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LYFE SCIENCES
Project: HERA
NM_000314.8:c.263A>G
p.Tyr88Cys  ·  PTEN
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Classification rationale
1

The PTEN c.263A>G (p.Tyr88Cys; p.Y88C) variant has been observed in somatic cancers in COSMIC (11 occurrences) and has not been reported in ClinVar.

clinvar ↗
2

This variant is absent from gnomAD v2.1 and gnomAD v4.1, supporting rarity in the general population and meeting the PTEN Expert Panel PM2_Supporting threshold.

gnomad_v2 ↗ gnomad_v4 ↗ cspec ↗
3

In a published PTEN multiplex phosphatase assay, p.Tyr88Cys had a cumulative functional score of -1.228, which is below the PTEN Expert Panel PS3_Moderate threshold of -1.11 and supports a damaging effect on PTEN function.

cspec ↗
4

Computational evidence supports a deleterious effect, with REVEL 0.927 above the PTEN Expert Panel PP3 threshold of 0.7 and BayesDel 0.567202, while SpliceAI predicts no meaningful splice impact with a maximum delta score of 0.03.

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
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. PTEN, a lipid and protein phosphatase, is one of the most frequently mutated genes in cancer.
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.03). REVEL score = 0.927. BayesDel score = 0.567202.
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; COSV64295989, n = 11 times).
COSMIC ↗
Cancer hotspots evidence
06
Cancer hotspots Not found
This variant does not lie in a statistically significant hotspot.
ResidueY88
Hotspots ↗