Submissions for variant NM_207122.2(EXT2):c.1087G>A (p.Val363Met)

gnomAD frequency: 0.00046  dbSNP: rs138943091

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000821752	SCV000371845	likely benign	Exostoses, multiple, type 2	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Invitae	RCV000821752	SCV000962521	likely benign	Exostoses, multiple, type 2	2023-11-18	criteria provided, single submitter	clinical testing
St. Jude Molecular Pathology, St. Jude Children's Research Hospital	RCV000821752	SCV002584571	uncertain significance	Exostoses, multiple, type 2	2022-07-05	criteria provided, single submitter	clinical testing	The EXT2 c.1186G>A (p.Val396Met) missense change has a maximum subpopulation frequency of 0.073% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL predicts a deleterious effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with hereditary multiple exostoses. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003316474	SCV004017521	likely benign	Exostoses, multiple, type 1	2023-07-07	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003391070	SCV004120553	uncertain significance	EXT2-related disorder	2023-01-18	criteria provided, single submitter	clinical testing	The EXT2 c.1087G>A variant is predicted to result in the amino acid substitution p.Val363Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.073% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-44151602-G-A), which is likely too common for an undocumented disease-causing variant. Although we suspect this variant may be benign, at this time its clinical significance is uncertain due to the absence of conclusive functional and genetic evidence.