5-88722488-CT-C

Position:

• chr5-88722488-CT-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_002397.5(MEF2C):​c.*115del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0277 in 686,466 control chromosomes in the GnomAD database, including 24 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.0040 (2 hom., cov: 32)
  • Exomes 𝑓: 0.034 (22 hom.)
• Consequence: MEF2C NM_002397.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 2.63

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.

• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEF2C	NM_002397.5	c.*115del		3_prime_UTR_variant	11/11	ENST00000504921.7	NP_002388.2
MEF2C-AS2	NR_146284.1	n.256-125del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEF2C	ENST00000504921.7	c.*115del		3_prime_UTR_variant	11/11	1	NM_002397.5	ENSP00000421925
MEF2C-AS2	ENST00000657578.1	n.232-39498del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00400 AC: 581 AN: 145152 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00545

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00277

Gnomad ASJ AF: 0.00563

Gnomad EAS AF: 0.00260

Gnomad SAS AF: 0.0229

Gnomad FIN AF: 0.00101

Gnomad MID AF: 0.00658

Gnomad NFE AF: 0.00261

Gnomad OTH AF: 0.00252

GnomAD4 exome AF: 0.0340 AC: 18400 AN: 541282 Hom.: 22 Cov.: 8 AF XY: 0.0350 AC XY: 9673 AN XY: 276352

Gnomad4 AFR exome AF: 0.0339

Gnomad4 AMR exome AF: 0.0375

Gnomad4 ASJ exome AF: 0.0367

Gnomad4 EAS exome AF: 0.0266

Gnomad4 SAS exome AF: 0.0646

Gnomad4 FIN exome AF: 0.0290

Gnomad4 NFE exome AF: 0.0313

Gnomad4 OTH exome AF: 0.0359

GnomAD4 genome AF: 0.00402 AC: 583 AN: 145184 Hom.: 2 Cov.: 32 AF XY: 0.00394 AC XY: 278 AN XY: 70522

Gnomad4 AFR AF: 0.00546

Gnomad4 AMR AF: 0.00283

Gnomad4 ASJ AF: 0.00563

Gnomad4 EAS AF: 0.00261

Gnomad4 SAS AF: 0.0233

Gnomad4 FIN AF: 0.00101

Gnomad4 NFE AF: 0.00261

Gnomad4 OTH AF: 0.00251

Alfa AF: 0.000555 Hom.: 0

Bravo AF: 0.00380

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Intellectual Disability, Stereotypic Movements, Epilepsy, and/or Cerebral Malformations Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs553216678; hg19: chr5-88018305;