Back
LYFE SCIENCES
Project: HERA
NM_006218.2:c.2198A>G
p.Lys733Arg  ·  PIK3CA
Starting
Initialising…
0%
Legacy Engine
Ready
View Legacy →
Classification rationale
1

The PIK3CA c.2198A>G (p.Lys733Arg) variant has been reported in ClinVar as Benign, including an expert-panel benign classification from the ClinGen Brain Malformations Variant Curation Expert Panel.

clinvar ↗ cspec ↗
2

This variant is present in population databases at a frequency above the Brain Malformations VCEP benign thresholds, with East Asian AF 0.56428% in gnomAD v2.1 and 0.25756% in gnomAD v4.1, exceeding both the BS1 threshold of 0.0185% and the BA1 threshold of 0.0926%.

gnomad_v2 ↗ gnomad_v4 ↗ cspec ↗
3

In silico review does not support a splice-disrupting effect, with SpliceAI max delta score 0.12; REVEL was 0.269 and BayesDel was -0.264459, although PP3 and BP4 are not applicable to this missense gain-of-function interpretation under the Brain Malformations VCEP.

spliceai ↗ cspec ↗
Applied criteria
Met
Not met
Not assessed
N/A
Very strong
Strong
Moderate
Supporting
Pathogenic evidence
PVS
PVS1
PS
PS1
PS2
PS3
PS4
PM
PM1
PM2
PM3
PM4
PM5
PM6
PP
PP1
PP2
PP3
PP4
PP5
Benign evidence
BA
BA1
BS
BS1
BS2
BS3
BS4
BP
BP1
BP2
BP3
BP4
BP5
BP6
BP7
PVS1
—
—
Rationale
Select a criterion to inspect its explanation.
Evidence used
  • —
Gaps remaining
  • —
Rule
—
Publications
—
Research and evidence
gnomAD v2.1 evidence
v2.1
gnomAD v4.1 evidence
v4.1
01
Population
gnomAD v2.1This variant is present in gnomAD v2.1 (AF= 0.000417941; MAF= 0.04179%, 117/279944 alleles, homozygotes = 2) and has highest observed frequency in the East Asian population (AF= 0.00564276; MAF= 0.56428%, 110/19494 alleles, homozygotes = 2); grpmax FAF= 0.00484339.
gnomAD v4.1This variant is present in gnomAD v4.1 (AF= 8.99951e-05; MAF= 0.00900%, 143/1588976 alleles, homozygotes = 2) and has highest observed frequency in the East Asian population (AF= 0.00257559; MAF= 0.25756%, 115/44650 alleles, homozygotes = 2); grpmax FAF= 0.00219327.
gnomAD v2 ↗ gnomAD v4 ↗
ClinVar evidence
02
ClinVar
This variant has been reported in ClinVar as Benign (1 clinical laboratory) and as Benign by ClinGen Brain Malformations Variant Curation Expert Panel (expert panel).
ClinVar ↗
Functional evidence
03
Functional
OncoKB: Unknown Oncogenic Effect
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. PIK3CA, the catalytic subunit of PI3-kinase, is frequently mutated in a diverse range of cancers including breast, endometrial and cervical cancers.
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.12). REVEL score = 0.269. BayesDel score = -0.264459.
SpliceAI ↗
COSMIC evidence
05
COSMIC
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV55938496, n = 5 times).
COSMIC ↗
Cancer hotspots evidence
06
Cancer hotspots Not found
This variant does not lie in a statistically significant hotspot.
ResidueK733
Hotspots ↗