Funcotator maf has different alt allele than vcf for some variants
REQUIRED for all errors and issues:
a) GATK version used:
Funcotator Version=4.1.9.0
b) Exact command used:
Funcotator --output out.vcf --ref-version hg38 --data-sources-path .../Funcotator/funcotator_dataSources.v1.7.20200521s --output-file-
format VCF --variant not_annotated.vcf
--reference genome.fasta --disable-sequence-dictionary-validation true --remove-filtered
-variants false --five-prime-flank-size 5000 --three-prime-flank-size 0 --force-b37-to-hg19-reference-contig-conversion false --transcript-selection-mode CANONICAL --lookahead-cache-bp 100000 --min-num-bases-for-segment-funcotation 150
--interval-set-rule UNION --interval-padding 0 --interval-exclusion-padding 0 --interval-merging-rule ALL --read-validation-stringency SILENT --seconds-between-progress-updates 10.0 --create-output-bam-index true --create-output-bam-md5
false --create-output-variant-index true --create-output-variant-md5 false --lenient false --add-output-sam-program-record true --add-output-vcf-command-line true --cloud-prefetch-buffer 40 --cloud-index-prefetch-buffer -1 --disable-ba
m-index-caching false --sites-only-vcf-output false --help false --version false --showHidden false --verbosity INFO --QUIET false --use-jdk-deflater false --use-jdk-inflater false --gcs-max-retries 20 --gcs-project-for-requester-pays
--disable-tool-default-read-filters false
When running Funcotator on the same not annotated file, we get differing output for some variants in the VCF and in the MAF file:
MAF output:
Chromosome Start_Position End_Position Reference_Allele Tumor_Seq_Allele1 Tumor_Seq_Allele2
chr11 118436656 118436657 - - G
Genome_Change cDNA_Change Protein_Change Variant_Classification
g.chr11:118436656_118436657insGGGGG c.144_145insG p.G52fs Frame_Shift_Ins
Annotation_Transcript
ENST00000534358.8
VCF output:
chr11 118436656 . TGGC GGGGG (selected FUNCOTATION:) FRAME_SHIFT_INS g.chr11:118436656_118436657insGGGGG ENST00000534358.8 c.144_145insG
Notice the differing REF and ALT output between MAF and VCF. I was also wondering, why the cDNA change is only insG.
Best regards,
Balthasar
-
Hi Balthasar,
do you also see an adjacent multi-nucleotide variant TGGC>GGGG in the maf? I think Mutect2 chooses a reducible form of indels in the form of MNV + pure indel, here TGGC>GGGG plus G insertion. Funcotator with VCF output has probably combined those two variants into TGGC>GGGGG.
Best,
Philipp
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