Variant 15-48178216-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016132.5(MYEF2):c.22G>A(p.Glu8Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000138 in 1,305,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

MYEF2
NM_016132.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.75

Variant links:

Genes affected

MYEF2 (HGNC:17940): (myelin expression factor 2) Enables RNA binding activity. Involved in myotube differentiation and neuron differentiation. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MYEF2 links:

CTXN2 (HGNC:31109): (cortexin 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

CTXN2 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;

BP4

Computational evidence support a benign effect (MetaRNN=0.15741298).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYEF2	NM_016132.5 linkuse as main transcript	c.22G>A	p.Glu8Lys	missense_variant	1/17	ENST00000324324.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYEF2	ENST00000324324.12 linkuse as main transcript	c.22G>A	p.Glu8Lys	missense_variant	1/17	1	NM_016132.5	P4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000163

AC:

AN:

61260

Hom.:

AF XY:

0.0000289

AC XY:

AN XY:

34626

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000110

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:

0.0000138

AC:

AN:

1305844

Hom.:

Cov.:

AF XY:

0.0000109

AC XY:

AN XY:

641652

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000995

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:

0.0000125

Gnomad4 OTH exome

AF:

0.0000373

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000200

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 20, 2023

The c.22G>A (p.E8K) alteration is located in exon 1 (coding exon 1) of the MYEF2 gene. This alteration results from a G to A substitution at nucleotide position 22, causing the glutamic acid (E) at amino acid position 8 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.018

T;.;T

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.21

LIST_S2

Uncertain

0.86

D;D;D

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.79

N;N

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.56

N;N;.

REVEL

Benign

0.027

Sift

Pathogenic

0.0

D;D;.

Sift4G

Benign

0.24

T;T;T

Vest4

0.19

MVP

0.27

MPC

0.42

ClinPred

0.74

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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