Table 3 Precise splicing outcomes of the pathogenic SPINK1 intronic variants described to date
From: Toward a clinical diagnostic pipeline for SPINK1 intronic variants
Region | Variant nomenclaturea | Description on splicing mechanisms and outcomes | Reference pertaining to functional analysis | ||
|---|---|---|---|---|---|
At DNA level | At RNA level | At protein level | |||
Intron 1 | c.55 + 1G > A | r.7_55del; and r.55_56ins55 + 1_55 + 140 | p.Gly5Leufs*74; and p.Gly19Aspfs*11 | Activation of a cryptic splice donor site within exon 1 (at position c.7_8), resulting in the deletion of the 3′ end of exon 1; and activation of a cryptic splice acceptor site within intron 1 (at position c.55 + 141_55 + 142), resulting in the insertion of the 5′ end of intron 1 into the transcript | This study |
Intron 2 | c.87 + 1G > A | r.56_87del | p.Asn20Glnfs*5 | Exon 2 skipping | [12] |
Intron 2 | c.[88-1G > A; 88-7 T > A] | r.88del | p.Ala30Profs*65 | Skipping of the first nucleotide of exon 3 (the functional effect was derived entirely from the c.88_1G > A component variant) | This study |
Intron 3 | c.194 + 1G > A | r.88_194del | p.Ala30Glufs*35 | Complete exon 3 skipping | This study |
Intron 3 | c.194 + 2 T > C | r.88_194del | p.Ala30Glufs*35 | Skipping of exon 3 in 90% of transcripts | [12] |
Intron 3 | c.194 + 5G > A | r.88_194del | p.Ala30Glufs*35 | Almost complete exon 3 skipping | This study |