CanVIG-UK Consensus Specification
Specifications
v3.0
Approved: 13/12/2024
For the full consensus specification, click 'Download PDF'.
To help identify where new changes have been made we now also provide a tracked version of the specification with recent changes highlighted in red text. To access this version, please click 'Tracked Version'.
General Guidance Notes:
● Evidence items for which CanVIG-UK has offered additional specification are shaded in grey. Evidence items are shaded in white where there is no additional specification beyond ACGS Best Practice Guidelines version 1.2 (20/02/2024).
● Gene specific guidance for specific CSGs can be viewed at https://www.cangene-canvaruk.org/gene-specific-recommendations and should be followed for genes where these exist. These include CanVIG-UK gene specific guidance and gene specific guidance from ClinGen Sequence Variant Interpretation (SVI) Working Groups (+/- notes from CanVIG-UK).
● Evidence items can be combined using evidence (exponent) points for evidence towards pathogenicity (Very Strong= 8, Strong= 4, Moderate= 2, Supporting= 1) or towards benignity (Very Strong= -8, Strong= -4, Moderate= -2, Supporting= -1). Thresholds: ≥10 (Pathogenic), 6-9 (Likely Pathogenic), (-1) – (-5) (Likely Benign), ≤-6 (Benign). It is recommended that evidence criteria and evidence (exponent) scores are included on clinical reports.
● ≥2 concordant evidence items are required for a classification of likely pathogenic/pathogenic/likely benign/benign, with the exception of BA1, which provides standalone evidence towards benignity
● Variants should be reported using HGVS nomenclature, including the clinically appropriate transcript and version number (e.g. MANE select and/or MANE clinical plus) and human reference genome build.
● This specification can be used for small sequence variants and intragenic copy number variants. For copy number variants including the whole gene, or overlapping either end of the gene (including UTRs), refer to the ACMG CNV guidance and ACGS Best Practice Guidelines 2024. Professional judgement should always be used when evaluating the evidence surrounding a particular genomic variant and assigning a classification.
v1.1
Approved: 30/01/2025
For the full reduced penetrance specification, click 'Download PDF'.
To help identify where new changes have been made we now also provide a tracked version of the specification with recent changes highlighted in red text. To access this version, please click 'Tracked Version'.
Changelog:
-
v1.1: Added clarification that BS2 may also be downgraded by one benignity evidence strength level
v1.0
Approved: 02/09/2022
CanVIG-UK Reclassification framework, as published in Genetics in Medicine https://doi.org/10.1016/j.gim.2022.05.002. For the full framework, click 'Download PDF'.
General Guidance Notes: None
Yearly Reduced Penetrance Framework Review
Following publication of the initial guidelines, CanVIG-UK plan to review the framework on a regular (yearly) basis. This review will be documented, and any updates made as a result of yearly review will be posted on this page.
Following publication of the initial guidelines, CanVIG-UK plan to review the Reduced Penetrance framework on a regular (yearly) basis. This review, and any updates made as a result of yearly review, will be documented here.