NM_001110792.2(MECP2):c.799C>T (p.Arg267Ter) AND Severe neonatal-onset encephalopathy with microcephaly

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 25, 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:: RCV000553858.16

Allele description [Variation Report for NM_001110792.2(MECP2):c.799C>T (p.Arg267Ter)]

NM_001110792.2(MECP2):c.799C>T (p.Arg267Ter)

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.799C>T (p.Arg267Ter)

Other names:

p.R255*:CGA>TGA; NM_001110792.2(MECP2):c.799C>T; p.Arg267Ter

HGVS:

NC_000023.11:g.154031065G>A
NG_007107.3:g.111039C>T
NM_001110792.2:c.799C>TMANE SELECT
NM_001316337.2:c.484C>T
NM_001369391.2:c.484C>T
NM_001369392.2:c.484C>T
NM_001369393.2:c.484C>T
NM_001369394.2:c.484C>T
NM_001386137.1:c.94C>T
NM_001386138.1:c.94C>T
NM_001386139.1:c.94C>T
NM_004992.4:c.763C>T
NP_001104262.1:p.Arg267Ter
NP_001303266.1:p.Arg162Ter
NP_001356320.1:p.Arg162Ter
NP_001356321.1:p.Arg162Ter
NP_001356322.1:p.Arg162Ter
NP_001356323.1:p.Arg162Ter
NP_001373066.1:p.Arg32Ter
NP_001373067.1:p.Arg32Ter
NP_001373068.1:p.Arg32Ter
NP_004983.1:p.Arg255Ter
NP_004983.1:p.Arg255Ter
LRG_764t1:c.799C>T
LRG_764t2:c.763C>T
AJ132917.1:c.763C>T
LRG_764:g.111039C>T
LRG_764p1:p.Arg267Ter
LRG_764p2:p.Arg255Ter
NC_000023.10:g.153296516G>A
NG_007107.2:g.111063C>T
NM_001110792.1:c.799C>T
NM_004992.3:c.763C>T
NM_004992.4:c.763C>T
NP_004983.1:p.Arg255*
p.(Arg255*)
p.Arg255X

Protein change:

R162*; ARG255TER

Links:

OMIM: 300005.0021; dbSNP: rs61749721

NCBI 1000 Genomes Browser:

rs61749721

Molecular consequence:

NM_001110792.2:c.799C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001316337.2:c.484C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001369391.2:c.484C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001369392.2:c.484C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001369393.2:c.484C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001369394.2:c.484C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001386137.1:c.94C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001386138.1:c.94C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001386139.1:c.94C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_004992.4:c.763C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Severe neonatal-onset encephalopathy with microcephaly
Synonyms:: Encephalopathy, neonatal severe; Encephalopathy, neonatal severe, due to MECP2 mutations
Identifiers:: MONDO: MONDO:0010397; MedGen: C1968556; Orphanet: 209370; OMIM: 300673

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000645677	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 25, 2023)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 1241840, 10508514, 17089071, 23270700, 25634563, 11058114, 11241840, 18174548, 23238081, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000645677

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 25, 2023)

germline

clinical testing

PubMed (10)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

[Technic of the entire cochleogram for the study of the cochlea in guinea pigs].

Crifò S, Sidoli A.

Boll Soc Ital Biol Sper. 1975 Dec 15;51(23):1850-3. Italian. No abstract available.

PubMed [citation]

PMID:: 1241840

Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2.

Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY.

Nat Genet. 1999 Oct;23(2):185-8.

PubMed [citation]

PMID:: 10508514

See all PubMed Citations (10)

Details of each submission

From Invitae, SCV000645677.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

Description

This sequence change creates a premature translational stop signal (p.Arg255*) in the MECP2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 232 amino acid(s) of the MECP2 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Rett syndrome (PMID: 1241840, 10508514, 17089071, 23270700). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 11829). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects MECP2 function (PMID: 11058114, 23238081, 25634563). This variant disrupts a region of the MECP2 protein in which other variant(s) (p.Arg270*) have been determined to be pathogenic (PMID: 11058114, 11241840, 18174548, 23238081). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	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: Jun 17, 2024

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