NM_001110792.2(MECP2):c.140_144del (p.Lys47fs) AND Severe neonatal-onset encephalopathy with microcephaly

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 28, 2021
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:: RCV001874032.4

Allele description [Variation Report for NM_001110792.2(MECP2):c.140_144del (p.Lys47fs)]

NM_001110792.2(MECP2):c.140_144del (p.Lys47fs)

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.140_144del (p.Lys47fs)

HGVS:

NC_000023.11:g.154032477_154032481del
NG_007107.3:g.109624_109628del
NM_001110792.2:c.140_144delMANE SELECT
NM_001316337.2:c.-176_-172del
NM_001369391.2:c.-176_-172del
NM_001369392.2:c.-176_-172del
NM_001369393.2:c.-176_-172del
NM_001369394.2:c.-176_-172del
NM_001386137.1:c.-457_-453del
NM_001386138.1:c.-457_-453del
NM_001386139.1:c.-457_-453del
NM_004992.4:c.104_108del
NP_001104262.1:p.Lys47fs
NP_004983.1:p.Lys35fs
LRG_764t1:c.140_144del
LRG_764t2:c.104_108del
LRG_764:g.109624_109628del
LRG_764p1:p.Lys47fs
LRG_764p2:p.Lys35fs
NC_000023.10:g.153297927_153297931del
NC_000023.10:g.153297928_153297932del
NG_007107.2:g.109648_109652del

Protein change:

K35fs

Links:

dbSNP: rs2148667088

NCBI 1000 Genomes Browser:

rs2148667088

Molecular consequence:

NM_001316337.2:c.-176_-172del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001369391.2:c.-176_-172del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001369392.2:c.-176_-172del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001369393.2:c.-176_-172del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001369394.2:c.-176_-172del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001386137.1:c.-457_-453del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001386138.1:c.-457_-453del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001386139.1:c.-457_-453del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001110792.2:c.140_144del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004992.4:c.104_108del - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002120129	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 28, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 12180070, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002120129

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 28, 2021)

germline

clinical testing

PubMed (2)
[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 MECP2 mutations in Rett syndrome.

Bienvenu T, Villard L, De Roux N, Bourdon V, Fontes M, Beldjord C, Tardieu M, Jonveaux P, Chelly J; French Consortium for MECP2 Gene Analysis..

Genet Test. 2002 Spring;6(1):1-6.

PubMed [citation]

PMID:: 12180070

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, SCV002120129.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with MECP2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Lys35Argfs*8) in the MECP2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MECP2 are known to be pathogenic (PMID: 12180070).

#	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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