rs310617

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.594T>C(p.Gly198Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 1,611,412 control chromosomes in the GnomAD database, including 268,138 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 25576 hom., cov: 34)

Exomes 𝑓: 0.57 ( 242562 hom. )

Consequence

EEF1A2
NM_001958.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -5.77

Publications

21 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), G2P, Ambry Genetics
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

new If you want to explore the variant's impact on the transcript NM_001958.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.95).

BP6

Variant 20-63494832-A-G is Benign according to our data. Variant chr20-63494832-A-G is described in ClinVar as Benign. ClinVar VariationId is 379689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.77 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001958.5. 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
	EEF1A2	NM_001958.5	MANE Select	c.594T>C	p.Gly198Gly	synonymous	Exon 4 of 8	NP_001949.1	Q05639

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EEF1A2	ENST00000217182.6	TSL:1 MANE Select	c.594T>C	p.Gly198Gly	synonymous	Exon 4 of 8	ENSP00000217182.3	Q05639
EEF1A2	ENST00000298049.13	TSL:1	c.594T>C	p.Gly198Gly	synonymous	Exon 4 of 9	ENSP00000298049.9	A0A2U3TZH3
EEF1A2	ENST00000706949.1		c.594T>C	p.Gly198Gly	synonymous	Exon 4 of 9	ENSP00000516669.1	A0A9L9PYI8

Frequencies

GnomAD3 genomes

AF:

0.578

AC:

87924

AN:

152002

Hom.:

25563

Cov.:

show subpopulations

Gnomad AFR

AF:

0.596

Gnomad AMI

AF:

0.603

Gnomad AMR

AF:

0.505

Gnomad ASJ

AF:

0.561

Gnomad EAS

AF:

0.635

Gnomad SAS

AF:

0.614

Gnomad FIN

AF:

0.632

Gnomad MID

AF:

0.601

Gnomad NFE

AF:

0.570

Gnomad OTH

AF:

0.576

GnomAD2 exomes

AF:

0.562

AC:

139295

AN:

247972

AF XY:

0.569

show subpopulations

Gnomad AFR exome

AF:

0.595

Gnomad AMR exome

AF:

0.395

Gnomad ASJ exome

AF:

0.567

Gnomad EAS exome

AF:

0.619

Gnomad FIN exome

AF:

0.635

Gnomad NFE exome

AF:

0.568

Gnomad OTH exome

AF:

0.571

GnomAD4 exome

AF:

0.575

AC:

838538

AN:

1459292

Hom.:

242562

Cov.:

AF XY:

0.576

AC XY:

418045

AN XY:

725820

show subpopulations

African (AFR)

AF:

0.593

AC:

19851

AN:

33470

American (AMR)

AF:

0.409

AC:

18250

AN:

44660

Ashkenazi Jewish (ASJ)

AF:

0.562

AC:

14685

AN:

26118

East Asian (EAS)

AF:

0.658

AC:

26079

AN:

39638

South Asian (SAS)

AF:

0.611

AC:

52689

AN:

86248

European-Finnish (FIN)

AF:

0.634

AC:

32826

AN:

51764

Middle Eastern (MID)

AF:

0.601

AC:

3468

AN:

5768

European-Non Finnish (NFE)

AF:

0.572

AC:

635925

AN:

1111290

Other (OTH)

AF:

0.576

AC:

34765

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

23586

47173

70759

94346

117932

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17692

35384

53076

70768

88460

<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:

0.578

AC:

87973

AN:

152120

Hom.:

25576

Cov.:

AF XY:

0.584

AC XY:

43460

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.596

AC:

24710

AN:

41484

American (AMR)

AF:

0.504

AC:

7703

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.561

AC:

1948

AN:

3472

East Asian (EAS)

AF:

0.636

AC:

3285

AN:

5168

South Asian (SAS)

AF:

0.612

AC:

2947

AN:

4814

European-Finnish (FIN)

AF:

0.632

AC:

6697

AN:

10596

Middle Eastern (MID)

AF:

0.602

AC:

177

AN:

294

European-Non Finnish (NFE)

AF:

0.570

AC:

38734

AN:

67978

Other (OTH)

AF:

0.578

AC:

1222

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

2006

4011

6017

8022

10028

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

750

1500

2250

3000

3750

<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:

0.581

Hom.:

8594

Bravo

AF:

0.563

Asia WGS

AF:

0.620

AC:

2154

AN:

3478

EpiCase

AF:

0.562

EpiControl

AF:

0.564

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

Developmental and epileptic encephalopathy, 33 (2)

not provided (2)

Inborn genetic diseases (1)

Intellectual disability, autosomal dominant 38 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.027

(source)

DANN

Benign

0.43

PhyloP100

-5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=98/2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over