NM_001110792.2(MECP2):c.511del (p.Thr170_Val171insTer) AND Rett syndrome

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Jan 15, 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:: RCV000133131.4

Allele description [Variation Report for NM_001110792.2(MECP2):c.511del (p.Thr170_Val171insTer)]

NM_001110792.2(MECP2):c.511del (p.Thr170_Val171insTer)

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.511del (p.Thr170_Val171insTer)

Other names:

NM_001110792.2(MECP2):c.511del; p.Thr170_Val171insTer

HGVS:

NC_000023.11:g.154031354del
NG_007107.3:g.110751del
NM_001110792.2:c.511delMANE SELECT
NM_001316337.2:c.196del
NM_001369391.2:c.196del
NM_001369392.2:c.196del
NM_001369393.2:c.196del
NM_001369394.2:c.196del
NM_001386137.1:c.-129+43del
NM_001386138.1:c.-129+43del
NM_001386139.1:c.-129+43del
NM_004992.4:c.475del
NP_001104262.1:p.Thr170_Val171insTer
NP_001303266.1:p.Thr65_Val66insTer
NP_001356320.1:p.Thr65_Val66insTer
NP_001356321.1:p.Thr65_Val66insTer
NP_001356322.1:p.Thr65_Val66insTer
NP_001356323.1:p.Thr65_Val66insTer
NP_004983.1:p.Thr158_Val159insTer
LRG_764t1:c.511del
LRG_764t2:c.475del
AJ132917.1:c.475delG
LRG_764:g.110751del
LRG_764p1:p.Thr170_Val171insTer
LRG_764p2:p.Thr158_Val159insTer
NC_000023.10:g.153296805del
NG_007107.2:g.110775del
NM_004992.3:c.475delG

Links:

dbSNP: rs267608485

NCBI 1000 Genomes Browser:

rs267608485

Molecular consequence:

NM_001386137.1:c.-129+43del - intron variant - [Sequence Ontology: SO:0001627]
NM_001386138.1:c.-129+43del - intron variant - [Sequence Ontology: SO:0001627]
NM_001386139.1:c.-129+43del - intron variant - [Sequence Ontology: SO:0001627]
NM_001110792.2:c.511del - nonsense - [Sequence Ontology: SO:0001587]
NM_001316337.2:c.196del - nonsense - [Sequence Ontology: SO:0001587]
NM_001369391.2:c.196del - nonsense - [Sequence Ontology: SO:0001587]
NM_001369392.2:c.196del - nonsense - [Sequence Ontology: SO:0001587]
NM_001369393.2:c.196del - nonsense - [Sequence Ontology: SO:0001587]
NM_001369394.2:c.196del - nonsense - [Sequence Ontology: SO:0001587]
NM_004992.4:c.475del - 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

Recent activity

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solute carrier family 25 member 3 isoform b precursor [Homo sapiens]
solute carrier family 25 member 3 isoform b precursor [Homo sapiens]
gi|4505775|ref|NP_002626.1|

Protein
PRPS1L1 [Oryctolagus cuniculus]
PRPS1L1 [Oryctolagus cuniculus]
Gene ID:100357904

Gene
MGLL [Sorex araneus]
MGLL [Sorex araneus]
Gene ID:101549443

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000188123	RettBASE	no assertion criteria provided	Pathogenic (Jan 21, 2008)	unknown	curation	PubMed (1) [See all records that cite this PMID]
SCV004232193	Centre for Population Genomics, CPG	criteria provided, single submitter (McKnight et al. (Hum Mutat. 2022))	Likely pathogenic (Jan 15, 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

SCV000188123

RettBASE

no assertion criteria provided

Pathogenic
(Jan 21, 2008)

unknown

curation

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

SCV004232193

Centre for Population Genomics, CPG

criteria provided, single submitter

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

Likely pathogenic
(Jan 15, 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	unknown	yes	1	not provided	not provided	1	not provided	curation
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

Spectrum and distribution of MECP2 mutations in 424 Rett syndrome patients: a molecular update.

Philippe C, Villard L, De Roux N, Raynaud M, Bonnefond JP, Pasquier L, Lesca G, Mancini J, Jonveaux P, Moncla A, Chelly J, Bienvenu T.

Eur J Med Genet. 2006 Jan-Feb;49(1):9-18.

PubMed [citation]

PMID:: 16473305

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, SCV000188123.2

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

Description

"Rett syndrome - not certain"

PubMed [ID: 16473305]

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

From Centre for Population Genomics, CPG, SCV004232193.1

#	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: Predicted to result in loss of function, and LOF is a known mechanism of disease (PVS1). 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: Feb 28, 2024

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