rs34012995

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001961.4(EEF2):c.2530C>T(p.Leu844Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00074 in 1,610,816 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 Benign (★★).

Frequency

Genomes: 𝑓 0.0038 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 3 hom. )

Consequence

EEF2
NM_001961.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.43

Publications

2 publications found

Variant links:

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: Orphanet, Labcorp Genetics (formerly Invitae)
neurodevelopmental disorder
Inheritance: AD Classification: MODERATE, LIMITED Submitted by: G2P, Ambry Genetics

EEF2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 19-3976601-G-A is Benign according to our data. Variant chr19-3976601-G-A is described in CliVar as Benign. Clinvar id is 447301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-3976601-G-A is described in CliVar as Benign. Clinvar id is 447301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-3976601-G-A is described in CliVar as Benign. Clinvar id is 447301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-3976601-G-A is described in CliVar as Benign. Clinvar id is 447301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-3976601-G-A is described in CliVar as Benign. Clinvar id is 447301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-3976601-G-A is described in CliVar as Benign. Clinvar id is 447301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-3976601-G-A is described in CliVar as Benign. Clinvar id is 447301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-3976601-G-A is described in CliVar as Benign. Clinvar id is 447301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-3976601-G-A is described in CliVar as Benign. Clinvar id is 447301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-3976601-G-A is described in CliVar as Benign. Clinvar id is 447301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-3976601-G-A is described in CliVar as Benign. Clinvar id is 447301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-3976601-G-A is described in CliVar as Benign. Clinvar id is 447301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-3976601-G-A is described in CliVar as Benign. Clinvar id is 447301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-3976601-G-A is described in CliVar as Benign. Clinvar id is 447301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-3976601-G-A is described in CliVar as Benign. Clinvar id is 447301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-3976601-G-A is described in CliVar as Benign. Clinvar id is 447301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-3976601-G-A is described in CliVar as Benign. Clinvar id is 447301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-3976601-G-A is described in CliVar as Benign. Clinvar id is 447301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-3976601-G-A is described in CliVar as Benign. Clinvar id is 447301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-3976601-G-A is described in CliVar as Benign. Clinvar id is 447301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-3976601-G-A is described in CliVar as Benign. Clinvar id is 447301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-3976601-G-A is described in CliVar as Benign. Clinvar id is 447301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-3976601-G-A is described in CliVar as Benign. Clinvar id is 447301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.43 with no splicing effect.

BS2

High AC in GnomAd4 at 574 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EEF2	NM_001961.4 link	c.2530C>T	p.Leu844Leu	synonymous_variant	Exon 15 of 15	ENST00000309311.7	NP_001952.1	P13639

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EEF2	ENST00000309311.7 link	c.2530C>T	p.Leu844Leu	synonymous_variant	Exon 15 of 15	5	NM_001961.4	ENSP00000307940.5		P13639
EEF2	ENST00000600794.1 link	c.107-301C>T		intron_variant	Intron 1 of 1	3		ENSP00000471265.1		M0R0I6

Frequencies

GnomAD3 genomes

AF:

0.00374

AC:

569

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0129

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.000884

AC:

214

AN:

242160

AF XY:

0.000646

show subpopulations

Gnomad AFR exome

AF:

0.0124

Gnomad AMR exome

AF:

0.000354

Gnomad ASJ exome

AF:

0.000203

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000458

Gnomad OTH exome

AF:

0.000506

GnomAD4 exome

AF:

0.000424

AC:

618

AN:

1458490

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

282

AN XY:

725304

show subpopulations

African (AFR)

AF:

0.0147

AC:

491

AN:

33414

American (AMR)

AF:

0.000451

AC:

AN:

44344

Ashkenazi Jewish (ASJ)

AF:

0.0000384

AC:

AN:

26034

East Asian (EAS)

AF:

0.00

AC:

AN:

39602

South Asian (SAS)

AF:

0.0000234

AC:

AN:

85606

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52718

Middle Eastern (MID)

AF:

0.00330

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000288

AC:

AN:

1110736

Other (OTH)

AF:

0.000879

AC:

AN:

60272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

110

146

183

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00377

AC:

574

AN:

152326

Hom.:

Cov.:

AF XY:

0.00352

AC XY:

262

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.0129

AC:

538

AN:

41570

American (AMR)

AF:

0.00170

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68024

Other (OTH)

AF:

0.00237

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

125

156

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00222

Hom.:

Bravo

AF:

0.00442

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 23, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Dec 02, 2024

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

3.4

Mutation Taster

=99/1

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over