NM_001110792.2(MECP2):c.500T>G (p.Phe167Cys) AND Rett syndrome

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Mar 14, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000170275.2

Allele description [Variation Report for NM_001110792.2(MECP2):c.500T>G (p.Phe167Cys)]

NM_001110792.2(MECP2):c.500T>G (p.Phe167Cys)

Gene:

MECP2:methyl-CpG binding protein 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq28

Genomic location:

Preferred name:

NM_001110792.2(MECP2):c.500T>G (p.Phe167Cys)

Other names:

NM_001110792.2(MECP2):c.500T>G; p.Phe167Cys

HGVS:

NC_000023.11:g.154031364A>C
NG_007107.3:g.110740T>G
NM_001110792.2:c.500T>GMANE SELECT
NM_001316337.2:c.185T>G
NM_001369391.2:c.185T>G
NM_001369392.2:c.185T>G
NM_001369393.2:c.185T>G
NM_001369394.2:c.185T>G
NM_001386137.1:c.-129+32T>G
NM_001386138.1:c.-129+32T>G
NM_001386139.1:c.-129+32T>G
NM_004992.4:c.464T>G
NP_001104262.1:p.Phe167Cys
NP_001303266.1:p.Phe62Cys
NP_001356320.1:p.Phe62Cys
NP_001356321.1:p.Phe62Cys
NP_001356322.1:p.Phe62Cys
NP_001356323.1:p.Phe62Cys
NP_004983.1:p.Phe155Cys
NP_004983.1:p.Phe155Cys
LRG_764t1:c.500T>G
LRG_764t2:c.464T>G
AJ132917.1:c.464T>G
LRG_764:g.110740T>G
LRG_764p1:p.Phe167Cys
LRG_764p2:p.Phe155Cys
NC_000023.10:g.153296815A>C
NG_007107.2:g.110764T>G
NM_004992.3:c.464T>G

Protein change:

F155C

Links:

dbSNP: rs28934905

NCBI 1000 Genomes Browser:

rs28934905

Molecular consequence:

NM_001386137.1:c.-129+32T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001386138.1:c.-129+32T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001386139.1:c.-129+32T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001110792.2:c.500T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001316337.2:c.185T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369391.2:c.185T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369392.2:c.185T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369393.2:c.185T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369394.2:c.185T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_004992.4:c.464T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Rett syndrome (RTT)
Synonyms:: Autism, dementia, ataxia, and loss of purposeful hand use; Rett's disorder
Identifiers:: MONDO: MONDO:0010726; MedGen: C0035372; Orphanet: 3095; Orphanet: 778; OMIM: 312750

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000222607	RettBASE	no assertion criteria provided	Uncertain significance	unknown	curation
SCV004808727	Centre for Population Genomics, CPG	criteria provided, single submitter (McKnight et al. (Hum Mutat. 2022))	Likely pathogenic (Mar 14, 2024)	germline	curation	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000222607

RettBASE

no assertion criteria provided

Uncertain significance

unknown

curation

SCV004808727

Centre for Population Genomics, CPG

criteria provided, single submitter

(McKnight et al. (Hum Mutat. 2022))

Likely pathogenic
(Mar 14, 2024)

germline

curation

PubMed (1)
[See all records that cite this PMID]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	curation
not provided	unknown	yes	1	not provided	not provided	1	not provided	curation
not provided	unknown	unknown	1	not provided	not provided	1	not provided	curation

Citations

PubMed

Recommendations by the ClinGen Rett/Angelman-like expert panel for gene-specific variant interpretation methods.

McKnight D, Bean L, Karbassi I, Beattie K, Bienvenu T, Bonin H, Fang P, Chrisodoulou J, Friez M, Helgeson M, Krishnaraj R, Meng L, Mighion L, Neul J, Percy A, Ramsden S, Zoghbi H, Das S.

Hum Mutat. 2022 Aug;43(8):1097-1113. doi: 10.1002/humu.24302. Epub 2021 Dec 2.

PubMed [citation]

PMID:: 34837432
PMCID:: PMC9135956

Details of each submission

From RettBASE, SCV000222607.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	curation	not provided
2	not provided	1	not provided	not provided	curation	not provided

Description

Not known

Rett syndrome - Atypical

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	1	Blood	not provided		1	not provided	not provided	not provided
2	unknown	yes	1	Blood or skin	not provided		1	not provided	not provided	not provided

From Centre for Population Genomics, CPG, SCV004808727.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (1)

Description

This variant has been collected from RettBASE and curated to current modified ACMG/AMP criteria. Based on the classification scheme defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders Specifications to the ACMG/AMP Variant Interpretation Guidelines VCEP 3.0, this variant is classified as likely pathogenic. At least the following criteria are met: >=2 different missense variants in the same codon have been classified as pathogenic (PM5_Strong). Occurs in the well-characterized Methyl-DNA binding (MDB) functional domain of MECP2 (PM1). Computational prediction analysis tools suggests a deleterious impact (REVEL score>= 0.75) (PP3). This variant is absent from gnomAD (PM2_Supporting).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 15, 2024

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