ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8352G>T (p.Arg2784=) (rs747664806)

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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) RCV000495423 SCV000578674 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/).
Ambry Genetics RCV000217568 SCV000274827 likely benign Hereditary cancer-predisposing syndrome 2015-03-24 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae RCV001082202 SCV000560373 likely benign Hereditary breast and ovarian cancer syndrome 2020-12-06 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000506394 SCV000600797 benign not specified 2020-04-03 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000757043 SCV000885107 likely benign not provided 2017-07-06 criteria provided, single submitter clinical testing
Color Health, Inc RCV000217568 SCV000911618 likely benign Hereditary cancer-predisposing syndrome 2018-03-19 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000506394 SCV000917038 likely benign not specified 2018-10-12 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.8352G>T 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 5.3e-05 in 246210 control chromosomes, predominantly at a frequency of 0.00036 within the Latino subpopulation in the gnomAD database. This frequency is not significantly higher than expected for a pathogenic variant in BRCA2 causing Hereditary Breast and Ovarian Cancer (5.3e-05 vs 0.00075), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.8352G>T in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Co-occurrences with other likely pathogenic variant(s) have been reported (PALB2 c.8352G>T, p.Ser779X) in our internal database, providing supporting evidence for a benign role. Four 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 likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
GeneDx RCV000757043 SCV001939395 benign not provided 2015-05-29 criteria provided, single submitter clinical testing

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