ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6591_6592del (p.Glu2198fs) (rs80359605)

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Total submissions: 23
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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) RCV000009904 SCV000301071 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 RCV000044989 SCV000073002 pathogenic Hereditary breast and ovarian cancer syndrome 2018-10-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu2198Asnfs*4) 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 individuals and families affected with breast, ovarian, and prostate cancer (PMID: 8524414, 16683254, 20736950, 21324516, 23569316, 26187060, 26219728). This variant is also known as 6819delTG in the literature. ClinVar contains an entry for this variant (Variation ID: 9319). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000131037 SCV000185967 pathogenic Hereditary cancer-predisposing syndrome 2018-05-03 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
GeneDx RCV000215210 SCV000278870 pathogenic not provided 2019-01-15 criteria provided, single submitter clinical testing This deletion of 2 nucleotides in BRCA2 is denoted c.6591_6592delTG at the cDNA level and p.Glu2198AsnfsX4 (E2198NfsX4) at the protein level. The normal sequence, with the bases that are deleted in brackets, is AAAC[delTG]AAAC. The deletion causes a frameshift, which changes a Glutamic Acid to an Asparagine at codon 2198, and creates a premature stop codon at position 4 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.6591_6592delTG, previously reported as 6819delTG, has been observed in association with breast, ovarian, pancreatic, and prostate cancer (Wooster 1995, White 2001, Edwards 2010, Zhang 2011, Zhang 2012, Finch 2015, Pritchard 2016, Pritzlaff 2017). We consider this variant to be pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000009904 SCV000296709 pathogenic Breast-ovarian cancer, familial 2 2015-03-11 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000009904 SCV000327469 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000009904 SCV000488858 pathogenic Breast-ovarian cancer, familial 2 2016-07-06 criteria provided, single submitter clinical testing
Department of Pathology and Molecular Medicine,Queen's University RCV000044989 SCV000588110 pathogenic Hereditary breast and ovarian cancer syndrome 2017-04-20 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000044989 SCV000592064 pathogenic Hereditary breast and ovarian cancer syndrome 2013-11-08 criteria provided, single submitter clinical testing
Department of Medical Genetics,Oslo University Hospital RCV000009904 SCV000605693 pathogenic Breast-ovarian cancer, familial 2 2016-01-26 criteria provided, single submitter clinical testing
GeneKor MSA RCV000215210 SCV000693576 pathogenic not provided 2017-11-01 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000044989 SCV000694982 pathogenic Hereditary breast and ovarian cancer syndrome 2016-10-19 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.6591_6592delTG (p.Glu2198Asnfs) variant, alternatively also known as 6819delTG, results in a premature termination codon, predicted to cause a truncated or absent BRCA2 protein due to nonsense mediated decay (NMD), which are commonly known mechanisms for disease. If this variant escapes NMD, it is predicted to truncate helical domain, Tower domain, oligonucleotide/oligosaccharide-binding region and nucleic acid-binding regions (InterPro). Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. p.Leu2253fs). This variant is absent in 120206 control chromosomes. The variant has been reported in several HBOC patients/families in literature and clinical databases (UMD, BIC). In addition, multiple clinical diagnostic laboratories/reputable databases have classified this variant as pathogenic. Taken together, this variant is classified as Pathogenic.
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000009904 SCV000744495 pathogenic Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000215210 SCV000805749 pathogenic not provided 2017-11-15 criteria provided, single submitter clinical testing
Mendelics RCV000044989 SCV000838843 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000215210 SCV000889104 pathogenic not provided 2015-03-11 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000735588 SCV000901116 pathogenic Breast and/or ovarian cancer 2016-03-03 criteria provided, single submitter clinical testing
OMIM RCV000009904 SCV000030125 pathogenic Breast-ovarian cancer, familial 2 1995-12-21 no assertion criteria provided literature only
Sharing Clinical Reports Project (SCRP) RCV000009904 SCV000054245 pathogenic Breast-ovarian cancer, familial 2 2012-06-22 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000009904 SCV000146886 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 RCV000044989 SCV000587857 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000009904 SCV000733285 pathogenic Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735588 SCV000863726 pathogenic Breast and/or ovarian cancer 2013-07-10 no assertion criteria provided clinical testing

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