ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.3256A>G (p.Ile1086Val) (rs80358571)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000044158 SCV000072171 likely benign Hereditary breast and ovarian cancer syndrome 2020-09-09 criteria provided, single submitter clinical testing
Laboratory of Molecular Diagnosis of Cancer,West China Hospital, Sichuan University RCV000240692 SCV000265944 uncertain significance Breast neoplasm 2015-11-01 criteria provided, single submitter research
GeneDx RCV000419030 SCV000522022 likely benign not specified 2017-03-20 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000419030 SCV000600543 uncertain significance not specified 2016-09-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV000509892 SCV000608139 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-19 criteria provided, single submitter clinical testing The p.I1086V variant (also known as c.3256A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 3256. The isoleucine at codon 1086 is replaced by valine, an amino acid with highly similar properties. In one study, this variant was identified in 1 of 200 Asian Americans with a personal and/or family history of breast and/or ovarian cancer and was not detected in any of the 200 matched white individuals (Kurian AW et al. J. Clin. Oncol. 2008 Oct;26:4752-8). In another study, this alteration was identified in 1/507 unselected Chinese breast cancer patients (Zhong X et al. PLoS One. 2016 Jun 3;11:e0156789). This alteration has also been reported with a carrier frequency of 1 in 7051 unselected breast cancer patients and 1 in 11241 female controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 10;9:4083). Additionally, this alteration has been classified as likely benign by a study utilizing multifactorial likelihood analysis (Lee JS et al. J. Med. Genet., 2018 Dec;55:794-802). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589377 SCV000694683 uncertain significance not provided 2016-11-14 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.3256A>G (p.Ile1086Val) variant involves the alteration of a non-conserved nucleotide. 4/4 in silico tools predict a benign outcome for this substitution (SNPs&GO not captured due to low reliability index). This variant was found in 3/118360 control chromosomes at a frequency of 0.0000253, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). It was reported at least one individual with breast cancer, however without strong evidence for causality such as co-segregation. Multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance/likely benign. Taken together, this variant is classified as VUS.
Color Health, Inc RCV000509892 SCV000903421 likely benign Hereditary cancer-predisposing syndrome 2016-03-02 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077300 SCV000109097 likely benign Breast-ovarian cancer, familial 2 2012-02-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077300 SCV000146197 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing

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