5-88722571-GAAA-GAAAAAA

Variant names:

• chr5-88722571-G-GAAA
• rs56660854
• NM_002397.5:c.*30_*32dupTTT

Variant summary

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

The NM_002397.5(MEF2C):​c.*30_*32dupTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000022 in 1,182,710 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 28)
  • Exomes 𝑓: 0.000022 (0 hom.)
• 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.*30_*32dupTTT		3_prime_UTR	Exon 11 of 11	NP_002388.2
	MEF2C	NM_001193347.1		c.*30_*32dupTTT		3_prime_UTR	Exon 12 of 12	NP_001180276.1	Q06413-5
	MEF2C	NM_001193350.2		c.*30_*32dupTTT		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.*30_*32dupTTT		3_prime_UTR	Exon 11 of 11	ENSP00000421925.5	Q06413-1
	MEF2C	ENST00000340208.9	TSL:1	c.*30_*32dupTTT		3_prime_UTR	Exon 12 of 12	ENSP00000340874.5	Q06413-5
	MEF2C	ENST00000437473.6	TSL:1	c.*30_*32dupTTT		3_prime_UTR	Exon 11 of 11	ENSP00000396219.2	Q06413-1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD2 exomes AF: 0.0000873 AC: 9 AN: 103102 AF XY: 0.000127

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000786

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000301

Gnomad NFE exome AF: 0.0000213

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000220 AC: 26 AN: 1182710 Hom.: 0 Cov.: 8 AF XY: 0.0000272 AC XY: 16 AN XY: 588916

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

African (AFR) AF: 0.00 AC: 0 AN: 27904

American (AMR) AF: 0.0000576 AC: 2 AN: 34694

Ashkenazi Jewish (ASJ) AF: 0.0000474 AC: 1 AN: 21114

East Asian (EAS) AF: 0.00 AC: 0 AN: 34542

South Asian (SAS) AF: 0.0000980 AC: 7 AN: 71394

European-Finnish (FIN) AF: 0.0000458 AC: 2 AN: 43704

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4646

European-Non Finnish (NFE) AF: 0.0000156 AC: 14 AN: 895154

Other (OTH) AF: 0.00 AC: 0 AN: 49558

⚠️ 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 Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.81

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;