HGVS translation of delins fails with missing reference

[xiamaz]

Jannovar fails to generate an VCF if the supplied HGVS string describing an indel variant does not contain the reference sequence, although it is an valid HGVS annotation.

For example the following sample can be used to generate an VCF against hg19

NM_003220.2:c.826_842delCTGCCTGCAGGGAGACGinsAGGAT

But the following results in an erroneuos vcf:

NM_003220.2:c.826_842delinsAGGAT

##fileformat=VCFv4.2
##ALT=<ID=ERROR,Description="Error in conversion">
##FILTER=<ID=PARSE_ERROR,Description="Problem in parsing original HGVS variant string, written out as variant at 1:g.1N>N">
##INFO=<ID=ERROR_MESSAGE,Number=1,Type=String,Description="Error message">
##INFO=<ID=ORIG_VAR,Number=1,Type=String,Description="Original HGVS variant string from input file to hgvs-to-vcf">
##contig=<ID=1,length=249250621>
##contig=<ID=2,length=243199373>
##contig=<ID=3,length=198022430>
##contig=<ID=4,length=191154276>
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#CHROM	POS	ID	REF	ALT	QUAL	FILTER	INFO
1	1	.	N	<ERROR>	.	PARSE_ERROR	ERROR_MESSAGE=Could+not+translate+HGVS+to+genomic+variant;ORIG_VAR=NM_003220.2%3Ac.826_842delinsAGGAT

[visze]

which jannovar version?

[xiamaz]

We are using jannovar version 0.25.

…

On 26.04.2018 16:21, Max wrote: which jannovar version? — You are receiving this because you authored the thread. Reply to this email directly, view it on GitHub <#408 (comment)>, or mute the thread <https://github.com/notifications/unsubscribe-auth/ADL5sDMmGjIHD-NUs5lZSzr9mK84C-O_ks5tsdf2gaJpZM4TlJwV>.

[visze]

It seems that jannovar do not support all HGVS notations. Can you suggest a code change?

[xiamaz]

Jannovar seems to translate the delins sequence incorrectly to delAGGATins, while interfacing with the antlr bridge for the conversion process. In theory the parser structure seems to handle delins, but misinterprets the hgvs notation.

[holtgrewe]

The error on the console is

Could not translate variant NucleotideVariant [seqType=CODING_DNA, refID=NM_003220, proteinID=null, transcriptVersion=2]: de.charite.compbio.jannovar.hgvs.bridge.CannotTranslateHGVSVariant: Nucleotides must be given but were not in 826_842delAGGATins

The issue is that the parser does not correctly check whether the deleted nucletoides are given.

[holtgrewe]

Good catch, the indel tests were testing deletions only.

[holtgrewe]

Fixed in d67c185, will be part of next release.