rs533090086

chr19-3977267-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.2331C>T(p.Ala777=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000138 in 1,612,634 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00014 (2 hom.)
• Consequence: EEF2 NM_001961.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.08

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 19-3977267-G-A is Benign according to our data. Variant chr19-3977267-G-A is described in ClinVar as [Benign]. Clinvar id is 585830.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.08 with no splicing effect.
• BS2: High AC in GnomAd at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EEF2	NM_001961.4	c.2331C>T	p.Ala777=	synonymous_variant	14/15	ENST00000309311.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EEF2	ENST00000309311.7	c.2331C>T	p.Ala777=	synonymous_variant	14/15	5	NM_001961.4	P1
EEF2	ENST00000600794.1	c.107+761C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152170 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000199 AC: 49 AN: 246430 Hom.: 1 AF XY: 0.000262 AC XY: 35 AN XY: 133692

Gnomad AFR exome AF: 0.000126

Gnomad AMR exome AF: 0.0000292

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000890

Gnomad FIN exome AF: 0.0000952

Gnomad NFE exome AF: 0.000144

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.000142 AC: 207 AN: 1460346 Hom.: 2 Cov.: 30 AF XY: 0.000164 AC XY: 119 AN XY: 726378

Gnomad4 AFR exome AF: 0.000120

Gnomad4 AMR exome AF: 0.0000449

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000757

Gnomad4 SAS exome AF: 0.000732

Gnomad4 FIN exome AF: 0.0000942

Gnomad4 NFE exome AF: 0.000104

Gnomad4 OTH exome AF: 0.000149

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152288 Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9 AN XY: 74478

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000205 Hom.: 0

Bravo AF: 0.000113

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Sep 20, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Nov 13, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	0.43
Dann	Benign	0.87
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: rs533090086; hg19: chr19-3977265; COSMIC: COSV58579595; COSMIC: COSV58579595;