19-3976671-C-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

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 (★★). Synonymous variant affecting the same amino acid position (i.e. L820L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (4 hom.)
• Consequence: EEF2 NM_001961.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.238

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 -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 GnomAd at 216 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EEF2	NM_001961.4	c.2460G>C	p.Leu820=	synonymous_variant	15/15	ENST00000309311.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EEF2	ENST00000309311.7	c.2460G>C	p.Leu820=	synonymous_variant	15/15	5	NM_001961.4	P1
EEF2	ENST00000600794.1	c.108-371G>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.00142 AC: 216 AN: 152214 Hom.: 0 Cov.: 33

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.: 0 AF XY: 0.00152 AC XY: 196 AN XY: 129304

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.: 4 Cov.: 31 AF XY: 0.00164 AC XY: 1190 AN XY: 724092

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.: 0 Cov.: 33 AF XY: 0.00136 AC XY: 101 AN XY: 74492

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.: 0

Bravo AF: 0.00141

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: 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	GeneDx	Jun 26, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 21, 2024	- -

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

Other links and lift over

dbSNP: rs145279867; hg19: chr19-3976669;