Genetic Variant MEF2A:c.*2838A>T (chr15-99715609-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001319206.4(MEF2A):c.*2838A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 152,158 control chromosomes in the GnomAD database, including 49,634 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.80 ( 49630 hom., cov: 32)

Exomes 𝑓: 1.0 ( 4 hom. )

Consequence

MEF2A
NM_001319206.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.315

Publications

14 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:

LYSMD4 (HGNC:26571): (LysM domain containing 4) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LYSMD4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEF2A	NM_001319206.4 link	c.*2838A>T		3_prime_UTR_variant	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.*2838A>T		3_prime_UTR_variant	Exon 12 of 12	5	NM_001319206.4	ENSP00000453095.1		Q02078-2

Frequencies

GnomAD3 genomes

AF:

0.802

AC:

121901

AN:

152032

Hom.:

49590

Cov.:

show subpopulations

Gnomad AFR

AF:

0.670

Gnomad AMI

AF:

0.945

Gnomad AMR

AF:

0.765

Gnomad ASJ

AF:

0.920

Gnomad EAS

AF:

0.745

Gnomad SAS

AF:

0.881

Gnomad FIN

AF:

0.924

Gnomad MID

AF:

0.937

Gnomad NFE

AF:

0.861

Gnomad OTH

AF:

0.826

GnomAD4 exome

AF:

1.00

AC:

AN:

Hom.:

Cov.:

AF XY:

1.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.802

AC:

121996

AN:

152150

Hom.:

49630

Cov.:

AF XY:

0.804

AC XY:

59844

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.670

AC:

27790

AN:

41480

American (AMR)

AF:

0.764

AC:

11684

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.920

AC:

3193

AN:

3472

East Asian (EAS)

AF:

0.747

AC:

3863

AN:

5174

South Asian (SAS)

AF:

0.882

AC:

4244

AN:

4814

European-Finnish (FIN)

AF:

0.924

AC:

9792

AN:

10598

Middle Eastern (MID)

AF:

0.942

AC:

277

AN:

294

European-Non Finnish (NFE)

AF:

0.861

AC:

58543

AN:

68004

Other (OTH)

AF:

0.828

AC:

1750

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1176

2352

3527

4703

5879

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.824

Hom.:

6481

Bravo

AF:

0.782

Asia WGS

AF:

0.812

AC:

2825

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.034

(source)

DANN

Benign

0.72

PhyloP100

-0.32

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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15-99715609-A-T

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