PS1
Not met: the exact p.Ser390Gly variant was classified as a class 3 VUS, with no established pathogenic same-amino-acid substitution identified.
PS2
Not assessed: parental genotypes and confirmed maternity/paternity are not reported for the exact variant in the available patient record.
PS3
Not assessed: the exact variant was reported clinically, but no variant-specific functional assay result or experimental readout was provided.
PS4
Not met: one reported case provides no case-control enrichment or statistically significant excess for the exact AXIN2 variant.
PM1
Not met: no approved AXIN2 domain entry covers Ser390, and hotspot review found no statistically significant hotspot at residue 390.
PM2
Not met: gnomAD v4.1 total allele frequency is 0.00103457, exceeding the generic PM2 threshold of 0.0001.
PM3
Not assessed: no documented biallelic observation, pathogenic variant in trans, phase, or inheritance mode is available for AXIN2 c.1168A>G.
PM5
Not assessed: no same-residue comparator was available, and the PM5 search artifact could not confirm complete classic PM5 semantics.
PM6
Not assessed: no unconfirmed-parentage de novo observation is reported for the exact variant, and parental testing details are absent.
PP1
Not assessed: zero informative familial meioses or relative genotype-phenotype observations are reported for the exact variant.
PP2
Not met: AXIN2 disease mechanism is supported as loss of function, not as a gene with an established pathogenic-missense mechanism and rare benign missense variation.
PP3
Not met: SpliceAI max delta 0.004 and REVEL 0.286 are below the PP3 supporting thresholds of 0.2 and 0.644, respectively.
PP4
Not met: colorectal cancer with MSH2/MSH6 loss and high microsatellite instability is not a phenotype highly specific for AXIN2.
PP5
Not met: ClinVar shows zero expert-panel submissions and no exact-variant Pathogenic or Likely pathogenic expert-panel classification.
