ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.841G>A (p.Asp281Asn) (rs80359088)

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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 RCV000130406 SCV000185267 uncertain significance Hereditary cancer-predisposing syndrome 2017-11-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Breast Cancer Information Core (BIC) (BRCA2) RCV000077438 SCV000145778 uncertain significance Breast-ovarian cancer, familial 2 2002-06-20 no assertion criteria provided clinical testing
Color RCV000130406 SCV000683965 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-03 criteria provided, single submitter clinical testing
GeneDx RCV000586972 SCV000566347 uncertain significance not provided 2018-03-28 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.841G>A at the cDNA level, p.Asp281Asn (D281N) at the protein level, and results in the change of an Aspartic Acid to an Asparagine (GAC>AAC). Using alternate nomenclature, this variant would be defined as BRCA2 1069G>A. This variant has been observed in individuals with lung and pancreatic cancer (Lu 2015, O'Reilly 2018). BRCA2 Asp281Asn was observed at an allele frequency of 0.039% (6/15144 alleles) in individuals of African ancestry in large population cohorts (Lek 2016). BRCA2 Asp281Asn is not located in a known functional domain. In-silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on the currently available information, we consider BRCA2 Asp281Asn to be a variant of uncertain significance.
Integrated Genetics/Laboratory Corporation of America RCV000586972 SCV000695151 uncertain significance not provided 2017-03-24 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.841G>A (p.Asp281Asn) variant causes a missense change involving the alteration of a conserved nucleotide. 3/5 in silico tools predict a damaging outcome for this variant. The variant of interest has been found in a large, broad control population, ExAC, in 2/120106 control chromosomes at a frequency of 0.0000167, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). This variant has been reported in one patient with lung adenocarcinoma and LOH in tumor was not found. Breast Cancer Information Core lists two patients who carry the variant of interest with one of them (ID#31600) carrying a BRCA1 c.4611_4612insG/p.Gln1537_Gln1538?fs (Class 5 pathogenic, not found in our internal database). Multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance, except Sharing Clinical Reports Project which classified this variant as likely benign without providing evidence for independent review. Taken together, this variant is classified as VUS.
Invitae RCV000045512 SCV000073525 likely benign Hereditary breast and ovarian cancer syndrome 2017-10-04 criteria provided, single submitter clinical testing
PreventionGenetics RCV000586972 SCV000805779 uncertain significance not provided 2017-02-20 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000482899 SCV000600802 uncertain significance not specified 2017-05-12 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077438 SCV000109236 likely benign Breast-ovarian cancer, familial 2 2012-03-29 no assertion criteria provided clinical testing

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