Genetic Variant NM_001319206.4:c.1283_1285dupAGC (chr15-99712504-C-CCAG) – 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.1283_1285dupAGC(p.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 0.0044 ( 2 hom., cov: 0)

Exomes 𝑓: 0.0029 ( 3 hom. )

Consequence

MEF2A
NM_001319206.4 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.55

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 663 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEF2A	NM_001319206.4 link	c.1283_1285dupAGC	p.Gln428dup	disruptive_inframe_insertion	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.1283_1285dupAGC	p.Gln428dup	disruptive_inframe_insertion	Exon 12 of 12	5	NM_001319206.4	ENSP00000453095.1		Q02078-2

Frequencies

GnomAD3 genomes

AF:

0.00440

AC:

661

AN:

150280

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00887

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00291

Gnomad ASJ

AF:

0.00433

Gnomad EAS

AF:

0.00236

Gnomad SAS

AF:

0.00106

Gnomad FIN

AF:

0.000974

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00289

Gnomad OTH

AF:

0.00830

GnomAD2 exomes

AF:

0.00333

AC:

403

AN:

121148

AF XY:

0.00324

show subpopulations

Gnomad AFR exome

AF:

0.0108

Gnomad AMR exome

AF:

0.00301

Gnomad ASJ exome

AF:

0.00361

Gnomad EAS exome

AF:

0.00269

Gnomad FIN exome

AF:

0.00183

Gnomad NFE exome

AF:

0.00327

Gnomad OTH exome

AF:

0.00265

GnomAD4 exome

AF:

0.00285

AC:

3938

AN:

1380958

Hom.:

Cov.:

AF XY:

0.00278

AC XY:

1896

AN XY:

681030

show subpopulations

African (AFR)

AF:

0.00919

AC:

287

AN:

31242

American (AMR)

AF:

0.00294

AC:

104

AN:

35366

Ashkenazi Jewish (ASJ)

AF:

0.00383

AC:

AN:

24828

East Asian (EAS)

AF:

0.00262

AC:

AN:

35112

South Asian (SAS)

AF:

0.00225

AC:

176

AN:

78088

European-Finnish (FIN)

AF:

0.00136

AC:

AN:

47944

Middle Eastern (MID)

AF:

0.00354

AC:

AN:

5652

European-Non Finnish (NFE)

AF:

0.00272

AC:

2898

AN:

1065394

Other (OTH)

AF:

0.00351

AC:

201

AN:

57332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

202

403

605

806

1008

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

220

330

440

550

<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:

0.00441

AC:

663

AN:

150398

Hom.:

Cov.:

AF XY:

0.00388

AC XY:

285

AN XY:

73374

show subpopulations

African (AFR)

AF:

0.00885

AC:

362

AN:

40926

American (AMR)

AF:

0.00290

AC:

AN:

15158

Ashkenazi Jewish (ASJ)

AF:

0.00433

AC:

AN:

3464

East Asian (EAS)

AF:

0.00237

AC:

AN:

5072

South Asian (SAS)

AF:

0.00106

AC:

AN:

4706

European-Finnish (FIN)

AF:

0.000974

AC:

AN:

10272

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00289

AC:

195

AN:

67536

Other (OTH)

AF:

0.00918

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

131

164

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00220

Hom.:

638

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

6.5

Mutation Taster

=56/44

polymorphism

(source)

Splicing

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

Publications

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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