ClinVar

Description

Variant summary: DHCR7 c.521T>C (p.Phe174Ser) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 251044 control chromosomes. c.521T>C has been reported in the literature as a compound heterozygous genotype in at-least two individuals affected with Smith-Lemli-Opitz Syndrome, one of whom was reported as having a milder phenotypic presentation (example, Cardoso_2005, Tucci_2016). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely pathogenic and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.