NM_001110792.2(MECP2):c.1496G>C (p.Ter499Ser) AND Severe neonatal-onset encephalopathy with microcephaly

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 7, 2019
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:: RCV001035415.9

Allele description [Variation Report for NM_001110792.2(MECP2):c.1496G>C (p.Ter499Ser)]

NM_001110792.2(MECP2):c.1496G>C (p.Ter499Ser)

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.1496G>C (p.Ter499Ser)

Other names:

*499S; *394S; *487S

HGVS:

NC_000023.11:g.154030368C>G
NG_007107.3:g.111736G>C
NM_001110792.2:c.1496G>CMANE SELECT
NM_001316337.2:c.1181G>C
NM_001369391.2:c.1181G>C
NM_001369392.2:c.1181G>C
NM_001369393.2:c.1181G>C
NM_001369394.2:c.1181G>C
NM_001386137.1:c.791G>C
NM_001386138.1:c.791G>C
NM_001386139.1:c.791G>C
NM_004992.4:c.1460G>C
NP_001104262.1:p.Ter499Ser
NP_001303266.1:p.Ter394Ser
NP_001356320.1:p.Ter394Ser
NP_001356321.1:p.Ter394Ser
NP_001356322.1:p.Ter394Ser
NP_001356323.1:p.Ter394Ser
NP_001373066.1:p.Ter264Ser
NP_001373067.1:p.Ter264Ser
NP_001373068.1:p.Ter264Ser
NP_004983.1:p.Ter487Ser
NP_004983.1:p.Ter487Ser
LRG_764t1:c.1496G>C
LRG_764t2:c.1460G>C
LRG_764:g.111736G>C
LRG_764p1:p.Ter499Ser
LRG_764p2:p.Ter487Ser
NC_000023.10:g.153295819C>G
NG_007107.2:g.111760G>C
NM_004992.3:c.1460G>C

Links:

dbSNP: rs267608399

NCBI 1000 Genomes Browser:

rs267608399

Molecular consequence:

NM_001110792.2:c.1496G>C - stop lost - [Sequence Ontology: SO:0001578]
NM_001316337.2:c.1181G>C - stop lost - [Sequence Ontology: SO:0001578]
NM_001369391.2:c.1181G>C - stop lost - [Sequence Ontology: SO:0001578]
NM_001369392.2:c.1181G>C - stop lost - [Sequence Ontology: SO:0001578]
NM_001369393.2:c.1181G>C - stop lost - [Sequence Ontology: SO:0001578]
NM_001369394.2:c.1181G>C - stop lost - [Sequence Ontology: SO:0001578]
NM_001386137.1:c.791G>C - stop lost - [Sequence Ontology: SO:0001578]
NM_001386138.1:c.791G>C - stop lost - [Sequence Ontology: SO:0001578]
NM_001386139.1:c.791G>C - stop lost - [Sequence Ontology: SO:0001578]
NM_004992.4:c.1460G>C - stop lost - [Sequence Ontology: SO:0001578]

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
SCV001198741	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Mar 7, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001198741

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Mar 7, 2019)

germline

clinical testing

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

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001198741.5

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

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Disruption of the stop codon has been observed in individuals affected with Rett syndrome (PMID:¬†10814719,¬†11469283,¬†19722030). This variant is not present in population databases (ExAC no frequency). This sequence change disrupts the translational stop signal of the MECP2 mRNA. It is expected to extend the length of the MECP2 protein by 27 additional amino acid residues.

#	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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