Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • See Evidence submitted by expert panel for details.

Variant: NM_001110792.1(MECP2):c.916C>T (p.Arg306Ter)

CA121700

11819 (ClinVar)

Gene: MECP2
Condition: Rett syndrome
Inheritance Mode: X-linked inheritance
Link to MONDO
UUID: ede88874-946c-4213-9897-197e908f3c6d
Approved on: 2021-03-26
Published on: 2021-05-17

HGVS expressions

NM_001110792.1:c.916C>T
NM_001110792.1(MECP2):c.916C>T (p.Arg306Ter)
NC_000023.11:g.154030948G>A
CM000685.2:g.154030948G>A
NC_000023.10:g.153296399G>A
CM000685.1:g.153296399G>A
NC_000023.9:g.152949593G>A
NG_007107.2:g.111180C>T
NG_007107.3:g.111156C>T
ENST00000303391.11:c.880C>T
ENST00000453960.7:c.916C>T
ENST00000637917.1:n.66-12C>T
ENST00000303391.10:c.880C>T
ENST00000407218.5:c.*252C>T
ENST00000453960.6:c.916C>T
ENST00000619732.4:c.880C>T
ENST00000622433.4:c.866C>T
ENST00000628176.2:c.*252C>T
NM_001316337.1:c.601C>T
NM_004992.3:c.880C>T
NM_001110792.2:c.916C>T
NM_001316337.2:c.601C>T
NM_001369391.2:c.601C>T
NM_001369392.2:c.601C>T
NM_001369393.2:c.601C>T
NM_001369394.1:c.601C>T
NM_001369394.2:c.601C>T
NM_001386137.1:c.211C>T
NM_001386138.1:c.211C>T
NM_001386139.1:c.211C>T
NM_004992.4:c.880C>T
More

Pathogenic

The Expert Panel has overridden the computationally generated classification - "Likely Pathogenic"
Met criteria codes 5
PS3_Supporting PS4 PVS1 PM2_Supporting PS2_Very Strong

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Rett and Angelman-like Disorders VCEP
The p.Arg294* 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. There is significant evidence that loss of this region of the gene is pathogenic (PVS1). The p.Arg294* variant in MECP2 has been reported as a de novo occurrence (biological parentage confirmed) in at least 2 individuals with Rett syndrome (internal database, GeneDx) (PS2_very strong). The p.Arg294* variant in MECP2 has been observed in at least 5 other individuals with Rett syndrome (PMID: 15737703, 11960578, 19722030, 21982064, RettBASE) (PS4). A transcription assay performed in Xenopus oocytes has shown that this variant impacts protein function (PMID 11058114) (PS3_supporting). The p.Arg294* variant in MECP2 is absent from gnomAD (PM2_supporting). In summary, the p.Arg294* variant in MECP2 is classified as Pathogenic for Rett syndrome based on the ACMG/AMP criteria (PVS1, PS2_very strong, PS4, PS3_supporting, PM2_supporting).
Met criteria codes
PS3_Supporting
The p.Arg294* variant in MECP2 failed to repress transcription in oocytes in the transcription assay and decreased levels of protein stability.
PS4
The p.Arg294* variant in MECP2 has been observed in at least 5 other individuals with RettSyndrome (15737703, 11960578, 19722030, 21982064, RettBASE)
PVS1
The variant p.Arg294* 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.
PM2_Supporting
The p.Arg306Ter variant in MECP2 is absent from gnomAD.
PS2_Very Strong
This variant has been observed confirmed de novo in over 2 affected individuals at GeneDx and in the literature.
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.