ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8487+47C>T (rs11571744)

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
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000113946 SCV000245178 benign Breast-ovarian cancer, familial 2 2015-01-12 reviewed by expert panel curation Class 1 not pathogenic based on frequency >1% in an outbred sampleset. Frequency 0.05488 (African), derived from 1000 genomes (2012-04-30).
Michigan Medical Genetics Laboratories,University of Michigan RCV000113946 SCV000196015 benign Breast-ovarian cancer, familial 2 2014-11-03 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000113946 SCV000743347 likely benign Breast-ovarian cancer, familial 2 2014-10-09 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113946 SCV000147379 uncertain significance Breast-ovarian cancer, familial 2 1998-11-30 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000499878 SCV000592201 benign not specified no assertion criteria provided clinical testing The BRCA2 c.8487+47C>T variant was identified in the literature. The variant was also identified in dbSNP (ID: rs11571744) “With Uncertain significance allele”, with a minor allele frequency of 0.0162 (1000 Genomes Project), NHLBI Exome Sequencing Project (Exome Variant Server), Exome Aggregation Consortium (ExAC) database, Clinvitae database (X1), LOVD, the ClinVar database, GeneInsight COGR database (1X), the BIC database (2X with no clinical importance), and UMD (37X as a neutral variant). In UMD the variant was identified with a co-occurring pathogenic BRCA1 and BRCA2 variants (BRCA1 (c.1813dup (p.Ile605AsnfsX11); c.5576_5579delTTAA (p.Ile1859LysfsX3); c.1310_1313delAAGA (p.Lys437IlefsX22); BRCA2 (c.IVS16+6T>C (c.4986+6T>C); c.1488delT (p.Leu498SerfsX5)), increasing the likelihood that the c.8487+47C>T variant does not have clinical significance. In BIC database variant was reported to occur in outbred control reference groups at an allele frequency >1% (MAF>0.01), and classifies the variant as not pathogenic/low clinical significance. This variant was identified in the 1000 Genomes Project in 81 of 5000 chromosomes (frequency: 0.0162), Exome Variant Server project in 1 of 8600 European American and in 197 of 4404 African American alleles, increasing the likelihood that this may be a low frequency benign variant in certain populations of origin. The variant was also found in the Exome Aggregation Consortium (ExAC) database (released Jan 13, 2015) in 436 of 9658 chromosomes (frequency: 0.045) and nine times in homozygous state from a population of African individuals, increasing the likelihood that this may be a low frequency benign variant in certain populations of origin. The variant was also identified in 39 of 91040 European (Non-Finnish)/ Latino / South Asian/European (Finnish) individuals, increasing the likelihood this could be a low frequency benign variant. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In addition, global sequence diversity analysis identified the variant has global heterozygosity 0.018 and classified the variant as polymorphism (Wagner 1999). In summary, based on the above information, this variant meets our laboratory's criteria to be classified as 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.