ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.2484T>C (p.Tyr828=) (rs45619134)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163556 SCV000214114 likely benign Hereditary cancer-predisposing syndrome 2014-08-04 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000513645 SCV000608677 uncertain significance not provided 2017-03-31 criteria provided, single submitter clinical testing
Color RCV000163556 SCV000683486 benign Hereditary cancer-predisposing syndrome 2016-09-16 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000495313 SCV000578731 likely benign Breast-ovarian cancer, familial 2 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 RCV000123953 SCV000167344 benign not specified 2013-10-18 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.
Integrated Genetics/Laboratory Corporation of America RCV000123953 SCV000919014 likely benign not specified 2018-10-16 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.2484T>C 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 4.7e-05 in 235830 control chromosomes (gnomAD). This frequency is not higher than expected for a pathogenic variant in BRCA2 causing Hereditary Breast and Ovarian Cancer (4.7e-05 vs. 0.00075), allowing no conclusion about variant significance. c.2484T>C has been reported in the literature in at least one individual affected with Hereditary Breast and Ovarian Cancer (Cardenosa 2008, Salgado 2005). These reports however do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. A co-occurrence with a pathogenic BRCA2 variant has been reported in an internal sample (c.2836delG (p.Asp946fsX14)), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (2 labs classifying it as 'benign', 2 calling it 'likely benign' and one as 'VUS'). Based on the evidence outlined above, the variant was classified as likely benign.
Invitae RCV000196054 SCV000253003 benign Hereditary breast and ovarian cancer syndrome 2017-12-06 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000123953 SCV000600514 likely benign not specified 2017-02-28 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000513645 SCV000887777 likely benign not provided 2018-05-04 criteria provided, single submitter clinical testing

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