NM_001319206.4:c.1268_1285dupAGCAGCAGCAGCAGCAGC

Variant names:

• chr15-99712504-C-CCAGCAGCAGCAGCAGCAG
• rs3138597
• NM_001319206.4:c.1268_1285dupAGCAGCAGCAGCAGCAGC

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP3 BS2_Supporting

The NM_001319206.4(MEF2A):​c.1268_1285dupAGCAGCAGCAGCAGCAGC​(p.Gln423_Gln428dup) variant causes a disruptive inframe insertion change. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000072 (0 hom.)
• Consequence: MEF2A NM_001319206.4 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.55
• 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: Likely_benign. The variant received -2 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001319206.4
• BS2: High AC in GnomAdExome4 at 10 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEF2A	NM_001319206.4	MANE Select	c.1268_1285dupAGCAGCAGCAGCAGCAGC	p.Gln423_Gln428dup	disruptive_inframe_insertion	Exon 12 of 12	NP_001306135.1	Q02078-2
	MEF2A	NM_001400028.1		c.1382_1399dupAGCAGCAGCAGCAGCAGC	p.Gln461_Gln466dup	disruptive_inframe_insertion	Exon 12 of 12	NP_001386957.1
	MEF2A	NM_001365201.3		c.1286_1303dupAGCAGCAGCAGCAGCAGC	p.Gln429_Gln434dup	disruptive_inframe_insertion	Exon 12 of 12	NP_001352130.1	A0A8I5KVQ4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEF2A	ENST00000557942.6	TSL:5 MANE Select	c.1268_1285dupAGCAGCAGCAGCAGCAGC	p.Gln423_Gln428dup	disruptive_inframe_insertion	Exon 12 of 12	ENSP00000453095.1	Q02078-2
	MEF2A	ENST00000354410.9	TSL:1	c.1250_1267dupAGCAGCAGCAGCAGCAGC	p.Gln417_Gln422dup	disruptive_inframe_insertion	Exon 11 of 11	ENSP00000346389.5	Q02078-5
	MEF2A	ENST00000947006.1		c.1406_1423dupAGCAGCAGCAGCAGCAGC	p.Gln469_Gln474dup	disruptive_inframe_insertion	Exon 12 of 12	ENSP00000617065.1

Frequencies

GnomAD3 genomes AF: 0.0000266 AC: 4 AN: 150286 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000245

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000444

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000724 AC: 10 AN: 1381130 Hom.: 0 Cov.: 0 AF XY: 0.0000103 AC XY: 7 AN XY: 681108

African (AFR) AF: 0.0000637 AC: 2 AN: 31386

American (AMR) AF: 0.00 AC: 0 AN: 35370

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24828

East Asian (EAS) AF: 0.00 AC: 0 AN: 35112

South Asian (SAS) AF: 0.0000128 AC: 1 AN: 78090

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47946

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 0.00000657 AC: 7 AN: 1065412

Other (OTH) AF: 0.00 AC: 0 AN: 57334

GnomAD4 genome AF: 0.0000266 AC: 4 AN: 150286 Hom.: 0 Cov.: 0 AF XY: 0.0000273 AC XY: 2 AN XY: 73250

African (AFR) AF: 0.0000245 AC: 1 AN: 40806

American (AMR) AF: 0.00 AC: 0 AN: 15140

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5084

South Asian (SAS) AF: 0.00 AC: 0 AN: 4710

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000444 AC: 3 AN: 67544

Other (OTH) AF: 0.00 AC: 0 AN: 2048

Alfa AF: 0.00 Hom.: 638

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.5
Mutation Taster		=56/44	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;