ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2634A>G (p.Ala878=) (rs730881451)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000495552 SCV000578242 likely benign Breast-ovarian cancer, familial 1 2017-06-29 reviewed by expert panel curation Synonymous substitution variant, with low bioinformatic likelihood to result in a splicing aberration (Splicing prior probability 0.02; http://priors.hci.utah.edu/PRIORS/).
GeneDx RCV000159876 SCV000209943 benign not specified 2014-08-15 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.
Ambry Genetics RCV000163881 SCV000214471 likely benign Hereditary cancer-predisposing syndrome 2014-06-13 criteria provided, single submitter clinical testing
Invitae RCV000679689 SCV000259984 likely benign not provided 2019-02-15 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000159876 SCV000591399 likely benign not specified 2015-06-04 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000159876 SCV000600297 likely benign not specified 2017-06-20 criteria provided, single submitter clinical testing
Color RCV000163881 SCV000683051 likely benign Hereditary cancer-predisposing syndrome 2016-12-13 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000679689 SCV000806924 likely benign not provided 2017-03-22 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000679689 SCV000887650 benign not provided 2018-09-07 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000159876 SCV000916728 likely benign not specified 2018-05-31 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.2634A>G alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 8.9e-05 in 245860 control chromosomes. This frequency is not higher than expected for a pathogenic variant in BRCA1 causing Hereditary Breast and Ovarian Cancer (8.9e-05 vs 0.001), allowing no conclusion about variant significance. c.2634A>G has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer. However, these reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. One publication reports experimental evidence evaluating an impact on protein function, but does not provide convincing conclusions about the variant effect. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.

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