Variant: NM_000314.7(PTEN):c.635-3C>G

CA645294060

427599 (ClinVar)

Gene: PTEN

Condition: PTEN hamartoma tumor syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: 757c122c-05dc-41a9-bad0-40ff4ea79d3d

Approved on: 2023-10-11

Published on: 2023-10-18

HGVS expressions

NM_000314.7:c.635-3C>G
NM_000314.7(PTEN):c.635-3C>G
NC_000010.11:g.87957850C>G
CM000672.2:g.87957850C>G
NC_000010.10:g.89717607C>G
CM000672.1:g.89717607C>G
NC_000010.9:g.89707587C>G
NG_007466.2:g.99412C>G
ENST00000686459.1:c.*221-3C>G
ENST00000688158.1:c.*746-3C>G
ENST00000688308.1:c.635-3C>G
ENST00000688922.1:c.556-3C>G
ENST00000693560.1:c.1154-3C>G
ENST00000371953.8:c.635-3C>G
ENST00000371953.7:c.635-3C>G
ENST00000472832.2:c.62-3C>G
NM_000314.5:c.635-3C>G
NM_000314.6:c.635-3C>G
NM_001304717.2:c.1154-3C>G
NM_001304718.1:c.44-3C>G
NM_001304717.5:c.1154-3C>G
NM_001304718.2:c.44-3C>G
NM_000314.8:c.635-3C>G
NM_000314.8(PTEN):c.635-3C>G

Likely Pathogenic

• Met criteria codes: PS4_Supporting PP3 PM2_Supporting PM6_Strong

• Not Met criteria codes: BS4 BS3 BS1 BS2 BP7 BP5 BP3 BP2 BP4 BP1 PS1 PS3 PS2 PP1 PP4 PP2 PM5 PM1 PM4 PM3 PVS1 BA1

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.635-3C>G (IVS6-3C>G) meets criteria to be classified as likely pathogenic for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria 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_P: Absent in large sequenced populations (PMID:27535533). PM6_S: One proband with presumed de novo occurrence (maternity/paternity not confirmed) for a patient with highly specific phenotype. (PMID:19265751) PP3: SpliceAI predicts a splicing impact. PS4_P: Proband(s) with phenotype specificity score of 1-1.5. (PMID:35278038)

Met criteria codes

• PS4_Supporting: Leibowitz 2022: female child with neuroblastoma dx 16mo, angiosarcoma dx 4yo, lipoma, macrocephaly, another benign vascular malformation. TP53 negative. Peds score = 5, 1 PS4 point. (PMID: 35278038)
• PP3: SpliceAI in silico model predicts a splicing impact (acceptor loss 0.85, acceptor gain 0.69)
• PM2_Supporting: Not present in gnomAD (coverage >60X).
• PM6_Strong: One proband with presumed de novo occurrence (maternity/paternity not confirmed) for a patient with highly specific phenotype. Assumed de novo in a male 6 yr, 11 mo child with macrocephaly (58 cm) +4.2 SD, PDD, multiple small nevi, freckling of the glans penis. CC = 6 Varga EA et al. 2009 (PMID:19265751)

Not Met criteria codes

• BS4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS3: 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
• BS2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP7: 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
• BP3: 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
• BP4: 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
• PS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS2: 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
• PP4: Wrapped into PS4.
• PP2: 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
• 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
• PM3: 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
• BA1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline