ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8572C>A (p.Gln2858Lys) (rs80359112)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000045560 SCV000073573 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-21 criteria provided, single submitter clinical testing This sequence change replaces glutamine with lysine at codon 2858 of the BRCA2 protein (p.Gln2858Lys). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and lysine. 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. It has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 52623). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). An algorithm developed specifically for the BRCA2 gene also returned an uncertain effect on protein function (PMID: 19043619). 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 RCV000766652 SCV000210477 uncertain significance not provided 2017-04-19 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.8572C>A at the cDNA level, p.Gln2858Lys (Q2858K) at the protein level, and results in the change of a Glutamine to a Lysine (CAA>AAA). Using alternate nomenclature, this variant would be defined as BRCA2 8800C>A. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Gln2858Lys was not observed in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Glutamine and Lysine differ in some properties, this is considered a semi-conservative amino acid substitution. BRCA2 Gln2858Lys occurs at a position that is conserved in mammals and is located in the DNA binding domain (Yang 2002). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether BRCA2 Gln2858Lys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000166603 SCV000217407 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-19 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000212278 SCV000600814 uncertain significance not specified 2017-02-06 criteria provided, single submitter clinical testing
Color RCV000166603 SCV000689135 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-13 criteria provided, single submitter clinical testing
Counsyl RCV000113961 SCV000785961 uncertain significance Breast-ovarian cancer, familial 2 2018-01-23 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113961 SCV000147401 uncertain significance Breast-ovarian cancer, familial 2 2003-12-23 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.