Here, exome variant prioritization, including specific analysis of synonymous variants and CNVs, pointed to the NM_006729.4:c.868A>G (p.I290V) variant in DIAPH2 as the most likely candidate for prelingual HL in an Italian NSHL family, which was supported by segregation analyses. Here, DIAPH2 is linked to nodular sclerosis classical Hodgkin lymphoma.