ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8134G>A (p.Asp2712Asn) (rs80359056)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130697 SCV000185584 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or Conflicting Evidence
Breast Cancer Information Core (BIC) (BRCA2) RCV000083144 SCV000147278 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Counsyl RCV000083144 SCV000786077 uncertain significance Breast-ovarian cancer, familial 2 2018-02-23 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000083144 SCV000744533 likely benign Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
GeneDx RCV000218294 SCV000279256 uncertain significance not provided 2017-10-03 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.8134G>A at the cDNA level, p.Asp2712Asn (D2712N) at the protein level, and results in the change of an Aspartic Acid to an Asparagine (GAT>AAT). Using alternate nomenclature, this variant would be defined as BRCA2 8362G>A. This variant was observed in an individual with bilateral breast cancer (Borg 2010). BRCA2 Asp2712Asn was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Aspartic Acid and Asparagine differ in some properties, this is considered a semi-conservative amino acid substitution. BRCA2 Asp2712Asn 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 information, it is unclear whether BRCA2 Asp2712Asn is pathogenic or benign. We consider it to be a variant of uncertain significance.
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000083144 SCV000743342 likely benign Breast-ovarian cancer, familial 2 2017-07-28 criteria provided, single submitter clinical testing
Invitae RCV000045427 SCV000073440 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-10-01 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 2712 of the BRCA2 protein (p.Asp2712Asn). The aspartic acid residue is weakly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with breast cancer (PMID: 20104584). ClinVar contains an entry for this variant (Variation ID: 52509). Experimental studies have shown that this missense change does not have a significant effect on the homology directed repair activity of BRCA2 (PMID: 29884841). 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) RCV000083144 SCV000115218 uncertain significance Breast-ovarian cancer, familial 2 2013-07-02 no assertion criteria provided clinical testing

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