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NM_001110792.2(MECP2):c.474C>T (p.Gly158=) AND Rett syndrome

Germline classification:
Likely benign (2 submissions)
Last evaluated:
Nov 24, 2021
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:
RCV001800454.5

Allele description [Variation Report for NM_001110792.2(MECP2):c.474C>T (p.Gly158=)]

NM_001110792.2(MECP2):c.474C>T (p.Gly158=)

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.474C>T (p.Gly158=)
Other names:
NM_001110792.2(MECP2):c.474C>T; p.Gly158=
HGVS:
  • NC_000023.11:g.154031390G>A
  • NG_007107.3:g.110714C>T
  • NM_001110792.2:c.474C>TMANE SELECT
  • NM_001316337.2:c.159C>T
  • NM_001369391.2:c.159C>T
  • NM_001369392.2:c.159C>T
  • NM_001369393.2:c.159C>T
  • NM_001369394.2:c.159C>T
  • NM_001386137.1:c.-129+6C>T
  • NM_001386138.1:c.-129+6C>T
  • NM_001386139.1:c.-129+6C>T
  • NM_004992.4:c.438C>T
  • NP_001104262.1:p.Gly158=
  • NP_001303266.1:p.Gly53=
  • NP_001356320.1:p.Gly53=
  • NP_001356321.1:p.Gly53=
  • NP_001356322.1:p.Gly53=
  • NP_001356323.1:p.Gly53=
  • NP_004983.1:p.Gly146=
  • NP_004983.1:p.Gly146=
  • LRG_764t1:c.474C>T
  • LRG_764t2:c.438C>T
  • AJ132917.1:c.438C>T
  • LRG_764:g.110714C>T
  • LRG_764p1:p.Gly158=
  • LRG_764p2:p.Gly146=
  • NC_000023.10:g.153296841G>A
  • NG_007107.2:g.110738C>T
  • NM_004992.3:c.438C>T
  • NP_004983.1:p.(=)
Links:
dbSNP: rs61748386
NCBI 1000 Genomes Browser:
rs61748386
Molecular consequence:
  • NM_001386137.1:c.-129+6C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001386138.1:c.-129+6C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001386139.1:c.-129+6C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001110792.2:c.474C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001316337.2:c.159C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001369391.2:c.159C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001369392.2:c.159C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001369393.2:c.159C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001369394.2:c.159C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_004992.4:c.438C>T - synonymous variant - [Sequence Ontology: SO:0001819]

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002047346ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel
reviewed by expert panel

(ClinGen RettAS ACMG Specifications V2)		Likely benign
(Nov 24, 2021) 		germlinecuration

Citation Link,

SCV005040719Centre for Population Genomics, CPG
criteria provided, single submitter

(McKnight et al. (Hum Mutat. 2022))		Benign
(Apr 22, 2024) 		germlinecuration

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

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

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 ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel, SCV002047346.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The c.438C>T (p.Gly146=) variant in MECP2 (NM_004992.3) is absent from gnomAD (PM2_supporting). The p.Gly146= variant is observed in at least 1 unaffected individual (internal database - Invitae) (BS2_supporting). The p.Gly146= variant is found in a patient with an alternate molecular basis of disease (internal database - Invitae) (BP5). The Rett and Angelman-like Disorders Variant Curation Expert Panel classified this variant as Likely Benign based on BS2_supporting and BP5.

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

From Centre for Population Genomics, CPG, SCV005040719.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration 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 benign. At least the following criteria are met: The variant is observed in at least 2 individuals with no features of Rett Syndrome (BS2).The allele frequency of this variant in at least one population in gnomAD V3, V4 is between 0.008% and 0.03% , including 6 hemizygous (BS1).

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

Last Updated: Oct 26, 2024