ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.829-4G>A (rs376424003)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000441755 SCV000515741 likely benign not specified 2016-12-22 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000457361 SCV000561389 likely benign Arrhythmogenic right ventricular cardiomyopathy, type 10 2020-11-11 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000441755 SCV000711381 likely benign not specified 2016-05-27 criteria provided, single submitter clinical testing c.829-4G>A in intron 7 of DSG2: This variant is not expected to have clinical si gnificance because it is not located within the splice consensus sequence. It ha s been identified in 1/3660 African American chromosomes by the NHLBI Exome Sequ encing Project (; dbSNP rs376424003).
Ambry Genetics RCV000618425 SCV000735838 uncertain significance Cardiovascular phenotype 2020-03-27 criteria provided, single submitter clinical testing The c.829-4G>A intronic variant results from a G to A substitution 4 nucleotides upstream from coding exon 8 in the DSG2 gene. This nucleotide position is not well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this splice acceptor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000441755 SCV000917289 uncertain significance not specified 2018-07-31 criteria provided, single submitter clinical testing Variant summary: DSG2 c.829-4G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 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 6.5e-05 in 30968 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.829-4G>A in individuals affected with Arrhythmia and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 with conflicting assessments, including uncertain significance (1x) and likely benign (3x). Based on the evidence outlined above, the variant was classified as uncertain significance.
Color Health, Inc RCV001184559 SCV001350568 likely benign Cardiomyopathy 2019-01-06 criteria provided, single submitter clinical testing

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