NM_001110792.2(MECP2):c.265_274del (p.Ala89fs) AND Rett syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Oct 12, 2023
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:: RCV003389404.1

Allele description [Variation Report for NM_001110792.2(MECP2):c.265_274del (p.Ala89fs)]

NM_001110792.2(MECP2):c.265_274del (p.Ala89fs)

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.265_274del (p.Ala89fs)

Other names:

NM_001110792.2(MECP2):c.265_274del; p.Ala89fs

HGVS:

NC_000023.11:g.154032346_154032355del
NG_007107.3:g.109749_109758del
NM_001110792.2:c.265_274delMANE SELECT
NM_001316337.2:c.-51_-42del
NM_001369391.2:c.-51_-42del
NM_001369392.2:c.-51_-42del
NM_001369393.2:c.-51_-42del
NM_001369394.2:c.-51_-42del
NM_001386137.1:c.-332_-323del
NM_001386138.1:c.-332_-323del
NM_001386139.1:c.-332_-323del
NM_004992.4:c.229_238del
NP_001104262.1:p.Ala89fs
NP_004983.1:p.Ala77fs
LRG_764t1:c.265_274del
LRG_764t2:c.229_238del
AJ132917.1:c.229_238del10
LRG_764:g.109749_109758del
LRG_764p1:p.Ala89fs
LRG_764p2:p.Ala77fs
NC_000023.10:g.153297797_153297806del
NG_007107.2:g.109773_109782del
NM_004992.3:c.229_238del10

Protein change:

A77fs

Links:

dbSNP: rs63749009

NCBI 1000 Genomes Browser:

rs63749009

Molecular consequence:

NM_001316337.2:c.-51_-42del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001369391.2:c.-51_-42del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001369392.2:c.-51_-42del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001369393.2:c.-51_-42del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001369394.2:c.-51_-42del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001386137.1:c.-332_-323del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001386138.1:c.-332_-323del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001386139.1:c.-332_-323del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001110792.2:c.265_274del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004992.4:c.229_238del - frameshift variant - [Sequence Ontology: SO:0001589]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004101596	Centre for Population Genomics, CPG	criteria provided, single submitter (McKnight et al. (Hum Mutat. 2022))	Likely pathogenic (Oct 12, 2023)	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

SCV004101596

Centre for Population Genomics, CPG

criteria provided, single submitter

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

Likely pathogenic
(Oct 12, 2023)

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	germline	unknown	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

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 Centre for Population Genomics, CPG, SCV004101596.1

#	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 2.0, this variant is classified as likely pathogenic. At least the following criteria are met: Predicted to result in loss of function, and LOF is a known mechanism of disease (PVS1). 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: Nov 20, 2023

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