[ensembl-dev] Inconsistent RefSeq coding HGVS in VEP

[Sarah Hunt]

Hi Wallace,

RefSeq transcripts occasionally differ from the genome assembly 
sequence. We calculate HGVS based on the reference assembly, so in a 
small number of cases, discrepancies can arise

This is particularly an issue for GRCh37 as many rare reference alleles 
have been replaced in the creation of GRCh38. If you look at the results 
for rs9332964/ NC_000002.12:g.31529325C>T on GRCh38, you will see the 
predicted HGVS is NM_000348.3:c.680G>A, as you would expect.

We have recently started taking alignments NCBI provide into account 
when calling consequences on RefSeq sequences, and plan to update VEP to 
use these alignments in HGVS creation, though this will not be a quick 
process.

Best wishes,

Sarah


On 01/02/2018 03:59, Wallace Ko wrote:
> Hello,
>
> For the variant NC_000002.11:g.31754395C>T, VEP GRCh37 gives HGVSc of 
> NM_000348.3:c.679G>A 
> <http://grch37.rest.ensembl.org/vep/human/hgvs/NC_000002.11:g.31754395C%3ET?content-type=application/json&refseq=1&hgvs=1> (rs9332964).
>
> By searching dbSNP, we can see that GRCh38 HGVS of rs9332964 
> is NC_000002.12:g.31529325C>T and VEP GRCh38 gives HGVSc of 
> NM_000348.3:c.680G>A 
> <http://rest.ensembl.org/vep/human/hgvs/NC_000002.12:g.31529325C%3ET?content-type=application/json&refseq=1&hgvs=1>.
>
> Searching ClinVar, NM_000348.3:c.680G>A gives result that correspond 
> to NC_000002.11:g.31754395C>T while NM_000348.3:c.679G>A doesn't.
>
> Querying NM_000348.3:c.679G>A in Mutalyzer Name Checker 
> <https://mutalyzer.nl/name-checker?description=NM_000348.3%3Ac.679G%3EA>, 
> an error is shown that the reference base should be C instead of G. 
> This make me wonder if the HGVSc from VEP GRCH37 is incorrect.
>
> Regards,
> Wallace Ko
>
>
> _______________________________________________
> Dev mailing list    Dev at ensembl.org
> Posting guidelines and subscribe/unsubscribe info: http://lists.ensembl.org/mailman/listinfo/dev
> Ensembl Blog: http://www.ensembl.info/

-------------- next part --------------
An HTML attachment was scrubbed...
URL: <http://mail.ensembl.org/pipermail/dev_ensembl.org/attachments/20180201/7765e3a1/attachment.html>