ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9583A>G (p.Thr3195Ala) (rs80359227)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129471 SCV000184241 likely benign Hereditary cancer-predisposing syndrome 2016-07-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Other data supporting benign classification
Breast Cancer Information Core (BIC) (BRCA2) RCV000083162 SCV000147669 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Color RCV000129471 SCV000911111 benign Hereditary cancer-predisposing syndrome 2017-01-09 criteria provided, single submitter clinical testing
Counsyl RCV000083162 SCV000487986 uncertain significance Breast-ovarian cancer, familial 2 2015-12-10 criteria provided, single submitter clinical testing
GeneDx RCV000427171 SCV000532127 likely benign not specified 2018-02-27 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.
Integrated Genetics/Laboratory Corporation of America RCV000589931 SCV000695253 uncertain significance not provided 2015-01-04 criteria provided, single submitter clinical testing
Invitae RCV000045861 SCV000073874 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-06-21 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 3195 of the BRCA2 protein (p.Thr3195Ala). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in population databases (rs80359227, ExAC 0.001%). This variant has been reported in a single family with at least one individual affected with either breast cancer or ovarian cancer (PMID: 16905680). ClinVar contains an entry for this variant (Variation ID: 52872). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000083162 SCV000296504 uncertain significance Breast-ovarian cancer, familial 2 2016-06-07 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000083162 SCV000115236 likely benign Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing

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