Version 84 Update

We are happy to introduce several enhancements and new features in our latest update:

We have introduced a significant update to Franklin's gene curation capabilities. With this enhancement, the curation of gene-condition associations now directly impacts priority scoring and variant filtration within your analyses. This advanced functionality allows for more refined and accurate prioritization of results, tailored specifically to your organization. Please note that activating this feature requires specific configuration by our support team. To enable and customize this feature for your organization, please contact our support team ([email protected]).

As part of Franklin/Dragen compatibility capabilities, more confidence-related information is now available for SV variants called by Manta caller. The Genotype Quality (GQ), Likelihoods (PL), Strand Bias (SB), Fisher Strand Bias (FS), and Variant Fragment (VF) are now displayed in the Confidence section. Furthermore, filtering option for Genotype Quality (GQ) is now available under the Confidence filters section.

Franklin now displays gnomAD v4.1 CNV occurrences data in hg38 cases. The gnomAD occurrence data is displayed under the Occurrence section on expanded variant tiles in cases, and is also accessible in the CNV region viewer for both cases and CNV searches specific to hg38. In hg19 cases, Franklin displays gnomAD v2.1 CNV occurrences.

Franklin has enhanced its capabilities for compound heterozygous (compound het) variant filtering (SNVs and indels) by introducing a powerful new filter called "Tree Compound." Leveraging filter decision trees, this new capability enables precise filtering and protection of variants to generate targeted lists for compound het analysis.

The "Tree Compound" filter specifically outputs only variants that have a corresponding paired variant within the same gene. In family analyses, this filter automatically incorporates family inheritance patterns, effectively pairing variants inherited from different parents or identified de novo variants.

Additionally, the "Tree Compound" filter supports defining two distinct sets of input filter chains, allowing users to pair variants in the same gene—one variant selected from List A and the second from List B. A practical example of this enhancement is identifying compound pairs consisting of one clearly Pathogenic variant combined with a Variant of Uncertain Significance (VUS), thereby excluding pairs that are both classified as VUS.

Note: The "Tree Compound" is a specialized filter and must always be positioned as the final node in the decision tree.

You can now group and visually collapse merged filters to reduce the complexity of the filter tree. Collapsed groups will contain all filter results and can be expanded or collapsed as needed. Additionally, groups can connect to other filters, and quick filters within a group will show a visual indication.

A new filter is added in tumor (somatic) cases under the "Mechanism of Disease" section of the “Gene properties” filter, called “Tumor Suppressor”. This enhancement allows users to show know tumor suppressor genes based on COSMIC and TSGene database classifications, thus improving oncogenic classification within their analysis workflows.

In tumor (somatic) cases, you can now utilize additional gene property filters, including "Sensitivity to LOF," "Sensitivity to Missense," "LOEUF," "pLI," "Missense Z-score," and "Missense o\e (upper)". These filters are designed to enhance the specificity of oncogenic classification and filtering, aligned with germline classification logic. This provides a more refined and precise analysis in somatic contexts.
Note: "Sensitivity to LOF" and "Sensitivity to Missense," apply to both SNV and CNV, while the rest of the filters apply only to SNVs.
These filters will be activated only in the upcoming annotation version; for earlier cases, they will remain inactive, clearly marked with a tooltip indicating their unavailability.

In tumor (somatic) cases, therapeutic clinical evidence (drugs) added by your organization for SNP variants can now be included in the Report. Reminder: when a variant is added to the Report, its associated drugs appear on the Case Summary tab of the Workbench, where they can be added to or removed from the Evidence section of the Report. Added drugs show on Report Preview under the variant’s Evidence\Therapeutic section and are included in the exportable formats, alongside Franklin-suggested drugs.

We additionally enhanced our support in clinical evidence for gene fusion variants. You can now add clinical evidence (therapeutic, diagnostic, prognostic) for fusion variants on a variant’s Somatic Clinical Evidence tab. When adding evidence, selecting the “Gene pair” scope associates the evidence with any fusion variant of the same gene pair (e.g. EML4::ALK), and will hence appear on their Somatic Clinical evidence tabs.