NM_001110792.2(MECP2):c.63-7080_1196del AND Severe neonatal-onset encephalopathy with microcephaly

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 31, 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:: RCV001233088.2

Allele description [Variation Report for NM_001110792.2(MECP2):c.63-7080_1196del]

NM_001110792.2(MECP2):c.63-7080_1196del

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.63-7080_1196del

HGVS:

NC_000023.11:g.154030668_154039637del
NC_000023.11:g.154030672_154039641del
NG_007107.2:g.102491_111460del
NM_001110792.2:c.63-7080_1196delMANE SELECT
NM_001316337.2:c.-253-7080_881del
NM_001369391.2:c.-253-7080_881del
NM_001369392.2:c.-254+155_881del
NM_001369393.2:c.-254+155_881del
NM_001369394.2:c.-253-7080_881del
NM_001386137.1:c.-535+155_491del
NM_001386138.1:c.-534-7080_491del
NM_001386139.1:c.-534-7080_491del
NM_004992.4:c.27-7080_1160del
LRG_764t1:c.63-7080_1196del
LRG_764t2:c.27-7080_1160del
NC_000023.10:g.153296123_153305092del
NM_004992.3:c.27-7080_1160del

Molecular consequence:

NM_001316337.2:c.-253-7080_881del - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001369391.2:c.-253-7080_881del - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001369392.2:c.-254+155_881del - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001369393.2:c.-254+155_881del - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001369394.2:c.-253-7080_881del - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001386137.1:c.-535+155_491del - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001386138.1:c.-534-7080_491del - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001386139.1:c.-534-7080_491del - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001110792.2:c.63-7080_1196del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001316337.2:c.-253-7080_881del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001369391.2:c.-253-7080_881del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001369392.2:c.-254+155_881del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001369393.2:c.-254+155_881del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001369394.2:c.-253-7080_881del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001386137.1:c.-535+155_491del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001386138.1:c.-534-7080_491del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001386139.1:c.-534-7080_491del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_004992.4:c.27-7080_1160del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001110792.2:c.63-7080_1196del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001316337.2:c.-253-7080_881del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001369391.2:c.-253-7080_881del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001369392.2:c.-254+155_881del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001369393.2:c.-254+155_881del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001369394.2:c.-253-7080_881del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001386137.1:c.-535+155_491del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001386138.1:c.-534-7080_491del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001386139.1:c.-534-7080_491del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_004992.4:c.27-7080_1160del - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001405668	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 31, 2019)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 21160487, 11746022, 12075485, 19914908, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001405668

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 31, 2019)

germline

clinical testing

PubMed (5)
[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

Analysis of Hungarian patients with Rett syndrome phenotype for MECP2, CDKL5 and FOXG1 gene mutations.

Hadzsiev K, Polgar N, Bene J, Komlosi K, Karteszi J, Hollody K, Kosztolanyi G, Renieri A, Melegh B.

J Hum Genet. 2011 Mar;56(3):183-7. doi: 10.1038/jhg.2010.156. Epub 2010 Dec 16.

PubMed [citation]

PMID:: 21160487

Preserved speech variants of the Rett syndrome: molecular and clinical analysis.

Zappella M, Meloni I, Longo I, Hayek G, Renieri A.

Am J Med Genet. 2001 Nov 15;104(1):14-22.

PubMed [citation]

PMID:: 11746022

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001405668.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This variant results in the deletion of exon 4 and part of exon 3 of the MECP2 gene (c.27-7080_1160delins59). While this is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant has not been reported in the literature in individuals with MECP2-related conditions. This variant disrupts the C-terminus of the MECP2 protein. Other variant(s) that disrupt this region (p.Leu386Argfs*8) have been determined to be pathogenic (PMID:19914908, 21160487, 11746022, 12075485, Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

#	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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