ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5621_5624del (p.Ile1874fs) (rs80359526)

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Total submissions: 12
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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) RCV000031561 SCV000300907 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 RCV000416547 SCV000072711 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-10 criteria provided, single submitter clinical testing This sequence change deletes 4 nucleotides from exon 11 of the BRCA2 mRNA (c.5621_5624delTTAA), causing a frameshift at codon 1874. This creates a premature translational stop signal (p.Ile1874Argfs*34) and 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: 9042907, 10449599, 19620486, 219131812, 26681312, 18042939). This variant is also known as 5849del4 in the literature. ClinVar contains an entry for this variant (Variation ID: 37980). 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 RCV000131115 SCV000186045 pathogenic Hereditary cancer-predisposing syndrome 2017-09-14 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 RCV000223208 SCV000278863 pathogenic not provided 2018-07-03 criteria provided, single submitter clinical testing This deletion of 4 nucleotides is denoted BRCA2 c.5621_5624delTTAA at the cDNA level and p.Ile1874ArgfsX34 (I1874RfsX34) at the protein level. The normal sequence, with the bases that are deleted in brackets, is GTAA[delTTAA]GGAA. The deletion causes a frameshift, which changes an Isoleucine to an Arginine at codon 1874, and creates a premature stop codon at position 34 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 5621_5624delTTAA, previously reported as 5849del4 using alternate nomenclature, has been observed in association with breast and/or ovarian cancer (Serova 1997, Tai 2007, Litton 2012). We therefore consider this variant to be pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000031561 SCV000296575 pathogenic Breast-ovarian cancer, familial 2 2016-01-25 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031561 SCV000327247 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000416547 SCV000494294 pathogenic Hereditary breast and ovarian cancer syndrome 2014-10-08 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000416547 SCV000591978 pathogenic Hereditary breast and ovarian cancer syndrome criteria provided, single submitter clinical testing
Color RCV000131115 SCV000683716 pathogenic Hereditary cancer-predisposing syndrome 2016-04-15 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031561 SCV000054166 pathogenic Breast-ovarian cancer, familial 2 2010-06-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031561 SCV000146647 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 RCV000416547 SCV000587782 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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