Genetic Variant MEF2A:c.*2058G>T (chr15-99714829-G-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS2_Supporting

The NM_001319206.4(MEF2A):c.*2058G>T 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 0.00029 ( 0 hom., cov: 16)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MEF2A
NM_001319206.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.753

Publications

6 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BS2

High AC in GnomAd4 at 27 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MEF2A	NM_001319206.4	MANE Select	c.*2058G>T	3_prime_UTR	Exon 12 of 12	NP_001306135.1	Q02078-2
MEF2A	NM_001400028.1		c.*2058G>T	3_prime_UTR	Exon 12 of 12	NP_001386957.1
MEF2A	NM_001365201.3		c.*2058G>T	3_prime_UTR	Exon 12 of 12	NP_001352130.1	A0A8I5KVQ4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MEF2A	ENST00000557942.6	TSL:5 MANE Select	c.*2058G>T	3_prime_UTR	Exon 12 of 12	ENSP00000453095.1	Q02078-2
MEF2A	ENST00000354410.9	TSL:1	c.*2058G>T	3_prime_UTR	Exon 11 of 11	ENSP00000346389.5	Q02078-5
MEF2A	ENST00000946992.1		c.*2058G>T	3_prime_UTR	Exon 13 of 13	ENSP00000617051.1

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

93436

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00120

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000298

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:

0.0000190

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.000289

AC:

AN:

93462

Hom.:

Cov.:

AF XY:

0.000258

AC XY:

AN XY:

42576

show subpopulations

African (AFR)

AF:

0.00120

AC:

AN:

20074

American (AMR)

AF:

0.000298

AC:

AN:

6718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2702

East Asian (EAS)

AF:

0.00

AC:

AN:

3200

South Asian (SAS)

AF:

0.00

AC:

AN:

2616

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3518

Middle Eastern (MID)

AF:

0.00

AC:

AN:

134

European-Non Finnish (NFE)

AF:

0.0000190

AC:

AN:

52564

Other (OTH)

AF:

0.00

AC:

AN:

1196

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.42

(source)

DANN

Benign

0.68

PhyloP100

-0.75

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over