All PROACTIVE samples were subjected to whole genome sequencing at the Broad Institute of MIT and Harvard before the raw data (CRAM files) were uploaded to CGAP. Strategies for identification of causal variants include CGAP assisted variant filtration and prioritization based on predicted biological impact and population allele frequency (link to CGAP pipeline diagram). The performance assessment study showed CGAP could identify all previously reported causal germline variants in all clinical cancer cases.
The pilot project for the PROACTIVE research study was in collaboration with Dana Farber Cancer Institute. The goal of this project was to evaluate the ability of CGAP’s pipeline to identify germline genetic variants in patient samples suspected of having a heritable cancer disorder. This performance assessment study was conducted using 24 clinical cases with collectively 51 known and well-characterized variants in diagnostic genes reported by NGS panel testing in CLIA laboratories. Variant types included missense, nonsense, frameshift, splice site, UTR, indels, and copy number (one deletion) that were reported as pathogenic, likely pathogenic, or variants of uncertain clinical significance by clinical laboratories.