NM_001110792.2(MECP2):c.602del (p.Gly201fs) AND Rett syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 18, 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:: RCV000133161.3

Allele description [Variation Report for NM_001110792.2(MECP2):c.602del (p.Gly201fs)]

NM_001110792.2(MECP2):c.602del (p.Gly201fs)

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.602del (p.Gly201fs)

Other names:

NM_001110792.2(MECP2):c.602del; p.Gly201fs

HGVS:

NC_000023.11:g.154031265del
NG_007107.3:g.110842del
NM_001110792.2:c.602delMANE SELECT
NM_001316337.2:c.287del
NM_001369391.2:c.287del
NM_001369392.2:c.287del
NM_001369393.2:c.287del
NM_001369394.2:c.287del
NM_001386137.1:c.-104del
NM_001386138.1:c.-104del
NM_001386139.1:c.-104del
NM_004992.4:c.566del
NP_001104262.1:p.Gly201fs
NP_001303266.1:p.Gly96fs
NP_001356320.1:p.Gly96fs
NP_001356321.1:p.Gly96fs
NP_001356322.1:p.Gly96fs
NP_001356323.1:p.Gly96fs
NP_004983.1:p.Gly189fs
LRG_764t1:c.602del
LRG_764t2:c.566del
AJ132917.1:c.566delG
LRG_764:g.110842del
LRG_764p1:p.Gly201fs
LRG_764p2:p.Gly189fs
NC_000023.10:g.153296716del
NG_007107.2:g.110866del
NM_004992.3:c.566delG

Protein change:

G189fs

Links:

dbSNP: rs61749708

NCBI 1000 Genomes Browser:

rs61749708

Molecular consequence:

NM_001386137.1:c.-104del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001386138.1:c.-104del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001386139.1:c.-104del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001110792.2:c.602del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001316337.2:c.287del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369391.2:c.287del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369392.2:c.287del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369393.2:c.287del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369394.2:c.287del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004992.4:c.566del - 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
SCV000188153	RettBASE	no assertion criteria provided	Pathogenic (Sep 5, 2002)	unknown	curation	PubMed (1) [See all records that cite this PMID]
SCV004808809	Centre for Population Genomics, CPG	criteria provided, single submitter (McKnight et al. (Hum Mutat. 2022))	Pathogenic (Mar 18, 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

SCV000188153

RettBASE

no assertion criteria provided

Pathogenic
(Sep 5, 2002)

unknown

curation

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

SCV004808809

Centre for Population Genomics, CPG

criteria provided, single submitter

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

Pathogenic
(Mar 18, 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	1	not provided	not provided	1	No	curation

Citations

PubMed

Mutation analysis of the MECP2 gene in British and Italian Rett syndrome females.

Vacca M, Filippini F, Budillon A, Rossi V, Mercadante G, Manzati E, Gualandi F, Bigoni S, Trabanelli C, Pini G, Calzolari E, Ferlini A, Meloni I, Hayek G, Zappella M, Renieri A, D'Urso M, D'Esposito M, MacDonald F, Kerr A, Dhanjal S, Hultén M.

J Mol Med (Berl). 2001;78(11):648-55.

PubMed [citation]

PMID:: 11269512

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, SCV000188153.2

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

Description

"Rett syndrome - Classical"

PubMed [ID: 11269512]

#	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, SCV004808809.1

#	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). At least one individual with this variant has been reported with a clinical phenotype consistent with Rett syndrome (PP4). PMID 11269512 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: Apr 15, 2024

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