ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5319G>A (p.Glu1773=) (rs376257217)

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
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000495236 SCV000578699 likely benign Breast-ovarian cancer, familial 2 2017-06-29 reviewed by expert panel curation Synonymous substitution variant, with low bioinformatic likelihood to result in a splicing aberration (Splicing prior probability 0.02; http://priors.hci.utah.edu/PRIORS/).
Invitae RCV000119238 SCV000153985 likely benign Hereditary breast and ovarian cancer syndrome 2020-12-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV000164005 SCV000214608 likely benign Hereditary cancer-predisposing syndrome 2015-05-02 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Illumina Clinical Services Laboratory,Illumina RCV000284760 SCV000383715 uncertain significance Fanconi anemia 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000119238 SCV000383716 uncertain significance Hereditary breast and ovarian cancer syndrome 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000437579 SCV000512366 benign not specified 2015-06-01 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.
Color Health, Inc RCV000164005 SCV000683696 likely benign Hereditary cancer-predisposing syndrome 2017-03-06 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000437579 SCV000694858 likely benign not specified 2020-11-19 criteria provided, single submitter clinical testing
Counsyl RCV000495236 SCV000785148 likely benign Breast-ovarian cancer, familial 2 2017-05-08 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353691 SCV000591960 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The BRCA2 c.5319G>A variant was identified in dbSNP (ID: rs376257217) as “With Likely benign allele”, Clinvitae database (likely benign by ClinVar and Invitae), the ClinVar database (likely benign by Ambry Genetics and Invitae), UMD (5x with an “unclassified variant” classification). This variant was also identified in the NHLBI GO Exome Sequencing Project in 1 of 4402 African American alleles, the Exome Aggregation Consortium database (August 8, 2016) in 2 of 120574 chromosomes (freq. 0.00002) in the following populations: African in 1 of 10222 chromosomes (freq. 0.0001), European in 1 of 66222 chromosomes (freq. 0.00002), increasing the likelihood that this may be a low frequency benign variant in certain populations of origin. The c.5319G>A variant is not expected to have clinical significance because it does not result in a change of amino acid (p.Glu1773Glu) and is not located in a known consensus splice site. The variant occurs outside of the splicing consensus sequence and 2 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing: this is not very predictive of pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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.