ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8351G>A (p.Arg2784Gln) (rs80359076)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000045488 SCV000073501 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-11-07 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 2784 of the BRCA2 protein (p.Arg2784Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs80359076, ExAC 0.01%). This variant has been reported in individuals and families affected with breast and/or ovarian cancer, and prostate cancer (PMID: 21952622, 19200354, 19563646, 21232165, 27914478). However, currently there is insufficient evidence to conclude whether this variant segregates with disease (PMID: 19563646). This variant has also been reported in an individual in the Breast Cancer Information Core database (PMID: 10923033). However, pathogenic alleles have been identified in BRCA1 and BRCA2, which suggest that this c.8351G>A substitution is not the primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 52559). Based on a multifactorial likelihood algorithm using genetic, in silico, and statistical data, this variant has been determined to have a high probability of being pathogenic (PMID: 19200354). In addition, experimental studies have shown that this variant impairs homology-directed DNA break repair activity in vitro (PMID: 23108138, 29394989). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000129468 SCV000184238 uncertain significance Hereditary cancer-predisposing syndrome 2018-02-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000129468 SCV000292176 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-30 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000500633 SCV000600796 uncertain significance not specified 2017-03-27 criteria provided, single submitter clinical testing
Mendelics RCV000045488 SCV000838874 likely pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769704 SCV000901122 uncertain significance Breast and/or ovarian cancer 2016-11-17 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077435 SCV000109233 uncertain significance Breast-ovarian cancer, familial 2 2012-08-21 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077435 SCV000147330 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
CSER_CC_NCGL; University of Washington Medical Center RCV000148441 SCV000190140 uncertain significance Neoplasm of the breast 2014-06-01 no assertion criteria provided research
True Health Diagnostics RCV000129468 SCV000787954 uncertain significance Hereditary cancer-predisposing syndrome 2018-02-20 no assertion criteria provided clinical testing

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