The PIK3CA c.2782C>T (p.Gln928Ter; p.Q928*) variant has not been observed in somatic cancers in COSMIC and has not been reported in ClinVar.1 This variant is absent from gnomAD v2.1 and gnomAD v4.1, which is within the Brain Malformations VCEP PM2_Supporting threshold of at most 1 occurrence in population data and below the BS1 (>0.0185%) and BA1 (>0.0926%) thresholds.2 The variant lies within the PIK3CA kinase domain approved for PM1_Supporting by the Brain Malformations VCEP (amino acids 797-1068), supporting location in a critical functional region.3 SpliceAI predicts no significant splice impact for this variant with a maximum delta score of 0.10, although PP3 and BP4 are not applicable to this nonsense variant under the Brain Malformations VCEP specifications.4
PIK3CA
Final classification
VUS
PIK3CA c.2782C>T · p.Gln928Ter
PIK3CA
The PIK3CA c.2782C>T (p.Gln928Ter; p.Q928*) variant has not been observed in somatic cancers in COSMIC and has not been reported in ClinVar.
Generic ACMG/AMP final classification combination rules were used as fallback because the retrieved Brain Malformations Specification final-classification framework was present but not complete for direct application.
Classification rationale
PM1PM2
VUS
PIK3CA c.2782C>T
PM1 + PM2
→
VUS
Gene diagram
· NM_006218.4 · variants mapped to exon structure
PIK3CA
NM_006218.4
Fetching transcript structure from UCSC…
Applied criteria · 2 met · select any tile
Met
Not met
Not assessed
N/A
Strength
very strong
supporting
Pathogenic evidence
PVS
PS
PM
PP
Benign evidence
BA
BS
BP
—
—
—
Rationale
Select a criterion.
Sources
Evidence used
Gaps remaining
Rule
—
Research & evidence
Population frequency
gnomAD v4.1
gnomAD v2.1
v4.1
Absent from gnomAD v4.1.
v2.1
Absent from gnomAD v2.1.
Allele frequency by ancestry
three datasets · side by side
gnomAD v4.1
Absent
· 0 / ?
0 hom
0 hom
Not observed in any ancestry group.
gnomAD v2.1
Absent
· 0 / ?
0 hom
0 hom
Not observed in any ancestry group.
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.10).
Functional
Unknown Oncogenic Effect
OncoKB oncogenicity for this specific variant: Unknown Oncogenic Effect (variant has not been individually curated).
COSMIC
Cancer hotspots
Somatic evidence
Not in COSMIC / hotspots
COSMIC
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
Hotspots
This variant does not lie in a statistically significant hotspot.
Sources & reference links