NM_001110792.2(MECP2):c.413+6_413+9del AND Severe neonatal-onset encephalopathy with microcephaly

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 18, 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:: RCV002512555.9

Allele description [Variation Report for NM_001110792.2(MECP2):c.413+6_413+9del]

NM_001110792.2(MECP2):c.413+6_413+9del

Gene:

MECP2:methyl-CpG binding protein 2 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

Xq28

Genomic location:

Preferred name:

NM_001110792.2(MECP2):c.413+6_413+9del

HGVS:

NC_000023.11:g.154032201ACTT[1]
NG_007107.3:g.109899TAAG[1]
NM_001110792.2:c.413+6_413+9delMANE SELECT
NM_001316337.2:c.98+6_98+9del
NM_001369391.2:c.98+6_98+9del
NM_001369392.2:c.98+6_98+9del
NM_001369393.2:c.98+6_98+9del
NM_001369394.2:c.98+6_98+9del
NM_001386137.1:c.-184+6_-184+9del
NM_001386138.1:c.-184+6_-184+9del
NM_001386139.1:c.-184+6_-184+9del
NM_004992.4:c.377+6_377+9del
LRG_764t1:c.413+6_413+9del
LRG_764t2:c.377+6_377+9del
AJ132917.1:c.377+6_377+9del
LRG_764:g.109899TAAG[1]
NC_000023.10:g.153297649_153297652del
NC_000023.10:g.153297652ACTT[1]
NC_000023.10:g.153297656_153297659delACTT
NC_000023.11:g.154032205_154032208del
NG_007107.2:g.109923TAAG[1]
NM_004992.3:c.377+6_377+9del
NM_004992.3:c.377+6_377+9delTAAG
NM_004992.4:c.377+6_377+9delTAAG

Links:

dbSNP: rs267608459

NCBI 1000 Genomes Browser:

rs267608459

Molecular consequence:

NM_001110792.2:c.413+6_413+9del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001316337.2:c.98+6_98+9del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001369391.2:c.98+6_98+9del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001369392.2:c.98+6_98+9del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001369393.2:c.98+6_98+9del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001369394.2:c.98+6_98+9del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001386137.1:c.-184+6_-184+9del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001386138.1:c.-184+6_-184+9del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001386139.1:c.-184+6_-184+9del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_004992.4:c.377+6_377+9del - splice donor variant - [Sequence Ontology: SO:0001575]

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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RecName: Full=Fusion glycoprotein F0; Short=Protein F; Contains: RecName: Full=F...
RecName: Full=Fusion glycoprotein F0; Short=Protein F; Contains: RecName: Full=Fusion glycoprotein F2; Contains: RecName: Full=Fusion glycoprotein F1; Flags: Precursor
gi|75549953|sp|Q6WB98.1|FUS_HMPVC

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003450123	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 18, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 11106359, 17576681, 9536098, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003450123

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 18, 2022)

germline

clinical testing

PubMed (4)
[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

Spectrum of mutations in the MECP2 gene in patients with infantile autism and Rett syndrome.

Lam CW, Yeung WL, Ko CH, Poon PM, Tong SF, Chan KY, Lo IF, Chan LY, Hui J, Wong V, Pang CP, Lo YM, Fok TF.

J Med Genet. 2000 Dec;37(12):E41. No abstract available.

PubMed [citation]

PMID:: 11106359
PMCID:: PMC1734495

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]

PMID:: 17576681
PMCID:: PMC1934990

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003450123.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change falls in intron 3 of the MECP2 gene. It does not directly change the encoded amino acid sequence of the MECP2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs267608459, gnomAD 0.02%), including at least one homozygous and/or hemizygous individual. This variant has been observed in individual(s) with autism (PMID: 11106359). This variant is also known as IVS+2delTAAG. ClinVar contains an entry for this variant (Variation ID: 156059). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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: Nov 3, 2024

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