PS1
No pathogenic variant causing the same amino acid change was identified in the available germline database evidence, so PS1 was not assessed.
PS2
No de novo data with confirmed maternity and paternity were identified, so PS2 was not assessed.
PS3
No well-established functional studies demonstrating a damaging effect of this specific variant were identified, so PS3 was not assessed.
PS4
No case-control or enrichment data were identified showing this variant is more prevalent in affected individuals than in controls, so PS4 was not assessed.
PM1
Available hotspot review did not confirm that this variant lies in a well-established mutational hotspot or critical functional domain without benign variation, so PM1 was not assessed.
PM3
No data were identified showing this variant in trans with a pathogenic variant for a recessive disorder, so PM3 was not assessed.
PM5
No pathogenic missense comparison at the same codon was identified from the available evidence, so PM5 was not assessed.
PM6
No assumed de novo occurrence without confirmed parental relationships was identified, so PM6 was not assessed.
PP1
No segregation data were identified, so PP1 was not assessed.
PP2
Available evidence did not establish that missense variation is a common disease mechanism for IDH2 with a low rate of benign missense variation, so PP2 was not assessed.
PP3
SpliceAI predicts no significant splice impact for this variant (max delta score 0.01), but the available registered sources do not provide sufficient missense-prediction evidence to support a damaging computational conclusion, so PP3 was not assessed.
PP4
No phenotype data were provided to determine whether the clinical presentation is highly specific for an IDH2-related disorder, so PP4 was not assessed.
PP5
No reputable external source classification for this specific variant was identified, so PP5 was not assessed.
