ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8036A>G (p.Asp2679Gly) (rs80359041)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000045397 SCV000073410 uncertain significance Hereditary breast and ovarian cancer syndrome 2020-10-20 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glycine at codon 2679 of the BRCA2 protein (p.Asp2679Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is present in population databases (rs80359041, ExAC 0.009%). This variant has been reported in individuals in the Breast Cancer Information Core database (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 52481). This variant has been reported not to substantially affect BRCA2 protein function (PMID: 23108138, 29884841). 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.
Ambry Genetics RCV000131797 SCV000186848 likely benign Hereditary cancer-predisposing syndrome 2020-06-04 criteria provided, single submitter clinical testing Other data supporting benign classification;Structural Evidence
Counsyl RCV000113859 SCV000489186 uncertain significance Breast-ovarian cancer, familial 2 2016-08-31 criteria provided, single submitter clinical testing
GeneDx RCV000484310 SCV000567541 likely benign not specified 2018-02-22 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Color Health, Inc RCV000131797 SCV000683938 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-20 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759667 SCV000889149 uncertain significance not provided 2019-06-06 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000484310 SCV000916951 uncertain significance not specified 2020-09-28 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.8036A>G (p.Asp2679Gly) results in a non-conservative amino acid change located in the DNA binding domain (Guidugli_2012) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. In addition, in silico studies also predicted that the variant probably impairs protein function (Karchin_2008, Doss_2014). The variant allele was found at a frequency of 2.5e-05 in 282620 control chromosomes, predominantly at a frequency of 0.00017 within the Latino subpopulation in the gnomAD database. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant, c.8036A>G, has been reported in 2 individuals in the Breast Cancer Information Core database (PMID: 10923033). These reports do not provide unequivocal conclusions about association of the variant with HBOC. In vitro functional studies reported that this variant results in an activity comparable to the wild type in homology-directed DNA repair (HDR) assays (Guidugli_2012, Guidugli_2018). Seven ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (6x) and likely benign (1x). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Mendelics RCV000113859 SCV001139204 uncertain significance Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113859 SCV000147255 uncertain significance Breast-ovarian cancer, familial 2 2001-10-29 no assertion criteria provided clinical testing

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