rs121918530

Variant names:

• chr15-99690352-A-G
• rs121918530
• NM_001319206.4:c.782A>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

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. 16/21 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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1 B:2
• Conservation: PhyloP100: -0.0310
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 8950.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 143 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001319206.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEF2A	NM_001319206.4	MANE Select	c.782A>G	p.Asn261Ser	missense	Exon 8 of 12	NP_001306135.1
	MEF2A	NM_001400028.1		c.920A>G	p.Asn307Ser	missense	Exon 9 of 12	NP_001386957.1
	MEF2A	NM_001365201.3		c.800A>G	p.Asn267Ser	missense	Exon 8 of 12	NP_001352130.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEF2A	ENST00000557942.6	TSL:5 MANE Select	c.782A>G	p.Asn261Ser	missense	Exon 8 of 12	ENSP00000453095.1
	MEF2A	ENST00000354410.9	TSL:1	c.788A>G	p.Asn263Ser	missense	Exon 8 of 11	ENSP00000346389.5
	MEF2A	ENST00000338042.11	TSL:2	c.800A>G	p.Asn267Ser	missense	Exon 8 of 12	ENSP00000337202.8

Frequencies

GnomAD3 genomes AF: 0.000940 AC: 143 AN: 152182 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.000785 AC: 195 AN: 248492 AF XY: 0.000727

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 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.: 5 Cov.: 31 AF XY: 0.00138 AC XY: 1006 AN XY: 726882

African (AFR) AF: 0.000329 AC: 11 AN: 33468

American (AMR) AF: 0.000269 AC: 12 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86164

European-Finnish (FIN) AF: 0.000393 AC: 21 AN: 53394

Middle Eastern (MID) AF: 0.00176 AC: 10 AN: 5670

European-Non Finnish (NFE) AF: 0.00173 AC: 1922 AN: 1111748

Other (OTH) AF: 0.00123 AC: 74 AN: 60348

GnomAD4 genome AF: 0.000939 AC: 143 AN: 152300 Hom.: 0 Cov.: 32 AF XY: 0.000980 AC XY: 73 AN XY: 74476

African (AFR) AF: 0.000217 AC: 9 AN: 41556

American (AMR) AF: 0.000261 AC: 4 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00185 AC: 126 AN: 68018

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00125 Hom.: 0

Bravo AF: 0.000839

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00182 AC: 7

ESP6500AA AF: 0.000265 AC: 1

ESP6500EA AF: 0.00158 AC: 13

ExAC AF: 0.000910 AC: 110

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00120

EpiControl AF: 0.000950

ClinVar

Significance: Benign/Likely benign

Submissions summary: Pathogenic:1 Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Coronary artery disease/myocardial infarction Pathogenic:1

Dec 15, 2004

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

not specified Benign:1

Jul 18, 2015

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Jul 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MEF2A: BP4, BS1, BS2

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.65	T
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	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		-0.031
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.14
Sift	Benign	0.33	T
Sift4G	Benign	0.64	T
Polyphen		0.0020	B
Vest4		0.16
MVP		0.39
MPC		0.057
ClinPred		0.0068	T
GERP RS		-9.3
gMVP		0.28
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs121918530; hg19: chr15-100230557;