Pipeline Overview

The primary diagnostic analysis consented to as part of the Genomic Medicine Service aims to provide prioritised variants for patients with sufficient evidence for diagnostic reporting related to their primary condition.

The Genomics England pipeline aims to facilitate this by annotating a shortlist of 'tiered' variants that are likely or plausibly disease causing for assessment by NHS GLH staff. It should be noted that Genomics England is not performing a clinical interpretation of the genome sequencing data. It is the responsibility of NHS GLH staff to perform a full clinical review as would be standard in a diagnostic laboratory, confirm the presence of selected variants where required, and report and authorise any results.

A major component of the Tiering process is the application of diagnostic grade virtual panels relevant to each family’s phenotype. These reflect the current EuroGentest and ESHG guidelines that state:

'For diagnostic purpose, only genes with a known (i.e., published and confirmed) relationship between the aberrant genotype and the pathology, should be included in the analysis.'

Note

Variants that are prioritised by the Genomics England Tiering process are available, along with their associated annotations in the Interpreted Genome output files (available in json format).

The Genomics England Interpretation Portal and Clinical Interpretation Partner’s tools also allow NHS GLH staff to explore the genome beyond the tiered variants so that variants outside the virtual gene panels applied or that do not pass default filters can be explored.

Feedback

If you have any feedback on the Genomics England Rare Disease bioinformatics pipeline please contact the Genomics England Service Desk at ge-servicedesk@genomicsengland.co.uk.