Description
When two inter-chromosomal BND records are present in a VCF, VEP produces incorrect annotation for an unrelated small variant located ~99 Mb away on the same chromosome.
The issue is reproducible both in offline VEP and in the current VEP web interface.
Minimal reproducing VCF
##fileformat=VCFv4.2
#CHROM POS ID REF ALT QUAL FILTER INFO
chr9 37015062 MantaBND:2936:1:2:0:1:0:0 C [chr6:116311629[C . MaxDepth SVTYPE=BND;MATEID=MantaBND:2936:1:2:0:1:0:1;CIPOS=0,1;HOMLEN=1;HOMSEQ=C
chr9 37020792 MantaBND:4862:0:1:0:3:0:0 C [chr6:136912382[C . MaxDepth SVTYPE=BND;MATEID=MantaBND:4862:0:1:0:3:0:1;CIPOS=0,1;HOMLEN=1;HOMSEQ=C
chr9 136496196 . CAG C . PASS
Expected result
The deletion at chr9:136496196 is annotated as:
NM_017617.5:c.7541_7542del
p.(Pro2514Argfs*4)
Observed result
With both BND records present, VEP produces an incorrect annotation for the deletion.
Examples observed:
Offline VEP
NM_017617.5:c.7543_7544del
p.(Glu2515ValfsTer3)
Current VEP web interface
The deletion is not annotated against NOTCH1 and instead appears as:
NM_003980.6:c.67+54146_67+54147del
HGVS_OFFSET=-2
Removing either BND restores the expected annotation.
Description
When two inter-chromosomal BND records are present in a VCF, VEP produces incorrect annotation for an unrelated small variant located ~99 Mb away on the same chromosome.
The issue is reproducible both in offline VEP and in the current VEP web interface.
Minimal reproducing VCF
Expected result
The deletion at chr9:136496196 is annotated as:
Observed result
With both BND records present, VEP produces an incorrect annotation for the deletion.
Examples observed:
Offline VEP
Current VEP web interface
The deletion is not annotated against NOTCH1 and instead appears as:
Removing either BND restores the expected annotation.