[ensembl-dev] PolyPhen2 prediction discrepancies between VEP 88 and dbNSFP v3.0

[Sarah Hunt]

Hi Brad,


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:


http://grch37.ensembl.org/Homo_sapiens/Variation/Mappings?db=core;r=1:103427257-103428257;v=rs754273408;vdb=variation;vf=119985449

http://www.ensembl.org/Homo_sapiens/Variation/Mappings?db=core;r=1:102961701-102962701;v=rs754273408;vdb=variation;vf=119958041


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?


Best wishes,


Sarah


On 12/06/2017 17:05, Crone, Bradley wrote:
>
> Hello,
>
>
> I'm working with PolyPhen2 scores and predictions in VEP 88 and 
> comparing these back to scores reported in dbNSFP v3.0.
>
> I find a large number of discrepancies between HumDiv scores from VEP 
> and dbNSFP. I've looked at a small subset of 10 mismatches.
>
> Directly comparing scores/predictions with PolyPhen2's website, all 
> PolyPhen2 scores match with a dbNSFP score, and not a VEP score:
>
>
> 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
> 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
> 1    216011417    A    T    USH2A    NM_206933.2    MODERATE 
>  missense_variant    0.155    B    0.933    P    0.933 0.0573         
> 0.804
> 12    48398104    T    C    COL2A1    NM_001844.4    HIGH 
>  start_lost    0    U    0.219,0.14    B    0.14 0.136         0.923
> 1    103427757    C    G    COL11A1    NM_080629.2  MODERATE   
>  missense_variant    0    U    0.999    D  0.999       0.00574         
> 0.136
> 12    48377197    G    T    COL2A1    NM_001844.4  MODERATE   
>  missense_variant    0.784    P    0.001,0.0  B    0             1   
>           1
> 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
> 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
> 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
> 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
> 1    103462662    C    T    COL11A1    NM_001190709.1  MODERATE   
>  missense_variant    1    P    1.0    D    1 0.00026       0.00018
>
> Any idea for this discrepancy?
>
>
> Thanks,
>
> Brad
>
>
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