ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9538C>T (p.Leu3180Phe) (rs200598289)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165783 SCV000216528 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-03 criteria provided, single submitter clinical testing The p.L3180F variant (also known as c.9538C>T), located in coding exon 25 of the BRCA2 gene, results from a C to T substitution at nucleotide position 9538. The leucine at codon 3180 is replaced by phenylalanine, an amino acid with highly similar properties. This alteration was seen in 1/2089 breast cancer patients and 2/1448 healthy controls in a multi-ethnic Asian cohort (Lai KN et al. BMC Cancer. 2017 Feb;17:149). This amino acid position is highly 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.
GeneDx RCV000482475 SCV000567649 uncertain significance not provided 2018-01-25 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.9538C>T at the cDNA level, p.Leu3180Phe (L3180F) at the protein level, and results in the change of a Leucine to a Phenylalanine (CTT>TTT). Using alternate nomenclature, this variant would be defined as BRCA2 9766C>T. This variant was detected in 1/2089 breast cancer cases and 2/1448 controls in a study of multi-ethnic Asian individuals (Lai 2017). BRCA2 Leu3180Phe was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the DNA binding domain (Yang 2002). In-silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether BRCA2 Leu3180Phe is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000165783 SCV000684069 uncertain significance Hereditary cancer-predisposing syndrome 2019-12-05 criteria provided, single submitter clinical testing
Counsyl RCV000077472 SCV000785683 uncertain significance Breast-ovarian cancer, familial 2 2017-11-01 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000482475 SCV000887969 uncertain significance not provided 2018-08-22 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765145 SCV000896371 uncertain significance Familial cancer of breast; Breast-ovarian cancer, familial 2; Fanconi anemia, complementation group D1; Medulloblastoma; Wilms tumor 1; Malignant tumor of prostate; Pancreatic cancer 2; Glioma susceptibility 3 2018-10-31 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077472 SCV000109270 uncertain significance Breast-ovarian cancer, familial 2 2012-06-12 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077472 SCV000147663 uncertain significance Breast-ovarian cancer, familial 2 2010-09-18 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.