ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5065_5066delinsAAA (p.Ala1689fs) (rs276174852)

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Total submissions: 6
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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) RCV000113372 SCV000300822 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Color RCV000584719 SCV000688915 pathogenic Hereditary cancer-predisposing syndrome 2017-09-20 criteria provided, single submitter clinical testing
GeneDx RCV000657228 SCV000778954 pathogenic not provided 2017-06-14 criteria provided, single submitter clinical testing This combined deletion and insertion is denoted BRCA2 c.5065_5066delGCinsAAA at the cDNA level and p.Ala1689LysfsX6 (A1689KfsX6) at the protein level. The surrounding sequence is TGAA[delGC][insAAA]AAAAAAAT. The variant causes a frameshift which changes an Alanine to a Lysine at codon 1689, and creates a premature stop codon at position 6 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. Also published as BRCA2 5293delGCinsAAA using alternate nomenclature, this variant has been reported in at least one family with breast and/or ovarian cancer (Lubinski 2004). We consider BRCA2 c.5065_5066delGCinsAAA to be pathogenic.
Invitae RCV000496795 SCV000831497 pathogenic Hereditary breast and ovarian cancer syndrome 2018-11-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ala1689Lysfs*6) 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 a family affected with cancer, although the exact type of cancer(s) observed in this family was not specified (PMID: 15131399). This variant is also known as 5293delGCinsAAA in the literature. ClinVar contains an entry for this variant (Variation ID: 51761). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Breast Cancer Information Core (BIC) (BRCA2) RCV000113372 SCV000146527 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 RCV000496795 SCV000587740 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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