Variant: NM_000314.6(PTEN):c.75G>A (p.Leu25=)

CA000197

184505 (ClinVar)

Gene: PTEN

Condition: PTEN hamartoma tumor syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: e5e35031-cdfe-44ec-ad5e-0f3892c0a7b1

HGVS expressions

NM_000314.6:c.75G>A
NM_000314.6(PTEN):c.75G>A (p.Leu25=)
NC_000010.11:g.87864544G>A
CM000672.2:g.87864544G>A
NC_000010.10:g.89624301G>A
CM000672.1:g.89624301G>A
NC_000010.9:g.89614281G>A
NG_007466.2:g.6106G>A
NG_033079.1:g.3894C>T
ENST00000686459.1:c.75G>A
ENST00000688158.1:c.75G>A
ENST00000688308.1:c.75G>A
ENST00000693560.1:c.594G>A
ENST00000371953.8:c.75G>A
ENST00000371953.7:c.75G>A
ENST00000462694.1:n.77G>A
ENST00000487939.1:n.96G>A
ENST00000610634.1:c.-28G>A
ENST00000618586.1:n.44G>A
NM_000314.5:c.75G>A
NM_001304717.2:c.594G>A
NM_001304718.1:c.-631G>A
NM_000314.7:c.75G>A
NM_001304717.5:c.594G>A
NM_001304718.2:c.-631G>A
NM_000314.8:c.75G>A
NM_000314.8(PTEN):c.75G>A (p.Leu25=)

Likely Benign

• Met criteria codes: PM2_Supporting BS3 BP7

• Not Met criteria codes: PS2 PS4 PS3 PS1 PP4 PP1 PP3 PP2 PVS1 PM6 PM3 PM1 PM4 PM5 BA1 BS2 BS4 BS1 BP2 BP3 BP4 BP1 BP5

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.75G>A (p.Leu25=) meets criteria to be classified as likely benign 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). BS3: Synonymous variant with RNA, mini-gene, or other splicing assay demonstrating no splicing impact. (internal laboratory contributor) BP7: Variant is synonymous and no splicing impact is predicted. PM2_P: Absent in gnomAD. Using the Bayesian point system (PMID: 29300386) for this variant with conflicting evidence: 1 benign strong, 1 benign supporting and 1 pathogenic supporting codes get -4 + (-1) + 1 points; total is – 4 (likely benign).

Met criteria codes

• PM2_Supporting: Absent in gnomAD.
• BS3: Synonymous variant with RNA, mini-gene, or other splicing assay demonstrating no splicing impact. (internal laboratory contributor)
• BP7: Variant is synonymous and no splicing impact is predicted.

Not Met criteria codes

• PS2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS4: 1 internal case from CCF PTEN study with CC Score of 22. OFC: unknown; Papillary Thyroid Carcinoma dx age 15; Fibrocystic Breast Disease; Left breast cancer, dx 37- ductal carcinoma + left DCIS (cribriform), mastectomy; Fibroadenoma of Breast; Uterine Fibroids; Fibroma; Oral Mucosa Papilloma. Doesn't meet criteria for PS4, PS4_moderate, or PS4_supporting.
• 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: See PS4.
• 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
• PP2: 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
• 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
• PM4: 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
• 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
• BS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP2: 1 internal lab observation in cis with D24N (LPATH per this lab), need 3 observations in cis or phase unknown with different variants to apply BP2.
• BP3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP4: In silico predictors unable to provide prediction for nearby SDS.
• BP1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP5: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Approved on: 2023-10-11

Published on: 2023-10-18