NM_001110792.2(MECP2):c.731del (p.Gly244fs) AND Rett syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 22, 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:: RCV000133203.4

Allele description [Variation Report for NM_001110792.2(MECP2):c.731del (p.Gly244fs)]

NM_001110792.2(MECP2):c.731del (p.Gly244fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

Xq28

Genomic location:

Preferred name:

NM_001110792.2(MECP2):c.731del (p.Gly244fs)

Other names:

NM_001110792.2(MECP2):c.731del; p.Gly244fs

HGVS:

NC_000023.11:g.154031137del
NG_007107.3:g.110971del
NM_001110792.2:c.731delMANE SELECT
NM_001316337.2:c.416del
NM_001369391.2:c.416del
NM_001369392.2:c.416del
NM_001369393.2:c.416del
NM_001369394.2:c.416del
NM_001386137.1:c.26del
NM_001386138.1:c.26del
NM_001386139.1:c.26del
NM_004992.3:c.695del
NM_004992.4:c.695del
NP_001104262.1:p.Gly244fs
NP_001303266.1:p.Gly139fs
NP_001356320.1:p.Gly139fs
NP_001356321.1:p.Gly139fs
NP_001356322.1:p.Gly139fs
NP_001356323.1:p.Gly139fs
NP_001373066.1:p.Gly9fs
NP_001373067.1:p.Gly9fs
NP_001373068.1:p.Gly9fs
NP_004983.1:p.Gly232fs
LRG_764t1:c.731del
LRG_764t2:c.695del
AJ132917.1:c.695delG
LRG_764:g.110971del
LRG_764p1:p.Gly244fs
LRG_764p2:p.Gly232fs
NC_000023.10:g.153296584del
NC_000023.10:g.153296588del
NG_007107.2:g.110995del
NM_004992.3:c.695delG

Protein change:

G139fs

Links:

dbSNP: rs63260260

NCBI 1000 Genomes Browser:

rs63260260

Molecular consequence:

NM_001110792.2:c.731del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001316337.2:c.416del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369391.2:c.416del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369392.2:c.416del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369393.2:c.416del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369394.2:c.416del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001386137.1:c.26del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001386138.1:c.26del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001386139.1:c.26del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004992.4:c.695del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV000188201	RettBASE	no assertion criteria provided	Pathogenic (Feb 18, 2008)	de novo, unknown	curation	PubMed (4) [See all records that cite these PMIDs] 10991688, 11738864, 15057977, 15737703
SCV004808882	Centre for Population Genomics, CPG	criteria provided, single submitter (McKnight et al. (Hum Mutat. 2022))	Pathogenic (Mar 22, 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

SCV000188201

RettBASE

no assertion criteria provided

Pathogenic
(Feb 18, 2008)

de novo, unknown

curation

PubMed (4)
[See all records that cite these PMIDs]

SCV004808882

Centre for Population Genomics, CPG

criteria provided, single submitter

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

Pathogenic
(Mar 22, 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	3	not provided	not provided	3	No	curation
not provided	de novo	yes	2	not provided	not provided	2	No	curation

Citations

PubMed

Mutation analysis of the methyl-CpG binding protein 2 gene (MECP2) in patients with Rett syndrome.

Obata K, Matsuishi T, Yamashita Y, Fukuda T, Kuwajima K, Horiuchi I, Nagamitsu S, Iwanaga R, Kimura A, Omori I, Endo S, Mori K, Kondo I.

J Med Genet. 2000 Aug;37(8):608-10. No abstract available.

PubMed [citation]

PMID:: 10991688
PMCID:: PMC1734655

Mutation analysis of the methyl-CpG-binding protein 2 gene (MECP2) in Rett patients with preserved speech.

Yamashita Y, Kondo I, Fukuda T, Morishima R, Kusaga A, Iwanaga R, Matsuishi T.

Brain Dev. 2001 Dec;23 Suppl 1:S157-60.

PubMed [citation]

PMID:: 11738864

See all PubMed Citations (5)

Details of each submission

From RettBASE, SCV000188201.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	No	curation	PubMed (4)
2	not provided	1	not provided	not provided	curation	PubMed (4)
3	not provided	1	not provided	No	curation	PubMed (4)
4	not provided	1	not provided	No	curation	PubMed (4)
5	not provided	1	not provided	No	curation	PubMed (4)

Description

Rett syndrome - Classical

"Rett syndrome - Classical"

PubMed [ID: 10991688]

"Rett syndrome - atypical"

PubMed [ID: 11738864]

"Rett syndrome - classical"

PubMed [ID: 15057977]

"Rett syndrome - classical"

PubMed [ID: 15737703]

#	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	unknown	yes	1	Blood or skin	not provided		1	not provided	not provided	not provided
3	unknown	yes	1	Blood	not provided		1	not provided	not provided	not provided
4	de novo	yes	1	blood	not provided		1	not provided	not provided	not provided
5	unknown	yes	1	blood	not provided		1	not provided	not provided	not provided

From Centre for Population Genomics, CPG, SCV004808882.1

#	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). Has been observed in at least 5 individuals with phenotypes consistent with MECP2-related disease (PS4). PubMed: PMID:10508514 ,10991688‚Äö 11738864‚Äö 15057977‚Äö 15737703, ClinVar Variation ID: 143662 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: Sep 29, 2024

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