Genetic Variant MEF2C:p.Asp104Glu (chr5-88761275-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_002397.5(MEF2C):c.312C>A(p.Asp104Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. D104D) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

MEF2C
NM_002397.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.12

Publications

0 publications found

Variant links:

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]

MEF2C links:

MEF2C-AS2 (HGNC:53115): (MEF2C antisense RNA 2)

MEF2C-AS2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27367997).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002397.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MEF2C	NM_002397.5	MANE Select	c.312C>A	p.Asp104Glu	missense	Exon 4 of 11	NP_002388.2
MEF2C	NM_001193347.1		c.312C>A	p.Asp104Glu	missense	Exon 5 of 12	NP_001180276.1	Q06413-5
MEF2C	NM_001193350.2		c.312C>A	p.Asp104Glu	missense	Exon 4 of 11	NP_001180279.1	Q06413-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MEF2C	ENST00000504921.7	TSL:1 MANE Select	c.312C>A	p.Asp104Glu	missense	Exon 4 of 11	ENSP00000421925.5	Q06413-1
MEF2C	ENST00000340208.9	TSL:1	c.312C>A	p.Asp104Glu	missense	Exon 5 of 12	ENSP00000340874.5	Q06413-5
MEF2C	ENST00000437473.6	TSL:1	c.312C>A	p.Asp104Glu	missense	Exon 4 of 11	ENSP00000396219.2	Q06413-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.082

Eigen

Benign

-0.027

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.72

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.27

MetaSVM

Uncertain

-0.11

MutationAssessor

Benign

1.3

PhyloP100

3.1

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.90

REVEL

Benign

0.16

Sift

Benign

0.33

Sift4G

Benign

0.45

Polyphen

0.027

Vest4

0.53

MutPred

0.18

Loss of stability (P = 0.0649)

MVP

0.81

MPC

1.5

ClinPred

0.79

GERP RS

5.1

Varity_R

0.35

gMVP

0.48

Mutation Taster

=77/23

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over