5-88882866-T-C

Position:

• chr5-88882866-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002397.5(MEF2C):​c.-143+89A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 151,962 control chromosomes in the GnomAD database, including 2,812 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (2812 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MEF2C NM_002397.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.470

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 5-88882866-T-C is Benign according to our data. Variant chr5-88882866-T-C is described in ClinVar as [Benign]. Clinvar id is 1229073.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEF2C	NM_002397.5	c.-143+89A>G		intron_variant		ENST00000504921.7	NP_002388.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEF2C	ENST00000504921.7	c.-143+89A>G		intron_variant		1	NM_002397.5	ENSP00000421925.5

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28308 AN: 151842 Hom.: 2806 Cov.: 31

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.0974

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.212

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 8 Hom.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.187 AC: 28345 AN: 151962 Hom.: 2812 Cov.: 31 AF XY: 0.187 AC XY: 13868 AN XY: 74296

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.0971

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.216

Alfa AF: 0.186 Hom.: 1533

Bravo AF: 0.200

Asia WGS AF: 0.197 AC: 686 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.8
DANN	Benign	0.65

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: rs10044342; hg19: chr5-88178683;