Case Report: Early-onset bilateral and multifocal clear cell renal cell carcinoma in a carrier of the germline likely pathogenic CHEK2 splice-region variant NM_007194.4:c.846 + 4_846 + 7del

Early-onset bilateral and multifocal clear cell renal cell carcinoma (ccRCC) is rare and suggests hereditary predisposition. We report a 36-year-old Polish male who presented with hematuria and flank pain. Imaging revealed a right renal mass; nephron-sparing surgery confirmed low-grade ccRCC (pT1a). One year later, multifocal left-sided ccRCC was diagnosed, requiring radical nephrectomy (pT1b). Germline testing identified a heterozygous likely pathogenic splice-region variant CHEK2 (NM_007194.4:c.846 + 4_846 + 7del). Functional data support aberrant splicing and reduced kinase activity. During 11 years of follow-up, the patient remained recurrence-free, with a stable Bosniak IIF lesion in the remaining kidney. This case documents the co-occurrence of early-onset bilateral and multifocal ccRCC with a germline likely pathogenic CHEK2 variant but does not establish a causal relationship. It underscores the value of comprehensive germline testing in atypical RCC and highlights the need for integrated germline-somatic studies to clarify whether CHEK2 variants are associated with renal cancer susceptibility.