NM_001110792.2(MECP2):c.*14G>A AND Rett syndrome

Germline classification:: Benign (3 submissions)
Last evaluated:: May 10, 2022
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

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:: RCV000169941.5

Allele description [Variation Report for NM_001110792.2(MECP2):c.*14G>A]

NM_001110792.2(MECP2):c.*14G>A

Gene:

MECP2:methyl-CpG binding protein 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq28

Genomic location:

Preferred name:

NM_001110792.2(MECP2):c.*14G>A

HGVS:

NC_000023.11:g.154030353C>T
NG_007107.3:g.111751G>A
NM_001110792.2:c.*14G>AMANE SELECT
NM_001316337.2:c.*14G>A
NM_001369391.2:c.*14G>A
NM_001369392.2:c.*14G>A
NM_001369393.2:c.*14G>A
NM_001369394.2:c.*14G>A
NM_001386137.1:c.*14G>A
NM_001386138.1:c.*14G>A
NM_001386139.1:c.*14G>A
NM_004992.4:c.*14G>A
LRG_764t1:c.*14G>A
LRG_764t2:c.*14G>A
AJ132917.1:c.*14G>A
LRG_764:g.111751G>A
NC_000023.10:g.153295804C>T
NG_007107.2:g.111775G>A
NM_004992.3:c.*14G>A

Links:

dbSNP: rs199963992

NCBI 1000 Genomes Browser:

rs199963992

Molecular consequence:

NM_001110792.2:c.*14G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001316337.2:c.*14G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001369391.2:c.*14G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001369392.2:c.*14G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001369393.2:c.*14G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001369394.2:c.*14G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001386137.1:c.*14G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001386138.1:c.*14G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001386139.1:c.*14G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_004992.4:c.*14G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]

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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ATP6AP2 [Malurus melanocephalus]
ATP6AP2 [Malurus melanocephalus]
Gene ID:130580617

Gene
ATP6V1A [Mesitornis unicolor]
ATP6V1A [Mesitornis unicolor]
Gene ID:104541713

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000187753	RettBASE	no assertion criteria provided	Uncertain significance (Dec 5, 2013)	unknown	curation	PubMed (1) [See all records that cite this PMID]
SCV002540720	ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel	reviewed by expert panel (ClinGen RettAS ACMG Specifications V2)	Benign (May 10, 2022)	germline	curation	Citation Link,
SCV004101621	Centre for Population Genomics, CPG	criteria provided, single submitter (McKnight et al. (Hum Mutat. 2022))	Benign (Oct 4, 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

SCV000187753

RettBASE

no assertion criteria provided

Uncertain significance
(Dec 5, 2013)

unknown

curation

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

SCV002540720

ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel

reviewed by expert panel

(ClinGen RettAS ACMG Specifications V2)

Benign
(May 10, 2022)

germline

curation

Citation Link,

SCV004101621

Centre for Population Genomics, CPG

criteria provided, single submitter

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

Benign
(Oct 4, 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	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

MECP2 gene study in a large cohort: testing of 240 female patients and 861 healthy controls (519 females and 342 males).

Maortua H, Martínez-Bouzas C, García-Ribes A, Martínez MJ, Guillen E, Domingo MR, Calvo MT, Guitart M, Gabau E, Botella MP, Gener B, Rubio I, López-Aríztegui MA, Tejada MI.

J Mol Diagn. 2013 Sep;15(5):723-9. doi: 10.1016/j.jmoldx.2013.05.002. Epub 2013 Jun 26.

PubMed [citation]

PMID:: 23810759

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, SCV000187753.2

#	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: 23810759]

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

From ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel, SCV002540720.1

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

Description

The allele frequency of the c.*14G>A variant in MECP2 (NM_004992) is 0.34% in South Asian sub population in gnomAD, which is high enough to be classified as benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BA1). In summary the c.*14G>A variant in MECP2 is classified as Benign based on the ACMG/AMP criteria (BA1).

#	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

From Centre for Population Genomics, CPG, SCV004101621.1

#	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 benign. At least the following criteria are met: The allele frequency of this variant in at least one population in gnomAD is higher than the 0.03% threshold defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders VCEP 2.0 (BA1).

#	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 3, 2024

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