Starting
Initialising…
0%
PTEN
Final classification
Likely Pathogenic
PTEN c.449_456del · p.Glu150GlyfsTer27
PTEN

The PTEN c.449_456del (p.Glu150GlyfsTer27) variant has not been observed in somatic cancers in COSMIC and has not been reported in ClinVar.

Gene
PTEN
Transcript
NM_000314.8
HGVS · transcript:coding
NM_000314.8:c.449_456del
Consequence
N/A
GRCh38
chr10:87933207 GAGGCCCTA>G
GRCh37
chr10:89692964 GAGGCCCTA>G
Basis Richards et.al., 2015 - Combining rules v3.2.0 criteria-combination framework: matched Rule20 (1 Pathogenic.Very Strong + 1 Pathogenic.Supporting) with applied criteria: PVS1 very strong, PM2 supporting; maps to Likely Pathogenic. ▾
Richards et.al., 2015 - Combining rules v3.2.0 criteria-combination framework: matched Rule20 (1 Pathogenic.Very Strong + 1 Pathogenic.Supporting) with applied criteria: PVS1 very strong, PM2 supporting; maps to Likely Pathogenic.
Classification rationale
PVS1PM2 Likely Pathogenic
PTEN c.449_456del

The PTEN c.449_456del (p.Glu150GlyfsTer27) variant has not been observed in somatic cancers in COSMIC and has not been reported in ClinVar.1 This variant is absent from gnomAD v2.1 and gnomAD v4.1, placing it below the PTEN Expert Panel PM2 population threshold of 0.001%.2 This deletion is predicted to cause a frameshift with premature protein truncation, and under the PTEN-specific PVS1 decision tree its position 5' of c.1121 (p.D375) supports loss of function; SpliceAI does not predict an additional splice effect (maximum delta score 0.01).3

PVS1 + PM2 → Likely Pathogenic
1 clinvar ↗
2 gnomad_v2 ↗gnomad_v4 ↗cspec ↗
3 vcep_pvs1_decisiontree_ptenpvs1_variant_assessmentspliceai ↗
Gene diagram · NM_000314.8 · variants mapped to exon structure
PTEN NM_000314.8
Fetching transcript structure from UCSC…
Applied criteria · 2 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 · supports pathogenic
      gnomAD v4.1 screenshot
      gnomAD v4.1
      gnomAD v2.1 screenshot
      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 screenshot
      ClinVar
      This variant is absent from ClinVar.
      ClinVar ↗
      SpliceAI screenshot
      In silico
      SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).
      SpliceAI ↗
      Functional / OncoKB screenshot
      Functional 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 ↗
      COSMIC screenshot
      COSMIC
      Cancer hotspots screenshot
      Cancer hotspots
      Somatic evidence Not in COSMIC / hotspots
      COSMIC
      This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
      Hotspots
      This variant does not lie in a statistically significant hotspot.
      COSMIC ↗ Hotspots ↗
      Sources & reference links
      8Sources
      CSpec VCEP
      ClinVar
      gnomAD v2.1
      gnomAD v4.1
      SpliceAI
      OncoKB
      COSMIC
      Cancer hotspots
      Triaged references · 2 PMIDs not cited in assessment
      11237521 ↗ PTEN: life as a tumor suppressor. ONCOKB
      17218262 ↗ Essential role for nuclear PTEN in maintaining chromosomal integrity. ONCOKB