ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5351del (p.Asn1784fs) (rs80359507)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000509991 SCV000607810 pathogenic Hereditary cancer-predisposing syndrome 2017-01-30 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)
Breast Cancer Information Core (BIC) (BRCA2) RCV000031542 SCV000146604 pathogenic Breast-ovarian cancer, familial 2 1997-11-13 no assertion criteria provided clinical testing
Color RCV000509991 SCV000905015 pathogenic Hereditary cancer-predisposing syndrome 2017-11-09 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031542 SCV000327204 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031542 SCV000300861 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 RCV000657230 SCV000778956 pathogenic not provided 2019-01-11 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA2 is denoted c.5351delA at the cDNA level and p.Asn1784ThrfsX7 (N1784TfsX7) at the protein level. The normal sequence, with the base that is deleted in brackets, is CAAAAAA[delA]CACT. The deletion causes a frameshift which changes an Asparagine to a Threonine at codon 1784, and creates a premature stop codon at position 7 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. Also reported as BRCA2 5573delA and 5579delA using alternate nomenclature, BRCA2 c.5351delA has been observed in multiple individuals with a personal and/or family history of breast and/or ovarian cancer and in association with familial prostate cancer. (Gayther 1997, Pages 2001, Thomassen 2008, Kang 2015, Roed Nielsen 2016). We consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000044641 SCV000694863 pathogenic Hereditary breast and ovarian cancer syndrome 2017-05-30 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.5351delA (p.Asn1784Thrfs) 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. This variant is absent in 120684 control chromosomes. This variant has been reported in multiple affected individuals. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Variants at the same location such as c.5351dupA, c.5350_5351delAA have been reported in affected individuals and classified as pathogenic suggesting this is a mutaiton hospot. Taken together, this variant is classified as pathogenic.
Invitae RCV000044641 SCV000072654 pathogenic Hereditary breast and ovarian cancer syndrome 2018-09-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asn1784Thrfs*7) 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 affected with breast, ovarian, and prostate cancer (PMID: 25863477, 8988179, 26360800, 22923021). This variant is also known as 5573delA, 5579delA and c.5351insA (p.Asn1784Lysfs*3) in the literature. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000031542 SCV000054147 pathogenic Breast-ovarian cancer, familial 2 2011-03-18 no assertion criteria provided clinical testing

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