ClinVar

Description

Variant summary: HSD11B2 c.440G>A (p.Arg147His) results in a non-conservative amino acid change in 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 0.0002 in 250992 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in HSD11B2 causing Apparent Mineralocorticoid Excess (0.0002 vs 0.0035), allowing no conclusion about variant significance. c.440G>A has been reported in the literature in individuals affected with hypertension without strong evidence of causality and at a similar frequency as the general population (Kamide_2006). This report does not provide unequivocal conclusions about association of the variant with Apparent Mineralocorticoid Excess. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 16778331). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014, and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.