ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8135A>T (p.Asp2712Val) (rs80359057)

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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 RCV000130071 SCV000184898 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-26 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Breast Cancer Information Core (BIC) (BRCA2) RCV000077428 SCV000147279 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Color RCV000130071 SCV000683945 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-06 criteria provided, single submitter clinical testing
GeneDx RCV000236985 SCV000293647 uncertain significance not provided 2015-11-27 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.8135A>T at the cDNA level, p.Asp2712Val (D2712V) at the protein level, and results in the change of an Aspartic Acid to a Valine (GAT>GTT). Using alternate nomenclature, this variant would be defined as BRCA2 8363A>T. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Asp2712Val was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Aspartic Acid and Valine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA2 Asp2712Val occurs at a position that is not conserved and is located within the DNA binding domain (Borg 2010). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether BRCA2 Asp2712Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000045428 SCV000073441 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-08-22 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with valine at codon 2712 of the BRCA2 protein (p.Asp2712Val). The aspartic acid residue is weakly conserved and there is a large physicochemical difference between aspartic acid and valine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in an individual affected with breast cancer (PMID: 20104584). ClinVar contains an entry for this variant (Variation ID: 52510). While 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"), an algorithm developed specifically for the BRCA2 gene (PMID: 19043619) suggests that this missense change may be neutral. 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.
Sharing Clinical Reports Project (SCRP) RCV000077428 SCV000109226 uncertain significance Breast-ovarian cancer, familial 2 2011-11-23 no assertion criteria provided clinical testing

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