ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.206-2A>G (rs786203700)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000167120 SCV000217950 likely pathogenic Hereditary cancer-predisposing syndrome 2017-11-02 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity
Color RCV000167120 SCV000903619 likely pathogenic Hereditary cancer-predisposing syndrome 2018-10-31 criteria provided, single submitter clinical testing
Counsyl RCV000576661 SCV000677820 likely pathogenic Fanconi anemia, complementation group J; Neoplasm of ovary 2016-12-22 criteria provided, single submitter clinical testing
GeneDx RCV000214974 SCV000279366 likely pathogenic not provided 2018-09-13 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.206-2A>G or IVS3-2A>G and consists of an A>G nucleotide substitution at the -2 position of intron 3 of the BRIP1 gene. The variant destroys a canonical splice acceptor site and is predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. This variant has been reported in at least one individual with ovarian cancer (Norquist 2016), but has also been observed in one control (Weber-Lassalle 2018). Based on currently available evidence, we consider BRIP1 c.206-2A>G to be a likely pathogenic variant.
Invitae RCV000526148 SCV000633507 likely pathogenic Familial cancer of breast; Fanconi anemia, complementation group J 2018-04-15 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 3 of the BRIP1 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 an individual affected with ovarian cancer (PMID: 26720728). ClinVar contains an entry for this variant (Variation ID: 187396). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BRIP1 are known to be pathogenic (PMID: 16116423, 17033622, 21964575). 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.

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