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.1 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.2 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.3 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 0.03.4
PTEN
Final classification
VUS
PTEN c.263A>G · p.Tyr88Cys
PTEN
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.
Richards et.al., 2015 - Combining rules v3.2.0 criteria-combination framework was evaluated deterministically with applied criteria: PS3 moderate, PM2 supporting, PP2 supporting, PP3 supporting; no rule matched the adjudicated criteria.
Classification rationale
PS3PM2PP2PP3
VUS
PTEN c.263A>G
PS3 + PM2 + PP2 + PP3
→
VUS
Gene diagram
· NM_000314.8 · variants mapped to exon structure
PTEN
NM_000314.8
Fetching transcript structure from UCSC…
Applied criteria · 4 met · select any tile
Met
Not met
Not assessed
N/A
Strength
very strong
supporting
Pathogenic evidence
PVS
PS
PM
PP
Benign evidence
BA
BS
BP
—
—
—
Rationale
Select a criterion.
Sources
Evidence used
Gaps remaining
Rule
—
Research & evidence
Population frequency
gnomAD v4.1
gnomAD v2.1
v4.1
Absent from gnomAD v4.1.
v2.1
Absent from gnomAD v2.1.
Allele frequency by ancestry
three datasets · side by side
gnomAD v4.1
Absent
· 0 / ?
0 hom
0 hom
Not observed in any ancestry group.
gnomAD v2.1
Absent
· 0 / ?
0 hom
0 hom
Not observed in any ancestry group.
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.03). REVEL score = 0.927. BayesDel score = 0.567202.
Functional
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.
COSMIC
Cancer hotspots
Somatic evidence
Not in COSMIC / hotspots
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).
Hotspots
This variant does not lie in a statistically significant hotspot.
Literature · how each cited paper was used
1papers cited
Each card is an audit: what was searched, what was found, whether it names the variant, which criteria it fed, and why.
PMID PMID:29706350
Found
Structured finding pending for this record — see source link.
Applied to
→PS3 supports · met
Sources & reference links