SV annotation - merge order looses some translocation annotation

[dnil]

VEP annotation should precede merger of SV files. Caller VCFs (manta, TIDDIT) have separate (linked) entries for both ends of a translocation. While this may be redundant, VEP is not yet translocation aware, and fails to annotate one (the numerically higher chromosome) if applied after merge.

[henrikstranneheim]

Was this related to the issue you posted on VEP some time ago? If so, could you ask VEP if they have made any progress or have a plan for implementing a solution?

Otherwise we have to fix something in the meantime.

[dnil]

I could ping them, but I’m not alone requesting updates to VEP SV. Without having any inside, my guess is that we should solve this ourselves for now. That’s what we opted for with FindSV way back when. Jesper and I talked to @jemten about this: should be no more than switching the order of merging and annotation of the SV VCFs.

[dnil]

Tentatively we have a case affected now (fitwalrus):

1       233122847       SV_1670_1:tiddit|MantaBND:10784:0:1:0:0:0:1:manta|MantaBND:10784:0:1:1:0:0:0:manta|MantaBND:10784:0:1:1:0:0:1:manta|MantaBND:10784:0:1:0:0:0:0:manta    N       ]17:29663424]N  .       PASS    Annotation=PCNXL2;BND_DEPT
H=41;CSQ=BND|intron_variant|MODIFIER|PCNX2|80003|Transcript|NM_014801.4|protein_coding||32/33||||||||||-1||EntrezGene||YES||||NP_055616.3||||||RefSeq|||||||,BND|downstream_gene_variant|MODIFIER|NTPCR|ENSG00000135778|Transcript|ENST00000366628
|protein_coding|||||||||||3220|1||HGNC|28204|YES|||CCDS1597.1|ENSP00000355587|NTPCR_HUMAN|Q5TDE9_HUMAN|UPI00000411DD|||Ensembl|||||||,BND|intron_variant|MODIFIER|PCNXL2|ENSG00000135749|Transcript|ENST00000258229|protein_coding||32/33|||||||||
|-1||HGNC|8736|YES|||CCDS44335.1|ENSP00000258229|PCX2_HUMAN|B3KNZ5_HUMAN|UPI0000F58F23|||Ensembl|||||||;CTG=ACCTTGCTTGAAACCAATTTCACATTTCCAGAAGCCAAAGCTACAGCAGTATCTGCCATCACCTCAGCAAGCTATTCTGGAAAAGAGGCGAGGGCATGGGCTTTCAGCTCTCCTCCCCTTTCTTCTTTTTTCAT
GGCAAATAAAAATGACAGAACCCTGCACGTTTTCCTTTATCACTGCTGATCGGATGAGCATGGGAACC;EVENT=MantaBND:10784:0:1:0:0:0:0;FOUNDBY=2;GeneticModels=fitwalrus:AD;JUNCTION_QUAL=810;LFA=43,32;LFB=43,32;LTE=38,31;MATEID=MantaBND:10784:0:1:0:0:0:1;MATE_BND_DEPTH=49;REG
IONA=233122589,233123043;REGIONB=29663258,29663605;RankResult=6|0|1|0|3|0|0|0;RankScore=fitwalrus:10;SUPP_VEC=011;SVTYPE=BND;VARID=MantaBND:10784:0:1:0:0:0:1:manta|MantaBND:10784:0:1:1:0:0:0:manta|MantaBND:10784:0:1:1:0:0:1:manta|MantaBND:107
84:0:1:0:0:0:0:manta;fitwalrus_tiddit_ACC12039A1_CHROM=SV_1670_1|1,SV_1670_2|17;fitwalrus_tiddit_ACC12039A1_FILTERS=SV_1670_1|PASS,SV_1670_2|PASS;fitwalrus_tiddit_ACC12039A1_INFO=SV_1670_1|SVTYPE:BND|REGIONA:233122589:233123043|REGIONB:296632
58:29663605|LFA:43:32|LFB:43:32|LTE:38:31|CTG:ACCTTGCTTGAAACCAATTTCACATTTCCAGAAGCCAAAGCTACAGCAGTATCTGCCATCACCTCAGCAAGCTATTCTGGAAAAGAGGCGAGGGCATGGGCTTTCAGCTCTCCTCCCCTTTCTTCTTTTTTCATGGCAAATAAAAATGACAGAACCCTGCACGTTTTCCTTTATCACTGCTGATCGGATGAGCATG
GGAACC,SV_1670_2|SVTYPE:BND|REGIONA:233122589:233123043|REGIONB:29663258:29663605|LFA:43:32|LFB:43:32|LTE:38:31|CTG:ACCTTGCTTGAAACCAATTTCACATTTCCAGAAGCCAAAGCTACAGCAGTATCTGCCATCACCTCAGCAAGCTATTCTGGAAAAGAGGCGAGGGCATGGGCTTTCAGCTCTCCTCCCCTTTCTTCT
TTTTTCATGGCAAATAAAAATGACAGAACCCTGCACGTTTTCCTTTATCACTGCTGATCGGATGAGCATGGGAACC;fitwalrus_tiddit_ACC12039A1_POS=SV_1670_1|233122847,SV_1670_2|29663424;fitwalrus_tiddit_ACC12039A1_QUAL=SV_1670_1|.,SV_1670_2|.;fitwalrus_tiddit_ACC12039A1_SAMPLE=SV
_1670_1|ACC12039A1|GT:0/1|CN:.|COV:42:0:35|DV:38|RV:31|LQ:0.0:0.0|RR:25:17|DR:30:17,SV_1670_2|ACC12039A1|GT:0/1|CN:.|COV:42:0:35|DV:38|RV:31|LQ:0.0:0.0|RR:25:17|DR:30:17;manta_CHROM=MantaBND_10784_0_1_0_0_0_1|1,MantaBND_10784_0_1_1_0_0_0|1,Ma
ntaBND_10784_0_1_1_0_0_1|17,MantaBND_10784_0_1_0_0_0_0|17;manta_FILTERS=MantaBND_10784_0_1_0_0_0_1|PASS,MantaBND_10784_0_1_1_0_0_0|PASS,MantaBND_10784_0_1_1_0_0_1|PASS,MantaBND_10784_0_1_0_0_0_0|PASS;manta_INFO=MantaBND_10784_0_1_0_0_0_1|SVTY
PE:BND|JUNCTION_QUAL:810|BND_DEPTH:49|MATE_BND_DEPTH:41,MantaBND_10784_0_1_1_0_0_0|SVTYPE:BND|JUNCTION_QUAL:999|BND_DEPTH:49|MATE_BND_DEPTH:41,MantaBND_10784_0_1_1_0_0_1|SVTYPE:BND|JUNCTION_QUAL:999|BND_DEPTH:41|MATE_BND_DEPTH:49,MantaBND_107
84_0_1_0_0_0_0|SVTYPE:BND|JUNCTION_QUAL:810|BND_DEPTH:41|MATE_BND_DEPTH:49;manta_POS=MantaBND_10784_0_1_0_0_0_1|233122845,MantaBND_10784_0_1_1_0_0_0|233122847,MantaBND_10784_0_1_1_0_0_1|29663423,MantaBND_10784_0_1_0_0_0_0|29663426;manta_QUAL=
MantaBND_10784_0_1_0_0_0_1|999,MantaBND_10784_0_1_1_0_0_0|999,MantaBND_10784_0_1_1_0_0_1|999,MantaBND_10784_0_1_0_0_0_0|999;manta_SAMPLE=MantaBND_10784_0_1_0_0_0_1,MantaBND_10784_0_1_1_0_0_0,MantaBND_10784_0_1_1_0_0_1,MantaBND_10784_0_1_0_0_0
_0;most_severe_consequence=28204:BND|downstream_gene_variant,8736:BND|intron_variant;set=tiddit-manta;svdb_origin=tiddit|manta;tiddit_CHROM=SV_1670_1|1;tiddit_FILTERS=SV_1670_1|PASS;tiddit_INFO=SV_1670_1|SVTYPE:BND|REGIONA:233122589:233123043
|REGIONB:29663258:29663605|LFA:43:32|LFB:43:32|LTE:38:31|CTG:ACCTTGCTTGAAACCAATTTCACATTTCCAGAAGCCAAAGCTACAGCAGTATCTGCCATCACCTCAGCAAGCTATTCTGGAAAAGAGGCGAGGGCATGGGCTTTCAGCTCTCCTCCCCTTTCTTCTTTTTTCATGGCAAATAAAAATGACAGAACCCTGCACGTTTTCCTTTATCACTGCT
GATCGGATGAGCATGGGAACC|SUPP_VEC:1;tiddit_POS=SV_1670_1|233122847;tiddit_QUAL=SV_1670_1|.;tiddit_SAMPLE=SV_1670_1       GT:CN:COV:DV:RV:LQ:RR:DR        0/1:.:42,0,35:38:31:0,0:25,17:30,17

The OTHER end goes straight through an exon of NF1, but this is not annotated - only the chr1 part.

[dnil]

Ok, seems like this was finally merged in VEP 110! Shall we try to nudge the version and test?