Variant 5-88722641-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 3P and 3B. PM2PP2BP4BP6_Moderate

The NM_002397.5(MEF2C):c.1385T>C(p.Val462Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MEF2C
NM_002397.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 8.92

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), MEF2C. . Gene score misZ 3.9523 (greater than the threshold 3.09). Trascript score misZ 4.8218 (greater than threshold 3.09). GenCC has associacion of gene with intellectual disability, autosomal dominant 20, complex neurodevelopmental disorder.

BP4

Computational evidence support a benign effect (MetaRNN=0.30317467).

BP6

Variant 5-88722641-A-G is Benign according to our data. Variant chr5-88722641-A-G is described in ClinVar as [Benign]. Clinvar id is 652831.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEF2C	NM_002397.5 linkuse as main transcript	c.1385T>C	p.Val462Ala	missense_variant	11/11	ENST00000504921.7
MEF2C-AS2	NR_146284.1 linkuse as main transcript	n.273A>G		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEF2C	ENST00000504921.7 linkuse as main transcript	c.1385T>C	p.Val462Ala	missense_variant	11/11	1	NM_002397.5		Q06413-1
MEF2C-AS2	ENST00000657578.1 linkuse as main transcript	n.232-39356A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

249034

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135096

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461662

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727104

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Intellectual disability, autosomal dominant 20

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 25, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.011

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

T;.;.;T;.;.;T;T;.;T;.;.;.;T;T;.;.;.;.

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

.;D;.;D;.;D;.;D;.;D;.;D;.;D;D;D;D;D;D

M_CAP

Benign

0.046

MetaRNN

Benign

0.30

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.49

MutationAssessor

Benign

1.9

L;.;.;.;.;.;L;.;.;.;.;.;.;L;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-2.3

N;N;N;.;.;.;N;.;.;.;.;D;.;.;.;.;.;.;.

REVEL

Benign

0.24

Sift

Benign

0.035

D;D;D;.;.;.;D;.;.;.;.;T;.;.;.;.;.;.;.

Sift4G

Benign

0.11

T;T;T;.;.;T;T;T;T;T;.;T;T;.;T;T;.;T;T

Polyphen

0.58

P;.;.;.;.;.;P;.;.;.;.;.;P;P;.;P;.;.;.

Vest4

0.24

MutPred

0.14

Loss of stability (P = 0.0571);.;.;.;.;.;Loss of stability (P = 0.0571);.;.;.;.;.;.;Loss of stability (P = 0.0571);.;.;.;.;.;

MVP

0.87

MPC

2.1

ClinPred

0.51

GERP RS

5.5

Varity_R

0.13

gMVP

0.27

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over