rs587783748
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_002397.5(MEF2C):c.810+10A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000236 in 1,610,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000024 ( 0 hom. )
Consequence
MEF2C
NM_002397.5 intron
NM_002397.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.117
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 Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
?
Variant 5-88731719-T-A is Benign according to our data. Variant chr5-88731719-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 158887.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High AC in GnomAdExome at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MEF2C | NM_002397.5 | c.810+10A>T | intron_variant | ENST00000504921.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEF2C | ENST00000504921.7 | c.810+10A>T | intron_variant | 1 | NM_002397.5 | ||||
MEF2C-AS2 | ENST00000657578.1 | n.232-30278T>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152154Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000242 AC: 6AN: 248226Hom.: 0 AF XY: 0.0000297 AC XY: 4AN XY: 134746
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GnomAD4 exome AF: 0.0000240 AC: 35AN: 1458578Hom.: 0 Cov.: 29 AF XY: 0.0000317 AC XY: 23AN XY: 725780
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ClinVar
Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 01, 2014 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 05, 2015 | 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. - |
MEF2C-related condition Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 17, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Intellectual disability, autosomal dominant 20 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 10, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at