ClinVar Genomic variation as it relates to human health
NM_001110792.2(MECP2):c.820C>T (p.Gln274Ter)
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.820C>T (p.Gln274Ter)
Variation ID: 143696 Accession: VCV000143696.4
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: Xq28 X: 154031044 (GRCh38) [ NCBI UCSC ] X: 153296495 (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 Apr 24, 2015 Apr 6, 2024 Mar 25, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001110792.2:c.820C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001104262.1:p.Gln274Ter nonsense NM_004992.4:c.784C>T MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004983.1:p.Gln262Ter nonsense NM_001316337.2:c.505C>T NP_001303266.1:p.Gln169Ter nonsense NM_001369391.2:c.505C>T NP_001356320.1:p.Gln169Ter nonsense NM_001369392.2:c.505C>T NP_001356321.1:p.Gln169Ter nonsense NM_001369393.2:c.505C>T NP_001356322.1:p.Gln169Ter nonsense NM_001369394.2:c.505C>T NP_001356323.1:p.Gln169Ter nonsense NM_001386137.1:c.115C>T NP_001373066.1:p.Gln39Ter nonsense NM_001386138.1:c.115C>T NP_001373067.1:p.Gln39Ter nonsense NM_001386139.1:c.115C>T NP_001373068.1:p.Gln39Ter nonsense NC_000023.11:g.154031044G>A NC_000023.10:g.153296495G>A NG_007107.3:g.111060C>T LRG_764:g.111060C>T LRG_764t1:c.820C>T LRG_764p1:p.Gln274Ter LRG_764t2:c.784C>T LRG_764p2:p.Gln262Ter AJ132917.1:c.784C>T - Protein change
- Q262*, Q274*, Q169*, Q39*
- Other names
- NM_001110792.2(MECP2):c.820C>T
- p.Gln274Ter
- Canonical SPDI
- NC_000023.11:154031043:G:A
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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 |
1824 | 2145 |
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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Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Mar 25, 2024 | RCV000133237.5 | |
Pathogenic (1) |
criteria provided, single submitter
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Sep 7, 2022 | RCV003422031.4 |
Submissions - Germline
Classification
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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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Pathogenic
(Oct 10, 2013)
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criteria provided, single submitter
Method: clinical testing
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Rett's disorder
(X-linked dominant inheritance)
Affected status: unknown
Allele origin:
germline
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Athena Diagnostics Inc
Accession: SCV000255793.2
First in ClinVar: Oct 19, 2015 Last updated: Oct 19, 2015 |
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Pathogenic
(Sep 07, 2022)
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criteria provided, single submitter
Method: clinical testing
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MECP2-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004118621.1
First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023 |
Comment:
The MECP2 c.784C>T variant is predicted to result in premature protein termination (p.Gln262*). This variant was reported in multiple individuals with Rett syndrome or intellectual … (more)
The MECP2 c.784C>T variant is predicted to result in premature protein termination (p.Gln262*). This variant was reported in multiple individuals with Rett syndrome or intellectual disability (Milunsky et al. 2001. PubMed ID: 11960578; Table S1, Wen et al. 2020. PubMed ID: 32472557; described as c.820C>T, Chen et al. 2021. PubMed ID: 33753861; https://jtggjournal.com/article/view/3461?). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Nonsense variants in MECP2 are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
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Pathogenic
(Mar 25, 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: SCV004808886.1
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 pathogenic. At least the following criteria are met: Predicted to result in loss of function, and LOF is a known mechanism of disease (PVS1). Has been observed in at least 3 individuals with phenotypes consistent with MECP2-related disease(PS4_Moderate). PMID: 30670340, 28351539, 26003587, 11960578, 28272783). This variant is absent from gnomAD (PM2_Supporting). (less)
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Pathogenic
(Jul 13, 2010)
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no assertion criteria provided
Method: curation
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Rett syndrome
Affected status: unknown, yes
Allele origin:
unknown
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RettBASE
Accession: SCV000188239.2
First in ClinVar: Aug 17, 2014 Last updated: Apr 24, 2015 |
Observation 1:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Not known
Observation 2:
Number of individuals with the variant: 1
Family history: No
Sex: female
Tissue: blood
Comment on evidence:
Rett syndrome - classical
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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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Mutation analysis in Rett syndrome. | Milunsky JM | Genetic testing | 2001 | PMID: 11960578 |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/d5e0d001-46c4-447a-a74d-f130d98d5355 | - | - | - | - |
Text-mined citations for rs267608525 ...
HelpRecord last updated Apr 15, 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.