NM_001110792.2(MECP2):c.724C>G (p.Pro242Ala) AND Severe neonatal-onset encephalopathy with microcephaly

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 10, 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:: RCV001900325.4

Allele description [Variation Report for NM_001110792.2(MECP2):c.724C>G (p.Pro242Ala)]

NM_001110792.2(MECP2):c.724C>G (p.Pro242Ala)

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.724C>G (p.Pro242Ala)

HGVS:

NC_000023.11:g.154031140G>C
NG_007107.3:g.110964C>G
NM_001110792.2:c.724C>GMANE SELECT
NM_001316337.2:c.409C>G
NM_001369391.2:c.409C>G
NM_001369392.2:c.409C>G
NM_001369393.2:c.409C>G
NM_001369394.2:c.409C>G
NM_001386137.1:c.19C>G
NM_001386138.1:c.19C>G
NM_001386139.1:c.19C>G
NM_004992.4:c.688C>G
NP_001104262.1:p.Pro242Ala
NP_001303266.1:p.Pro137Ala
NP_001356320.1:p.Pro137Ala
NP_001356321.1:p.Pro137Ala
NP_001356322.1:p.Pro137Ala
NP_001356323.1:p.Pro137Ala
NP_001373066.1:p.Pro7Ala
NP_001373067.1:p.Pro7Ala
NP_001373068.1:p.Pro7Ala
NP_004983.1:p.Pro230Ala
LRG_764t1:c.724C>G
LRG_764t2:c.688C>G
LRG_764:g.110964C>G
LRG_764p1:p.Pro242Ala
LRG_764p2:p.Pro230Ala
NC_000023.10:g.153296591G>C
NG_007107.2:g.110988C>G

Protein change:

P137A

Links:

dbSNP: rs1209806388

NCBI 1000 Genomes Browser:

rs1209806388

Molecular consequence:

NM_001110792.2:c.724C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001316337.2:c.409C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369391.2:c.409C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369392.2:c.409C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369393.2:c.409C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369394.2:c.409C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001386137.1:c.19C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001386138.1:c.19C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001386139.1:c.19C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_004992.4:c.688C>G - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002138385	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 10, 2023)	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

SCV002138385

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 10, 2023)

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, SCV002138385.3

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

Description

This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 230 of the MECP2 protein (p.Pro230Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MECP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1373281). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MECP2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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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