rs244750

Variant names:

• chr5-88851375-T-C
• rs244750
• NM_002397.5:c.-142-27445A>G

Variant summary

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

The NM_002397.5(MEF2C):​c.-142-27445A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,064 control chromosomes in the GnomAD database, including 2,956 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 0.19 (2956 hom., cov: 31)
• Consequence: MEF2C NM_002397.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385
• Publications: 4 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEF2C	NM_002397.5	c.-142-27445A>G		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.-142-27445A>G		intron_variant	Intron 1 of 10	1	NM_002397.5	ENSP00000421925.5

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28841 AN: 151946 Hom.: 2950 Cov.: 31

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.0957

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.190 AC: 28880 AN: 152064 Hom.: 2956 Cov.: 31 AF XY: 0.190 AC XY: 14116 AN XY: 74346

African (AFR) AF: 0.209 AC: 8685 AN: 41460

American (AMR) AF: 0.277 AC: 4228 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 770 AN: 3462

East Asian (EAS) AF: 0.0953 AC: 494 AN: 5184

South Asian (SAS) AF: 0.237 AC: 1140 AN: 4818

European-Finnish (FIN) AF: 0.156 AC: 1653 AN: 10572

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11175 AN: 67974

Other (OTH) AF: 0.218 AC: 459 AN: 2106

Alfa AF: 0.182 Hom.: 927

Bravo AF: 0.204

Asia WGS AF: 0.196 AC: 681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.7
DANN	Benign	0.66
PhyloP100		-0.39
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: rs244750; hg19: chr5-88147192;