PS2
Not assessed: no proband genotype, parental testing, confirmed parentage, or documented de novo event is available for this variant.
PS3
Not assessed: no validated RNA, protein, or minigene assay is documented; SpliceAI maximum delta 0.002 is computational, not functional evidence.
PS4
Not assessed: no affected-case series, control comparison, or case-control enrichment metric is available for this exact intronic POLD1 variant.
PM2
Not met: gnomAD v4.1 overall allele frequency is 0.00231565, exceeding the generic PM2 cutoff of 0.0001.
PM3
Not assessed: no affected proband, second pathogenic allele, or phase result documents this variant in trans for a recessive disorder.
PM6
Not assessed: no clinical report supports a presumed de novo occurrence without parental testing for this variant.
PP1
Not assessed: no affected relatives, unaffected tested carriers, informative meioses, or genotype-phenotype segregation data are documented.
PP3
Not met: SpliceAI maximum delta 0.002 is below the >=0.2 PP3 supporting threshold.
PP4
Not assessed: no patient phenotype or disease-specific clinical features are provided to evaluate specificity for a POLD1-associated disorder.
PP5
Not met: ClinVar variation 676636 has zero expert-panel submissions and only exact-variant laboratory classifications of Benign or Likely benign.
