NM_001110792.2(MECP2):c.524_1225del (p.Gly175_Ser408del) AND Rett syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 16, 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:: RCV000170206.3

Allele description [Variation Report for NM_001110792.2(MECP2):c.524_1225del (p.Gly175_Ser408del)]

NM_001110792.2(MECP2):c.524_1225del (p.Gly175_Ser408del)

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.524_1225del (p.Gly175_Ser408del)

Other names:

NM_001110792.2(MECP2):c.524_1225del; p.Gly175_Ser408del

HGVS:

NC_000023.11:g.154030640_154031341del
NG_007107.3:g.110764_111465del
NM_001110792.2:c.524_1225delMANE SELECT
NM_001316337.2:c.209_910del
NM_001369391.2:c.209_910del
NM_001369392.2:c.209_910del
NM_001369393.2:c.209_910del
NM_001369394.2:c.209_910del
NM_001386137.1:c.-128-54_520del
NM_001386138.1:c.-128-54_520del
NM_001386139.1:c.-128-54_520del
NM_004992.4:c.488_1189del
NP_001104262.1:p.Gly175_Ser408del
NP_001303266.1:p.Gly70_Ser303del
NP_001356320.1:p.Gly70_Ser303del
NP_001356321.1:p.Gly70_Ser303del
NP_001356322.1:p.Gly70_Ser303del
NP_001356323.1:p.Gly70_Ser303del
NP_004983.1:p.Gly163_Ser396del
LRG_764t1:c.524_1225del
LRG_764t2:c.488_1189del
LRG_764:g.110764_111465del
LRG_764p1:p.Gly175_Ser408del
LRG_764p2:p.Gly163_Ser396del
NC_000023.10:g.153296091_153296792del
NG_007107.2:g.110788_111489del
NM_004992.3:c.488_1189del702

Links:

dbVar: nssv7487114; dbVar: nsv1197414; dbSNP: rs1557135461

NCBI 1000 Genomes Browser:

rs1557135461

Molecular consequence:

NM_001110792.2:c.524_1225del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001316337.2:c.209_910del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001369391.2:c.209_910del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001369392.2:c.209_910del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001369393.2:c.209_910del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001369394.2:c.209_910del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_004992.4:c.488_1189del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001386137.1:c.-128-54_520del - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001386138.1:c.-128-54_520del - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001386139.1:c.-128-54_520del - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001386137.1:c.-128-54_520del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001386138.1:c.-128-54_520del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001386139.1:c.-128-54_520del - splice acceptor variant - [Sequence Ontology: SO:0001574]

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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Homo sapiens FA core complex associated protein 20 (FAAP20), transcript variant ...
Homo sapiens FA core complex associated protein 20 (FAAP20), transcript variant 6, mRNA
gi|1890328008|ref|NM_001282670.2|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000222535	RettBASE	no assertion criteria provided	Pathogenic (Jan 21, 2008)	unknown	curation	PubMed (1) [See all records that cite this PMID]
SCV004232241	Centre for Population Genomics, CPG	criteria provided, single submitter (McKnight et al. (Hum Mutat. 2022))	Pathogenic (Jan 16, 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

SCV000222535

RettBASE

no assertion criteria provided

Pathogenic
(Jan 21, 2008)

unknown

curation

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

SCV004232241

Centre for Population Genomics, CPG

criteria provided, single submitter

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

Pathogenic
(Jan 16, 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	unknown	yes	1	not provided	not provided	1	not provided	curation
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

Spectrum and distribution of MECP2 mutations in 424 Rett syndrome patients: a molecular update.

Philippe C, Villard L, De Roux N, Raynaud M, Bonnefond JP, Pasquier L, Lesca G, Mancini J, Jonveaux P, Moncla A, Chelly J, Bienvenu T.

Eur J Med Genet. 2006 Jan-Feb;49(1):9-18.

PubMed [citation]

PMID:: 16473305

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, SCV000222535.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	curation	PubMed (1)

Description

"Rett syndrome - not certain"

PubMed [ID: 16473305]

#	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, SCV004232241.1

#	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: This variant removes >20% of the protein, including the transcriptional repression domain (TRD) of MECP2. Predicted to result in loss of function, and LOF is a known mechanism of disease (PVS1). Protein length changes due to in-frame deletions/insertions in a non-repeat region (PM4). 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: Feb 28, 2024

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