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NM_001110792.2(MECP2):c.136_139del (p.Asp46fs) AND Severe neonatal-onset encephalopathy with microcephaly

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 1, 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:
RCV001219819.8

Allele description [Variation Report for NM_001110792.2(MECP2):c.136_139del (p.Asp46fs)]

NM_001110792.2(MECP2):c.136_139del (p.Asp46fs)

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.136_139del (p.Asp46fs)
Other names:
NM_001110792.2(MECP2):c.136_139del; p.Asp46fs
HGVS:
  • NC_000023.11:g.154032482_154032485del
  • NG_007107.3:g.109620_109623del
  • NM_001110792.2:c.136_139delMANE SELECT
  • NM_001316337.2:c.-180_-177del
  • NM_001369391.2:c.-180_-177del
  • NM_001369392.2:c.-180_-177del
  • NM_001369393.2:c.-180_-177del
  • NM_001369394.2:c.-180_-177del
  • NM_001386137.1:c.-461_-458del
  • NM_001386138.1:c.-461_-458del
  • NM_001386139.1:c.-461_-458del
  • NM_004992.4:c.100_103del
  • NP_001104262.1:p.Asp46fs
  • NP_004983.1:p.Asp34fs
  • NP_004983.1:p.Asp34fs
  • LRG_764t1:c.136_139del
  • LRG_764t2:c.100_103del
  • AJ132917.1:c.100_103delGATA
  • LRG_764:g.109620_109623del
  • LRG_764p1:p.Asp46fs
  • LRG_764p2:p.Asp34fs
  • NC_000023.10:g.153297932_153297935del
  • NC_000023.10:g.153297933_153297936del
  • NG_007107.2:g.109644_109647del
  • NM_004992.3:c.100_103del
  • NM_004992.3:c.100_103delGATA
Protein change:
D34fs
Links:
dbSNP: rs61754428
NCBI 1000 Genomes Browser:
rs61754428
Molecular consequence:
  • NM_001316337.2:c.-180_-177del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001369391.2:c.-180_-177del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001369392.2:c.-180_-177del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001369393.2:c.-180_-177del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001369394.2:c.-180_-177del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001386137.1:c.-461_-458del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001386138.1:c.-461_-458del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001386139.1:c.-461_-458del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001110792.2:c.136_139del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_004992.4:c.100_103del - frameshift variant - [Sequence Ontology: SO:0001589]

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001391777Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Apr 1, 2022) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

[Technic of the entire cochleogram for the study of the cochlea in guinea pigs].

Crifò S, Sidoli A.

Boll Soc Ital Biol Sper. 1975 Dec 15;51(23):1850-3. Italian. No abstract available.

PubMed [citation]
PMID:
1241840

Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2.

Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY.

Nat Genet. 1999 Oct;23(2):185-8.

PubMed [citation]
PMID:
10508514
See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001391777.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change creates a premature translational stop signal (p.Asp34Argfs*90) in the MECP2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 453 amino acid(s) of the MECP2 protein. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the MECP2 protein in which other variant(s) (p.Arg255*) have been determined to be pathogenic (PMID: 1241840, 10508514, 17089071, 23270700). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 143304). This variant is also known as 100del4. This premature translational stop signal has been observed in individual(s) with Rett syndrome (PMID: 11524741). This variant is not present in population databases (gnomAD no frequency).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024