ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9839C>A (p.Pro3280His) (rs80359246)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000045904 SCV000073917 likely benign Hereditary breast and ovarian cancer syndrome 2018-01-12 criteria provided, single submitter clinical testing
Ambry Genetics RCV000130774 SCV000185667 uncertain significance Hereditary cancer-predisposing syndrome 2016-07-28 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Counsyl RCV000077477 SCV000488003 uncertain significance Breast-ovarian cancer, familial 2 2015-12-16 criteria provided, single submitter clinical testing
GeneDx RCV000430520 SCV000517197 likely benign not specified 2018-01-11 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.
Color RCV000130774 SCV000911112 likely benign Hereditary cancer-predisposing syndrome 2017-09-11 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000430520 SCV000917028 uncertain significance not specified 2018-09-28 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.9839C>A (p.Pro3280His) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 246074 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.9839C>A has been reported in the literature in an individual affected with Hereditary Breast and Ovarian Cancer (Azzollini_2016), who was also indicated to carry another pathogenic variant, although the variant was not indicated. These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. An in vitro study demonstrated the variant to behave similar to wild type BRCA2 in DNA damaging agent sensitivity and Rad51 foci formation assays indicating a possible neutral impact (Hucl_2008). Four ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant twice as likely benign and twice as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Sharing Clinical Reports Project (SCRP) RCV000077477 SCV000109275 benign Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077477 SCV000145719 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing

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