NM_001110792.2(MECP2):c.231del (p.Glu78fs) AND Severe neonatal-onset encephalopathy with microcephaly

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 15, 2020
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:: RCV001390003.7

Allele description [Variation Report for NM_001110792.2(MECP2):c.231del (p.Glu78fs)]

NM_001110792.2(MECP2):c.231del (p.Glu78fs)

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.231del (p.Glu78fs)

HGVS:

NC_000023.11:g.154032389del
NG_007107.3:g.109715del
NM_001110792.2:c.231delMANE SELECT
NM_001316337.2:c.-85del
NM_001369391.2:c.-85del
NM_001369392.2:c.-85del
NM_001369393.2:c.-85del
NM_001369394.2:c.-85del
NM_001386137.1:c.-366del
NM_001386138.1:c.-366del
NM_001386139.1:c.-366del
NM_004992.4:c.195del
NP_001104262.1:p.Glu78fs
NP_004983.1:p.Glu66fs
LRG_764t1:c.231del
LRG_764t2:c.195del
LRG_764:g.109715del
LRG_764p1:p.Glu78fs
LRG_764p2:p.Glu66fs
NC_000023.10:g.153297840del
NG_007107.2:g.109739del

Protein change:

E66fs

Links:

dbSNP: rs2148666876

NCBI 1000 Genomes Browser:

rs2148666876

Molecular consequence:

NM_001316337.2:c.-85del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001369391.2:c.-85del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001369392.2:c.-85del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001369393.2:c.-85del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001369394.2:c.-85del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001386137.1:c.-366del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001386138.1:c.-366del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001386139.1:c.-366del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001110792.2:c.231del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004992.4:c.195del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV001591571	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 15, 2020)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 10577905, 23270700, 24511209, 11058114, 24283265, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001591571

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 15, 2020)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Rett syndrome and beyond: recurrent spontaneous and familial MECP2 mutations at CpG hotspots.

Wan M, Lee SS, Zhang X, Houwink-Manville I, Song HR, Amir RE, Budden S, Naidu S, Pereira JL, Lo IF, Zoghbi HY, Schanen NC, Francke U.

Am J Hum Genet. 1999 Dec;65(6):1520-9.

PubMed [citation]

PMID:: 10577905
PMCID:: PMC1288362

Pubertal trajectory in females with Rett syndrome: a population-based study.

Knight O, Bebbington A, Siafarikas A, Woodhead H, Girdler S, Leonard H.

Brain Dev. 2013 Nov;35(10):912-20. doi: 10.1016/j.braindev.2012.11.007. Epub 2012 Dec 25.

PubMed [citation]

PMID:: 23270700

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001591571.4

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the MECP2 protein. Other variant(s) that disrupt this region (p.Arg168*) have been determined to be pathogenic (PMID: 10577905, 23270700, 24511209, 11058114, 24283265). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has not been reported in the literature in individuals with MECP2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the MECP2 gene (p.Glu66Lysfs*59). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 421 amino acids of the MECP2 protein.

#	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: Sep 29, 2024

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