NM_001110792.2(MECP2):c.411del (p.Asn138fs) AND Rett syndrome

Germline classification:: 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:: RCV000133084.4

Allele description [Variation Report for NM_001110792.2(MECP2):c.411del (p.Asn138fs)]

NM_001110792.2(MECP2):c.411del (p.Asn138fs)

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.411del (p.Asn138fs)

Other names:

NM_001110792.2(MECP2):c.411del; p.Asn138fs

HGVS:

NC_000023.11:g.154032209del
NG_007107.3:g.109895del
NM_001110792.2:c.411delMANE SELECT
NM_001316337.2:c.96del
NM_001369391.2:c.96del
NM_001369392.2:c.96del
NM_001369393.2:c.96del
NM_001369394.2:c.96del
NM_001386137.1:c.-186del
NM_001386138.1:c.-186del
NM_001386139.1:c.-186del
NM_004992.4:c.375del
NP_001104262.1:p.Asn138fs
NP_001303266.1:p.Asn33fs
NP_001356320.1:p.Asn33fs
NP_001356321.1:p.Asn33fs
NP_001356322.1:p.Asn33fs
NP_001356323.1:p.Asn33fs
NP_004983.1:p.Asn126fs
LRG_764t1:c.411del
LRG_764t2:c.375del
AJ132917.1:c.375delC
LRG_764:g.109895del
LRG_764p1:p.Asn138fs
LRG_764p2:p.Asn126fs
NC_000023.10:g.153297660del
NG_007107.2:g.109919del
NM_004992.3:c.375delC

Protein change:

N126fs

Links:

dbSNP: rs267608457

NCBI 1000 Genomes Browser:

rs267608457

Molecular consequence:

NM_001386137.1:c.-186del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001386138.1:c.-186del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001386139.1:c.-186del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001110792.2:c.411del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001316337.2:c.96del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369391.2:c.96del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369392.2:c.96del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369393.2:c.96del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369394.2:c.96del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004992.4:c.375del - 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
SCV000188073	RettBASE	no assertion criteria provided	Pathogenic (Feb 18, 2008)	de novo	curation	PubMed (2) [See all records that cite these PMIDs] 10991688, 15737703
SCV004808734	Centre for Population Genomics, CPG	criteria provided, single submitter (McKnight et al. (Hum Mutat. 2022))	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

SCV000188073

RettBASE

no assertion criteria provided

Pathogenic
(Feb 18, 2008)

de novo

curation

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

SCV004808734

Centre for Population Genomics, CPG

criteria provided, single submitter

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

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	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

Methyl-CpG binding protein 2 gene (MECP2) variations in Japanese patients with Rett syndrome: pathological mutations and polymorphisms.

Fukuda T, Yamashita Y, Nagamitsu S, Miyamoto K, Jin JJ, Ohmori I, Ohtsuka Y, Kuwajima K, Endo S, Iwai T, Yamagata H, Tabara Y, Miki T, Matsuishi T, Kondo I.

Brain Dev. 2005 Apr;27(3):211-7.

PubMed [citation]

PMID:: 15737703

See all PubMed Citations (3)

Details of each submission

From RettBASE, SCV000188073.2

#	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 - classical"

PubMed [ID: 10991688]

"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	blood	not provided		1	not provided	not provided	not provided
2	de novo	yes	1	not provided	not provided		1	not provided	not provided	not provided

From Centre for Population Genomics, CPG, SCV004808734.1

#	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 is absent from gnomAD (PM2_Supporting). Has been observed in at least 2 individuals with phenotypes consistent with MECP2-related disease (PS4_Supporting). PubMed: 10991688‚Äö 15737703

#	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 23, 2024

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