Variant 19-3977978-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001961.4(EEF2):c.1908C>G(p.Ala636=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000542 in 1,613,038 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00053 ( 3 hom. )

Consequence

EEF2
NM_001961.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.76

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 19-3977978-G-C is Benign according to our data. Variant chr19-3977978-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 585825.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.76 with no splicing effect.

BS2

High AC in GnomAd4 at 101 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EEF2	NM_001961.4 linkuse as main transcript	c.1908C>G	p.Ala636=	synonymous_variant	12/15	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.1908C>G	p.Ala636=	synonymous_variant	12/15	5	NM_001961.4	ENSP00000307940	P1
EEF2	ENST00000600794.1 linkuse as main transcript	c.107+50C>G		intron_variant		3		ENSP00000471265

Frequencies

GnomAD3 genomes

AF:

0.000644

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000688

AC:

172

AN:

249890

Hom.:

AF XY:

0.000701

AC XY:

AN XY:

135426

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.000377

Gnomad ASJ exome

AF:

0.00739

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.000785

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000434

Gnomad OTH exome

AF:

0.00148

GnomAD4 exome

AF:

0.000530

AC:

774

AN:

1460784

Hom.:

Cov.:

AF XY:

0.000549

AC XY:

399

AN XY:

726666

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.000447

Gnomad4 ASJ exome

AF:

0.00727

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000777

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000359

Gnomad4 OTH exome

AF:

0.000961

GnomAD4 genome

AF:

0.000663

AC:

101

AN:

152254

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.0101

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00141

Hom.:

Bravo

AF:

0.000627

EpiCase

AF:

0.000709

EpiControl

AF:

0.000296

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 27, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Aug 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

0.13

DANN

Benign

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

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