ClinVar Miner

Submissions for variant NM_024422.6(DSC2):c.1971C>A (p.Gly657=) (rs397517396)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000039416 SCV000063100 likely benign not specified 2012-08-22 criteria provided, single submitter clinical testing Gly657Gly in exon 13 of DSC2: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. Gly657Gly in exon 13 of DSC2 (allele frequenc y = n/a)
Integrated Genetics/Laboratory Corporation of America RCV000039416 SCV000917285 benign not specified 2018-12-26 criteria provided, single submitter clinical testing Variant summary: DSC2 c.1971C>A alters a non-conserved nucleotide resulting in a synonymous change. 4/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 6.9e-05 in 245192 control chromosomes, predominantly within the East Asian subpopulation at a frequency of 0.001 in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 100-fold of the estimated maximal expected allele frequency for a pathogenic variant in DSC2 causing Arrhythmia phenotype (1e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. To our knowledge, no occurrence of c.1971C>A in individuals affected with Arrhythmia and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign.
Illumina Clinical Services Laboratory,Illumina RCV001126574 SCV001285794 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 11 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory 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, this variant 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, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Color RCV001182266 SCV001347659 likely benign Cardiomyopathy 2018-12-13 criteria provided, single submitter clinical testing

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