Activity
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| Intellectual disability v11.24 | GIGYF1 | Achchuthan Shanmugasundram Publications for gene: GIGYF1 were set to 33057194; 35917186; 36924980 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v11.23 | GIGYF1 |
Achchuthan Shanmugasundram changed review comment from: Comment on list classification: This gene is identified with significant enrichment in multiple large cohorts of autism spectrum disorder patients. Detailed clinical information was only available for a small subset of patients, from which intellectual disability was reported in 11/25 patients. However, severity of ID was not provided for any of these patients. Hence, this gene is rated amber with 'watchlist' tag added.; to: Comment on list classification: GIGYF1 shows statistically robust de novo enrichment for a complex neurodevelopmental disorder across three large cohorts of autism spectrum disorder patients (PMID:33057194, PMID:35917192, PMID:36924980), with supporting functional data in cell and animal models. However, only 25 individuals across the literature have detailed clinical phenotyping, of whom 11 had confirmed ID (no severity reported). Although ClinGen rated it 'Definitive' for complex neurodevelopmental disorder, ClinGen's own review flags unresolved penetrance given recurrence of variants in unaffected parents/population controls. Gene2Phenotype recently downgraded this gene from 'moderate' to 'limited' confidence on the DD panel, and OMIM has no phenotype association as of August 2026. Hence, this gene is rated amber based on all these evidences. The 'watchlist' tag has been added as recommendation for re-review as additional deeply phenotyped ID/GDD cases are published. |
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| Intellectual disability v11.23 | GIGYF1 |
Achchuthan Shanmugasundram changed review comment from: PMID:33057194 (2020) - This gene has been identified with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 14 de novo variants (4 frameshift, 5 missense, 1 splice donor, 3 stopgain, 1 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided). PMID:35917186 (2022) - 60 individuals carrying 35 distinct GIGYF1 likely gene-disruptive (LGD) variants, identified from SPARK/SSC autism cohorts (20,452 trios + 12,227 singletons) plus 7 additional GeneMatcher-ascertained probands. This cohort was ascertained specifically through ASD registries, so detailed non-ASD clinical/developmental phenotyping (including formal ID assessment) was not systematically reported for most of the 60 individuals. However, detailed clinical information was available for 11 patients, of which 9 patients had ASD, 10 had speech-language issues, 3 had motor delays, and 6 had ID. Severity of ID has not been provided for any of these patients. PMID:36924980 (2023) - 26 de novo variants identified across a combined 44,665 NDD trios (ASD-primary and DD-primary cohorts). Of these, detailed clinical information was obtained for only 14 probands, of which 12 had ASD, 5 had DD, 5 had ID, 3 had motor delay and 8 had speech delay. Severity of ID has not been provided for any of these patients. This gene has not yet been associated with any relevant phenotype in OMIM (last accessed 16 August 2026), but associated with GIGYF1-related developmental disorder with 'limited' rating on the DD panel of Gene2Phenotype. This gene has been associated with 'Definitive' rating for complex neurodevelopmental disorder (MONDO:0100038) by Intellectual Disability and Autism GCEP in ClinGen (https://search.clinicalgenome.org/CCID:009351).; to: PMID:33057194 (2020) - This gene has been identified with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 14 de novo variants (4 frameshift, 5 missense, 1 splice donor, 3 stopgain, 1 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided). PMID:35917186 (2022) - 60 individuals carrying 35 distinct GIGYF1 likely gene-disruptive (LGD) variants, identified from SPARK/SSC autism cohorts (20,452 trios + 12,227 singletons) plus 7 additional GeneMatcher-ascertained probands. This cohort was ascertained specifically through ASD registries, so detailed non-ASD clinical/developmental phenotyping (including formal ID assessment) was not systematically reported for most of the 60 individuals. However, detailed clinical information was available for 11 patients, of which 9 patients had ASD, 10 had speech-language issues, 3 had motor delays, and 6 had ID. Severity of ID has not been provided for any of these patients. PMID:36924980 (2023) - 26 de novo variants identified across a combined 44,665 NDD trios (ASD-primary and DD-primary cohorts). Of these, detailed clinical information was obtained for only 14 probands, of which 12 had ASD, 5 had DD, 5 had ID, 3 had motor delay and 8 had speech delay. Severity of ID has not been provided for any of these patients. The pLI = 0 in gnomAD v4.1.1 for GIGYF indicating lack of constraint against LOF. This gene has not yet been associated with any relevant phenotype in OMIM (last accessed 16 August 2026), but associated with GIGYF1-related developmental disorder with 'limited' rating on the DD panel of Gene2Phenotype. This gene was previously rated 'moderate/ on the DD panel in G2P and has been demoted in the last year. This gene has been associated with 'Definitive' rating for complex neurodevelopmental disorder (MONDO:0100038) by Intellectual Disability and Autism GCEP in ClinGen (https://search.clinicalgenome.org/CCID:009351). However, ClinGen review noted that individuals with similar variants have also been observed in the general population or in reportedly unaffected parents of affected individuals, and deep phenotyping of parents in these studies is often unavailable. In addition, the extent of reduced penetrance and variable expressivity is currently unknown (PMID:35917186). |
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| Intellectual disability v11.23 | GIGYF1 | Achchuthan Shanmugasundram Classified gene: GIGYF1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v11.23 | GIGYF1 | Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene is identified with significant enrichment in multiple large cohorts of autism spectrum disorder patients. Detailed clinical information was only available for a small subset of patients, from which intellectual disability was reported in 11/25 patients. However, severity of ID was not provided for any of these patients. Hence, this gene is rated amber with 'watchlist' tag added. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v11.23 | GIGYF1 | Achchuthan Shanmugasundram Gene: gigyf1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v11.22 | GIGYF1 | Achchuthan Shanmugasundram Tag watchlist tag was added to gene: GIGYF1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v11.22 | GIGYF1 | Achchuthan Shanmugasundram Phenotypes for gene: GIGYF1 were changed from Developmental disorder to autism spectrum disorder, MONDO:0005258; neurodevelopmental disorder, MONDO:0700092 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v11.21 | GIGYF1 | Achchuthan Shanmugasundram Publications for gene: GIGYF1 were set to 33057194 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v11.20 | GIGYF1 | Achchuthan Shanmugasundram reviewed gene: GIGYF1: Rating: AMBER; Mode of pathogenicity: None; Publications: 33057194, 35917186, 36924980; Phenotypes: autism spectrum disorder, MONDO:0005258, neurodevelopmental disorder, MONDO:0700092; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v10.30 | GIGYF1 | Jana Jezkova reviewed gene: GIGYF1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 35917186, 36924980, 36189799, 31439631; Phenotypes: ASD, NDD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.580 | GIGYF1 | Ivone Leong Classified gene: GIGYF1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.580 | GIGYF1 | Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). There is not enough evidence to support a gene-disease association so this gene has been given an Amber rating. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.580 | GIGYF1 | Ivone Leong Gene: gigyf1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v3.510 | GIGYF1 |
Zornitza Stark gene: GIGYF1 was added gene: GIGYF1 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: GIGYF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GIGYF1 were set to 33057194 Phenotypes for gene: GIGYF1 were set to Developmental disorder Review for gene: GIGYF1 was set to AMBER Added comment: PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 14 de novo variants (4 frameshift, 5 missense, 1 splice donor, 3 stopgain, 1 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided hence Amber rating). Sources: Literature |
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