ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7480C>T (p.Arg2494Ter) (rs80358972)

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Total submissions: 17
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131084 SCV000186014 pathogenic Hereditary cancer-predisposing syndrome 2018-02-23 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) RCV000031681 SCV000147102 pathogenic Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Color RCV000131084 SCV000683877 pathogenic Hereditary cancer-predisposing syndrome 2017-01-02 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031681 SCV000327668 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000031681 SCV000677697 pathogenic Breast-ovarian cancer, familial 2 2015-07-28 criteria provided, single submitter clinical testing
Department of Medical Genetics,Oslo University Hospital RCV000031681 SCV000605694 pathogenic Breast-ovarian cancer, familial 2 2016-03-03 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000225750 SCV000592114 pathogenic Hereditary breast and ovarian cancer syndrome 2015-02-17 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000045227 SCV000226199 pathogenic not provided 2015-03-12 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031681 SCV000282443 pathogenic Breast-ovarian cancer, familial 2 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Fulgent Genetics,Fulgent Genetics RCV000515398 SCV000611180 pathogenic Familial cancer of breast; Breast-ovarian cancer, familial 2; Fanconi anemia, complementation group D1; Medulloblastoma; Wilms tumor 1; Malignant tumor of prostate; Pancreatic cancer 2; Glioma susceptibility 3; Tracheoesophageal fistula 2017-05-18 criteria provided, single submitter clinical testing
GeneDx RCV000045227 SCV000210426 pathogenic not provided 2018-07-27 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA2 c.7480C>T at the cDNA level and p.Arg2494Ter (R2494X) at the protein level. The substitution creates a nonsense variant, which changes an Arginine to a premature stop codon (CGA>TGA). This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, also defined as BRCA2 7708C>T using alternate nomenclature, has been described as a recurrent variant in both Finnish and Korean hereditary breast and ovarian cancer families (Seong 2009, Janavicius 2010, Kim, 2012, Kang 2015, Lee 2017, Park 2017) . We consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000225750 SCV000916927 pathogenic Hereditary breast and ovarian cancer syndrome 2017-10-04 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.7480C>T (p.Arg2494X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g., c.7543dupA [p.Thr2515fsX24] and c.7556dupC [p.Arg2520fsX19]). One in silico tool predicts a damaging outcome for this variant. This variant was found in 8/246212 control chromosomes at a frequency of 0.0000325, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). The variant has been identified in numerous HBOC patients and has been reported as a common mutation in the Korean and Finnish populations (Kim_2012; Sarantaus_2000). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000225750 SCV000073240 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.Arg2494*) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs80358972, ExAC 0.05%). This variant has been observed as a frequent causative variant in Finnish and Korean populations with breast and/or ovarian cancer (PMID: 9361038, 19656164, 16455195, 24312913, 22798144, 23199084). This variant is also known as 7708C>T in the literature. ClinVar contains an entry for this variant (Variation ID: 38099). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Michigan Medical Genetics Laboratories,University of Michigan RCV000031681 SCV000267807 pathogenic Breast-ovarian cancer, familial 2 2016-04-21 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000045227 SCV000296715 pathogenic not provided 2015-03-06 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000225750 SCV000587896 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031681 SCV000054288 pathogenic Breast-ovarian cancer, familial 2 2012-09-07 no assertion criteria provided clinical testing

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