ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.2908G>A (p.Asp970Asn) (rs397507295)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129877 SCV000184694 uncertain significance Hereditary cancer-predisposing syndrome 2018-11-16 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000196636 SCV000254177 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-12-18 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 970 of the BRCA2 protein (p.Asp970Asn). The aspartic acid residue is weakly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs397507295, ExAC 0.002%). This variant has not been reported in the literature in individuals with a BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 37806). 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 asparagine 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 and their clinical significance is uncertain. In summary, this variant has uncertain impact on BRCA2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000588181 SCV000279290 uncertain significance not provided 2018-09-14 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.2908G>A at the cDNA level, p.Asp970Asn (D970N) 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 3136G>A. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Asp970Asn was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether BRCA2 Asp970Asn is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000220683 SCV000591834 uncertain significance not specified 2015-11-26 criteria provided, single submitter clinical testing
Color RCV000129877 SCV000683510 uncertain significance Hereditary cancer-predisposing syndrome 2020-02-25 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000588181 SCV000694645 uncertain significance not provided 2016-02-19 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763884 SCV000894819 uncertain significance Familial cancer of breast; Breast-ovarian cancer, familial 2; Fanconi anemia, complementation group D1; Medulloblastoma; Wilms tumor 1; Malignant tumor of prostate; Pancreatic cancer 2; Glioma susceptibility 3 2018-10-31 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000735533 SCV000901103 uncertain significance Breast and/or ovarian cancer 2017-06-26 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031387 SCV000053992 uncertain significance Breast-ovarian cancer, familial 2 2008-07-15 no assertion criteria provided clinical testing
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735533 SCV000863671 uncertain significance Breast and/or ovarian cancer 2013-02-28 no assertion criteria provided clinical testing

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