Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_001110792.2(MECP2):c.380G>A (p.Arg127His)

CA10558640

2505626 (ClinVar)

Gene: MECP2 (HGNC:4204)

Condition: Rett syndrome (MONDO:0010726)

Inheritance Mode: X-linked inheritance

UUID: 05ef9c22-bf70-4244-9624-e0a6ffa5a371

Approved on: 2024-08-30

Published on: 2024-12-23

HGVS expressions

NM_001110792.2:c.380G>A

NM_001110792.2(MECP2):c.380G>A (p.Arg127His)

NC_000023.11:g.154032240C>T

CM000685.2:g.154032240C>T

NC_000023.10:g.153297691C>T

CM000685.1:g.153297691C>T

NC_000023.9:g.152950885C>T

NG_007107.2:g.109888G>A

NG_007107.3:g.109864G>A

ENST00000303391.11:c.344G>A

ENST00000453960.7:c.380G>A

ENST00000303391.10:c.344G>A

ENST00000369957.5:c.*398G>A

ENST00000407218.5:c.380G>A

ENST00000453960.6:c.380G>A

ENST00000486506.5:n.2692G>A

ENST00000611468.1:c.332G>A

ENST00000619732.4:c.344G>A

ENST00000622433.4:c.332G>A

ENST00000628176.2:c.344G>A

NM_001110792.1:c.380G>A

NM_001316337.1:c.65G>A

NM_004992.3:c.344G>A

NM_001316337.2:c.65G>A

NM_001369391.2:c.65G>A

NM_001369392.2:c.65G>A

NM_001369393.2:c.65G>A

NM_001369394.1:c.65G>A

NM_001369394.2:c.65G>A

NM_001386137.1:c.-217G>A

NM_001386138.1:c.-217G>A

NM_001386139.1:c.-217G>A

NM_004992.4:c.344G>A

Pathogenic

PP3 PM1 PS4_Moderate PS2_Very Strong

PM2

Evidence Links 0

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

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The p.Arg115His variant in MECP2 (NM_004992.4) has been reported as a de novo occurrence (biological parentage confirmed) in at least 2 male individuals with neurodevelopmental disorders (internal database - GeneDx) (PS2_Very Strong). The p.Arg115His variant has been observed in 3 male individuals with neurodevelopmental disorders (internal database) (PS4_Moderate). The p.Arg115His variant occurs in the well-characterized Methyl-DNA binding (MDB) functional domain of the MECP2 gene (PM1). Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3). The p.Arg115His variant in MECP2 is absent from gnomAD v4.1; however, this variant is present in 1 XX individual in gnomAD v2.1.1. In summary, the p.Arg115His variant in MECP2 (NM_004992.4) is classified as pathogenic for Rett syndrome based on the ACMG/AMP criteria (PS2_Very Strong, PS4_Moderate, PM1, PP3). (MECP2 Specification v.3.0.0, curation approved on 8/30/2024)

PP3

Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3).

PM1

The p.Arg115His variant (NM_004992.4) occurs in the well-characterized Methyl-DNA binding (MDB) functional domain of the MECP2 gene (PM1).

PS4_Moderate

The p.Arg115His variant (NM_004992.4) has been observed in 3 male individuals with neurodevelopmental disorders (internal database) (PS4_Moderate).

PS2_Very Strong

PM2

The p.Arg115His variant in MECP2 (NM_004992.4) is absent from gnomAD v4.1; however, this variant is present in 1 XX individual in gnomAD v2.1.1.

Curation History

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