The low allele frequencies of USP35 and CIC, coupled with the absence of DNMT3A allele frequency data in our population, strongly suggest the need for larger, population-specific studies to accurately interpret the significance of these variants in RDD pathogenesis, and to determine whether these low frequency VUS variants are pathogenic in our population or others. Here, USP35 is linked to sinus histiocytosis with massive lymphadenopathy.