ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3569G>A (p.Arg1190Gln) (rs80358605)

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 RCV000130051 SCV000184878 likely benign Hereditary cancer-predisposing syndrome 2017-12-04 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Other strong data supporting benign classification
Breast Cancer Information Core (BIC) (BRCA2) RCV000031428 SCV000146258 uncertain significance Breast-ovarian cancer, familial 2 2003-12-23 no assertion criteria provided clinical testing
Color RCV000130051 SCV000903953 likely benign Hereditary cancer-predisposing syndrome 2017-06-19 criteria provided, single submitter clinical testing
Counsyl RCV000031428 SCV000488036 uncertain significance Breast-ovarian cancer, familial 2 2015-12-22 criteria provided, single submitter clinical testing
GeneDx RCV000422219 SCV000512356 likely benign not specified 2017-08-17 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Integrated Genetics/Laboratory Corporation of America RCV000587455 SCV000694705 uncertain significance not provided 2016-03-25 criteria provided, single submitter clinical testing Variant Summary: The c.3569G>A variant in BRCA2 gene is a missense change that alters a non-conserved and 4/5 in silico tools predict benign outcome. The variant is found in the large control population dataset of ExAC at a frequency of 0.006%, exclusively in individuals of South Asian descent (0.04%). This frequency does not exceed the maximal expected frequency of a pathogenic allele (0.075%), however the variant may be a functional ethnic specific polymorphism. To our knowledge, variant carrier patients were not reported in the literature and studies assessing the functional impact the variant may have on the BRCA2 protein have not been published either at the time of scoring. Reputable databases/diagnostic centers listed the variant of interest with a classification of Likely Benign. Due to the absence of clinical data and functional studies, the variant was classified as a variant of uncertain significance until more information becomes available.
Invitae RCV000044224 SCV000072237 uncertain significance Hereditary breast and ovarian cancer syndrome 2017-12-24 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 1190 of the BRCA2 protein (p.Arg1190Gln). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs80358605, ExAC 0.04%). This variant has been reported in an individual affected with uterine serous carcinoma (PMID: 22811390). ClinVar contains an entry for this variant (Variation ID: 37847). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The glutamine amino acid residue is also found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. It has been reported in both the population and affected individuals, but the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Sharing Clinical Reports Project (SCRP) RCV000031428 SCV000054033 likely benign Breast-ovarian cancer, familial 2 2012-05-01 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.