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 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.784C>T (p.Arg262Cys)

CA205183

211466 (ClinVar)

Gene: MECP2
Condition: Rett syndrome
Inheritance Mode: X-linked inheritance
Link to MONDO
UUID: 42d1d263-dfac-4cab-832f-a8ddefada4fb
Approved on: 2025-10-28
Published on: 2025-12-23

HGVS expressions

NM_001110792.2:c.784C>T
NM_001110792.2(MECP2):c.784C>T (p.Arg262Cys)
NC_000023.11:g.154031080G>A
CM000685.2:g.154031080G>A
NC_000023.10:g.153296531G>A
CM000685.1:g.153296531G>A
NC_000023.9:g.152949725G>A
NG_007107.2:g.111048C>T
NG_007107.3:g.111024C>T
ENST00000303391.11:c.748C>T
ENST00000453960.7:c.784C>T
ENST00000637917.1:c.66-144C>T
ENST00000303391.10:c.748C>T
ENST00000407218.5:c.*120C>T
ENST00000453960.6:c.784C>T
ENST00000619732.4:c.748C>T
ENST00000622433.4:c.736C>T
ENST00000628176.2:c.*120C>T
NM_001110792.1:c.784C>T
NM_001316337.1:c.469C>T
NM_004992.3:c.748C>T
NM_001316337.2:c.469C>T
NM_001369391.2:c.469C>T
NM_001369392.2:c.469C>T
NM_001369393.2:c.469C>T
NM_001369394.1:c.469C>T
NM_001369394.2:c.469C>T
NM_001386137.1:c.79C>T
NM_001386138.1:c.79C>T
NM_001386139.1:c.79C>T
NM_004992.4:c.748C>T
More

Benign

Met criteria codes 5
PP3 PM6 BA1 BS2 BP5
Not Met criteria codes 4
PS4 PM5 PM1 BP4

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 5.0.0

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 p.Arg250Cys variant in MECP2 (NM_004992.4) in gnomAD v4.1.0 is 0.0006301 in the "remaining" population, which is higher than the ClinGen Rett and Angelman-like Disorders VCEP threshold (≥0.000083) for BA1, and therefore meets this criterion (BA1). The p.Arg250Cys variant is observed in at least 9 unaffected individuals (PMID: 25649377; internal database - GeneDx; internal database - LabCorp (formerly Invitae)) (BS2). The p.Arg250Cys variant is found in at least 2 patients with an alternate molecular basis of disease (internal database - Ambry; internal database - LabCorp (formerly Invitae)) (BP5). The p.Arg250Cys variant in MECP2 (NM_004992.4) has been reported as a de novo occurrence (biological parentage unconfirmed) in an individual with developmental and epileptic encephalopathy (PMID: 38074073) (PM6). The p.Arg250Cys variant has been observed in at least 4 individuals with a neurodevelopmental phenotype (PMID: 30405208, 38074073, 26350204, 25649377); however PS4 cannot be applied at any strength due to the gnomAD frequency. Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3). Because this variant has been observed in at least 9 unaffected individuals and 2 individuals with an alternate molecular diagnosis, and has been reported in gnomAD v4.1.0 at a frequency that meets the ClinGen Rett and Angelman-like Disorders VCEP threshold for BA1, the ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel has agreed to override the PM6 and PP3 criteria and classified this variant as Benign (BA1, BS2, BP5). (MECP2 Specifications v5.0; curation approved on 10/28/2025)
Met criteria codes
PP3
Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3).
PM6
The p.Arg250Cys variant in MECP2 has been reported as a de novo occurrence (biological parentage unconfirmed) in an individual with developmental and epileptic encephalopathy (PMID: 38074073) (PM6).
BA1
The highest population minor allele frequency of the p.Arg250Cys variant in MECP2 (NM_004992.4) in gnomAD v4.1.0 is 0.0006301 in the "remaining" population, which is higher than the ClinGen Rett and Angelman-like Disorders VCEP threshold (≥0.000083) for BA1, and therefore meets this criterion (BA1).
BS2
The p.Arg250Cys variant is observed in at least 9 unaffected individuals (PMID: 25649377; internal database - GeneDx; internal database - LabCorp (formerly Invitae)).
BP5
The p.Arg250Cys variant is found in at least 2 patients with an alternate molecular basis of disease (internal database - Ambry; internal database - LabCorp (formerly Invitae)) (BP5).
Not Met criteria codes
PS4
The p.Arg250Cys variant has been observed in at least 4 individuals with a neurodevelopmental phenotype (PMID: 30405208, 38074073, 26350204, 25649377); however PS4 cannot be applied at any strength due to the gnomAD frequency.
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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