ClinVar

Description

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)."