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NM_001110792.2(MECP2):c.63-6214_1227del AND Rett syndrome

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Apr 3, 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:
RCV000170186.2

Allele description [Variation Report for NM_001110792.2(MECP2):c.63-6214_1227del]

NM_001110792.2(MECP2):c.63-6214_1227del

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.63-6214_1227del
HGVS:
  • NC_000023.11:g.154030638_154038772del
  • NG_007107.3:g.103333_111467del
  • NM_001110792.2:c.63-6214_1227delMANE SELECT
  • NM_001316337.2:c.-253-6214_912del
  • NM_001369391.2:c.-253-6214_912del
  • NM_001369392.2:c.-254+1021_912del
  • NM_001369393.2:c.-254+1021_912del
  • NM_001369394.2:c.-253-6214_912del
  • NM_001386137.1:c.-535+1021_522del
  • NM_001386138.1:c.-534-6214_522del
  • NM_001386139.1:c.-534-6214_522del
  • NM_004992.4:c.27-6214_1191del
  • LRG_764t1:c.63-6214_1227del
  • LRG_764t2:c.27-6214_1191del
  • LRG_764:g.103333_111467del
  • NC_000023.10:g.153296089_153304223del
  • NG_007107.2:g.103357_111491del
  • NM_004992.3:c.27-6215_1190del
Links:
dbVar: nssv7487113; dbVar: nsv1197413
Molecular consequence:
  • NM_001316337.2:c.-253-6214_912del - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_001369391.2:c.-253-6214_912del - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_001369392.2:c.-254+1021_912del - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_001369393.2:c.-254+1021_912del - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_001369394.2:c.-253-6214_912del - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_001386137.1:c.-535+1021_522del - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_001386138.1:c.-534-6214_522del - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_001386139.1:c.-534-6214_522del - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_001110792.2:c.63-6214_1227del - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001316337.2:c.-253-6214_912del - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001369391.2:c.-253-6214_912del - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001369392.2:c.-254+1021_912del - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001369393.2:c.-254+1021_912del - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001369394.2:c.-253-6214_912del - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001386137.1:c.-535+1021_522del - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001386138.1:c.-534-6214_522del - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001386139.1:c.-534-6214_522del - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_004992.4:c.27-6214_1191del - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001110792.2:c.63-6214_1227del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001316337.2:c.-253-6214_912del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001369391.2:c.-253-6214_912del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001369392.2:c.-254+1021_912del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001369393.2:c.-254+1021_912del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001369394.2:c.-253-6214_912del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001386137.1:c.-535+1021_522del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001386138.1:c.-534-6214_522del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001386139.1:c.-534-6214_522del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_004992.4:c.27-6214_1191del - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV000222515RettBASE
no assertion criteria provided
Pathogenic
(Nov 15, 2007) 		unknowncuration

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

SCV004809347Centre for Population Genomics, CPG
criteria provided, single submitter

(McKnight et al. (Hum Mutat. 2022))		Pathogenic
(Apr 3, 2024) 		germlinecuration

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

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownyes1not providednot provided1Nocuration
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Citations

PubMed

Gross rearrangements in the MECP2 gene in three patients with Rett syndrome: implications for routine diagnosis of Rett syndrome.

Schollen E, Smeets E, Deflem E, Fryns JP, Matthijs G.

Hum Mutat. 2003 Aug;22(2):116-20.

PubMed [citation]
PMID:
12872251

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, SCV000222515.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providedNocuration PubMed (1)

Description

"Rett syndrome - classical"

PubMed [ID: 12872251]

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyes1not knownnot provided1not providednot providednot provided

From Centre for Population Genomics, CPG, SCV004809347.1

#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 pathogenic. At least the following criteria are met: Predicted to result in loss of function, and LOF is a known mechanism of disease (PVS1). Genomic rearrangements with breakpoints within the deletion prone region have been observed in at least 5 individuals with phenotypes consistent with MECP2-related disease (PS4, PMID 12872251, PMID: 14974082, PMID 31206249) This variant is absent from gnomAD (PM2_Supporting).

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

Last Updated: Apr 15, 2024