Submissions for variant NM_000059.4(BRCA2):c.2679A>G (p.Gln893=)

dbSNP: rs786203640

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000167041	SCV000217866	uncertain significance	Hereditary cancer-predisposing syndrome	2021-12-29	criteria provided, single submitter	clinical testing	The c.2679A>G variant (also known as p.Q893Q), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 2679. This nucleotide substitution does not change the glutamine at codon 893. This nucleotide position is well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to create a new alternate splice acceptor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV002478517	SCV000600519	uncertain significance	not provided	2023-05-31	criteria provided, single submitter	clinical testing	To the best of our knowledge, this variant has not been reported in the published literature. It also has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on BRCA2 mRNA splicing yielded predictions that this variant may result in the gain of a cryptic splice site without affecting the natural splice sites . Based on the available information, we are unable to determine the clinical significance of this variant.
Color Diagnostics, LLC DBA Color Health	RCV000167041	SCV000911755	likely benign	Hereditary cancer-predisposing syndrome	2017-02-01	criteria provided, single submitter	clinical testing
Invitae	RCV001062992	SCV001227820	likely benign	Hereditary breast ovarian cancer syndrome	2022-11-07	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000506813	SCV001363202	uncertain significance	not specified	2019-01-18	criteria provided, single submitter	clinical testing	Variant summary: The variant BRCA2 c.2679A>G (p.Gln893=) alters a non-conserved nucleotide resulting in a synonymous change. Several computational tools predict a significant impact on normal splicing through creation of new or activation of existing cryptic exonic splice donor/acceptor sites. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 233462 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2679A>G in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.