15-99712504-CCAGCAGCAGCAGCAGCAGCAGCAGCAG-CCAGCAGCAGCAGCAGCAG

Position:

• chr15-99712504-CCAGCAGCAGCAGCAGCAGCAGCAGCAG-CCAGCAGCAGCAGCAGCAG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001319206.4(MEF2A):​c.1277_1285delAGCAGCAGC​(p.Gln426_Gln428del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00213 in 1,474,778 control chromosomes in the GnomAD database, including 7 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0053 (5 hom., cov: 0)
  • Exomes 𝑓: 0.0018 (2 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 Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00177 (2340/1324426) while in subpopulation AFR AF= 0.0176 (552/31320). AF 95% confidence interval is 0.0164. There are 2 homozygotes in gnomad4_exome. There are 1105 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 795 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEF2A	NM_001319206.4	c.1277_1285delAGCAGCAGC	p.Gln426_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.1277_1285delAGCAGCAGC	p.Gln426_Gln428del	disruptive_inframe_deletion	12/12	5	NM_001319206.4	ENSP00000453095.1

Frequencies

GnomAD3 genomes AF: 0.00527 AC: 792 AN: 150234 Hom.: 4 Cov.: 0

Gnomad AFR AF: 0.0156

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00350

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00846

Gnomad SAS AF: 0.000425

Gnomad FIN AF: 0.000195

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000770

Gnomad OTH AF: 0.00244

GnomAD3 exomes AF: 0.00370 AC: 448 AN: 121148 Hom.: 10 AF XY: 0.00353 AC XY: 227 AN XY: 64250

Gnomad AFR exome AF: 0.0217

Gnomad AMR exome AF: 0.00322

Gnomad ASJ exome AF: 0.000901

Gnomad EAS exome AF: 0.0113

Gnomad SAS exome AF: 0.00175

Gnomad FIN exome AF: 0.00242

Gnomad NFE exome AF: 0.00196

Gnomad OTH exome AF: 0.00177

GnomAD4 exome AF: 0.00177 AC: 2340 AN: 1324426 Hom.: 2 AF XY: 0.00170 AC XY: 1105 AN XY: 651504

Gnomad4 AFR exome AF: 0.0176

Gnomad4 AMR exome AF: 0.00248

Gnomad4 ASJ exome AF: 0.000300

Gnomad4 EAS exome AF: 0.00759

Gnomad4 SAS exome AF: 0.00123

Gnomad4 FIN exome AF: 0.00104

Gnomad4 NFE exome AF: 0.00114

Gnomad4 OTH exome AF: 0.00221

GnomAD4 genome AF: 0.00529 AC: 795 AN: 150352 Hom.: 5 Cov.: 0 AF XY: 0.00492 AC XY: 361 AN XY: 73362

Gnomad4 AFR AF: 0.0156

Gnomad4 AMR AF: 0.00350

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00848

Gnomad4 SAS AF: 0.000425

Gnomad4 FIN AF: 0.000195

Gnomad4 NFE AF: 0.000770

Gnomad4 OTH AF: 0.00242

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;