15-99712504-CCAGCAGCAGCAGCAGCAGCAGCAGCAG-CCAGCAGCAGCAGCAGCAGCAGCAG

Position:

• chr15-99712504-CCAGCAGCAGCAGCAGCAGCAGCAGCAG-CCAGCAGCAGCAGCAGCAGCAGCAG

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_001319206.4(MEF2A):​c.1283_1285delAGC​(p.Gln428del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.145 in 1,481,606 control chromosomes in the GnomAD database, including 9,671 homozygotes. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.14 (1598 hom., cov: 0)
  • Exomes 𝑓: 0.14 (8073 hom.)
• Consequence: MEF2A NM_001319206.4 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.55

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 -9 ACMG points.

• BP6: Variant 15-99712504-CCAG-C is Benign according to our data. Variant chr15-99712504-CCAG-C is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEF2A	NM_001319206.4	c.1283_1285delAGC	p.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.1283_1285delAGC	p.Gln428del	disruptive_inframe_deletion	12/12	5	NM_001319206.4	ENSP00000453095.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21466 AN: 150166 Hom.: 1596 Cov.: 0

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.0556

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0653

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.142

GnomAD3 exomes AF: 0.153 AC: 18574 AN: 121148 Hom.: 646 AF XY: 0.153 AC XY: 9821 AN XY: 64250

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.174

Gnomad ASJ exome AF: 0.141

Gnomad EAS exome AF: 0.243

Gnomad SAS exome AF: 0.142

Gnomad FIN exome AF: 0.0799

Gnomad NFE exome AF: 0.154

Gnomad OTH exome AF: 0.156

GnomAD4 exome AF: 0.145 AC: 192729 AN: 1331322 Hom.: 8073 AF XY: 0.144 AC XY: 94513 AN XY: 654858

Gnomad4 AFR exome AF: 0.157

Gnomad4 AMR exome AF: 0.166

Gnomad4 ASJ exome AF: 0.127

Gnomad4 EAS exome AF: 0.163

Gnomad4 SAS exome AF: 0.124

Gnomad4 FIN exome AF: 0.0778

Gnomad4 NFE exome AF: 0.148

Gnomad4 OTH exome AF: 0.148

GnomAD4 genome AF: 0.143 AC: 21488 AN: 150284 Hom.: 1598 Cov.: 0 AF XY: 0.140 AC XY: 10283 AN XY: 73316

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.0653

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.141

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: rs3138597; hg19: chr15-100252709;