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]
  • Gene label mismatch: MECP2 vs undefined
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_001110792.2(MECP2):c.1364C>T (p.Ala455Val)

CA208615

211456 (ClinVar)

Gene: MECP2
Condition: Rett syndrome
Inheritance Mode: X-linked inheritance
Link to MONDO
UUID: 9935f438-3ac6-443b-a10c-eb654bc4ef0e
Approved on: 2025-02-28
Published on: 2025-03-26

HGVS expressions

NM_001110792.2:c.1364C>T
NM_001110792.2(MECP2):c.1364C>T (p.Ala455Val)
NC_000023.11:g.154030500G>A
CM000685.2:g.154030500G>A
NC_000023.10:g.153295951G>A
CM000685.1:g.153295951G>A
NC_000023.9:g.152949145G>A
NG_007107.2:g.111628C>T
NG_007107.3:g.111604C>T
ENST00000303391.11:c.1328C>T
ENST00000453960.7:c.1364C>T
ENST00000303391.10:c.1328C>T
ENST00000453960.6:c.1364C>T
ENST00000619732.4:c.1328C>T
ENST00000628176.2:c.*700C>T
NM_001110792.1:c.1364C>T
NM_001316337.1:c.1049C>T
NM_004992.3:c.1328C>T
NM_001316337.2:c.1049C>T
NM_001369391.2:c.1049C>T
NM_001369392.2:c.1049C>T
NM_001369393.2:c.1049C>T
NM_001369394.1:c.1049C>T
NM_001369394.2:c.1049C>T
NM_001386137.1:c.659C>T
NM_001386138.1:c.659C>T
NM_001386139.1:c.659C>T
NM_004992.4:c.1328C>T
More

Likely Benign

Met criteria codes 1
BS2
Not Met criteria codes 5
PM1 BS1 BP4 PS4 PP3

Evidence Links 0

Expert Panel

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 NM_004992.4:c.1328C>T p.Ala443Val variant in gnomAD v4.1 is 0.00007 in the European (non-Finnish) population (not sufficient to meet BS1 criteria). The p.Ala443Val variant is observed in at least 2 unaffected individuals (internal data, Labcorp Genetics Inc.) (BS2). The p.Ala443Val variant is not currently published and is not present in additional databases (internal and publicly available), therefore, no additional criteria are applicable at this time. Computational prediction analysis tools are inconclusive for this variant (REVEL gives a score of 0.492). In the absence of conflicting evidence, this is sufficient evidence to classify the p.Ala443Val variant as likely benign based on the specifications defined by the ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel (BS2) (MECP2 Specifications v3.0; curation approved on 02/28/2025).
Met criteria codes
BS2
The p.Ala443Val variant (NM_004992.4) is observed in at least 2 unaffected individuals (internal data, LabCorp Genetics Inc.) (BS2).
Not Met criteria codes
PM1
Outside PM1 region.
BS1
The highest population minor allele frequency of the p.Ala443Val variant in MECP2 (NM_004992.4) in gnomAD v4.1 is 0.00007 in the European (non-Finnish) population (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
PS4
The p.Ala443Val variant (NM_004992.4) is not currently published and is not present in additional databases (internal and publicly available), therefore, no additional criteria are applicable at this time.
PP3
Computational prediction analysis tools are inconclusive for this variant (REVEL gives a score of 0.492).
Curation History
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