ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.2510C>A (p.Ala837Asp) (rs756338201)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589319 SCV000697886 uncertain significance not provided 2017-03-13 criteria provided, single submitter clinical testing Variant summary: The DSG2 c.2510C>A (p.Ala837Asp) variant located in the Catenin binding domain (via InterPro) involves the alteration of a conserved nucleotide that 4/4 in silico tools (SNPs&GO not captured due to low reliability index) predict a damaging outcome, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 3/120474 (1/40160), which does exceed the estimated maximal expected allele frequency for a pathogenic DSG2 variant of 1/100000, suggesting this variant could be a rare benign polymorphism. However, this observation needs to be cautiously considered due to the cohort containing individuals that could harbor a DSG2 phenotype. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories. Therefore, until additional information becomes available (ie, clinical and functional studies), the variant of interest has been classified as a "Variant of Uncertain Significance - Possibly Benign (VUS)."
Color Health, Inc RCV001185321 SCV001351510 uncertain significance Cardiomyopathy 2019-11-05 criteria provided, single submitter clinical testing
Invitae RCV001201605 SCV001372682 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 10 2020-06-27 criteria provided, single submitter clinical testing This sequence change replaces alanine with aspartic acid at codon 837 of the DSG2 protein (p.Ala837Asp). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and aspartic acid. This variant is present in population databases (rs756338201, ExAC 0.01%). This variant has not been reported in the literature in individuals with DSG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 496149). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.