ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.26del (p.Pro9fs) (rs80359343)

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Total submissions: 12
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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) RCV000077284 SCV000282371 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 RCV000044041 SCV000072054 pathogenic Hereditary breast and ovarian cancer syndrome 2018-11-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Pro9Glnfs*16) 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 particular variant has been reported in the literature in multiple individuals with hereditary breast and ovarian cancer (PMID: 17636422, 8988179, 23028338, 22711857, 11044354). This variant is also known as 253delC in the literature. ClinVar contains an entry for this variant (Variation ID: 51330). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000132408 SCV000187500 pathogenic Hereditary cancer-predisposing syndrome 2019-04-08 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense);Rarity in general population databases (dbsnp, esp, 1000 genomes)
GeneDx RCV000215325 SCV000278834 pathogenic not provided 2018-12-24 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA2 is denoted c.26delC at the cDNA level and p.Pro9GlnfsX16 (P9QfsX16) at the protein level. The normal sequence, with the bases that are deleted in brackets, is AGGC[delC]AACA. The deletion causes a frameshift, which changes a Proline to a Glutamine at codon 9, and creates a premature stop codon at position 16 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.26delC, previously reported as 253delC and 254delC using alternate nomenclature, has been reported in several individuals with personal and family history of breast and/or ovarian cancer (Gayther 1997, Basham 2002, Evans 2008, Tutt 2010, Alsop 2012, Thompson 2012) and is considered pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000077284 SCV000296580 pathogenic Breast-ovarian cancer, familial 2 2015-12-30 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077284 SCV000326745 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000077284 SCV000489184 pathogenic Breast-ovarian cancer, familial 2 2016-08-31 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000044041 SCV000591654 pathogenic Hereditary breast and ovarian cancer syndrome 2014-04-23 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000044041 SCV000694620 pathogenic Hereditary breast and ovarian cancer syndrome 2016-05-02 criteria provided, single submitter clinical testing Variant summary: The c.26delC (p.Pro9Glnfs) variant in the BRCA2 gene is a frame shift predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The variant has been reported in multiple affected individuals and was shown to segregate with the disease in multiple HBOC families. The variant is absent from the large control population dataset of ExAC. Lastly, multiple reputable databases/diagnostic centers classified the variant of interest as Pathogenic. Taken together, the variant was classified as Pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000077284 SCV000109081 pathogenic Breast-ovarian cancer, familial 2 2007-02-15 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077284 SCV000146029 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 RCV000044041 SCV000587527 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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