Aim 2

Consistent reporting of genomic variants

The second key objective of the TGMI is to develop standardised frameworks and tools for consistent clinical annotation and reporting of gene variation. This will be achieved through the following initiatives:

Matched Annotation from the NCBI and EMBL-EBI (MANE)

There are two main transcript datasets: RefSeq from NCBI, predominantly used in clinical reporting, and Ensembl/GENCODE from EMBL-EBI, predominantly used for the major genomics-based projects. In collaboration with NCBI, the TGMI is working to ensure that the same default transcript is used in all the major data sources (for example Ensembl, ClinVar, gnomAD, UniProt, COSMIC) that are likely to be interrogated for the consequence of any variant.  Through this initiative, variant interpretation will be simplified – it will no longer be necessary to convert between the two annotation sets, which will prevent errors and speed up clinical variant interpretation.

Visit the MANE project page in the outcomes section for more information.

Minimal Clinical Reporting Set (MCRS)

A large number of biologically plausible transcripts can give rise to a different consequence from a single genomic variant.  The MCRS will encompass the minimal subset of transcripts at each disease locus that are relevant to clinical reporting, preventing the otherwise impractical requirement of considering every transcript identified.

Transcript Archive (Tark)

The Transcript Archive (Tark) is a repository of all transcripts and versions from all sources. It has a layer of functionality that allows users to search, retrieve and compare transcripts. The aim of Tark is to 1) ensure full transparency about changes to transcripts over time, 2) to help users understand how transcripts from different sources relate to one another and 3) to ensure that transcripts used on historical clinical reports are available in perpetuity and can be reconciled with current genome-based reporting practices.

Back to The Plan