chr15-99712504-C-CCAGCAGCAG

Variant names:

• chr15-99712504-C-CCAGCAGCAG
• rs3138597
• NM_001319206.4:c.1277_1285dupAGCAGCAGC

Variant summary

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

The NM_001319206.4(MEF2A):​c.1277_1285dupAGCAGCAGC​(p.Gln426_Gln428dup) variant causes a disruptive inframe insertion change. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00085 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00067 (3 hom.)
• Consequence: MEF2A NM_001319206.4 disruptive_inframe_insertion
• 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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 128 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEF2A	NM_001319206.4	c.1277_1285dupAGCAGCAGC	p.Gln426_Gln428dup	disruptive_inframe_insertion	Exon 12 of 12	ENST00000557942.6	NP_001306135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEF2A	ENST00000557942.6	c.1277_1285dupAGCAGCAGC	p.Gln426_Gln428dup	disruptive_inframe_insertion	Exon 12 of 12	5	NM_001319206.4	ENSP00000453095.1

Frequencies

GnomAD3 genomes AF: 0.000845 AC: 127 AN: 150286 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00172

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000859

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00354

Gnomad SAS AF: 0.000849

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000326

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000665 AC: 919 AN: 1381120 Hom.: 3 Cov.: 0 AF XY: 0.000681 AC XY: 464 AN XY: 681102

Gnomad4 AFR exome AF: 0.00226

Gnomad4 AMR exome AF: 0.000876

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0116

Gnomad4 SAS exome AF: 0.000474

Gnomad4 FIN exome AF: 0.0000834

Gnomad4 NFE exome AF: 0.000283

Gnomad4 OTH exome AF: 0.000942

GnomAD4 genome AF: 0.000851 AC: 128 AN: 150404 Hom.: 0 Cov.: 0 AF XY: 0.000886 AC XY: 65 AN XY: 73376

Gnomad4 AFR AF: 0.00173

Gnomad4 AMR AF: 0.000858

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00355

Gnomad4 SAS AF: 0.000850

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000326

Gnomad4 OTH AF: 0.00

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;