20-63495943-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001958.5(EEF1A2):c.237G>A(p.Lys79Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00483 in 1,613,388 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0034 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0050 ( 85 hom. )

Consequence

EEF1A2
NM_001958.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.19

Publications

6 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 20-63495943-C-T is Benign according to our data. Variant chr20-63495943-C-T is described in ClinVar as Benign. ClinVar VariationId is 383878.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.19 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00337 (514/152310) while in subpopulation SAS AF = 0.0354 (171/4830). AF 95% confidence interval is 0.0311. There are 5 homozygotes in GnomAd4. There are 293 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 514 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEF1A2	NM_001958.5	MANE Select	c.237G>A	p.Lys79Lys	synonymous	Exon 3 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.237G>A	p.Lys79Lys	synonymous	Exon 3 of 8	ENSP00000217182.3	Q05639
EEF1A2	ENST00000298049.13	TSL:1	c.237G>A	p.Lys79Lys	synonymous	Exon 3 of 9	ENSP00000298049.9	A0A2U3TZH3
EEF1A2	ENST00000706949.1		c.237G>A	p.Lys79Lys	synonymous	Exon 3 of 9	ENSP00000516669.1	A0A9L9PYI8

Frequencies

GnomAD3 genomes

AF:

0.00338

AC:

514

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000628

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00635

Gnomad SAS

AF:

0.0354

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00365

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00679

AC:

1701

AN:

250604

AF XY:

0.00810

show subpopulations

Gnomad AFR exome

AF:

0.000680

Gnomad AMR exome

AF:

0.000781

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00598

Gnomad FIN exome

AF:

0.00111

Gnomad NFE exome

AF:

0.00412

Gnomad OTH exome

AF:

0.00605

GnomAD4 exome

AF:

0.00498

AC:

7277

AN:

1461078

Hom.:

Cov.:

AF XY:

0.00573

AC XY:

4164

AN XY:

726840

show subpopulations

African (AFR)

AF:

0.000777

AC:

AN:

33480

American (AMR)

AF:

0.000783

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.000153

AC:

AN:

26132

East Asian (EAS)

AF:

0.00270

AC:

107

AN:

39700

South Asian (SAS)

AF:

0.0324

AC:

2791

AN:

86258

European-Finnish (FIN)

AF:

0.00173

AC:

AN:

52704

Middle Eastern (MID)

AF:

0.00416

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00348

AC:

3875

AN:

1111936

Other (OTH)

AF:

0.00537

AC:

324

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

387

775

1162

1550

1937

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

158

316

474

632

790

<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:

0.00337

AC:

514

AN:

152310

Hom.:

Cov.:

AF XY:

0.00393

AC XY:

293

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.000626

AC:

AN:

41550

American (AMR)

AF:

0.00118

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00636

AC:

AN:

5188

South Asian (SAS)

AF:

0.0354

AC:

171

AN:

4830

European-Finnish (FIN)

AF:

0.000847

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00365

AC:

248

AN:

68022

Other (OTH)

AF:

0.00284

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

116

145

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:

0.00295

Hom.:

Bravo

AF:

0.00229

Asia WGS

AF:

0.0250

AC:

AN:

3478

EpiCase

AF:

0.00382

EpiControl

AF:

0.00368

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Developmental and epileptic encephalopathy, 33 (1)

EEF1A2-related disorder (1)

Inborn genetic diseases (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

9.8

(source)

DANN

Benign

0.97

PhyloP100

1.2

Mutation Taster

=98/2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over