Variant: NM_001110792.2(MECP2):c.686C>T (p.Pro229Leu)

CA10581615

236302 (ClinVar)

Gene: MECP2

Condition: Rett syndrome

Inheritance Mode: X-linked inheritance

UUID: f2c5bce1-28a5-423f-911e-2ae5970fcbb4

Approved on: 2024-10-30

Published on: 2024-11-29

HGVS expressions

NM_001110792.2:c.686C>T
NM_001110792.2(MECP2):c.686C>T (p.Pro229Leu)
NC_000023.11:g.154031178G>A
CM000685.2:g.154031178G>A
NC_000023.10:g.153296629G>A
CM000685.1:g.153296629G>A
NC_000023.9:g.152949823G>A
NG_007107.2:g.110950C>T
NG_007107.3:g.110926C>T
ENST00000303391.11:c.650C>T
ENST00000453960.7:c.686C>T
ENST00000637917.1:c.65+218C>T
ENST00000303391.10:c.650C>T
ENST00000407218.5:c.*22C>T
ENST00000453960.6:c.686C>T
ENST00000619732.4:c.650C>T
ENST00000622433.4:c.638C>T
ENST00000628176.2:c.*22C>T
NM_001110792.1:c.686C>T
NM_001316337.1:c.371C>T
NM_004992.3:c.650C>T
NM_001316337.2:c.371C>T
NM_001369391.2:c.371C>T
NM_001369392.2:c.371C>T
NM_001369393.2:c.371C>T
NM_001369394.1:c.371C>T
NM_001369394.2:c.371C>T
NM_001386137.1:c.-20C>T
NM_001386138.1:c.-20C>T
NM_001386139.1:c.-20C>T
NM_004992.4:c.650C>T

Likely Pathogenic

• Met criteria codes: PS2 PS4_Moderate PM2_Supporting

Expert Panel

Rett and Angelman-like Disorders VCEP

Criteria Specification Information

Criteria Specification: ClinGen Rett and Angelman-like Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for MECP2 Version 3.0.0

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The p.Pro217Leu variant in MECP2 (NM_004992.3) has been reported as a de novo occurrence (biological parentage both confirmed and unconfirmed) in 2 individuals with neurodevelopmental disorders (PMID: 27824329, LabCorp) (PS2). The p.Pro217Leu variant has been observed in individuals with neurodevelopmental disorders (PMID: 27824329, LabCorp, Invitae internal database) (PS4_moderate). The p.Pro217Leu in MECP2 is absent from gnomAD (PM2_supporting). In summary, the p.Pro217Leu variant in MECP2 is classified as likely pathogenic for Rett syndrome based on the ACMG/AMP criteria (PS2, PS4_moderate, PM2_supporting).

Met criteria codes

• PS2: The p.Pro217Leu variant in MECP2 (NM_004992.3) has been reported as a de novo occurrence (biological parentage both confirmed and unconfirmed) in 2 individuals with neurodevelopmental disorders (PMID: 27824329, LabCorp)
• PS4_Moderate: The p.Pro217Leu variant has been observed in individuals with neurodevelopmental disorders (PMID: 27824329, LabCorp, Invitae internal database) (PS4_moderate).
• PM2_Supporting: The p.Pro217Leu in MECP2 (NM_004992.4) is absent from gnomAD.