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Release notes

Release 12

Release 12.0 - December 2025

  • Software update from DRAGEN v4.0.5b to DRAGEN v4.0.5c. Validation analysis.
  • QIAGEN has been removed as a variant prioritisation source. The same variants may still be prioritised through other sources.

Release 11

Release 11.0 - November 2025

  • Update of the ClinVar version used to prioritise variants, from April 2023 to April 2025. Validation of this update can be found here: Report (accessible to Genomics England employees only).
  • There is an existing issue in which a small number of ClinVar variants are not prioritised despite passing the rules for prioritisation. This occurs for variants which have conflicting interpretations with no submissions with assertion criteria provided. These are expected to be exceptionally rare, and the issue will be fixed in a future release.
  • Refactoring work for variants components used in the pipeline. No new features have been introduced and there is no change to the prioritisation rules.

Release 10

Release 10.0 - October 2025

  • Protein matching changes: only prioritise protein-matched variants when the matched protein change is in a MANE Select, MANE Clinical or pre-defined transcript. For a protein-matched variant to be prioritised by matching a ClinVar variant, the variant itself must not be classified as benign or likely benign.
  • FECH gene changes: prevent the prioritisation of homozygous FECH variant (18_57571588_A_G) when no other FECH variants are prioritised in the gene.

Release 9

Release 9.1 - August 2025

  • New tranche of QIAGEN variants available for prioritisation.
  • Excluded two repeatedly prioritised but unreportable variants: EDAR 2-108930972-C-T, GH1 17-63918961-A-G.
  • No impact on rules for variant prioritisation.

Release 9.0 - June 2025

  • MNV prioritisation bug fix. In previous releases, a pipeline bug has resulted in failure to appropriately prioritise MNVs that are phased, predicted to cause loss-of-function of the protein, and not present in any inclusion list. For an MNV, a component of the decomposed MNV was incorrectly prioritised if it alone was predicted to cause loss-of-function of the protein, regardless of whether the MNV as a whole was pathogenic. If none of the decomposed components were individually predicted to cause loss-of-function, then neither a subset nor the whole MNV was prioritised. This means a pathogenic MNV would have been missed, resulting in a potential false negative. In this release, a fix has been introduced to ensure these MNVs are now correctly prioritised.

Release 8

Release 8.0 - May 2025

  • Fix to prevent variants being prioritised if they are more than 2kb from the annotated gene (previously these variants could be prioritised if they were additionally within proximity to a different green gene).
  • Pipeline infrastructure changes.

Release 7

Release 7.1 - March 2025

  • Refresh of Qiagen variant data.
  • Update to Panel v0.643, including removing SERPING1 from the study.
  • Adding 291 CFTR variants to the internal inclusion list.

Release 7.0 - January 2025

  • No impact on rules or analysis for variant prioritisation.
  • Fix to prevent older versions of CRAM files being made available to users of VRT to visualise in IGV.

Release 6

Release 6.0 - January 2025

  • No impact on rules for variant prioritisation.
  • Upgrade of DRAGEN mapping and variant calling software from v4.0.5 to v4.0.5b. Minimal changes in output as a result: Report.
  • RefSeq transcript IDs added to pipeline outputs when available for MANE transcripts.

Release 5

Release 5.0 - December 2024

  • Bug fix for prioritising compound heterozygous variants. Previously, in the following set of circumstances, a compound heterozygous case could be missed:
    • The gene MOI is biallelic (or X-linked biallelic in females).
    • All variants that could be prioritised are small variants (or MNVs).
    • All of the small variants being considered in the compound-het check are phased.
    • All of the small variants (or MNVs that they are a part of) are heterozygous.
    • All of the variants have the same GT recorded in the VCF, regardless of phase set (e.g., 0|1)

This bug is now fixed and variants in the above scenario can be prioritised.

Release 4

Release 4.0 - October 2024

  • Variants up to 2kb from a gene on the panel are considered for prioritisation, increased from 50bp.
  • Changes to MNV prioritisation logic. Current limitations of MNV prioritisation can be found in the MNVs section. Further information can be found in a dedicated analysis report(accesible to Genomics England employees only).
  • Haplotype bug fix(accesible to Genomics England employees only).
  • Updated analytical validity results for sensitivity and specificity of the pipeline.

Release 3

Release 3.0 - September 2024

  • Decoupling from future Cellbase changes
  • No impact on rules or analysis from release 2

Release 2

Release 2.2 - September 2024

  • Addition of QIAGEN tranche 3 variants and updates to internal inclusion and exclusion lists – Updated analytical validity results and resources
  • Added more details on caveats of multinucleotide variant prioritisation

Release 2.1 - July 2024

  • Removal of 10 genes from the study – Updated analytical validity results and resources

Release 2.0 - June 2024

  • Addition of QIAGEN inclusion list variant prioritisation
  • Addition of protein matching of internal inclusion list variants
  • Update to analytical validity results
  • Update to contamination threshold
  • Fix of bugs described in release 1.0
    • Uses Cellbase v5.4.19, with fix of ClinVar record retrieval bug present in release 1.0
    • VUS classifications do not count against ClinVar variants for prioritisation
    • SMN1 variants only prioritised through targeted caller

Release 1

Release 1.0 - March 2024

  • First release

Release guide versions

Previous release documentation

Versions of this guide prior to release 3.0 can be found in the PDF format from the internal confluence page