ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5585_5588del (p.Val1862fs) (rs80359523)

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Total submissions: 9
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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) RCV000077354 SCV000300899 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics RCV000162925 SCV000213412 pathogenic Hereditary cancer-predisposing syndrome 2017-08-30 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)
GeneDx RCV000223488 SCV000278861 pathogenic not provided 2017-12-28 criteria provided, single submitter clinical testing This deletion of four nucleotides in BRCA2 is denoted c.5585_5588delTGAA at the cDNA level and p.Val1862GlufsX11 (V1862EfsX11) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA2 5813_5816delTGAA. The normal sequence, with the bases that are deleted in brackets, is AAAG[delTGAA]AGAC. The deletion causes a frameshift, which changes a Valine to a Glutamic Acid at codon 1862 and creates a premature stop codon at position 11 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.5585_5588delTGAA has been observed in at least one individual with prostate cancer (Pritchard 2016). We consider this variant to be pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077354 SCV000327237 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000223488 SCV000885098 pathogenic not provided 2018-03-13 criteria provided, single submitter clinical testing The BRCA2 c.5585_5588del; p.Val1862fs variant (rs80359523) has been described in individuals affected with breast and prostate cancer (Pritchard 2016, Tung 2015). It is reported as pathogenic by multiple laboratories in ClinVar (Variation ID: 51885) and is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. This variant causes a frameshift by deleting 4 nucleotides, so is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered pathogenic. REFERENCES Pritchard C et al. Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer. N Engl J Med. 2016 Aug 4;375(5):443-53. Tung N et al. Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next-generation sequencing with a 25-gene panel. Cancer. 2015 Jan 1;121(1):25-33.
Integrated Genetics/Laboratory Corporation of America RCV000496517 SCV000916831 pathogenic Hereditary breast and ovarian cancer syndrome 2018-01-26 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.5585_5588delTGAA (p.Val1862GlufsX11) 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. One in silico tool predicts a damaging outcome for this variant. This variant is absent in 240986 control chromosomes. The variant of interest has been reported in individuals affected by breast cancer (Tung 2014) and prostate cancer (Pritchard 2016). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000077354 SCV000109151 pathogenic Breast-ovarian cancer, familial 2 2011-09-09 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077354 SCV000146638 pathogenic Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496517 SCV000587776 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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