Variant: NM_000314.7(PTEN):c.1093G>A (p.Val365Ile)

CA059160

237639 (ClinVar)

Gene: PTEN

Condition: PTEN hamartoma tumor syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: 1ebd3f87-9825-4ccc-aa05-14d1b0b78d24

Approved on: 2023-12-01

Published on: 2023-12-14

HGVS expressions

NM_000314.7:c.1093G>A
NM_000314.7(PTEN):c.1093G>A (p.Val365Ile)
NC_000010.11:g.87965353G>A
CM000672.2:g.87965353G>A
NC_000010.10:g.89725110G>A
CM000672.1:g.89725110G>A
NC_000010.9:g.89715090G>A
NG_007466.2:g.106915G>A
ENST00000686459.1:c.*679G>A
ENST00000688158.1:c.*1204G>A
ENST00000688308.1:c.1093G>A
ENST00000688922.1:c.1014G>A
ENST00000693560.1:c.1612G>A
ENST00000371953.8:c.1093G>A
ENST00000371953.7:c.1093G>A
NM_000314.5:c.1093G>A
NM_000314.6:c.1093G>A
NM_001304717.2:c.1612G>A
NM_001304718.1:c.502G>A
NM_001304717.5:c.1612G>A
NM_001304718.2:c.502G>A
NM_000314.8:c.1093G>A
NM_000314.8(PTEN):c.1093G>A (p.Val365Ile)

Uncertain Significance

• Met criteria codes: PP2 PM2_Supporting BP4

• Not Met criteria codes: PS2 PS4 PS3 PS1 PP4 PP1 PP3 PM6 PM3 PM1 PM5 PM4 BA1 BS2 BS4 BS3 BS1 BP5 BP7 BP2 BP1 BP3 PVS1

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

PTEN c.1093G>A (p.Val365Ile) 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: 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=0.441) Using the Bayesian point system (PMID: 29300386) for this variant with conflicting evidence: 1 benign supporting and 2 pathogenic supporting codes get -1 + (1*2) 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.
• PM2_Supporting: Present at extremely low (<0.00001, 0.001%) allele frequency in the gnomAD cohort. AF=0.000004973 in gnomAD 4.0
• BP4: REVEL score < 0.5 (score=0.441)

Not Met criteria codes

• PS2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS4: GeneDx internal data: 2 patients with CC score = 1.
• PS3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM6: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM1: 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
• PM4: 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
• BS2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS3: Matreyek results is WT-like (1.140914254). Mighell results is WT-like (-0.102592235) but not >0 so BS3 does not apply.
• BS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP5: GeneDx internal data: 1 patient with breast and CRC dx 40s and father brain dx 50s. Harbors ATM variant.
• BP7: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP2: 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
• BP3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PVS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline