Variant: NM_000314.8(PTEN):c.44G>C (p.Arg15Thr)

CA377781931

428243 (ClinVar)

Gene: PTEN

Condition: PTEN hamartoma tumor syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: c0525249-345f-416d-89cd-fa8b4de862c3

Approved on: 2023-08-04

Published on: 2023-10-19

HGVS expressions

NM_000314.8:c.44G>C
NM_000314.8(PTEN):c.44G>C (p.Arg15Thr)
NC_000010.11:g.87864513G>C
CM000672.2:g.87864513G>C
NC_000010.10:g.89624270G>C
CM000672.1:g.89624270G>C
NC_000010.9:g.89614250G>C
NG_007466.2:g.6075G>C
NG_033079.1:g.3925C>G
ENST00000686459.1:c.44G>C
ENST00000688158.1:c.44G>C
ENST00000688308.1:c.44G>C
ENST00000693560.1:c.563G>C
ENST00000371953.8:c.44G>C
ENST00000371953.7:c.44G>C
ENST00000462694.1:n.46G>C
ENST00000487939.1:n.65G>C
ENST00000610634.1:c.-59G>C
ENST00000618586.1:n.13G>C
NM_000314.5:c.44G>C
NM_000314.6:c.44G>C
NM_001304717.2:c.563G>C
NM_001304718.1:c.-662G>C
NM_000314.7:c.44G>C
NM_001304717.5:c.563G>C
NM_001304718.2:c.-662G>C

Likely Pathogenic

• Met criteria codes: PP3 PP2 PS2 PS3_Moderate PM2_Supporting

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

Evidence submitted by expert panel

PTEN VCEP

NM_000314.8(PTEN):c.44G>C (p.Arg15Thr) meets criteria to be classified as likely 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(s)] PS3_M: Functional studies showing a damaging effect on protein function. Phosphatase activity ≤ -1.11 per Mighell et al. 2018 (PMID: 29706350). This variant: score of -1.2. PM2_Supporting: Absent in large sequenced populations OR present at extremely low (<0.00001, 0.001%) allele frequency in the gnomAD cohort. (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: in silico REVEL score of 0.87 (>0.7)

Met criteria codes

• PP3: in silico REVEL score of 0.87 (>0.7)
• 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.
• PS2: Confirmed de novo case from Invitae. Patient (child) with macrocephaly, thickened corpus callosum, mild asymmetry, and autism with mild delay. Paternity/maternity were confirmed. Peds score of 4 (internal laboratory contributor).
• PS3_Moderate: Mighell et al. 2018 PMID: 29706350 Lipid phosphatase activity score in the hypomorphic range, -1.2 (TRUE).
• PM2_Supporting: Absent in gnomAD