ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2352G>A (p.Ser784=) (rs372017932)

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Total submissions: 8
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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) RCV000169468 SCV000578267 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 RCV000123905 SCV000167255 benign not specified 2014-05-24 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 RCV000163134 SCV000213648 likely benign Hereditary cancer-predisposing syndrome 2014-10-08 criteria provided, single submitter clinical testing
Counsyl RCV000169468 SCV000220907 likely benign Breast-ovarian cancer, familial 1 2014-11-24 criteria provided, single submitter literature only
Invitae RCV000206665 SCV000260817 likely benign not provided 2019-03-05 criteria provided, single submitter clinical testing
Color RCV000163134 SCV000537456 likely benign Hereditary cancer-predisposing syndrome 2015-07-15 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000123905 SCV000591382 benign not specified 2014-02-20 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000123905 SCV000916753 likely benign not specified 2018-04-30 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.2352G>A 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 4e-05 in 276350 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in BRCA1 causing Hereditary Breast and Ovarian Cancer (4e-05 vs 0.001), allowing no conclusion about variant significance. c.2352G>A has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer. These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Co-occurrences with other pathogenic variant(s) have been reported (BRCA1 c.886_889delAGAA, p.Arg296X; BRCA1 c.3748G>T, p.Glu1250X), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three 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 benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign.

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