Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_001110792.2(MECP2):c.428C>A (p.Ala143Asp)

CA270384

143556 (ClinVar)

Gene: MECP2
Condition: Rett syndrome
Inheritance Mode: X-linked inheritance
Link to MONDO
UUID: 10c3d5fc-80ef-42cc-8516-179b38b9707a
Approved on: 2024-08-30
Published on: 2024-10-25

HGVS expressions

NM_001110792.2:c.428C>A
NM_001110792.2(MECP2):c.428C>A (p.Ala143Asp)
NC_000023.11:g.154031436G>T
CM000685.2:g.154031436G>T
NC_000023.10:g.153296887G>T
CM000685.1:g.153296887G>T
NC_000023.9:g.152950081G>T
NG_007107.2:g.110692C>A
NG_007107.3:g.110668C>A
ENST00000303391.11:c.392C>A
ENST00000453960.7:c.428C>A
ENST00000637917.1:c.25C>A
ENST00000303391.10:c.392C>A
ENST00000369957.5:c.*446C>A
ENST00000407218.5:c.428C>A
ENST00000453960.6:c.428C>A
ENST00000486506.5:n.2740C>A
ENST00000611468.1:c.380C>A
ENST00000619732.4:c.392C>A
ENST00000622433.4:c.380C>A
ENST00000628176.2:c.392C>A
NM_001110792.1:c.428C>A
NM_001316337.1:c.113C>A
NM_004992.3:c.392C>A
NM_001316337.2:c.113C>A
NM_001369391.2:c.113C>A
NM_001369392.2:c.113C>A
NM_001369393.2:c.113C>A
NM_001369394.1:c.113C>A
NM_001369394.2:c.113C>A
NM_001386137.1:c.-169C>A
NM_001386138.1:c.-169C>A
NM_001386139.1:c.-169C>A
NM_004992.4:c.392C>A
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Pathogenic

Met criteria codes 3
PM1 PM2_Supporting PS2_Very Strong

Evidence Links 0

Expert Panel

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

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Rett and Angelman-like Disorders VCEP
The p.Ala131Asp variant in MECP2 (NM_004992.3) has been reported as a de novo occurrence (biological parentage confirmed) in an individual with features of Rett syndrome (internal database - GeneDx) and reported in at least 2 de novo occurrences (biological parentage unconfirmed) in individuals with features of Rett syndrome (PMID 15737703 and 26984561) (PS2_Very strong). The p.Ala131Asp variant occurs in the well-characterized Methyl-DNA binding [MDB] functional domain of the MECP2 (PM1). The p.Ala131Asp variant in MECP2 is absent from gnomAD v4.1 (PM2_Supporting). In summary, the p.Ala131Asp variant in MECP2 (NM_004992.3) is classified as pathogenic for Rett syndrome based on the ACMG/AMP criteria (PS2_Very strong, PM1, PM2_Supporting).
Met criteria codes
PM1
The p.Ala131Asp variant occurs in the well-characterized Methyl-DNA binding [MDB] functional domain of the MECP2 (PM1).
PM2_Supporting
The p.Ala131Asp variant in MECP2 is absent from gnomAD v4.1 (PM2_Supporting).
PS2_Very Strong
The p.Ala131Asp variant in MECP2 (NM_004992.3) has been reported as a de novo occurrence (biological parentage confirmed) in an individual with features of Rett syndrome (internal database - GeneDx) and reported in at least 2 de novo occurrences (biological parentage unconfirmed) in individuals with features of Rett syndrome (PMID 15737703 and 26984561) (PS2_Very strong).
Curation History
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