15-99706737-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001319206.4(MEF2A):c.891G>A(p.Gln297=) 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 (★).

• Frequency:
  • Genomes: 𝑓 0.89 (62563 hom., cov: 30)
  • Exomes 𝑓: 0.99 (715785 hom.)
• Consequence: MEF2A NM_001319206.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.129

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]

ACMG classification

Verdict is Benign. Variant got -15 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 criteria_provided_single_submitter, 1 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/exons	MANE	UniProt
MEF2A	NM_001319206.4	c.891G>A	p.Gln297=	synonymous_variant	10/12	ENST00000557942.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEF2A	ENST00000557942.6	c.891G>A	p.Gln297=	synonymous_variant	10/12	5	NM_001319206.4

Frequencies

GnomAD3 genomes AF: 0.891 AC: 135464 AN: 151968 Hom.: 62531 Cov.: 30

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

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.: 45 AF XY: 0.990 AC XY: 719356 AN XY: 726812

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.: 30 AF XY: 0.896 AC XY: 66611 AN XY: 74372

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: criteria provided, single submitter

Submissions by phenotype

MEF2A-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

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

Other links and lift over

dbSNP: rs325407; hg19: chr15-100246942;