15-99714841-A-G

Position:

• chr15-99714841-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001319206.4(MEF2A):​c.*2070A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.29 (4765 hom., cov: 17)
  • Exomes 𝑓: 0.33 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MEF2A NM_001319206.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.332

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEF2A	NM_001319206.4	c.*2070A>G		3_prime_UTR_variant	12/12	ENST00000557942.6	NP_001306135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEF2A	ENST00000557942.6	c.*2070A>G		3_prime_UTR_variant	12/12	5	NM_001319206.4	ENSP00000453095.1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 33697 AN: 114390 Hom.: 4761 Cov.: 17

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.447

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.286

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.333 AC: 2 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.295 AC: 33704 AN: 114414 Hom.: 4765 Cov.: 17 AF XY: 0.301 AC XY: 15875 AN XY: 52658

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.286

Alfa AF: 0.292 Hom.: 9663

Asia WGS AF: 0.338 AC: 1173 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs325383; hg19: chr15-100255046; COSMIC: COSV57531178; COSMIC: COSV57531178;