NM_001110792.2(MECP2):c.1168_1243del (p.Ala390fs) AND Rett syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 21, 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:: RCV003991408.1

Allele description [Variation Report for NM_001110792.2(MECP2):c.1168_1243del (p.Ala390fs)]

NM_001110792.2(MECP2):c.1168_1243del (p.Ala390fs)

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.1168_1243del (p.Ala390fs)

Other names:

NM_004992.4:c.1132_1207del

HGVS:

NC_000023.11:g.154030621_154030696del
NG_007107.3:g.111408_111483del
NM_001110792.2:c.1168_1243delMANE SELECT
NM_001316337.2:c.853_928del
NM_001369391.2:c.853_928del
NM_001369392.2:c.853_928del
NM_001369393.2:c.853_928del
NM_001369394.2:c.853_928del
NM_001386137.1:c.463_538del
NM_001386138.1:c.463_538del
NM_001386139.1:c.463_538del
NM_004992.4:c.1132_1207del
NP_001104262.1:p.Ala390fs
NP_001303266.1:p.Ala285fs
NP_001356320.1:p.Ala285fs
NP_001356321.1:p.Ala285fs
NP_001356322.1:p.Ala285fs
NP_001356323.1:p.Ala285fs
NP_001373066.1:p.Ala155fs
NP_001373067.1:p.Ala155fs
NP_001373068.1:p.Ala155fs
NP_004983.1:p.Ala378fs
LRG_764t1:c.1168_1243del
LRG_764t2:c.1132_1207del
LRG_764:g.111408_111483del
LRG_764p1:p.Ala390fs
LRG_764p2:p.Ala378fs
NC_000023.10:g.153296072_153296147del

Protein change:

A155fs

Molecular consequence:

NM_001110792.2:c.1168_1243del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001316337.2:c.853_928del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369391.2:c.853_928del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369392.2:c.853_928del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369393.2:c.853_928del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369394.2:c.853_928del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001386137.1:c.463_538del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001386138.1:c.463_538del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001386139.1:c.463_538del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004992.4:c.1132_1207del - 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

Recent activity

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RecName: Full=Anamorsin; AltName: Full=Cytokine-induced apoptosis inhibitor 1; A...
RecName: Full=Anamorsin; AltName: Full=Cytokine-induced apoptosis inhibitor 1; AltName: Full=Fe-S cluster assembly protein DRE2 homolog
gi|57012707|sp|Q8WTY4.1|CPIN1_MOUSE

Protein
LOC127885211 [Homo sapiens]
LOC127885211 [Homo sapiens]
Gene ID:127885211

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004808947	Centre for Population Genomics, CPG	criteria provided, single submitter (McKnight et al. (Hum Mutat. 2022))	Pathogenic (Feb 21, 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

SCV004808947

Centre for Population Genomics, CPG

criteria provided, single submitter

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

Pathogenic
(Feb 21, 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, SCV004808947.1

#	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). Has been observed in at least 5 individuals with phenotypes consistent with MECP2-related disease (PS4). PMID: 31958484, 21178819, 12075485, 19914908, 11738879 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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