ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.1517T>C (p.Phe506Ser)

dbSNP: rs1249900164
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000637551 SCV000759015 uncertain significance Hereditary breast ovarian cancer syndrome 2024-04-24 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 506 of the BRCA2 protein (p.Phe506Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 531316). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function with a negative predictive value of 95%. 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 RCV001570107 SCV001794324 uncertain significance not provided 2020-09-28 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 1745T>C
Ambry Genetics RCV002388048 SCV002709849 uncertain significance Hereditary cancer-predisposing syndrome 2024-12-09 criteria provided, single submitter clinical testing The p.F506S variant (also known as c.1517T>C), located in coding exon 9 of the BRCA2 gene, results from a T to C substitution at nucleotide position 1517. The phenylalanine at codon 506 is replaced by serine, an amino acid with highly dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002492982 SCV002788213 uncertain significance Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 2; Fanconi anemia complementation group D1; Medulloblastoma; Wilms tumor 1; Malignant tumor of prostate; Pancreatic cancer, susceptibility to, 2; Glioma susceptibility 3 2022-05-16 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine, University of Washington RCV002388048 SCV003851451 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).

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.