rs244749

Variant names:

• chr5-88845145-T-C
• rs244749
• NM_002397.5:c.-142-21215A>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.-142-21215A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 152,110 control chromosomes in the GnomAD database, including 10,688 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 0.34 (10688 hom., cov: 32)
• Consequence: MEF2C NM_002397.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.255
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEF2C	NM_002397.5	c.-142-21215A>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.-142-21215A>G		intron_variant	Intron 1 of 10	1	NM_002397.5	ENSP00000421925.5

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50920 AN: 151992 Hom.: 10669 Cov.: 32

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.335 AC: 50988 AN: 152110 Hom.: 10688 Cov.: 32 AF XY: 0.333 AC XY: 24743 AN XY: 74376

African (AFR) AF: 0.581 AC: 24099 AN: 41456

American (AMR) AF: 0.381 AC: 5825 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 901 AN: 3462

East Asian (EAS) AF: 0.341 AC: 1770 AN: 5184

South Asian (SAS) AF: 0.310 AC: 1495 AN: 4822

European-Finnish (FIN) AF: 0.179 AC: 1899 AN: 10590

Middle Eastern (MID) AF: 0.380 AC: 111 AN: 292

European-Non Finnish (NFE) AF: 0.205 AC: 13956 AN: 67990

Other (OTH) AF: 0.333 AC: 705 AN: 2116

Alfa AF: 0.282 Hom.: 6330

Bravo AF: 0.368

Asia WGS AF: 0.361 AC: 1256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.5
DANN	Benign	0.43
PhyloP100		0.26
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: rs244749; hg19: chr5-88140962;