Back
LYFE SCIENCES
Project: HERA
NM_006218.4:c.1930T>C
p.Tyr644His  ·  PIK3CA
Starting
Initialising…
0%
Legacy Engine
Processing…
Classification rationale
1

The PIK3CA c.1930T>C (p.Tyr644His) variant has not been reported in ClinVar, and Cancer Hotspots did not identify a statistically significant hotspot at Tyr644 in the reviewed record.

clinvar ↗ hotspots ↗
2

This variant is absent from gnomAD v2.1 and is present once in gnomAD v4.1 (1/1,607,506 alleles; AF 6.22082e-07; 0 homozygotes), which satisfies PM2_Supporting under the Brain Malformations VCEP and is far below the BA1 and BS1 population thresholds.

gnomad_v2 ↗ gnomad_v4 ↗ cspec ↗
3

Tyr644 lies outside the PIK3CA Table 4 PM1 domains (amino acids 322-483 and 797-1068), so domain-based PM1 support was not established.

cspec ↗
4

SpliceAI predicts no significant splice impact for this variant (max delta score 0.02); REVEL 0.613 and BayesDel 0.183264 were available, but PP3 and BP4 are not applicable to this missense variant 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 v2.1Absent from gnomAD v2.1.
gnomAD v4.1This variant is present in gnomAD v4.1 (AF= 6.22082e-07; MAF= 0.00006%, 1/1607506 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.49193e-07; MAF= 0.00008%, 1/1177588 alleles, homozygotes = 0).
gnomAD v2 ↗ gnomAD v4 ↗
ClinVar evidence
02
ClinVar
This variant is absent from ClinVar.
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 = 0.02). REVEL score = 0.613. BayesDel score = 0.183264.
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.
ResidueY644
Hotspots ↗