5-88818659-T-C

Variant names:

• chr5-88818659-T-C
• rs160044
• NM_002397.5:c.54+5076A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002397.5(MEF2C):​c.54+5076A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 151,758 control chromosomes in the GnomAD database, including 15,728 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.43 (15728 hom., cov: 32)
• Consequence: MEF2C NM_002397.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880
• Publications: 10 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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

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.54+5076A>G		intron	N/A	NP_002388.2
	MEF2C	NM_001193347.1		c.54+5076A>G		intron	N/A	NP_001180276.1	Q06413-5
	MEF2C	NM_001193350.2		c.54+5076A>G		intron	N/A	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.54+5076A>G		intron	N/A	ENSP00000421925.5	Q06413-1
	MEF2C	ENST00000340208.9	TSL:1	c.54+5076A>G		intron	N/A	ENSP00000340874.5	Q06413-5
	MEF2C	ENST00000437473.6	TSL:1	c.54+5076A>G		intron	N/A	ENSP00000396219.2	Q06413-1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64458 AN: 151640 Hom.: 15691 Cov.: 32

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.421

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.425 AC: 64549 AN: 151758 Hom.: 15728 Cov.: 32 AF XY: 0.421 AC XY: 31255 AN XY: 74154

African (AFR) AF: 0.668 AC: 27664 AN: 41418

American (AMR) AF: 0.452 AC: 6869 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1284 AN: 3468

East Asian (EAS) AF: 0.348 AC: 1781 AN: 5112

South Asian (SAS) AF: 0.381 AC: 1835 AN: 4816

European-Finnish (FIN) AF: 0.300 AC: 3172 AN: 10578

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.303 AC: 20567 AN: 67858

Other (OTH) AF: 0.424 AC: 892 AN: 2106

Alfa AF: 0.355 Hom.: 32575

Bravo AF: 0.455

Asia WGS AF: 0.403 AC: 1402 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.3
DANN	Benign	0.64
PhyloP100		-0.088
Mutation Taster		=100/0	polymorphism (auto)

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: rs160044; hg19: chr5-88114476;