ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.1744A>C (p.Thr582Pro) (rs80358457)

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Total submissions: 13
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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) RCV000031334 SCV000244425 benign Breast-ovarian cancer, familial 2 2015-08-10 reviewed by expert panel curation IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.0000224
Invitae RCV001079595 SCV000071882 benign Hereditary breast and ovarian cancer syndrome 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000162597 SCV000213016 benign Hereditary cancer-predisposing syndrome 2014-11-19 criteria provided, single submitter clinical testing
Soonchunhyang University Bucheon Hospital,Soonchunhyang University Medical Center RCV000031334 SCV000267233 uncertain significance Breast-ovarian cancer, familial 2 2016-03-18 criteria provided, single submitter reference population
GeneDx RCV000422713 SCV000512339 likely benign not specified 2017-10-06 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.
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency RCV000422713 SCV000586929 benign not specified 2017-04-18 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000422713 SCV000591762 benign not specified 2015-11-20 criteria provided, single submitter clinical testing
Color RCV000162597 SCV000683441 likely benign Hereditary cancer-predisposing syndrome 2015-12-08 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000758864 SCV000887756 benign not provided 2019-02-14 criteria provided, single submitter clinical testing
Mendelics RCV000031334 SCV001139008 benign Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000422713 SCV001362933 benign not specified 2019-09-23 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.1744A>C (p.Thr582Pro) results in a non-conservative amino acid change in 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 0.00023 in 250296 control chromosomes, predominantly at a frequency of 0.0032 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 4 fold of the estimated maximal expected allele frequency for a pathogenic variant in BRCA2 causing Hereditary Breast and Ovarian Cancer phenotype (0.00075), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. c.1744A>C has been reported in the literature in individuals affected with Breast and Ovarian Cancer. However, these reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Co-occurrence with a pathogenic variant has been reported (BRCA1 c.505C>T, p.Gln169Ter), providing supporting evidence for a benign role. At least one publication reports experimental evidence evaluating an impact on protein function. These results showed no damaging effect of this variant (Mondal_2012). Eight clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (4x benign-including one expert panel, 3x likely benign, 1x VUS). Based on the evidence outlined above, the variant was classified as benign.
Sharing Clinical Reports Project (SCRP) RCV000031334 SCV000053939 benign Breast-ovarian cancer, familial 2 2009-08-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031334 SCV000145923 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing

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