5-88720336-AT-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_002397.5(MEF2C):c.*2267del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0028 (0 hom.)
• Consequence: MEF2C NM_002397.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00700

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 Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00239 (356/149240) while in subpopulation NFE AF= 0.00296 (199/67136). AF 95% confidence interval is 0.00263. There are 0 homozygotes in gnomad4. There are 174 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High AC in GnomAd at 356 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEF2C	NM_002397.5	c.*2267del		3_prime_UTR_variant	11/11	ENST00000504921.7
MEF2C-AS2	NR_146284.1	n.256-2276del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEF2C	ENST00000504921.7	c.*2267del		3_prime_UTR_variant	11/11	1	NM_002397.5
MEF2C-AS2	ENST00000657578.1	n.232-41649del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00239 AC: 356 AN: 149134 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00211

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00261

Gnomad ASJ AF: 0.00146

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.00148

Gnomad FIN AF: 0.000921

Gnomad MID AF: 0.00327

Gnomad NFE AF: 0.00296

Gnomad OTH AF: 0.00439

GnomAD4 exome AF: 0.00278 AC: 1 AN: 360 Hom.: 0 Cov.: 0 AF XY: 0.00450 AC XY: 1 AN XY: 222

Gnomad4 FIN exome AF: 0.00282

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00239 AC: 356 AN: 149240 Hom.: 0 Cov.: 0 AF XY: 0.00239 AC XY: 174 AN XY: 72716

Gnomad4 AFR AF: 0.00211

Gnomad4 AMR AF: 0.00260

Gnomad4 ASJ AF: 0.00146

Gnomad4 EAS AF: 0.000196

Gnomad4 SAS AF: 0.00148

Gnomad4 FIN AF: 0.000921

Gnomad4 NFE AF: 0.00296

Gnomad4 OTH AF: 0.00435

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

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)		0.0		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: rs3841444; hg19: chr5-88016153;