Phailed SV phasing

[agatafant]

I am using the complete wf-human-variation pipeline v.2.2.4 (previously I used dorado 0.6.0) with --sv --snp --phased --cnv options. I have 3 affected siblings (A1, A2 and A3) with both the deletion and the duplication; sample H1 has only the deletion. The deletion is of 405kb (Chr6:162154938-162560714​) and the duplication of 509kb (Chr6:162185434-162695422​). Keep into account that this 2 SVs have a big overlap. After having added in nextflow config Sniffles2 options (--long-del-length 520000 and --long-dup-length 520000), the 2 SVs are detected but, except in one case, it isn't able to phase (actually I know,from different experiment, that A1, A2 and A3 has inherited the del from the father and dup from the mother ).

Since the two SVs are in two different alleles for A1, A2 and A3, I was expecting 1|0 for one and 0|1 for the other. For A2 I obtain the right genotypes also with phasing. For the other 2 I obtained:

• for A3: 0/1 for DEL and 1|0 for DUP
• for A1: 1/1 for DEL and 1|0 for DUP

In sample H1 (that has only the deletion) it identifies the DEL with GT:1/1.

Here below IGV screenshots (color by HP and sort by HP) of beginning and end coordinates of del and dup for A1 and H1 samples.

Why does it call the deletion in homozygosis? Why isn't able to phase?