ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9097dupA (p.Thr3033Asnfs) (rs397507419)

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Total submissions: 20
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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) RCV000031791 SCV000282467 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 RCV000195406 SCV000073724 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr3033Asnfs*11) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant has been reported in individuals affected with breast and ovarian cancer, pancreatic cancer, and Fanconi anemia (PMID: 22970155, 9150172, 25940717, 21138478). This variant is also known as c.9097_9098insA, 9325insA and 9317insA in the literature. ClinVar contains an entry for this variant (Variation ID: 38208). 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 RCV000130439 SCV000185303 pathogenic Hereditary cancer-predisposing syndrome 2018-01-12 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),Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Michigan Medical Genetics Laboratories,University of Michigan RCV000031791 SCV000196022 pathogenic Breast-ovarian cancer, familial 2 2016-04-21 criteria provided, single submitter clinical testing
GeneDx RCV000045711 SCV000210799 pathogenic not provided 2018-09-05 criteria provided, single submitter clinical testing This duplication of one nucleotide in BRCA2 is denoted c.9097dupA at the cDNA level and p.Thr3033AsnfsX11 (T3033NfsX11) at the protein level. The normal sequence, with the base that is duplicated in brackets, is CAAAAAAA[dupA]CTCA. The duplication causes a frameshift, which changes a Threonine to an Asparagine at codon 3033, and creates a premature stop codon at position 11 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.9097dupA, previously reported as c.9097_9098insA, 9325insA, and 9317insA using alternate nomenclature, has been observed in association with breast, ovarian and pancreatic cancer, and in the compound heterozygous state in an individual with Fanconi Anemia (Serova-Sinilnikova 1997, Kopic 2011, Kwong 2012, Holter 2015). We consider this variant to be pathogenic.
University of Washington Department of Laboratory Medicine,University of Washington RCV000210094 SCV000266049 pathogenic Breast-ovarian cancer, familial 1 2015-11-20 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000045711 SCV000296658 pathogenic not provided 2019-06-12 criteria provided, single submitter clinical testing The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and not found in general population data.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031791 SCV000328046 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000031791 SCV000488294 pathogenic Breast-ovarian cancer, familial 2 2016-02-18 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000195406 SCV000592254 pathogenic Hereditary breast and ovarian cancer syndrome 2013-05-22 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000195406 SCV000605794 pathogenic Hereditary breast and ovarian cancer syndrome 2016-10-28 criteria provided, single submitter clinical testing The p.Thr3033fs variant in BRCA2 has been reported in >20 individuals with BRCA2 -associated cancers (Serova-Sinilnikova 1997, Kopic 2011, Kwong 2012, Holter 201 5, Wong-Brown 2015, Breast Cancer Information Core (BIC) database). This variant has been identified in 0.02% (10/62160) of European chromosomes by the Exome Ag gregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs754205122). This frequency is low enough to be consistent with the frequency of hereditary b reast and ovarian cancer (HBOC) in the general population. This variant is predi cted to cause a frameshift, which alters the protein?s amino acid sequence begin ning at position 3033 and leads to a premature termination codon 11 amino acids downstream. This alteration is then predicted to lead to a truncated or absent p rotein. Heterozygous loss of function of the BRCA2 gene is an established diseas e mechanism in hereditary breast and ovarian cancer (HBOC). In addition, this va riant was classified as Pathogenic on April 22, 2016 by the ClinGen-approved ENI GMA expert panel (ClinVar SCV000282467.1). In summary, this variant meets our cr iteria to be classified as pathogenic for HBOC in an autosomal dominant manner.
Color RCV000130439 SCV000684022 pathogenic Hereditary cancer-predisposing syndrome 2016-07-20 criteria provided, single submitter clinical testing
GeneKor MSA RCV000585671 SCV000693591 pathogenic Familial cancer of breast 2018-08-01 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000195406 SCV000695208 pathogenic Hereditary breast and ovarian cancer syndrome 2017-06-23 criteria provided, single submitter clinical testing
Mendelics RCV000195406 SCV000838892 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031791 SCV000054399 pathogenic Breast-ovarian cancer, familial 2 2013-03-01 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000195406 SCV000587986 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735619 SCV000863757 pathogenic Breast and/or ovarian cancer 2013-06-08 no assertion criteria provided clinical testing
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785367 SCV000923938 pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research
Bioscientia Institut fuer Medizinische Diagnostik GmbH,Sonic Healthcare RCV000585671 SCV000925778 pathogenic Familial cancer of breast 2018-09-27 no assertion criteria provided clinical testing

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