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NM_006218.4:c.331_336del
p.Lys111_Ile112del · PIK3CA
0%
complete
Final classification
VUS
PS4PM2
PIK3CA
c.331_336del
p.Lys111_Ile112del
in_frame_indel_unknown · exon 2

PIK3CA encodes the p110α catalytic subunit of phosphoinositide 3-kinase (PI3K), an enzyme that converts the membrane lipid PIP2 into PIP3, thereby activating signaling cascades such as the AKT-mTOR pathway that promote cell survival, proliferation, growth, and motility. It is among the most commonly mutated genes in cancer, and aberrant activation of PI3K signaling is a driving event in tumor development, with the gene implicated in cancers including cervical cancer. Because this pathway is central to tumor growth, it is a major target of cancer therapies, although drug-induced pathway activation can also contribute to treatment resistance.

This variant

This in-frame deletion affects PIK3CA, which encodes the p110α catalytic subunit of PI3K, a central regulator of AKT-mTOR signaling involved in cell survival, proliferation, growth, and motility.

Transcript
NM_006218.4
HGVS · transcript:coding
NM_006218.4:c.331_336del
GRCh38
chr3:179199155 AAAGATC>A
GRCh37
chr3:178916943 AAAGATC>A
VUS: PS4 (supporting) plus PM2 (supporting) provide two supporting criteria, insufficient for a pathogenic, likely pathogenic, benign, or likely benign ACMG combination.
Classification rationale
PS4PM2 VUS
PIK3CA c.331_336del in_frame_indel_unknown · exon 2

VUS: PS4 supporting reflects two COSMIC occurrences totaling 0.5 VCEP points. VUS: PM2 supporting reflects complete absence from the available gnomAD datasets.

PS4 + PM2 → VUS
LYFE Sciences is an AI system, and it can make mistakes. Criteria may be applied incorrectly, sources may be misread, and a confident-looking classification can still be wrong. Double-check every criterion and its underlying evidence before relying on any call.
Gene diagram · NM_006218.4 · variants mapped to exon structure
PIK3CA NM_006218.4
Fetching transcript structure from UCSC…
Applied criteria · 2 applied · 8 assessed
MetEvidence satisfies this criterion.
Not metEvaluated against available evidence; threshold not reached.
Not assessedApplies in principle, but no evidence was found to evaluate it.
N/ADoesn't apply to this variant type.
Applied · 2
Strength Supporting Moderate Strong Very strong
PS4 supporting review Pathogenic
Met at supporting: two COSMIC occurrences contribute 0.5 points, which falls within the VCEP PS4 supporting range of 0.5–1.25 points after PM2 is satisfied.
The ClinGen Brain Malformations VCEP specification states that PS4 phenotype criteria require PM2 and that tumor-sample presence contributes 0.25 points per occurrence in Table 2A.The same specification states: "PS4_Supporting = 0.5 – 1.25 points." The explicit range check is 0.5 <= 0.5 <= 1.25? yes.The case evidence reports the exact variant as absent from gnomAD v2.1, gnomAD v4.1, and gnomAD-Canada.
PM2 supporting Pathogenic
Met at supporting strength: the variant is absent from gnomAD v2.1, v4.1, and non-cancer subsets, with 0 observed people versus the VCEP maximum of 1.
The ClinGen Brain Malformations VCEP specifies PM2 at supporting strength for an absent or rare variant in an ethnically matched population sample, with a one-person maximum.The variant was reported absent from gnomAD v2.1, gnomAD v4.1, gnomAD v2.1 non-cancer, and gnomAD v3.1 non-cancer; the observed count is 0.The VCEP text was searched for c.331_336del, p.Lys111_Ile112del, and p.K111_I112del, with no variant-specific entry found.
Assessed · not applied · 3 not met · 5 not assessed
Pathogenic
PS2 Not assessed: no documented proband allele fraction, parental maternity/paternity testing, or affected-versus-other-tissue comparison satisfies the VCEP PS2 criteria.
PS3 Not assessed: no validated assay result for the exact p.K111_I112del variant was identified, and the available paper tested only the distinct nearby K111delK variant.
Benign
BA1 Not met: the variant is absent from gnomAD v2.1 and v4.1, giving observed allele frequency 0 versus the VCEP BA1 threshold of >0.0926%.
BS1 Not met: the variant is absent from gnomAD v2.1 and v4.1, giving observed allele frequency 0 versus the VCEP BS1 threshold of >0.0185%.
BS2 Not met: gnomAD v2.1 and v4.1 report 0 variant observations, below the VCEP requirement of at least 3 homozygotes or qualifying family heterozygotes.
BS3 Not assessed: no validated benign functional result for the exact p.K111_I112del variant was identified; PMID:29533785 tested a different nearby variant.
BP2 Not assessed: no cis/trans observation with a known pathogenic PIK3CA variant or phase result is available for this variant.
BP5 Not assessed: two COSMIC cancer occurrences are reported, but no alternate molecular basis in a different gene is documented for those cases.
N/A · 18 PVS1 · PS1 · PM1 · PM3 · PM4 · PM5 · PM6 · PP1 · PP2 · PP3 · PP4 · PP5 · BS4 · BP1 · BP3 · BP4 · BP6 · BP7
Research & evidence
Population frequency
gnomAD v4.1 screenshot
gnomAD v4.1
gnomAD v2.1 screenshot
gnomAD v2.1
v4.1
Absent from gnomAD v4.1.
v2.1
Absent from gnomAD v2.1.
🇨🇦 CA
Absent from gnomAD-Canada v1.0.
Allele frequency by ancestry
three datasets · side by side
gnomAD v4.1
Absent · 0 / ?
0 hom
Not observed in any ancestry group.
gnomAD v2.1
Absent · 0 / ?
0 hom
Not observed in any ancestry group.
gnomAD Canada 🇨🇦
Absent · 0 / ?
0 hom
Not observed in any ancestry group.
ClinVar screenshot
ClinVar
This variant is absent from ClinVar.
SpliceAI screenshot
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.11).
Functional / OncoKB screenshot
Functional Likely Oncogenic
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Gain-of-function; curated oncogenicity label: Likely Oncogenic.
OncoKB ↗
COSMIC screenshot
COSMIC
Cancer hotspots screenshot
Cancer hotspots
Somatic evidence Hotspot
COSMIC
This variant lies in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV55941739, n = 2 times).
Hotspots
This variant lies in a statistically significant hotspot.
Literature · how each cited paper was used
1papers cited
Each card is an audit: what was searched, what was found, whether it names the variant, which criteria it fed, and why.
Rule & framework references · cited for criterion definitions, not variant evidence
29533785 ↗ Systematic Functional Annotation of Somatic Mutations in Cancer.
Sources & reference links
9Sources
CSpec VCEP
ClinVar
gnomAD v2.1
gnomAD v4.1
gnomAD-Canada
SpliceAI
OncoKB
COSMIC
Cancer hotspots