VarSome Picks is a new algorithmic filter that takes into account parameters as phenotype, gene and variant data in order to rank higher the potential causative variants in a disease-specific context.
Specifically, VarSome Picks ranks higher variants found in Top 10 genes* associated with the phenotype(s) selected by the user. The data regarding the gene-disease association and phenotype ontology are coming from the following datasources:
*Of note, there is no single source from which all relevant genes can reliably be mined. As a result, extracting data for gene-disease associations from multiple databases is likely to produce a more comprehensive list of variants found to be causative for the disease. Some of those are likely to have been classified as VUS.
VarSome Picks, also, takes into account
- Zygosity (variant-related information)
- VarSome germline classification (based on the ACMG criteria)
- Mode of inheritance (gene-related information)
As well as,quality parameters of:
- Allelic Balance (threshold for germline variants)
- Coverage in the sample
User Experience
The filter can be run on-demand (Analysis actions > New algorithm filter analysis) once the main analysis has finished. It can also run automatically for all analyses if the group supervisor enables this option in the analysis preferences.
VarSome Picks runs only for:
- Single sample germline analysis
- Gene lists analysis
Note that users should provide the suspected disease and phenotype.
Note to the User-Disclaimer:
Parameters that might affect the accuracy of VarSome Picks:
- Non-specific or highly genetically heterogeneous phenotype/phenotypic expansion
- Idiosyncrasies in search functionality ( e.g. hearing loss” instead of a query using the term “deafness” may not return the relevant gene)
- variable expressivity/age-related penetrance which are parameters that the algorithm does NOT take into account.
Therefore, the decision regarding the appropriateness of this approach has to be at the discretion of the experts-the users.