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LYFE SCIENCES
Project: HERA
NM_006218.2:c.1173A>G
p.Ile391Met  ·  PIK3CA
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Classification rationale
1

The PIK3CA c.1173A>G (p.Ile391Met) variant has been reported in ClinVar as Benign, including a Benign expert-panel classification from the ClinGen Brain Malformations Variant Curation Expert Panel.

clinvar ↗
2

This variant is common in population databases, with allele frequency 6.57058% in gnomAD v2.1 and 6.60819% in gnomAD v4.1, greatly exceeding the VCEP BA1 threshold of 0.0926% and BS1 threshold of 0.0185%, and it is also observed in numerous homozygous individuals.

gnomad_v2 ↗ gnomad_v4 ↗ cspec ↗
3

Curated literature resources identified functional publications relevant to this variant, but the retrieved evidence did not provide validated variant-specific assay results sufficient to apply either PS3 or BS3.

oncokb ↗ PMID:20530683 ↗ PMID:29533785 ↗ cspec ↗
4

SpliceAI predicts no significant splice impact for this variant with a maximum delta score of 0.00, while REVEL is 0.236 and BayesDel is -0.391355; however, PP3 is not applicable and BP4 is restricted to non-missense variants in this VCEP framework.

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
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Rationale
Select a criterion to inspect its explanation.
Evidence used
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Gaps remaining
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Rule
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Publications
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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= 0.0657058; MAF= 6.57058%, 18372/279610 alleles, homozygotes = 1032) and has highest observed frequency in the African/African American population (AF= 0.211283; MAF= 21.12834%, 5097/24124 alleles, homozygotes = 531); grpmax FAF= 0.204728.
gnomAD v4.1This variant is present in gnomAD v4.1 (AF= 0.0660819; MAF= 6.60819%, 106360/1609518 alleles, homozygotes = 4921) and has highest observed frequency in the African/African American population (AF= 0.211487; MAF= 21.14870%, 15815/74780 alleles, homozygotes = 1715); grpmax FAF= 0.208728.
gnomAD v2 ↗ gnomAD v4 ↗
ClinVar evidence
02
ClinVar
This variant has been reported in ClinVar as Benign (7 clinical laboratories) and as Benign by ClinGen Brain Malformations Variant Curation Expert Panel (expert panel).
ClinVar ↗
Functional evidence
03
Functional
OncoKB: Inconclusive
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Inconclusive; curated oncogenicity label: Inconclusive.
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.236. BayesDel score = -0.391355.
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; COSV55885079, n = 104 times).
COSMIC ↗
Cancer hotspots evidence
06
Cancer hotspots Not found
This variant does not lie in a statistically significant hotspot.
ResidueI391
Hotspots ↗