ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.1473+4_1473+8delAGATA (rs730881650)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000773171 SCV000906724 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-20 criteria provided, single submitter clinical testing
GeneDx RCV000160365 SCV000210872 uncertain significance not provided 2018-03-12 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.1473+4_1473+8delAGATA or IVS10+4_IVS10+8delAGATA and consists of a deletion of five nucleotides at the +4 to +8 position in intron 10 of the BRIP1 gene. The normal sequence, with the bases that are deleted in brackets, is Ggta[delagata]ttttttc, where the capital letters are exonic and lowercase are intronic. In silico analyses, which include splice predictors and evolutionary conservation, are inconsistent in their assessment as to whether or not the variant is damaging.? This variant was not observed in large population cohorts (Lek 2016). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. Based on currently available evidence, it is unclear whether BRIP1 c.1473+4_1473+8delAGATA is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000706610 SCV000835673 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-02-16 criteria provided, single submitter clinical testing This sequence change falls in intron 10 of the BRIP1 gene. It does not directly change the encoded amino acid sequence of the BRIP1 protein, but it affects nucleotides within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRIP1-related disease. ClinVar contains an entry for this variant (Variation ID: 182373). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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