15-99690321-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001319206.4(MEF2A):​c.751A>G​(p.Thr251Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T251S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

MEF2A
NM_001319206.4 missense

Scores

2
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.95

Publications

0 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]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.22586861).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MEF2ANM_001319206.4 linkc.751A>G p.Thr251Ala missense_variant Exon 8 of 12 ENST00000557942.6 NP_001306135.1 Q02078-2A0A0S2Z4N0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MEF2AENST00000557942.6 linkc.751A>G p.Thr251Ala missense_variant Exon 8 of 12 5 NM_001319206.4 ENSP00000453095.1 Q02078-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461306
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726920
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33470
American (AMR)
AF:
0.00
AC:
0
AN:
44690
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26108
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39694
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86180
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53394
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5658
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111766
Other (OTH)
AF:
0.0000166
AC:
1
AN:
60346
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.055
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
21
DANN
Benign
0.55
Eigen
Benign
-0.0055
Eigen_PC
Benign
0.20
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.85
T;D;T;.;D;T
M_CAP
Benign
0.022
T
MetaRNN
Benign
0.23
T;T;T;T;T;T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
0.27
N;.;.;.;.;.
PhyloP100
6.0
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
0.61
N;N;N;N;N;N
REVEL
Benign
0.19
Sift
Benign
1.0
T;T;T;T;T;T
Sift4G
Benign
1.0
T;T;T;T;T;T
Polyphen
0.032
B;.;D;D;.;D
Vest4
0.45
MutPred
0.19
Loss of glycosylation at T253 (P = 0.0021);.;.;.;.;.;
MVP
0.41
MPC
0.39
ClinPred
0.97
D
GERP RS
5.8
gMVP
0.49

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

Other links and lift over

dbSNP: rs199751824; hg19: chr15-100230526; API