NM_001110792.2(MECP2):c.1451_1452del (p.Glu484fs) AND Rett syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 17, 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:: RCV003483515.2

Allele description [Variation Report for NM_001110792.2(MECP2):c.1451_1452del (p.Glu484fs)]

NM_001110792.2(MECP2):c.1451_1452del (p.Glu484fs)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

Xq28

Genomic location:

Preferred name:

NM_001110792.2(MECP2):c.1451_1452del (p.Glu484fs)

Other names:

NM_004992.4:c.1415_1416del

HGVS:

NC_000023.11:g.154030412CT[2]
NG_007107.3:g.111687AG[2]
NM_001110792.2:c.1451_1452delMANE SELECT
NM_001316337.2:c.1136_1137del
NM_001369391.2:c.1136_1137del
NM_001369392.2:c.1136_1137del
NM_001369393.2:c.1136_1137del
NM_001369394.2:c.1136_1137del
NM_001386137.1:c.746_747del
NM_001386138.1:c.746_747del
NM_001386139.1:c.746_747del
NM_004992.4:c.1415_1416del
NP_001104262.1:p.Glu484fs
NP_001303266.1:p.Glu379fs
NP_001356320.1:p.Glu379fs
NP_001356321.1:p.Glu379fs
NP_001356322.1:p.Glu379fs
NP_001356323.1:p.Glu379fs
NP_001373066.1:p.Glu249fs
NP_001373067.1:p.Glu249fs
NP_001373068.1:p.Glu249fs
NP_004983.1:p.Glu472fs
LRG_764t1:c.1451_1452del
LRG_764t2:c.1415_1416del
AJ132917.1:c.1415_1416delAG
LRG_764:g.111687AG[2]
LRG_764p1:p.Glu484fs
LRG_764p2:p.Glu472fs
NC_000023.10:g.153295863CT[2]
NC_000023.11:g.154030416_154030417del
NG_007107.2:g.111711AG[2]
NM_004992.3:c.1415_1416del
NM_004992.3:c.1415_1416delAG

Protein change:

E249fs

Links:

dbSNP: rs267608634

NCBI 1000 Genomes Browser:

rs267608634

Molecular consequence:

NM_001110792.2:c.1451_1452del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001316337.2:c.1136_1137del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369391.2:c.1136_1137del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369392.2:c.1136_1137del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369393.2:c.1136_1137del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369394.2:c.1136_1137del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001386137.1:c.746_747del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001386138.1:c.746_747del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001386139.1:c.746_747del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004992.4:c.1415_1416del - 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
SCV004232255	Centre for Population Genomics, CPG	criteria provided, single submitter (McKnight et al. (Hum Mutat. 2022))	Likely pathogenic (Jan 17, 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

SCV004232255

Centre for Population Genomics, CPG

criteria provided, single submitter

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

Likely pathogenic
(Jan 17, 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

Citations

PubMed

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 Centre for Population Genomics, CPG, SCV004232255.1

#	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: This variant has been identified as a de novo occurrence in an individual with MECP2 related disease with confirmed parental relationships (PS2) PMID: 12111644, PMID: 12081720 This variant is absent from gnomAD (PM2_Supporting). Truncating variant distal of p.Glu472 which is the most distal truncating variant in an affected patient reported to date (PMID: 12081720). LOF is a known mechanism of disease (PVS1_Moderate).

#	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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