ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3708dup (p.Ala1237fs) (rs34575057)

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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) RCV000077713 SCV000300656 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 RCV000160278 SCV000210731 pathogenic not provided 2018-03-13 criteria provided, single submitter clinical testing This duplication of one nucleotide in BRCA2 is denoted c.3708dupA at the cDNA level and p.Ala1237SerfsX6 (A1237SfsX6) at the protein level. The normal sequence, with the base that is duplicated in brackets, is CAAAA[dupA]GCTG. The duplication causes a frameshift which changes an Alanine to a Serine at codon 1237, 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. BRCA2 c.3708dupA, also known as 3936dupA using alternate nomenclature, has been reported in association with hereditary breast and ovarian cancer (Meisel 2017) and is considered pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077713 SCV000326900 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Invitae RCV000496326 SCV000836751 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ala1237Serfs*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 observed in an individual with a family history indicative of hereditary breast or ovarian cancer (PMID: 28324225). ClinVar contains an entry for this variant (Variation ID: 91805). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000077713 SCV000109516 pathogenic Breast-ovarian cancer, familial 2 2011-11-10 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496326 SCV000587678 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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