ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5554G>A (p.Val1852Ile) (rs80358777)

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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 RCV000164924 SCV000215612 likely benign Hereditary cancer-predisposing syndrome 2017-05-11 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Other strong data supporting benign classification
Breast Cancer Information Core (BIC) (BRCA2) RCV000031554 SCV000146633 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Color RCV000164924 SCV000903906 likely benign Hereditary cancer-predisposing syndrome 2016-10-31 criteria provided, single submitter clinical testing
Counsyl RCV000031554 SCV000488985 uncertain significance Breast-ovarian cancer, familial 2 2016-07-29 criteria provided, single submitter clinical testing
GeneDx RCV000656609 SCV000618094 uncertain significance not provided 2018-11-01 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.5554G>A at the cDNA level, p.Val1852Ile (V1852I) at the protein level, and results in the change of a Valine to an Isoleucine (GTT>ATT). Using alternate nomenclature, this variant would be defined as BRCA2 5782G>A. This variant was observed in at least one individual with prostate cancer and in two individuals with breast cancer; however, it was also present in unaffected controls (Haiman 2013, Momozawa 2018). BRCA2 Val1852Ile was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the BRC6 domain and the RAD51 binding domains (Cole 2011, Roy 2012). 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 Val1852Ile is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000044680 SCV000072693 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-11-15 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 1852 of the BRCA2 protein (p.Val1852Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs80358777, ExAC 0.008%). This variant has been reported in an individual with breast cancer in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 37973). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The isoleucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000656609 SCV000778686 uncertain significance not provided 2017-06-23 no assertion criteria provided clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000656609 SCV000889072 uncertain significance not provided 2018-02-21 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031554 SCV000054159 uncertain significance Breast-ovarian cancer, familial 2 2012-04-18 no assertion criteria provided clinical testing

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