ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3188A>G (p.Gln1063Arg) (rs775030825)

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 RCV000206648 SCV000260227 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-09-02 criteria provided, single submitter clinical testing This sequence change replaces glutamine with arginine at codon 1063 of the BRCA2 protein (p.Gln1063Arg). The glutamine residue is weakly conserved and there is a small physicochemical difference between glutamine and arginine. This variant is present in population databases (rs775030825, ExAC 0.002%). This variant has not been reported in the literature in individuals with BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 220008). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000501582 SCV000591850 uncertain significance not specified 2013-11-21 criteria provided, single submitter clinical testing
Ambry Genetics RCV000571902 SCV000665978 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence,In silico models in agreement (benign)
Integrated Genetics/Laboratory Corporation of America RCV000586508 SCV000694673 uncertain significance not provided 2016-07-05 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.3188A>G (p.Gln1063Arg) variant involves the alteration of a conserved nucleotide. 3/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). 4/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect multiple ESE sites. Gln1063 is not located in a known functional domain and is not highly conserved across species. However, these predictions have yet to be confirmed by functional studies. This variant was found in 1/119998 control chromosomes at a frequency of 0.0000083, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). 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.
Color RCV000571902 SCV000906060 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-24 criteria provided, single submitter 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.