ClinVar

Description

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. This variant has not been reported in the literature in individuals with ELANE-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 4 of the ELANE gene. It does not directly change the encoded amino acid sequence of the ELANE protein, but it affects a nucleotide within the consensus splice site of the intron. This variant disrupts the c.597+5 nucleotide in the ELANE gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 10581030, 23463630, 20049848, 30040071). This suggests that this nucleotide is clinically-significant, and that variants that disrupt this position are likely to be disease-causing. 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.