ClinVar

Description

A variant of uncertain significance has been identified in the DHCR7 gene. The G423S variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The G423S variant is not observed large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The G423S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Furthermore, missense variants in nearby residues (G424C, H426P) have been reported in the Human Gene Mutation Database in association with Smith-Lemli-Opitz syndrome (Stenson et al., 2014). Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.