ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.115del (p.Ala39fs) (rs397507573)

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Total submissions: 7
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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) RCV000241066 SCV000300296 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 RCV000043749 SCV000071762 pathogenic Hereditary breast and ovarian cancer syndrome 2017-01-24 criteria provided, single submitter clinical testing This sequence change deletes 1 nucleotide from exon 3 of the BRCA2 mRNA (c.115delG), causing a frameshift at codon 39. This creates a premature translational stop signal (p.Ala39Leufs*41) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic. This particular variant has been reported in the literature in individuals with a personal or family history of breast and/or ovarian cancer (PMID: 16683254, 19949876, 26287763). For these reasons, this variant has been classified as Pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000241066 SCV000326506 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000483184 SCV000566556 pathogenic not provided 2017-12-11 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA2 is denoted c.115delG at the cDNA level and p.Ala39LeufsX41 (A39LfsX41) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA2 343delG. The normal sequence, with the base that is deleted in brackets, is AGAA[delG]CTCC. The deletion causes a frameshift, which changes an Alanine to a Leucine at codon 39, and creates a premature stop codon at position 41 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.115delG has been reported in multiple families with breast and/or ovarian cancer (van der Hout 2006, van Harssel 2009, Pal 2014). We consider this variant to be pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000483184 SCV000600467 pathogenic not provided 2016-07-06 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000241066 SCV000744378 pathogenic Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000241066 SCV000733207 pathogenic Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing

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