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_004992.3(MECP2):c.378-3C>G

CA233152

156068 (ClinVar)

Gene: MECP2

Condition: Rett syndrome

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: ebca151d-4737-4a75-b5f1-1cb0d64bae0f

HGVS expressions

NM_004992.3:c.378-3C>G

NM_004992.3(MECP2):c.378-3C>G

ENST00000303391.11:c.378-3C>G

ENST00000453960.7:c.414-3C>G

ENST00000637917.1:n.11-3C>G

ENST00000303391.10:c.378-3C>G

ENST00000369957.5:c.*432-3C>G

ENST00000407218.5:c.414-3C>G

ENST00000453960.6:c.414-3C>G

ENST00000486506.5:n.2726-3C>G

ENST00000611468.1:c.366-3C>G

ENST00000619732.4:c.378-3C>G

ENST00000622433.4:c.366-3C>G

ENST00000628176.2:c.378-3C>G

NM_001110792.1:c.414-3C>G

NM_001316337.1:c.99-3C>G

NM_001110792.2:c.414-3C>G

NM_001316337.2:c.99-3C>G

NM_001369391.2:c.99-3C>G

NM_001369392.2:c.99-3C>G

NM_001369393.2:c.99-3C>G

NM_001369394.1:c.99-3C>G

NM_001369394.2:c.99-3C>G

NM_001386137.1:c.-183-3C>G

NM_001386138.1:c.-183-3C>G

NM_001386139.1:c.-183-3C>G

NM_004992.4:c.378-3C>G

NC_000023.11:g.154031453G>C

CM000685.2:g.154031453G>C

NC_000023.10:g.153296904G>C

CM000685.1:g.153296904G>C

NC_000023.9:g.152950098G>C

NG_007107.2:g.110675C>G

NG_007107.3:g.110651C>G

Pathogenic

PM2_Supporting PM6_Strong PS4 PP3

PS2

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 c.378-3C>G variant in MECP2 has been observed in at least 5 individuals with Angelman syndrome (PMID: 15737703, Rettbase, GeneDx internal data) (PS4). It has been reported in at least 2 unconfirmed de novo occurrences in individuals with Rett syndrome (PMID 15737703, 20142466) (PM6_strong). The c.378-3C>G variant in MECP2 is absent from gnomAD (PM2_supporting). Splice prediction analysis using multiple computational tools suggests an impact to splicing (PP3). In summary, the c.378-3C>G variant in MECP2 is classified as Pathogenic for Rett syndrome based on the ACMG/AMP criteria (PS4, PM6_strong, PM2_supporting, PP3).

PM2_Supporting

The c.378-3C>G in MECP2 is absent from gnomAD.

PM6_Strong

The c.378-3C>G variant in MECP2 has been reported in at least 2 unconfirmed de novo occurrences in individuals with Rett syndrome (PMID 15737703, 20142466).

PS4

The c.378-3C>G variant in MECP2 has been observed in at least 5 individuals with Angelman syndrome (PMID: 15737703, Rettbase, GeneDx internal data).

PP3

Splicing prediction softwares MaxEnt and NNSPLICE predict the variant c.378-3C>G in MECP2 to change splice acceptor site 3 bps downstream (PP3)

PS2

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

Approved on: 2021-03-26

Published on: 2021-05-17

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