NM_001110792.2(MECP2):c.916C>T (p.Arg306Ter) AND Severe neonatal-onset encephalopathy with microcephaly

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 31, 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:: RCV000474366.9

Allele description [Variation Report for NM_001110792.2(MECP2):c.916C>T (p.Arg306Ter)]

NM_001110792.2(MECP2):c.916C>T (p.Arg306Ter)

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.916C>T (p.Arg306Ter)

Other names:

NP_004983.1:p.Arg294*; p.R294X:CGA>TGA; NM_001110792.2(MECP2):c.916C>T

HGVS:

NC_000023.11:g.154030948G>A
NG_007107.3:g.111156C>T
NM_001110792.1(MECP2):c.916C>T
NM_001110792.2:c.916C>TMANE SELECT
NM_001316337.2:c.601C>T
NM_001369391.2:c.601C>T
NM_001369392.2:c.601C>T
NM_001369393.2:c.601C>T
NM_001369394.2:c.601C>T
NM_001386137.1:c.211C>T
NM_001386138.1:c.211C>T
NM_001386139.1:c.211C>T
NM_004992.4:c.880C>T
NP_001104262.1:p.Arg306Ter
NP_001303266.1:p.Arg201Ter
NP_001356320.1:p.Arg201Ter
NP_001356321.1:p.Arg201Ter
NP_001356322.1:p.Arg201Ter
NP_001356323.1:p.Arg201Ter
NP_001373066.1:p.Arg71Ter
NP_001373067.1:p.Arg71Ter
NP_001373068.1:p.Arg71Ter
NP_004983.1:p.Arg294Ter
NP_004983.1:p.Arg294Ter
LRG_764t1:c.916C>T
LRG_764t2:c.880C>T
AJ132917.1:c.880C>T
LRG_764:g.111156C>T
LRG_764p1:p.Arg306Ter
LRG_764p2:p.Arg294Ter
NC_000023.10:g.153296399G>A
NG_007107.2:g.111180C>T
NM_001110792.1(MECP2):c.916C>T
NM_001110792.1:c.916C>T
NM_001110792.2:c.916C>T
NM_004992.3:c.880C>T
NM_004992.3:c.[880C>T]
p.Arg294X
p.Arg306Ter
p.R294X

Protein change:

R201*; ARG294TER

Links:

OMIM: 300005.0011; dbSNP: rs61751362

NCBI 1000 Genomes Browser:

rs61751362

Molecular consequence:

NM_001110792.2:c.916C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001316337.2:c.601C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001369391.2:c.601C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001369392.2:c.601C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001369393.2:c.601C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001369394.2:c.601C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001386137.1:c.211C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001386138.1:c.211C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001386139.1:c.211C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_004992.4:c.880C>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
SCV000544614	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 31, 2024)	germline	clinical testing	PubMed (12) [See all records that cite these PMIDs] 11241840, 15737703, 16473305, 17236109, 18332345, 19722030, 23270700, 11058114, 26604147, 27442528, 28785396, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000544614

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 31, 2024)

germline

clinical testing

PubMed (12)
[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

Mutation spectrum in patients with Rett syndrome in the German population: Evidence of hot spot regions.

Laccone F, Huppke P, Hanefeld F, Meins M.

Hum Mutat. 2001 Mar;17(3):183-90.

PubMed [citation]

PMID:: 11241840

Methyl-CpG binding protein 2 gene (MECP2) variations in Japanese patients with Rett syndrome: pathological mutations and polymorphisms.

Fukuda T, Yamashita Y, Nagamitsu S, Miyamoto K, Jin JJ, Ohmori I, Ohtsuka Y, Kuwajima K, Endo S, Iwai T, Yamagata H, Tabara Y, Miki T, Matsuishi T, Kondo I.

Brain Dev. 2005 Apr;27(3):211-7.

PubMed [citation]

PMID:: 15737703

See all PubMed Citations (12)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000544614.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (12)

Description

This sequence change creates a premature translational stop signal (p.Arg294*) in the MECP2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 193 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 individuals with Rett syndrome (PMID: 11241840, 15737703, 16473305, 17236109, 18332345, 19722030, 23270700). ClinVar contains an entry for this variant (Variation ID: 11819). 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, 26604147, 27442528, 28785396). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant disrupts a region of the MECP2 protein in which other variant(s) (p.Pro389*) have been determined to be pathogenic (Invitae). 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: Nov 24, 2024

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