19-3976716-G-A

Variant names:

• chr19-3976716-G-A
• rs143122141
• NM_001961.4:c.2415C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001961.4(EEF2):​c.2415C>T​(p.Gly805Gly) 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
• Publications: 1 publications found

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]

EEF2 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia type 26

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 447299.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.5 with no splicing effect.
• BS2: High AC in GnomAd4 at 177 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001961.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEF2	NM_001961.4	MANE Select	c.2415C>T	p.Gly805Gly	synonymous	Exon 15 of 15	NP_001952.1	P13639

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEF2	ENST00000309311.7	TSL:5 MANE Select	c.2415C>T	p.Gly805Gly	synonymous	Exon 15 of 15	ENSP00000307940.5	P13639
	EEF2	ENST00000858190.1		c.2466C>T	p.Gly822Gly	synonymous	Exon 15 of 15	ENSP00000528249.1
	EEF2	ENST00000939496.1		c.2445C>T	p.Gly815Gly	synonymous	Exon 15 of 15	ENSP00000609555.1

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

GnomAD2 exomes AF: 0.000919 AC: 211 AN: 229696 AF XY: 0.000919

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 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

African (AFR) AF: 0.000210 AC: 7 AN: 33324

American (AMR) AF: 0.000229 AC: 10 AN: 43702

Ashkenazi Jewish (ASJ) AF: 0.00474 AC: 121 AN: 25552

East Asian (EAS) AF: 0.00 AC: 0 AN: 39542

South Asian (SAS) AF: 0.00 AC: 0 AN: 84814

European-Finnish (FIN) AF: 0.000646 AC: 30 AN: 46436

Middle Eastern (MID) AF: 0.000350 AC: 2 AN: 5718

European-Non Finnish (NFE) AF: 0.00207 AC: 2289 AN: 1107880

Other (OTH) AF: 0.00285 AC: 171 AN: 59964

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

African (AFR) AF: 0.000241 AC: 10 AN: 41440

American (AMR) AF: 0.000262 AC: 4 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00663 AC: 23 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.000659 AC: 7 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00194 AC: 132 AN: 68026

Other (OTH) AF: 0.000479 AC: 1 AN: 2088

Alfa AF: 0.00178 Hom.: 0

Bravo AF: 0.00104

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	2.3
DANN	Benign	0.90
PhyloP100		-3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs143122141; hg19: chr19-3976714;