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.1240C>A (p.Pro414Thr)

CA10558469

379509 (ClinVar)

Gene: MECP2 (HGNC:4204)

Condition: Rett syndrome (MONDO:0010726)

Inheritance Mode: X-linked inheritance

UUID: 34cac9de-909c-453c-b528-ba903eb30918

Approved on: 2024-08-30

Published on: 2024-12-23

HGVS expressions

NM_001110792.2:c.1240C>A

NM_001110792.2(MECP2):c.1240C>A (p.Pro414Thr)

NC_000023.11:g.154030624G>T

CM000685.2:g.154030624G>T

NC_000023.10:g.153296075G>T

CM000685.1:g.153296075G>T

NC_000023.9:g.152949269G>T

NG_007107.2:g.111504C>A

NG_007107.3:g.111480C>A

ENST00000303391.11:c.1204C>A

ENST00000453960.7:c.1240C>A

ENST00000303391.10:c.1204C>A

ENST00000407218.5:c.*576C>A

ENST00000453960.6:c.1240C>A

ENST00000619732.4:c.1204C>A

ENST00000628176.2:c.*576C>A

NM_001110792.1:c.1240C>A

NM_001316337.1:c.925C>A

NM_004992.3:c.1204C>A

NM_001316337.2:c.925C>A

NM_001369391.2:c.925C>A

NM_001369392.2:c.925C>A

NM_001369393.2:c.925C>A

NM_001369394.1:c.925C>A

NM_001369394.2:c.925C>A

NM_001386137.1:c.535C>A

NM_001386138.1:c.535C>A

NM_001386139.1:c.535C>A

NM_004992.4:c.1204C>A

Benign

BS2 BS1 BP5

PM2 BA1 BP4

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.Pro402Thr variant in MECP2 (NM_004992.4) in gnomAD v4.1 is 0.0002474 in South 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.Pro402Thr variant is observed in at least 2 unaffected individuals (internal database - GeneDx) (BS2). The p.Pro402Thr variant is found in a patient with an alternate molecular basis of disease (internal database - GeneDx) (BP5). In summary, the p.Pro402Thr variant in MECP2 is classified as benign based on the ACMG/AMP criteria (BS1, BS2, BP5). (MECP2 Specification v3.0.0, curation approved on 8/30/2024)

BS2

The p.Pro402Thr variant is observed in at least 2 unaffected individuals (internal database - GeneDx) (BS2).

BS1

BP5

The p.Pro402Thr variant is found in a patient with an alternate molecular basis of disease (internal database - GeneDx) (BP5).

PM2

The highest population minor allele frequency of the p.Pro402Thr variant in MECP2 (NM_004992.4) in gnomAD v4.1 is 0.0002474 in South Asian population (not sufficient to meet PM2 criteria).

BA1

The highest population minor allele frequency of the p.Pro402Thr variant in MECP2 (NM_004992.4) in gnomAD v4.1 is 0.0002474 in South Asian population (not sufficient to meet BA1 criteria).

BP4

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

Curation History

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