Genetic Variant MEF2C:c.*2267dupA (chr5-88720336-A-AT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.00700

Publications

3 publications found

Variant links:

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 links:

MEF2C-AS2 (HGNC:53115): (MEF2C antisense RNA 2)

MEF2C-AS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	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

Gene	Transcript	Tags	HGVSc	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.:

show subpopulations

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.:

Cov.:

AF XY:

0.670

AC XY:

150

AN XY:

224

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.628

AC:

225

AN:

358

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.662

AC:

98717

AN:

149186

Hom.:

33279

Cov.:

AF XY:

0.665

AC XY:

48328

AN XY:

72686

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1572

3144

4716

6288

7860

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

798

1596

2394

3192

3990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.558

Hom.:

1128

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

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)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

5-88720336-ATTTT-ATTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over