exomiser
False positive hits to Orphanet copy-number diseases.
Exomiser <= 14.0.0 will give false positive hits for small sequence variants located in genes associated with contiguous gene deletion disorders mainly from Orphanet, e.g. Williams syndrome ORPHA:904 / OMIM:194050
The confusion arises from the disease-gene associations and the way Exomiser treats the disease type 'C' (copy-number) the same as 'D' (disease). In the case of disease.type = 'C' then the 'gene' needs to be treated as a large contiguous region covering all the associated genes and only matched to large deletions covering ~80/90+% of this region.
DISEASE_ID DISEASENAME OMIM_GENE_ID GENE_ID SYMBOL TYPE INHERITANCE
ORPHA:904 Williams syndrome OMIM:186590 6804 STX1A C D
ORPHA:904 Williams syndrome OMIM:605842 26608 TBL2 C D
ORPHA:904 Williams syndrome OMIM:608899 84163 GTF2IRD2 C D
ORPHA:904 Williams syndrome OMIM:610039 155382 VPS37D C D
ORPHA:904 Williams syndrome OMIM:604839 8468 FKBP6 C D
ORPHA:904 Williams syndrome OMIM:600404 5982 RFC2 D D
ORPHA:904 Williams syndrome OMIM:608512 653361 NCF1 C D
ORPHA:904 Williams syndrome OMIM:612547 135886 TMEM270 C D
ORPHA:904 Williams syndrome OMIM:605678 51085 MLXIPL D D
ORPHA:904 Williams syndrome OMIM:603431 7458 EIF4H C D
ORPHA:904 Williams syndrome OMIM:618202 84277 DNAJC30 D D
ORPHA:904 Williams syndrome OMIM:605846 9275 BCL7B D D
ORPHA:904 Williams syndrome OMIM:612546 155368 METTL27 C D
ORPHA:904 Williams syndrome OMIM:615733 114049 BUD23 C D
ORPHA:904 Williams syndrome OMIM:605681 9031 BAZ1B C D
ORPHA:904 Williams syndrome OMIM:603432 7461 CLIP2 C D
ORPHA:904 Williams syndrome OMIM:130160 2006 ELN C D
ORPHA:904 Williams syndrome OMIM:601679 2969 GTF2I C D
ORPHA:904 Williams syndrome OMIM:604318 9569 GTF2IRD1 C D
ORPHA:904 Williams syndrome OMIM:601329 3984 LIMK1 C D
This would be great. Caveat: Some of the entries are set to "D" without any obvious reason, e.g. RFC2, which is not listed as a disease gene in OMIM.
Yes - spotted that as well and we are going to investigate where that is coming from. Presumably the Orphanet XML. What do you think it means if it is genuine - that LoF of BCL7B alone would cause the syndrome or at least a good part of the symptoms?
On Sat, Apr 13, 2024 at 9:20 AM Peter Robinson @.***> wrote:
This would be great. Caveat: Some of the entries are set to "D" without any obvious reason, e.g. RFC2, which is not listed as a disease gene in OMIM.
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