PS1
No evidence was identified that a different nucleotide change causing the same amino acid substitution, p.(Gly530Asp), is already established as pathogenic or likely pathogenic, so PS1 was not assessed.
PS2
No confirmed de novo occurrence with established maternity and paternity was identified, so PS2 was not assessed.
PS3
No well-established functional study demonstrating a damaging effect of p.(Gly530Asp) on DDX41 function was identified, so PS3 was not assessed.
PS4
This variant has been observed in somatic cancers in COSMIC (COSV57250947, n=4) and is listed in ClinVar as Uncertain significance, but no case-control enrichment or clearly quantified excess in unrelated individuals with DDX41-related hematologic malignancy predisposition was identified, so PS4 is not met.
PM1
This variant has not been shown to lie in a well-established mutational hotspot or a critical domain without benign variation; Cancer Hotspots did not identify a statistically significant hotspot at residue G530, so PM1 is not met.
PM5
No evidence was identified that a different missense change at codon 530 is already established as pathogenic or likely pathogenic, so PM5 was not assessed.
PM6
No assumed de novo occurrence without full parental confirmation was identified, so PM6 was not assessed.
PP1
No segregation data were identified showing this variant tracking with DDX41-related hematologic malignancy predisposition in a family, so PP1 was not assessed.
PP2
Available evidence was insufficient to determine whether missense variation is a well-established pathogenic mechanism for DDX41 with a sufficiently low benign missense rate to support PP2, so PP2 was not assessed.
PP4
No individual-level phenotype, tumor, or family history details were identified that are sufficiently specific for DDX41-related hematologic malignancy predisposition to support PP4, so PP4 was not assessed.
