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<p>Hi Brad,</p>
<p><br>
</p>
<p>We do find differences between different PolyPhen analyses,
dependent on code version and protein databases used. Our GRCh37
database will be updated to the latest PolyPhen version in July,
so do expect some changes. There are a number of genes returning
unknown classifications in our GRCh37 databases, which have calls
in our GRCh38 databases which have already been updated to the
newer version, so we hope the update improves GRCh37 coverage. An
example from your list:<br>
</p>
<p><br>
</p>
<p><a class="moz-txt-link-freetext" href="http://grch37.ensembl.org/Homo_sapiens/Variation/Mappings?db=core;r=1:103427257-103428257;v=rs754273408;vdb=variation;vf=119985449">http://grch37.ensembl.org/Homo_sapiens/Variation/Mappings?db=core;r=1:103427257-103428257;v=rs754273408;vdb=variation;vf=119985449</a><br>
</p>
<p><a class="moz-txt-link-freetext" href="http://www.ensembl.org/Homo_sapiens/Variation/Mappings?db=core;r=1:102961701-102962701;v=rs754273408;vdb=variation;vf=119958041">http://www.ensembl.org/Homo_sapiens/Variation/Mappings?db=core;r=1:102961701-102962701;v=rs754273408;vdb=variation;vf=119958041</a></p>
<p><br>
</p>
<p>Thanks for the examples, but I find them a little confusing.
Don't 2 of them (10-73377145 & 1-103462662) show agreement
across all three versions?<br>
</p>
<p><br>
</p>
<p>Best wishes,</p>
<p><br>
</p>
<p>Sarah<br>
</p>
<p><br>
</p>
<div class="moz-cite-prefix">On 12/06/2017 17:05, Crone, Bradley
wrote:<br>
</div>
<blockquote
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<p>Hello,</p>
<p><br>
</p>
<p>I'm working with PolyPhen2 scores and predictions in VEP 88
and comparing these back to scores reported in dbNSFP v3.0.</p>
<p>I find a large number of discrepancies between HumDiv scores
from VEP and dbNSFP. I've looked at a small subset of 10
mismatches.</p>
<p>Directly comparing scores/predictions with PolyPhen2's
website, all PolyPhen2 scores match with a dbNSFP score, and
not a VEP score:</p>
<p><br>
</p>
<div>CHROM POS REF ALT GENE VEP-FEATURE
VEP-IMPACT VEP_CSQ VEP_POLYPHEN_SCORE
VEP_POLYPHEN_PRED DBNSFP_POLYPHEN2_HDIV_SCORE
DBNSFP_POLYPHEN2_HDIV_PRED pph2_prob pph2_FPR
pph2_TPR<br>
2 73679572 C A ALMS1 NM_015120.4 MODERATE
missense_variant 0.952 P 0.987,0.972,0.026
D,D,B 0.026 0.188 0.949<br>
1 216011417 A T USH2A NM_206933.2 MODERATE
missense_variant 0.155 B 0.933 P 0.933
0.0573 0.804<br>
12 48398104 T C COL2A1 NM_001844.4 HIGH
start_lost 0 U 0.219,0.14 B 0.14
0.136 0.923<br>
1 103427757 C G COL11A1 NM_080629.2
MODERATE missense_variant 0 U 0.999 D
0.999 0.00574 0.136<br>
12 48377197 G T COL2A1 NM_001844.4
MODERATE missense_variant 0.784 P 0.001,0.0
B 0 1 1<br>
6 70981396 C A COL9A1 NM_001851.4 MODERATE
missense_variant 0.555 P 0.31,0.0 B 0.31
0.112 0.904<br>
10 73377145 G A CDH23 NM_001171930.1
MODERATE missense_variant 1 P 1.0,1.0,0.998
D 1 0.00026 0.00018<br>
1 216496954 T C USH2A NM_206933.2 MODERATE
missense_variant 1 P 0.971,0.413 D,B 0.413
0.103 0.893<br>
17 18064707 C A MYO15A NM_016239.3
MODERATE missense_variant 0 U
0.941,0.761,0.165,0.523,0.981,0.953 P,P,B,P,D,P 0.523
0.0959 0.882<br>
1 103462662 C T COL11A1 NM_001190709.1
MODERATE missense_variant 1 P 1.0 D 1
0.00026 0.00018</div>
<br>
<p>Any idea for this discrepancy?</p>
<p><br>
</p>
<p>Thanks,</p>
<p>Brad<br>
</p>
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