ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6475C>G (p.Gln2159Glu) (rs398122558)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000588031 SCV000210390 uncertain significance not provided 2018-04-08 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.6475C>G at the cDNA level, p.Gln2159Glu (Q2159E) at the protein level, and results in the change of a Glutamine to a Glutamic Acid (CAA>GAA). Using alternate nomenclature, this variant would be defined as/ has been previously published as BRCA2 6703C>G. This variant has not, to our knowledge, been published in the literature as a germline variant; however, it has been reported as a somatic variant in a rhabdomyosarcoma (Kohsaka 2014). BRCA2 Gln2159Glu was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether BRCA2 Gln2159Glu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000166819 SCV000217633 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-25 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000588031 SCV000254200 likely benign not provided 2019-01-19 criteria provided, single submitter clinical testing
Counsyl RCV000076967 SCV000488282 uncertain significance Breast-ovarian cancer, familial 2 2016-02-12 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000160111 SCV000600706 uncertain significance not specified 2016-10-13 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000160111 SCV000694977 uncertain significance not specified 2019-09-09 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.6475C>G (p.Gln2159Glu) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.3e-06 in 230162 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.6475C>G has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Diaz-Zabala_2018). These report(s) do 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. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Based on the evidence outlined above, the variant was classified as uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000588031 SCV000887883 uncertain significance not provided 2019-04-16 criteria provided, single submitter clinical testing
Color RCV000166819 SCV000903842 likely benign Hereditary cancer-predisposing syndrome 2017-05-11 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000076967 SCV000108764 benign Breast-ovarian cancer, familial 2 2013-09-24 no assertion criteria provided clinical testing

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