5-88720336-A-AT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002397.5(MEF2C):c.*2267_*2268insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.66 (33279 hom., cov: 0)
  • Exomes 𝑓: 0.63 (70 hom.)
• Consequence: MEF2C NM_002397.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B: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 Benign. Variant got -10 ACMG points.

• BP6: Variant 5-88720336-A-AT is Benign according to our data. Variant chr5-88720336-A-AT is described in ClinVar as [Benign]. Clinvar id is 354574.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEF2C	NM_002397.5	c.*2267_*2268insA		3_prime_UTR_variant	11/11	ENST00000504921.7
MEF2C-AS2	NR_146284.1	n.256-2276dup		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEF2C	ENST00000504921.7	c.*2267_*2268insA		3_prime_UTR_variant	11/11	1	NM_002397.5
MEF2C-AS2	ENST00000657578.1	n.232-41649dup		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.662 AC: 98671 AN: 149080 Hom.: 33274 Cov.: 0

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.904

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.662

GnomAD4 exome AF: 0.635 AC: 231 AN: 364 Hom.: 70 Cov.: 0 AF XY: 0.670 AC XY: 150 AN XY: 224

Gnomad4 FIN exome AF: 0.628

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.662 AC: 98717 AN: 149186 Hom.: 33279 Cov.: 0 AF XY: 0.665 AC XY: 48328 AN XY: 72686

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.634

Gnomad4 ASJ AF: 0.670

Gnomad4 EAS AF: 0.905

Gnomad4 SAS AF: 0.683

Gnomad4 FIN AF: 0.694

Gnomad4 NFE AF: 0.723

Gnomad4 OTH AF: 0.660

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Benign, 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;