ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8539G>A (p.Glu2847Lys) (rs80359108)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000045551 SCV000073564 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-31 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 2847 of the BRCA2 protein (p.Glu2847Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs80359108, ExAC 0.001%). This variant has been reported in an individual affected with endometrial cancer (PMID: 26689913). ClinVar contains an entry for this variant (Variation ID: 52616). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but 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.
GeneDx RCV000767049 SCV000565868 uncertain significance not provided 2015-03-04 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.8539G>A at the cDNA level, p.Glu2847Lys (E2847K) at the protein level, and results in the change of a Glutamic Acid to a Lysine (GAA>AAA). Using alternate nomenclature, this variant would be defined as BRCA2 8767G>A. BRCA2 Glu2847Lys 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 Glutamic Acid and Lysine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA2 Glu2847Lys occurs at a position that is conserved across species and is located in the In DNA binding domain (Borg 2010). In-house in silico analyses and published computational models predict that this variant is probably damaging to protein structure and function (Karchin 2008). Based on currently available information, it is unclear whether BRCA2 Glu2847Lys is pathogenic or benign. We consider it to be a variant of uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000479458 SCV000600812 uncertain significance not specified 2016-12-29 criteria provided, single submitter clinical testing
Ambry Genetics RCV000564844 SCV000665393 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000564844 SCV000683980 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-31 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113958 SCV000147397 uncertain significance Breast-ovarian cancer, familial 2 2000-11-10 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.