ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1889del (p.Thr630fs) (rs80359315)

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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 RCV000221409 SCV000277553 pathogenic Hereditary cancer-predisposing syndrome 2017-12-05 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) RCV000077271 SCV000145973 pathogenic Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077271 SCV000326631 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077271 SCV000300476 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 RCV000478099 SCV000568458 pathogenic not provided 2019-01-04 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA2 is denoted c.1889delC at the cDNA level and p.Thr630AsnfsX14 (T630NfsX14) at the protein level. The normal sequence, with the base that is deleted in brackets, is CTTA[delC]ATTT. The deletion causes a frameshift, which changes a Threonine to an Asparagine at codon 630, and creates a premature stop codon at position 14 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA2 c.1889delC, also known as 2117delC using alternate nomenclature, has been observed in at least two individuals with breast cancer as well as in a man with prostate cancer (Edwards 2010, Wong-Brown 2015, Davies 2017). We consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000043918 SCV000694582 pathogenic Hereditary breast and ovarian cancer syndrome 2016-09-08 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.1889delC (p.Thr630Asnfs) 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.1929delG (p.Arg645fs), c.2103_2106delTATT (p.Phe701fs), and c.2212dupT (p.Cys738fs). The variant of interest has not been observed in controls (ExAC, 1000 Gs, or ESP) and has been reported in multiple affected individuals via publications and databases. In addition, multiple clinical diagnostic laboratories cite the variant as "pathogenic." Therefore, the variant of interest has been classified as "Pathogenic."
Invitae RCV000043918 SCV000071931 pathogenic Hereditary breast and ovarian cancer syndrome 2018-10-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr630Asnfs*14) 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 the literature in individuals affected with breast cancer and prostate cancer (PMID: 20736950, 25682074). This variant is also known as 2117delC in the literature. ClinVar contains an entry for this variant (Variation ID: 51221). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000043918 SCV000587618 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000077271 SCV000109068 pathogenic Breast-ovarian cancer, familial 2 2011-04-29 no assertion criteria provided clinical testing

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