Starting

Initialising…

PTEN

Final classification

Likely Benign

PTEN c.-307C>G · p.?

PTEN

The PTEN c.-307C>G (NP_000305.3:p.?) 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.-307C>G

Consequence

N/A

GRCh38

chr10:87864163 C>G

GRCh37

chr10:89623920 C>G

Basis Richards et.al., 2015 - Combining rules v3.2.0 criteria-combination framework: matched Rule20 (1 Benign.Strong) with applied criteria: BS1 strong; maps to Likely Benign. ▾

Richards et.al., 2015 - Combining rules v3.2.0 criteria-combination framework: matched Rule20 (1 Benign.Strong) with applied criteria: BS1 strong; maps to Likely Benign.

Classification rationale

BS1 Likely Benign

PTEN c.-307C>G

The PTEN c.-307C>G (NP_000305.3:p.?) 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, but in gnomAD v4.1 it is present at an overall allele frequency of 5.31e-06 and reaches 1.23e-04 in the Ashkenazi Jewish population, which meets the PTEN BS1 strong frequency range and is above the PTEN PM2 subpopulation threshold.² SpliceAI predicts no significant splice impact for this variant, with a maximum delta score of 0.00, and no PTEN-specific computational evidence supporting a deleterious effect was identified.³

BS1 → Likely Benign

1 clinvar ↗

2 gnomad_v2 ↗gnomad_v4 ↗cspec ↗

3 spliceai ↗cspec ↗

Gene diagram · NM_000314.8 · variants mapped to exon structure

PTEN NM_000314.8

Fetching transcript structure from UCSC…

Applied criteria · 1 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 benign

gnomAD v4.1

gnomAD v2.1

v4.1

This variant is present in gnomAD v4.1 (AF= 5.30724e-06; MAF= 0.00053%, 3/565266 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.000122745; MAF= 0.01227%, 2/16294 alleles, homozygotes = 0).

v2.1

Absent from gnomAD v2.1.

Allele frequency by ancestry

three datasets · side by side

gnomAD v4.1

0.00053% · 3 / 565,266
0 hom

Ashkenazi Jewish 2 / 16,294	0.012%
European (non-Finnish) 1 / 316,368	0.00032%

+ 8 not observed (Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, African/African American)

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 = 0.00).

SpliceAI ↗

Functional No data

No calibrated functional assay or RNA evidence was identified for this variant.

OncoKB ↗

COSMIC

Somatic evidence

COSMIC

This variant has not previously been reported in somatic cancers (COSMIC).

Hotspots

This variant does not lie in a statistically significant cancer hotspot.

COSMIC ↗

Sources & reference links

7Sources

CSpec VCEP

ClinVar

gnomAD v2.1

gnomAD v4.1

SpliceAI

OncoKB

COSMIC