ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3362C>G (p.Ser1121Ter) (rs80358579)

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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 RCV000131100 SCV000186030 pathogenic Hereditary cancer-predisposing syndrome 2017-07-12 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) RCV000077302 SCV000146219 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000131100 SCV000905009 pathogenic Hereditary cancer-predisposing syndrome 2018-06-11 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077302 SCV000326857 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000504065 SCV000591857 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-16 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077302 SCV000300627 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 RCV000219700 SCV000279245 pathogenic not provided 2018-09-12 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA2 c.3362C>G at the cDNA level and p.Ser1121Ter (S1121X) at the protein level. This variant is also known as BRCA2 3590C>G using alternate nomenclature. The substitution creates a nonsense variant, which changes a Serine to a premature stop codon (TCA>TGA), 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 a large cohort of self-identified Ashkenazi Jewish women with hereditary breast and/or ovarian cancer as well as in two affected members of a Filipino family with early-onset breast cancer (De Leon 2002, Finkelman 2012). We consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000504065 SCV000694692 pathogenic Hereditary breast and ovarian cancer syndrome 2016-09-20 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.3362C>G (p.Ser1121X) 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.3455T>G, p.Leu1152X; c.3545_3546delTT, p.Phe1182fsX1; c.3570delG, p.Lys1191fsX6). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 120614 control chromosomes but has been reported in affected individuals in the literature, including two affected sisters. 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) RCV000077302 SCV000109099 pathogenic Breast-ovarian cancer, familial 2 2008-12-12 no assertion criteria provided clinical testing

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