5-88722571-GAAA-GAAAAA

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002397.5(MEF2C):​c.*31_*32dupTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002397.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEF2C	NM_002397.5	MANE Select	c.*31_*32dupTT		3_prime_UTR	Exon 11 of 11	NP_002388.2
	MEF2C	NM_001193347.1		c.*31_*32dupTT		3_prime_UTR	Exon 12 of 12	NP_001180276.1	Q06413-5
	MEF2C	NM_001193350.2		c.*31_*32dupTT		3_prime_UTR	Exon 11 of 11	NP_001180279.1	Q06413-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEF2C	ENST00000504921.7	TSL:1 MANE Select	c.*31_*32dupTT		3_prime_UTR	Exon 11 of 11	ENSP00000421925.5	Q06413-1
	MEF2C	ENST00000340208.9	TSL:1	c.*31_*32dupTT		3_prime_UTR	Exon 12 of 12	ENSP00000340874.5	Q06413-5
	MEF2C	ENST00000437473.6	TSL:1	c.*31_*32dupTT		3_prime_UTR	Exon 11 of 11	ENSP00000396219.2	Q06413-1

Frequencies

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

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

GnomAD2 exomes AF: 0.00121 AC: 125 AN: 103102 AF XY: 0.00151

Gnomad AFR exome AF: 0.000192

Gnomad AMR exome AF: 0.000786

Gnomad ASJ exome AF: 0.00152

Gnomad EAS exome AF: 0.000309

Gnomad FIN exome AF: 0.00150

Gnomad NFE exome AF: 0.00145

Gnomad OTH exome AF: 0.000408

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000396 AC: 11 AN: 27778

American (AMR) AF: 0.000581 AC: 20 AN: 34418

Ashkenazi Jewish (ASJ) AF: 0.00105 AC: 22 AN: 20916

East Asian (EAS) AF: 0.000233 AC: 8 AN: 34300

South Asian (SAS) AF: 0.000807 AC: 57 AN: 70640

European-Finnish (FIN) AF: 0.000714 AC: 31 AN: 43414

Middle Eastern (MID) AF: 0.000652 AC: 3 AN: 4602

European-Non Finnish (NFE) AF: 0.000750 AC: 664 AN: 884882

Other (OTH) AF: 0.000571 AC: 28 AN: 49056

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.00 AC: 0 AN: 38604

American (AMR) AF: 0.00 AC: 0 AN: 13870

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3292

East Asian (EAS) AF: 0.00 AC: 0 AN: 4806

South Asian (SAS) AF: 0.00 AC: 0 AN: 4372

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7946

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 63398

Other (OTH) AF: 0.00 AC: 0 AN: 1904

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.81
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs56660854; hg19: chr5-88018388;