ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7360del (p.Ile2454fs) (rs80359646)

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Total submissions: 7
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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) RCV000113747 SCV000282441 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 RCV000045191 SCV000073204 pathogenic Hereditary breast and ovarian cancer syndrome 2018-06-08 criteria provided, single submitter clinical testing This sequence change deletes 1 nucleotide from exon 14 of the BRCA2 mRNA (c.7360delA), causing a frameshift at codon 2454. This creates a premature translational stop signal (p.Ile2454Phefs*15) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature in individuals with BRCA-related disease, loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). For these reasons, this variant has been classified as Pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000113747 SCV000327639 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000484324 SCV000568474 pathogenic not provided 2016-05-31 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA2 is denoted c.7360delA at the cDNA level and p.Ile2454PhefsX15 (I2454FfsX15) at the protein level. The normal sequence, with the base that is deleted in braces, is TGAG[A]TTCA. The deletion causes a frameshift which changes an Isoleucine to a Phenylalanine at codon 2454, and creates a premature stop codon at position 15 of the new reading frame. Although this variant has not, to our knowledge, been reported in the clinical literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000484324 SCV000600745 pathogenic not provided 2016-12-05 criteria provided, single submitter clinical testing
Color RCV000773269 SCV000906934 pathogenic Hereditary cancer-predisposing syndrome 2018-08-13 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113747 SCV000147069 pathogenic Breast-ovarian cancer, familial 2 1999-04-13 no assertion criteria provided clinical testing

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