NM_007194.4:c.1376-23G>C is a deep intronic variant in CHEK2 intron 12, located 23 bases upstream of exon 13. This variant is present at extremely low frequency in population databases: gnomAD v2.1 allele frequency = 0.0064% (15/233,494 alleles) and gnomAD v4.1 allele frequency = 0.0018% (27/1,501,478 alleles), with all observations restricted to the South Asian population and no homozygotes observed (PM2_Supporting).¹ Computational splicing analysis with SpliceAI predicts no impact on splicing (max delta score = 0.00; all four delta scores for acceptor gain, acceptor loss, donor gain, and donor loss are 0.00), consistent with a benign computational profile (BP4_Supporting).² The variant does not fall into any PVS1 null-variant category (not a nonsense, frameshift, or canonical splice variant), and SpliceAI confirms no predicted cryptic splice alteration.³ No functional studies, segregation data, de novo observations, case-control data, or ClinVar classifications are available for this variant. Applying the generic ACMG/AMP 2015 final combination rules (PMID:25741868), the evidence profile consists of one supporting pathogenic criterion (PM2) and one supporting benign criterion (BP4). With only one supporting criterion on each side, the evidence is indeterminate, resulting in a classification of Variant of Uncertain Significance (VUS).⁴