ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9286G>A (p.Glu3096Lys) (rs80359199)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000580932 SCV000684050 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-16 criteria provided, single submitter clinical testing
GeneDx RCV000074561 SCV000108646 uncertain significance not provided 2015-04-03 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.9286G>A at the cDNA level, p.Glu3096Lys (E3096K) 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 9514G>A. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Glu3096Lys 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 Glu3096Lys occurs at a position that is conserved across species and is located in the DNA binding domain (UniProt). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether BRCA2 Glu3096Lys is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000527692 SCV000635735 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-02-27 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 3096 of the BRCA2 protein (p.Glu3096Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs80359199, 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: 89054). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.

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.