Variant rs980260154 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP2PP3BS2

The NM_001961.4(EEF2):c.1088C>T(p.Thr363Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000236 in 1,565,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

EEF2
NM_001961.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.94

Variant links:

Genes affected

EEF2 (HGNC:3214): (eukaryotic translation elongation factor 2) This gene encodes a member of the GTP-binding translation elongation factor family. This protein is an essential factor for protein synthesis. It promotes the GTP-dependent translocation of the nascent protein chain from the A-site to the P-site of the ribosome. This protein is completely inactivated by EF-2 kinase phosporylation. [provided by RefSeq, Jul 2008]

EEF2 links:

EEF2 (HGNC:):

EEF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), EEF2. . Gene score misZ 4.8778 (greater than the threshold 3.09). Trascript score misZ 3.5943 (greater than threshold 3.09). GenCC has associacion of gene with spinocerebellar ataxia type 26.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.786

BS2

High AC in GnomAdExome4 at 34 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EEF2	NM_001961.4 linkuse as main transcript	c.1088C>T	p.Thr363Met	missense_variant	8/15	ENST00000309311.7	NP_001952.1	P13639

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
EEF2	ENST00000309311.7 linkuse as main transcript	c.1088C>T	p.Thr363Met	missense_variant	8/15	5	NM_001961.4	ENSP00000307940.5	P13639
EEF2	ENST00000598182.5 linkuse as main transcript	n.365C>T		non_coding_transcript_exon_variant	4/4	2
EEF2	ENST00000598436.1 linkuse as main transcript	n.*37C>T		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000343

AC:

AN:

174842

Hom.:

AF XY:

0.0000107

AC XY:

AN XY:

93804

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000763

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000700

Gnomad NFE exome

AF:

0.0000549

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000241

AC:

AN:

1413532

Hom.:

Cov.:

AF XY:

0.0000172

AC XY:

AN XY:

699214

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000270

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000211

Gnomad4 NFE exome

AF:

0.0000294

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000283

Hom.:

Bravo

AF:

0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Athena Diagnostics

Apr 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.0038

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.46

Eigen

Pathogenic

0.68

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.071

MetaRNN

Pathogenic

0.79

MetaSVM

Benign

-0.62

MutationAssessor

Pathogenic

3.0

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-2.8

REVEL

Uncertain

0.31

Sift

Uncertain

0.0030

Sift4G

Benign

0.12

Polyphen

0.98

Vest4

0.83

MVP

0.60

ClinPred

0.77

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.72

gMVP

0.63

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