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]

Link to SEPIO compliant JSON-LD document

Variant: NM_001110792.2(MECP2):c.553C>G (p.Pro185Ala)

CA270458

143608 (ClinVar)

Gene: MECP2

Condition: Rett syndrome

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: 08f6e1b8-034e-4d11-b2f0-d9e0543e6161

HGVS expressions

NM_001110792.2:c.553C>G

NM_001110792.2(MECP2):c.553C>G (p.Pro185Ala)

NC_000023.11:g.154031311G>C

CM000685.2:g.154031311G>C

NC_000023.10:g.153296762G>C

CM000685.1:g.153296762G>C

NC_000023.9:g.152949956G>C

NG_007107.2:g.110817C>G

NG_007107.3:g.110793C>G

ENST00000303391.11:c.517C>G

ENST00000453960.7:c.553C>G

ENST00000637917.1:n.65+85C>G

ENST00000303391.10:c.517C>G

ENST00000407218.5:c.469-25C>G

ENST00000453960.6:c.553C>G

ENST00000486506.5:n.2865C>G

ENST00000611468.1:c.503C>G

ENST00000619732.4:c.517C>G

ENST00000622433.4:c.505C>G

ENST00000628176.2:c.433-25C>G

NM_001110792.1:c.553C>G

NM_001316337.1:c.238C>G

NM_004992.3:c.517C>G

NM_001316337.2:c.238C>G

NM_001369391.2:c.238C>G

NM_001369392.2:c.238C>G

NM_001369393.2:c.238C>G

NM_001369394.1:c.238C>G

NM_001369394.2:c.238C>G

NM_001386137.1:c.-128-25C>G

NM_001386138.1:c.-128-25C>G

NM_001386139.1:c.-128-25C>G

NM_004992.4:c.517C>G

Likely Benign

BS2 BP5

PP4 PM1 PM2 BS1 BP4

Evidence Links 0

Expert Panel

Rett and Angelman-like Disorders VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The p.Pro173Ala variant in MECP2 (NM_004992.3) has been reported in an individual with a clinical phenotype suggestive of Rett syndrome; this individual was reported to have a second variant in MECP2 that was classified as Pathogenic (PMID 11241840). The p.Pro173Ala variant in MECP2 (NM_004992.3) is observed in at least 2 unaffected individuals (internal database - GeneDx; internal database - Invitae) (BS2). The p.Pro173Ala variant is found in at least 2 patients with an alternate molecular basis of disease (internal database - GeneDx; internal database - Invitae) (BP5). The p.Pro173Ala variant in MECP2 is present in 3 female and 2 male individual(s) in gnomAD (0.0024%) (not sufficient to meet BS1 criteria). In summary, the p.Pro173Ala variant in MECP2 is classified as Likely Benign based on the ACMG/AMP criteria (BS2, BP5).

BS2

The p.Pro173Ala variant in MECP2 (NM_004992.3) is observed in at least 2 unaffected individuals (internal database - GeneDx; internal database - Invitae) (BS2).

BP5

The p.Pro173Ala variant is found in at least 2 patients with an alternate molecular basis of disease (internal database - GeneDx; internal database - Invitae) (BP5).

PP4

The p.Pro173Ala variant in MECP2 has been reported in an individual with a clinical phenotype suggestive of Rett syndrome; this individual was reported to have a second variant in MECP2 that was classified as Pathogenic (PMID 11241840).

PM1

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

PM2

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

BS1

The p.Pro173Ala variant in MECP2 is present in 3 female and 2 male individual(s) in gnomAD (0.0024%) (not sufficient to meet BS1 criteria).

BP4

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

Approved on: 2022-10-11

Published on: 2022-12-02

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