NM_001319206.4:c.1271_1285delAGCAGCAGCAGCAGC

Variant names:

• chr15-99712504-CCAGCAGCAGCAGCAG-C
• rs3138597
• NM_001319206.4:c.1271_1285delAGCAGCAGCAGCAGC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP3 BP6 BS1 BS2

The NM_001319206.4(MEF2A):​c.1271_1285delAGCAGCAGCAGCAGC​(p.Gln424_Gln428del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00569 in 1,531,508 control chromosomes in the GnomAD database, including 84 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0056 (3 hom., cov: 0)
  • Exomes 𝑓: 0.0057 (81 hom.)
• Consequence: MEF2A NM_001319206.4 disruptive_inframe_deletion
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 6.73
• Publications: 9 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 -10 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001319206.4
• BP6: Variant 15-99712504-CCAGCAGCAGCAGCAG-C is Benign according to our data. Variant chr15-99712504-CCAGCAGCAGCAGCAG-C is described in ClinVar as Benign. ClinVar VariationId is 3039553.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00556 (836/150398) while in subpopulation SAS AF = 0.0227 (107/4706). AF 95% confidence interval is 0.0192. There are 3 homozygotes in GnomAd4. There are 450 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 836 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEF2A	NM_001319206.4	c.1271_1285delAGCAGCAGCAGCAGC	p.Gln424_Gln428del	disruptive_inframe_deletion	Exon 12 of 12	ENST00000557942.6	NP_001306135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEF2A	ENST00000557942.6	c.1271_1285delAGCAGCAGCAGCAGC	p.Gln424_Gln428del	disruptive_inframe_deletion	Exon 12 of 12	5	NM_001319206.4	ENSP00000453095.1

Frequencies

GnomAD3 genomes AF: 0.00555 AC: 834 AN: 150280 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.00137

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0194

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.000983

Gnomad SAS AF: 0.0227

Gnomad FIN AF: 0.00195

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.00477

Gnomad OTH AF: 0.00732

GnomAD2 exomes AF: 0.0143 AC: 1737 AN: 121148 AF XY: 0.0160

Gnomad AFR exome AF: 0.00171

Gnomad AMR exome AF: 0.0291

Gnomad ASJ exome AF: 0.00210

Gnomad EAS exome AF: 0.00196

Gnomad FIN exome AF: 0.00191

Gnomad NFE exome AF: 0.00669

Gnomad OTH exome AF: 0.0147

GnomAD4 exome AF: 0.00570 AC: 7871 AN: 1381110 Hom.: 81 AF XY: 0.00658 AC XY: 4482 AN XY: 681090

African (AFR) AF: 0.00108 AC: 34 AN: 31386

American (AMR) AF: 0.0209 AC: 740 AN: 35368

Ashkenazi Jewish (ASJ) AF: 0.000926 AC: 23 AN: 24828

East Asian (EAS) AF: 0.00194 AC: 68 AN: 35112

South Asian (SAS) AF: 0.0328 AC: 2564 AN: 78086

European-Finnish (FIN) AF: 0.00150 AC: 72 AN: 47942

Middle Eastern (MID) AF: 0.0269 AC: 152 AN: 5652

European-Non Finnish (NFE) AF: 0.00364 AC: 3879 AN: 1065402

Other (OTH) AF: 0.00591 AC: 339 AN: 57334

GnomAD4 genome AF: 0.00556 AC: 836 AN: 150398 Hom.: 3 Cov.: 0 AF XY: 0.00613 AC XY: 450 AN XY: 73372

African (AFR) AF: 0.00137 AC: 56 AN: 40928

American (AMR) AF: 0.0195 AC: 295 AN: 15154

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3464

East Asian (EAS) AF: 0.000986 AC: 5 AN: 5072

South Asian (SAS) AF: 0.0227 AC: 107 AN: 4706

European-Finnish (FIN) AF: 0.00195 AC: 20 AN: 10274

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.00477 AC: 322 AN: 67536

Other (OTH) AF: 0.00725 AC: 15 AN: 2070

Alfa AF: 0.00361 Hom.: 638

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

MEF2A-related disorder Benign:1

Nov 01, 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
PhyloP100		6.7
Mutation Taster		=198/2	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3138597; hg19: chr15-100252709;