<html><head><meta http-equiv="Content-Type" content="text/html; charset=utf-8"></head><body style="word-wrap: break-word; -webkit-nbsp-mode: space; line-break: after-white-space;" class="">Hi David,<div class=""><br class=""></div><div class="">Thanks for your query - 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. We have some documentation (that we are in the process of improving) on the matter here: <a href="http://www.ensembl.org/info/docs/tools/vep/vep_formats.html#hgvs" class="">http://www.ensembl.org/info/docs/tools/vep/vep_formats.html#hgvs</a></div><div class=""><br class=""></div><div class="">It may be more appropriate for you to use our variant recoder tool, also contained within the ensembl-vep repository, rather than VEP itself, as this will give you HGVSg output. However, without a particular transcript within the input, then it is possible that the variant could map to multiple locations. Variant Recoder will often guess at a solution (in the BRCA2 example you gave then it suggests <span style="font-family: Menlo; font-size: 11px; background-color: rgb(255, 255, 255);" class="">NC_000013.11:g.32336340_32336341delinsAA)</span>, however as you have noticed, unless the correct genomic/transcript nomenclature is used then a result cannot be guaranteed.</div><div class=""><br class=""></div><div class="">We are currently in the process of improving how we handle HGVS inputs, however this work is still in development. Sorry that I couldn’t give you a more beneficial response.</div><div class=""><br class=""></div><div class="">Kind Regards,</div><div class="">Andrew</div><div class=""><br class=""></div><div class=""><div><br class=""><blockquote type="cite" class=""><div class="">On 5 Dec 2018, at 09:27, David Tamborero <<a href="mailto:david.tamborero@gmail.com" class="">david.tamborero@gmail.com</a>> wrote:</div><br class="Apple-interchange-newline"><div class=""><div dir="ltr" class=""><div class="gmail_quote"><div dir="ltr" class=""><div dir="ltr" class=""><div dir="ltr" class=""><div dir="ltr" class=""><div dir="ltr" class=""><div dir="ltr" class=""><div dir="ltr" class=""><div dir="ltr" class=""><div class="">Hi there,</div><div class=""><br class=""></div><div class="">I m badly interested in converting protein changes to genomic changes via the VEP standalone perl script. Of note, I have the gene (but not the specific transcript) in which such a change is annotated (eg NRAS:Q61L).</div><div class=""><br class=""></div><div class="">I m experiencing some problems that I cannot figure it out how to solve; I ve tried to find any documentation to address those in the dev list archives etc but I failed. So I hope this is a good way to look for help (thanks in advance!). <br class=""></div><div class=""><br class=""></div><div class="">I m using VEP 93.3 with hg19 (I do not think that the vep parameters are relevant, but note that I m using vcf as output format since I need the coordinates in chr-pos-ref-alt ---and not HGVS--- format). <br class=""></div><div class=""><br class=""></div><div class="">-- insertion of stop codons--</div><div class=""><br class=""></div><div class="">so for cases as CDKN2A:p.Q50* or PTEN:p.R233*, VEP works smooth; however, for other cases (eg BRCA2:p.S662*) VEP does not seem happy and does not give an output. <br class=""></div><div class=""><br class=""></div><div class="">My guess is that this has to be with the fact that the ones that work are stop codons caused by a specific nucleotide change (eg. CDKN2A:p.Q50* -> chr10 89717672 C>T) whereas those that do not work are caused by insertions, which I guess it gives a larger universe of possible nucleotide changes. <br class=""></div><div class=""><br class=""></div><div class=""> However, why not to have a 'more possible' guess? e.g. for BRCA2:p.S662*, TransVar gives a fair chr13:g.32910477_32910478delCTinsAA try.</div><div class=""><br class=""></div><div class="">--indels--</div><div class=""><br class=""></div><div class="">here I m failing badly. I m not even sure that I m using the correct nomenclature. For instance, for frameshifts, DTX1:p.P11fs*2 is giving a 'Unable to parse HGVS notation' error. I went to the variant recoder API REST, and this specific variant in cdna nomenclature (which i retrieved also by TransVar), is represented as <span class=""><span class="m_-5679131016372609052gmail-objectBox-string m_-5679131016372609052gmail-objectBox">"ENSP00000257600.3:p.Pro11LeufsTer2" in protein coordinates<br class=""></span></span></div><div class=""><br class=""></div><div class=""><a href="https://rest.ensembl.org/variant_recoder/human/DTX1:c.32delC?content-type=application/json" target="_blank" class="">https://rest.ensembl.org/variant_recoder/human/DTX1:c.32delC?content-type=application/json</a></div><div class=""><br class=""></div><div class=""><span class=""><span class="m_-5679131016372609052gmail-objectBox-string m_-5679131016372609052gmail-objectBox">but when I input this representation to the VEP command, I m having the format error anyway, even after changing <span class=""><span class="m_-5679131016372609052gmail-objectBox-string m_-5679131016372609052gmail-objectBox">ENSP00000257600 for the gene (DTX1) or transcript (ENST00000257600) <span class=""><span class="m_-5679131016372609052gmail-objectBox-string m_-5679131016372609052gmail-objectBox"><span class=""><span class="m_-5679131016372609052gmail-objectBox-string m_-5679131016372609052gmail-objectBox">name</span></span></span></span> plus some alterntives to the <span class=""><span class="m_-5679131016372609052gmail-objectBox-string m_-5679131016372609052gmail-objectBox">p.Pro11LeufsTer2 representation.</span></span></span></span></span></span></div><div class=""><span class=""><span class="m_-5679131016372609052gmail-objectBox-string m_-5679131016372609052gmail-objectBox"><span class=""><span class="m_-5679131016372609052gmail-objectBox-string m_-5679131016372609052gmail-objectBox"><span class=""><span class="m_-5679131016372609052gmail-objectBox-string m_-5679131016372609052gmail-objectBox"><br class=""></span></span></span></span></span></span></div><div class=""><span class=""><span class="m_-5679131016372609052gmail-objectBox-string m_-5679131016372609052gmail-objectBox"><span class=""><span class="m_-5679131016372609052gmail-objectBox-string m_-5679131016372609052gmail-objectBox"><span class=""><span class="m_-5679131016372609052gmail-objectBox-string m_-5679131016372609052gmail-objectBox">Am I missing some point?</span></span></span></span></span></span></div><div class=""><span class=""><span class="m_-5679131016372609052gmail-objectBox-string m_-5679131016372609052gmail-objectBox"><span class=""><span class="m_-5679131016372609052gmail-objectBox-string m_-5679131016372609052gmail-objectBox"><span class=""><span class="m_-5679131016372609052gmail-objectBox-string m_-5679131016372609052gmail-objectBox"><br class=""></span></span></span></span></span></span></div><div class=""><span class=""><span class="m_-5679131016372609052gmail-objectBox-string m_-5679131016372609052gmail-objectBox"><span class=""><span class="m_-5679131016372609052gmail-objectBox-string m_-5679131016372609052gmail-objectBox"><span class=""><span class="m_-5679131016372609052gmail-objectBox-string m_-5679131016372609052gmail-objectBox">many thanks in advance (and congratulations for such a great tool!)</span></span></span></span></span></span></div><div class=""><span class=""><span class="m_-5679131016372609052gmail-objectBox-string m_-5679131016372609052gmail-objectBox"><span class=""><span class="m_-5679131016372609052gmail-objectBox-string m_-5679131016372609052gmail-objectBox"><span class=""><span class="m_-5679131016372609052gmail-objectBox-string m_-5679131016372609052gmail-objectBox">br</span></span></span></span></span></span></div><div class=""><span class=""><span class="m_-5679131016372609052gmail-objectBox-string m_-5679131016372609052gmail-objectBox"><span class=""><span class="m_-5679131016372609052gmail-objectBox-string m_-5679131016372609052gmail-objectBox"><span class=""><span class="m_-5679131016372609052gmail-objectBox-string m_-5679131016372609052gmail-objectBox">d<br class=""></span></span></span></span></span></span></div></div></div></div></div></div></div></div></div>
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