ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3206C>T (p.Ser1069Phe) (rs80358563)

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
Invitae RCV000044147 SCV000072160 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-10 criteria provided, single submitter clinical testing This sequence change replaces serine with phenylalanine at codon 1069 of the BRCA2 protein (p.Ser1069Phe). The serine residue is moderately conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 51423). 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000165150 SCV000215861 uncertain significance Hereditary cancer-predisposing syndrome 2016-04-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Counsyl RCV000113147 SCV000785152 uncertain significance Breast-ovarian cancer, familial 2 2017-05-08 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000781122 SCV000918970 uncertain significance not specified 2018-05-21 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.3206C>T (p.Ser1069Phe) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 119698 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating its impact on protein function have been reported. Two co-occurrences with a pathogenic variant (one derived from literature, and another derived from our internal testing experience) have been reported (BRCA2 c.5042_5043delTG, p.Val1681Glufs*7), providing supporting evidence for a benign role. Given the age (50 year old female) of the patient reported in literature, the possibility of a diagnosis of Fanconi Anemia can be possibly ruled out, although the authors make no firm statements to this effect. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Breast Cancer Information Core (BIC) (BRCA2) RCV000113147 SCV000146190 uncertain significance Breast-ovarian cancer, familial 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.