In summary, WGS data analysis of three families with reported recurrence of HL allowed us to prioritize 45 coding and 79 non-coding variants from which we subsequently selected and validated one for family I (DICER1), short-listed three in family II (ALAD, CERCAM, and SPTAN1) and two in family III (RAD51 and LPP), to investigate further with validation and functional studies. This evidence concerns the gene SPTAN1 and Hodgkins lymphoma.