ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.93+1G>T (rs587782047)

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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 RCV000130514 SCV000185383 likely pathogenic Hereditary cancer-predisposing syndrome 2015-06-23 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,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Color RCV000130514 SCV000910014 likely pathogenic Hereditary cancer-predisposing syndrome 2018-06-25 criteria provided, single submitter clinical testing
GeneDx RCV000223400 SCV000279514 likely pathogenic not provided 2017-05-02 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.93+1G>T or IVS2+1G>T and consists of a G>T nucleotide substitution at the +1 position of intron 2 of the BRIP1 gene. This variant destroys a canonical splice donor 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 two individuals with ovarian cancer and was absent from healthy controls (Norquist 2015, Ramus 2015). Based on the currently available information, we consider BRIP1 c.93+1G>T to be a likely pathogenic variant.
Invitae RCV000558720 SCV000633521 likely pathogenic Familial cancer of breast; Fanconi anemia, complementation group J 2018-10-25 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 2 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 the literature in individuals affected with ovarian cancer (PMID: 26315354, 26720728). ClinVar contains an entry for this variant (Variation ID: 141838). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
PreventionGenetics RCV000223400 SCV000807159 likely pathogenic not provided 2017-12-21 criteria provided, single submitter clinical testing

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