NM_001110792.2(MECP2):c.649G>T (p.Glu217Ter) AND Rett syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 25, 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:: RCV000133176.3

Allele description [Variation Report for NM_001110792.2(MECP2):c.649G>T (p.Glu217Ter)]

NM_001110792.2(MECP2):c.649G>T (p.Glu217Ter)

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.649G>T (p.Glu217Ter)

Other names:

NM_001110792.2(MECP2):c.649G>T; p.Glu217Ter

HGVS:

NC_000023.11:g.154031215C>A
NG_007107.3:g.110889G>T
NM_001110792.2:c.649G>TMANE SELECT
NM_001316337.2:c.334G>T
NM_001369391.2:c.334G>T
NM_001369392.2:c.334G>T
NM_001369393.2:c.334G>T
NM_001369394.2:c.334G>T
NM_001386137.1:c.-57G>T
NM_001386138.1:c.-57G>T
NM_001386139.1:c.-57G>T
NM_004992.4:c.613G>T
NP_001104262.1:p.Glu217Ter
NP_001303266.1:p.Glu112Ter
NP_001356320.1:p.Glu112Ter
NP_001356321.1:p.Glu112Ter
NP_001356322.1:p.Glu112Ter
NP_001356323.1:p.Glu112Ter
NP_004983.1:p.Glu205Ter
NP_004983.1:p.Glu205Ter
LRG_764t1:c.649G>T
LRG_764t2:c.613G>T
AJ132917.1:c.613G>T
LRG_764:g.110889G>T
LRG_764p1:p.Glu217Ter
LRG_764p2:p.Glu205Ter
NC_000023.10:g.153296666C>A
NG_007107.2:g.110913G>T
NM_004992.3:c.613G>T

Protein change:

E112*

Links:

dbSNP: rs61749726

NCBI 1000 Genomes Browser:

rs61749726

Molecular consequence:

NM_001386137.1:c.-57G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001386138.1:c.-57G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001386139.1:c.-57G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001110792.2:c.649G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001316337.2:c.334G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001369391.2:c.334G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001369392.2:c.334G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001369393.2:c.334G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001369394.2:c.334G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_004992.4:c.613G>T - nonsense - [Sequence Ontology: SO:0001587]

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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Saccharomyces cerevisiae S288C ribosomal 60S subunit protein L9B (RPL9B), partia...
Saccharomyces cerevisiae S288C ribosomal 60S subunit protein L9B (RPL9B), partial mRNA
gi|296147700|ref|NM_001182905.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000188174	RettBASE	no assertion criteria provided	Pathogenic (Sep 5, 2002)	de novo	curation	PubMed (2) [See all records that cite these PMIDs] 11241840, 11309679
SCV004808889	Centre for Population Genomics, CPG	criteria provided, single submitter (McKnight et al. (Hum Mutat. 2022))	Pathogenic (Mar 25, 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

SCV000188174

RettBASE

no assertion criteria provided

Pathogenic
(Sep 5, 2002)

de novo

curation

PubMed (2)
[See all records that cite these PMIDs]

SCV004808889

Centre for Population Genomics, CPG

criteria provided, single submitter

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

Pathogenic
(Mar 25, 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	de novo	yes	2	not provided	not provided	2	No	curation

Citations

PubMed

Mutation spectrum in patients with Rett syndrome in the German population: Evidence of hot spot regions.

Laccone F, Huppke P, Hanefeld F, Meins M.

Hum Mutat. 2001 Mar;17(3):183-90.

PubMed [citation]

PMID:: 11241840

MECP2 mutations in sporadic cases of Rett syndrome are almost exclusively of paternal origin.

Trappe R, Laccone F, Cobilanschi J, Meins M, Huppke P, Hanefeld F, Engel W.

Am J Hum Genet. 2001 May;68(5):1093-101. Epub 2001 Apr 17.

PubMed [citation]

PMID:: 11309679
PMCID:: PMC1226090

See all PubMed Citations (3)

Details of each submission

From RettBASE, SCV000188174.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	No	curation	PubMed (2)
2	not provided	1	not provided	No	curation	PubMed (2)

Description

"Rett syndrome - Not certain"

PubMed [ID: 11241840]

"Rett syndrome - Not certain"

PubMed [ID: 11309679]

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

From Centre for Population Genomics, CPG, SCV004808889.1

#	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: Predicted to result in loss of function, and LOF is a known mechanism of disease (PVS1). This variant has been identified as a de novo occurrence in an individual with Rett syndrome without confirmation of paternity and maternity (PM6). PMID: 11241840. This variant is absent from gnomAD (PM2_Supporting). Has been observed in at least 2 individuals with phenotypes consistent with MECP2-related disease (PS4_Supporting).(PMID: 11309679, 11241840)

#	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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