ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3264dupT (p.Gln1089Serfs) (rs80359380)

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Total submissions: 16
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131493 SCV000186481 pathogenic Hereditary cancer-predisposing syndrome 2018-03-09 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)
Baylor Genetics RCV000459431 SCV000541003 pathogenic Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031411 SCV000146201 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000131493 SCV000683540 pathogenic Hereditary cancer-predisposing syndrome 2015-04-03 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031411 SCV000326841 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000031411 SCV000220688 likely pathogenic Breast-ovarian cancer, familial 2 2014-09-11 criteria provided, single submitter literature only
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031411 SCV000300607 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 RCV000044163 SCV000210736 pathogenic not provided 2018-09-18 criteria provided, single submitter clinical testing This duplication of one nucleotide in BRCA2 is denoted c.3264dupT at the cDNA level and p.Gln1089SerfsX10 (Q1089SfsX10) at the protein level. The normal sequence, with the base that is duplicated in brackets, is ACCCC[dupT]CAGA. The duplication causes a frameshift, which changes a Glutamine to a Serine at codon 1089, and creates a premature stop codon at position 10 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.3264dupT, also published as BRCA2 3492insT and BRCA2 3264_3265insT, has been observed in many breast/ovarian cancer families, the majority of which are of Spanish descent (Diez 2003, Esteban Carde?osa 2010, Weitzel 2013, de Juan Jim?nez 2013, Nahleh 2015, Gabald? Barrios 2017). Additionally, this variant has been observed in the compound heterozygous state in a patient with Fanconi Anemia (Myers 2012). Based on currently available evidence, we consider this variant to be pathogenic.
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785218 SCV000923786 pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research
Integrated Genetics/Laboratory Corporation of America RCV000203627 SCV000694685 pathogenic Hereditary breast and ovarian cancer syndrome 2016-08-03 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.3264dupT (p.Gln1089Serfs) 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. The variant of interest was not found in controls (ExAC, 1000 Gs or ESP) and has been reported in multiple affected individuals by publications. Multiple reputable databases/clinical laboratories cite the variant as "pathogenic." Therefore, taking all available lines of evidence into consideration, the variant of interest has been classified as Pathogenic.
Invitae RCV000203627 SCV000072176 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1089Serfs*10) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported in individuals and families affected with breast and/or ovarian cancer (PMID: 12845657, 20033483, 22426013, 24123850, 25136594), as well as in an individual affected with Fanconi anemia (PMID: 23613520). This variant is a common cause of breast and ovarian cancer among Spanish and American individuals of Latin American descent (PMID: 16030099, 19941167). This variant is also known as 3492insT and 3492_3493insT in the literature. ClinVar contains an entry for this variant (Variation ID: 37830). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000203627 SCV000838786 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
PreventionGenetics RCV000044163 SCV000805689 pathogenic not provided 2018-01-17 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000044163 SCV000296687 pathogenic not provided 2015-06-27 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000203627 SCV000587668 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031411 SCV000054016 pathogenic Breast-ovarian cancer, familial 2 2012-12-27 no assertion criteria provided clinical testing

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