5-88883302-AGAG-A

Variant names:

• chr5-88883302-AGAG-A
• rs1380356639
• ENST00000437473.6:c.-490_-488delCTC

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP6

The ENST00000437473.6(MEF2C):​c.-490_-488delCTC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000788 in 152,308 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 27)
  • Exomes 𝑓: 0.0064 (0 hom.)
• Consequence: MEF2C ENST00000437473.6 5_prime_UTR
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.93
• Publications: 0 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-AS1 (HGNC:48908): (MEF2C antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP6: Variant 5-88883302-AGAG-A is Benign according to our data. Variant chr5-88883302-AGAG-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3056591.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000437473.6. 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_001193347.1		c.-143+4197_-143+4199delCTC		intron	N/A	NP_001180276.1	Q06413-5
	MEF2C	NM_001364329.2		c.-140+4197_-140+4199delCTC		intron	N/A	NP_001351258.1	Q06413-1
	MEF2C	NM_001364330.2		c.-143+4197_-143+4199delCTC		intron	N/A	NP_001351259.1	Q06413-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEF2C	ENST00000437473.6	TSL:1	c.-490_-488delCTC		5_prime_UTR	Exon 1 of 11	ENSP00000396219.2	Q06413-1
	MEF2C	ENST00000340208.9	TSL:1	c.-143+4197_-143+4199delCTC		intron	N/A	ENSP00000340874.5	Q06413-5
	MEF2C	ENST00000424173.6	TSL:1	c.-143+4197_-143+4199delCTC		intron	N/A	ENSP00000389610.2	Q06413-6

Frequencies

GnomAD3 genomes AF: 0.0000199 AC: 3 AN: 150902 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000198

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00640 AC: 9 AN: 1406 Hom.: 0 AF XY: 0.00751 AC XY: 7 AN XY: 932

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 16

American (AMR) AF: 0.100 AC: 1 AN: 10

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10

East Asian (EAS) AF: 0.00 AC: 0 AN: 42

South Asian (SAS) AF: 0.00617 AC: 3 AN: 486

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 8

European-Non Finnish (NFE) AF: 0.00663 AC: 5 AN: 754

Other (OTH) AF: 0.00 AC: 0 AN: 62

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000199 AC: 3 AN: 150902 Hom.: 0 Cov.: 27 AF XY: 0.0000272 AC XY: 2 AN XY: 73662

African (AFR) AF: 0.00 AC: 0 AN: 41068

American (AMR) AF: 0.00 AC: 0 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.000198 AC: 1 AN: 5056

South Asian (SAS) AF: 0.00 AC: 0 AN: 4766

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67716

Other (OTH) AF: 0.00 AC: 0 AN: 2070

Alfa AF: 0.00 Hom.: 0

Asia WGS AF: 0.000869 AC: 3 AN: 3468

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	MEF2C-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.9
Mutation Taster		=300/0	polymorphism

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: rs1380356639; hg19: chr5-88179119;