ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5200G>A (p.Glu1734Lys) (rs786202543)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165399 SCV000216126 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-22 criteria provided, single submitter clinical testing The p.E1734K variant (also known as c.5200G>A), located in coding exon 10 of the BRCA2 gene, results from a G to A substitution at nucleotide position 5200. The glutamic acid at codon 1734 is replaced by lysine, an amino acid with similar properties. This alteration has been reported in multiple individuals with personal and/or family history of breast and/or ovarian cancers (Konstantopoulou I et al. Clin. Genet., 2014 Jan;85:36-42; Singh J et al. Breast Cancer Res. Treat., 2018 Jul;170:189-196; Momozawa Y et al. Nat Commun, 2018 10;9:4083; Zuntini R et al. Front Genet, 2018 Sep;9:378). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000205413 SCV000260139 uncertain significance Hereditary breast and ovarian cancer syndrome 2020-10-14 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 1734 of the BRCA2 protein (p.Glu1734Lys). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been reported individuals affected with hereditary breast and/or ovarian cancer (PMID: 24010542, 29470806, 30254663). ClinVar contains an entry for this variant (Variation ID: 185896). 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 tolerated, 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 RCV000485722 SCV000572788 uncertain significance not provided 2018-08-22 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.5200G>A at the cDNA level, p.Glu1734Lys (E1734K) at the protein level, and results in the change of a Glutamic Acid to a Lysine (GAA>AAA). This variant, also defined as BRCA2 5428G>A using alternate nomenclature, has been reported in at least one family with breast and/or ovarian cancer (Konstantopoulou 2014). BRCA2 Glu1734Lys was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the RAD51 and POLH binding domains (Roy 2012, Buisson 2014). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether BRCA2 Glu1734Lys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color Health, Inc RCV000165399 SCV000903154 likely benign Hereditary cancer-predisposing syndrome 2016-09-09 criteria provided, single submitter 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.