Genetic Variant MEF2A:p.Gln426_Gln428del (chr15-99712504-CCAGCAGCAG-C) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP3BS1BS2

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

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.73

Publications

9 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEF2A	NM_001319206.4 link	c.1277_1285delAGCAGCAGC	p.Gln426_Gln428del	disruptive_inframe_deletion	Exon 12 of 12	ENST00000557942.6	NP_001306135.1	Q02078-2A0A0S2Z4N0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEF2A	ENST00000557942.6 link	c.1277_1285delAGCAGCAGC	p.Gln426_Gln428del	disruptive_inframe_deletion	Exon 12 of 12	5	NM_001319206.4	ENSP00000453095.1		Q02078-2

Frequencies

GnomAD3 genomes

AF:

0.00527

AC:

792

AN:

150234

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.00170

AC XY:

1105

AN XY:

651504

show subpopulations

African (AFR)

AF:

0.0176

AC:

552

AN:

31320

American (AMR)

AF:

0.00248

AC:

AN:

34320

Ashkenazi Jewish (ASJ)

AF:

0.000300

AC:

AN:

23372

East Asian (EAS)

AF:

0.00759

AC:

253

AN:

33348

South Asian (SAS)

AF:

0.00123

AC:

AN:

71384

European-Finnish (FIN)

AF:

0.00104

AC:

AN:

45110

Middle Eastern (MID)

AF:

0.00345

AC:

AN:

5512

European-Non Finnish (NFE)

AF:

0.00114

AC:

1167

AN:

1024952

Other (OTH)

AF:

0.00221

AC:

122

AN:

55108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.437

Heterozygous variant carriers

190

286

381

476

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

124

186

248

310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00529

AC:

795

AN:

150352

Hom.:

Cov.:

AF XY:

0.00492

AC XY:

361

AN XY:

73362

show subpopulations

African (AFR)

AF:

0.0156

AC:

638

AN:

40926

American (AMR)

AF:

0.00350

AC:

AN:

15156

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00848

AC:

AN:

5070

South Asian (SAS)

AF:

0.000425

AC:

AN:

4706

European-Finnish (FIN)

AF:

0.000195

AC:

AN:

10242

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000770

AC:

AN:

67524

Other (OTH)

AF:

0.00242

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

110

146

183

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0168

Hom.:

638

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

6.7

Mutation Taster

=198/2

polymorphism

(source)

Splicing

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

Publications

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15-99712504-CCAGCAGCAGCAGCAGCAGCAGCAGCAG-CCAGCAGCAGCAGCAGCAG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over