ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.7448G>A (p.Ser2483Asn) (rs80358967)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001082083 SCV000073233 likely benign Hereditary breast and ovarian cancer syndrome 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000129898 SCV000184716 likely benign Hereditary cancer-predisposing syndrome 2018-08-17 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other strong data supporting benign classification
GeneDx RCV000045220 SCV000210649 likely benign not specified 2017-06-29 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.
Counsyl RCV000083134 SCV000487957 uncertain significance Breast-ovarian cancer, familial 2 2015-12-10 criteria provided, single submitter clinical testing
Department of Pathology and Molecular Medicine,Queen's University RCV000045220 SCV000588113 uncertain significance not specified 2017-04-20 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000045220 SCV000592111 likely benign not specified 2013-08-07 criteria provided, single submitter clinical testing
Color RCV000129898 SCV000683873 likely benign Hereditary cancer-predisposing syndrome 2017-04-13 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000045220 SCV000695068 likely benign not specified 2020-04-06 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.7448G>A (p.Ser2483Asn) results in a conservative amino acid change located in the Breast cancer type 2 susceptibility protein, helical domain (IPR015252) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 251306 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.7448G>A has been reported in the literature in individuals affected with breast cancer and also in individuals at risk of hereditary breast cancer (Spearman_2008, Carr_2011, Lu_2012, Fernandes_2016, Vendrell_2018) without strong evidence of causality. These reports therefore, do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Co-occurrence with another likely pathogenic variant has been reported (BRCA2 c.7115C>G, p.Ser2372X) in the UMD database, 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 (Hart_2019). Nine other ClinVar Submitters (evaluation after 2014) cite the variant as benign (n=6) or uncertain significance (n=3). Based on the evidence outlined above, the variant was classified as likely benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000586632 SCV001133897 likely benign not provided 2019-03-11 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000586632 SCV001148990 uncertain significance not provided 2019-07-01 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000083134 SCV000115208 benign Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000083134 SCV000147091 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000586632 SCV000778709 likely benign not provided 2018-02-09 no assertion criteria provided clinical testing

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