Genetic Variant MEF2A:p.Gln425_Gln428del (chr15-99712504-CCAGCAGCAGCAG-C) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3BS2

The NM_001319206.4(MEF2A):c.1274_1285delAGCAGCAGCAGC(p.Gln425_Gln428del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00116 in 1,531,496 control chromosomes in the GnomAD database, including 4 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0012 ( 4 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: Likely_benign. The variant received -5 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001319206.4

BS2

High AC in GnomAd4 at 187 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEF2A	NM_001319206.4 link	c.1274_1285delAGCAGCAGCAGC	p.Gln425_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.1274_1285delAGCAGCAGCAGC	p.Gln425_Gln428del	disruptive_inframe_deletion	Exon 12 of 12	5	NM_001319206.4	ENSP00000453095.1		Q02078-2

Frequencies

GnomAD3 genomes

AF:

0.00125

AC:

188

AN:

150282

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00112

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00964

Gnomad SAS

AF:

0.00127

Gnomad FIN

AF:

0.000195

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000948

Gnomad OTH

AF:

0.000977

GnomAD4 exome

AF:

0.00115

AC:

1594

AN:

1381096

Hom.:

AF XY:

0.00118

AC XY:

805

AN XY:

681096

show subpopulations

African (AFR)

AF:

0.00140

AC:

AN:

31384

American (AMR)

AF:

0.00206

AC:

AN:

35370

Ashkenazi Jewish (ASJ)

AF:

0.000846

AC:

AN:

24828

East Asian (EAS)

AF:

0.00738

AC:

259

AN:

35112

South Asian (SAS)

AF:

0.00128

AC:

100

AN:

78088

European-Finnish (FIN)

AF:

0.000334

AC:

AN:

47942

Middle Eastern (MID)

AF:

0.00124

AC:

AN:

5652

European-Non Finnish (NFE)

AF:

0.000933

AC:

994

AN:

1065388

Other (OTH)

AF:

0.00140

AC:

AN:

57332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

148

223

297

371

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

184

230

<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:

0.00124

AC:

187

AN:

150400

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

104

AN XY:

73376

show subpopulations

African (AFR)

AF:

0.00112

AC:

AN:

40926

American (AMR)

AF:

0.00112

AC:

AN:

15158

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00966

AC:

AN:

5072

South Asian (SAS)

AF:

0.00127

AC:

AN:

4706

European-Finnish (FIN)

AF:

0.000195

AC:

AN:

10274

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000948

AC:

AN:

67536

Other (OTH)

AF:

0.000966

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000157

Hom.:

638

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

6.7

Mutation Taster

=194/6

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-CCAGCAGCAGCAGCAG

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