5-88883337-A-AAGG

Variant names:

• chr5-88883337-A-AAGG
• rs567979916
• ENST00000437473.6:c.-525_-523dupCCT

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The ENST00000437473.6(MEF2C):​c.-525_-523dupCCT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00779 in 151,608 control chromosomes in the GnomAD database, including 7 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0078 (7 hom., cov: 27)
  • Exomes 𝑓: 0.0021 (0 hom.)
• Consequence: MEF2C ENST00000437473.6 5_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:1
• Conservation: PhyloP100: -0.154

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

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP6: Variant 5-88883337-A-AAGG is Benign according to our data. Variant chr5-88883337-A-AAGG is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 354604.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=2}.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00784 (1178/150180) while in subpopulation NFE AF= 0.0112 (754/67406). AF 95% confidence interval is 0.0105. There are 7 homozygotes in gnomad4. There are 597 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1178 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEF2C	NM_002397.5	c.-528_-526dupCCT		upstream_gene_variant		ENST00000504921.7	NP_002388.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEF2C	ENST00000504921.7	c.-528_-526dupCCT		upstream_gene_variant		1	NM_002397.5	ENSP00000421925.5

Frequencies

GnomAD3 genomes AF: 0.00782 AC: 1174 AN: 150082 Hom.: 7 Cov.: 27

Gnomad AFR AF: 0.00312

Gnomad AMI AF: 0.0456

Gnomad AMR AF: 0.00696

Gnomad ASJ AF: 0.00549

Gnomad EAS AF: 0.000197

Gnomad SAS AF: 0.00127

Gnomad FIN AF: 0.0102

Gnomad MID AF: 0.00641

Gnomad NFE AF: 0.0112

Gnomad OTH AF: 0.00730

GnomAD4 exome AF: 0.00210 AC: 3 AN: 1428 Hom.: 0 Cov.: 0 AF XY: 0.00109 AC XY: 1 AN XY: 916

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: 0.00445

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00784 AC: 1178 AN: 150180 Hom.: 7 Cov.: 27 AF XY: 0.00813 AC XY: 597 AN XY: 73396

Gnomad4 AFR AF: 0.00318

Gnomad4 AMR AF: 0.00695

Gnomad4 ASJ AF: 0.00549

Gnomad4 EAS AF: 0.000198

Gnomad4 SAS AF: 0.00127

Gnomad4 FIN AF: 0.0102

Gnomad4 NFE AF: 0.0112

Gnomad4 OTH AF: 0.00722

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Intellectual Disability, Stereotypic Movements, Epilepsy, and/or Cerebral Malformations Uncertain:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MEF2C: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs567979916; hg19: chr5-88179154;