ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7565C>T (p.Ser2522Phe) (rs80358985)

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 RCV000045249 SCV000073262 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-10 criteria provided, single submitter clinical testing This sequence change replaces serine with phenylalanine at codon 2522 of the BRCA2 protein (p.Ser2522Phe). The serine residue is moderately conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is present in population databases (rs80358985, ExAC 0.002%). This variant has been reported in the literature in several individuals affected with breast and/or ovarian cancer (PMID: 11873550, 15944772, 21120943, 25782689). It has also been reported in one individual with personal and family history of prostate cancer (PMID: 24556621). This variant is also known as c.7793C>T in the literature. ClinVar contains an entry for this variant (Variation ID: 38104). Experimental studies have shown that this missense change does not have a significant effect on the homology directed repair activity of BRCA2 (PMID: 29394989, 29884841). 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 RCV000212261 SCV000210429 likely benign not specified 2018-02-23 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics RCV000162600 SCV000213021 uncertain significance Hereditary cancer-predisposing syndrome 2016-11-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbSNP, ESP, 1000 Genomes),in silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Insufficient or Conflicting Evidence
Color RCV000162600 SCV000683889 likely benign Hereditary cancer-predisposing syndrome 2018-06-21 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000587666 SCV000695080 uncertain significance not provided 2017-07-18 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.7565C>T (p.Ser2522Phe) variant located in the helical domain (Salgado_2005) involves the alteration of a conserved nucleotide and 5/5 in silico tools predict a damaging outcome for this variant. However, these predictions have yet to be functionally assessed. This variant was found in 1/120720 control chromosomes at a frequency of 0.0000083, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). Multiple publications have cited the variant in affected individuals, however, with limited information (ie, lack of co-occurrence and/or cosegregation data). In addition, multiple clinical diagnostic laboratories cite the variant with conflicting classifications "likely benign" or "uncertain significance." Therefore, due to the limited available information, the variant of interest has been classified as a "Variant of Uncertain Significance (VUS)," until additional information becomes available (ie, clinical and functional studies).
Sharing Clinical Reports Project (SCRP) RCV000031686 SCV000054293 likely benign Breast-ovarian cancer, familial 2 2012-04-27 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031686 SCV000147125 uncertain significance Breast-ovarian cancer, familial 2 2013-05-21 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.