Splicing removes introns from a raw RNA transcript and joins exons together. A splice variant changes that process. It can skip an exon, add part of an intron, create a shorter transcript, or change which protein form is made.
What splice variants can change
Genes contain exons, which usually contribute to the final RNA, and introns, which are usually removed. Alternative splicing lets one gene produce more than one transcript. This is normal biology. A harmful splice variant is different: it disrupts the expected transcript in a way that can affect protein function.
Protein effects
- Truncated proteins: exon skipping can remove a protein region. In CHEK2, splice changes can remove sequence needed for DNA repair (source).
- Altered binding sites: a transcript change can remove or change a domain used for binding or signaling.
- Early stop signals: some abnormal transcripts introduce a stop signal that shortens the protein.
What to check
Location
Variants at conserved splice boundaries are more likely to disrupt exon joining. Deep intronic variants can also matter if they create a new splice site (source).
Transcript evidence
RNA sequencing or a functional assay can show whether the variant changes splicing. DNA data alone often cannot prove the transcript effect.
Population data
Very common variants are less likely to cause a severe rare disorder. Rare variants need more evidence, including consequence, inheritance, phenotype fit, and any published functional data.
How to review in Gene Inspector
Use splice annotations as a reason to review the variant more closely. Check the affected transcript, genotype quality, allele frequency, ClinVar entries, inheritance, and source evidence. For clinical questions, splice findings usually need confirmation outside a consumer DNA file.