Starting

Initialising…

PTEN

Final classification

Likely Pathogenic

PTEN c.570_571delinsT · p.Val191TrpfsTer8

PTEN

The PTEN c.570_571delinsT (p.Val191TrpfsTer8; p.V191Wfs*8) 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.570_571delinsT

Consequence

N/A

GRCh38

chr10:87952195 AG>T

GRCh37

chr10:89711952 AG>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.570_571delinsT

The PTEN c.570_571delinsT (p.Val191TrpfsTer8; p.V191Wfs*8) 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 is below the PTEN VCEP PM2_Supporting population threshold of 0.001%.² This frameshift is predicted to introduce a premature stop codon after 8 altered amino acids at codon 191, and the PTEN VCEP PVS1 decision tree supports PVS1 for truncating variants at or 5' to p.D375 in the biologically relevant transcript NM_000314.8.³ SpliceAI predicts no significant splice impact for this variant, with a maximum delta score of 0.06.⁴

PVS1 + PM2 → Likely Pathogenic

1 clinvar ↗

2 cspec ↗gnomad_v2 ↗gnomad_v4 ↗

3 pvs1_gene_contextpvs1_variant_assessmentvcep_pvs1_decisiontree_pten

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

Benign evidence

—

Rationale

Select a criterion.

Sources

Evidence used

Gaps remaining

Rule

—

Research & evidence

Population frequency · supports pathogenic

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 = 0.06).

SpliceAI ↗

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

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