Not called deletion in mtDNA

[1ctw]

There is a mtDNA deletion in case 23103, which is not called in Scout. We have confirmed it with MLPA and also sequenced the breakpoints by sanger sequencing. I recently found mtDNA deletions in two other cases (23102 and 18157) and they are both called.

It would be good if you investigate why the one in 23103 is not called while the others are.

Thanks!

[dnil]

Hi,

yes, high load of discordant pairs noted on the MT-report:

Normal MT read pair count	Discordant MT read pair count	MT discordant ratio (ppk)
15664116	96026	6,09297

Looks very clearly like a del from drop of coverage and discordant read pairs (though the latter is a tad noisy, perhaps from numts or such?). Picture from downsample:

Lets forward to MIP and if they also can't find anything in particular off, perhaps TIDDIT in particular which should be the caller expected to perform reasonably on the MT side.

[jemten]

Hello,
sad to see that this wasn't picked up. Just talked to @J35P312 about this one and tiddit got a bit confused by the high number of different discordant reads. Everything got bundled into one.

MT      1       SV_1_1  N       <DEL>   .       FewLinks        SVTYPE=DEL;SVLEN=14318;END=14319;REGIONA=1,16471;REGIONB=73,16570;LFA=671990,165824;LFB=688221,199264;LTE=122304,49535;CTG=.;vocallizard_tiddit_ACC11570A4_CHROM=SV_1_1|MT;vocallizard_tiddit_ACC11570A4_POS=SV_1_1|1;vocallizard_tiddit_ACC11570A4_QUAL=SV_1_1|.;vocallizard_tiddit_ACC11570A4_FILTERS=SV_1_1|FewLinks;vocallizard_tiddit_ACC11570A4_SAMPLE=SV_1_1|ACC11570A4|GT:0/1|CN:4092|COV:90325:87893.35281005001:90466|DV:122304|RV:49535|LQ:0.009611923950776652:0.010609060685667745|RR:0:61751|DR:17966:96118;vocallizard_tiddit_ACC11570A4_INFO=SV_1_1|SVTYPE:DEL|SVLEN:14318|END:14319|REGIONA:1:16471|REGIONB:73:16570|LFA:671990:165824|LFB:688221:199264|LTE:122304:49535|CTG:.;SUPP_VEC=1;set=filterIntiddit;FOUNDBY=1;tiddit_CHROM=SV_1_1|MT;tiddit_POS=SV_1_1|1;tiddit_QUAL=SV_1_1|.;tiddit_FILTERS=SV_1_1|FewLinks;tiddit_SAMPLE=SV_1_1;tiddit_INFO=SV_1_1|SVTYPE:DEL|SVLEN:14318|END:14319|REGIONA:1:16471|REGIONB:73:16570|LFA:671990:165824|LFB:688221:199264|LTE:122304:49535|CTG:.|SUPP_VEC:1;svdb_origin=tiddit;SUPP_VEC=001 GT:CN:COV:DV:RV:LQ:RR:DR        0/1:4092:90325,87893.4,90466:122304:49535:0.00961192,0.0106091:0,61751:17966,96118

If we can identify 10 to 20 cases with MT deletions Jesper thinks he can calibrate the algorithm for the MT. Good that MT-report picked it up though. For now we can use that can use that as an indication for MT deletions and in those cases do a manual inspection in IGV.

[dnil]

I know of like four other cases, where we have wgs, from a list by @NicoleCMMS a couple of years back. Presumably there are more known now (@1ctw)!

[1ctw]

Thanks! We always do a manual inspection of mtDNA in all samples of suspected mitochondrial disease, and as you say good that it is picked up in the mtDNA report. I am at a conference and will start my vacation directly after the conference tomorrow. Nicole will get back to you with an updated list of cases with mtDNA deletions. Skickat från Outlook för Android<https://aka.ms/AAb9ysg>

…

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[Lucpen]

@J35P312 suggested to try eklipse, a tool to detect MT dels that will be incorporated to the nf-core raredisease pipeline, on this sample and the del was called (from 6334 to 15625). It outputted a nice circos plot, let me know if you want to take a look at the results.