ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4570_4573del (p.Phe1524fs) (rs1057517565)

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
Counsyl RCV000410419 SCV000488611 likely pathogenic Breast-ovarian cancer, familial 2 2016-05-05 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000781039 SCV000918811 likely pathogenic Hereditary breast and ovarian cancer syndrome 2018-04-23 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.4570_4573delTTTC (p.Phe1524IlefsX18) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (eg. c.4587dupG, p.Lys1530fsX4; c.4631delA, p.Asn1544fsX24; c.4631dupA, p.Asn1544fsX4). The variant was absent in 120602 control chromosomes. c.4570_4573delTTTC has been reported in the literature in one individual affected with breast cancer (Kwong_2015). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Invitae RCV000781039 SCV001198370 pathogenic Hereditary breast and ovarian cancer syndrome 2019-11-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Phe1524Ilefs*18) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with breast cancer (PMID: 26187060). ClinVar contains an entry for this variant (Variation ID: 371845). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Color Health, Inc RCV001180643 SCV001345611 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 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.