rs138319587

Variant names:

• chr19-3977569-G-A
• rs138319587
• NM_001961.4:c.2109C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-3977569-G-A
• chr19-3977569-G-C

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.2109C>T​(p.Asp703Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000284 in 1,566,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00028 (0 hom.)
• Consequence: EEF2 NM_001961.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.112
• Publications: 0 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=-0.72).
• BP6: Variant 19-3977569-G-A is Benign according to our data. Variant chr19-3977569-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 447297.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.112 with no splicing effect.
• BS2: High AC in GnomAd4 at 50 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.2109C>T	p.Asp703Asp	synonymous	Exon 13 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.2109C>T	p.Asp703Asp	synonymous	Exon 13 of 15	ENSP00000307940.5	P13639
	EEF2	ENST00000858190.1		c.2160C>T	p.Asp720Asp	synonymous	Exon 13 of 15	ENSP00000528249.1
	EEF2	ENST00000939496.1		c.2139C>T	p.Asp713Asp	synonymous	Exon 13 of 15	ENSP00000609555.1

Frequencies

GnomAD3 genomes AF: 0.000322 AC: 49 AN: 152230 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000289

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000198 AC: 39 AN: 196998 AF XY: 0.000150

Gnomad AFR exome AF: 0.000138

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000111

Gnomad NFE exome AF: 0.000280

Gnomad OTH exome AF: 0.000205

GnomAD4 exome AF: 0.000279 AC: 395 AN: 1414264 Hom.: 0 Cov.: 33 AF XY: 0.000301 AC XY: 211 AN XY: 701050

African (AFR) AF: 0.000276 AC: 9 AN: 32598

American (AMR) AF: 0.0000251 AC: 1 AN: 39784

Ashkenazi Jewish (ASJ) AF: 0.0000423 AC: 1 AN: 23624

East Asian (EAS) AF: 0.00 AC: 0 AN: 39262

South Asian (SAS) AF: 0.000397 AC: 32 AN: 80608

European-Finnish (FIN) AF: 0.0000506 AC: 2 AN: 39514

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5514

European-Non Finnish (NFE) AF: 0.000312 AC: 341 AN: 1094610

Other (OTH) AF: 0.000153 AC: 9 AN: 58750

GnomAD4 genome AF: 0.000328 AC: 50 AN: 152348 Hom.: 0 Cov.: 32 AF XY: 0.000268 AC XY: 20 AN XY: 74496

African (AFR) AF: 0.000313 AC: 13 AN: 41586

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000500 AC: 34 AN: 68024

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000900 Hom.: 0

Bravo AF: 0.000302

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.53
DANN	Benign	0.88
PhyloP100		-0.11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs138319587; hg19: chr19-3977567;