5-88856300-C-T

Variant names:

• chr5-88856300-C-T
• rs700585
• NM_002397.5:c.-143+26655G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002397.5(MEF2C):​c.-143+26655G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.822 in 152,198 control chromosomes in the GnomAD database, including 51,783 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.82 (51783 hom., cov: 32)
• Consequence: MEF2C NM_002397.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82
• Publications: 13 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEF2C	NM_002397.5	c.-143+26655G>A		intron_variant	Intron 1 of 10	ENST00000504921.7	NP_002388.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEF2C	ENST00000504921.7	c.-143+26655G>A		intron_variant	Intron 1 of 10	1	NM_002397.5	ENSP00000421925.5

Frequencies

GnomAD3 genomes AF: 0.822 AC: 125058 AN: 152080 Hom.: 51726 Cov.: 32

Gnomad AFR AF: 0.923

Gnomad AMI AF: 0.923

Gnomad AMR AF: 0.792

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.812

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.811

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.822 AC: 125173 AN: 152198 Hom.: 51783 Cov.: 32 AF XY: 0.823 AC XY: 61258 AN XY: 74404

African (AFR) AF: 0.923 AC: 38348 AN: 41536

American (AMR) AF: 0.791 AC: 12103 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.793 AC: 2750 AN: 3470

East Asian (EAS) AF: 0.773 AC: 4007 AN: 5184

South Asian (SAS) AF: 0.812 AC: 3908 AN: 4814

European-Finnish (FIN) AF: 0.806 AC: 8527 AN: 10582

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.775 AC: 52736 AN: 68004

Other (OTH) AF: 0.814 AC: 1717 AN: 2110

Alfa AF: 0.793 Hom.: 32514

Bravo AF: 0.829

Asia WGS AF: 0.818 AC: 2847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.39
DANN	Benign	0.45
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs700585; hg19: chr5-88152117;