Genetic Variant MEF2A:p.Gln297Gln (chr15-99706737-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001319206.4(MEF2A):c.891G>A(p.Gln297Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.979 in 1,613,008 control chromosomes in the GnomAD database, including 778,348 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.89 ( 62563 hom., cov: 30)

Exomes 𝑓: 0.99 ( 715785 hom. )

Consequence

MEF2A
NM_001319206.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.129

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 made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 15-99706737-G-A is Benign according to our data. Variant chr15-99706737-G-A is described in ClinVar as [Benign]. Clinvar id is 3059607.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.129 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEF2A	NM_001319206.4 link	c.891G>A	p.Gln297Gln	synonymous_variant	Exon 10 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.891G>A	p.Gln297Gln	synonymous_variant	Exon 10 of 12	5	NM_001319206.4	ENSP00000453095.1		Q02078-2

Frequencies

GnomAD3 genomes

AF:

0.891

AC:

135464

AN:

151968

Hom.:

62531

Cov.:

show subpopulations

Gnomad AFR

AF:

0.623

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.959

Gnomad ASJ

AF:

0.999

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.953

Gnomad NFE

AF:

0.998

Gnomad OTH

AF:

0.928

GnomAD3 exomes

AF:

0.972

AC:

242354

AN:

249252

Hom.:

118868

AF XY:

0.979

AC XY:

132375

AN XY:

135232

show subpopulations

Gnomad AFR exome

AF:

0.620

Gnomad AMR exome

AF:

0.981

Gnomad ASJ exome

AF:

0.997

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.999

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.998

Gnomad OTH exome

AF:

0.986

GnomAD4 exome

AF:

0.988

AC:

1443589

AN:

1460922

Hom.:

715785

Cov.:

AF XY:

0.990

AC XY:

719356

AN XY:

726812

show subpopulations

Gnomad4 AFR exome

AF:

0.614

Gnomad4 AMR exome

AF:

0.978

Gnomad4 ASJ exome

AF:

0.997

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.999

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

0.998

Gnomad4 OTH exome

AF:

0.975

GnomAD4 genome

AF:

0.891

AC:

135546

AN:

152086

Hom.:

62563

Cov.:

AF XY:

0.896

AC XY:

66611

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.624

Gnomad4 AMR

AF:

0.959

Gnomad4 ASJ

AF:

0.999

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.999

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.998

Gnomad4 OTH

AF:

0.928

Alfa

AF:

0.947

Hom.:

47532

Bravo

AF:

0.876

Asia WGS

AF:

0.981

AC:

3412

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MEF2A-related disorder

Benign:1

Oct 28, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.19

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over