15-99712504-CCAGCAGCAGCAGCAGCAGCAGCAGCAG-CCAGCAGCAG

Position:

• chr15-99712504-CCAGCAGCAGCAGCAGCAGCAGCAGCAG-CCAGCAGCAG

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001319206.4(MEF2A):​c.1268_1285delAGCAGCAGCAGCAGCAGC​(p.Gln423_Gln428del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00198 in 1,531,506 control chromosomes in the GnomAD database, including 20 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0034 (3 hom., cov: 0)
  • Exomes 𝑓: 0.0018 (17 hom.)
• Consequence: MEF2A NM_001319206.4 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.73

Genes affected

MEF2A (HGNC:6993): (myocyte enhancer factor 2A) The protein encoded by this gene is a DNA-binding transcription factor that activates many muscle-specific, growth factor-induced, and stress-induced genes. The encoded protein can act as a homodimer or as a heterodimer and is involved in several cellular processes, including muscle development, neuronal differentiation, cell growth control, and apoptosis. Defects in this gene could be a cause of autosomal dominant coronary artery disease 1 with myocardial infarction (ADCAD1). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]

MEF2A (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 516 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEF2A	NM_001319206.4	c.1268_1285delAGCAGCAGCAGCAGCAGC	p.Gln423_Gln428del	disruptive_inframe_deletion	12/12	ENST00000557942.6	NP_001306135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEF2A	ENST00000557942.6	c.1268_1285delAGCAGCAGCAGCAGCAGC	p.Gln423_Gln428del	disruptive_inframe_deletion	12/12	5	NM_001319206.4	ENSP00000453095.1

Frequencies

GnomAD3 genomes AF: 0.00343 AC: 516 AN: 150286 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.00809

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00106

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.00197

Gnomad SAS AF: 0.0115

Gnomad FIN AF: 0.000389

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000859

Gnomad OTH AF: 0.00342

GnomAD4 exome AF: 0.00182 AC: 2509 AN: 1381102 Hom.: 17 AF XY: 0.00205 AC XY: 1398 AN XY: 681098

Gnomad4 AFR exome AF: 0.00739

Gnomad4 AMR exome AF: 0.00124

Gnomad4 ASJ exome AF: 0.0109

Gnomad4 EAS exome AF: 0.00436

Gnomad4 SAS exome AF: 0.00925

Gnomad4 FIN exome AF: 0.000292

Gnomad4 NFE exome AF: 0.000868

Gnomad4 OTH exome AF: 0.00225

GnomAD4 genome AF: 0.00343 AC: 516 AN: 150404 Hom.: 3 Cov.: 0 AF XY: 0.00333 AC XY: 244 AN XY: 73376

Gnomad4 AFR AF: 0.00809

Gnomad4 AMR AF: 0.00106

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.00197

Gnomad4 SAS AF: 0.0113

Gnomad4 FIN AF: 0.000389

Gnomad4 NFE AF: 0.000859

Gnomad4 OTH AF: 0.00338

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3138597; hg19: chr15-100252709;