ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9581C>A (p.Pro3194Gln) (rs28897760)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000045860 SCV000073873 likely benign Hereditary breast and ovarian cancer syndrome 2020-10-13 criteria provided, single submitter clinical testing
Ambry Genetics RCV000131306 SCV000186278 likely benign Hereditary cancer-predisposing syndrome 2018-12-24 criteria provided, single submitter clinical testing Co-occurence with a mutation in another gene that clearly explains a proband's phenotype;Other data supporting benign classification
GeneDx RCV001719713 SCV000210511 likely benign not provided 2019-08-19 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 22875147, 23704879, 18724707, 27223485, 21702907, 29116469, 27403073, 32854451)
Counsyl RCV000031833 SCV000487802 uncertain significance Breast-ovarian cancer, familial 2 2015-11-18 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000160173 SCV000600868 uncertain significance not specified 2017-03-24 criteria provided, single submitter clinical testing
Color Health, Inc RCV000131306 SCV000689208 likely benign Hereditary cancer-predisposing syndrome 2017-06-12 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000160173 SCV000917016 likely benign not specified 2018-08-05 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.9581C>A (p.Pro3194Gln) results in a non-conservative amino acid change located in the no known domain of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.4e-05 in 277716 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.9581C>A has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer(Palmero_2015, Yilmaz_2016, Brianese_2018). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. This variant has been reported in one individual who was older than age 70 and cancer free. Co-occurrences with other pathogenic variant(s) have been reported (BRCA2 c.3978_3979ins4, p.Ala1327fsX4; BRCA1 c.5266dupC, p.Gln1756Profs*74), providing supporting evidence for a benign role. One publication reports experimental evidence evaluating an impact on protein function, however, does not allow convincing conclusions about the variant effect (Tram_2013). Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments. Based on the evidence outlined above, the variant was classified as likely benign.
Research and Development, ARUP Laboratories RCV001642523 SCV001852856 likely benign Breast-ovarian cancer, familial 2; Breast-ovarian cancer, familial 1; Hereditary breast and ovarian cancer syndrome 2020-01-20 criteria provided, single submitter curation
Sharing Clinical Reports Project (SCRP) RCV000031833 SCV000054441 benign Breast-ovarian cancer, familial 2 2012-02-08 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031833 SCV000147668 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing

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