New Features:

• • Uniparental disomy (UPD) occurs when an individual receives both copies of a chromosome from one parent, which can result in rare disorders. UPD is now calculated when running trio exomes and genomes in Geneyx Analysis by comparing each variant of the proband to the parents. This feature will be displayed under the identity by descent (IBD) field when viewing the VCF level information and will display the chromosome, significance, and predicted inheritance pattern of the UPD event.

• • Whole genome sequencing contains thousands of common variants that may lack clinical importance, leading to low-priority variants being imported into the platform. On the other side, rare non-coding variants are often overlooked. Geneyx Analysis now enables Smart filtering whereby users can define frequency and CADD score thresholds to filter out irrelevant variants prior to the VCF annotation step. This feature is configured at the enrichment kit level (now called “Enrichment kits & Smart filtering”) and should improve the capture of deep intronic variants and minimize the number of annotated variants.

• • The Variant Browser now supports the lookup of copy number and structural variants (CNV/SV). With this feature, users can query events based on relevant annotations, including events that overlap given gene(s), as well as events that overlap enhancers that impact specific genes.

• • Pharmacogenomics (PGx) testing is now available for beta testers. This feature is optimized when starting from fastq and works with exome and whole genome data. The report contains interpretations for 13 CPIC Level A and B genes, with gene summaries, drug metabolism, interpretations, and recommendations. The user also has functionality to define the SNP array and select which genes to report on. Please contact us if interested.

Improvements:

• • The secondary pipeline VCF caller, DRAGEN, has been updated to the most recent version (v4.0). Release notes for this update can be found here, DRAGEN v4.0.

• • GnomAD and ClinVar have been updated to support annotations for CNV/SV. This improvement will provide supporting evidence for damaging or deleterious CNV/SV mutations.

• • Combined Annotation Dependent Depletion (CADD) scores have now been updated to the most recent version (v1.6). CADD scores are computed for all SNVs and ~20 million known indel variants in the human genome.

• • Automatic gender calculation is now available, which uses variant ratios on chromosome X that are not in pseudo autosomal regions. If the calculation differs from the assigned gender, the user will receive a notification regarding the discrepancy.

• • GnomAD loss of function intolerant (pLi) scores are now available for filtering in the “Effect and Prediction” tab. This score reflects the tolerance of a given gene to the loss of function based on the number of protein-truncating variants for this gene in control databases, weighted by size and sequence coverage.

• • All public annotation sources have been updated to the most recent version.

• • Carrier screening workflows create a virtual proband to determine if damaging or deleterious mutations could be inherited. This workflow now supports copy number variants/structural variants (CNV/SV). For example, if a matching event is identified, the user will be able to prioritize and create an interpretation for this overlapping CNV/SV.

• • Updates to the report configurations have been made in which there are now 4 assorted color templates to select from. This can be modified by the user and applied to different protocols.

In summary, the Geneyx team has worked hard to ensure that the platform is a leading-edge solution for hospitals and clinical diagnostic companies. This is not only evident from the updates observed in this release, but also from our marketing presence. We had great discussions with many users from hospitals and diagnostic companies at the American Society for Human Genetics (ASHG) conference in Los Angeles, CA and in the National Society for Genetic Counselors meeting in Nashville, TN. To all who visited our booths, thank you! 

As always, we are grateful to our customers that continue to use Geneyx for their NGS interpretation. If there are features that you would like to see in Geneyx Analysis, please contact support@geneyx.com with your suggestions.

Important note: In case your organization enabled strict access to Geneyx Analysis, you may have to enable analysis-files.geneyx.com domain at your firewall rules.