most severe consequence polypyrimidine stretch

[dnil]

Describe the bug

We are seeing more issues with the most severe consequence. We recently fixed the clinical filter in scout (https://github.com/Clinical-Genomics/scout/issues/3858) to allow showing these nice little fellows, but that falls a bit short when the variant is not loaded. Currently, they also get a penalty from the rank model for being less clinically important, like this causative one from pureamoeba:

1       216210952       SV_221_1:tiddit|CNVnator_del_142:cnvnator|MantaDEL:10115:0:1:0:0:0:manta        N       <DEL>   .       PASS    Annotation=USH2A;CIEND=0,2;CIPOS=0,2;CSQ=deletion|splice_polypyrimidine_tract_variant&coding_sequence_variant&intron_variant&feature_truncation|LOW|USH2A|7399|Transcript|NM_206933.4|protein_coding|22-32/72|21-32/71||||||||||-1||EntrezGene|12601|YES||||NP_996816.3||||||RefSeq|||||||;CTG=CTCTTAGTAGCCATTGCTTTGATTGTTCTTTGTTTTCAGGATTGTACTGGTAAAGCCATATTTCAACTCCTATTACAATTATTTGATAAAATGTTTCAGGATATTGATTCCACCTGTTTAAAATTTCCATTGAAATTTGTGAGCCTAAAAATCAATGAGTGAAGAGTAAGTTTCAAAGGATTCAAATTAAATGCTGTTGTAGCAAAACTGTCAATTATCCCGCATTCTTTTATTAATTTTGCTTTTATTTGTAGAATGGCCTTTCCT;END=216301040;FOUNDBY=3;GeneticModels=pureamoeba:AD;HOMLEN=2;HOMSEQ=AA;IMPRECISE;LFA=16,11;LFB=19,11;LTE=14,11;REGIONA=216210823,216210952;REGIONB=216301040,216301211;RankResult=4|-12|5|0|3|0|3|0;RankScore=pureamoeba:3;SUPP_VEC=111;SVLEN=90088;SVTYPE=DEL;VARID=CNVnator_del_142:cnvnator|MantaDEL:10115:0:1:0:0:0:manta;clingen_cgh_benign=1;clinical_genomics_loqusFrq=0.00042;clinical_genomics_loqusObs=3;cnvnator_CHROM=CNVnator_del_142|1;cnvnator_FILTERS=CNVnator_del_142|PASS;cnvnator_INFO=CNVnator_del_142|END:216301000|SVTYPE:DEL|SVLEN:-90000|IMPRECISE|natorRD:0.498228|natorP1:1.77081e-12|natorP2:0|natorP3:1.81105e-12|natorP4:0|natorQ0:0.0024426;cnvnator_POS=CNVnator_del_142|216211001;cnvnator_QUAL=CNVnator_del_142|.;cnvnator_SAMPLE=CNVnator_del_142;manta_CHROM=MantaDEL_10115_0_1_0_0_0|1;manta_FILTERS=MantaDEL_10115_0_1_0_0_0|PASS;manta_INFO=MantaDEL_10115_0_1_0_0_0|END:216301039|SVTYPE:DEL|SVLEN:-90090|CIPOS:0:2|CIEND:0:2|HOMLEN:2|HOMSEQ:AA;manta_POS=MantaDEL_10115_0_1_0_0_0|216210949;manta_QUAL=MantaDEL_10115_0_1_0_0_0|819;manta_SAMPLE=MantaDEL_10115_0_1_0_0_0;most_severe_consequence=12601:deletion|splice_polypyrimidine_tract_variant;natorP1=1.77081e-12;natorP2=0;natorP3=1.81105e-12;natorP4=0;natorQ0=0.0024426;natorRD=0.498228;pureamoeba_tiddit_ACC11683A12_CHROM=SV_221_1|1;pureamoeba_tiddit_ACC11683A12_FILTERS=SV_221_1|PASS;pureamoeba_tiddit_ACC11683A12_INFO=SV_221_1|SVTYPE:DEL|SVLEN:90088|END:216301040|REGIONA:216210823:216210952|REGIONB:216301040:216301211|LFA:16:11|LFB:19:11|LTE:14:11|CTG:CTCTTAGTAGCCATTGCTTTGATTGTTCTTTGTTTTCAGGATTGTACTGGTAAAGCCATATTTCAACTCCTATTACAATTATTTGATAAAATGTTTCAGGATATTGATTCCACCTGTTTAAAATTTCCATTGAAATTTGTGAGCCTAAAAATCAATGAGTGAAGAGTAAGTTTCAAAGGATTCAAATTAAATGCTGTTGTAGCAAAACTGTCAATTATCCCGCATTCTTTTATTAATTTTGCTTTTATTTGTAGAATGGCCTTTCCT;pureamoeba_tiddit_ACC11683A12_POS=SV_221_1|216210952;pureamoeba_tiddit_ACC11683A12_QUAL=SV_221_1|.;pureamoeba_tiddit_ACC11683A12_SAMPLE=SV_221_1|ACC11683A12|GT:0/1|CN:1|COV:37:16.750621529891426:36|DV:14|RV:11|LQ:0.0:0.0|RR:22:20|DR:24:30;set=Intersection;svdb_origin=tiddit|cnvnator|manta;tiddit_CHROM=SV_221_1|1;tiddit_FILTERS=SV_221_1|PASS;tiddit_INFO=SV_221_1|SVTYPE:DEL|SVLEN:90088|END:216301040|REGIONA:216210823:216210952|REGIONB:216301040:216301211|LFA:16:11|LFB:19:11|LTE:14:11|CTG:CTCTTAGTAGCCATTGCTTTGATTGTTCTTTGTTTTCAGGATTGTACTGGTAAAGCCATATTTCAACTCCTATTACAATTATTTGATAAAATGTTTCAGGATATTGATTCCACCTGTTTAAAATTTCCATTGAAATTTGTGAGCCTAAAAATCAATGAGTGAAGAGTAAGTTTCAAAGGATTCAAATTAAATGCTGTTGTAGCAAAACTGTCAATTATCCCGCATTCTTTTATTAATTTTGCTTTTATTTGTAGAATGGCCTTTCCT|SUPP_VEC:1;tiddit_POS=SV_221_1|216210952;tiddit_QUAL=SV_221_1|.;tiddit_SAMPLE=SV_221_1 GT:CN:COV:DV:RV:LQ:RR:DR        0/1:1:37,16.7506,36:14:11:0,0:22,20:24,30

It's a clear het deletion of several exons, called by all callers, but the most severe consequence becomes splice_polypyrimidine_tract_variant.

We can update the SV rank score model to also include this as a (potentially) severe consequence for now perhaps?

Any chances of getting VEP adapt, eg the SO scale? I still feel from the textual definition, these warrant a "transcript_ablation" though the entire transcript is not gone.

Other options could include to revert to having coding_sequence_variant higher on the severity tree. It seems to be a fallback that is usually present on this kind of variants.

Software version (please complete the following information):

• MIP: 11.1.3

Additional context Add any other context about the problem here.