NM_001110792.2(MECP2):c.1188_*29del (p.Pro396_Ter499delinsXaa) AND Rett syndrome

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Aug 14, 2023
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:: RCV000170144.2

Allele description [Variation Report for NM_001110792.2(MECP2):c.1188_*29del (p.Pro396_Ter499delinsXaa)]

NM_001110792.2(MECP2):c.1188_*29del (p.Pro396_Ter499delinsXaa)

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.1188_*29del (p.Pro396_Ter499delinsXaa)

Other names:

NM_001110792.2(MECP2):c.1188_*29del; p.Pro396_Ter499delinsXaa

HGVS:

NC_000023.11:g.154030339_154030677del
NG_007107.3:g.111428_111766del
NM_001110792.2:c.1188_*29delMANE SELECT
NM_001316337.2:c.873_*29del
NM_001369391.2:c.873_*29del
NM_001369392.2:c.873_*29del
NM_001369393.2:c.873_*29del
NM_001369394.2:c.873_*29del
NM_001386137.1:c.483_*29del
NM_001386138.1:c.483_*29del
NM_001386139.1:c.483_*29del
NM_004992.4:c.1152_*29del
NP_001104262.1:p.Pro396_Ter499delinsXaa
NP_001303266.1:p.Pro291_Ter394delinsXaa
NP_001356320.1:p.Pro291_Ter394delinsXaa
NP_001356321.1:p.Pro291_Ter394delinsXaa
NP_001356322.1:p.Pro291_Ter394delinsXaa
NP_001356323.1:p.Pro291_Ter394delinsXaa
NP_001373066.1:p.Pro161_Ter264delinsXaa
NP_001373067.1:p.Pro161_Ter264delinsXaa
NP_001373068.1:p.Pro161_Ter264delinsXaa
NP_004983.1:p.Pro384_Ter487delinsXaa
LRG_764t1:c.1188_*29del
LRG_764t2:c.1152_*29del
LRG_764:g.111428_111766del
LRG_764p1:p.Pro396_Ter499delinsXaa
LRG_764p2:p.Pro384_Ter487delinsXaa
NC_000023.10:g.153295790_153296128del
NG_007107.2:g.111452_111790del

Links:

dbVar: nssv7487073; dbVar: nsv1197465; dbSNP: rs1557134779

NCBI 1000 Genomes Browser:

rs1557134779

Molecular consequence:

NM_001110792.2:c.1188_*29del - stop lost - [Sequence Ontology: SO:0001578]
NM_001316337.2:c.873_*29del - stop lost - [Sequence Ontology: SO:0001578]
NM_001369391.2:c.873_*29del - stop lost - [Sequence Ontology: SO:0001578]
NM_001369392.2:c.873_*29del - stop lost - [Sequence Ontology: SO:0001578]
NM_001369393.2:c.873_*29del - stop lost - [Sequence Ontology: SO:0001578]
NM_001369394.2:c.873_*29del - stop lost - [Sequence Ontology: SO:0001578]
NM_001386137.1:c.483_*29del - stop lost - [Sequence Ontology: SO:0001578]
NM_001386138.1:c.483_*29del - stop lost - [Sequence Ontology: SO:0001578]
NM_001386139.1:c.483_*29del - stop lost - [Sequence Ontology: SO:0001578]
NM_004992.4:c.1152_*29del - stop lost - [Sequence Ontology: SO:0001578]

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
SCV000222472	RettBASE	no assertion criteria provided	Pathogenic (Jun 12, 2013)	unknown	curation	PubMed (1) [See all records that cite this PMID]
SCV004098777	Centre for Population Genomics, CPG	criteria provided, single submitter (McKnight et al. (Hum Mutat. 2022))	Likely pathogenic (Aug 14, 2023)	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

SCV000222472

RettBASE

no assertion criteria provided

Pathogenic
(Jun 12, 2013)

unknown

curation

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

SCV004098777

Centre for Population Genomics, CPG

criteria provided, single submitter

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

Likely pathogenic
(Aug 14, 2023)

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	No	curation
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

Spectrum of MECP2 gene mutations in a cohort of Indian patients with Rett syndrome: report of two novel mutations.

Das DK, Raha S, Sanghavi D, Maitra A, Udani V.

Gene. 2013 Feb 15;515(1):78-83. doi: 10.1016/j.gene.2012.11.024. Epub 2012 Dec 20.

PubMed [citation]

PMID:: 23262346

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, SCV000222472.1

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

Description

"Rett syndrome - atypical"

PubMed [ID: 23262346]

#	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, SCV004098777.1

#	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 2.0, 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: Oct 28, 2023

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