ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3717del (p.Lys1239fs) (rs80359401)

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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) RCV000031436 SCV000300657 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 RCV000044250 SCV000072263 pathogenic Hereditary breast and ovarian cancer syndrome 2018-11-06 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys1239Asnfs*20) 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 a family affected with breast, ovarian, or possibly other cancers (PMID: 15131399), and in an individual affected with breast cancer (PMID: 18042939). This variant is also known as 3945delA in the literature. ClinVar contains an entry for this variant (Variation ID: 37855). 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 RCV000132471 SCV000187565 pathogenic Hereditary cancer-predisposing syndrome 2017-02-28 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)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000031436 SCV000296571 pathogenic Breast-ovarian cancer, familial 2 2016-02-12 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031436 SCV000326902 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Baylor Genetics RCV000464504 SCV000540992 pathogenic Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
GeneDx RCV000486579 SCV000566557 pathogenic not provided 2015-05-07 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA2 is denoted c.3717delA at the cDNA level and p.Lys1239AsnfsX20 (K1239NfsX20) at the protein level. The normal sequence, with the base that is deleted in braces, is TGAA[A]CTGT. The deletion causes a frameshift, which changes a Lysine to an Asparagine at codon 1239, and creates a premature stop codon at position 20 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.3717delA, previously reported as 3945delA, has been identified in individuals with personal/family history of male and female breast cancer and ovarian cancer (Tai 2007, Watson 2009, Walsh 2015). we consider this variant to be pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000486579 SCV000889032 pathogenic not provided 2016-02-12 criteria provided, single submitter clinical testing
Color RCV000132471 SCV000905010 pathogenic Hereditary cancer-predisposing syndrome 2018-04-11 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031436 SCV000054041 pathogenic Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031436 SCV000146284 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000044250 SCV000587679 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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