5-88722488-CTTT-CTTTT

Variant names:

• chr5-88722488-C-CT
• rs553216678
• NM_002397.5:c.*115dupA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_002397.5(MEF2C):​c.*115dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0387 in 681,416 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 32)
  • Exomes 𝑓: 0.049 (0 hom.)
• Consequence: MEF2C NM_002397.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.63
• 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000207 (30/145204) while in subpopulation AMR AF = 0.000415 (6/14470). AF 95% confidence interval is 0.00018. There are 0 homozygotes in GnomAd4. There are 12 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 30 AD gene.

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.*115dupA		3_prime_UTR	Exon 11 of 11	NP_002388.2
	MEF2C	NM_001193347.1		c.*115dupA		3_prime_UTR	Exon 12 of 12	NP_001180276.1	Q06413-5
	MEF2C	NM_001193350.2		c.*115dupA		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.*115dupA		3_prime_UTR	Exon 11 of 11	ENSP00000421925.5	Q06413-1
	MEF2C	ENST00000340208.9	TSL:1	c.*115dupA		3_prime_UTR	Exon 12 of 12	ENSP00000340874.5	Q06413-5
	MEF2C	ENST00000437473.6	TSL:1	c.*115dupA		3_prime_UTR	Exon 11 of 11	ENSP00000396219.2	Q06413-1

Frequencies

GnomAD3 genomes AF: 0.000207 AC: 30 AN: 145172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000252

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000415

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000400

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000898

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000606

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0491 AC: 26345 AN: 536212 Hom.: 0 Cov.: 8 AF XY: 0.0485 AC XY: 13287 AN XY: 273838

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

African (AFR) AF: 0.0486 AC: 621 AN: 12766

American (AMR) AF: 0.0485 AC: 830 AN: 17110

Ashkenazi Jewish (ASJ) AF: 0.0499 AC: 496 AN: 9948

East Asian (EAS) AF: 0.0401 AC: 843 AN: 20998

South Asian (SAS) AF: 0.0561 AC: 2159 AN: 38462

European-Finnish (FIN) AF: 0.0394 AC: 968 AN: 24554

Middle Eastern (MID) AF: 0.0343 AC: 92 AN: 2682

European-Non Finnish (NFE) AF: 0.0497 AC: 19164 AN: 385718

Other (OTH) AF: 0.0489 AC: 1172 AN: 23974

⚠️ 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 AF: 0.000207 AC: 30 AN: 145204 Hom.: 0 Cov.: 32 AF XY: 0.000170 AC XY: 12 AN XY: 70538

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

African (AFR) AF: 0.000252 AC: 10 AN: 39736

American (AMR) AF: 0.000415 AC: 6 AN: 14470

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3372

East Asian (EAS) AF: 0.000402 AC: 2 AN: 4980

South Asian (SAS) AF: 0.00 AC: 0 AN: 4556

European-Finnish (FIN) AF: 0.000898 AC: 8 AN: 8910

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.0000606 AC: 4 AN: 66006

Other (OTH) AF: 0.00 AC: 0 AN: 1996

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000726234), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.6
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs553216678; hg19: chr5-88018305;