Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000314.8(PTEN):c.64G>C (p.Asp22His)

Curation Version - 1.0
Curation History
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CA10578904

233456 (ClinVar)

Gene: PTEN

Condition: PTEN hamartoma tumor syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: f16fe142-883f-4de7-9f82-815a073aa806

Approved on: 2023-08-04

Published on: 2023-10-19

HGVS expressions

NM_000314.8:c.64G>C

NM_000314.8(PTEN):c.64G>C (p.Asp22His)

NC_000010.11:g.87864533G>C

CM000672.2:g.87864533G>C

NC_000010.10:g.89624290G>C

CM000672.1:g.89624290G>C

NC_000010.9:g.89614270G>C

NG_007466.2:g.6095G>C

NG_033079.1:g.3905C>G

ENST00000686459.1:c.64G>C

ENST00000688158.1:c.64G>C

ENST00000688308.1:c.64G>C

ENST00000693560.1:c.583G>C

ENST00000371953.8:c.64G>C

ENST00000371953.7:c.64G>C

ENST00000462694.1:n.66G>C

ENST00000487939.1:n.85G>C

ENST00000610634.1:c.-39G>C

ENST00000618586.1:n.33G>C

NM_000314.5:c.64G>C

NM_000314.6:c.64G>C

NM_001304717.2:c.583G>C

NM_001304718.1:c.-642G>C

NM_000314.7:c.64G>C

NM_001304717.5:c.583G>C

NM_001304718.2:c.-642G>C

Likely Pathogenic

PM6_Strong PM2_Supporting PP3 PP2

PM5 PS1 PS3

Evidence Links 0

Expert Panel

PTEN VCEP

Criteria Specification Information

Criteria Specification: ClinGen PTEN Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for PTEN Version 3.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

PTEN VCEP

PTEN c.64G>C (p.Asp22His) meets criteria to be classified as likely pathogenic for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (PMID 30311380). Please see a summary of the rules and criteria codes in the “PTEN ACMG Specifications Summary” document (assertion method column). PM6_Strong: De novo (parentage not confirmed) in two patients with the disease and no family history (Internal laboratory contributor(s) SCV000577329.3). PM2_Supporting: Absent in large sequenced populations (PMID 27535533). PP2: PTEN is defined by the PTEN Expert Panel as a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease. PP3: REVEL score = 0.965 (>0.7).

PM6_Strong

GeneDx: Two cases, both proven de novo via targeted testing only (parentage not confirmed). Both children with macrocephaly NOS, autism, and developmental delays.

PM2_Supporting

absent in gnomAD

PP3

REVEL score = 0.965 (> 0.75)

PP2

PTEN is defined by the PTEN Expert Panel as a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease.

PM5

3 close matches in ClinVar p.Asp22Tyr: N/A (BLOSUM = -3) p.Asp22Gly: VUS – Ambry (BLOSUM = -1) p.Asp22Glu: VUS – 3billion (BLOSUM = 2)

PS1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PS3

Mighell et al (2018): High confidence variant, cum_score = -0.8245 (> -1.11)

Curation History

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