ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9821T>G (p.Leu3274Trp) (rs431825380)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131538 SCV000186533 uncertain significance Hereditary cancer-predisposing syndrome 2016-07-09 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000131538 SCV000906825 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-23 criteria provided, single submitter clinical testing
Counsyl RCV000083010 SCV000786202 uncertain significance Breast-ovarian cancer, familial 2 2018-03-16 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000590068 SCV000695273 uncertain significance not provided 2017-08-04 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.9821T>G (p.Leu3274Trp) variant involves the alteration of a conserved nucleotide and 5/5 in silico tools predict a damaging outcome. However, these predictions have yet to be functionally assessed. This variant is absent in 30962 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications. However, multiple clinical diagnostic laboratories classified this variant as uncertain significance. Taken together, this variant is classified as a "Variant of Uncertain Significance (VUS)."
Invitae RCV000477120 SCV000549842 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-21 criteria provided, single submitter clinical testing This sequence change replaces leucine with tryptophan at codon 3274 of the BRCA2 protein (p.Leu3274Trp). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with breast and/or ovarian cancer (PMID: 24249303, 29176636, 24504028) and an individual affected with duodenal adenocarcinoma (PMID: 28767289). ClinVar contains an entry for this variant (Variation ID: 96889). 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 disruptive, but these predictions have not been confirmed by published functional 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 RCV000590068 SCV000889193 uncertain significance not provided 2018-05-20 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000083010 SCV000115084 uncertain significance Breast-ovarian cancer, familial 2 2009-09-03 no assertion criteria provided clinical testing

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