rs563092089

chr19-3977563-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001961.4(EEF2):c.2115C>T(p.His705=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000864 in 1,573,310 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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000091 (1 hom.)
• Consequence: EEF2 NM_001961.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.893

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 19-3977563-G-A is Benign according to our data. Variant chr19-3977563-G-A is described in ClinVar as [Benign]. Clinvar id is 585826.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.893 with no splicing effect.
• BS2: High AC in GnomAd at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EEF2	NM_001961.4	c.2115C>T	p.His705=	synonymous_variant	13/15	ENST00000309311.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EEF2	ENST00000309311.7	c.2115C>T	p.His705=	synonymous_variant	13/15	5	NM_001961.4	P1
EEF2	ENST00000600794.1	c.107+465C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152232 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000137 AC: 28 AN: 204578 Hom.: 0 AF XY: 0.000188 AC XY: 21 AN XY: 111492

Gnomad AFR exome AF: 0.0000685

Gnomad AMR exome AF: 0.0000341

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000865

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000416

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000915 AC: 130 AN: 1420960 Hom.: 1 Cov.: 33 AF XY: 0.000105 AC XY: 74 AN XY: 705056

Gnomad4 AFR exome AF: 0.000214

Gnomad4 AMR exome AF: 0.0000743

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000964

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000273

Gnomad4 OTH exome AF: 0.000186

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152350 Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4 AN XY: 74502

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000264

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	0.045
Dann	Benign	0.88
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: rs563092089; hg19: chr19-3977561;