ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5351dupA (p.Asn1784Lysfs) (rs80359507)

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Total submissions: 17
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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) RCV000031541 SCV000300862 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 RCV000195402 SCV000072655 pathogenic Hereditary breast and ovarian cancer syndrome 2018-11-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asn1784Lysfs*3) 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 patients and families affected with breast and ovarian cancer (PMID: 10550133, 21232165, 22006311, 25863477). It is also known as 5579insA and 5579dupA in the literature. ClinVar contains an entry for this variant (Variation ID: 37960). 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 RCV000131977 SCV000187035 pathogenic Hereditary cancer-predisposing syndrome 2017-09-26 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)
GeneDx RCV000044642 SCV000210764 pathogenic not provided 2018-02-20 criteria provided, single submitter clinical testing This duplication of one nucleotide in BRCA2 is denoted c.5351dupA at the cDNA level and p.Asn1784LysfsX3 (N1784KfsX3) at the protein level. The normal sequence, with the base that is duplicated in brackets, is CAAAAAA[dupA]CACT. This duplication causes a frameshift, which changes an Asparagine to a Lysine at codon 1784, and creates a premature stop codon at position 3 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.5351dupA, previously described as 5579insA using alternate nomenclature, has been reported in association with breast and ovarian cancer and is considered a founder pathogenic variant in individuals of Dutch ancestry (Verhoog 1999, Peelen 2000, Spitzer 2000, Janavicius 2010, Walsh 2011, Kang 2015). Based on the currently available evidence, we consider this variant to be pathogenic.
Michigan Medical Genetics Laboratories,University of Michigan RCV000031541 SCV000267780 pathogenic Breast-ovarian cancer, familial 2 2016-04-21 criteria provided, single submitter clinical testing
Color RCV000131977 SCV000292171 pathogenic Hereditary cancer-predisposing syndrome 2016-08-17 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031541 SCV000327205 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency RCV000195402 SCV000586959 pathogenic Hereditary breast and ovarian cancer syndrome 2017-04-18 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000195402 SCV000591963 pathogenic Hereditary breast and ovarian cancer syndrome 2014-06-02 criteria provided, single submitter clinical testing
Counsyl RCV000031541 SCV000677683 pathogenic Breast-ovarian cancer, familial 2 2017-01-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000195402 SCV000694864 pathogenic Hereditary breast and ovarian cancer syndrome 2017-06-07 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.5351dupA (p.Asn1784Lysfs) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.5386_5387delGA/ p.Asp1796fs). One in silico tool predicts a damaging outcome for this variant. The variant is absent from the large control population datasets of ExAC and gnomAD. The variant of interest has been reported in multiple affected individuals and is cited as pathogenic by multiple reputable databases/clinical laboratories and published reports. Taken together, this variant is classified as pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000044642 SCV000889063 pathogenic not provided 2018-06-24 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031541 SCV000054146 pathogenic Breast-ovarian cancer, familial 2 2011-02-16 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031541 SCV000146603 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Pathway Genomics RCV000031541 SCV000189897 pathogenic Breast-ovarian cancer, familial 2 2014-07-24 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000195402 SCV000587764 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785592 SCV000924167 pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research

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