chr15-99706731-T-C

Variant names:

• chr15-99706731-T-C
• rs325408
• NM_001319206.4:c.885T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001319206.4(MEF2A):​c.885T>C​(p.Asn295Asn) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 1,611,158 control chromosomes in the GnomAD database, including 482,743 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.65 (35909 hom., cov: 31)
  • Exomes 𝑓: 0.78 (446834 hom.)
• Consequence: MEF2A NM_001319206.4 splice_region, synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.353
• Publications: 25 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 15-99706731-T-C is Benign according to our data. Variant chr15-99706731-T-C is described in ClinVar as [Benign]. Clinvar id is 3058865.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.353 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEF2A	NM_001319206.4	c.885T>C	p.Asn295Asn	splice_region_variant, synonymous_variant	Exon 10 of 12	ENST00000557942.6	NP_001306135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEF2A	ENST00000557942.6	c.885T>C	p.Asn295Asn	splice_region_variant, synonymous_variant	Exon 10 of 12	5	NM_001319206.4	ENSP00000453095.1

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98568 AN: 152008 Hom.: 35887 Cov.: 31

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.936

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.848

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.847

Gnomad FIN AF: 0.836

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.792

Gnomad OTH AF: 0.702

GnomAD2 exomes AF: 0.752 AC: 187356 AN: 249158 AF XY: 0.769

Gnomad AFR exome AF: 0.279

Gnomad AMR exome AF: 0.669

Gnomad ASJ exome AF: 0.859

Gnomad EAS exome AF: 0.733

Gnomad FIN exome AF: 0.824

Gnomad NFE exome AF: 0.794

Gnomad OTH exome AF: 0.783

GnomAD4 exome AF: 0.778 AC: 1134689 AN: 1459032 Hom.: 446834 Cov.: 42 AF XY: 0.782 AC XY: 568024 AN XY: 725950

African (AFR) AF: 0.279 AC: 9318 AN: 33398

American (AMR) AF: 0.671 AC: 30011 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.861 AC: 22483 AN: 26124

East Asian (EAS) AF: 0.795 AC: 31537 AN: 39676

South Asian (SAS) AF: 0.849 AC: 73197 AN: 86194

European-Finnish (FIN) AF: 0.820 AC: 43806 AN: 53394

Middle Eastern (MID) AF: 0.871 AC: 5020 AN: 5766

European-Non Finnish (NFE) AF: 0.787 AC: 872966 AN: 1109494

Other (OTH) AF: 0.769 AC: 46351 AN: 60276

GnomAD4 genome AF: 0.648 AC: 98631 AN: 152126 Hom.: 35909 Cov.: 31 AF XY: 0.656 AC XY: 48768 AN XY: 74378

African (AFR) AF: 0.292 AC: 12093 AN: 41484

American (AMR) AF: 0.680 AC: 10390 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.848 AC: 2939 AN: 3466

East Asian (EAS) AF: 0.745 AC: 3844 AN: 5160

South Asian (SAS) AF: 0.846 AC: 4084 AN: 4826

European-Finnish (FIN) AF: 0.836 AC: 8865 AN: 10608

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.792 AC: 53822 AN: 67986

Other (OTH) AF: 0.705 AC: 1487 AN: 2110

Alfa AF: 0.687 Hom.: 33797

Bravo AF: 0.620

Asia WGS AF: 0.775 AC: 2692 AN: 3478

EpiCase AF: 0.799

EpiControl AF: 0.799

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

MEF2A-related disorder Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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	-0.78
CADD	Benign	6.6
DANN	Benign	0.75
PhyloP100		0.35
Mutation Taster		=98/2	polymorphism (auto)

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: rs325408; hg19: chr15-100246936; COSMIC: COSV57530047;