Variant 19-3976707-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4BP6_Very_StrongBP7BA1

The NM_001961.4(EEF2):c.2424G>A(p.Ala808=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00367 in 1,603,144 control chromosomes in the GnomAD database, including 205 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 114 hom., cov: 33)

Exomes 𝑓: 0.0020 ( 91 hom. )

Consequence

EEF2
NM_001961.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.27

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.17).

BP6

Variant 19-3976707-C-T is Benign according to our data. Variant chr19-3976707-C-T is described in ClinVar as [Benign]. Clinvar id is 791348.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.27 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EEF2	NM_001961.4 linkuse as main transcript	c.2424G>A	p.Ala808=	synonymous_variant	15/15	ENST00000309311.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EEF2	ENST00000309311.7 linkuse as main transcript	c.2424G>A	p.Ala808=	synonymous_variant	15/15	5	NM_001961.4	P1
EEF2	ENST00000600794.1 linkuse as main transcript	c.108-407G>A		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0199

AC:

3023

AN:

152162

Hom.:

115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0702

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00484

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000413

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.00497

AC:

1165

AN:

234196

Hom.:

AF XY:

0.00378

AC XY:

482

AN XY:

127628

show subpopulations

Gnomad AFR exome

AF:

0.0685

Gnomad AMR exome

AF:

0.00270

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000102

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000271

Gnomad OTH exome

AF:

0.00259

GnomAD4 exome

AF:

0.00197

AC:

2865

AN:

1450864

Hom.:

Cov.:

AF XY:

0.00170

AC XY:

1226

AN XY:

721538

show subpopulations

Gnomad4 AFR exome

AF:

0.0683

Gnomad4 AMR exome

AF:

0.00332

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000129

Gnomad4 FIN exome

AF:

0.0000209

Gnomad4 NFE exome

AF:

0.000132

Gnomad4 OTH exome

AF:

0.00439

GnomAD4 genome

AF:

0.0199

AC:

3023

AN:

152280

Hom.:

114

Cov.:

AF XY:

0.0186

AC XY:

1383

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0700

Gnomad4 AMR

AF:

0.00484

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.00136

Hom.:

Bravo

AF:

0.0228

Asia WGS

AF:

0.00664

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Dec 31, 2019

- -

EEF2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 10, 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

-0.17

CADD

Benign

DANN

Benign

0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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