ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.1_2del (p.Met1fs) (rs876661246)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000221782 SCV000279883 likely pathogenic not provided 2016-02-11 criteria provided, single submitter clinical testing This deletion of two nucleotides is denoted BRIP1 c.1_2delAT at the cDNA level and alters the initiator Methionine codon. The resultant protein would be described as p.Met1?" to signify that it is not known if the loss of Met1 prevents all protein translation or if an abnormal protein is produced using an alternate Methionine codon. Although BRIP1 c.1_2delAT has not, to our knowledge, been previously published as pathogenic or benign, it is predicted to alter normal protein production. Based on the currently available evidence, we consider BRIP1 c.1_2delAT to be a likely pathogenic variant."
Invitae RCV000230644 SCV000290967 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2016-02-01 criteria provided, single submitter clinical testing This sequence change deletes 2 nucleotides from exon 2 of the BRIP1 mRNA (c.1_2delAT), affecting the initiator methionine. While it is expected to result in an absent or disrupted protein product, alternate in-frame methionines closely located downstream of the initiator codon could potentially rescue the translation initiation. However, functional work has not been performed to assess whether these potential alternate start sites are utilized. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature. In summary, this is a novel deletion of two nucleotides located within the initiator codon that has an uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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