Dear all,

I have a clear deletion signature in my germline WES DNA sequencing data, the problem is - it is EXACTLY whole intron. So, I see split reads at both ends (exactly at exons borders) and also insert distance of reads shows that this is a deletion. The gene has tens of exons - so it can't be "retroduplication-style" structural variant. This is literally a whole intron cut out with up to 1bp resolution. The coverage of each exons is more than 100x and I see a sharp "drop" of coverage where the split reads are.

The question: 1) is there an alternative explanation to split-reads and paired-end distance? not a deletion but crazy 2-exon retroduplication, for example? (but it has to be cut and paste, not copy and paste - coverage remained at expected levels)

2) what may be a mechanism for 1bp resolution intron deletion inside a gene of tens of exons (other exons/introns are not affected)?

This picture may be easily explained by RNA-postprocessing and insertion of mRNA, but then more introns would be removed! I've tried to look for this gene (CACNA1B) pre-mRNA, but they are mostly concentrated on alternative splicing in the another end of the gene...

Q3) Is there a catalogue of RNA isoforms, stage-by-stage, from pre-mRNA to mature RNA?I still hope it can be explained by some very early pre-RNA that had only one intron spliced out.

The coverage remains normal - it is not a duplication at all, same amount of genomic material for both exons as expected.