ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7617+1G>A (rs397507922)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000579436 SCV000683893 pathogenic Hereditary cancer-predisposing syndrome 2017-05-25 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000083138 SCV000327692 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Department of Medical Genetics,Oslo University Hospital RCV000083138 SCV000605707 pathogenic Breast-ovarian cancer, familial 2 2017-01-20 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000045259 SCV000592128 pathogenic Hereditary breast and ovarian cancer syndrome criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000083138 SCV000282250 pathogenic Breast-ovarian cancer, familial 2 2016-04-15 reviewed by expert panel curation Allele-specific assay on patient-derived mRNA demonstrated that the variant allele produces only predicted non-functional transcripts. Variant allele produces r.7436_7617del transcript (encoding predicted non-functional protein).
GeneDx RCV000486153 SCV000568483 pathogenic not provided 2018-02-21 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.7617+1G>A or IVS15+1G>A and consists of a G>A nucleotide substitution at the +1 position of intron 15 of the BRCA2 gene. Using alternate nomenclature, this variant would be defined as BRCA2 7845+1G>A or 7829+1G>A. This variant destroys a canonical splice donor site and is predicted to cause abnormal gene splicing and several assays have identified that this variant results in abnormal splicing leading to skipping of exon 15 and a truncated protein (Bergthorsson 2001, Thomassen 2011, de Garibar 2014). This variant has been reported in association with breast and ovarian cancer and is a frequently observed variant in Danish and Spanish individuals (Bergthorsson 2001, Gutierrez-Enriquez 2009, Thomassen 2011, Zhang 2011, de Juan Jimenez 2013, de Garibay 2014, Roed Nielsen 2016). We consider this variant to be pathogenic.
Invitae RCV000045259 SCV000073272 pathogenic Hereditary breast and ovarian cancer syndrome 2019-01-05 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 15 of the BRCA2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature to segregate in many families (PMID: 21184276, 24123850). Experimental studies have shown that this donor splice site change causes skipping of exon 15, which results in an out of frame transcript with an early stop codon (PMID: 21184276, 24123850, 18712473). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000045259 SCV000838856 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000083138 SCV000115212 pathogenic Breast-ovarian cancer, familial 2 2011-12-29 no assertion criteria provided clinical testing

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