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LYFE SCIENCES
Project: HERA
NM_000314.8:c.418_430del
p.Leu140AsnfsTer3  ·  PTEN
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Classification rationale
1

The PTEN c.418_430del (p.Leu140AsnfsTer3; p.L140Nfs*3) variant has not been observed in somatic cancers in COSMIC and has not been reported in ClinVar.

clinvar ↗
2

This variant is absent from gnomAD v2.1 and gnomAD v4.1, which supports PM2 at supporting strength under the PTEN Expert Panel threshold for rarity.

cspec ↗ gnomad_v2 ↗ gnomad_v4 ↗
3

This deletion causes a frameshift with premature termination after codon 140, and under the PTEN-specific PVS1 decision tree the premature stop is 5' to p.D375 (c.1121), supporting a loss-of-function effect.

cspec ↗
4

SpliceAI predicts possible splice impact with a maximum delta score of 0.28, but this alone does not meet the PTEN Expert Panel requirement for concordant computational evidence for PP3 or BP4.

cspec ↗ spliceai ↗
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
ClinVar evidence
02
ClinVar
This variant is absent from ClinVar.
ClinVar ↗
Functional evidence
03
Functional
OncoKB: Likely Oncogenic
OncoKB classifies this variant as Likely Oncogenic; biological effect: Likely Loss-of-function.
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts possible splice impact for this variant (max delta score = 0.28).
SpliceAI ↗
COSMIC evidence
05
COSMIC
This variant lies 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 lies in a statistically significant hotspot.
ResidueL140
Hotspots ↗