ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5303_5304del (p.Leu1768fs) (rs80359505)

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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 RCV000162923 SCV000213410 pathogenic Hereditary cancer-predisposing syndrome 2017-08-25 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) RCV000031538 SCV000146596 pathogenic Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Color RCV000162923 SCV000683693 pathogenic Hereditary cancer-predisposing syndrome 2017-05-07 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031538 SCV000327196 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Division Human Genetics,Medical University Innsbruck RCV000031538 SCV000212020 pathogenic Breast-ovarian cancer, familial 2 2015-02-11 no assertion criteria provided clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031538 SCV000300858 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 RCV000235139 SCV000108621 pathogenic not provided 2018-04-16 criteria provided, single submitter clinical testing This deletion of two nucleotides is denoted BRCA2 c.5303_5304delTT at the cDNA level and p.Leu1768ArgfsX5 (L1768RfsX5) at the protein level. The normal sequence, with the bases that are deleted in brackets, is AAAC[delTT]GATT. The deletion causes a frameshift, which changes a Leucine to an Arginine at codon 1768, and creates a premature stop codon at position 5 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 5303_5304delTT, previously reported as 5531delTT, has been observed in individuals with personal and/or family histories of breast, ovarian, and/or prostate cancer (Gayther 2000, Gutierrez Espeleta 2012, Song 2014). We consider this variant to be pathogenic
Integrated Genetics/Laboratory Corporation of America RCV000074536 SCV000694857 pathogenic Hereditary breast and ovarian cancer syndrome 2016-10-18 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.5303_5304delTT (p.Leu1768Argfs) 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.5350_5351delAA; c.5351dupA, c.5386_5387delGA). One in silico tool predicts a damaging outcome for this variant. This variant was found in 1/120690 control chromosomes at a frequency of 0.0000083, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). The variant has been cited in breast, ovarian, and postate cancer patients in the literature. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000074536 SCV000072646 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu1768Argfs*5) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs80359505, ExAC 0.002%). This particular variant has been reported in the literature in individuals and families affected with breast and/or ovarian cancer, and prostate cancer (PMID: 21895635, 22762150, 10969800). This variant is also known as 5531delTT in the literature. ClinVar contains an entry for this variant (Variation ID: 37957). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000074536 SCV000838813 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000235139 SCV000889060 pathogenic not provided 2018-06-25 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000074536 SCV000587759 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031538 SCV000054143 pathogenic Breast-ovarian cancer, familial 2 2012-07-10 no assertion criteria provided clinical testing

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