NM_001110792.2(MECP2):c.1133_*13del (p.His378_Ter499delinsXaa) AND Rett syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 12, 2024
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:: RCV000170129.3

Allele description [Variation Report for NM_001110792.2(MECP2):c.1133_*13del (p.His378_Ter499delinsXaa)]

NM_001110792.2(MECP2):c.1133_*13del (p.His378_Ter499delinsXaa)

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.1133_*13del (p.His378_Ter499delinsXaa)

Other names:

NM_001110792.2(MECP2):c.1133_*13del; p.His378_Ter499delinsXaa

HGVS:

NC_000023.11:g.154030359_154030736del
NG_007107.3:g.111373_111750del
NM_001110792.2:c.1133_*13delMANE SELECT
NM_001316337.2:c.818_*13del
NM_001369391.2:c.818_*13del
NM_001369392.2:c.818_*13del
NM_001369393.2:c.818_*13del
NM_001369394.2:c.818_*13del
NM_001386137.1:c.428_*13del
NM_001386138.1:c.428_*13del
NM_001386139.1:c.428_*13del
NM_004992.4:c.1097_*13del
NP_001104262.1:p.His378_Ter499delinsXaa
NP_001303266.1:p.His273_Ter394delinsXaa
NP_001356320.1:p.His273_Ter394delinsXaa
NP_001356321.1:p.His273_Ter394delinsXaa
NP_001356322.1:p.His273_Ter394delinsXaa
NP_001356323.1:p.His273_Ter394delinsXaa
NP_001373066.1:p.His143_Ter264delinsXaa
NP_001373067.1:p.His143_Ter264delinsXaa
NP_001373068.1:p.His143_Ter264delinsXaa
NP_004983.1:p.His366_Ter487delinsXaa
LRG_764t1:c.1133_*13del
LRG_764t2:c.1097_*13del
LRG_764:g.111373_111750del
LRG_764p1:p.His378_Ter499delinsXaa
LRG_764p2:p.His366_Ter487delinsXaa
NC_000023.10:g.153295810_153296187del
NG_007107.2:g.111397_111774del
NM_004992.3:c.1097_*13del378

Links:

dbVar: nssv7487075; dbVar: nsv1197467; dbSNP: rs1557134819

NCBI 1000 Genomes Browser:

rs1557134819

Molecular consequence:

NM_001110792.2:c.1133_*13del - stop lost - [Sequence Ontology: SO:0001578]
NM_001316337.2:c.818_*13del - stop lost - [Sequence Ontology: SO:0001578]
NM_001369391.2:c.818_*13del - stop lost - [Sequence Ontology: SO:0001578]
NM_001369392.2:c.818_*13del - stop lost - [Sequence Ontology: SO:0001578]
NM_001369393.2:c.818_*13del - stop lost - [Sequence Ontology: SO:0001578]
NM_001369394.2:c.818_*13del - stop lost - [Sequence Ontology: SO:0001578]
NM_001386137.1:c.428_*13del - stop lost - [Sequence Ontology: SO:0001578]
NM_001386138.1:c.428_*13del - stop lost - [Sequence Ontology: SO:0001578]
NM_001386139.1:c.428_*13del - stop lost - [Sequence Ontology: SO:0001578]
NM_004992.4:c.1097_*13del - stop lost - [Sequence Ontology: SO:0001578]

Condition(s)

Name:: Rett syndrome (RTT)
Synonyms:: Autism, dementia, ataxia, and loss of purposeful hand use; Rett's disorder
Identifiers:: MONDO: MONDO:0010726; MedGen: C0035372; Orphanet: 3095; Orphanet: 778; OMIM: 312750

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LOC103435689 [Malus domestica]
LOC103435689 [Malus domestica]
Gene ID:103435689

Gene
UGGT1 [Pterocles gutturalis]
UGGT1 [Pterocles gutturalis]
Gene ID:104465539

Gene
FUT8 [Gavia stellata]
FUT8 [Gavia stellata]
Gene ID:104254562

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000222457	RettBASE	no assertion criteria provided	Pathogenic (Sep 5, 2002)	unknown	curation	PubMed (1) [See all records that cite this PMID]
SCV004232335	Centre for Population Genomics, CPG	criteria provided, single submitter (McKnight et al. (Hum Mutat. 2022))	Uncertain significance (Jan 12, 2024)	germline	curation	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000222457

RettBASE

no assertion criteria provided

Pathogenic
(Sep 5, 2002)

unknown

curation

PubMed (1)
[See all records that cite this PMID]

SCV004232335

Centre for Population Genomics, CPG

criteria provided, single submitter

(McKnight et al. (Hum Mutat. 2022))

Uncertain significance
(Jan 12, 2024)

germline

curation

PubMed (1)
[See all records that cite this PMID]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	yes	1	not provided	not provided	1	No	curation
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

Mutation spectrum in patients with Rett syndrome in the German population: Evidence of hot spot regions.

Laccone F, Huppke P, Hanefeld F, Meins M.

Hum Mutat. 2001 Mar;17(3):183-90.

PubMed [citation]

PMID:: 11241840

Recommendations by the ClinGen Rett/Angelman-like expert panel for gene-specific variant interpretation methods.

McKnight D, Bean L, Karbassi I, Beattie K, Bienvenu T, Bonin H, Fang P, Chrisodoulou J, Friez M, Helgeson M, Krishnaraj R, Meng L, Mighion L, Neul J, Percy A, Ramsden S, Zoghbi H, Das S.

Hum Mutat. 2022 Aug;43(8):1097-1113. doi: 10.1002/humu.24302. Epub 2021 Dec 2.

PubMed [citation]

PMID:: 34837432
PMCID:: PMC9135956

Details of each submission

From RettBASE, SCV000222457.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	No	curation	PubMed (1)

Description

"Rett syndrome - Not certain"

PubMed [ID: 11241840]

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	1	Blood	not provided		1	not provided	not provided	not provided

From Centre for Population Genomics, CPG, SCV004232335.1

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

Description

This variant has been collected from RettBASE and curated to current modified ACMG/AMP criteria. Based on the classification scheme defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders Specifications to the ACMG/AMP Variant Interpretation Guidelines VCEP 3.0, this variant is classified as a variant of uncertain significance. At least the following criteria are met: At least the following criteria are met: Protein length changes due to in-frame deletions/insertions in a non-repeat region (PM4). At least one individual with this variant has been reported with a clinical phenotype consistent with Rett syndrome (PP4).PMID 11241840 This variant is absent from gnomAD (PM2_Supporting).

#	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: Feb 28, 2024

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