Variant 15-99690352-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001319206.4(MEF2A):c.782A>G(p.Asn261Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,613,574 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00094 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 5 hom. )

Consequence

MEF2A
NM_001319206.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1B:2

Conservation

PhyloP100: -0.0310

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 made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05635968).

BP6

Variant 15-99690352-A-G is Benign according to our data. Variant chr15-99690352-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 8950.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 143 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEF2A	NM_001319206.4 linkuse as main transcript	c.782A>G	p.Asn261Ser	missense_variant	8/12	ENST00000557942.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEF2A	ENST00000557942.6 linkuse as main transcript	c.782A>G	p.Asn261Ser	missense_variant	8/12	5	NM_001319206.4		Q02078-2

Frequencies

GnomAD3 genomes

AF:

0.000940

AC:

143

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00185

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000785

AC:

195

AN:

248492

Hom.:

AF XY:

0.000727

AC XY:

AN XY:

134804

show subpopulations

Gnomad AFR exome

AF:

0.000389

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000262

Gnomad FIN exome

AF:

0.000325

Gnomad NFE exome

AF:

0.00145

Gnomad OTH exome

AF:

0.000498

GnomAD4 exome

AF:

0.00141

AC:

2067

AN:

1461274

Hom.:

Cov.:

AF XY:

0.00138

AC XY:

1006

AN XY:

726882

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.000269

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.000393

Gnomad4 NFE exome

AF:

0.00173

Gnomad4 OTH exome

AF:

0.00123

GnomAD4 genome

AF:

0.000939

AC:

143

AN:

152300

Hom.:

Cov.:

AF XY:

0.000980

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00185

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00136

Hom.:

Bravo

AF:

0.000839

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000265

AC:

ESP6500EA

AF:

0.00158

AC:

ExAC

AF:

0.000910

AC:

110

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00120

EpiControl

AF:

0.000950

ClinVar

Significance: Benign/Likely benign

Submissions summary: Pathogenic:1Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Coronary artery disease/myocardial infarction

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 15, 2004

- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 18, 2015

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

MEF2A: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.010

DANN

Benign

0.93

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.27

LIST_S2

Uncertain

0.89

D;D;D;.;D;D

M_CAP

Benign

0.0033

MetaRNN

Benign

0.056

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;.;.;.;.;.

MutationTaster

Benign

0.0034

A;A;A;A;A;A;A

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.99

N;N;N;N;N;N

REVEL

Benign

0.14

Sift

Benign

0.33

T;T;T;T;T;T

Sift4G

Benign

0.64

T;T;T;T;T;T

Polyphen

0.0020

B;.;B;B;.;B

Vest4

0.16

MVP

0.39

MPC

0.057

ClinPred

0.0068

GERP RS

-9.3

gMVP

0.28

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

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