ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6124C>T (p.Gln2042Ter) (rs80358851)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000563525 SCV000661157 pathogenic Hereditary cancer-predisposing syndrome 2017-10-26 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) RCV000077369 SCV000146772 pathogenic Breast-ovarian cancer, familial 2 2003-12-23 no assertion criteria provided clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077369 SCV000327357 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000077369 SCV000488909 pathogenic Breast-ovarian cancer, familial 2 2016-07-21 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077369 SCV000300985 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 RCV000223048 SCV000279249 pathogenic not provided 2018-07-12 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA2 c.6124C>T at the cDNA level and p.Gln2042Ter (Q2042X) at the protein level. 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, previously published as BRCA2 6352C>T using alternate nomenclature, has been reported in several families with Hereditary Breast and Ovarian Cancer (Veschi 2007, Litton 2012) and is considered pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000044850 SCV000694939 pathogenic Hereditary breast and ovarian cancer syndrome 2016-10-18 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.6124C>T (p.Gln2042X) 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.7133C>G/p.Ser2378X). One in silico tool predicts a damaging outcome for this variant. This variant was found in 1/122188 control chromosomes at a frequency of 0.0000082, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). This variant has been reported in multiple affected individuals. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000044850 SCV000072863 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln2042*) 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 an individual affected with breast or ovarian cancer (PMID: 18703817). ClinVar contains an entry for this variant (Variation ID: 52017). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000077369 SCV000109166 pathogenic Breast-ovarian cancer, familial 2 2010-07-26 no assertion criteria provided clinical testing

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