ClinVar

Description

Variant summary: IGHMBP2 c.790C>T (p.Arg264Cys) results in a non-conservative amino acid change located in the AAA+ ATPase domain (IPR003593) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.2e-05 in 251456 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.790C>T has been reported in the literature in a heterozygous individual affected with Charcot-Marie-Tooth Disease without a second variant identified (Yalcintepe_2021). This report does not provide unequivocal conclusions about association of the variant with Charcot-Marie-Tooth Disease, Axonal, Type 2S. 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: 34169998). One submitter has cited a clinical-significance assessment for this variant to ClinVar after 2014 and has classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as uncertain significance.