[ensembl-dev] VEP creates bad hgvsc

Michael Yourshaw myourshaw at gmail.com
Wed Oct 24 20:32:08 BST 2018


This question relates to VEP 93 Human.


I've seen a few cases where the hgvsc computed by VEP seems to be wrong.

for example the genomic variant chr1:942451T>C (rs6672356) for the
canonical transcripts produces these hgvsc values in VEP:

    - 'ENST00000342066.7:c.1027T>C'

    - 'NM_152486.2:c.1027T>C'


Looking at the cDNA sequence, the reference for NM_152486.2:c.1027 is not T
but C.


As best I can tell, chr1:942451 does not map to cDNA NM_152486.2 at 1027,
but rather to 1099, which contains the expected T as a reference.


The Alamut annotator for this variant fails with the reason "Transcript
NM_152486.2: Genome/Transcript discrepancy: Alternate genomic nucleotide
(C) same as transcript nucleotide (Assembly: GRCh38)"


dbSNP for rs6672356 contains

    NM_152486.2:c.1027C=
    NM_152486.2:c.1027C>T


This particular issue has a discussion in BioStars (
https://www.biostars.org/p/239892/). But I do not think the explanation
suggested there applies: that it is just a difference between RefSeq and
the reference genome.


These variants also seem to have a similar problem:

rs10902758 NC_000004.12:g.654854G>A NM_000283.3:c.958G>A
*** NM_000283.3:c.958G>A: Variant reference (G) does not agree with
reference sequence (A)
rs10902758 NC_000004.12:g.654854G>A NM_001145291.1:c.958G>A
*** NM_001145291.1:c.958G>A: Variant reference (G) does not agree with
reference sequence (A)
rs10902758 NC_000004.12:g.654854G>A NM_001145292.1:c.121G>A
*** NM_001145292.1:c.121G>A: Variant reference (G) does not agree with
reference sequence (A)
rs10902758 NC_000004.12:g.654854G>A XM_011513473.2:c.1177G>A

ॐ
Michael Yourshaw
myourshaw at gmail.com <myourshaw at ucla.edu>

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