ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1714G>A (p.Val572Ile) (rs587782713)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000132189 SCV000187269 uncertain significance Hereditary cancer-predisposing syndrome 2014-12-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (benign)
Counsyl RCV000412238 SCV000487765 uncertain significance Breast-ovarian cancer, familial 2 2015-11-21 criteria provided, single submitter clinical testing
Invitae RCV000468570 SCV000549493 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-11-27 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 572 of the BRCA2 protein (p.Val572Ile). The valine residue is weakly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs587782713, ExAC 0.02%). This variant has been reported in individuals affected with breast and/or ovarian cancer (PMID: 23683081, 29021639). ClinVar contains an entry for this variant (Variation ID: 142782). 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: "Tolerated"; PolyPhen-2: "Possibly 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.
GeneDx RCV000587521 SCV000565802 uncertain significance not provided 2018-12-13 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.1714G>A at the cDNA level, p.Val572Ile (V572I) at the protein level, and results in the change of a Valine to an Isoleucine (GTA>ATA). Using alternate nomenclature, this variant would be defined as BRCA2 1942G>A. This variant has been observed in at least one family with breast and/or ovarian cancer (Blay 2013). BRCA2 Val572Ile was not observed at a significant allele frequency in large population cohorts (Lek 2016). BRCA2 Val572Ile is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether BRCA2 Val572Ile is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Integrated Genetics/Laboratory Corporation of America RCV000587521 SCV000694559 uncertain significance not provided 2016-02-29 criteria provided, single submitter clinical testing
Color RCV000132189 SCV000911748 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-02 criteria provided, single submitter clinical testing

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