rs2230566

Variant names:

• chr19-3976551-C-T
• rs2230566
• NM_001961.4:c.*3G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-3976551-C-T
• chr19-3976551-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001961.4(EEF2):​c.*3G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0171 in 1,601,522 control chromosomes in the GnomAD database, including 3,871 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.090 (2048 hom., cov: 33)
  • Exomes 𝑓: 0.0094 (1823 hom.)
• Consequence: EEF2 NM_001961.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.355
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 19-3976551-C-T is Benign according to our data. Variant chr19-3976551-C-T is described in ClinVar as Benign. ClinVar VariationId is 994601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

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.*3G>A		3_prime_UTR	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.*3G>A		3_prime_UTR	Exon 15 of 15	ENSP00000307940.5	P13639
	EEF2	ENST00000858190.1		c.*3G>A		3_prime_UTR	Exon 15 of 15	ENSP00000528249.1
	EEF2	ENST00000939496.1		c.*3G>A		3_prime_UTR	Exon 15 of 15	ENSP00000609555.1

Frequencies

GnomAD3 genomes AF: 0.0900 AC: 13678 AN: 152020 Hom.: 2043 Cov.: 33

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0362

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00122

Gnomad OTH AF: 0.0599

GnomAD2 exomes AF: 0.0227 AC: 5192 AN: 228478 AF XY: 0.0161

Gnomad AFR exome AF: 0.321

Gnomad AMR exome AF: 0.0165

Gnomad ASJ exome AF: 0.000312

Gnomad EAS exome AF: 0.0000584

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000989

Gnomad OTH exome AF: 0.0105

GnomAD4 exome AF: 0.00939 AC: 13616 AN: 1449384 Hom.: 1823 Cov.: 31 AF XY: 0.00805 AC XY: 5800 AN XY: 720060

African (AFR) AF: 0.323 AC: 10704 AN: 33156

American (AMR) AF: 0.0175 AC: 756 AN: 43200

Ashkenazi Jewish (ASJ) AF: 0.0000386 AC: 1 AN: 25890

East Asian (EAS) AF: 0.0000256 AC: 1 AN: 39100

South Asian (SAS) AF: 0.000878 AC: 74 AN: 84274

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51620

Middle Eastern (MID) AF: 0.0225 AC: 129 AN: 5722

European-Non Finnish (NFE) AF: 0.000664 AC: 735 AN: 1106546

Other (OTH) AF: 0.0203 AC: 1216 AN: 59876

GnomAD4 genome AF: 0.0901 AC: 13711 AN: 152138 Hom.: 2048 Cov.: 33 AF XY: 0.0873 AC XY: 6496 AN XY: 74394

African (AFR) AF: 0.312 AC: 12936 AN: 41444

American (AMR) AF: 0.0361 AC: 552 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.00122 AC: 83 AN: 67996

Other (OTH) AF: 0.0592 AC: 125 AN: 2110

Alfa AF: 0.0413 Hom.: 449

Bravo AF: 0.104

Asia WGS AF: 0.0190 AC: 68 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	EEF2-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.4
DANN	Benign	0.92
PhyloP100		-0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs2230566; hg19: chr19-3976549;