ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3109C>T (p.Gln1037Ter) (rs80358557)

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Total submissions: 12
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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) RCV000031400 SCV000300589 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 RCV000044120 SCV000072133 pathogenic Hereditary breast and ovarian cancer syndrome 2018-11-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1037*) 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 individuals affected with breast and/or ovarian cancer (PMID: 10874312, 22970155, 26757417, 18489799, 19353265, 26187060, 26852015, 20104584). It has been identified predominantly in individuals of Asian ancestry. Haplotype analysis suggests that this may be a common founder mutation (PMID: 22970155). This variant is also known as 3337C>T in the literature. ClinVar contains an entry for this variant (Variation ID: 37819). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000160056 SCV000210305 pathogenic not provided 2018-06-28 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.3109C>T at the cDNA level and p.Gln1037Ter (Q1037X) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA2 3337C>T. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAA>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 as a Chinese founder variant and has been observed in individuals of various ancestries with breast and/or ovarian cancer (Khoo 2000, Liede 2002, Machackova 2008, Kwong 2009, Cao 2016, Yang 2017). We consider this variant to be pathogenic.
Ambry Genetics RCV000216711 SCV000274469 pathogenic Hereditary cancer-predisposing syndrome 2018-03-02 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)
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031400 SCV000326814 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000044120 SCV000591848 pathogenic Hereditary breast and ovarian cancer syndrome 2015-08-26 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000762916 SCV000893328 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 2018-10-31 criteria provided, single submitter clinical testing
Color RCV000216711 SCV000903411 pathogenic Hereditary cancer-predisposing syndrome 2017-03-20 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000044120 SCV000916864 pathogenic Hereditary breast and ovarian cancer syndrome 2017-09-18 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.3109C>T (p.Gln1037X) 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.3166C>T [p.Gln1056X], c.3187C>T [p.Gln1063X], and c.3199delA [p.Thr1067fsX10]). MutationTaster predicts a damaging outcome for this variant. This variant was found in 1/244370 control chromosomes at a frequency of 0.0000041, 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 is considered a recurrent mutation in Chinese populations. 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) RCV000031400 SCV000054005 pathogenic Breast-ovarian cancer, familial 2 2011-11-07 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031400 SCV000146171 not provided Breast-ovarian cancer, familial 2 no assertion provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000044120 SCV000587657 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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