Variant: NM_000314.8(PTEN):c.35A>G (p.Asn12Ser)

CA377781898

1320976 (ClinVar)

Gene: PTEN

Condition: PTEN hamartoma tumor syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: 6ac0b004-3cd3-4da9-b13c-0912fc731a00

Approved on: 2023-08-04

Published on: 2023-10-19

HGVS expressions

NM_000314.8:c.35A>G
NM_000314.8(PTEN):c.35A>G (p.Asn12Ser)
NC_000010.11:g.87864504A>G
CM000672.2:g.87864504A>G
NC_000010.10:g.89624261A>G
CM000672.1:g.89624261A>G
NC_000010.9:g.89614241A>G
NG_007466.2:g.6066A>G
NG_033079.1:g.3934T>C
ENST00000686459.1:c.35A>G
ENST00000688158.1:c.35A>G
ENST00000688308.1:c.35A>G
ENST00000693560.1:c.554A>G
ENST00000371953.8:c.35A>G
ENST00000371953.7:c.35A>G
ENST00000462694.1:n.37A>G
ENST00000487939.1:n.56A>G
ENST00000610634.1:c.-68A>G
ENST00000618586.1:n.4A>G
NM_000314.5:c.35A>G
NM_000314.6:c.35A>G
NM_001304717.2:c.554A>G
NM_001304718.1:c.-671A>G
NM_000314.7:c.35A>G
NM_001304717.5:c.554A>G
NM_001304718.2:c.-671A>G

Uncertain Significance

• Met criteria codes: PP2 BP4 PM2_Supporting

• Not Met criteria codes: PP3 PM5 BS3 BS1 BP1 BA1 PS3

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.35A>G (p.Asn12Ser) is currently classified as a variant of uncertain significance 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). 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. BP4: REVEL score < 0.5 (score=0.287) Using the Bayesian point system (PMID: 29300386) for this variant with conflicting evidence: 2 pathogenic supporting and 1 benign supporting codes get (1*2) + (- 1*1) points = total is 1 (VUS).

Met criteria codes

• 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.
• BP4: REVEL score < 0.5 (score=0.287)
• PM2_Supporting: absent gnomAD

Not Met criteria codes

• PP3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM5: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BA1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline