5-88722571-GAAA-GAAAA

Variant names:

• chr5-88722571-G-GA
• rs56660854
• NM_002397.5:c.*32dupT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_002397.5(MEF2C):​c.*32dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00474 in 139,172 control chromosomes in the GnomAD database, including 4 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0047 (4 hom., cov: 28)
  • Exomes 𝑓: 0.21 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: MEF2C NM_002397.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.815

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-AS2 (HGNC:53115): (MEF2C antisense RNA 2)

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00474 (659/139172) while in subpopulation AFR AF= 0.00835 (323/38676). AF 95% confidence interval is 0.0076. There are 4 homozygotes in gnomad4. There are 350 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 659 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEF2C	NM_002397.5	c.*32dupT		3_prime_UTR_variant	Exon 11 of 11	ENST00000504921.7	NP_002388.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEF2C	ENST00000504921	c.*32dupT		3_prime_UTR_variant	Exon 11 of 11	1	NM_002397.5	ENSP00000421925.5

Frequencies

GnomAD3 genomes AF: 0.00475 AC: 661 AN: 139140 Hom.: 4 Cov.: 28

Gnomad AFR AF: 0.00840

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00339

Gnomad ASJ AF: 0.000304

Gnomad EAS AF: 0.000834

Gnomad SAS AF: 0.000915

Gnomad FIN AF: 0.0145

Gnomad MID AF: 0.00355

Gnomad NFE AF: 0.00243

Gnomad OTH AF: 0.00578

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.205 AC: 189586 AN: 924444 Hom.: 2 Cov.: 8 AF XY: 0.204 AC XY: 93337 AN XY: 457596

Gnomad4 AFR exome AF: 0.0825

Gnomad4 AMR exome AF: 0.185

Gnomad4 ASJ exome AF: 0.198

Gnomad4 EAS exome AF: 0.257

Gnomad4 SAS exome AF: 0.219

Gnomad4 FIN exome AF: 0.150

Gnomad4 NFE exome AF: 0.211

Gnomad4 OTH exome AF: 0.197

GnomAD4 genome AF: 0.00474 AC: 659 AN: 139172 Hom.: 4 Cov.: 28 AF XY: 0.00521 AC XY: 350 AN XY: 67140

Gnomad4 AFR AF: 0.00835

Gnomad4 AMR AF: 0.00339

Gnomad4 ASJ AF: 0.000304

Gnomad4 EAS AF: 0.000837

Gnomad4 SAS AF: 0.000691

Gnomad4 FIN AF: 0.0145

Gnomad4 NFE AF: 0.00244

Gnomad4 OTH AF: 0.00575

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs56660854; hg19: chr5-88018388;