ClinVar Miner

Submissions for variant NM_000059.3(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
Ambry Genetics RCV000509892 SCV000608139 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-23 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Breast Cancer Information Core (BIC) (BRCA2) RCV000077300 SCV000146197 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Color RCV000509892 SCV000903421 likely benign Hereditary cancer-predisposing syndrome 2016-03-02 criteria provided, single submitter clinical testing
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.
Integrated Genetics/Laboratory Corporation of America 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.
Invitae RCV000044158 SCV000072171 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-17 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 1086 of the BRCA2 protein (p.Ile1086Val). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs80358571, ExAC 0.02%). This variant has been reported in an individual affected with breast cancer (PMID: 27257965) and an individual with a history of hereditary breast and ovarian cancer (PMID: 18779604). ClinVar contains an entry for this variant (Variation ID: 51433). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional 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.
Laboratory of Molecular Diagnosis of Cancer,West China Hospital, Sichuan University RCV000240692 SCV000265944 uncertain significance Neoplasm of the breast 2015-11-01 criteria provided, single submitter research
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000419030 SCV000600543 uncertain significance not specified 2016-09-08 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

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