Variant 2-232550743-G-A 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_004846.4(EIF4E2):c.19G>A(p.Ala7Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,430,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

EIF4E2
NM_004846.4 missense, splice_region

Scores

Splicing: ADA: 0.9366

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.42

Variant links:

Genes affected

EIF4E2 (HGNC:3293): (eukaryotic translation initiation factor 4E family member 2) Enables ubiquitin protein ligase binding activity. Involved in positive regulation of miRNA mediated inhibition of translation. Acts upstream of or within negative regulation of translation. Located in P-body. Part of mRNA cap binding activity complex. [provided by Alliance of Genome Resources, Apr 2022]

EIF4E2 links:

EIF4E2 (HGNC:):

EIF4E2 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=0.21598783).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF4E2	NM_004846.4 linkuse as main transcript	c.19G>A	p.Ala7Thr	missense_variant, splice_region_variant	1/7	ENST00000258416.8	NP_004837.1	O60573-1Q53RG0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF4E2	ENST00000258416.8 linkuse as main transcript	c.19G>A	p.Ala7Thr	missense_variant, splice_region_variant	1/7	1	NM_004846.4	ENSP00000258416.3		O60573-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.99e-7

AC:

AN:

1430942

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

709794

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000121

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

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

Dec 16, 2023

The c.19G>A (p.A7T) alteration is located in exon 1 (coding exon 1) of the EIF4E2 gene. This alteration results from a G to A substitution at nucleotide position 19, causing the alanine (A) at amino acid position 7 to be replaced by a threonine (T). 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

Pathogenic

0.86

BayesDel_addAF

Benign

0.011

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.035

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

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.83

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

M_CAP

Benign

0.0067

MetaRNN

Benign

0.22

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

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.3

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

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.1

N;N;N;N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.10

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

Sift4G

Benign

0.16

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

Polyphen

0.38

B;P;.;.;P;.;.

Vest4

0.41

MutPred

0.15

Gain of phosphorylation at A7 (P = 0.0153);Gain of phosphorylation at A7 (P = 0.0153);Gain of phosphorylation at A7 (P = 0.0153);Gain of phosphorylation at A7 (P = 0.0153);Gain of phosphorylation at A7 (P = 0.0153);Gain of phosphorylation at A7 (P = 0.0153);Gain of phosphorylation at A7 (P = 0.0153);

MVP

0.35

MPC

0.90

ClinPred

0.91

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.27

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.94

dbscSNV1_RF

Benign

0.59

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