ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.5268+5G>C

dbSNP: rs864622551
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001063765 SCV001228626 likely pathogenic Neurofibromatosis, type 1 2019-12-27 criteria provided, single submitter clinical testing 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. Disruption of this splice site has been observed in individual(s) with a diagnosis of, or clinical features of, neurofibromatosis type 1 (PMID: 16835897, 23913538, 12807981, Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 36 of the NF1 gene. It does not directly change the encoded amino acid sequence of the NF1 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant disrupts the c.5205+5 nucleotide in the NF1 gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 21354044, 12807981). This suggests that this nucleotide is clinically-significant, and that variants that disrupt this position are likely to be disease-causing. 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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