rs150801930

chr19-3982296-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.741C>T(p.Ala247=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000274 in 1,613,992 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00029 (1 hom.)
• Consequence: EEF2 NM_001961.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.56

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=-0.66).
• BP6: Variant 19-3982296-G-A is Benign according to our data. Variant chr19-3982296-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 447306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.56 with no splicing effect.
• BS2: High AC in GnomAd at 23 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EEF2	NM_001961.4	c.741C>T	p.Ala247=	synonymous_variant	5/15	ENST00000309311.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EEF2	ENST00000309311.7	c.741C>T	p.Ala247=	synonymous_variant	5/15	5	NM_001961.4	P1
EEF2	ENST00000598182.5	n.18C>T		non_coding_transcript_exon_variant	1/4	2
EEF2	ENST00000598436.1	n.239C>T		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 152134 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000231 AC: 58 AN: 251176 Hom.: 0 AF XY: 0.000272 AC XY: 37 AN XY: 135842

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000467

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.000287 AC: 420 AN: 1461858 Hom.: 1 Cov.: 32 AF XY: 0.000305 AC XY: 222 AN XY: 727234

Gnomad4 AFR exome AF: 0.0000597

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.0000375

Gnomad4 NFE exome AF: 0.000361

Gnomad4 OTH exome AF: 0.000215

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152134 Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5 AN XY: 74324

Gnomad4 AFR AF: 0.0000483

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000278 Hom.: 0

Bravo AF: 0.000219

EpiCase AF: 0.000218

EpiControl AF: 0.000356

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Jul 12, 2017

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Apr 13, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	0.26
Dann	Benign	0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs150801930; hg19: chr19-3982294;