ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6761T>A (p.Phe2254Tyr) (rs786202915)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 10
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165980 SCV000216738 uncertain significance Hereditary cancer-predisposing syndrome 2016-10-31 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000479534 SCV000296752 uncertain significance not specified 2016-12-30 criteria provided, single submitter clinical testing
Counsyl RCV000238769 SCV000488286 uncertain significance Breast-ovarian cancer, familial 2 2016-02-16 criteria provided, single submitter clinical testing
GeneDx RCV000587444 SCV000566695 uncertain significance not provided 2018-09-20 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.6761T>A at the cDNA level, p.Phe2254Tyr (F2254Y) at the protein level, and results in the change of a Phenylalanine to a Tyrosine (TTT>TAT). Using alternate nomenclature, this variant would be defined as BRCA2 6989T>A. This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. BRCA2 Phe2254Tyr was not observed in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure or function. Based on currently available evidence, it is unclear whether BRCA2 Phe2254Tyr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000479534 SCV000592073 likely benign not specified 2012-10-01 criteria provided, single submitter clinical testing
Invitae RCV000530254 SCV000635529 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-10-09 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with tyrosine at codon 2254 of the BRCA2 protein (p.Phe2254Tyr). The phenylalanine residue is moderately conserved and there is a small physicochemical difference between phenylalanine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 186392). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Color RCV000165980 SCV000683808 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-04 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000587444 SCV000694994 uncertain significance not provided 2017-01-18 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.6761T>A (p.Phe2254Tyr) variant involves the alteration of a non-conserved nucleotide. 3/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant is absent in 121018 control chromosomes. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. The variant of interest has not, to our knowledge, been reported in affected individuals via publications; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000587444 SCV000887890 uncertain significance not provided 2018-01-17 criteria provided, single submitter clinical testing
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735581 SCV000863719 uncertain significance Breast and/or ovarian cancer 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.