.67",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: ALDH1A2 were changed from Multiple congenital anomalies, ALDH1A2-related, MONDO:0019042 to Diaphragmatic hernia 4, with cardiovascular defects, MIM# 620025",
"entity_name": "ALDH1A2",
"entity_type": "gene"
},
{
"created": "2022-09-05T08:17:07.587690+10:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "1.66",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: ALDH1A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diaphragmatic hernia 4, with cardiovascular defects, MIM# 620025; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "ALDH1A2",
"entity_type": "gene"
},
{
"created": "2022-09-05T08:16:32.873757+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.316",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: ALDH1A2 were changed from congenital heart defects; diaphragmatic eventration; pulmonary hypoplasia; dysmorphic features to Diaphragmatic hernia 4, with cardiovascular defects, MIM# 620025",
"entity_name": "ALDH1A2",
"entity_type": "gene"
},
{
"created": "2022-09-05T08:15:29.697754+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.315",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: ALDH1A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diaphragmatic hernia 4, with cardiovascular defects, MIM# 620025; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "ALDH1A2",
"entity_type": "gene"
},
{
"created": "2022-09-05T08:14:52.346984+10:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.262",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: ALDH1A2 were changed from Congenital heart defects; diaphragmatic eventration; pulmonary hypoplasia; dysmorphic features to Diaphragmatic hernia 4, with cardiovascular defects, MIM# 620025",
"entity_name": "ALDH1A2",
"entity_type": "gene"
},
{
"created": "2022-09-05T08:14:15.939016+10:00",
"panel_name": "Congenital Heart Defect",
"panel_id": 76,
"panel_version": "0.261",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: ALDH1A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diaphragmatic hernia 4, with cardiovascular defects, MIM# 620025; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "ALDH1A2",
"entity_type": "gene"
},
{
"created": "2022-09-05T08:12:57.733346+10:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "1.66",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: CHKA were changed from neurodevelopmental disorder, CHKA-related MONDO#0700092 to Neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures, MIM#620023",
"entity_name": "CHKA",
"entity_type": "gene"
},
{
"created": "2022-09-05T08:12:43.458918+10:00",
"panel_name": "Fetal anomalies",
"panel_id": 3763,
"panel_version": "1.65",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: CHKA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures, MIM#620023; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "CHKA",
"entity_type": "gene"
},
{
"created": "2022-09-05T08:11:45.809813+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.4929",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: CHKA were changed from Neurodevelopmental disorder, MONDO:0700092; Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature to Neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures, MIM#620023",
"entity_name": "CHKA",
"entity_type": "gene"
},
{
"created": "2022-09-05T08:11:06.140551+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.4928",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: CHKA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures, MIM#620023; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "CHKA",
"entity_type": "gene"
},
{
"created": "2022-09-05T08:09:26.278648+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.1658",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: CHKA were changed from Neurodevelopmental disorder, MONDO:0700092; Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature to Neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures, MIM#620023",
"entity_name": "CHKA",
"entity_type": "gene"
},
{
"created": "2022-09-05T08:08:47.786502+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.1657",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: CHKA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures, MIM#620023; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "CHKA",
"entity_type": "gene"
},
{
"created": "2022-09-05T08:08:30.837943+10:00",
"panel_name": "Microcephaly",
"panel_id": 138,
"panel_version": "1.151",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: CHKA were changed from Neurodevelopmental disorder, MONDO:0700092; Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature to Neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures, MIM#620023",
"entity_name": "CHKA",
"entity_type": "gene"
},
{
"created": "2022-09-05T08:01:58.042816+10:00",
"panel_name": "Microcephaly",
"panel_id": 138,
"panel_version": "1.150",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: CHKA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures, MIM#620023; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "CHKA",
"entity_type": "gene"
},
{
"created": "2022-09-05T08:01:29.657431+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.315",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: CHKA were changed from Neurodevelopmental disorder, MONDO:0700092; Abnormal muscle tone; Global developmental delay; Intellectual disability; Seizures; Microcephaly; Abnormality of movement; Abnormality of nervous system morphology; Short stature to Neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures, MIM#620023",
"entity_name": "CHKA",
"entity_type": "gene"
},
{
"created": "2022-09-05T08:01:02.812411+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.314",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: CHKA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures, MIM#620023; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "CHKA",
"entity_type": "gene"
},
{
"created": "2022-09-03T20:24:37.308725+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.1657",
"user_name": "Konstantinos Varvagiannis",
"item_type": "entity",
"text": "reviewed gene: CAPRIN1: Rating: AMBER; Mode of pathogenicity: None; Publications: 35979925, 35977029, 28135719, 31398340, https://doi.org/10.1101/2021.12.20.21267194; Phenotypes: Global developmental delay, Delayed speech and language development, Intellectual disability, Autistic behavior, Seizures; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown",
"entity_name": "CAPRIN1",
"entity_type": "gene"
},
{
"created": "2022-09-03T20:24:27.200908+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.4928",
"user_name": "Konstantinos Varvagiannis",
"item_type": "entity",
"text": "reviewed gene: CAPRIN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35979925, 35977029, 28135719, 31398340, https://doi.org/10.1101/2021.12.20.21267194; Phenotypes: Global developmental delay, Delayed speech and language development, Intellectual disability, Autistic behavior, Seizures; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown",
"entity_name": "CAPRIN1",
"entity_type": "gene"
},
{
"created": "2022-09-03T20:14:04.152271+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.1657",
"user_name": "Konstantinos Varvagiannis",
"item_type": "entity",
"text": "gene: UBAP2L was added\ngene: UBAP2L was added to Genetic Epilepsy. Sources: Literature\nMode of inheritance for gene: UBAP2L was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown\nPublications for gene: UBAP2L were set to 35977029\nPhenotypes for gene: UBAP2L were set to Delayed speech and language development; Motor delay; Intellectual disability; Autistic behavior; Seizures; Microcephaly; Abnormality of head or neck; Short stature; Abnormality of the skeletal system\nPenetrance for gene: UBAP2L were set to unknown\nReview for gene: UBAP2L was set to AMBER\nAdded comment: Seizures have been reported in several individuals although a formal diagnosis of epilepsy was retained in ~30% in a small cohort discussed below. Consider inclusion with amber rating.\r\n\r\n-----\r\n\r\nBased on Jia et al (2022 - PMID: 35977029) speech, motor delay as well as ID are observed in individuals harboring de novo pLoF variants in UBAP2L. The gene encodes a regulator of the stress granule (SG) assembly. Extensive evidence is provided on the effect of variants as well as the role of UBAP2L and other genes for components and/or regulation of SG in pathogenesis of NDDs. Among others a Ubap2l htz deletion mouse model (behavioral and cognitive impairment, abnormal cortical development due to impaired SG assembly, etc). Data from 26 previous studies, aggregating 40,853 probands with NDDs (mostly DD/ID, also ASD) suggest enrichment for DNMs in UBAP2L or other genes previously known and further shown to be important for SG formation (incl. G3BP1/G3BP2, CAPRIN1). \r\n\r\nDetails provided below.\r\n\r\nNot associated with any phenotype in OMIM, G2P or SysNDD.\r\n\r\n--------\r\n\r\nJia et al (2022 - PMID: 35977029) describe 12 affected individuals with heterozygous de novo pLoF variants in UBAP2L. \r\n\r\nPhenotype: Features included hypotonia, speech (11/11) and motor delay (8/12), ID (8/10 with formal evaluation), variable behavioral concerns (ADHD 5/11, ASD in 4/10, etc). Seizures were reported in 7/12 with 3/10 having a formal diagnosis of epilepsy. Few had microcephaly (3/10). Facial dysmorphisms were common (9/9) and included abnormal palpebral fissures, deep prominent concha, high broad forehead, hypertelorism, thin upper lip and mild synophrys (each in 4 or less individuals). Short stature or skeletal alterations were described in some (4/10 each).\r\n\r\nRole of the gene: UBAP2L encodes an essential regulator of stress granule assembly. Stress granules are membraneless cytoplasmic compartments in eukaryotic cells, induced upon a variety of stressors and playing a role in regulation of gene expression. \r\n\r\nVariants identified : 9 nonsense/frameshift UBAP2L variants and 3 splicing ones were reported, in all cases as de novo events, upon trio/quad exome sequencing. All were absent from gnomAD. There were no other causative variants.\r\n\r\nVariant effect/studies (NM_014847.4 / NP_055662.3) : \r\n- Minigene assays revealed that the 3 splice variants all resulted in out-of-frame exon skipping. \r\n- In patient fibroblasts one of these splice variants was demonstrated to result to reduced protein levels.\r\n- 8 of the 9 nonsense/frameshift variants were predicted to result to NMD.\r\n- 1 nonsense variant (c.88C>T/p.Q30*) was shown to result to decreased protein expression in patient fibroblasts, with detection of the protein using an antibody for the C terminus but not the N terminus. Protein N-terminal sequencing confirmed that the protein lacked the N terminus, with utilization of an alternative start site (11 codons downstream).\r\n- Generation of HeLa UBAP2L KO cell lines resulted in significant reduction of SG numbers which was also the case for 4 variants studied, under stress conditions.\r\n- The protein has a DUF domain (aa 495-526) known to mediate interaction of UBAP2L with G3BP1 (a stress granule marker) with deletions of this domain leading to shuttling of UBAP2L from the cytoplasm to the nucleus. Truncating variants upstream of the DUF domain were shown to result in nuclear localization.\r\n\r\nMouse model : \r\n- The authors generated Ubap2l KO model with hmz deletion of Ubap2l resulting in a lethal phenotype (2.6% survived) and htz deletion leading to behavioral issues (low preference for social novelty, anxious-like behaviors) and cognitive impairment.\r\n- Ubap2l haploinsufficiency resulted in abnormal cortical development and lamination with reduction of neural progenitor proliferation.\r\n- Ubap2l deficiency was shown to impair SG assembly during cortical development both under physiological stress conditions or upon utilization of an oxidative stress inducer.\r\n\r\nAdditional evidence of UBAP2L and SG overall in pathogenesis of NDDs:\r\n- Based on DNMs from 40,853 individuals with NDDs from 26 studies (9,228 with ASD, 31,625 with DD/ID) the authors demonstrate significant excess of DNM in 31 genes encoding SG components, regulators or both, the latter being the case for UBAP2L and 2 further genes (G3BP1 and G3BP2 - both with crucial roles in SG assembly).\r\n- Excess dn splice-site (N=3) and missense (N=5) variants in G3BP1 were observed in the above cohort [c.95+1G>A, c.353+1G>T, c.539+1G>A / p.S208C, R320C, V366M].\r\n- Excess dn missense (N=7) variants in G3BP2 were observed in the above cohort [p.R13W, D151N, E158K, L209P, E399D, K408E, R438C].\r\n- Generation of G3BP1 or G3BP2 KO HeLa cell lines and immunofluorescence upon use of oxidative stress inducer revealed significant reduction of stress granules.\r\n- Generation of HeLa cell lines for 5 G3BP1 mutants (R78C*, R132I*, S208C*, R320C*, V366M) and 7 G3BP2 mutants (p.R13W*, D151N*, E158K, L209P*, E399D, K408E, R438C) revealed that several (those in asterisk) resulted in significantly fewer SG formation under oxidative stress compared to WT while the subcellular distribution of the proteins under stress was identical to WT.\r\n- Among the identified genes for SG enriched for DNMs, CAPRIN1 was implicated in previous publications as a NDD risk gene with 3 dn missense SNVs reported (p.I373K, p.Q446H, p.L484P). CAPRIN1 binding to G3BP1/2 has been shown to promote SG formation. Significant reduction of SG was observed in CAPRIN1 KO HeLa lines. p.I373K abolished interaction with G3BP1/2 and disrupted SG formation. \nSources: Literature",
"entity_name": "UBAP2L",
"entity_type": "gene"
},
{
"created": "2022-09-03T20:14:00.257672+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.4928",
"user_name": "Konstantinos Varvagiannis",
"item_type": "entity",
"text": "gene: UBAP2L was added\ngene: UBAP2L was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: UBAP2L was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown\nPublications for gene: UBAP2L were set to 35977029\nPhenotypes for gene: UBAP2L were set to Delayed speech and language development; Motor delay; Intellectual disability; Autistic behavior; Seizures; Microcephaly; Abnormality of head or neck; Short stature; Abnormality of the skeletal system\nPenetrance for gene: UBAP2L were set to unknown\nReview for gene: UBAP2L was set to GREEN\nAdded comment: Based on Jia et al (2022 - PMID: 35977029) speech, motor delay as well as ID are observed in individuals harboring de novo pLoF variants in UBAP2L. The gene encodes a regulator of the stress granule (SG) assembly. Extensive evidence is provided on the effect of variants as well as the role of UBAP2L and other genes for components and/or regulation of SG in pathogenesis of NDDs. Among others a Ubap2l htz deletion mouse model (behavioral and cognitive impairment, abnormal cortical development due to impaired SG assembly, etc). Data from 26 previous studies, aggregating 40,853 probands with NDDs (mostly DD/ID, also ASD) suggest enrichment for DNMs in UBAP2L or other genes previously known and further shown to be important for SG formation (incl. G3BP1/G3BP2, CAPRIN1). \r\n\r\nDetails provided below.\r\n\r\nNot associated with any phenotype in OMIM, G2P or SysNDD.\r\n\r\n--------\r\n\r\nJia et al (2022 - PMID: 35977029) describe 12 affected individuals with heterozygous de novo pLoF variants in UBAP2L. \r\n\r\nPhenotype: Features included hypotonia, speech (11/11) and motor delay (8/12), ID (8/10 with formal evaluation), variable behavioral concerns (ADHD 5/11, ASD in 4/10, etc). Seizures were reported in 7/12 with 3/10 having a formal diagnosis of epilepsy. Few had microcephaly (3/10). Facial dysmorphisms were common (9/9) and included abnormal palpebral fissures, deep prominent concha, high broad forehead, hypertelorism, thin upper lip and mild synophrys (each in 4 or less individuals). Short stature or skeletal alterations were described in some (4/10 each).\r\n\r\nRole of the gene: UBAP2L encodes an essential regulator of stress granule assembly. Stress granules are membraneless cytoplasmic compartments in eukaryotic cells, induced upon a variety of stressors and playing a role in regulation of gene expression. \r\n\r\nVariants identified : 9 nonsense/frameshift UBAP2L variants and 3 splicing ones were reported, in all cases as de novo events, upon trio/quad exome sequencing. All were absent from gnomAD. There were no other causative variants.\r\n\r\nVariant effect/studies (NM_014847.4 / NP_055662.3) : \r\n- Minigene assays revealed that the 3 splice variants all resulted in out-of-frame exon skipping. \r\n- In patient fibroblasts one of these splice variants was demonstrated to result to reduced protein levels.\r\n- 8 of the 9 nonsense/frameshift variants were predicted to result to NMD.\r\n- 1 nonsense variant (c.88C>T/p.Q30*) was shown to result to decreased protein expression in patient fibroblasts, with detection of the protein using an antibody for the C terminus but not the N terminus. Protein N-terminal sequencing confirmed that the protein lacked the N terminus, with utilization of an alternative start site (11 codons downstream).\r\n- Generation of HeLa UBAP2L KO cell lines resulted in significant reduction of SG numbers which was also the case for 4 variants studied, under stress conditions.\r\n- The protein has a DUF domain (aa 495-526) known to mediate interaction of UBAP2L with G3BP1 (a stress granule marker) with deletions of this domain leading to shuttling of UBAP2L from the cytoplasm to the nucleus. Truncating variants upstream of the DUF domain were shown to result in nuclear localization.\r\n\r\nMouse model : \r\n- The authors generated Ubap2l KO model with hmz deletion of Ubap2l resulting in a lethal phenotype (2.6% survived) and htz deletion leading to behavioral issues (low preference for social novelty, anxious-like behaviors) and cognitive impairment.\r\n- Ubap2l haploinsufficiency resulted in abnormal cortical development and lamination with reduction of neural progenitor proliferation.\r\n- Ubap2l deficiency was shown to impair SG assembly during cortical development both under physiological stress conditions or upon utilization of an oxidative stress inducer.\r\n\r\nAdditional evidence of UBAP2L and SG overall in pathogenesis of NDDs:\r\n- Based on DNMs from 40,853 individuals with NDDs from 26 studies (9,228 with ASD, 31,625 with DD/ID) the authors demonstrate significant excess of DNM in 31 genes encoding SG components, regulators or both, the latter being the case for UBAP2L and 2 further genes (G3BP1 and G3BP2 - both with crucial roles in SG assembly).\r\n- Excess dn splice-site (N=3) and missense (N=5) variants in G3BP1 were observed in the above cohort [c.95+1G>A, c.353+1G>T, c.539+1G>A / p.S208C, R320C, V366M].\r\n- Excess dn missense (N=7) variants in G3BP2 were observed in the above cohort [p.R13W, D151N, E158K, L209P, E399D, K408E, R438C].\r\n- Generation of G3BP1 or G3BP2 KO HeLa cell lines and immunofluorescence upon use of oxidative stress inducer revealed significant reduction of stress granules.\r\n- Generation of HeLa cell lines for 5 G3BP1 mutants (R78C*, R132I*, S208C*, R320C*, V366M) and 7 G3BP2 mutants (p.R13W*, D151N*, E158K, L209P*, E399D, K408E, R438C) revealed that several (those in asterisk) resulted in significantly fewer SG formation under oxidative stress compared to WT while the subcellular distribution of the proteins under stress was identical to WT.\r\n- Among the identified genes for SG enriched for DNMs, CAPRIN1 was implicated in previous publications as a NDD risk gene with 3 dn missense SNVs reported (p.I373K, p.Q446H, p.L484P). CAPRIN1 binding to G3BP1/2 has been shown to promote SG formation. Significant reduction of SG was observed in CAPRIN1 KO HeLa lines. p.I373K abolished interaction with G3BP1/2 and disrupted SG formation. \nSources: Literature",
"entity_name": "UBAP2L",
"entity_type": "gene"
},
{
"created": "2022-09-02T17:25:44.740882+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.189",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Classified gene: ARSK as Green List (high evidence)",
"entity_name": "ARSK",
"entity_type": "gene"
},
{
"created": "2022-09-02T17:25:44.729909+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.189",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Gene: arsk has been classified as Green List (High Evidence).",
"entity_name": "ARSK",
"entity_type": "gene"
},
{
"created": "2022-09-02T17:20:19.804461+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.188",
"user_name": "Bryony Thompson",
"item_type": "panel",
"text": "Panel types changed to Victorian Clinical Genetics Services; Royal Melbourne Hospital",
"entity_name": null,
"entity_type": null
},
{
"created": "2022-09-02T17:17:20.253720+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.187",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Marked gene: PAM16 as ready",
"entity_name": "PAM16",
"entity_type": "gene"
},
{
"created": "2022-09-02T17:17:20.245891+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.187",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Gene: pam16 has been classified as Green List (High Evidence).",
"entity_name": "PAM16",
"entity_type": "gene"
},
{
"created": "2022-09-02T17:17:06.788709+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.187",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Classified gene: PAM16 as Green List (high evidence)",
"entity_name": "PAM16",
"entity_type": "gene"
},
{
"created": "2022-09-02T17:17:06.777458+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.187",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Gene: pam16 has been classified as Green List (High Evidence).",
"entity_name": "PAM16",
"entity_type": "gene"
},
{
"created": "2022-09-02T17:15:31.344356+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.186",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Marked gene: MIR17HG as ready",
"entity_name": "MIR17HG",
"entity_type": "gene"
},
{
"created": "2022-09-02T17:15:31.329967+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.186",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Gene: mir17hg has been classified as Green List (High Evidence).",
"entity_name": "MIR17HG",
"entity_type": "gene"
},
{
"created": "2022-09-02T17:14:01.879991+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.186",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Classified gene: MIR17HG as Green List (high evidence)",
"entity_name": "MIR17HG",
"entity_type": "gene"
},
{
"created": "2022-09-02T17:14:01.870839+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.186",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Gene: mir17hg has been classified as Green List (High Evidence).",
"entity_name": "MIR17HG",
"entity_type": "gene"
},
{
"created": "2022-09-02T16:44:00.610549+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.185",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Deleted their review",
"entity_name": "WDPCP",
"entity_type": "gene"
},
{
"created": "2022-09-02T16:43:55.273589+10:00",
"panel_name": "Skeletal dysplasia",
"panel_id": 258,
"panel_version": "0.185",
"user_name": "Bryony Thompson",
"item_type": "entity",
"text": "Deleted their review",
"entity_name": "TTC8",
"entity_type": "gene"
},
{
"created": "2022-09-02T16:07:06.753042+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.1657",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: SLC31A1 as ready",
"entity_name": "SLC31A1",
"entity_type": "gene"
},
{
"created": "2022-09-02T16:07:06.741377+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.1657",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: slc31a1 has been classified as Red List (Low Evidence).",
"entity_name": "SLC31A1",
"entity_type": "gene"
},
{
"created": "2022-09-02T16:06:59.008313+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.1657",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: SLC31A1 as Red List (low evidence)",
"entity_name": "SLC31A1",
"entity_type": "gene"
},
{
"created": "2022-09-02T16:06:59.001002+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.1657",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: slc31a1 has been classified as Red List (Low Evidence).",
"entity_name": "SLC31A1",
"entity_type": "gene"
},
{
"created": "2022-09-02T16:06:10.379955+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.314",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: SLC31A1 as ready",
"entity_name": "SLC31A1",
"entity_type": "gene"
},
{
"created": "2022-09-02T16:06:10.368522+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.314",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: slc31a1 has been classified as Red List (Low Evidence).",
"entity_name": "SLC31A1",
"entity_type": "gene"
},
{
"created": "2022-09-02T16:05:51.982401+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.314",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: SLC31A1 as Red List (low evidence)",
"entity_name": "SLC31A1",
"entity_type": "gene"
},
{
"created": "2022-09-02T16:05:51.974459+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "1.314",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: slc31a1 has been classified as Red List (Low Evidence).",
"entity_name": "SLC31A1",
"entity_type": "gene"
},
{
"created": "2022-09-02T16:04:45.408649+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.4928",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: SLC31A1 as ready",
"entity_name": "SLC31A1",
"entity_type": "gene"
}
]
}