CanVar-UK: an online data platform supporting collaborative diagnostic interpretation of germline variants in cancer susceptibility genes

Abstract

Interpretation of germline variants in cancer susceptibility genes (CSGs) requires the collation of variant-level data from diverse sources, as well as the assembly of comprehensive clinical data, often necessitating sharing of information between genomic testing centers. Although a number of variant interpretation tools exist, there remains a need for a CSG-focused platform tailored to the diverse range of ClinGen variant curation expert panel guidance in these difficult-to-interpret genes. Here, we describe CanVar-UK, a freely-accessible web platform to assist in the interpretation of germline CSG variants. CanVar-UK contains variant-level data for over 1.7 million single nucleotide variants, comprising all coding variants in 115 established CSGs. These data include: in silico scores from 11 tools of clinical relevance; population allele frequencies from gnomAD v4.1 and case counts from NHS genomic testing via linkage to the National Disease Registration Service; variant-level readouts from 31 different functional and splicing studies across 13 CSGs; genetic epidemiology studies of the BRCA1/2 genes; and live linkage to existing consensus classifications in the ClinVar database. CanVar-UK additionally has a diagnostic discussion forum functionality, via which users are able to email the rest of the user base with queries and/or suggested classifications, facilitating the exchange of clinical and classification data between diagnostic centers. Already widely used by the NHS clinical workforce in the CSG space (with 879 registered NHS users), CanVar-UK has a rapidly growing international user base, with 607 registered users based outside the UK. We believe CanVar-UK to be an invaluable resource for germline CSG variant interpretation.