Variant 19-3976551-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001961.4(EEF2):c.*3G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0171 in 1,601,522 control chromosomes in the GnomAD database, including 3,871 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.090 ( 2048 hom., cov: 33)

Exomes 𝑓: 0.0094 ( 1823 hom. )

Consequence

EEF2
NM_001961.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.355

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 19-3976551-C-T is Benign according to our data. Variant chr19-3976551-C-T is described in ClinVar as [Benign]. Clinvar id is 994601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-3976551-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EEF2	NM_001961.4 linkuse as main transcript	c.*3G>A		3_prime_UTR_variant	15/15	ENST00000309311.7	NP_001952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EEF2	ENST00000309311.7 linkuse as main transcript	c.*3G>A		3_prime_UTR_variant	15/15	5	NM_001961.4	ENSP00000307940	P1
EEF2	ENST00000600794.1 linkuse as main transcript	c.108-251G>A		intron_variant		3		ENSP00000471265

Frequencies

GnomAD3 genomes

AF:

0.0900

AC:

13678

AN:

152020

Hom.:

2043

Cov.:

show subpopulations

Gnomad AFR

AF:

0.312

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0362

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.00122

Gnomad OTH

AF:

0.0599

GnomAD3 exomes

AF:

0.0227

AC:

5192

AN:

228478

Hom.:

679

AF XY:

0.0161

AC XY:

2003

AN XY:

124158

show subpopulations

Gnomad AFR exome

AF:

0.321

Gnomad AMR exome

AF:

0.0165

Gnomad ASJ exome

AF:

0.000312

Gnomad EAS exome

AF:

0.0000584

Gnomad SAS exome

AF:

0.000952

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000989

Gnomad OTH exome

AF:

0.0105

GnomAD4 exome

AF:

0.00939

AC:

13616

AN:

1449384

Hom.:

1823

Cov.:

AF XY:

0.00805

AC XY:

5800

AN XY:

720060

show subpopulations

Gnomad4 AFR exome

AF:

0.323

Gnomad4 AMR exome

AF:

0.0175

Gnomad4 ASJ exome

AF:

0.0000386

Gnomad4 EAS exome

AF:

0.0000256

Gnomad4 SAS exome

AF:

0.000878

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000664

Gnomad4 OTH exome

AF:

0.0203

GnomAD4 genome

AF:

0.0901

AC:

13711

AN:

152138

Hom.:

2048

Cov.:

AF XY:

0.0873

AC XY:

6496

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.312

Gnomad4 AMR

AF:

0.0361

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00122

Gnomad4 OTH

AF:

0.0592

Alfa

AF:

0.0413

Hom.:

449

Bravo

AF:

0.104

Asia WGS

AF:

0.0190

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Nov 07, 2019

- -

EEF2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

1.4

DANN

Benign

0.92

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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