rs34851361

chr15-99712687-A-G

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.1434A>G(p.Pro478=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0842 in 1,561,912 control chromosomes in the GnomAD database, including 6,251 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.063 (428 hom., cov: 32)
  • Exomes 𝑓: 0.087 (5823 hom.)
• Consequence: MEF2A NM_001319206.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.14

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=-0.96).
• BP6: Variant 15-99712687-A-G is Benign according to our data. Variant chr15-99712687-A-G is described in ClinVar as [Benign]. Clinvar id is 3056661.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.14 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEF2A	NM_001319206.4	c.1434A>G	p.Pro478=	synonymous_variant	12/12	ENST00000557942.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEF2A	ENST00000557942.6	c.1434A>G	p.Pro478=	synonymous_variant	12/12	5	NM_001319206.4

Frequencies

GnomAD3 genomes AF: 0.0630 AC: 9579 AN: 151940 Hom.: 428 Cov.: 32

Gnomad AFR AF: 0.0245

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.0613

Gnomad ASJ AF: 0.0888

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0268

Gnomad FIN AF: 0.0464

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0944

Gnomad OTH AF: 0.0724

GnomAD3 exomes AF: 0.0615 AC: 10754 AN: 174956 Hom.: 442 AF XY: 0.0614 AC XY: 5683 AN XY: 92522

Gnomad AFR exome AF: 0.0202

Gnomad AMR exome AF: 0.0451

Gnomad ASJ exome AF: 0.0896

Gnomad EAS exome AF: 0.0000816

Gnomad SAS exome AF: 0.0282

Gnomad FIN exome AF: 0.0474

Gnomad NFE exome AF: 0.0931

Gnomad OTH exome AF: 0.0751

GnomAD4 exome AF: 0.0865 AC: 121964 AN: 1409854 Hom.: 5823 Cov.: 38 AF XY: 0.0845 AC XY: 58846 AN XY: 696290

Gnomad4 AFR exome AF: 0.0225

Gnomad4 AMR exome AF: 0.0480

Gnomad4 ASJ exome AF: 0.0884

Gnomad4 EAS exome AF: 0.000191

Gnomad4 SAS exome AF: 0.0298

Gnomad4 FIN exome AF: 0.0499

Gnomad4 NFE exome AF: 0.0987

Gnomad4 OTH exome AF: 0.0812

GnomAD4 genome AF: 0.0630 AC: 9578 AN: 152058 Hom.: 428 Cov.: 32 AF XY: 0.0594 AC XY: 4416 AN XY: 74316

Gnomad4 AFR AF: 0.0245

Gnomad4 AMR AF: 0.0612

Gnomad4 ASJ AF: 0.0888

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0266

Gnomad4 FIN AF: 0.0464

Gnomad4 NFE AF: 0.0944

Gnomad4 OTH AF: 0.0716

Alfa AF: 0.0820 Hom.: 324

Bravo AF: 0.0643

Asia WGS AF: 0.0140 AC: 50 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

Nov 12, 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	-0.96
Cadd	Benign	0.28
Dann	Benign	0.62

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

LitVar

Other links and lift over

dbSNP: rs34851361; hg19: chr15-100252892; COSMIC: COSV57537893; COSMIC: COSV57537893;