Panels disease gene

Last update: 20241205

The main source of our panel data is from Genomics England panelapp https://panelapp.genomicsengland.co.uk. The PanelApp database includes all the gene panels that relate to genomic tests listed in the NHS National Genomic Test Directory, as well as the virtual gene panels that were used in the 100,000 Genomes Project.

We explicitly aim to develop methods that avoid the bias of virtual panel analysis. However, the knowledge of known disease-gene mechanisms are a valuable scoring feature in variant classification.

For example, ACMG variant classification standards include eight stages which use knowledge of genes with a known mechanism of disease. These apply when classifying evidence related to both pathogenic or benign effects. The affected ACGM criteria are: PVS1, PS1, PM1, PP1, BVS1, BS1, BM1, BP1. A subsequent example is the ACMG classification step, PVS1, which is defined as a “null variant (nonsense, frameshift, canonical +- 2 splice sites, initiation codon, single or multiexon deletion) in a gene where LOF is a known mechanism of disease”. Thus to define a gene as belonging to a known disease mechanism we must use a stable and reliable source of disease-genes. Read more here.

Current usage

1. Human inborn errors of immunity
   • File: 10876_2022_1289_MOESM2_ESM_DLcleaned.tsv
   • Source: https://lawlessgenomics.com/topic/iuis-iei-table-page via International Union of Immunological Societies (IUIS) Inborn Errors of Immunity Committee (IEI) (https://iuis.org)
   • Caveat: Cleaning was implemented here
2. Likely inborn error of metabolism
   • File: Likely_inborn_error_of_metabolism_targeted_testing_not_possible.tsv
   • Source: https://panelapp.genomicsengland.co.uk/panels/467/
   • Caveat: None
3. Pending: All 451 panels of GE panel app
   • File: Not shown
   • Source: GE panel app via the API
   • Caveat: Login required - this database has been locally downloaded and processed for our pipelines. This notice will be replaced when it is ready for use.