ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.10159A>G (p.Thr3387Ala)

dbSNP: rs786202571
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
Ambry Genetics RCV000217613 SCV000274598 uncertain significance Hereditary cancer-predisposing syndrome 2015-03-20 criteria provided, single submitter clinical testing The p.T3387A variant (also known as c.10159A>G and 10387A>G), located in coding exon 26 of the BRCA2 gene, results from an A to G substitution at nucleotide position 10159. The threonine at codon 3387 is replaced by alanine, an amino acid with similar properties. Residue 3387 has been shown to be a Chk2 consensus phosphorylation site; substitution of threonine by alanine abolished in vitro phosphorylation by Chk1 and Chk2 (Bahassi EM et al. Oncogene 2008 Jun; 27(28):3977-85). Authors demonstrated that the p.T3387A alteration interferes with Rad51 release from the carboxy-terminal domain of BRCA2 in vivo following DNA damage. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 105000 alleles tested) in our clinical cohort. This amino acid position is not well 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 p.T3387A remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001219199 SCV001391124 uncertain significance Hereditary breast ovarian cancer syndrome 2019-10-14 criteria provided, single submitter clinical testing 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. This variant has been reported to affect BRCA2 protein function (PMID: 18317453). This variant has not been reported in the literature in individuals with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 230907). This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with alanine at codon 3387 of the BRCA2 protein (p.Thr3387Ala). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and alanine.
Fulgent Genetics, Fulgent Genetics RCV005008161 SCV005634001 uncertain significance Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 2; Fanconi anemia complementation group D1; Medulloblastoma; Wilms tumor 1; Pancreatic cancer, susceptibility to, 2; Glioma susceptibility 3; Familial prostate cancer 2024-06-14 criteria provided, single submitter clinical testing
BRCAlab, Lund University RCV003493516 SCV004243896 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2020-03-02 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.