15-99712504-CCAGCAGCAGCAGCAGCAGCAGCAGCAG-CCAGCAGCAGCAGCAGCAG

Variant names:

• chr15-99712504-CCAGCAGCAG-C
• rs3138597
• NM_001319206.4:c.1277_1285delAGCAGCAGC

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP3 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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -9 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001319206.4
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 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 GnomAdExome4. There are 1105 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check.
• BS2: High AC in GnomAd4 at 795 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001319206.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEF2A	NM_001319206.4	MANE Select	c.1277_1285delAGCAGCAGC	p.Gln426_Gln428del	disruptive_inframe_deletion	Exon 12 of 12	NP_001306135.1	Q02078-2
	MEF2A	NM_001400028.1		c.1391_1399delAGCAGCAGC	p.Gln464_Gln466del	disruptive_inframe_deletion	Exon 12 of 12	NP_001386957.1
	MEF2A	NM_001365201.3		c.1295_1303delAGCAGCAGC	p.Gln432_Gln434del	disruptive_inframe_deletion	Exon 12 of 12	NP_001352130.1	A0A8I5KVQ4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEF2A	ENST00000557942.6	TSL:5 MANE Select	c.1277_1285delAGCAGCAGC	p.Gln426_Gln428del	disruptive_inframe_deletion	Exon 12 of 12	ENSP00000453095.1	Q02078-2
	MEF2A	ENST00000354410.9	TSL:1	c.1259_1267delAGCAGCAGC	p.Gln420_Gln422del	disruptive_inframe_deletion	Exon 11 of 11	ENSP00000346389.5	Q02078-5
	MEF2A	ENST00000947006.1		c.1415_1423delAGCAGCAGC	p.Gln472_Gln474del	disruptive_inframe_deletion	Exon 12 of 12	ENSP00000617065.1

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

GnomAD2 exomes AF: 0.00370 AC: 448 AN: 121148 AF XY: 0.00353

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 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

African (AFR) AF: 0.0176 AC: 552 AN: 31320

American (AMR) AF: 0.00248 AC: 85 AN: 34320

Ashkenazi Jewish (ASJ) AF: 0.000300 AC: 7 AN: 23372

East Asian (EAS) AF: 0.00759 AC: 253 AN: 33348

South Asian (SAS) AF: 0.00123 AC: 88 AN: 71384

European-Finnish (FIN) AF: 0.00104 AC: 47 AN: 45110

Middle Eastern (MID) AF: 0.00345 AC: 19 AN: 5512

European-Non Finnish (NFE) AF: 0.00114 AC: 1167 AN: 1024952

Other (OTH) AF: 0.00221 AC: 122 AN: 55108

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

African (AFR) AF: 0.0156 AC: 638 AN: 40926

American (AMR) AF: 0.00350 AC: 53 AN: 15156

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00848 AC: 43 AN: 5070

South Asian (SAS) AF: 0.000425 AC: 2 AN: 4706

European-Finnish (FIN) AF: 0.000195 AC: 2 AN: 10242

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000770 AC: 52 AN: 67524

Other (OTH) AF: 0.00242 AC: 5 AN: 2070

Alfa AF: 0.0168 Hom.: 638

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.7
Mutation Taster		=198/2	polymorphism

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3138597;

hg19: chr15-100252709;