rs1554110298
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_002397.5(MEF2C):c.614_626delinsGTCTCCAC(p.Thr205SerfsTer25) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T205T) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Consequence
MEF2C
NM_002397.5 frameshift
NM_002397.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.56
Genes affected
MEF2C (HGNC:6996): (myocyte enhancer factor 2C) This locus encodes a member of the MADS box transcription enhancer factor 2 (MEF2) family of proteins, which play a role in myogenesis. The encoded protein, MEF2 polypeptide C, has both trans-activating and DNA binding activities. This protein may play a role in maintaining the differentiated state of muscle cells. Mutations and deletions at this locus have been associated with severe cognitive disability, stereotypic movements, epilepsy, and cerebral malformation. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2010]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MEF2C | NM_002397.5 | c.614_626delinsGTCTCCAC | p.Thr205SerfsTer25 | frameshift_variant | 6/11 | ENST00000504921.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEF2C | ENST00000504921.7 | c.614_626delinsGTCTCCAC | p.Thr205SerfsTer25 | frameshift_variant | 6/11 | 1 | NM_002397.5 | ||
MEF2C-AS2 | ENST00000657578.1 | n.232-12916_232-12904delinsGTGGAGAC | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Intellectual disability, autosomal dominant 20 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 20, 2018 | 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. This variant has not been reported in the literature in individuals with MEF2C-related disease. However, it has been observed in several individuals who were not affected with MEF2C-related disease (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Thr205Serfs*28) in the MEF2C gene. It is expected to result in an absent or disrupted protein product. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at