ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.2836del (p.Asp946fs) (rs80359358)

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Total submissions: 9
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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) RCV000113102 SCV000300566 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 RCV000044072 SCV000072085 pathogenic Hereditary breast and ovarian cancer syndrome 2018-09-28 criteria provided, single submitter clinical testing This sequence change deletes 1 nucleotide from exon 11 of the BRCA2 mRNA (c.2836delG), causing a frameshift at codon 946. This creates a premature translational stop signal (p.Asp946Ilefs*14) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). ClinVar contains an entry for this variant (Variation ID: 51357). For these reasons, this variant has been classified as Pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000113102 SCV000326776 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000480163 SCV000567926 pathogenic not provided 2015-09-16 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA2 is denoted c.2836delG at the cDNA level and p.Asp946IlefsX14 (D946IfsX14) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA2 3064delG. The normal sequence, with the base that is deleted in braces, is TAAAAAA[G]ATTT. The deletion causes a frameshift, which changes an Aspartic Acid to an Isoleucine at codon 946, and creates a premature stop codon at position 14 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. we consider this variant to be pathogenic.
Ambry Genetics RCV000571356 SCV000665082 pathogenic Hereditary cancer-predisposing syndrome 2017-09-07 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)
Color RCV000571356 SCV000683504 pathogenic Hereditary cancer-predisposing syndrome 2017-04-27 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113102 SCV000146127 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 RCV000044072 SCV000587647 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
GenomeConnect, ClinGen RCV000480163 SCV000607230 not provided not provided no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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