Variant 19-3976671-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001961.4(EEF2):c.2460G>C(p.Leu820=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00163 in 1,608,438 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 4 hom. )

Consequence

EEF2
NM_001961.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.238

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 19-3976671-C-G is Benign according to our data. Variant chr19-3976671-C-G is described in ClinVar as [Benign]. Clinvar id is 715638.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-3976671-C-G is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.238 with no splicing effect.

BS2

High AC in GnomAd4 at 216 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EEF2	NM_001961.4 linkuse as main transcript	c.2460G>C	p.Leu820=	synonymous_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.2460G>C	p.Leu820=	synonymous_variant	15/15	5	NM_001961.4	ENSP00000307940	P1
EEF2	ENST00000600794.1 linkuse as main transcript	c.108-371G>C		intron_variant		3		ENSP00000471265

Frequencies

GnomAD3 genomes

AF:

0.00142

AC:

216

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00222

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00150

AC:

357

AN:

237632

Hom.:

AF XY:

0.00152

AC XY:

196

AN XY:

129304

show subpopulations

Gnomad AFR exome

AF:

0.000739

Gnomad AMR exome

AF:

0.00170

Gnomad ASJ exome

AF:

0.00195

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000373

Gnomad FIN exome

AF:

0.000857

Gnomad NFE exome

AF:

0.00221

Gnomad OTH exome

AF:

0.00103

GnomAD4 exome

AF:

0.00165

AC:

2401

AN:

1456106

Hom.:

Cov.:

AF XY:

0.00164

AC XY:

1190

AN XY:

724092

show subpopulations

Gnomad4 AFR exome

AF:

0.000419

Gnomad4 AMR exome

AF:

0.00170

Gnomad4 ASJ exome

AF:

0.00146

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000456

Gnomad4 FIN exome

AF:

0.00112

Gnomad4 NFE exome

AF:

0.00187

Gnomad4 OTH exome

AF:

0.00155

GnomAD4 genome

AF:

0.00142

AC:

216

AN:

152332

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

101

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.000980

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00122

Gnomad4 NFE

AF:

0.00222

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00145

Hom.:

Bravo

AF:

0.00141

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 21, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Jun 10, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

6.5

DANN

Benign

0.80

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