5-88882866-T-C

Variant names:

• chr5-88882866-T-C
• rs10044342
• NM_002397.5:c.-143+89A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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 -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 VariationId 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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEF2C	NM_002397.5	MANE Select	c.-143+89A>G		intron	N/A	NP_002388.2
	MEF2C	NM_001193347.1		c.-143+4636A>G		intron	N/A	NP_001180276.1
	MEF2C	NM_001193350.2		c.-140+89A>G		intron	N/A	NP_001180279.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEF2C	ENST00000504921.7	TSL:1 MANE Select	c.-143+89A>G		intron	N/A	ENSP00000421925.5
	MEF2C	ENST00000340208.9	TSL:1	c.-143+4636A>G		intron	N/A	ENSP00000340874.5
	MEF2C	ENST00000437473.6	TSL:1	c.-140+89A>G		intron	N/A	ENSP00000396219.2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.198 AC: 8210 AN: 41390

American (AMR) AF: 0.276 AC: 4218 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 770 AN: 3466

East Asian (EAS) AF: 0.0971 AC: 502 AN: 5172

South Asian (SAS) AF: 0.239 AC: 1150 AN: 4808

European-Finnish (FIN) AF: 0.152 AC: 1612 AN: 10588

Middle Eastern (MID) AF: 0.291 AC: 85 AN: 292

European-Non Finnish (NFE) AF: 0.164 AC: 11154 AN: 67950

Other (OTH) AF: 0.216 AC: 455 AN: 2106

Alfa AF: 0.183 Hom.: 2098

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

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.8
DANN	Benign	0.65
PhyloP100		-0.47
PromoterAI		0.0014	Neutral
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: rs10044342; hg19: chr5-88178683;