ClinVar Miner

Submissions for variant NM_021957.4(GYS2):c.1974dup (p.Val659fs)

gnomAD frequency: 0.00001  dbSNP: rs1181756742
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000778362 SCV000914577 uncertain significance Glycogen storage disorder due to hepatic glycogen synthase deficiency 2018-12-05 criteria provided, single submitter clinical testing The GYS2 c.1974dupT (p.Val659CysfsTer4) variant results in a frameshift and is predicted to result in premature termination of the protein. It was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018) and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score for this variant, it could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene and cDNA change, and amino acid change. No publications were found based on this search. This variant is located in the last exon and may escape nonsense-mediated decay. Due to the potential impact of frameshift variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for this disease.
Invitae RCV000778362 SCV002167328 uncertain significance Glycogen storage disorder due to hepatic glycogen synthase deficiency 2021-03-03 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals with GYS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 631679). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Val659Cysfs*4) in the GYS2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 45 amino acid(s) of the GYS2 protein.

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