Genetic Variant NM_001319206.4:c.1265_1285delAGCAGCAGCAGCAGCAGCAGC (chr15-99712504-CCAGCAGCAGCAGCAGCAGCAG-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.1265_1285delAGCAGCAGCAGCAGCAGCAGC(p.Gln422_Gln428del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00103 in 1,531,530 control chromosomes in the GnomAD database, including 11 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: 0.0010 ( 11 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 eas. GnomAdExome4 allele frequency = 0.001 (1385/1381126) while in subpopulation EAS AF = 0.0179 (630/35110). AF 95% confidence interval is 0.0168. There are 11 homozygotes in GnomAdExome4. There are 715 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check.

BS2

High AC in GnomAd4 at 186 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEF2A	NM_001319206.4 link	c.1265_1285delAGCAGCAGCAGCAGCAGCAGC	p.Gln422_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.1265_1285delAGCAGCAGCAGCAGCAGCAGC	p.Gln422_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:

150286

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000196

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00125

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.0167

Gnomad SAS

AF:

0.00340

Gnomad FIN

AF:

0.00302

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000266

Gnomad OTH

AF:

0.00244

GnomAD4 exome

AF:

0.00100

AC:

1385

AN:

1381126

Hom.:

AF XY:

0.00105

AC XY:

715

AN XY:

681104

show subpopulations

African (AFR)

AF:

0.000319

AC:

AN:

31386

American (AMR)

AF:

0.000565

AC:

AN:

35370

Ashkenazi Jewish (ASJ)

AF:

0.00125

AC:

AN:

24828

East Asian (EAS)

AF:

0.0179

AC:

630

AN:

35110

South Asian (SAS)

AF:

0.00265

AC:

207

AN:

78090

European-Finnish (FIN)

AF:

0.00288

AC:

138

AN:

47946

Middle Eastern (MID)

AF:

0.000885

AC:

AN:

5652

European-Non Finnish (NFE)

AF:

0.000270

AC:

288

AN:

1065410

Other (OTH)

AF:

0.000977

AC:

AN:

57334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

109

163

218

272

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<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:

186

AN:

150404

Hom.:

Cov.:

AF XY:

0.00147

AC XY:

108

AN XY:

73376

show subpopulations

African (AFR)

AF:

0.000195

AC:

AN:

40928

American (AMR)

AF:

0.00125

AC:

AN:

15160

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3464

East Asian (EAS)

AF:

0.0166

AC:

AN:

5072

South Asian (SAS)

AF:

0.00340

AC:

AN:

4706

European-Finnish (FIN)

AF:

0.00302

AC:

AN:

10274

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000267

AC:

AN:

67536

Other (OTH)

AF:

0.00193

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

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:

0.00

Hom.:

638

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

6.7

Mutation Taster

=144/56

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