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<p>Hi Wendy,</p>
Yes - you are interpreting this correctly<br>
<br>
<span style="font-size:13.3333px">KMT2A:c.9982delCinsCA </span><span
style="font-size:13.3333px">is not compliant HGVS, but we try to
support and correct such descriptions. The HGVS version we
currently support requires the alleles be written in their minimal
representation - which would be an A not CA - and the change
described at the 3' most position. This allele should therefore be
described as </span><span style="font-size:13.3333px">c.9983dupA.
The prefixing of the C appears to be confounding the 3' shift in
the first instance - we will fix this for our July release.<br>
<br>
</span> The latest version of HGVS states the alleles should not be
listed, so the annotation would be <span
style="font-size:13.3333px"></span><span
style="font-size:13.3333px">c.9983dup. We plan to update to the
new HGVS version in July. <br>
</span><br>
<span style="font-size:13.3333px">Best wishes,<br>
<br>
</span><span style="font-size:13.3333px">Sarah<br>
</span>
<p><br>
</p>
<p>From: <b class="gmail_sendername">Wendy Jones</b> <span
dir="ltr"><<a href="mailto:wj1@sanger.ac.uk">wj1@sanger.ac.uk</a>></span><br>
Date: 22 May 2017 at 17:08<br>
Subject: FW: Mutations in VEP<br>
To: "<a href="mailto:dev@ensembl.org">dev@ensembl.org</a>" <<a
href="mailto:dev@ensembl.org">dev@ensembl.org</a>><br>
Cc: "<a href="mailto:wm2@ebi.ac.uk">wm2@ebi.ac.uk</a>" <<a
href="mailto:wm2@ebi.ac.uk">wm2@ebi.ac.uk</a>><br>
<br>
<br>
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<div>
<div
style="direction:ltr;font-family:Tahoma;color:#000000;font-size:10pt">Dear
Colleagues,<br>
<br>
I wonder if you might be able to answer this quesion in Will's
absence?<br>
<br>
Many thanks<br>
<br>
Best wishes<br>
<br>
Wendy<br>
<div style="font-family:Times New
Roman;color:#000000;font-size:16px">
<hr>
<div id="m_-3379751104023068568divRpF403529"
style="direction:ltr"><font face="Tahoma" color="#000000"
size="2"><b>Van:</b> Wendy Jones<br>
<b>Verzonden:</b> zondag 21 mei 2017 21:39<br>
<b>Aan:</b> <a href="mailto:wm2@ebi.ac.uk"
target="_blank">wm2@ebi.ac.uk</a><br>
<b>Onderwerp:</b> Mutations in VEP<br>
</font><br>
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<div class="h5">
<div>
<div
style="direction:ltr;font-family:Tahoma;color:#000000;font-size:10pt">
<div>Dear Will,</div>
<div><br>
</div>
<div>I wonder if you might be able to help me. I am a
clinician / staff scientist working at the Sanger
Institute. I am trying to interpret mutations in
<i>KMT2A</i> (human) I have been given by clinicians
to put into a paper using Assembly: GRCh37.p13.
Frustratingly I am often only given the coding
variant and the predicted protein variant by
clinicians (i.e. not the genomic co-ordinates or
transcript ID). I am using VEP to find out further
information about them for example the HGVS coding
variant location for my transcript of
interest ENST00000534358.1, and also to work out
their genomic co-ordinates. I find for the
frameshift mutations that the coding variant
position often changes when I ask for coding variant
in line with HGVS nomenclature (I concluded that
this was representing re-alignment due to repetitive
sequence to the most 3' position in line with the
way HGVS places variants). I have been running
variants through VEP twice to ensure the genomic
co-ordinates represent the HGVS coding variant (If I
have understood the way VEP works correctly if you
put in a variant the genomic co-ordinates represent
the position of the variant you entered, however if
HGVS interprets the variant as being in a slightly
different position the genomic co-ordinates will be
slightly out. </div>
<div><br>
</div>
<div>However I have noticed that when putting the
following variants through VEP a second time the
HGVS coding variant nomenclature changes again! I
wonder if you might be able to explain why this is?</div>
<div><br>
</div>
<div>For example <span style="font-size:13.3333px">KMT2A:c.9982delCinsCA</span><span
style="font-size:10pt"> <wbr>run through VEP, HGVS
nomenclature coding variant name changes this to </span><span
style="font-size:13.3333px">KMT2A:c.9982_9983insA</span><span
style="font-size:10pt">, however when run through
VEP a second time this becomes: </span><span
style="font-size:13.3333px">c.9983dupA.</span></div>
<div><br>
</div>
<div>It is also a similar story for the following
variants:</div>
<div><br>
</div>
<div>KMT2A:c.5166delT</div>
<div>KMT2A:c.5999_6002delTGTT</div>
<div>KMT2A:c.8098_8105delCTGGCATC</div>
<div><br>
</div>
<div>I wonder if you might be able to explain why the
variants continue to change (and what the correct
variant is?). And also if I have interpreted the way
VEP calculates genomic co-ordinates correctly?</div>
<div><br>
</div>
<div>Many thanks for your help,</div>
<div><br>
</div>
<div>Best wishes</div>
<div><br>
</div>
<div>Wendy</div>
</div>
</div>
</div>
</div>
</div>
</div>
<div>
<div class="h5">
<br>
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