Starting
Initialising…
0%
PTEN
Final classification
Likely Pathogenic
PTEN c.548del · p.Lys183ArgfsTer16
PTEN

The PTEN NM_000314.8:c.548del (NP_000305.3:p.(Lys183ArgfsTer16), p.(K183Rfs*16)) variant has been observed in somatic cancer databases once in COSMIC and has been reported in ClinVar as Pathogenic by a clinical laboratory.

Gene
PTEN
Transcript
NM_000314.8
HGVS · transcript:coding
NM_000314.8:c.548del
Consequence
N/A
GRCh38
chr10:87952170 TA>T
GRCh37
chr10:89711927 TA>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.548del

The PTEN NM_000314.8:c.548del (NP_000305.3:p.(Lys183ArgfsTer16), p.(K183Rfs*16)) variant has been observed in somatic cancer databases once in COSMIC and has been reported in ClinVar as Pathogenic by a clinical laboratory.1 This variant is absent from gnomAD v2.1 and gnomAD v4.1, with an observed allele frequency of 0, which is below the PTEN Expert Panel PM2 threshold of <0.00001 (0.001%).2 This variant is a frameshift predicted to create a premature termination codon, and because c.548 is upstream of the PTEN Expert Panel p.D375 (c.1121) truncation threshold in transcript NM_000314.8, the finding is consistent with full-strength PVS1.3 SpliceAI predicts no significant splice impact for this variant, with a maximum delta score of 0.03.4

PVS1 + PM2 → Likely Pathogenic
1 clinvar ↗
2 gnomad_v2 ↗gnomad_v4 ↗cspec ↗
3 cspec ↗vcep_p_v_s_1___d_e_c_i_s_i_o_n_t_r_e_e___p_t_e_npvs1_gene_contextpvs1_variant_assessment
4 spliceai ↗
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 has been reported in ClinVar as Pathogenic (1 clinical laboratory).
      ClinVar ↗
      SpliceAI screenshot
      In silico
      SpliceAI predicts no significant splice impact for this variant (max delta score = 0.03).
      SpliceAI ↗
      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 does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV64296982, n = 1 times).
      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