NM_001110792.2(MECP2):c.713_714insA (p.Phe238fs) AND Rett syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 12, 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:: RCV000133196.4

Allele description [Variation Report for NM_001110792.2(MECP2):c.713_714insA (p.Phe238fs)]

NM_001110792.2(MECP2):c.713_714insA (p.Phe238fs)

Gene:

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

Variant type:

Insertion

Cytogenetic location:

Xq28

Genomic location:

Preferred name:

NM_001110792.2(MECP2):c.713_714insA (p.Phe238fs)

Other names:

NM_001110792.2(MECP2):c.713_714insA; p.Phe238fs

HGVS:

NC_000023.11:g.154031150_154031151insT
NG_007107.3:g.110953_110954insA
NM_001110792.2:c.713_714insAMANE SELECT
NM_001316337.2:c.398_399insA
NM_001369391.2:c.398_399insA
NM_001369392.2:c.398_399insA
NM_001369393.2:c.398_399insA
NM_001369394.2:c.398_399insA
NM_001386137.1:c.8_9insA
NM_001386138.1:c.8_9insA
NM_001386139.1:c.8_9insA
NM_004992.4:c.677_678insA
NP_001104262.1:p.Phe238fs
NP_001303266.1:p.Phe133fs
NP_001356320.1:p.Phe133fs
NP_001356321.1:p.Phe133fs
NP_001356322.1:p.Phe133fs
NP_001356323.1:p.Phe133fs
NP_001373066.1:p.Phe3fs
NP_001373067.1:p.Phe3fs
NP_001373068.1:p.Phe3fs
NP_004983.1:p.Phe226fs
NP_004983.1:p.Phe226fs
LRG_764t1:c.713_714insA
LRG_764t2:c.677_678insA
AJ132917.1:c.677_678insA
LRG_764:g.110953_110954insA
LRG_764p1:p.Phe238fs
LRG_764p2:p.Phe226fs
NC_000023.10:g.153296601_153296602insT
NG_007107.2:g.110977_110978insA
NM_004992.3:c.677_678insA

Protein change:

F133fs

Links:

dbSNP: rs61749736

NCBI 1000 Genomes Browser:

rs61749736

Molecular consequence:

NM_001110792.2:c.713_714insA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001316337.2:c.398_399insA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369391.2:c.398_399insA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369392.2:c.398_399insA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369393.2:c.398_399insA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369394.2:c.398_399insA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001386137.1:c.8_9insA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001386138.1:c.8_9insA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001386139.1:c.8_9insA - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004992.4:c.677_678insA - 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
SCV000188194	RettBASE	no assertion criteria provided	Pathogenic (Apr 10, 2002)	de novo	curation	PubMed (1) [See all records that cite this PMID]
SCV004232327	Centre for Population Genomics, CPG	criteria provided, single submitter (McKnight et al. (Hum Mutat. 2022))	Pathogenic (Jan 12, 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

SCV000188194

RettBASE

no assertion criteria provided

Pathogenic
(Apr 10, 2002)

de novo

curation

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

SCV004232327

Centre for Population Genomics, CPG

criteria provided, single submitter

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

Pathogenic
(Jan 12, 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	de novo	yes	1	not provided	not provided	1	No	curation
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

MECP2 mutations account for most cases of typical forms of Rett syndrome.

Bienvenu T, Carrié A, de Roux N, Vinet MC, Jonveaux P, Couvert P, Villard L, Arzimanoglou A, Beldjord C, Fontes M, Tardieu M, Chelly J.

Hum Mol Genet. 2000 May 22;9(9):1377-84.

PubMed [citation]

PMID:: 10814719

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, SCV000188194.2

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

Description

"Rett syndrome - Classical"

PubMed [ID: 10814719]

#	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

From Centre for Population Genomics, CPG, SCV004232327.1

#	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: 11313764 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: 11313764, PMID: 10814719

#	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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