20-63488394-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001958.5(EEF1A2):c.1296G>A(p.Thr432Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00624 in 1,478,522 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T432T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0036 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0065 ( 41 hom. )

Consequence

EEF1A2
NM_001958.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.15

Publications

0 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=-0.53).

BP6

Variant 20-63488394-C-T is Benign according to our data. Variant chr20-63488394-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 383889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.15 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00362 (547/151232) while in subpopulation NFE AF = 0.00603 (409/67774). AF 95% confidence interval is 0.00555. There are 1 homozygotes in GnomAd4. There are 235 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 547 AD gene.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEF1A2	NM_001958.5	MANE Select	c.1296G>A	p.Thr432Thr	synonymous	Exon 8 of 8	NP_001949.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
EEF1A2	ENST00000217182.6	TSL:1 MANE Select	c.1296G>A	p.Thr432Thr	synonymous	Exon 8 of 8	ENSP00000217182.3
EEF1A2	ENST00000298049.13	TSL:1	c.1296G>A	p.Thr432Thr	synonymous	Exon 8 of 9	ENSP00000298049.9
EEF1A2	ENST00000706949.1		c.1296G>A	p.Thr432Thr	synonymous	Exon 8 of 9	ENSP00000516669.1

Frequencies

GnomAD3 genomes

AF:

0.00362

AC:

547

AN:

151124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00185

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00197

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.000199

Gnomad SAS

AF:

0.000627

Gnomad FIN

AF:

0.00181

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00603

Gnomad OTH

AF:

0.00339

GnomAD2 exomes

AF:

0.00288

AC:

275

AN:

95394

AF XY:

0.00308

show subpopulations

Gnomad AFR exome

AF:

0.00341

Gnomad AMR exome

AF:

0.00131

Gnomad ASJ exome

AF:

0.000580

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00167

Gnomad NFE exome

AF:

0.00522

Gnomad OTH exome

AF:

0.00156

GnomAD4 exome

AF:

0.00654

AC:

8686

AN:

1327290

Hom.:

Cov.:

AF XY:

0.00634

AC XY:

4151

AN XY:

654778

show subpopulations

African (AFR)

AF:

0.000785

AC:

AN:

26766

American (AMR)

AF:

0.00148

AC:

AN:

27050

Ashkenazi Jewish (ASJ)

AF:

0.000645

AC:

AN:

23270

East Asian (EAS)

AF:

0.0000702

AC:

AN:

28482

South Asian (SAS)

AF:

0.00129

AC:

AN:

72838

European-Finnish (FIN)

AF:

0.00264

AC:

107

AN:

40570

Middle Eastern (MID)

AF:

0.000198

AC:

AN:

5060

European-Non Finnish (NFE)

AF:

0.00767

AC:

8043

AN:

1048704

Other (OTH)

AF:

0.00665

AC:

363

AN:

54550

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

429

859

1288

1718

2147

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

332

664

996

1328

1660

<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:

0.00362

AC:

547

AN:

151232

Hom.:

Cov.:

AF XY:

0.00318

AC XY:

235

AN XY:

73886

show subpopulations

African (AFR)

AF:

0.00185

AC:

AN:

41180

American (AMR)

AF:

0.00197

AC:

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.000577

AC:

AN:

3464

East Asian (EAS)

AF:

0.000200

AC:

AN:

5010

South Asian (SAS)

AF:

0.000627

AC:

AN:

4784

European-Finnish (FIN)

AF:

0.00181

AC:

AN:

10498

Middle Eastern (MID)

AF:

0.00

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.00603

AC:

409

AN:

67774

Other (OTH)

AF:

0.00335

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

122

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00307

Hom.:

Bravo

AF:

0.00352

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

Developmental and epileptic encephalopathy, 33 (1)

Inborn genetic diseases (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

-2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(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

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over