ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8633-1G>A (rs398122711)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077639 SCV000327936 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Human Genome Sequencing Center Clinical Lab,Baylor College of Medicine RCV000077639 SCV000839915 pathogenic Breast-ovarian cancer, familial 2 2017-05-25 criteria provided, single submitter clinical testing This c.8633-1G>A variant in the BRCA2 gene has not been observed in our cohort database nor has been detected in the ExAC database. This variant was however reported in ClinVar but the clinical presentation of the patients was not available (https://www.ncbi.nlm.nih.gov/clinvar/variation/91731/). This variant affects the invariant acceptor splice site of intron 20 of the BRCA2 gene. While not validated for clinical use, computer-based algorithms predict this c.8633-1G>A variant change to disrupt the splice site. This variant is classified as pathogenic
Invitae RCV000698187 SCV000826835 likely pathogenic Hereditary breast and ovarian cancer syndrome 2018-05-17 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 20 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 observed in a family in a study of individuals with increased risk of breast and ovarian cancers (PMID: 29446198). ClinVar contains an entry for this variant (Variation ID: 91731). 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). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000077639 SCV000296645 pathogenic Breast-ovarian cancer, familial 2 2015-07-30 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077639 SCV000109442 likely pathogenic Breast-ovarian cancer, familial 2 2010-03-15 no assertion criteria provided clinical testing

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