Variant 19-3976601-G-A 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.2530C>T(p.Leu844=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00074 in 1,610,816 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0038 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 3 hom. )

Consequence

EEF2
NM_001961.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.43

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=-0.37).

BP6

Variant 19-3976601-G-A is Benign according to our data. Variant chr19-3976601-G-A is described in ClinVar as [Benign]. Clinvar id is 447301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.43 with no splicing effect.

BS2

High AC in GnomAd4 at 574 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EEF2	NM_001961.4 linkuse as main transcript	c.2530C>T	p.Leu844=	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.2530C>T	p.Leu844=	synonymous_variant	15/15	5	NM_001961.4	P1
EEF2	ENST00000600794.1 linkuse as main transcript	c.108-301C>T		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00374

AC:

569

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0129

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000884

AC:

214

AN:

242160

Hom.:

AF XY:

0.000646

AC XY:

AN XY:

131588

show subpopulations

Gnomad AFR exome

AF:

0.0124

Gnomad AMR exome

AF:

0.000354

Gnomad ASJ exome

AF:

0.000203

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000671

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000458

Gnomad OTH exome

AF:

0.000506

GnomAD4 exome

AF:

0.000424

AC:

618

AN:

1458490

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

282

AN XY:

725304

show subpopulations

Gnomad4 AFR exome

AF:

0.0147

Gnomad4 AMR exome

AF:

0.000451

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000234

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000288

Gnomad4 OTH exome

AF:

0.000879

GnomAD4 genome

AF:

0.00377

AC:

574

AN:

152326

Hom.:

Cov.:

AF XY:

0.00352

AC XY:

262

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0129

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00222

Hom.:

Bravo

AF:

0.00442

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 11, 2023	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Oct 14, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.95

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