chr5-88720336-A-AT

Variant names:

• chr5-88720336-A-AT
• rs3841444
• ENST00000437473.6:c.*2267dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000437473.6(MEF2C):​c.*2267dupA variant causes a splice region change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.66 (33279 hom., cov: 0)
  • Exomes 𝑓: 0.63 (70 hom.)
• Consequence: MEF2C ENST00000437473.6 splice_region
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00700
• Publications: 3 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-AS2 (HGNC:53115): (MEF2C antisense RNA 2)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 5-88720336-A-AT is Benign according to our data. Variant chr5-88720336-A-AT is described in ClinVar as Benign. ClinVar VariationId is 354574.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

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_002397.5	MANE Select	c.*2267dupA		3_prime_UTR	Exon 11 of 11	NP_002388.2
	MEF2C	NM_001193347.1		c.*2267dupA		3_prime_UTR	Exon 12 of 12	NP_001180276.1	Q06413-5
	MEF2C	NM_001193350.2		c.*2267dupA		3_prime_UTR	Exon 11 of 11	NP_001180279.1	Q06413-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEF2C	ENST00000437473.6	TSL:1	c.*2267dupA		splice_region	Exon 11 of 11	ENSP00000396219.2	Q06413-1
	MEF2C	ENST00000504921.7	TSL:1 MANE Select	c.*2267dupA		3_prime_UTR	Exon 11 of 11	ENSP00000421925.5	Q06413-1
	MEF2C	ENST00000340208.9	TSL:1	c.*2267dupA		3_prime_UTR	Exon 12 of 12	ENSP00000340874.5	Q06413-5

Frequencies

GnomAD3 genomes AF: 0.662 AC: 98671 AN: 149080 Hom.: 33274 Cov.: 0

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.904

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.662

GnomAD4 exome AF: 0.635 AC: 231 AN: 364 Hom.: 70 Cov.: 0 AF XY: 0.670 AC XY: 150 AN XY: 224

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: 0.628 AC: 225 AN: 358

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AF: 1.00 AC: 4 AN: 4

GnomAD4 genome AF: 0.662 AC: 98717 AN: 149186 Hom.: 33279 Cov.: 0 AF XY: 0.665 AC XY: 48328 AN XY: 72686

African (AFR) AF: 0.529 AC: 21592 AN: 40790

American (AMR) AF: 0.634 AC: 9482 AN: 14964

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 2300 AN: 3432

East Asian (EAS) AF: 0.905 AC: 4622 AN: 5106

South Asian (SAS) AF: 0.683 AC: 3234 AN: 4734

European-Finnish (FIN) AF: 0.694 AC: 6785 AN: 9780

Middle Eastern (MID) AF: 0.699 AC: 200 AN: 286

European-Non Finnish (NFE) AF: 0.723 AC: 48536 AN: 67124

Other (OTH) AF: 0.660 AC: 1363 AN: 2066

Alfa AF: 0.558 Hom.: 1128

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Intellectual Disability, Stereotypic Movements, Epilepsy, and/or Cerebral Malformations (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.0070
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: rs3841444; hg19: chr5-88016153;