ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9530A>G (p.Glu3177Gly) (rs876658365)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000222361 SCV000273483 uncertain significance Hereditary cancer-predisposing syndrome 2015-01-13 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765144 SCV000896370 uncertain significance Familial cancer of breast; Breast-ovarian cancer, familial 2; Fanconi anemia, complementation group D1; Medulloblastoma; Wilms tumor 1; Malignant tumor of prostate; Pancreatic cancer 2; Glioma susceptibility 3 2018-10-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000780013 SCV000917006 uncertain significance not specified 2018-05-21 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.9530A>G (p.Glu3177Gly) results in a non-conservative amino acid change located in the BRCA2 OB3 domain (IPR015188) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.1e-06 in 246134 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in BRCA2 causing Hereditary Breast and Ovarian Cancer (8.1e-06 vs 7.50e-04), allowing no conclusion about variant significance. The variant, c.9530A>G, has been reported in the literature in individuals affected or with family history of Hereditary Breast and Ovarian Cancer (Velasco_2005). This report does not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae RCV000550708 SCV000635749 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-06-24 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glycine at codon 3177 of the BRCA2 protein (p.Glu3177Gly). The glutamic acid residue is moderately conserved and there is a moderate physicochemical difference between glutamic acid and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with breast cancer (PMID: 15937982). This variant is also known as 9758A>G in the literature. ClinVar contains an entry for this variant (Variation ID: 230066). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000758978 SCV000887967 uncertain significance not provided 2017-11-15 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000239286 SCV000297580 uncertain significance Breast-ovarian cancer, familial 2 2012-02-02 no assertion criteria provided clinical testing

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