ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3007_3008CA[1] (p.His1003fs) (rs397507300)

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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) RCV000031395 SCV000300580 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics RCV000132309 SCV000187395 pathogenic Hereditary cancer-predisposing syndrome 2014-11-07 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)
Invitae RCV000232051 SCV000283199 pathogenic Hereditary breast and ovarian cancer syndrome 2018-05-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.His1003Glnfs*5) 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 variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 37814). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000255011 SCV000321455 pathogenic not provided 2016-07-18 criteria provided, single submitter clinical testing This deletion of two nucleotides in BRCA2 is denoted c.3009_3010delCA at the cDNA level and p.His1003GlnfsX5 (H1003QfsX5) at the protein level. The normal sequence, with the bases that are deleted in braces, is ATCA[CA]GTTT. The deletion causes a frameshift which changes a Histidine to a Glutamine at codon 1003, 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. Using alternate nomenclature, this variant has been reported in the literature as BRCA2 c.3237_3238delCA in at least one individual with pancreatic cancer and a family history of breast cancer (Sharma 2016). We consider this variant to be pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031395 SCV000326800 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000031395 SCV000677710 likely pathogenic Breast-ovarian cancer, familial 2 2017-01-25 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031395 SCV000054000 pathogenic Breast-ovarian cancer, familial 2 2011-08-09 no assertion criteria provided clinical testing

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