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.631C>T (p.Pro211Ser)

CA415173156

1604076 (ClinVar)

Gene: MECP2 (HGNC:4204)

Condition: Rett syndrome (MONDO:0010726)

Inheritance Mode: X-linked inheritance

UUID: 225454eb-ef99-4096-8e55-7a563085f9c2

Approved on: 2025-02-28

Published on: 2025-03-26

HGVS expressions

NM_001110792.2(MECP2):c.631C>T (p.Pro211Ser)

NM_001110792.2:c.631C>T

NC_000023.11:g.154031233G>A

CM000685.2:g.154031233G>A

NC_000023.10:g.153296684G>A

CM000685.1:g.153296684G>A

NC_000023.9:g.152949878G>A

NG_007107.2:g.110895C>T

NG_007107.3:g.110871C>T

ENST00000303391.11:c.595C>T

ENST00000453960.7:c.631C>T

ENST00000637917.1:c.65+163C>T

ENST00000303391.10:c.595C>T

ENST00000407218.5:c.522C>T

ENST00000453960.6:c.631C>T

ENST00000619732.4:c.595C>T

ENST00000622433.4:c.583C>T

ENST00000628176.2:c.486C>T

NM_001110792.1:c.631C>T

NM_001316337.1:c.316C>T

NM_004992.3:c.595C>T

NM_001316337.2:c.316C>T

NM_001369391.2:c.316C>T

NM_001369392.2:c.316C>T

NM_001369393.2:c.316C>T

NM_001369394.1:c.316C>T

NM_001369394.2:c.316C>T

NM_001386137.1:c.-75C>T

NM_001386138.1:c.-75C>T

NM_001386139.1:c.-75C>T

NM_004992.4:c.595C>T

Benign

BS1 BS2

PM1 PS4 BP4 BA1

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 NM_004992.4: c.595C>T (p.Pro199Ser) variant in MECP2 in gnomAD v4.1 is 0.0002 in the East Asian population, which is higher than the ClinGen Rett and Angelman-like Disorders VCEP threshold (≥0.00008) for BS1, and therefore meets this criterion (BS1). The p.Pro199Ser variant is observed in at least 2 unaffected individuals (internal data, LabCorp Genetics Inc.) (BS2). The p.Pro199Ser variant is not currently published and is not present in additional databases (internal and publicly available), therefore, no additional criteria are applicable at this time. In summary, the p.Pro199Ser variant in MECP2 is classified as Benign based on the ACMG/AMP criteria (BS1, BS2) (MECP2 Specifications v3.0; curation approved on 02/28/2025).

BS1

The highest population minor allele frequency of the p.Pro199Ser variant in MECP2 (NM_004992.4) in gnomAD v4.1 is 0.0002 in the East Asian population, which is higher than the ClinGen Rett and Angelman-like Disorders VCEP threshold (≥0.00008) for BS1, and therefore meets this criterion (BS1).

BS2

The p.Pro199Ser variant (NM_004992.4) is observed in at least 2 unaffected individuals (internal data, LabCorp Genetics Inc.) (BS2).

PM1

Outside PM1 region.

PS4

The p.Pro199Ser variant (NM_004992.4) is not currently published and is not present in additional databases (internal and publicly available), therefore, no additional criteria are applicable at this time.

BP4

Computational prediction analysis tools are inconclusive for this variant.

BA1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Curation History

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