ClinVar

Description

Variant summary: HSD3B2 c.809T>C (p.Ile270Thr) results in a non-conservative amino acid change located in the 3-beta hydroxysteroid dehydrogenase/isomerase domain (IPR00225) 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 0.00046 in 251256 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in HSD3B2 causing Congenital Adrenal Hyperplasia (0.00046 vs 0.0013), allowing no conclusion about variant significance. c.809T>C has been reported in the literature in at least one individual affected with clinical features of Congenital Adrenal Hyperplasia. However, this report does not provide unequivocal conclusions about association of the variant with Congenital Adrenal Hyperplasia. 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: 30668521). Five submitters have cited clinical-significance assessments for this variant to ClinVar after 2014; all submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.