19-3978140-C-A

Variant names:

• chr19-3978140-C-A
• rs148878859
• NM_001961.4:c.1746G>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 2P and 9B. PM2 BP4_Strong BP7 BS2

The NM_001961.4(EEF2):​c.1746G>T​(p.Thr582Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000038 in 1,314,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T582T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000038 (0 hom.)
• Consequence: EEF2 NM_001961.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -8.43
• 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 -7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=-8.43 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 5 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.1746G>T	p.Thr582Thr	synonymous	Exon 12 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.1746G>T	p.Thr582Thr	synonymous	Exon 12 of 15	ENSP00000307940.5	P13639
	EEF2	ENST00000858190.1		c.1797G>T	p.Thr599Thr	synonymous	Exon 12 of 15	ENSP00000528249.1
	EEF2	ENST00000939496.1		c.1776G>T	p.Thr592Thr	synonymous	Exon 12 of 15	ENSP00000609555.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000380 AC: 5 AN: 1314934 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 637432

African (AFR) AF: 0.00 AC: 0 AN: 29378

American (AMR) AF: 0.00 AC: 0 AN: 25246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20134

East Asian (EAS) AF: 0.00 AC: 0 AN: 34784

South Asian (SAS) AF: 0.00 AC: 0 AN: 65354

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5300

European-Non Finnish (NFE) AF: 0.00000484 AC: 5 AN: 1034042

Other (OTH) AF: 0.00 AC: 0 AN: 54280

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.0020
DANN	Benign	0.84
PhyloP100		-8.4
PromoterAI		0.055	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs148878859; hg19: chr19-3978138;