5-88722571-GAAA-GAAAAA

Variant names:

• chr5-88722571-G-GAA
• rs56660854
• NM_002397.5:c.*31_*32dupTT

Variant summary

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

The NM_002397.5(MEF2C):​c.*31_*32dupTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00072 (0 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 sas. gnomad4_exome allele frequency = 0.000721 (844/1170006) while in subpopulation SAS AF= 0.000807 (57/70640). AF 95% confidence interval is 0.000703. There are 0 homozygotes in gnomad4_exome. There are 444 alleles in male gnomad4_exome subpopulation. Median coverage is 8. This position pass quality control queck.
• BS2: High AC in GnomAdExome4 at 844 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEF2C	NM_002397.5	c.*31_*32dupTT		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.*31_*32dupTT		3_prime_UTR_variant	Exon 11 of 11	1	NM_002397.5	ENSP00000421925.5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 139346 Hom.: 0 Cov.: 28 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000721 AC: 844 AN: 1170006 Hom.: 0 Cov.: 8 AF XY: 0.000762 AC XY: 444 AN XY: 582576

Gnomad4 AFR exome AF: 0.000396

Gnomad4 AMR exome AF: 0.000581

Gnomad4 ASJ exome AF: 0.00105

Gnomad4 EAS exome AF: 0.000233

Gnomad4 SAS exome AF: 0.000807

Gnomad4 FIN exome AF: 0.000714

Gnomad4 NFE exome AF: 0.000750

Gnomad4 OTH exome AF: 0.000571

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 139346 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 67214

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

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: rs56660854; hg19: chr5-88018388;