<div dir="ltr"><div>that s great, thanks Sarah !</div><div><br></div><div>I will indeed come back with other issues if I found any, although for the moment I will move to other tools to address HGVS processing issues.</div><div><br></div><div>It would be indeed great if the Ensembl tools can cover that in the future! likely an API (as variant recoder) and not VEP should address these tasks, but it is important for VEP to not provide results that may be confusing/misinterpreted for the operations that are attempted.</div><div><br></div><div>thanks again for your great work!</div><div>br</div><div>d<br></div></div><br><div class="gmail_quote"><div dir="ltr">El mié., 2 ene. 2019 a las 13:14, Sarah Hunt (<<a href="mailto:seh@ebi.ac.uk">seh@ebi.ac.uk</a>>) escribió:<br></div><blockquote class="gmail_quote" style="margin:0px 0px 0px 0.8ex;border-left:1px solid rgb(204,204,204);padding-left:1ex">
<div bgcolor="#FFFFFF">
<p><br>
</p>
<p>Hi David,</p>
<p>Thanks for passing this on. Our March release of VEP will include
a check that the transcript picked to map the variant from
gene+protein change to genomic sequence is compatible with the
reference allele supplied. As Andrew says, we aim to add VCF
output to VariantRecoder in the future too.</p>
<p> Do let us know if you come across any other examples which do
not behave as you expect. While we may not be able to support some
of the stranger and more vague HGVS-like descriptions, we are very
interested to know about and consider common use cases.</p>
<p>Best wishes,</p>
<p>Sarah<br>
</p>
<p><br>
</p>
<div class="gmail-m_1226047979329586416moz-cite-prefix">On 30/12/2018 02:22, David Tamborero
wrote:<br>
</div>
<blockquote type="cite">
<div dir="auto">
<div>(Sorry for the late response, i m currenrly with no much
internet access)
<div dir="auto"><br>
</div>
<div dir="auto">Thanks Andrew for your answer. I m a bit
surprised of the general lack of tools addressing these
issues. Maybe it is not that required by the community,
although i would say the contrary. </div>
<div dir="auto"><br>
</div>
<div dir="auto">In any case, i will be tuned to see whether
your next releases can address some of them. </div>
<div dir="auto"><br>
</div>
<div dir="auto">Thanks again! </div>
<div dir="auto">Br</div>
<div dir="auto">D</div>
<br>
<br>
<div class="gmail_quote">
<div dir="ltr">El vie., 21 dic. 2018 20:57, Andrew Parton
<<a href="mailto:aparton@ebi.ac.uk" target="_blank">aparton@ebi.ac.uk</a>>
escribió:<br>
</div>
<blockquote class="gmail_quote" style="margin:0px 0px 0px 0.8ex;border-left:1px solid rgb(204,204,204);padding-left:1ex">
<div style="overflow-wrap: break-word;">Hi
David,
<div><br>
</div>
<div>One of the improvements that we could make that
would make this process a little easier would be if
variant_recoder gave a VCF output, this is something
that we will look into. Thanks.</div>
<div><br>
</div>
<div>VEP could definitely do a better job of predicting
HGVSg from HGVSp. Officially, we require that input
HGVS is relative to genomic or transcript coordinates.
VEP and Variant Recoder will successfully convert from
HGVSp to HGVSg sometimes, but as you’ve noticed, there
are distinct improvements that we can make. And while
the ability of variant recoder to convert from HGVSp
will improve over time, and I’ve added your comments
to our list of things to look at in the future, but I
can’t guarantee when or even if it’ll happen.</div>
<div><br>
</div>
<div>Kind Regards,</div>
<div>Andrew</div>
<div><br>
</div>
<div><br>
</div>
<div><br>
</div>
<div>
<div><br>
<blockquote type="cite">
<div>On 17 Dec 2018, at 15:24, David Tamborero
<<a href="mailto:david.tamborero@gmail.com" rel="noreferrer" target="_blank">david.tamborero@gmail.com</a>>
wrote:</div>
<br class="gmail-m_1226047979329586416m_1934897530215562167Apple-interchange-newline">
<div>
<div dir="ltr">
<div dir="ltr">
<div>thanks for your answer!</div>
<div><br>
</div>
<div>mmm i understand that the protein
representation can lead to a non-univocal
genomic mapping, but i m unsure of why VEP
tries to infer the genomic coordinates
without considering the passed aminoacid
of reference, (if this is what is
happening !). Note that this particular
aminoacid change (TP53:p.E285V) maps to a
unique genomic missense mutation in all
TP53 transcripts. <br>
</div>
<div><br>
</div>
<div>FYI (likely you know it), but when the
mapping is not univocal, is not uncommon
for other tools dealing with HGVS to give
a guess --which is normally the 'most
probable' based on different metrics-- as
a first 'hit' (and detail the rest). This
is specially needed when dealing with
indels. <br>
</div>
<div><br>
</div>
<div>Although maybe this is too complicated
for VEP. However, I m still not finding a
good way for --by using your tools--
passing from HGVS protein representation
to genomic coordinates (in 'vcf format',
meaning chr pos ref alt). This is not an
uncommon need in the field. If I may use
this forum to ask, are you planning to
support that in e.g. one of your API (i.e.
like the 'hgvs conversor' but supporting
the vcf-like output)?</div>
<div><br>
</div>
<div>many thanks for your time (and your
work!)</div>
<div>best regards from Stockholm</div>
<div>d<br>
</div>
</div>
</div>
<br>
<div class="gmail_quote">
<div dir="ltr">El dom., 16 dic. 2018 a las
14:19, Andrew Parton (<<a href="mailto:aparton@ebi.ac.uk" rel="noreferrer" target="_blank">aparton@ebi.ac.uk</a>>)
escribió:<br>
</div>
<blockquote class="gmail_quote" style="margin:0px 0px 0px 0.8ex;border-left:1px solid rgb(204,204,204);padding-left:1ex">
<div><span>Hi David,</span><span><br>
</span><span><br>
</span><span></span><span>I’ve taken a
look at this issue this morning and I
think I can see what’s going on. I can
reproduce this issue with the query: </span><span>perl
vep -id 'TP53:p.E285V' --database
--force_overwrite --hgvs --port 3337</span><span><br>
</span><span><br>
</span><span>VEP guesses the genomic
location based on this HGVS input
(17:7565261), and identifies that
overlapping transcript ENST00000413465
has a protein product. However, the
285th amino acid of this transcript is
not E, but Y. The alternate allele is
guessed by VEP from a collection of
options that it has. For example, with
the input HGVS 'TP53:p.M237I’, then VEP
has 3 potential alternate alleles it can
use to do this, by converting the given
ATG to one of ATA, ATC or ATT.<br>
</span><span><br>
</span><span>While VEP supports HGVS
input, due to the complexity of HGVS and
the variety of ways in which people use
it, then we require that input HGVS is
relative to genomic or transcript
coordinates. In protein cases, we give a
best guess where we can, but this is not
guaranteed.<br>
</span><span><br>
</span><span>Sorry that I couldn’t be of
more help.<br>
</span><span><br>
</span>
<div><span>Kind Regards,</span></div>
<div><span style="background-color:rgb(255,255,255)">Andrew<br>
</span><br>
<br>
<blockquote type="cite">On 14 Dec 2018,
at 18:00, David Tamborero <<a href="mailto:david.tamborero@gmail.com" rel="noreferrer" target="_blank">david.tamborero@gmail.com</a>>
wrote:<br>
<br>
Hi there, <br>
<br>
regarding the conversion from protein
to genomic representation supported by
VEP, I ve found a funny case; if I
input <br>
<br>
TP53:p.E285V<br>
<br>
VEP gives as output (vcf format)<br>
<br>
17 7565261 TP53:p.E285V T
A<br>
<br>
And then if I input to VEP that vcf
entry, I obtain two TP53 protein
annotations:<br>
<br>
downstream_gene_variant for
ENST00000359597<br>
missense_variant for ENST00000413465<br>
<br>
However, the missense variant is
annotated as 285 Y/F (and not the
E/V that I had at the start !)<br>
<br>
so it looks that some inconsistency
happened here, not sure why. Am I
missing some point ?<br>
<br>
thanks in advance!<br>
d<br>
<br>
<br>
<br>
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