ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.2492+5G>C (rs763222019)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000218546 SCV000275935 uncertain significance Hereditary cancer-predisposing syndrome 2015-05-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
GeneDx RCV000485890 SCV000572041 uncertain significance not provided 2016-10-17 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.2492+5G>C or IVS17+5G>C and consists of a G>C nucleotide substitution at the +5 position of intron 17 of the BRIP1 gene. Multiple in silico models predict that this variant may damage the natural splice donor site of intron 17 and lead to abnormal splicing. However, in the absence of RNA or functional studies, the actual effect of this variant is unknown. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRIP1 c.2492+5G>C was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. The guanine (G) nucleotide that is altered is conserved across species. Based on currently available evidence, it is unclear whether BRIP1 c.2492+5G>C is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000796530 SCV000936048 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-12-07 criteria provided, single submitter clinical testing This sequence change falls in intron 17 of the BRIP1 gene. It does not directly change the encoded amino acid sequence of the BRIP1 protein, but it affects a nucleotide 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 conditions. ClinVar contains an entry for this variant (Variation ID: 231934). 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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