NM_001110792.2(MECP2):c.42A>C (p.Gly14=) AND Severe neonatal-onset encephalopathy with microcephaly

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 15, 2022
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:: RCV002572166.3

Allele description [Variation Report for NM_001110792.2(MECP2):c.42A>C (p.Gly14=)]

NM_001110792.2(MECP2):c.42A>C (p.Gly14=)

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.42A>C (p.Gly14=)

HGVS:

NC_000023.11:g.154097624T>G
NG_007107.3:g.44480A>C
NM_001110792.2:c.42A>CMANE SELECT
NM_001316337.2:c.-566A>C
NM_001369391.2:c.-861A>C
NM_001369392.2:c.-510A>C
NM_001369393.2:c.-386A>C
NM_001386137.1:c.-791A>C
NM_001386138.1:c.-679A>C
NM_001386139.1:c.-555A>C
NM_004992.4:c.-119A>C
NP_001104262.1:p.Gly14=
LRG_764t1:c.42A>C
LRG_764t2:c.-119A>C
LRG_764:g.44480A>C
LRG_764p1:p.Gly14=
NC_000023.10:g.153363081T>G

Molecular consequence:

NM_001316337.2:c.-566A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001369391.2:c.-861A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001369392.2:c.-510A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001369393.2:c.-386A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001386137.1:c.-791A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001386138.1:c.-679A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001386139.1:c.-555A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_004992.4:c.-119A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001110792.2:c.42A>C - synonymous variant - [Sequence Ontology: SO:0001819]

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

Recent activity

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recombination activating protein 2, partial [Percichthys trucha]
recombination activating protein 2, partial [Percichthys trucha]
gi|2293348427|gb|UVW56683.1|

Protein
Mus musculus keratin 40, mRNA (cDNA clone MGC:141167 IMAGE:40055959), complete c...
Mus musculus keratin 40, mRNA (cDNA clone MGC:141167 IMAGE:40055959), complete cds
gi|115528516|gb|BC119522.2|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002932510	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 15, 2022)	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

SCV002932510

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 15, 2022)

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, SCV002932510.2

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

Description

Experimental studies and prediction algorithms are not available or were not evaluated, and the effect of this variant on mRNA splicing is currently unknown. This variant has not been reported in the literature in individuals affected with MECP2-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change affects codon 14 of the MECP2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the MECP2 protein. The MECP2 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_001110792.1, and corresponds to NM_004992.3:c.-119A>C in the primary transcript. 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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