[ensembl-dev] VEP result does not match start-end coordinate and allele for hgvs syntax

[Bhavana Harsha]

Hi Daniel,

Thank you for this. It works on VEP REST when I reverse the coordinates.
But from what I know reversing the coordinates is not compliant with the HGVS notation rules (i.e. the positions should be listed 5’ to 3’).

Besides, one of the results from Ensembl VEP (with input c.783_661+1del124) is again:

ENST00000460680.1:c.661_783+1delGAGCCCTACCACGACATCCGCTTCAACCTGATGGCAGTGGTGCCCGACCGCAGGATCAAGTATGAGGCCAGGCTGCATGTGCTGAAGGTGAACCGTCAGACAGTACTAGAGGCTCTGCAGCAGG

As far as I know, VEP returns HGVS compliant syntax. So, should it not also accept the same as input?

Cheers,
Bhavana


HI Bhavana,

I think the transcript is on the -1 strand so the start/end coordinates have to be swapped.
http://grch37.rest.ensembl.org/vep/human/hgvs/ENST00000460680.1:c.783_661+1del124?content-type=application/json;canonical=1&ccds=1&hgvs=1

But that's just a guess.
Best,
Daniel

From: <dev-bounces at ensembl.org<mailto:dev-bounces at ensembl.org>> on behalf of Bhavana Harsha <bh4 at sanger.ac.uk<mailto:bh4 at sanger.ac.uk>>
Reply-To: Ensembl developers list <dev at ensembl.org<mailto:dev at ensembl.org>>
Date: Friday, September 16, 2016 at 3:40 PM
To: "dev at ensembl.org<mailto:dev at ensembl.org>" <dev at ensembl.org<mailto:dev at ensembl.org>>
Subject: [ensembl-dev] VEP result does not match start-end coordinate and allele for hgvs syntax

Hello,

We?re trying to validate some mutations and see other co-located variants by using the VEP REST service for GRCh37, like this:

http://grch37.rest.ensembl.org/vep/human/hgvs/ENST00000460680.1:c.661_783+1del124?content-type=application/json;canonical=1&ccds=1&hgvs=1

And I get the following error:
{?error":"Start (52440390) must be less than or equal to end+1 (52440270)"}


If I include the deleted sequence in the hgvs syntax, I get a different error:

Input:
http://grch37.rest.ensembl.org/vep/human/hgvs/ENST00000460680.1:c.661_783+1delGAGCCCTACCACGACATCCGCTTCAACCTGATGGCAGTGGTGCCCGACCGCAGGATCAAGTATGAGGCCAGGCTGCATGTGCTGAAGGTGAACCGTCAGACAGTACTAGAGGCTCTGCAGCAGG?content-type=application/json;canonical=1&ccds=1&hgvs=1

Output:
{?error":"Reference allele extracted from ENST00000460680:52440390-52440269 (AGCCCTACCACGACATCCGCTTCAACCTGATGGCAGTGGTGCCCGACCGCAGGATCAAGTATGAGGCCAGGCTGCATGTGCTGAAGGTGAACCGTCAGACAGTACTAGAGGCTCTGCAGCAG) does not match reference allele given by HGVS notation ENST00000460680.1:c.661_783+1delGAGCCCTACCACGACATCCGCTTCAACCTGATGGCAGTGGTGCCCGACCGCAGGATCAAGTATGAGGCCAGGCTGCATGTGCTGAAGGTGAACCGTCAGACAGTACTAGAGGCTCTGCAGCAGG (GAGCCCTACCACGACATCCGCTTCAACCTGATGGCAGTGGTGCCCGACCGCAGGATCAAGTATGAGGCCAGGCTGCATGTGCTGAAGGTGAACCGTCAGACAGTACTAGAGGCTCTGCAGCAGG)"}


This is strange because shouldn?t the transcript coordinates ?ENST00000460680.1:c.661-783+1? correspond to ?3:g.52440268-52440391?? But these aren?t the coordinates returned and the allele sequence is inconsistent with the input.

Is there something I?m missing here?

Cheers,
Bhavana


---------------------------------------------
Bhavana Harsha
Bioinformatician
COSMIC
Wellcome Trust Sanger Institute
Hinxton, UK
CB10 1SA
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