ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3922G>T (p.Glu1308Ter) (rs80358638)

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Total submissions: 16
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031448 SCV000300685 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000167856 SCV000072325 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.Glu1308*) 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 individuals affected with breast and/or ovarian cancer (PMID: 12655567, 12955716, 23479189, 22682623, 20033483), prostate cancer (PMID: 27433846), male breast cancer (PMID: 28008555), and Fanconi anemia (PMID: 14559878). It is also known as 4150G>T in the literature. ClinVar contains an entry for this variant (Variation ID: 37867). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000128952 SCV000172830 pathogenic Hereditary cancer-predisposing syndrome 2017-08-23 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)
GeneDx RCV000044312 SCV000210325 pathogenic not provided 2018-09-19 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.3922G>T at the cDNA level and p.Glu1308Ter (E1308X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamic Acid to a premature stop codon (GAA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in several individuals with either a personal or family history of breast and/or ovarian cancer and is considered a recurrent variant in Hispanic individuals (Vogel 2007, Dutil 2012, de Juan Jimenez 2013). Additionally, BRCA2 Glu1308Ter has been observed in trans with another BRCA2 variant, p.Gln3066Ter, in a child with Fanconi anemia (Offit 2003). Based on current evidence, we consider this variant to be pathogenic.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000044312 SCV000225189 pathogenic not provided 2015-07-06 criteria provided, single submitter clinical testing
Color RCV000128952 SCV000292135 pathogenic Hereditary cancer-predisposing syndrome 2015-07-29 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000044312 SCV000296714 pathogenic not provided 2015-03-06 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031448 SCV000326942 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000031448 SCV000488095 pathogenic Breast-ovarian cancer, familial 2 2015-12-28 criteria provided, single submitter clinical testing
Baylor Genetics RCV000465243 SCV000541012 pathogenic Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
Genologica Medica RCV000031448 SCV000577953 pathogenic Breast-ovarian cancer, familial 2 2017-01-01 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000167856 SCV000694731 pathogenic Hereditary breast and ovarian cancer syndrome 2016-06-20 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.3922G>T (p.Glu1308X) 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.3967A>T/p.Lys1323X, c.4222C>T/p.Gln1408X). One in silico tool predicts a damaging outcome for this variant. This variant has been reported in numerous breast cancer patients and is absent in 88146 control chromosomes. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000031448 SCV000054053 pathogenic Breast-ovarian cancer, familial 2 2012-07-27 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031448 SCV000146336 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Pathway Genomics RCV000031448 SCV000207341 pathogenic Breast-ovarian cancer, familial 2 2014-11-06 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000167856 SCV000587691 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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