How to filter false positive somatic muations in short tandem repeat (STR) called by mutect2 ?

Somatic mutation calling usually uses bwa+GATK-mutect2 in our group. The output vcf file will show some information if a mutation located in short tandem repeat （STR）region, which contaions RPA, RU and STR. The explation as following:

##INFO=<ID=RPA,Number=.,Type=Integer,Description="Number of times tandem repeat unit is repeated, for each allele (in cluding reference)">

##INFO=<ID=RU,Number=1,Type=String,Description="Tandem repeat unit (bases)">

##INFO=<ID=STR,Number=0,Type=Flag,Description="Variant is a short tandem repeat">

When we to filter some using FilterMutectCalls, we also find some mutations will be marked with "str_contraction" in Filter column , and str_contraction means mutect2 reject the mutation. It shows that all the mutations marked with str_contraction have only one repeat number difference between reference and allele. Besides, these mutations must locates in the reference STR region with not less than 8bp.

I want to know whether or not reasonable to filter just based on "str_contraction", or there are some other useful methods ?

Thanks!

next-gen

• 2,313 views • link

updated 4.5 years ago by Raman2 •

• written 7.1 years ago by maoyonghn •

1 answer

Hello,

How does FilterMutectCalls classify some of the STR mutations as just deletions and the other ones as 'str_contraction'.

For example, below are three mutations from a TCGA vcf. All the three of them have 1 repeat unit deleted, but just one of them is classified as STR contraction.

I am confused how exactly a 'str contraction' differs from a deletion? Thanks very much!

chr1 5581147 rs536875083 ATG A . clustered_events;germline_risk;panel_of_normals;str_contraction CSQ=-|intergenic_variant|MODIFIER|||||||||||||||rs150348092|1||||deletion|||||||||||||||||||||||||||||||||||||||||||E_Multiple_observations&E_Freq&E_1000G;DB;ECNT=2;HCNT=3;MAX_ED=24;MIN_ED=24;NLOD=0.598;RPA=9,8;RU=TG;STR;TLOD=6.79 GT:AD:AF:ALT_F1R2:ALT_F2R1:QSS:REF_F1R2:REF_F2R1 0/0:3,0:0.00:0:0:69,0:0:3 0/1:4,4:0.500:2:1:120,121:2:2

chr1 11122204 . GT G . germline_risk;panel_of_normals CSQ=-|intron_variant|MODIFIER|MTOR|ENSG00000198793|Transcript|ENST00000361445|protein_coding||47/57|ENST00000361445.7:c.6663-79delA||-/8677|-/7650|-/2549||||1||-1||deletion|HGNC|HGNC:3942|YES|1||CCDS127.1|ENSP00000354558|P42345||UPI000012ABD3|NM_004958.3|||||||||||||||||||||||||||||||2475|,-|intron_variant|MODIFIER|MTOR|ENSG00000198793|Transcript|ENST00000376838|protein_coding||9/19|ENST00000376838.4:c.1278-79delA||-/4017|-/2265|-/754||||1||-1||deletion|HGNC|HGNC:3942||2|||ENSP00000366034||B1AKP8|UPI000047004A||||||||||||||||||||||||||||||||2475|;ECNT=1;HCNT=1;MAX_ED=.;MIN_ED=.;NLOD=2.29;RPA=10,9;RU=T;STR;TLOD=7.57 GT:AD:AF:ALT_F1R2:ALT_F2R1:QSS:REF_F1R2:REF_F2R1 0/0:10,0:0.00:0:0:242,0:4:5 0/1:12,11:0.263:3:7:232,331:1:6

chr1 22596237 . TG T . PASS CSQ=-|intron_variant|MODIFIER|EPHA8|ENSG00000070886|Transcript|ENST00000166244|protein_coding||9/16|ENST00000166244.6:c.1765+69delG||-/4943|-/3018|-/1005||||1||1||deletion|HGNC|HGNC:3391|YES|2||CCDS225.1|ENSP00000166244|P29322||UPI000012A07B|NM_020526.3|||||4||||||||||||||||||||||||||2046|;ECNT=1;HCNT=18;MAX_ED=.;MIN_ED=.;NLOD=9.61;RPA=5,4;RU=G;STR;TLOD=14.86 GT:AD:AF:ALT_F1R2:ALT_F2R1:QSS:REF_F1R2:REF_F2R1 0/0:36,0:0.00:0:0:1023,0:17:19 0/1:20,8:0.269:3:4:611,248:5:12

• 0 views • link

written 4.5 years ago by Raman2 •