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LYFE SCIENCES
Project: HERA
NM_006218.2:c.2040T>C
p.Val680=  ·  PIK3CA
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Classification rationale
1

The PIK3CA c.2040T>C (p.Val680=) variant has been reported in ClinVar and is classified as likely benign by the ClinGen Brain Malformations Variant Curation Expert Panel.

clinvar ↗
2

This variant is present in gnomAD at 0.00080% in v2.1 (2/248908 alleles) and 0.00248% in v4.1 (40/1612688 alleles), which is below the VCEP BS1 threshold of 0.0185% and BA1 threshold of 0.0926% but exceeds the VCEP PM2 one-person maximum.

gnomad_v2 ↗ gnomad_v4 ↗ cspec ↗
3

SpliceAI predicts no significant splice impact for this variant, with a maximum delta score of 0.01, although additional VCEP-specified splicing predictors and a conservation score were not identified for BP4 and BP7 assessment.

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
  • —
Gaps remaining
  • —
Rule
—
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= 8.0351e-06; MAF= 0.00080%, 2/248908 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 1.77001e-05; MAF= 0.00177%, 2/112994 alleles, homozygotes = 0); grpmax FAF= 2.94e-06.
gnomAD v4.1This variant is present in gnomAD v4.1 (AF= 2.48033e-05; MAF= 0.00248%, 40/1612688 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 3.22259e-05; MAF= 0.00322%, 38/1179176 alleles, homozygotes = 0); grpmax FAF= 2.395e-05.
gnomAD v2 ↗ gnomAD v4 ↗
ClinVar evidence
02
ClinVar
This variant has been reported in ClinVar as Likely benign (2 clinical laboratories) and as Likely benign by ClinGen Brain Malformations Variant Curation Expert Panel (expert panel). (ClinVarID = 456534)
ClinVar ↗
Functional evidence
03
Functional
OncoKB: Unknown Oncogenic Effect
OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).
SpliceAI ↗
COSMIC evidence
05
COSMIC
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
COSMIC ↗
Cancer hotspots evidence
06
Cancer hotspots Not found
This variant does not lie in a statistically significant hotspot.
ResidueV680
Hotspots ↗