5-88792622-G-C

Variant names:

• chr5-88792622-G-C
• rs770189
• NM_002397.5:c.258+11976C>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.258+11976C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 152,038 control chromosomes in the GnomAD database, including 27,634 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 0.58 (27634 hom., cov: 32)
• Consequence: MEF2C NM_002397.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.229
• Publications: 19 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEF2C	NM_002397.5	c.258+11976C>G		intron_variant	Intron 3 of 10	ENST00000504921.7	NP_002388.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEF2C	ENST00000504921.7	c.258+11976C>G		intron_variant	Intron 3 of 10	1	NM_002397.5	ENSP00000421925.5

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88758 AN: 151918 Hom.: 27632 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.632

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.596

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

GnomAD4 genome AF: 0.584 AC: 88792 AN: 152038 Hom.: 27634 Cov.: 32 AF XY: 0.584 AC XY: 43428 AN XY: 74322

African (AFR) AF: 0.375 AC: 15559 AN: 41464

American (AMR) AF: 0.498 AC: 7597 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.700 AC: 2425 AN: 3466

East Asian (EAS) AF: 0.577 AC: 2983 AN: 5170

South Asian (SAS) AF: 0.632 AC: 3049 AN: 4824

European-Finnish (FIN) AF: 0.667 AC: 7040 AN: 10558

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.707 AC: 48071 AN: 67984

Other (OTH) AF: 0.593 AC: 1253 AN: 2112

Alfa AF: 0.673 Hom.: 19194

Bravo AF: 0.555

Asia WGS AF: 0.571 AC: 1987 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.39
PhyloP100		-0.23
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: rs770189; hg19: chr5-88088439;