chr20-63494946-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001958.5(EEF1A2):c.480G>A(p.Pro160Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,612,748 control chromosomes in the GnomAD database, including 17,013 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1555 hom., cov: 34)

Exomes 𝑓: 0.13 ( 15458 hom. )

Consequence

EEF1A2
NM_001958.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -3.78

Publications

22 publications found

Variant links:

Genes affected

EEF1A2 (HGNC:3192): (eukaryotic translation elongation factor 1 alpha 2) This gene encodes an isoform of the alpha subunit of the elongation factor-1 complex, which is responsible for the enzymatic delivery of aminoacyl tRNAs to the ribosome. This isoform (alpha 2) is expressed in brain, heart and skeletal muscle, and the other isoform (alpha 1) is expressed in brain, placenta, lung, liver, kidney, and pancreas. This gene may be critical in the development of ovarian cancer. [provided by RefSeq, Mar 2014]

EEF1A2 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
developmental and epileptic encephalopathy, 33
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
autosomal dominant non-syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
undetermined early-onset epileptic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

EEF1A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 20-63494946-C-T is Benign according to our data. Variant chr20-63494946-C-T is described in ClinVar as Benign. ClinVar VariationId is 380779.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.78 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EEF1A2	NM_001958.5 link	c.480G>A	p.Pro160Pro	synonymous_variant	Exon 4 of 8	ENST00000217182.6	NP_001949.1	Q05639

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EEF1A2	ENST00000217182.6 link	c.480G>A	p.Pro160Pro	synonymous_variant	Exon 4 of 8	1	NM_001958.5	ENSP00000217182.3		Q05639

Frequencies

GnomAD3 genomes

AF:

0.113

AC:

17245

AN:

152172

Hom.:

1554

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0256

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.0895

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.441

Gnomad SAS

AF:

0.0695

Gnomad FIN

AF:

0.224

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.134

Gnomad OTH

AF:

0.116

GnomAD2 exomes

AF:

0.139

AC:

34691

AN:

250166

AF XY:

0.136

show subpopulations

Gnomad AFR exome

AF:

0.0226

Gnomad AMR exome

AF:

0.0810

Gnomad ASJ exome

AF:

0.123

Gnomad EAS exome

AF:

0.425

Gnomad FIN exome

AF:

0.224

Gnomad NFE exome

AF:

0.133

Gnomad OTH exome

AF:

0.132

GnomAD4 exome

AF:

0.131

AC:

191988

AN:

1460458

Hom.:

15458

Cov.:

AF XY:

0.129

AC XY:

93916

AN XY:

726520

show subpopulations

African (AFR)

AF:

0.0201

AC:

673

AN:

33480

American (AMR)

AF:

0.0807

AC:

3607

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.115

AC:

3014

AN:

26132

East Asian (EAS)

AF:

0.436

AC:

17293

AN:

39692

South Asian (SAS)

AF:

0.0585

AC:

5043

AN:

86258

European-Finnish (FIN)

AF:

0.219

AC:

11416

AN:

52090

Middle Eastern (MID)

AF:

0.0986

AC:

569

AN:

5768

European-Non Finnish (NFE)

AF:

0.128

AC:

142273

AN:

1111948

Other (OTH)

AF:

0.134

AC:

8100

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

12684

25368

38052

50736

63420

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5100

10200

15300

20400

25500

<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:

0.113

AC:

17242

AN:

152290

Hom.:

1555

Cov.:

AF XY:

0.119

AC XY:

8843

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0256

AC:

1063

AN:

41572

American (AMR)

AF:

0.0896

AC:

1371

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.122

AC:

424

AN:

3472

East Asian (EAS)

AF:

0.442

AC:

2283

AN:

5168

South Asian (SAS)

AF:

0.0686

AC:

331

AN:

4828

European-Finnish (FIN)

AF:

0.224

AC:

2374

AN:

10618

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.134

AC:

9087

AN:

68004

Other (OTH)

AF:

0.115

AC:

243

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

767

1535

2302

3070

3837

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

384

576

768

960

<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:

0.121

Hom.:

3238

Bravo

AF:

0.101

Asia WGS

AF:

0.206

AC:

714

AN:

3478

EpiCase

AF:

0.125

EpiControl

AF:

0.128

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 07, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Apr 20, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Developmental and epileptic encephalopathy, 33

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Dec 31, 2015

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.41

(source)

DANN

Benign

0.89

PhyloP100

-3.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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