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]

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Variant: NM_004992.3(MECP2):c.-99+2T>G

CA415300768

503729 (ClinVar)

Gene: MECP2

Condition: Rett syndrome

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: 24ff2099-d294-442d-b5e4-c9a13d900acd

HGVS expressions

NM_004992.3:c.-99+2T>G

NM_004992.3(MECP2):c.-99+2T>G

NC_000023.11:g.154097602A>C

CM000685.2:g.154097602A>C

NC_000023.10:g.153363059A>C

CM000685.1:g.153363059A>C

NC_000023.9:g.153016253A>C

NG_007107.2:g.44520T>G

NG_007107.3:g.44502T>G

ENST00000303391.11:c.-99+2T>G

ENST00000453960.7:c.62+2T>G

ENST00000676382.1:n.22+2T>G

ENST00000303391.10:c.-99+2T>G

ENST00000369957.5:c.-99+2T>G

ENST00000407218.5:c.62+2T>G

ENST00000453960.6:c.62+2T>G

ENST00000619732.4:c.-99+2T>G

ENST00000627864.1:n.77+2T>G

ENST00000628176.2:c.-99+2T>G

ENST00000631210.1:n.305+7179T>G

NM_001110792.1:c.62+2T>G

NM_001316337.1:c.-546+2T>G

NM_001110792.2:c.62+2T>G

NM_001316337.2:c.-546+2T>G

NM_001369391.2:c.-841+2T>G

NM_001369392.2:c.-490+2T>G

NM_001369393.2:c.-366+2T>G

NM_001386137.1:c.-771+2T>G

NM_001386138.1:c.-659+2T>G

NM_001386139.1:c.-535+2T>G

NM_004992.4:c.-99+2T>G

Pathogenic

PVS1 PS2 PM2_Supporting

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.-99+2T>G variant in MECP2 is predicted to affect a canonical splice site and lead to a truncated or absent protein in a gene where loss-of-function is an established mechanism. There is significant evidence that loss of this region of the gene is pathogenic (PVS1). The c.-99+2T>G variant in MECP2 occurs in the de novo state (biological parentage confirmed) in an individual with Rett syndrome (PS2). The c.-99+2T>G variant in MECP2 is absent from gnomAD (PM2_supporting). In summary, the c.-99+2T>G variant in MECP2 is classified as Pathogenic for Rett syndrome based on the ACMG/AMP criteria (PVS1, PS2, PM2_supporting).

PVS1

The c.-99+2T>G variant in MECP2 is predicted to cause a premature stop codon that leads to a truncated or absent protein in a gene where loss-of-function is an established mechanism. (PVS1)

PS2

The NM_004992.3:c.-99+2T>G variant in MECP2 occurs in the confirmed de novo state in this individual (PS2)

PM2_Supporting

The variant NM_004992.3(MECP2):c.-99+2T>G is absent from controls in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (PM2)

Approved on: 2021-03-26

Published on: 2021-05-17

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