chr20-63495973-G-A

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.207C>T(p.Arg69Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0442 in 1,613,086 control chromosomes in the GnomAD database, including 3,717 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. R69R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.042 ( 289 hom., cov: 33)

Exomes 𝑓: 0.044 ( 3428 hom. )

Consequence

EEF1A2
NM_001958.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.56

Publications

5 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=-0.74).

BP6

Variant 20-63495973-G-A is Benign according to our data. Variant chr20-63495973-G-A is described in ClinVar as Benign. ClinVar VariationId is 380903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.57 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EEF1A2	NM_001958.5 link	c.207C>T	p.Arg69Arg	synonymous_variant	Exon 3 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.207C>T	p.Arg69Arg	synonymous_variant	Exon 3 of 8	1	NM_001958.5	ENSP00000217182.3		Q05639

Frequencies

GnomAD3 genomes

AF:

0.0419

AC:

6367

AN:

152130

Hom.:

285

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0165

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.0993

Gnomad ASJ

AF:

0.0309

Gnomad EAS

AF:

0.0912

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.0310

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0301

Gnomad OTH

AF:

0.0344

GnomAD2 exomes

AF:

0.0678

AC:

16982

AN:

250516

AF XY:

0.0724

show subpopulations

Gnomad AFR exome

AF:

0.0144

Gnomad AMR exome

AF:

0.108

Gnomad ASJ exome

AF:

0.0358

Gnomad EAS exome

AF:

0.0985

Gnomad FIN exome

AF:

0.0324

Gnomad NFE exome

AF:

0.0270

Gnomad OTH exome

AF:

0.0525

GnomAD4 exome

AF:

0.0444

AC:

64864

AN:

1460838

Hom.:

3428

Cov.:

AF XY:

0.0490

AC XY:

35593

AN XY:

726726

show subpopulations

African (AFR)

AF:

0.0148

AC:

495

AN:

33480

American (AMR)

AF:

0.107

AC:

4768

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.0335

AC:

876

AN:

26132

East Asian (EAS)

AF:

0.116

AC:

4603

AN:

39700

South Asian (SAS)

AF:

0.210

AC:

18151

AN:

86254

European-Finnish (FIN)

AF:

0.0346

AC:

1815

AN:

52480

Middle Eastern (MID)

AF:

0.0199

AC:

115

AN:

5766

European-Non Finnish (NFE)

AF:

0.0280

AC:

31161

AN:

1111932

Other (OTH)

AF:

0.0477

AC:

2880

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

3751

7502

11253

15004

18755

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1414

2828

4242

5656

7070

<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:

0.0419

AC:

6377

AN:

152248

Hom.:

289

Cov.:

AF XY:

0.0482

AC XY:

3587

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0165

AC:

684

AN:

41544

American (AMR)

AF:

0.0991

AC:

1516

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0309

AC:

107

AN:

3468

East Asian (EAS)

AF:

0.0916

AC:

474

AN:

5174

South Asian (SAS)

AF:

0.226

AC:

1089

AN:

4820

European-Finnish (FIN)

AF:

0.0310

AC:

329

AN:

10618

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0301

AC:

2044

AN:

68012

Other (OTH)

AF:

0.0360

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

304

608

913

1217

1521

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

258

344

430

<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:

0.0241

Hom.:

Bravo

AF:

0.0401

Asia WGS

AF:

0.149

AC:

518

AN:

3478

EpiCase

AF:

0.0256

EpiControl

AF:

0.0241

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jan 14, 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. -

Jun 28, 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

Mar 21, 2016

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. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.0090

(source)

DANN

Benign

0.93

PhyloP100

-3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism (auto)

(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