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]

Variant: NM_001110792.2(MECP2):c.1466G>C (p.Ser489Thr)

Curation Version - 2.0
Curation History
JSON LD for Version 2.0

CA170245

143475 (ClinVar)

Gene: MECP2

Condition: Rett syndrome

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: 32d53fd8-0652-4c83-ba6a-b7a791fb3b20

Approved on: 2024-08-30

Published on: 2024-11-15

HGVS expressions

NM_001110792.2:c.1466G>C

NM_001110792.2(MECP2):c.1466G>C (p.Ser489Thr)

NC_000023.11:g.154030398C>G

CM000685.2:g.154030398C>G

NC_000023.10:g.153295849C>G

CM000685.1:g.153295849C>G

NC_000023.9:g.152949043C>G

NG_007107.2:g.111730G>C

NG_007107.3:g.111706G>C

ENST00000303391.11:c.1430G>C

ENST00000453960.7:c.1466G>C

ENST00000303391.10:c.1430G>C

ENST00000453960.6:c.1466G>C

ENST00000619732.4:c.1430G>C

ENST00000628176.2:c.*802G>C

NM_001110792.1:c.1466G>C

NM_001316337.1:c.1151G>C

NM_004992.3:c.1430G>C

NM_001316337.2:c.1151G>C

NM_001369391.2:c.1151G>C

NM_001369392.2:c.1151G>C

NM_001369393.2:c.1151G>C

NM_001369394.1:c.1151G>C

NM_001369394.2:c.1151G>C

NM_001386137.1:c.761G>C

NM_001386138.1:c.761G>C

NM_001386139.1:c.761G>C

NM_004992.4:c.1430G>C

Likely Benign

BS2

BA1 PM2 BS1 BP2

Evidence Links 0

Expert Panel

Rett and Angelman-like Disorders VCEP

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 p.Ser477Thr (NM_004992.3) variant is observed in at least 2 unaffected individuals (PMID: 12655490) (BS2). The p.Ser477Thr variant is observed in the MECP2 gene where a second pathogenic variant in the same gene is present in the patient (PMID 12655490); however, it is unknown if the variants are in cis or trans (BP5 - not met). The highest population minor allele frequency of the p.Ser477Thr variant in MECP2 (NM_004992.3) in gnomAD v4.1 is 0.000008933 in European (non-Finnish) population (not sufficient to meet BA1, BS1, or PM2 criteria). In the absence of conflicting evidence, this is sufficient evidence to classify as likely benign based on the specifications defined by the ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel. In summary, the p.Ser477Thr variant in MECP2 (NM_004992.3) is classified as likely benign for Rett syndrome based on the ACMG/AMP criteria (BS2).

BS2

The p.Ser477Thr variant is observed in at least 2 unaffected individuals (PMID 12655490) (BS2).

BA1

The highest population minor allele frequency of the p.Ser477Thr variant in MECP2 (NM_004992.3) in gnomAD v4.1 is 0.000008933 in European (non-Finnish) population (not sufficient to meet BA1 criteria).

PM2

BS1

BP2

The p.Ser477Thr variant is observed in the MECP2 gene where a second pathogenic variant in the same gene is present in the patient (PMID 12655490); however, it is unknown if the variants are in cis or trans (BP2_not_met).

Curation History

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