ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8585dupT (p.Glu2863Argfs) (rs80359720)

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Total submissions: 11
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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) RCV000031753 SCV000282460 pathogenic Breast-ovarian cancer, familial 2 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000045566 SCV000073579 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-06 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu2863Argfs*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 the literature in individuals affected with breast cancer (PMID: 12601471, 26976419). This variant is also known as 8813_8814insT in the literature. ClinVar contains an entry for this variant (Variation ID: 38170). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000258966 SCV000210796 pathogenic not provided 2018-02-26 criteria provided, single submitter clinical testing This duplication of one nucleotide is denoted BRCA2 c.8585dupT at the cDNA level and p.Glu2863ArgfsX6 (E2863RfsX6) at the protein level. The normal sequence, with the base that is duplicated in brackets, is AGAC[dupT]AGAA. The duplication causes a frameshift, which changes a Glutamic Acid to an Arginine at codon 2863, 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.8585dupT, previously reported as BRCA2 8813insT using alternate nomenclature, has been reported in association with hereditary breast and ovarian cancer syndrome (Scott 2003, Tung 2016, Taylor 2017). We consider this variant to be pathogenic.
Ambry Genetics RCV000218001 SCV000273433 pathogenic Hereditary cancer-predisposing syndrome 2016-04-08 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031753 SCV000327929 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Color RCV000218001 SCV000689136 pathogenic Hereditary cancer-predisposing syndrome 2015-03-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000045566 SCV000695165 pathogenic Hereditary breast and ovarian cancer syndrome 2016-05-23 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.8585dupT (p.Glu2863Argfs) frameshift variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Mutation taster predicts a damaging outcome for this variant. This variant is absent in 121206 control chromosomes while it was reported in HBOC patients indicating pathogenicity. The variant is located in a close proximity to other known pathogenic variants, such as c.8575delC (p.Gln2859Lysfs), c.8594dupT (p.Leu2865Phefs). These variants have been reported in UMD, BIC and HGMD > 25 times with a classification of pathogenic, indicating that the variant in interest is located in a mutational hot spot and further supporting a deleterious impact. The variant in interest shows strong evidence for pathogenicity: it is a truncating variant, located in a mutational hot spot, it is absent from controls (ExAC). Furthermore, reputable databases and clinical diagnostic centers classify this variant as pathogenic. Taken together the variant was classified as a Pathogenic.
Mendelics RCV000045566 SCV000838880 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031753 SCV000054361 pathogenic Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031753 SCV000147409 pathogenic Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000045566 SCV000587965 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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