19-3976551-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.355

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]

ACMG classification

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	UniProt
EEF2	NM_001961.4	c.*3G>A		3_prime_UTR_variant	15/15	ENST00000309311.7

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0900 AC: 13678 AN: 152020 Hom.: 2043 Cov.: 33

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

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.: 31 AF XY: 0.00805 AC XY: 5800 AN XY: 720060

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.: 33 AF XY: 0.0873 AC XY: 6496 AN XY: 74394

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: 68 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Nov 07, 2019

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

EEF2-related disorder Benign:1

Benign, criteria provided, single submitter

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

Other links and lift over

dbSNP: rs2230566; hg19: chr19-3976549;