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.1200A>C (p.Pro400=)

CA245265

197244 (ClinVar)

Gene: MECP2 (HGNC:4204)

Condition: Rett syndrome (MONDO:0010726)

Inheritance Mode: X-linked inheritance

UUID: 1dc25b77-b3c0-457f-a134-5cd058b41c6f

Approved on: 2024-08-30

Published on: 2024-11-15

HGVS expressions

NM_001110792.2(MECP2):c.1200A>C (p.Pro400=)

NM_001110792.2:c.1200A>C

NC_000023.11:g.154030664T>G

CM000685.2:g.154030664T>G

NC_000023.10:g.153296115T>G

CM000685.1:g.153296115T>G

NC_000023.9:g.152949309T>G

NG_007107.2:g.111464A>C

NG_007107.3:g.111440A>C

ENST00000303391.11:c.1164A>C

ENST00000453960.7:c.1200A>C

ENST00000303391.10:c.1164A>C

ENST00000407218.5:c.*536A>C

ENST00000453960.6:c.1200A>C

ENST00000619732.4:c.1164A>C

ENST00000628176.2:c.*536A>C

NM_001110792.1:c.1200A>C

NM_001316337.1:c.885A>C

NM_004992.3:c.1164A>C

NM_001316337.2:c.885A>C

NM_001369391.2:c.885A>C

NM_001369392.2:c.885A>C

NM_001369393.2:c.885A>C

NM_001369394.1:c.885A>C

NM_001369394.2:c.885A>C

NM_001386137.1:c.495A>C

NM_001386138.1:c.495A>C

NM_001386139.1:c.495A>C

NM_004992.4:c.1164A>C

Benign

BA1 BP5_Strong BS2 BP7

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 highest population minor allele frequency of the p.Pro388= variant in MECP2 (NM_004992.3) in gnomAD v4.1 is 0.0004921 in the Middle Eastern population, which is higher than the ClinGen Rett and Angelman-like Disorders VCEP threshold (≥0.0003) for BA1, and therefore meets this criterion (BA1). The p.Pro388= variant is observed in at least 2 unaffected individuals (internal database - GeneDx) (BS2). The p.Pro388= variant is found in at least 3 patients with an alternate molecular basis of disease (internal database - GeneDx) (BP5_Strong). The silent p.Pro388= variant is not predicted to affect splicing using multiple computational tools and does not affect a highly conserved nucleotide (BP7). In summary, the p.Pro388= variant in MECP2 is classified as benign based on the ACMG/AMP criteria (BA1, BS2, BP5_Strong, BP7).

BA1

BP5_Strong

The p.Pro388= variant is found in at least 3 patients with an alternate molecular basis of disease (internal database - GeneDx) (BP5_Strong).

BS2

The p.Pro388= variant is observed in at least 2 unaffected individuals (internal database - GeneDx) (BS2).

BP7

The silent p.Pro388= variant is not predicted to affect splicing using multiple computational tools and does not affect a highly conserved nucleotide (BP7).

PM2

The p.Pro400= variant in MECP2 is absent from gnomAD v2.

Curation History

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