rs776496777
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS1
The NM_002397.5(MEF2C):c.615G>A(p.Thr205=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000793 in 1,575,560 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 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000085 ( 0 hom. )
Consequence
MEF2C
NM_002397.5 synonymous
NM_002397.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.727
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 -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.25).
BP6
?
Variant 5-88749092-C-T is Benign according to our data. Variant chr5-88749092-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 380983.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.727 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.000085 (121/1423276) while in subpopulation NFE AF= 0.000108 (118/1091820). AF 95% confidence interval is 0.0000919. There are 0 homozygotes in gnomad4_exome. There are 60 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MEF2C | NM_002397.5 | c.615G>A | p.Thr205= | synonymous_variant | 6/11 | ENST00000504921.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEF2C | ENST00000504921.7 | c.615G>A | p.Thr205= | synonymous_variant | 6/11 | 1 | NM_002397.5 | ||
MEF2C-AS2 | ENST00000657578.1 | n.232-12905C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152166Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.0000850 AC: 121AN: 1423276Hom.: 0 Cov.: 30 AF XY: 0.0000852 AC XY: 60AN XY: 703856
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152284Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74458
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 07, 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. - |
Intellectual disability, autosomal dominant 20 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 10, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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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