ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5649A>C (p.Lys1883Asn) (rs80358787)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131541 SCV000186539 likely benign Hereditary cancer-predisposing syndrome 2017-12-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Other strong data supporting benign classification
Breast Cancer Information Core (BIC) (BRCA2) RCV000076938 SCV000146655 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000131541 SCV000905484 likely benign Hereditary cancer-predisposing syndrome 2015-07-22 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000502274 SCV000591982 uncertain significance not specified 2016-01-12 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000502274 SCV000918876 uncertain significance not specified 2018-06-11 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.5649A>C (p.Lys1883Asn) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 244700 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.5649A>C in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Three ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as uncertain significance (2x) or likely benign (1x). Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae RCV000637343 SCV000758795 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-11-26 criteria provided, single submitter clinical testing This sequence change replaces lysine with asparagine at codon 1883 of the BRCA2 protein (p.Lys1883Asn). The lysine residue is weakly conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 91421). 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, 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) RCV000076938 SCV000108735 uncertain significance Breast-ovarian cancer, familial 2 2008-03-13 no assertion criteria provided clinical testing

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