Glossary of Terms and Abbreviations

Terminology

Description

ACMG

American College of Medical Genetics and Genomics

Actionable gene

A gene responsible for a given disease is said to be 'actionable' if it has direct or indirect therapeutic applications.

API

Application Programming Interface: set of definitions and protocols for building and integrating application software.

BWA

Burrows-Wheeler Alignment algorithm

CNV

Copy Number Variation

DB

Data Base

DE

Dedicated Environment

ECS

Expanded Carrier Screening

Haplotype

A haplotype is a group of genes within an organism that was inherited from a single parent.

PE

Process Engine

QE

Query engine

RUO

Research use only

SNP

Single nucleotide polymorphism

SNP calling

Aims to determine in which positions there are polymorphisms, or in which positions at least one of the bases differs from a reference sequence

SNV

Single nucleotide variant

SV

Structural variants: large genomic alterations, where large is typically (and somewhat arbitrarily) defined as encompassing at least 50 bp. These genomic variants are typically classified as deletions, duplications, insertions, inversions, and translocations describing different combinations of DNA gains, losses, or rearrangements

VUS

Variant of Uncertain Significance

WGS

Whole Genome Sequencing

WB

Workbench - When the "WB" icon appears within the variant list, it means that the variant is included in the workbench. The Workbench is the primary interface for case analysis, providing essential information needed to evaluate a sample. Once processing is complete, the evaluation begins from this page. If you would like more information, please click here.

QC Metrics

Quality Control (QC) Metrics are a dedicated section within Franklin where all predefined configurations and thresholds are stored, as determined by the user. These metrics allow for the customization of quality control parameters, which can vary between different assays and users based on specific requirements. QC Metrics ensure that each analysis aligns with the predetermined standards, offering flexibility and precision. This section can be accessed via the “Workbench” tab. The setup of QC Metrics is guided through the user onboarding process in collaboration with Franklin’s team of experts. **QC is configured per the Assay

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CMA

Chromosomal microarray analysis

VCF

Variant Call Format is an output file of a bioinformatics pipeline used to store genetic sequence variations from DNA samples. Generated through next-generation sequencing (NGS), it records details about variants, their location, and associated data.

NR

Not Relevant - use this button in the variant strip to mark a variant as "not relevant."

B

Benign - On the left side of the Variant Strip, you’ll find a colorful circle with a letter indicating the ACMG classification. A turquoise ‘B’ indicates a Benign classification.

LP

Likely pathogenic - On the left side of the Variant Strip, you’ll find a colorful circle with a letter indicating the ACMG classification. An. orange ‘LP’ indicates a Likely Pathogenic classification.

P

Pathogenic - On the left side of the Variant Strip, you’ll find a colorful circle with a letter indicating the ACMG classification. A red ‘P’ indicates a Pathogenic classification.

Assay

A set of predefined configurations and protocols used in laboratory analysis, specifically designed to focus on and prioritize specific areas of interest. In Franklin, each Assay includes a configuration of parameters such as depth average and other QC-related settings. The Franklin team will create or modify assays upon customer request. BED files, which are part of the assay, define the genomic regions to be analyzed, and the workflow is pre-configured within the assay. Assays are essential for running specific workflows and uploading FASTQ files.

UPD

Uniparental Disomy - A genetic abnormality where both copies of a chromosome are inherited from one parent, while the corresponding chromosome from the other parent is missing.

P/M/DN

Parental / Maternal / De novo – On the left side of the variant strip, you’ll find the origin of the variant next to its zygosity. The variant might be inherited from the father (P) or the mother (M). In cases where the variant is a new mutation not inherited from either parent, it will be labeled as De novo (DN).

PS1, PS2, PS3, PS4

Strong evidence of pathogenicity

PM1, PM2, PM3, PM4, PM5, PM6

Moderate evidence of pathogenicity

PP1, PP2, PP3, PP4, PP5

Supporting evidence of pathogenicity

Solution Category

Solution Category in Franklin refers to the highest-level categorization of genetic analysis, such as genome, exome, or panel. Within the Germline solution category, for example, we have Whole Genome Sequencing (WGS), Whole Exome Sequencing (WES), which covers approximately 25,000 genes, Clinical Exome Sequencing (CES) that targets 6,000-8,000 genes, and Panels, which typically focus on fewer than 1,000 genes, including comprehensive cancer predisposition panels. A new solution category, PGX, is also being introduced, under which various workflows will be organized.

Workflow

A pre-configured set of parameters in Franklin, including the pipeline, kit, sequencer, file inputs, and quality control metrics, tailored for specific genetic tests (e.g., rare disease, tumor profile). Each workflow ensures optimal configurations for test accuracy and reporting, supporting various applications such as TSO500 or PGx + long reads.

Validated Workflow

Validated Workflow in Franklin refers to the combination of a specific kit and a corresponding workflow that has been verified for accuracy and performance. Examples of validated workflows include TSO500 by Illumina, Agilent CGP, Thermo Fisher OCA, and Oncomine Comprehensive. Franklin offers support for more than 500 validated workflows, each of which resides within an Assay. These workflows are essential for ensuring that each analysis is conducted according to the specifications of the kit used, making it possible to consistently deliver high-quality, reliable results.

Soft Panels

A soft panel is dynamic and acts as a filter to restrict the view of variants. It can be applied after the case has been generated, allowing for flexibility in addressing specific variants of interest. Additional soft panels can be added to refine the analysis further. Soft panels mask genes and offer the option to decide which variants to report, as seen in cases where broad tumor profiles, like TSO500, are used with soft panels applied post-analysis to maintain existing ordering procedures while expanding the scope of the analysis.

Hard Panels

Hard panels are applied before the annotation phase, and once implemented, they restrict the scope of analysis, preventing any expansion. This panel type is primarily used for regulatory compliance, ensuring that only the variants within the panel are reported and avoiding secondary findings. Hard panels require all variants found on the panel to be reported and are useful for fixed regulatory requirements, trimming the analysis before annotation for strict adherence to compliance standards.

The Solution

The Solution in Franklin refers to the complete, end-to-end genetic analysis and interpretation process within the Franklin software, a cloud-based tool. This solution covers everything from raw data to an entirely generated report. It includes all necessary components, such as workflows, panels, assays, and associated configurations, and encompasses both secondary and tertiary analysis. Each solution is designed to address specific clinical diagnostic or research needs, providing a seamless and integrated experience. Solutions are tailored to categories like germline, oncology, or pharmacogenomics (PGX), ensuring users have a comprehensive set of tools aligned with their clinical or research objectives.