19-3976716-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001961.4(EEF2):c.2415C>T(p.Gly805=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00176 in 1,599,120 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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0018 (5 hom.)
• Consequence: EEF2 NM_001961.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.50

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 19-3976716-G-A is Benign according to our data. Variant chr19-3976716-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 447299.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-3976716-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-3.5 with no splicing effect.
• BS2: High AC in GnomAd at 177 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EEF2	NM_001961.4	c.2415C>T	p.Gly805=	synonymous_variant	15/15	ENST00000309311.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EEF2	ENST00000309311.7	c.2415C>T	p.Gly805=	synonymous_variant	15/15	5	NM_001961.4	P1
EEF2	ENST00000600794.1	c.108-416C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.00116 AC: 177 AN: 152188 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00194

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.000919 AC: 211 AN: 229696 Hom.: 1 AF XY: 0.000919 AC XY: 115 AN XY: 125174

Gnomad AFR exome AF: 0.000201

Gnomad AMR exome AF: 0.000242

Gnomad ASJ exome AF: 0.00530

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000592

Gnomad NFE exome AF: 0.00131

Gnomad OTH exome AF: 0.000704

GnomAD4 exome AF: 0.00182 AC: 2630 AN: 1446932 Hom.: 5 Cov.: 31 AF XY: 0.00172 AC XY: 1239 AN XY: 719354

Gnomad4 AFR exome AF: 0.000210

Gnomad4 AMR exome AF: 0.000229

Gnomad4 ASJ exome AF: 0.00474

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000646

Gnomad4 NFE exome AF: 0.00207

Gnomad4 OTH exome AF: 0.00285

GnomAD4 genome AF: 0.00116 AC: 177 AN: 152188 Hom.: 0 Cov.: 33 AF XY: 0.00105 AC XY: 78 AN XY: 74356

Gnomad4 AFR AF: 0.000241

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00663

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.00194

Gnomad4 OTH AF: 0.000479

Alfa AF: 0.00178 Hom.: 0

Bravo AF: 0.00104

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2022	EEF2: BS1, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Sep 05, 2023	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Aug 16, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	2.3
Dann	Benign	0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs143122141; hg19: chr19-3976714;