ClinVar

Description

Variant summary: BBS10 c.1736A>G (p.Lys579Arg) results in a conservative amino acid change located in the Intermediate domain (Stoetzel_NatGen_2006) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00052 in 120630 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in BBS10 causing Bardet-Biedl Syndrome (0.00052 vs 0.0013), allowing no conclusion about variant significance. c.1736A>G has been reported in the literature in individuals affected with Bardet-Biedl Syndrome (Stoetzel_NatGen_2006). This report does not provide unequivocal conclusions about association of the variant with Bardet-Biedl Syndrome. At least one publication reports experimental evidence evaluating an impact on protein function, however, does not allow convincing conclusions about the variant effect. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.