ClinVar Genomic variation as it relates to human health
NM_001110792.2(MECP2):c.413+6_413+9del
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001110792.2(MECP2):c.413+6_413+9del
Variation ID: 156059 Accession: VCV000156059.13
- Type and length
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Microsatellite, 4 bp
- Location
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Cytogenetic: Xq28 X: 154032198-154032201 (GRCh38) [ NCBI UCSC ] X: 153297649-153297652 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Sep 26, 2014 Apr 6, 2024 Oct 26, 2021 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001110792.2:c.413+6_413+9del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice donor NM_004992.4:c.377+6_377+9del MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice donor NM_001316337.2:c.98+6_98+9del splice donor NM_001369391.2:c.98+6_98+9del splice donor NM_001369392.2:c.98+6_98+9del splice donor NM_001369393.2:c.98+6_98+9del splice donor NM_001369394.2:c.98+6_98+9del splice donor NM_001386137.1:c.-184+6_-184+9del splice donor NM_001386138.1:c.-184+6_-184+9del splice donor NM_001386139.1:c.-184+6_-184+9del splice donor NM_004992.3:c.377+6_377+9delTAAG NC_000023.11:g.154032201ACTT[1] NC_000023.10:g.153297652ACTT[1] NG_007107.3:g.109899TAAG[1] LRG_764:g.109899TAAG[1] LRG_764t1:c.413+6_413+9del LRG_764t2:c.377+6_377+9del AJ132917.1:c.377+6_377+9del - Protein change
- Other names
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- Canonical SPDI
- NC_000023.11:154032197:CTTACTTACTT:CTTACTT
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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MECP2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1825 | 2148 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Uncertain significance (2) |
criteria provided, single submitter
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Jul 14, 2021 | RCV000144106.16 | |
Uncertain significance (1) |
no assertion criteria provided
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Sep 5, 2002 | RCV000170270.9 | |
Likely benign (1) |
criteria provided, single submitter
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Feb 12, 2018 | RCV000614093.9 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jul 18, 2022 | RCV002512555.8 | |
Likely benign (2) |
reviewed by expert panel
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Oct 26, 2021 | RCV001800460.11 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
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The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Likely benign
(Oct 26, 2021)
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reviewed by expert panel
Method: curation
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Rett syndrome
(X-linked inheritance)
Affected status: unknown
Allele origin:
germline
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ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel
Accession: SCV002047353.1
First in ClinVar: Jan 03, 2022 Last updated: Jan 03, 2022 |
Comment:
The allele frequency of the c.377+6_377+9del variant in MECP2 (NM_004992.3) is 0.014% in the East Asian sub population in gnomAD, which is high enough to … (more)
The allele frequency of the c.377+6_377+9del variant in MECP2 (NM_004992.3) is 0.014% in the East Asian sub population in gnomAD, which is high enough to meet the BS1 criteria based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BS1). The c.377+6_377+9del variant is found in a patient with an alternate molecular basis of disease (internal database - GeneDx) (BP5). In summary, the c.377+6_377+9del variant in MECP2 is classified as Likely Benign based on the ACMG/AMP criteria (BS1, BP5). (less)
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Likely benign
(Feb 12, 2018)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000727486.1
First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
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Uncertain significance
(Jul 14, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV002048054.1
First in ClinVar: Jan 08, 2022 Last updated: Jan 08, 2022 |
Comment:
The MECP2 c.377+6_377+9delTAAG variant (rs267608459), also known as IVS2+2delTAAG, has not been reported in individuals with Rett syndrome but has been observed in an individual … (more)
The MECP2 c.377+6_377+9delTAAG variant (rs267608459), also known as IVS2+2delTAAG, has not been reported in individuals with Rett syndrome but has been observed in an individual with infantile autism (Lam 2000). This variant is also reported in ClinVar (Variation ID: 156059). This variant is found in the East Asian population with an allele frequency of 0.01% (2/13,856 alleles) in the Genome Aggregation Database. This is an intronic variant, and computational analyses (Alamut v.2.11) predict that this variant may impact splicing by weaking the nearby canonical donor splice site. However, given the lack of clinical and functional data, the significance of the c.377+6_377+9delTAAG variant is uncertain at this time. References: Lam CW et al. Spectrum of mutations in the MECP2 gene in patients with infantile autism and Rett syndrome. J Med Genet. 2000 Dec;37(12):E41. PMID: 11106359. (less)
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Uncertain significance
(Jul 18, 2022)
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criteria provided, single submitter
Method: clinical testing
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Severe neonatal-onset encephalopathy with microcephaly
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV003450123.1
First in ClinVar: Feb 07, 2023 Last updated: Feb 07, 2023 |
Comment:
This sequence change falls in intron 3 of the MECP2 gene. It does not directly change the encoded amino acid sequence of the MECP2 protein. … (more)
This sequence change falls in intron 3 of the MECP2 gene. It does not directly change the encoded amino acid sequence of the MECP2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs267608459, gnomAD 0.02%), including at least one homozygous and/or hemizygous individual. This variant has been observed in individual(s) with autism (PMID: 11106359). This variant is also known as IVS+2delTAAG. ClinVar contains an entry for this variant (Variation ID: 156059). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
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Likely benign
(Mar 18, 2024)
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criteria provided, single submitter
Method: curation
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Rett syndrome
(X-linked inheritance)
Affected status: unknown
Allele origin:
germline
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Centre for Population Genomics, CPG
Accession: SCV004808820.1
First in ClinVar: Apr 06, 2024 Last updated: Apr 06, 2024 |
Comment:
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 … (more)
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 likely benign. At least the following criteria are met: The allele frequency of this variant in at least one population in gnomAD is between 0.008% and 0.03% (BS1). (less)
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Uncertain significance
(Sep 05, 2002)
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no assertion criteria provided
Method: curation
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Austism susceptibility, X-linked
Affected status: yes
Allele origin:
de novo
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RettBASE
Accession: SCV000222602.1
First in ClinVar: Apr 22, 2015 Last updated: Apr 22, 2015 |
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: Blood
Comment on evidence:
Not Rett synd. - autism only
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not provided
(-)
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Flagged submission
flagged submission
Method: not provided
Reason: This record appears to be redundant with a more recent record from the same submitter.
Notes: SCV000189182 appears to be redundant with SCV000222602.
(less)
Notes: SCV000189182 appears to
(...more)
Source: NCBI
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not provided
Affected status: not provided
Allele origin:
not provided
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RettBASE
Accession: SCV000189182.1
First in ClinVar: Sep 26, 2014 Last updated: Sep 26, 2014 |
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Flagged submissions do not contribute to the aggregate classification or review status for the variant. Learn more |
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization. | Buratti E | Nucleic acids research | 2007 | PMID: 17576681 |
Spectrum of mutations in the MECP2 gene in patients with infantile autism and Rett syndrome. | Lam CW | Journal of medical genetics | 2000 | PMID: 11106359 |
Statistical features of human exons and their flanking regions. | Zhang MQ | Human molecular genetics | 1998 | PMID: 9536098 |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/d1a21afb-c08d-4e51-a8d3-9b7e4c179254 | - | - | - | - |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/d69f451d-1d32-430b-ba22-93a5cb1ef51a | - | - | - | - |
Text-mined citations for rs267608459 ...
HelpRecord last updated May 01, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.