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PTEN

Final classification

VUS

PTEN c.256G>C · p.Ala86Pro

PTEN

PTEN final classification was assigned using the explicit CSPEC/VCEP criteria-combination framework rather than generic ACMG/AMP combination rules.

Gene

PTEN

Transcript

NM_000314.8

HGVS · transcript:coding

NM_000314.8:c.256G>C

Consequence

N/A

GRCh38

chr10:87933015 G>C

GRCh37

chr10:89692772 G>C

Basis Used the explicit PTEN CSPEC/VCEP criteria-combination framework in final_classification_framework.json (source=cspec_ruleset, framework_mode=criteria_combination, version 3.2.0). Authoritative met criteria were PS3_Moderate, PM2_Supporting, PP2, and PP3. This yields 1 Moderate plus 3 Supporting pathogenic criteria, which does not satisfy any defined Pathogenic or Likely Pathogenic rule in the PTEN framework, and no benign or likely benign rule is met. ▾

Used the explicit PTEN CSPEC/VCEP criteria-combination framework in final_classification_framework.json (source=cspec_ruleset, framework_mode=criteria_combination, version 3.2.0). Authoritative met criteria were PS3_Moderate, PM2_Supporting, PP2, and PP3. This yields 1 Moderate plus 3 Supporting pathogenic criteria, which does not satisfy any defined Pathogenic or Likely Pathogenic rule in the PTEN framework, and no benign or likely benign rule is met.

Classification rationale

PS3PM2PP2PP3 VUS

PTEN c.256G>C

PTEN final classification was assigned using the explicit CSPEC/VCEP criteria-combination framework rather than generic ACMG/AMP combination rules.¹ The applicable pathogenic evidence consists of PS3_Moderate, PM2_Supporting, PP2, and PP3. This combination provides 1 Moderate and 3 Supporting pathogenic criteria, which does not match a defined PTEN rule for Likely Pathogenic or Pathogenic.² No benign standalone, strong, or supporting rule combination is satisfied, so the variant remains of uncertain significance.³

PS3 + PM2 + PP2 + PP3 → VUS

1 final_classification_framework

2 final_classification_framework

3 final_classification_framework

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

Benign evidence

—

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

Not observed in any ancestry group.

gnomAD v2.1

Absent · 0 / ?
0 hom

Not observed in any ancestry group.

gnomAD v4 ↗ gnomAD v2 ↗

ClinVar

This variant is absent from ClinVar.

ClinVar ↗

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).

SpliceAI ↗

Functional

OncoKB has not reviewed this specific variant; no variant-level oncogenicity or biological effect is available. Gene-level context: PTEN, a lipid and protein phosphatase, is one of the most frequently mutated genes in cancer.

OncoKB ↗

COSMIC

Cancer hotspots

Somatic evidence

COSMIC

This variant has previously been reported in somatic cancers (COSMIC; COSV64309575, n = 1 times).

Hotspots

This variant does not lie in a statistically significant cancer 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

PMID PMID:29706350 ↗

Found

Structured finding pending for this record — see source link.

Applied to

→PS3 supports · met

Sources & reference links

6Sources

CSpec VCEP

ClinVar

gnomAD v2.1

gnomAD v4.1

SpliceAI

OncoKB