ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4570T>G (p.Phe1524Val) (rs56386506)

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Total submissions: 12
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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) RCV000083108 SCV000244449 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 = 0.0000208
Invitae RCV001081703 SCV000072457 benign Hereditary breast and ovarian cancer syndrome 2019-12-31 criteria provided, single submitter clinical testing
GeneDx RCV000044444 SCV000210606 likely benign not specified 2017-11-14 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.
Ambry Genetics RCV000163006 SCV000213494 benign Hereditary cancer-predisposing syndrome 2014-11-19 criteria provided, single submitter clinical testing
Counsyl RCV000083108 SCV000488400 benign Breast-ovarian cancer, familial 2 2016-03-17 criteria provided, single submitter clinical testing
Color RCV000163006 SCV000537475 likely benign Hereditary cancer-predisposing syndrome 2015-04-28 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000044444 SCV000694782 benign not specified 2019-10-25 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.4570T>G (p.Phe1524Val) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 250548 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.4570T>G has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Caux-Moncoutier 2009, Haffty 2009, Meyer 2003, Meyer 2012). These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. A review of a multifactorial probability based model (Lindor 2012) that included a statistical weighting of segregation analysis, co-occurrence in trans, pathological profiles, personal and family history of cancer showed that, for this variant, odds in favor of causality was 1.02x10-3 and posterior probability of being deleterious was 2.08x10-5. Authors classify the variant as IARC Class 1 (Least Likely to be pathogenic) variant. Five ClinVar submissions including an expert panel (evaluation after 2014) cite the variant twice as benign and three times as likely benign. Based on the evidence outlined above, the variant was classified as benign.
Mendelics RCV000083108 SCV001139091 benign Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000167796 SCV001148984 uncertain significance not provided 2019-07-01 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000083108 SCV000115182 benign Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000083108 SCV000146451 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735551 SCV000863689 uncertain significance Breast and/or ovarian cancer 2003-02-07 no assertion criteria provided clinical testing

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