Starting
Initialising…
0%
PTEN
Final classification
Likely Pathogenic
PTEN c.418_430del · p.Leu140AsnfsTer3
PTEN

The PTEN c.418_430del (p.Leu140AsnfsTer3; p.L140Nfs*3) 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.418_430del
Consequence
N/A
GRCh38
chr10:87933175 TATTACATCGGGGC>T
GRCh37
chr10:89692932 TATTACATCGGGGC>T
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.418_430del

The PTEN c.418_430del (p.Leu140AsnfsTer3; p.L140Nfs*3) 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, which supports PM2 at supporting strength under the PTEN Expert Panel threshold for rarity.2 This deletion causes a frameshift with premature termination after codon 140, and under the PTEN-specific PVS1 decision tree the premature stop is 5' to p.D375 (c.1121), supporting a loss-of-function effect.3 SpliceAI predicts possible splice impact with a maximum delta score of 0.28, but this alone does not meet the PTEN Expert Panel requirement for concordant computational evidence for PP3 or BP4.4

PVS1 + PM2 Likely Pathogenic
3 cspec ↗pvs1_gene_contextpvs1_variant_assessmentvcep_p_v_s_1___d_e_c_i_s_i_o_n_t_r_e_e___p_t_e_n
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.
      ClinVar screenshot
      ClinVar
      This variant is absent from ClinVar.
      SpliceAI screenshot
      In silico
      SpliceAI predicts possible splice impact for this variant (max delta score = 0.28).
      Functional / OncoKB screenshot
      Functional Likely Oncogenic
      OncoKB classifies this variant as Likely Oncogenic; biological effect: Likely Loss-of-function.
      OncoKB ↗
      COSMIC screenshot
      COSMIC
      Cancer hotspots screenshot
      Cancer hotspots
      Somatic evidence Not in COSMIC / hotspots
      COSMIC
      This variant lies in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
      Hotspots
      This variant lies in a statistically significant hotspot.
      Sources & reference links
      8Sources
      CSpec VCEP
      ClinVar
      gnomAD v2.1
      gnomAD v4.1
      SpliceAI
      OncoKB
      COSMIC
      Cancer hotspots