rs777826971
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_002397.5(MEF2C):c.860C>T(p.Ser287Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,496 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. S287S) has been classified as Likely benign.
Frequency
Consequence
NM_002397.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MEF2C | NM_002397.5 | c.860C>T | p.Ser287Leu | missense_variant | 9/11 | ENST00000504921.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEF2C | ENST00000504921.7 | c.860C>T | p.Ser287Leu | missense_variant | 9/11 | 1 | NM_002397.5 | ||
MEF2C-AS2 | ENST00000657578.1 | n.232-32675G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000813 AC: 2AN: 246080Hom.: 0 AF XY: 0.00000749 AC XY: 1AN XY: 133452
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1459496Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 725968
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Intellectual disability, autosomal dominant 20 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 30, 2019 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has been observed in an individual with polymicrogyria, microcephaly, and tetraparesis (PMID: 29706646). It is also known as c.890C>T (p.Ser297Leu) in the literature. ClinVar contains an entry for this variant (Variation ID: 438583). This variant is present in population databases (rs777826971, ExAC 0.002%). This sequence change replaces serine with leucine at codon 287 of the MEF2C protein (p.Ser287Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. - |
Uncertain significance, criteria provided, single submitter | research | Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine | Sep 01, 2017 | this variant was indentified in an individual with malformations of cortical development - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at