In this project, our objective is to test the enrichment of rare variants in over 800 genes potentially associated with childhood cancer development. We'll compare children with cancer to a cancer-free control group (SweGen data) to identify new predisposition genes for childhood cancer. This study is a subproject of the Genomic Medicine Sweden Childhood Cancer Predisposition (ChiCaP) project, a nationwide effort analyzing germline genomes for cancer predisposition in children with cancer. We plan to analyze Whole Genome Sequencing (WGS) data from over 400 children diagnosed with cancer. The burden of pathogenic or likely pathogenic instances in this patient cohort will be compared to a control cohort from the 1000 SweGen project. The germline WGS data for the patients has been generated on the Clinical Genomics Stockholm (CGS) SciLifeLab platform, and we will obtain the cram/bam files for the patients from CGS. The NAISS SENS project will be utilized to analyze the germline WGS data from the patients (n=420) and controls (Swegen, n=1000). We will employ open-source tools such as DeepVariant and VEP to call and annotate variants. We require computational resources and storage. We will apply the same pipeline and filtering parameters to both cohorts. We will use Fisher’s exact test to compare the enrichment of pathogenic or likely pathogenic variants in patients with the cancer-free control cohort (Swegen). This comparison will also be executed across various cancer type subsets, including neuroblastoma, lymphoma, medulloblastoma, and low-grade astrocytoma, among others. We will also compare pathogenic or likely pathogenic variant enrichment at gene and pathway levels, using a Bonferroni correction for multiple testing. Upon completion of the computation, source files (bam/cram) will be deleted, retaining only the final vcf files. After the project's completion, we will store the raw data and output files for long-term storage on our local servers at the department (KI MMK). The results will be published in an open-access journal.