With this release, variants that have the same Phenotype Driven Ranking (PDR) score will now be further re-ranked using a tie-breaking logic. Diseases are rank-ordered first by score (high scores first), then as a tie-breaker by gene-disease causality (causal first), then disease prevalence (higher prevalence first), and finally alphabetical order.
In certain situations, there are a set of common variants that are report as pathogenic despite having greater than 1% population allele frequency.
While we typically want to exclude all variants above 1% otherwise, this creates a challenge when applying the Common Variants filter with 1% which will exclude these important pathogenic mutations when they occur, and raising the CV filter to 4% or higher includes too many irrelevant (non-pathogenic) variants that slows down review time.
This new improvement allows VA to be able to filter out variants above a % allele frequency threshold while keeping a short list of known common pathogenic variants. Generally these are ‘founder’ variants in the sense that they occurred recently in human evolution at a population bottleneck causing many people to inherit the mutation from that one affected founder. To enable this feature, you’ll need to check the “unless Established Pathogenic Common variant”.
A Biological Context (BC) filter, filters for variants based on known genes derived from the BC terms entered in the BC filter. However the scope of a gene can be modified through the Predicted Deleterious (PD) filter when the user specifies how many bases into the intron (from the intron/exon border) one wants to retain. For example to consider a gene ± 10 bases, one can specify “Keep only variants no more than 10 bases into intron…”. In this case, the BC filter will include variants within the gene’s exons as well as intronic variants within 10 bases from the exon’s border.
The improved UI of the PD filter makes this clearer and less confusing. If a user wants to consider a gene ± 10 bases, one can specify “Keep only variants no more than 10 bases into intron…”. The downstream BC filter will now consider variants within relevant genes including variants found within the gene’s exons as well as ± bases beyond the exon’s border. If one wants to consider possible variants in all intronic locations, one should not select this option.
Occasionally you open a large analysis that takes some time to open. In the middle of opening such an analysis, if the browser closes, changes webpage, or the computer is shutdown, an attempt to re-open such an analysis would have resulted in a warning with no option to cancel or resume the opening of the large analysis. With this new release, you’re now able to resume or cancel such a large analysis which was previously interrupted.
This latest release bow support/show correctly in the analysis the negative values from the BED files and also support more precision (decimals) for custom fields.
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