15-99706762-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001319206.4(MEF2A):c.916C>G(p.Gln306Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,516 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MEF2A NM_001319206.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.25

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEF2A	NM_001319206.4	c.916C>G	p.Gln306Glu	missense_variant	10/12	ENST00000557942.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEF2A	ENST00000557942.6	c.916C>G	p.Gln306Glu	missense_variant	10/12	5	NM_001319206.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461516 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727048

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 17, 2023

The c.898C>G (p.Q300E) alteration is located in exon 9 (coding exon 7) of the MEF2A gene. This alteration results from a C to G substitution at nucleotide position 898, causing the glutamine (Q) at amino acid position 300 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.096	D
BayesDel_noAF	Benign	-0.10
Cadd	Uncertain	25
Dann	Uncertain	0.99
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.97	D;D;D;.;D;D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.73	D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.69	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.0	N;N;N;N;N;N
REVEL	Benign	0.27
Sift	Uncertain	0.0090	D;D;D;D;D;D
Sift4G	Uncertain	0.038	D;T;D;D;D;T
Polyphen		0.98	D;.;D;D;.;D
Vest4		0.68
MVP		0.37
MPC		0.32
ClinPred		0.93	D
GERP RS		6.1
gMVP		0.63

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-100246967;