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]

Link to SEPIO compliant JSON-LD document

Variant: NM_000314.8(PTEN):c.209+4A>G

CA645553763

1182096 (ClinVar)

Gene: PTEN

Condition: PTEN hamartoma tumor syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: b8bde028-d5e9-469a-bf1b-19123d34a6d8

Approved on: 2024-02-09

Published on: 2024-03-04

HGVS expressions

NM_000314.8:c.209+4A>G

NM_000314.8(PTEN):c.209+4A>G

NC_000010.11:g.87925561A>G

CM000672.2:g.87925561A>G

NC_000010.10:g.89685318A>G

CM000672.1:g.89685318A>G

NC_000010.9:g.89675298A>G

NG_007466.2:g.67123A>G

ENST00000700029.2:c.209+4A>G

ENST00000710265.1:c.209+4A>G

ENST00000472832.3:c.209+4A>G

ENST00000688158.2:n.944+4A>G

ENST00000688922.2:c.209+4A>G

ENST00000700021.1:c.165-5485A>G

ENST00000700022.1:c.209+4A>G

ENST00000700029.1:c.43+4A>G

ENST00000706954.1:c.209+4A>G

ENST00000706955.1:c.*244+4A>G

ENST00000686459.1:c.209+4A>G

ENST00000688158.1:c.*320+4A>G

ENST00000688308.1:c.209+4A>G

ENST00000688922.1:c.78+4A>G

ENST00000693560.1:c.728+4A>G

ENST00000371953.8:c.209+4A>G

ENST00000371953.7:c.209+4A>G

ENST00000498703.1:n.35+4A>G

ENST00000610634.1:c.107+4A>G

NM_000314.5:c.209+4A>G

NM_000314.6:c.209+4A>G

NM_001304717.2:c.728+4A>G

NM_001304718.1:c.-541-5485A>G

NM_000314.7:c.209+4A>G

NM_001304717.5:c.728+4A>G

NM_001304718.2:c.-541-5485A>G

Pathogenic

PS2 PS3 PP3 PM2_Supporting

PP2 BP4

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

NM_000314.8(PTEN):c.209+4A>G meets criteria to be classified as pathogenic for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (ACMG Classification Rules Specified for PTEN Variant Curation version 3.0.0). Please see a summary of the rules and criteria codes in the “PTEN ACMG Specifications Summary” document (assertion method column). PS2: De novo (both maternity and paternity confirmed) observation in a patient with the disease and no family history. (internal laboratory contributor: SCV001757442.1) PS3: RNA, mini-gene, or other assay shows impact on splicing (Internal laboratory contributor, SCV002725031.1: results in whole exon skipping. Exon 3 in-frame but contains PATH missense variants). PM2_P: Absent in gnomAD (PMID 27535533). PP3: in silico models predict a splicing impact (SpliceAI: strong donor loss=0.71, and strong donor gain=0.65, impact OOF)

PS2

De novo (both maternity and paternity confirmed) observation in a patient with the disease and no family history. (internal laboratory contributor: SCV001757442.1)

PS3

Phosphatase activity <50% of wild type OR RNA, mini-gene, or other assay shows impact on splicing (Internal laboratory contributor, SCV002725031.1: results in whole exon skipping. Exon 3 in-frame but contains PATH missense variants).

PP3

in silico models predict a splicing impact (SpliceAI: strong donor loss=0.71, and strong donor gain=0.65, impact OOF)

PM2_Supporting

Absent in gnomAD

PP2

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

BP4

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

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