ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6008T>C (p.Ile2003Thr)

dbSNP: rs80358837
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
Labcorp Genetics (formerly Invitae), Labcorp RCV000044818 SCV000072831 uncertain significance Hereditary breast ovarian cancer syndrome 2024-10-23 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 2003 of the BRCA2 protein (p.Ile2003Thr). 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: 51987). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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.
Ambry Genetics RCV002354236 SCV002656187 uncertain significance Hereditary cancer-predisposing syndrome 2023-11-13 criteria provided, single submitter clinical testing The p.I2003T variant (also known as c.6008T>C), located in coding exon 10 of the BRCA2 gene, results from a T to C substitution at nucleotide position 6008. The isoleucine at codon 2003 is replaced by threonine, an amino acid with similar properties. This alteration was identified in an individual diagnosed with breast cancer (Boga I et al. Eur J Breast Health, 2023 Jul;19:235-252). This amino acid position is poorly 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV002354236 SCV003850851 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).
Breast Cancer Information Core (BIC) (BRCA2) RCV000113519 SCV000146750 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2003-12-23 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.