PVS1
This 5'UTR variant does not fall into the PTEN PVS1 decision tree categories for nonsense, frameshift, canonical +/-1,2 splice, or exon-level loss-of-function variants, so PVS1 is not met.
PS1
No previously established pathogenic variant causing the same amino acid change or an equivalent pathogenic splicing effect at this nucleotide was identified, so PS1 was not assessed.
PS2
No confirmed de novo occurrence in an affected individual was identified, so PS2 was not assessed.
PS3
No well-established functional study showing a damaging effect of this exact 5'UTR variant on PTEN splicing, transcript abundance, or gene function was identified, so PS3 was not assessed.
PS4
No enrichment data or counted affected probands meeting PTEN VCEP PS4 specifications were identified for this variant, so PS4 was not assessed.
PM2
This variant is absent from gnomAD v2.1 but is present in gnomAD v4.1 at AF 1.21927e-05, with highest subpopulation AF 4.45315e-05, which is above the PTEN PM2 threshold of <0.00001 overall and <0.00002 within a subpopulation when multiple alleles are observed; therefore PM2 is not met.
PM6
No presumed de novo occurrence without parental confirmation was identified, so PM6 was not assessed.
PP1
No segregation data were identified for this variant, so PP1 was not assessed.
PP3
The PTEN VCEP applies PP3 to concordant SpliceAI and VarSeak splicing predictions for synonymous or intronic variants, or to missense variants with REVEL >0.7.
