Variant 5-88883302-AGAG-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The ENST00000437473.6(MEF2C):c.-490_-488delCTC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000788 in 152,308 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 27)

Exomes 𝑓: 0.0064 ( 0 hom. )

Consequence

MEF2C
ENST00000437473.6 5_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.93

Variant links:

Genes affected

MEF2C (HGNC:6996): (myocyte enhancer factor 2C) This locus encodes a member of the MADS box transcription enhancer factor 2 (MEF2) family of proteins, which play a role in myogenesis. The encoded protein, MEF2 polypeptide C, has both trans-activating and DNA binding activities. This protein may play a role in maintaining the differentiated state of muscle cells. Mutations and deletions at this locus have been associated with severe cognitive disability, stereotypic movements, epilepsy, and cerebral malformation. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2010]

MEF2C links:

MEF2C-AS1 (HGNC:48908): (MEF2C antisense RNA 1)

MEF2C-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 5-88883302-AGAG-A is Benign according to our data. Variant chr5-88883302-AGAG-A is described in ClinVar as [Likely_benign]. Clinvar id is 3056591.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0064 (9/1406) while in subpopulation AMR AF= 0.1 (1/10). AF 95% confidence interval is 0.00261. There are 0 homozygotes in gnomad4_exome. There are 7 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	Protein
MEF2C	XM_047417217.1 link	c.-490_-488delCTC	5_prime_UTR_variant	3/13	XP_047273173.1
MEF2C	XM_047417181.1 link	c.-490_-488delCTC	5_prime_UTR_variant	3/13	XP_047273137.1
MEF2C	XM_047417182.1 link	c.-493_-491delCTC	5_prime_UTR_variant	3/13	XP_047273138.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Protein	UniProt
MEF2C	ENST00000437473.6 link	c.-490_-488delCTC	5_prime_UTR_variant	1/11	1	ENSP00000396219.2	Q06413-1
MEF2C	ENST00000340208.9 link	c.-143+4197_-143+4199delCTC	intron_variant		1	ENSP00000340874.5	Q06413-5
MEF2C	ENST00000424173.6 link	c.-143+4197_-143+4199delCTC	intron_variant		1	ENSP00000389610.2	Q06413-6

Frequencies

GnomAD3 genomes

AF:

0.0000199

AC:

AN:

150902

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000198

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00640

AC:

AN:

1406

Hom.:

AF XY:

0.00751

AC XY:

AN XY:

932

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.100

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00617

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00663

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000199

AC:

AN:

150902

Hom.:

Cov.:

AF XY:

0.0000272

AC XY:

AN XY:

73662

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000198

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000295

Gnomad4 OTH

AF:

0.00

Asia WGS

AF:

0.000869

AC:

AN:

3468

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MEF2C-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 13, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over