Submissions for variant NM_002180.2(IGHMBP2):c.1582G>A (p.Ala528Thr) (rs724159960)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000236327	SCV000293148	likely pathogenic	not provided	2015-09-23	criteria provided, single submitter	clinical testing	An A528T variant that is likely pathogenic has been identified in the IGHMBP2 gene. The A528T variant has been previously reported in two siblings with CMT2 who had another rare variant on the opposite allele (Cottenie et al., 2014). It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The A528T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, this variant is a strong candidate for a pathogenic mutation, however the possibility that it is a benign variant cannot be excluded
OMIM	RCV000149578	SCV000196554	pathogenic	Charcot-Marie-Tooth disease, axonal, type 2S	2014-11-06	no assertion criteria provided	literature only