19-19146373-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001145785.2(MEF2B):c.781G>A(p.Gly261Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MEF2B NM_001145785.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.538

Genes affected

MEF2B (HGNC:6995): (myocyte enhancer factor 2B) The product of this gene is a member of the MADS/MEF2 family of DNA binding proteins. The protein is thought to regulate gene expression, including expression of the smooth muscle myosin heavy chain gene. This region undergoes considerable alternative splicing, with transcripts supporting two non-overlapping loci (GeneID 729991 and 100271849) as well as numerous read-through transcripts that span both loci (annotated as GeneID 4207). Several isoforms of this protein are expressed from either this locus or from some of the read-through transcripts annotated on GeneID 4207. [provided by RefSeq, Jan 2014]

BORCS8-MEF2B (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3199538).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEF2B	NM_001145785.2	c.781G>A	p.Gly261Arg	missense_variant	8/9	ENST00000424583.7
BORCS8-MEF2B	NR_027308.2	n.1235+182G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEF2B	ENST00000424583.7	c.781G>A	p.Gly261Arg	missense_variant	8/9	5	NM_001145785.2	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 976732 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 478772

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 21, 2023

The c.781G>A (p.G261R) alteration is located in exon 8 (coding exon 7) of the MEF2B gene. This alteration results from a G to A substitution at nucleotide position 781, causing the glycine (G) at amino acid position 261 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
Cadd	Uncertain	24
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.037	T;.;.
Eigen	Benign	0.18
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.72	T;T;T
M_CAP	Pathogenic	0.56	D
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Uncertain	-0.066	T
MutationTaster	Benign	1.0	D;D;N;N;N;N
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-1.7	N;N;N
REVEL	Uncertain	0.35
Sift	Uncertain	0.0060	D;D;D
Sift4G	Benign	0.73	T;T;T
Polyphen		0.98	D;.;D
Vest4		0.38
MutPred		0.25		.;.;Gain of solvent accessibility (P = 0.0037);
MVP		0.14
ClinPred		0.81	D
GERP RS		4.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-19257182;