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:c.152ATG[1]

640550 (ClinVar)

Gene: PTEN

Condition: PTEN hamartoma tumor syndrome (MONDO:0017623)

Inheritance Mode: Autosomal dominant inheritance

UUID: 72ac9fd5-2f91-490d-a1de-f561657d95e4

Approved on: 2023-12-01

Published on: 2023-12-14

HGVS expressions

NM_000314.8:c.152ATG[1]

NM_000314.8(PTEN):c.152ATG[1] (p.Asp52del)

Likely Pathogenic

PS2 PS3_Moderate PS4_Moderate PM2_Supporting

PM4

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.892C>G (p.Gln298Glu) 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). PS2: De novo (both maternity and paternity confirmed) observation in a patient with the disease and no family history. (Internal laboratory contributor(s) SCV001905678.1). PS4_M: Probands with phenotype specificity score of 2-3.5. (PMID: 21194675, Internal laboratory contributor(s) SCV001905678.1). PS3_M: Massively parallel functional assay interrogating phosphatase activity demonstrating a statistically significant difference from wild type (PMID: 29706350). PM2_P: Absent in large sequenced populations (PMID: 27535533).

PS2

Confirmed de novo in a 2 yo patient with macrocephaly, DD and rectal polyps (ClinVar: SCV001905678.1).

PS3_Moderate

Mighell et al (2018): high confidence variant, score = -3.437

PS4_Moderate

Identified in 4 individuals: Father (43 yo) and son (16.9 yo), both with macrocephaly, lipomas and speckled penis’ [Tan et al 2011, PMID 21194675]; A 2 yo index patient with macrocephaly, DD and rectal polyps [University Hospital Tübingen - ClinVar: SCV001905678.1]; and a 19 yo M with macrocephaly (64.2 cm), lipoma, penile macules, >6 cutaneous signs (acral keratoses, palmar & plantar keratoses, facial papules), mucosal neuroma, tongue lesion [Lachlan et al 2007, PMID 17526800].

PM2_Supporting

Absent in gnomAD

PM4

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

Curation History

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