ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7633G>A (p.Val2545Ile) (rs80358990)

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 RCV000045272 SCV000073285 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-28 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 2545 of the BRCA2 protein (p.Val2545Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with hereditary breast and/or ovarian cancer (HBOC) (PMID: 21735045, 19043619). ClinVar contains an entry for this variant (Variation ID: 52374). 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 isoleucine 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.
Ambry Genetics RCV000130821 SCV000185717 uncertain significance Hereditary cancer-predisposing syndrome 2017-05-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
GeneDx RCV000212262 SCV000210437 uncertain significance not provided 2018-08-21 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.7633G>A at the cDNA level, p.Val2545Ile (V2545I) at the protein level, and results in the change of a Valine to an Isoleucine (GTT>ATT). Using alternate nomenclature, this variant would be defined as BRCA2 7861G>A. This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. BRCA2 Val2545Ile was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the DNA binding domain and the FANCD2 binding domain (Yang 2002). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether BRCA2 Val2545Ile is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Mendelics RCV000045272 SCV000838859 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Color RCV000130821 SCV000911873 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-27 criteria provided, single submitter clinical testing
Mendelics RCV000113799 SCV001139191 uncertain significance Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113799 SCV000147152 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 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.