The design of tumor-only sequencing pipelines may also limit the ability to detect intronic variants other than those affecting consensus splice sites (i.e. ±2) as well as Alu insertions, variants in highly homologous regions and pseudogenes.27,28 Consistent with this notion, PMS2, CHEK2 and MSH2 P/LP germline variants were frequently not detected by tumor-only sequencing, given the enrichment of these genes for intronic SNVs and/or for deletion/duplications. The gene discussed is PMS2; the disease is neoplasm.