ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.260_261CT[1] (p.Leu88fs) (rs276174825)

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Total submissions: 10
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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) RCV000113331 SCV000282370 pathogenic Breast-ovarian cancer, familial 2 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000044028 SCV000072041 pathogenic Hereditary breast and ovarian cancer syndrome 2018-11-08 criteria provided, single submitter clinical testing This sequence change deletes 2 nucleotides in exon 3 of the BRCA2 mRNA (c.262_263delCT), causing a frameshift at codon 88. This creates a premature translational stop signal (p.Leu88Alafs*12) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic. This particular variant has been reported in individuals and families affected with breast and/or ovarian cancer (PMID: 15146557, 20151322, 24578176, 23683081), as well as pancreatic cancer (PMID: 25940717). This variant is also known as 488delCT and 490delCT in the literature. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000162895 SCV000213382 pathogenic Hereditary cancer-predisposing syndrome 2017-07-07 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)
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000113331 SCV000326735 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000113331 SCV000489212 pathogenic Breast-ovarian cancer, familial 2 2016-09-07 criteria provided, single submitter clinical testing
GeneDx RCV000523679 SCV000617459 pathogenic not provided 2017-05-10 criteria provided, single submitter clinical testing This deletion of two nucleotides in BRCA2 is denoted c.262_263delCT at the cDNA level and p.Leu88AlafsX12 (L88AfsX12) at the protein level. The normal sequence, with the bases that are deleted in brackets, is GACT[delCT]GCCG. The deletion causes a frameshift, which changes a Leucine to an Alanine at codon 88 and creates a premature stop codon at position 12 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.262_263delCT, previously reported as BRCA2 488delCT, 490delCT, and 490_491delCT using alternate nomenclature, has been observed in association with breast, ovarian, male breast, and pancreatic cancer (Gorski 2004, Salgado 2010, Novakovic 2012, Blay 2013, Kang 2014, de Juan 2015, Holter 2015). We consider this variant to be pathogenic.
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000113331 SCV000744380 pathogenic Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000523679 SCV000889007 pathogenic not provided 2018-05-10 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113331 SCV000146469 pathogenic Breast-ovarian cancer, familial 2 2010-07-16 no assertion criteria provided clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000113331 SCV000733209 pathogenic Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing

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