ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1813del (p.Ile605fs) (rs80359306)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000132177 SCV000187256 pathogenic Hereditary cancer-predisposing syndrome 2017-06-23 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Breast Cancer Information Core (BIC) (BRCA2) RCV000031344 SCV000145952 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000132177 SCV000292131 pathogenic Hereditary cancer-predisposing syndrome 2015-10-16 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031344 SCV000326618 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Department of Pathology and Molecular Medicine,Queen's University RCV000203637 SCV000588079 pathogenic Hereditary breast and ovarian cancer syndrome 2017-04-20 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031344 SCV000282362 pathogenic Breast-ovarian cancer, familial 2 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000043896 SCV000210717 pathogenic not provided 2018-09-10 criteria provided, single submitter clinical testing This deletion of one nucleotide is denoted BRCA2 c.1813delA at the cDNA level and p.Ile605TyrfsX9 (I605YfsX9) at the protein level. This deletion is also known as BRCA2 2041delA using alternate nomenclature. The normal sequence, with the base that is deleted in brackets, is GAAAAAAA[delA]TACC. The deletion causes a frameshift, which changes an Isoleucine to a Tyrosine at codon 605, and creates a premature stop codon at position 9 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.1813delA has been reported in association with hereditary breast and/or ovarian cancer (Bergthorsson 2001, Spearman 2008, Sugano 2008, Hirasawa 2017, Dudley 2018). We consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000203637 SCV000694570 pathogenic Hereditary breast and ovarian cancer syndrome 2016-10-13 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.1813delA (p.Ile605Tyrfs) 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.1813dupA (p.Ile605fs), c.1832C>A (p.Ser611X), and c.1842dupT (p.Asn615X)). The variant of interest was not found in the large, broad control population, ExAC (115908 chrs tested). Multiple publications have cited the variant in affected individuals, along with multiple reputable databases/clinical diagnostic laboratories have cited the variant as "pathogenic." Therefore, the variant of interest has been classified as Pathogenic.
Invitae RCV000203637 SCV000071909 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ile605Tyrfs*9) 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 with breast and/or ovarian cancer (PMID: 11389159, 19016756, 24549055, 20104584, 23704984, 18824701). It has also been reported in an individual with prostate cancer (PMID: 23035815). This variant is also known as 2041delA in the literature. ClinVar contains an entry for this variant (Variation ID: 37763). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000203637 SCV000838763 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000043896 SCV000296624 pathogenic not provided 2015-08-21 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000203637 SCV000587613 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031344 SCV000053949 pathogenic Breast-ovarian cancer, familial 2 2012-10-22 no assertion criteria provided clinical testing

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