ClinVar

Description

Variant summary: BBS10 c.1956C>G (p.Tyr652X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein. While it is not expected to undergo nonsense-mediated decay, it eliminates the last 71 amino acids from the encoded protein. Variants downstream of this position have been classified as pathogenic by our laboratory (p.Val707X, CV ID 406221) and in ClinVar (c.2044dup/p.Met682fs CV ID 1454610, c.2052del/ p.Lys684fs CV ID 952132). This suggests that this is a clinically significant region of the protein. The variant was absent in 251128 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1956C>G in individuals affected with Bardet-Biedl Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as Pathogenic.