Genetic Variant MEF2A:p.Gln427_Gln428dup (chr15-99712504-C-CCAGCAG) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBA1

The NM_001319206.4(MEF2A):c.1280_1285dupAGCAGC(p.Gln427_Gln428dup) variant causes a disruptive inframe insertion change. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 185 hom., cov: 0)

Exomes 𝑓: 0.0031 ( 37 hom. )

Consequence

MEF2A
NM_001319206.4 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001319206.4

BP6

Variant 15-99712504-C-CCAGCAG is Benign according to our data. Variant chr15-99712504-C-CCAGCAG is described in ClinVar as Benign. ClinVar VariationId is 778574.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEF2A	NM_001319206.4 link	c.1280_1285dupAGCAGC	p.Gln427_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.1280_1285dupAGCAGC	p.Gln427_Gln428dup	disruptive_inframe_insertion	Exon 12 of 12	5	NM_001319206.4	ENSP00000453095.1		Q02078-2

Frequencies

GnomAD3 genomes

AF:

0.0277

AC:

4160

AN:

150260

Hom.:

181

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0931

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0155

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.000787

Gnomad SAS

AF:

0.00234

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000622

Gnomad OTH

AF:

0.0278

GnomAD2 exomes

AF:

0.00711

AC:

861

AN:

121148

AF XY:

0.00565

show subpopulations

Gnomad AFR exome

AF:

0.0991

Gnomad AMR exome

AF:

0.00846

Gnomad ASJ exome

AF:

0.00225

Gnomad EAS exome

AF:

0.00110

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000968

Gnomad OTH exome

AF:

0.00766

GnomAD4 exome

AF:

0.00311

AC:

4301

AN:

1381108

Hom.:

Cov.:

AF XY:

0.00276

AC XY:

1879

AN XY:

681094

show subpopulations

African (AFR)

AF:

0.0908

AC:

2848

AN:

31374

American (AMR)

AF:

0.00803

AC:

284

AN:

35370

Ashkenazi Jewish (ASJ)

AF:

0.00209

AC:

AN:

24828

East Asian (EAS)

AF:

0.000484

AC:

AN:

35106

South Asian (SAS)

AF:

0.00114

AC:

AN:

78088

European-Finnish (FIN)

AF:

0.0000209

AC:

AN:

47946

Middle Eastern (MID)

AF:

0.00902

AC:

AN:

5652

European-Non Finnish (NFE)

AF:

0.000445

AC:

474

AN:

1065412

Other (OTH)

AF:

0.00846

AC:

485

AN:

57332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

236

472

707

943

1179

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

106

212

318

424

530

<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:

0.0278

AC:

4178

AN:

150378

Hom.:

185

Cov.:

AF XY:

0.0270

AC XY:

1980

AN XY:

73356

show subpopulations

African (AFR)

AF:

0.0932

AC:

3814

AN:

40904

American (AMR)

AF:

0.0155

AC:

235

AN:

15158

Ashkenazi Jewish (ASJ)

AF:

0.00231

AC:

AN:

3464

East Asian (EAS)

AF:

0.000789

AC:

AN:

5072

South Asian (SAS)

AF:

0.00234

AC:

AN:

4706

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10274

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000622

AC:

AN:

67536

Other (OTH)

AF:

0.0275

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

174

347

521

694

868

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<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:

0.00199

Hom.:

638

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Coronary artery disease, autosomal dominant, 1

Benign:1

Dec 12, 2023

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

6.5

Mutation Taster

=56/44

polymorphism (auto)

(source)

Splicing

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

Publications

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15-99712504-CCAGCAGCAGCAGCAGCAGCAGCAGCAG-CCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over