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: 2019-11-22

Published on: 2020-01-02

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
ENST00000700029.2:c.635-3C>G
ENST00000710265.1:c.635-3C>G
ENST00000472832.3:c.635-3C>G
ENST00000688158.2:n.1370-3C>G
ENST00000688922.2:c.*465-3C>G
ENST00000700021.1:c.590-3C>G
ENST00000700022.1:c.493-3C>G
ENST00000700023.1:n.1793-3C>G
ENST00000700024.1:n.2027-3C>G
ENST00000700025.1:n.1404-3C>G
ENST00000700026.1:n.269C>G
ENST00000700029.1:c.469-3C>G
ENST00000706954.1:c.635-3C>G
ENST00000706955.1:c.*670-3C>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

Likely Pathogenic

• Met criteria codes: PS4_Supporting PP3 PM6 PM2

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

Expert Panel

PTEN VCEP

Criteria Specification Information

Evidence submitted by expert panel

PTEN VCEP

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 (PMID 30311380). Please see a summary of the rules and criteria codes in the “PTEN ACMG Specifications Summary” document (assertion method column). PM2: Absent in large sequenced populations (PMID 27535533). PM6: Assumed de novo, but without confirmation of paternity and maternity in a patient with the disease and no family history. (PMID 19265751) PP3: At least 2 out of 3 in silico models predict a splicing impact. PS4_P: Proband(s) with phenotype specificity score of 1-1.5. (PMID 19265751)

Met criteria codes

• PS4_Supporting: 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 (1 point) Varga et al 2009
• PP3: HSF predicts the native splice acceptor will be weakened and MaxEnt predicts the native splice acceptor site will be abolished.
• PM6: 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
• PM2: Not present in gnomAD (coverage >60X).

Not Met criteria codes

• 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
• BS1: 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: 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
• BP3: 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
• BP2: 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
• BP7: 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
• PP1: 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
• PP4: Wrapped into PS4.
• PM1: 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
• 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
• PVS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline