Variant rs2274316 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005920.4(MEF2D):c.876+44G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 1,601,862 control chromosomes in the GnomAD database, including 329,700 homozygotes. 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 0.55 ( 24981 hom., cov: 32)

Exomes 𝑓: 0.64 ( 304719 hom. )

Consequence

MEF2D
NM_005920.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0740

Variant links:

Genes affected

MEF2D (HGNC:6997): (myocyte enhancer factor 2D) This gene is a member of the myocyte-specific enhancer factor 2 (MEF2) family of transcription factors. Members of this family are involved in control of muscle and neuronal cell differentiation and development, and are regulated by class II histone deacetylases. Fusions of the encoded protein with Deleted in Azoospermia-Associated Protein 1 (DAZAP1) due to a translocation have been found in an acute lymphoblastic leukemia cell line, suggesting a role in leukemogenesis. The encoded protein may also be involved in Parkinson disease and myotonic dystrophy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2012]

MEF2D links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEF2D	NM_005920.4 linkuse as main transcript	c.876+44G>T		intron_variant		ENST00000348159.9	NP_005911.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
MEF2D	ENST00000348159.9 linkuse as main transcript	c.876+44G>T	intron_variant	1	NM_005920.4	ENSP00000271555		Q14814-1
MEF2D	ENST00000360595.7 linkuse as main transcript	c.855+562G>T	intron_variant	1		ENSP00000353803		Q14814-4
MEF2D	ENST00000464356.6 linkuse as main transcript	c.852+562G>T	intron_variant	5		ENSP00000476788	P1	Q14814-5
MEF2D	ENST00000475587.2 linkuse as main transcript	c.*224+562G>T	intron_variant, NMD_transcript_variant	5		ENSP00000477413

Frequencies

GnomAD3 genomes

AF:

0.551

AC:

83751

AN:

151994

Hom.:

24973

Cov.:

show subpopulations

Gnomad AFR

AF:

0.298

Gnomad AMI

AF:

0.525

Gnomad AMR

AF:

0.597

Gnomad ASJ

AF:

0.661

Gnomad EAS

AF:

0.730

Gnomad SAS

AF:

0.687

Gnomad FIN

AF:

0.573

Gnomad MID

AF:

0.712

Gnomad NFE

AF:

0.660

Gnomad OTH

AF:

0.612

GnomAD3 exomes

AF:

0.623

AC:

148448

AN:

238254

Hom.:

47304

AF XY:

0.636

AC XY:

81454

AN XY:

128134

show subpopulations

Gnomad AFR exome

AF:

0.286

Gnomad AMR exome

AF:

0.562

Gnomad ASJ exome

AF:

0.662

Gnomad EAS exome

AF:

0.730

Gnomad SAS exome

AF:

0.683

Gnomad FIN exome

AF:

0.577

Gnomad NFE exome

AF:

0.659

Gnomad OTH exome

AF:

0.648

GnomAD4 exome

AF:

0.645

AC:

934684

AN:

1449750

Hom.:

304719

Cov.:

AF XY:

0.648

AC XY:

466972

AN XY:

720206

show subpopulations

Gnomad4 AFR exome

AF:

0.287

Gnomad4 AMR exome

AF:

0.567

Gnomad4 ASJ exome

AF:

0.663

Gnomad4 EAS exome

AF:

0.720

Gnomad4 SAS exome

AF:

0.685

Gnomad4 FIN exome

AF:

0.581

Gnomad4 NFE exome

AF:

0.656

Gnomad4 OTH exome

AF:

0.631

GnomAD4 genome

AF:

0.551

AC:

83774

AN:

152112

Hom.:

24981

Cov.:

AF XY:

0.552

AC XY:

41068

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.297

Gnomad4 AMR

AF:

0.597

Gnomad4 ASJ

AF:

0.661

Gnomad4 EAS

AF:

0.731

Gnomad4 SAS

AF:

0.686

Gnomad4 FIN

AF:

0.573

Gnomad4 NFE

AF:

0.660

Gnomad4 OTH

AF:

0.617

Alfa

AF:

0.652

Hom.:

47709

Bravo

AF:

0.539

Asia WGS

AF:

0.697

AC:

2425

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

9.5

DANN

Benign

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over