ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5614A>T (p.Lys1872Ter) (rs80358783)

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
Ambry Genetics RCV000162926 SCV000213413 pathogenic Hereditary cancer-predisposing syndrome 2017-03-01 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)
Breast Cancer Information Core (BIC) (BRCA2) RCV000113450 SCV000146645 pathogenic Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Color RCV000162926 SCV000903717 pathogenic Hereditary cancer-predisposing syndrome 2018-04-11 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000113450 SCV000327244 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000113450 SCV000677686 pathogenic Breast-ovarian cancer, familial 2 2017-02-01 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000113450 SCV000300905 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000212241 SCV000210357 pathogenic not provided 2018-11-09 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.5614A>T at the cDNA level and p.Lys1872Ter (K1872X) at the protein level. The substitution creates a nonsense variant, which changes a Lysine to a premature stop codon (AAA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, also defined as 5842A>T using alternate nomenclature, has been reported in association with hereditary breast and ovarian cancer (Meyer 2003, Ramus 2007, Tea 2014) and is considered pathogenic.
Invitae RCV000044696 SCV000072709 pathogenic Hereditary breast and ovarian cancer syndrome 2018-09-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys1872*) 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 reported in the literature in a family with ovarian cancer and in an individual with a personal or family history of breast cancer or ovarian cancer (PMID: 17688236, 24156927). ClinVar contains an entry for this variant (Variation ID: 37979). 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 RCV000044696 SCV000605792 pathogenic Hereditary breast and ovarian cancer syndrome 2016-10-20 criteria provided, single submitter clinical testing The p.Lys1872X variant in BRCA2 has been previously reported in at least 3 indiv iduals with BRCA2-associated cancers (Meyer 2003, Ramus 2007, Tea 2014) and segr egated with ovarian cancer in 1 affected relative (Ramus 2007). It was absent fr om large population studies. This nonsense variant leads to a premature terminat ion codon at position 1872, which is predicted to lead to a truncated or absent protein. Heterozygous loss of function of the BRCA2 gene is an established disea se mechanism in hereditary breast and ovarian cancer (HBOC). In summary, this va riant meets our criteria to be classified as pathogenic for HBOC in an autosomal dominant manner.
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000044696 SCV000587780 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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.