NM_001110792.2(MECP2):c.455C>T (p.Ala152Val) AND Syndromic X-linked intellectual disability Lubs type

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 23, 2022
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:: RCV002466399.9

Allele description [Variation Report for NM_001110792.2(MECP2):c.455C>T (p.Ala152Val)]

NM_001110792.2(MECP2):c.455C>T (p.Ala152Val)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

Xq28

Genomic location:

Preferred name:

NM_001110792.2(MECP2):c.455C>T (p.Ala152Val)

Other names:

NM_001110792.2(MECP2):c.455C>T; p.Ala152Val

HGVS:

NC_000023.11:g.154031409G>A
NG_007107.3:g.110695C>T
NM_001110792.2:c.455C>TMANE SELECT
NM_001316337.2:c.140C>T
NM_001369391.2:c.140C>T
NM_001369392.2:c.140C>T
NM_001369393.2:c.140C>T
NM_001369394.2:c.140C>T
NM_001386137.1:c.-142C>T
NM_001386138.1:c.-142C>T
NM_001386139.1:c.-142C>T
NM_004992.4:c.419C>T
NP_001104262.1:p.Ala152Val
NP_001303266.1:p.Ala47Val
NP_001356320.1:p.Ala47Val
NP_001356321.1:p.Ala47Val
NP_001356322.1:p.Ala47Val
NP_001356323.1:p.Ala47Val
NP_004983.1:p.Ala140Val
NP_004983.1:p.Ala140Val
NP_004983.1:p.Ala140Val
LRG_764t1:c.455C>T
LRG_764t2:c.419C>T
AJ132917.1:c.419C>T
LRG_764:g.110695C>T
LRG_764p1:p.Ala152Val
LRG_764p2:p.Ala140Val
NC_000023.10:g.153296860G>A
NG_007107.2:g.110719C>T
NM_001110792.1:c.455C>T
NM_001369391.2:c.140C>T
NM_004992.3:c.419C>T
NM_004992.4:c.419C>T
P51608:p.Ala140Val

Protein change:

A140V; ALA140VAL

Links:

UniProtKB: P51608#VAR_010279; OMIM: 300005.0015; dbSNP: rs28934908

NCBI 1000 Genomes Browser:

rs28934908

Molecular consequence:

NM_001386137.1:c.-142C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001386138.1:c.-142C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001386139.1:c.-142C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001110792.2:c.455C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001316337.2:c.140C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001369391.2:c.140C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001369392.2:c.140C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001369393.2:c.140C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001369394.2:c.140C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004992.4:c.419C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Syndromic X-linked intellectual disability Lubs type (MRXSL)
Synonyms:: MENTAL RETARDATION, X-LINKED, WITH RECURRENT RESPIRATORY INFECTIONS; Lubs X-linked mental retardation syndrome; XLMR syndrome, Lubs type; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010283; MedGen: C1846058; OMIM: 300260

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Gene ID:173174

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F07G11.2 Methyltransferase FkbM domain-containing protein [Caenorhabditis elegan...
F07G11.2 Methyltransferase FkbM domain-containing protein [Caenorhabditis elegans]
Gene ID:184157

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002761554	Genetics and Molecular Pathology, SA Pathology See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 23, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 11007980, 12325019, 25473036, 26350204, 27465203, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002761554

Genetics and Molecular Pathology, SA Pathology

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 23, 2022)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

MECP2 mutation in male patients with non-specific X-linked mental retardation.

Orrico A, Lam C, Galli L, Dotti MT, Hayek G, Tong SF, Poon PM, Zappella M, Federico A, Sorrentino V.

FEBS Lett. 2000 Sep 22;481(3):285-8.

PubMed [citation]

PMID:: 11007980

Identification of a family with nonspecific mental retardation (MRX79) with the A140V mutation in the MECP2 gene: is there a need for routine screening?

Winnepenninckx B, Errijgers V, Hayez-Delatte F, Reyniers E, Frank Kooy R.

Hum Mutat. 2002 Oct;20(4):249-52.

PubMed [citation]

PMID:: 12325019

See all PubMed Citations (6)

Details of each submission

From Genetics and Molecular Pathology, SA Pathology, SCV002761554.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

The MECP2 c.455C>T variant is classified as PATHOGENIC (PS4, PP1_strong, PM2, PP3) The MECP2 c.455C>T variant is a single nucleotide change in exon 3/3 of the MECP2 gene, which is predicted to change the amino acid alanine at position 152 in the protein to valine. This recurrent variant has been reported in multiple individuals with a clinical presentation of X-linked syndromic Intellectual disability or non-classic Rett phenotype (PS4). This variant has been reported in dbSNP (rs28934908) but is absent from population databases (PM2). This variant has been reported to co-segregate with disease in a large number of individuals in multiple families (PMID:11007980, PMID:26350204, PMID:25473036, PMID:27465203, PMID:12325019) (PP1_strong). Computational predictions support a deleterious effect on the gene or gene product (PP3). This variant has been reported in ClinVar as Pathogenic / Likely Pathogenic by other diagnostic laboratories (ClinVar Variation ID: 11823) and is classified as damaging in the HGMD disease database (CM003325).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 10, 2024

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