ClinVar Genomic variation as it relates to human health
NM_002397.5(MEF2C):c.-8C>T
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_002397.5(MEF2C):c.-8C>T
Variation ID: 1202675 Accession: VCV001202675.27
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 5q14.3 5: 88823796 (GRCh38) [ NCBI UCSC ] 5: 88119613 (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 Aug 21, 2021 Oct 20, 2024 Sep 17, 2024 - HGVS
- ... more HGVS ... less HGVS
- Protein change
- Other names
- -8C-T, 5-PRIME UTR
- Canonical SPDI
- NC_000005.10:88823795: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
Help
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
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
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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MEF2C | Sufficient evidence for dosage pathogenicity | Little evidence for dosage pathogenicity |
GRCh38 GRCh37 |
461 | 570 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
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 (2) |
criteria provided, multiple submitters, no conflicts
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Jul 8, 2024 | RCV001568454.20 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Sep 17, 2024 | RCV001685531.6 | |
Pathogenic (1) |
criteria provided, single submitter
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Jun 11, 2021 | RCV001779254.2 |
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
Help
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
Help
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
(Jun 11, 2021)
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criteria provided, single submitter
Method: clinical testing
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Neurodevelopmental disorder
Affected status: yes
Allele origin:
germline
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Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes
Accession: SCV002016256.1
First in ClinVar: Nov 20, 2021 Last updated: Nov 20, 2021 |
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pathogenic
(Sep 19, 2023)
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criteria provided, single submitter
Method: clinical testing
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Intellectual disability, autosomal dominant 20
Affected status: yes
Allele origin:
de novo
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Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn
Accession: SCV004239261.1
First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024 |
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Pathogenic
(Jul 08, 2024)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001792327.3
First in ClinVar: Aug 21, 2021 Last updated: Oct 08, 2024 |
Comment:
Not observed at significant frequency in large population cohorts (gnomAD); Predicted to create ATG start codon in the 5UTR; This variant is associated with the … (more)
Not observed at significant frequency in large population cohorts (gnomAD); Predicted to create ATG start codon in the 5UTR; This variant is associated with the following publications: (PMID: 34022131, 35850704) (less)
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Pathogenic
(Sep 17, 2024)
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criteria provided, single submitter
Method: clinical testing
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Intellectual disability, autosomal dominant 20
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
de novo
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV005368226.1
First in ClinVar: Oct 13, 2024 Last updated: Oct 13, 2024 |
Comment:
Criteria applied: PM2,PS2_VSTR,PS4_MOD,PS3_SUP
Clinical Features:
Opisthotonus (present) , Gait disturbance (present) , Myopia (present) , Delayed ability to walk (present) , Severe global developmental delay (present) , Febrile seizure (within … (more)
Opisthotonus (present) , Gait disturbance (present) , Myopia (present) , Delayed ability to walk (present) , Severe global developmental delay (present) , Febrile seizure (within the age range of 3 months to 6 years) (present) , Hypotonia (present) , Hemangioma (present) , Strabismus (present) , Focal-onset seizure (present) , Absent speech (present) (less)
Sex: male
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Pathogenic
(Jun 01, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV002544957.16
First in ClinVar: Jul 09, 2022 Last updated: Oct 20, 2024 |
Comment:
MEF2C: PS2:Very Strong, PM2, PS4:Moderate, PS3:Supporting
Number of individuals with the variant: 1
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Pathogenic
(Dec 02, 2021)
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no assertion criteria provided
Method: literature only
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NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA, STEREOTYPIC HAND MOVEMENTS, AND IMPAIRED LANGUAGE
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV001900879.2
First in ClinVar: Sep 24, 2021 Last updated: Dec 04, 2021 |
Comment on evidence:
In 3 unrelated patients (patients 3, 4, and 5) with neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language (NEDHSIL; 613443), Wright et al. … (more)
In 3 unrelated patients (patients 3, 4, and 5) with neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language (NEDHSIL; 613443), Wright et al. (2021) identified a de novo heterozygous c.-8C-T transition in the 5-prime untranslated region (UTR) of the MEF2C gene. The mutation, which was found by specific analysis of 5-prime UTR variants in selected candidate genes, was not present in the gnomAD database. The mutation created an upstream AUG codon that was in-frame with the coding sequence, creating resulting in an N-terminal extension of 3 amino acids. In vitro functional expression studies using a luciferase reporter showed that the mutation significantly decreased MEF2C translational efficiency compared to controls. These findings were consistent with haploinsufficiency. (less)
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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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Non-coding region variants upstream of MEF2C cause severe developmental disorder through three distinct loss-of-function mechanisms. | Wright CF | American journal of human genetics | 2021 | PMID: 34022131 |
Text-mined citations for rs2153222958 ...
HelpRecord last updated Oct 20, 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.