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LYFE SCIENCES
Project: HERA
NM_000314.8:c.101_126del
p.Ala34GlyfsTer9  ·  PTEN
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Classification rationale
1

The PTEN c.101_126del (p.Ala34GlyfsTer9; p.A34Gfs*9) 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, placing it below the PTEN Expert Panel PM2 threshold of <0.00001 (0.001%) and supporting PM2 at the supporting level.

gnomad_v2 ↗ gnomad_v4 ↗ cspec ↗
3

No direct functional study of this exact deletion was identified, and the PTEN phosphatase activity assay resource curated by the Expert Panel applies to missense variants rather than this frameshift variant.

cspec ↗
4

This deletion causes an early frameshift predicted to produce p.(Ala34GlyfsTer9) [p.(A34Gfs*9)]; under the PTEN PVS1 decision tree, a truncating variant 5' to p.D375 in NM_000314.8 supports PVS1, and SpliceAI also predicts possible splice impact with a maximum delta score of 0.51.

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 identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts possible splice impact for this variant (max delta score = 0.51).
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.
ResidueA34
Hotspots ↗