ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7249_7250CA[1] (p.His2417fs) (rs397507907)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166921 SCV000217740 pathogenic Hereditary cancer-predisposing syndrome 2017-11-09 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)
Color RCV000166921 SCV000905021 pathogenic Hereditary cancer-predisposing syndrome 2018-05-16 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000083133 SCV000327620 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000083133 SCV000677717 pathogenic Breast-ovarian cancer, familial 2 2017-03-03 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000083133 SCV000301146 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735603 SCV000863741 pathogenic Breast and/or ovarian cancer 2015-04-22 no assertion criteria provided clinical testing
GeneDx RCV000519211 SCV000617471 pathogenic not provided 2018-01-19 criteria provided, single submitter clinical testing This deletion of two nucleotides in BRCA2 is denoted c.7251_7252delCA at the cDNA level and p.His2417GlnfsX3 (H2417QfsX3) at the protein level. The normal sequence, with the bases that are deleted in brackets, is TTCA[delCA]GAGT. Using alternate nomenclature, this variant may be defined as 7479_7480delCA or 7479delCA, as well as c.7249_7250delCA or c.7249delCA. The deletion causes a frameshift which changes a Histidine to a Glutamine at codon 2417, and creates a premature stop codon at position 3 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.7251_7252delCA has been reported in multiple individuals with breast and/or ovarian cancer (Lubinski 2004, Cybulski 2014, Kluska 2015). We consider this variant to be pathogenic.
Invitae RCV000045175 SCV000073188 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.His2417Glnfs*3) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant has been observed in a family affected with breast, ovarian, and possibly other cancers (PMID: 15131399). ClinVar contains an entry for this variant (Variation ID: 52298). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000519211 SCV000887909 pathogenic not provided 2017-12-03 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000083133 SCV000115207 pathogenic Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing

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