ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6986C>T (p.Pro2329Leu) (rs80358925)

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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 RCV000163085 SCV000213588 uncertain significance Hereditary cancer-predisposing syndrome 2016-08-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Breast Cancer Information Core (BIC) (BRCA2) RCV000077392 SCV000146985 uncertain significance Breast-ovarian cancer, familial 2 2002-06-20 no assertion criteria provided clinical testing
Color RCV000163085 SCV000906928 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Counsyl RCV000077392 SCV000786113 uncertain significance Breast-ovarian cancer, familial 2 2018-02-28 criteria provided, single submitter clinical testing
GeneDx RCV000045102 SCV000210641 likely benign not specified 2017-03-01 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 RCV000586419 SCV000695016 uncertain significance not provided 2016-12-19 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.6986C>T (p.Pro2329Leu) variant involves the alteration of a conserved nucleotide. 5/5 in silico tools predict a damaging outcome for this variant. This variant is absent in 118176 control chromosomes. This variant has been reported in BrC individual with no information on co-segregation provided. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance and one lab classified it as likely benign, all without evidence to independently evaluate. Taken together, due to lack of clinical information and functional data, this variant is classified as VUS.
Invitae RCV000167790 SCV000073115 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-10-17 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 2329 of the BRCA2 protein (p.Pro2329Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with early onset breast cancer and in another individual with personal and family history of breast and/or ovarian cancer (PMID: 26221963, 28828701). However, in an individual in the Breast Cancer Information Core (BIC) database (PMID: 10923033), a pathogenic variant was also identified in BRCA1, which suggests that this c.6986C>T variant was not the primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 52231). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 RCV000045102 SCV000600728 uncertain significance not specified 2017-06-19 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077392 SCV000109189 likely benign Breast-ovarian cancer, familial 2 2012-04-23 no assertion criteria provided clinical testing

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