20-63489162-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001958.5(EEF1A2):c.1030-10C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00053 in 1,609,874 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00055 ( 13 hom. )

Consequence

EEF1A2
NM_001958.5 intron

Scores

Splicing: ADA: 0.04003

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0220

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 20-63489162-G-T is Benign according to our data. Variant chr20-63489162-G-T is described in CliVar as Benign. Clinvar id is 385915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63489162-G-T is described in CliVar as Benign. Clinvar id is 385915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63489162-G-T is described in CliVar as Benign. Clinvar id is 385915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63489162-G-T is described in CliVar as Benign. Clinvar id is 385915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63489162-G-T is described in CliVar as Benign. Clinvar id is 385915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63489162-G-T is described in CliVar as Benign. Clinvar id is 385915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63489162-G-T is described in CliVar as Benign. Clinvar id is 385915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63489162-G-T is described in CliVar as Benign. Clinvar id is 385915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63489162-G-T is described in CliVar as Benign. Clinvar id is 385915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63489162-G-T is described in CliVar as Benign. Clinvar id is 385915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63489162-G-T is described in CliVar as Benign. Clinvar id is 385915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63489162-G-T is described in CliVar as Benign. Clinvar id is 385915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63489162-G-T is described in CliVar as Benign. Clinvar id is 385915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63489162-G-T is described in CliVar as Benign. Clinvar id is 385915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63489162-G-T is described in CliVar as Benign. Clinvar id is 385915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63489162-G-T is described in CliVar as Benign. Clinvar id is 385915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000335 (51/152366) while in subpopulation SAS AF = 0.0104 (50/4830). AF 95% confidence interval is 0.00807. There are 0 homozygotes in GnomAd4. There are 37 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 51 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EEF1A2	NM_001958.5 link	c.1030-10C>A		intron_variant	Intron 6 of 7	ENST00000217182.6	NP_001949.1	Q05639

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EEF1A2	ENST00000217182.6 link	c.1030-10C>A		intron_variant	Intron 6 of 7	1	NM_001958.5	ENSP00000217182.3		Q05639

Frequencies

GnomAD3 genomes

AF:

0.000342

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0106

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00105

AC:

259

AN:

246148

AF XY:

0.00148

show subpopulations

Gnomad AFR exome

AF:

0.0000633

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000272

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000550

AC:

802

AN:

1457508

Hom.:

Cov.:

AF XY:

0.000792

AC XY:

574

AN XY:

724512

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33438

American (AMR)

AF:

0.00

AC:

AN:

44644

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26090

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39650

South Asian (SAS)

AF:

0.00848

AC:

731

AN:

86188

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51704

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0000234

AC:

AN:

1109830

Other (OTH)

AF:

0.000698

AC:

AN:

60210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

148

197

246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000335

AC:

AN:

152366

Hom.:

Cov.:

AF XY:

0.000497

AC XY:

AN XY:

74518

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41584

American (AMR)

AF:

0.00

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.0104

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

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:

0.0000854

Hom.:

Bravo

AF:

0.0000907

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Oct 31, 2024

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 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. -

Developmental and epileptic encephalopathy, 33

Benign:1

Jan 17, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

9.8

(source)

DANN

Benign

0.67

PhyloP100

0.022

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.040

dbscSNV1_RF

Benign

0.11

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