NM_001961.4:c.1746G>C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001961.4(EEF2):​c.1746G>C​(p.Thr582Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. T582T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EEF2 NM_001961.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 19-3978140-C-G is Benign according to our data. Variant chr19-3978140-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 739204.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-8.43 with no splicing effect.

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>C	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>C	p.Thr582Thr	synonymous	Exon 12 of 15	ENSP00000307940.5	P13639
	EEF2	ENST00000858190.1		c.1797G>C	p.Thr599Thr	synonymous	Exon 12 of 15	ENSP00000528249.1
	EEF2	ENST00000939496.1		c.1776G>C	p.Thr592Thr	synonymous	Exon 12 of 15	ENSP00000609555.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000101 AC: 1 AN: 98652 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000103

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.0020
DANN	Benign	0.72
PhyloP100		-8.4
PromoterAI		0.036	Neutral

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;