NM_001110792.2(MECP2):c.504C>G (p.Asp168Glu) AND Rett syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (7 submissions)
Last evaluated:: Mar 8, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000169946.22

Allele description

NM_001110792.2(MECP2):c.504C>G (p.Asp168Glu)

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.504C>G (p.Asp168Glu)

Other names:

p.D156E:GAC>GAG; NM_001110792.2(MECP2):c.504C>G; p.Asp168Glu

HGVS:

NC_000023.11:g.154031360G>C
NG_007107.3:g.110744C>G
NM_001110792.2:c.504C>GMANE SELECT
NM_001316337.2:c.189C>G
NM_001369391.2:c.189C>G
NM_001369392.2:c.189C>G
NM_001369393.2:c.189C>G
NM_001369394.2:c.189C>G
NM_001386137.1:c.-129+36C>G
NM_001386138.1:c.-129+36C>G
NM_001386139.1:c.-129+36C>G
NM_004992.4:c.468C>G
NP_001104262.1:p.Asp168Glu
NP_001303266.1:p.Asp63Glu
NP_001356320.1:p.Asp63Glu
NP_001356321.1:p.Asp63Glu
NP_001356322.1:p.Asp63Glu
NP_001356323.1:p.Asp63Glu
NP_004983.1:p.Asp156Glu
NP_004983.1:p.Asp156Glu
LRG_764t1:c.504C>G
LRG_764t2:c.468C>G
AJ132917.1:c.468C>G
LRG_764:g.110744C>G
LRG_764p1:p.Asp168Glu
LRG_764p2:p.Asp156Glu
NC_000023.10:g.153296811G>C
NG_007107.2:g.110768C>G
NM_001110792.2:c.504C>G
NM_004992.3:c.468C>G

Protein change:

D156E

Links:

dbSNP: rs61748408

NCBI 1000 Genomes Browser:

rs61748408

Molecular consequence:

NM_001386137.1:c.-129+36C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001386138.1:c.-129+36C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001386139.1:c.-129+36C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001110792.2:c.504C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001316337.2:c.189C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369391.2:c.189C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369392.2:c.189C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369393.2:c.189C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369394.2:c.189C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_004992.4:c.468C>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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

Recent activity

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1-aminocyclopropane-1-carboxylate oxidase 1 [Salvia hispanica]
1-aminocyclopropane-1-carboxylate oxidase 1 [Salvia hispanica]
gi|2236147881|ref|XP_047943970.1|

Protein
LOC125190663 [Salvia hispanica]
LOC125190663 [Salvia hispanica]
Gene ID:125190663

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000188113	RettBASE	no assertion criteria provided	Pathogenic (Apr 26, 2016)	de novo	research
SCV000223858	Molecular Genetics Laboratory, Children's Mercy Hospital and Clinics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000247969	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2007)	Pathogenic (Feb 8, 2013)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001847692	Suma Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	de novo	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002526736	Institute of Human Genetics, University of Leipzig Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 1, 2022)	de novo	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002601737	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 17, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004808972	Centre for Population Genomics, CPG	criteria provided, single submitter (McKnight et al. (Hum Mutat. 2022))	Pathogenic (Mar 8, 2024)	germline	curation	PubMed (1) [See all records that cite this PMID] Citation Link

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	yes	1	1	not provided	not provided	not provided	clinical testing
not provided	de novo	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	de novo	unknown	16	not provided	not provided	not provided	not provided	research
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

ACMG recommendations for standards for interpretation and reporting of sequence variations: Revisions 2007.

Richards CS, Bale S, Bellissimo DB, Das S, Grody WW, Hegde MR, Lyon E, Ward BE; Molecular Subcommittee of the ACMG Laboratory Quality Assurance Committee..

Genet Med. 2008 Apr;10(4):294-300. doi: 10.1097/GIM.0b013e31816b5cae.

PubMed [citation]

PMID:: 18414213

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

See all PubMed Citations (3)

Details of each submission

From RettBASE, SCV000188113.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	16	not provided	not provided	research	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	de novo	unknown	not provided	not provided	not provided		16	not provided	not provided	not provided

From Molecular Genetics Laboratory, Children's Mercy Hospital and Clinics, SCV000223858.1

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

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

From Genetic Services Laboratory, University of Chicago, SCV000247969.1

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

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

From Suma Genomics, SCV001847692.1

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

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

From Institute of Human Genetics, University of Leipzig Medical Center, SCV002526736.1

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

Description

This variant was identified as de novo (maternity and paternity confirmed)._x000D_ Criteria applied: PS4, PS2_MOD, PS1_MOD, PM1, PM5, PM2_SUP, PP3

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

From Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV002601737.1

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

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

From Centre for Population Genomics, CPG, SCV004808972.1

#	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 pathogenic. At least the following criteria are met: Has been observed in at least 5 individuals with phenotypes consistent with MECP2-related disease (PS4). (PMID: 15737703, 16473305, 12075485, 27354166, 20728410, 19722030, 23103540, 30781346, 26984561, 31645865, 19652677, 11524741, 21982064, 16672765,ClinVar Variation ID: 95196). Occurs in the well-characterized Methyl-DNA binding (MDB) functional domain of MECP2 (PM1). This variant has been identified as a de novo occurrence in an individual with Rett syndrome without confirmation of paternity and maternity (PM6). (PMID: 15737703) 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: Jun 17, 2024

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