NM_002397.5:c.*115dupA

Variant names:

• chr5-88722488-C-CT
• rs553216678
• NM_002397.5:c.*115dupA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_002397.5(MEF2C):​c.*115dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0387 in 681,416 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 32)
  • Exomes 𝑓: 0.049 (0 hom.)
• Consequence: MEF2C NM_002397.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.63

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

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEF2C	NM_002397.5	c.*115dupA		3_prime_UTR_variant	Exon 11 of 11	ENST00000504921.7	NP_002388.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEF2C	ENST00000504921	c.*115dupA		3_prime_UTR_variant	Exon 11 of 11	1	NM_002397.5	ENSP00000421925.5

Frequencies

GnomAD3 genomes AF: 0.000207 AC: 30 AN: 145172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000252

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000415

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000400

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000898

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000606

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0491 AC: 26345 AN: 536212 Hom.: 0 Cov.: 8 AF XY: 0.0485 AC XY: 13287 AN XY: 273838

Gnomad4 AFR exome AF: 0.0486

Gnomad4 AMR exome AF: 0.0485

Gnomad4 ASJ exome AF: 0.0499

Gnomad4 EAS exome AF: 0.0401

Gnomad4 SAS exome AF: 0.0561

Gnomad4 FIN exome AF: 0.0394

Gnomad4 NFE exome AF: 0.0497

Gnomad4 OTH exome AF: 0.0489

GnomAD4 genome AF: 0.000207 AC: 30 AN: 145204 Hom.: 0 Cov.: 32 AF XY: 0.000170 AC XY: 12 AN XY: 70538

Gnomad4 AFR AF: 0.000252

Gnomad4 AMR AF: 0.000415

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000402

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000898

Gnomad4 NFE AF: 0.0000606

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs553216678; hg19: chr5-88018305;