[ensembl-dev] Ensembl VEP reports incorrect HGVSc for chr X variants

[Pär Engström]

I have now tried the VEP script as well and that produces correct HGVS strings for the two examples below, as well as several other chr X variants where the web version gives erroneous HGVS strings. Thus, the error seems to be specific to the web version of VEP. Is this a known bug?

Many thanks,

Pär

> On 29 Jan 2015, at 17:17 , Pär Engström <par.engstrom at scilifelab.se> wrote:
> 
> Hi,
> 
> I have come across an issue with Ensembl VEP. I have used the web version of VEP for GRCh37, but the same problem seems to occur with the web version for GRCh38.
> 
> VEP has an option to report HGVS strings. This works fine for variants on the autosomes, but not for X chromosome variants. For those, the cDNA HGVS strings are frequently incorrect. For example, try the two following variants (VCF format):
> 
> X 31222203 1 A G . .
> X 31697653 2 G C . .
> 
> These variants fall within the coding sequence of a minus strand gene, so the first should be reported as "T>C" in the HGVSc strings. However, VEP reports it as "A>C". The problem seems to be specific to the HGVSc field, because the Codons field is correct (TTT/CTT). The HGVSp field also seems to be correct.
> 
> For the second variant, the error is somewhat different: here the HGVSc string is empty for most Ensembl transcripts, although the Codons field lists the correct change (CGG/GGG).
> 
> The problem seems to occur with GRCh38 as well (i.e. current Ensembl). I tried the first variant listed above. The result was different compared to the GRCh37 version, but still wrong. Now the change was indicated as N>C in the HGVSc strings. The variant in GRCh38 coords:
> 
> X 31204086 1 A G . .
> 
> I have processed quite a few variants and not seen this problem for any autosomal variant, but for many chr X variants.
> 
> Kind regards,
> 
> Pär