Submissions for variant NM_207122.2(EXT2):c.497G>A (p.Arg166His)

gnomAD frequency: 0.00002  dbSNP: rs772821141

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV002044320	SCV002113575	uncertain significance	Exostoses, multiple, type 2	2023-08-25	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 166 of the EXT2 protein (p.Arg166His). This variant is present in population databases (rs772821141, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with EXT2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1348443). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt EXT2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University	RCV003154044	SCV003843836	benign	Ovarian cancer	2022-01-01	criteria provided, single submitter	clinical testing