ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8297del (p.Thr2766fs) (rs80359705)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 19
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163359 SCV000213895 pathogenic Hereditary cancer-predisposing syndrome 2017-11-01 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034463 SCV000043230 pathogenic Hereditary breast and ovarian cancer syndrome 2012-07-13 no assertion criteria provided research Converted during submission to Pathogenic.
Breast Cancer Information Core (BIC) (BRCA2) RCV000031732 SCV000147316 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency RCV000034463 SCV000586981 pathogenic Hereditary breast and ovarian cancer syndrome 2017-04-18 criteria provided, single submitter clinical testing
Color RCV000163359 SCV000683953 pathogenic Hereditary cancer-predisposing syndrome 2015-04-06 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031732 SCV000327853 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031732 SCV000282457 pathogenic Breast-ovarian cancer, familial 2 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000045466 SCV000210793 pathogenic not provided 2018-05-22 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA2 is denoted c.8297delC at the cDNA level and p.Thr2766AsnfsX11 (T2766NfsX11) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA2 8525delC. The normal sequence, with the base that is deleted in brackets, is TGTA[delC]ACCT. The deletion causes a frameshift, which changes a Threonine to an Asparagine at codon 2766, and creates a premature stop codon at position 11 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA2 c.8297delC has been observed in multiple individuals with a personal and/or family history of prostate, breast, and ovarian cancer (Tavtigian 1996, Evans 2003, Edwards 2010, Willems-Jones 2012, McVeigh 2014, Pritzlaff 2017). We consider this variant to be pathogenic.
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000031732 SCV000778589 pathogenic Breast-ovarian cancer, familial 2 2018-04-16 criteria provided, single submitter research
Institute for Biomarker Research,Medical Diagnostic Laboratories, L.L.C. RCV000163359 SCV000803159 pathogenic Hereditary cancer-predisposing syndrome 2018-05-23 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000034463 SCV000695139 pathogenic Hereditary breast and ovarian cancer syndrome 2016-07-01 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.8297delC (p.Thr2766Asnfs) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant of interest was not found in controls (ExAC, 1000 Gs or ESP). Multiple publications cite the variant in affected individuals, along with multiple reputable databases/clinical laboratories citing the variant as "pathogenic." Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as Pathogenic.
Invitae RCV000034463 SCV000073479 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr2766Asnfs*11) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in numerous individuals and families affected with breast, ovarian and/or prostate cancer (PMID: 8589730, 10682686, 12960223, 20736950, 23028338, 26681312, 25085752). This variant is also known as 8525delC in the literature. ClinVar contains an entry for this variant (Variation ID: 38149). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000034463 SCV000966960 pathogenic Hereditary breast and ovarian cancer syndrome 2018-02-22 criteria provided, single submitter clinical testing The p.Thr2766AsnfsX11 (NM_000059.3 c.8297delC) variant in BRCA2 (also referred t o as c.8285delC in the literature) has been previously reported in many individu als and families with breast, ovarian or prostate cancer (Tavtigian 1996, Castro 2013, McVeigh 2014, Wong-Brown 2015), and was absent from large population stud ies. In addition, this variant was classified as Pathogenic by the ClinGen-appr oved ENIGMA expert panel (ClinVar SCV000282457.1). This variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at position 2766 and leads to a premature termination codon 11 amino acids downstre am. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of BRCA2 function is an established disease mechanism in here ditary breast and ovarian cancer syndrome (HBOC). In summary, this variant meets our criteria to be classified as pathogenic for HBOC in an autosomal dominant m anner based on its occurrence in affected individuals and its predicted impact t o the protein. ACMG/AMP Criteria applied: PVS1, PM2, PS4_Moderate, PP5 (Richards 2015).
Michigan Medical Genetics Laboratories,University of Michigan RCV000031732 SCV000267818 pathogenic Breast-ovarian cancer, familial 2 2016-04-21 criteria provided, single submitter clinical testing
OMIM RCV000031732 SCV000030129 pathogenic Breast-ovarian cancer, familial 2 1996-03-01 no assertion criteria provided literature only
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000045466 SCV000296689 pathogenic not provided 2015-04-16 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000034463 SCV000587944 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031732 SCV000054339 pathogenic Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing
University of Washington Department of Laboratory Medicine,University of Washington RCV000210122 SCV000266047 pathogenic Breast-ovarian cancer, familial 1 2015-11-20 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.