ClinVar Miner

Submissions for variant NM_002072.5(GNAQ):c.143G>T (p.Gly48Val)

dbSNP: rs2118276763
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital RCV002254468 SCV002525659 pathogenic not provided 2021-01-28 criteria provided, single submitter clinical testing To our knowledge, this variant has not been reported in association with capillary malformations (CM) or arteriovenous malformations (AVM) before. Alteration of p.Gly48 in GNAQ has recently been reported as an oncogenic hotspot for uveal melanoma (PMID: 33229459). The p.Gly48Val variant is also reported in the cBioPortal and NCI Genomic Data Commons cancer databases and is a cause of cherry hemangiomas and cherry hemangioma-like hemangiomas (PMID: 31189994). This variant is absent from large population studies as a germline finding (Genome Aggregation Database v2.1.1).
Clinical Genomics Laboratory, Washington University in St. Louis RCV003458178 SCV004176901 likely pathogenic Sturge-Weber syndrome 2023-08-30 criteria provided, single submitter clinical testing The GNAQ c.143G>T (p.Gly48Val) variant was identified at an allelic fraction consistent with somatic origin. This variant has been reported in one individual affected with uveal melanoma and two individuals affected with atypical Sturge-Weber syndrome (Hitchman TD et al., PMID: 33229459; Yeom S et al., PMID: 36710374). It has been reported in the ClinVar database as a somatic pathogenic by a single submitter (ClinVar ID: 1691370). GNAQ c.143G>T (p.Gly48Val) is absent from the general population (gnomAD v.3.1.2), indicating it is not a common variant. Computational predictors indicate that the variant is damaging, evidence that correlates with impact to GNAQ function. Functional studies using cells generated with the variant of interest grafted into an organism results in an aberrant cell growth phenotype in the organism and hyperactivation of downstream signaling pathway (Huang L et al., PMID: 34670408; Hitchman TD et al., PMID: 33229459). Based on an internally-developed protocol informed by the ACMG/AMP guidelines (Richards S et al., PMID: 25741868), GNAQ c.143G>T (p.Gly48Val) variant is classified as likely pathogenic.

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