Rank 2 always missing in `ACMG_class` column

[ManavalanG]

I tried out AnnotSV v3.0.4 for about 20 samples, and none of their SVs are scored rank-2 in ACMG_class column. Here is an ranks for one of the WGS samples:

$cat out.tsv | awk 'BEGIN{FS="\t"} {if ($16=="full") {print $96}}' | sort | uniq -c
   2352 1
   3631 3
     10 4
     50 5
   5401 NA

Is this expected?

[lgmgeo]

Hi Manavalan,

To be ranked in class 2 (likely benign), a SV should be scored from −0.90 to −0.98 points according to the work provided by the joint consensus recommendation of ACMG and ClinGen (Riggs et al., 2020).

The comprehensive and detailed scoring guidelines used in AnnotSV are available in the Scoring_Criteria_AnnotSV_latest.xlsx file (see Table1 for loss SV and Table2 for gain SV). As you can see, this is indeed not yet possible to obtain such a score.

We especially took attention to scoring as well as possible SV via AnnotSV. New developments are planned (addition of a database of likely benign SV, addition of breakpoints scoring for SV that are not gain or loss SV...). But it might take time...

Of course, we appreciate the involvement of users in suggesting further improvements. Let us know of any new ranking ideas ;o)

Best,

Véronique