ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.68-7T>A (rs81002830)

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Total submissions: 24
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Breast Cancer Information Core (BIC) (BRCA2) RCV000077384 SCV000146100 uncertain significance Breast-ovarian cancer, familial 2 2010-12-17 no assertion criteria provided clinical testing
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency RCV000168529 SCV000586913 likely benign not specified 2017-04-18 criteria provided, single submitter clinical testing
Color RCV000579605 SCV000683813 benign Hereditary cancer-predisposing syndrome 2014-12-05 criteria provided, single submitter clinical testing
Counsyl RCV000077384 SCV000220412 likely benign Breast-ovarian cancer, familial 2 2014-06-13 criteria provided, single submitter literature only
Department of Medical Genetics,University Hospital of North Norway RCV000077384 SCV000301443 likely benign Breast-ovarian cancer, familial 2 2016-05-01 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000168529 SCV000591659 benign not specified 2014-11-19 criteria provided, single submitter clinical testing
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000045051 SCV000257614 uncertain significance Hereditary breast and ovarian cancer syndrome 2015-07-21 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000168529 SCV000228764 likely benign not specified 2014-10-23 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077384 SCV000783127 benign Breast-ovarian cancer, familial 2 2018-04-12 reviewed by expert panel curation IARC class based on combined odds from multifactorial likelihood analysis, thresholds for class as per Easton et al. 2007 (PMID: 17924331). Class 1 Not Pathogenic based on posterior probability of pathogenicity = 7.44x10-115. There was no evidence for increased risk of breast cancer (OR 1.03; 95%CI 0.86-1.24) from case-control analysis of 83636 individuals. Nor for a deleterious effect of the variant when co-occurring with a pathogenic variant. Quantitative splicing analysis revealed an exon 3 exclusion rate of 13% in carriers compared to 3% in controls. Exon 3 exclusion from the variant allele is estimated at 20%.
Fulgent Genetics,Fulgent Genetics RCV000077384 SCV000575752 benign Breast-ovarian cancer, familial 2 2015-12-30 criteria provided, single submitter clinical testing
GeneDx RCV000074550 SCV000108635 benign Familial cancer of breast 2014-04-25 criteria provided, single submitter clinical testing The variant is found in BRCA1-BRCA2,ENDOM-HEREDIC,BR-OV-HEREDIC panel(s).
Genetic Services Laboratory, University of Chicago RCV000168529 SCV000593697 likely benign not specified 2016-07-18 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000045051 SCV000383601 likely benign Hereditary breast and ovarian cancer syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000362403 SCV000383602 likely benign Fanconi anemia 2016-06-14 criteria provided, single submitter clinical testing
Institute for Biomarker Research,Medical Diagnostic Laboratories, L.L.C. RCV000045051 SCV000747802 likely benign Hereditary breast and ovarian cancer syndrome 2018-01-16 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000045051 SCV000494401 benign Hereditary breast and ovarian cancer syndrome 2016-08-23 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.68-7T>A variant involves the alteration of a non-conserved intronic nucleotide. 2/5 splice prediction tools predict a significant impact on normal splicing. Although functional studies evaluating the splicing effect of this variant show a production of a exon 3 deletion transcript wild type control DNA also showed the production of this exon 3 deletion transcript albeit at a lesser quantitative amount (Sanz_2010 and Muller_2010). Furthermore, an additional functional study evaluating the variant of interest's effect on key aspects of BRCA2 function such homologous recombination and sensitivity to DNA damaging agents showed comparable abilities to the wild-type BRCA2. This variant was found in 282/118368 control chromosomes at a frequency of 0.0023824, which is approximately 3.2 times the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503), suggesting this variant is likely a benign polymorphism. This variant has been reported in many HBOC patients/families. It has been shown not to cosegregate with disease in two families (Santos_2014). In addition, the variant has been reported to co-occur with multiple different deleterious variants in BRCA1/2 (UMD), strongly suggesting for a benign outcome. Most of the clinical diagnostic laboratories in ClinVar have classified this variant as benign/likely benign. Taken together, this variant is classified as benign.
Invitae RCV000045051 SCV000073064 benign Hereditary breast and ovarian cancer syndrome 2018-01-10 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000168529 SCV000538468 likely benign not specified 2016-03-28 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Multiple conflicting assertions about splice impact; ExAC: 0.5%(36/6594) Finnish chromosomes
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000656581 SCV000778631 likely benign not provided 2016-12-06 no assertion criteria provided clinical testing
Michigan Medical Genetics Laboratories,University of Michigan RCV000077384 SCV000195944 benign Breast-ovarian cancer, familial 2 2014-11-03 criteria provided, single submitter clinical testing
Pathway Genomics RCV000077384 SCV000223767 likely benign Breast-ovarian cancer, familial 2 2014-10-30 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000168529 SCV000587534 uncertain significance not specified 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000077384 SCV000109181 benign Breast-ovarian cancer, familial 2 2012-04-05 no assertion criteria provided clinical testing
True Health Diagnostics RCV000579605 SCV000787944 likely benign Hereditary cancer-predisposing syndrome 2017-06-27 no assertion criteria provided clinical testing

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