chr20-63488306-CCGCCTTCTG-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM4BS1_SupportingBS2

The NM_001958.5(EEF1A2):c.1375_1383delCAGAAGGCG(p.Gln459_Ala461del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.0000368 in 1,385,928 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

EEF1A2
NM_001958.5 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 5.14

Publications

1 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: Likely_benign. The variant received -3 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001958.5.

BS1

Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.000038 (47/1235298) while in subpopulation NFE AF = 0.0000433 (43/993412). AF 95% confidence interval is 0.0000326. There are 0 homozygotes in GnomAdExome4. There are 23 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High AC in GnomAdExome4 at 47 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EEF1A2	NM_001958.5 link	c.1375_1383delCAGAAGGCG	p.Gln459_Ala461del	conservative_inframe_deletion	Exon 8 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.1375_1383delCAGAAGGCG	p.Gln459_Ala461del	conservative_inframe_deletion	Exon 8 of 8	1	NM_001958.5	ENSP00000217182.3		Q05639

Frequencies

GnomAD3 genomes

AF:

0.0000266

AC:

AN:

150518

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000197

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000380

AC:

AN:

1235298

Hom.:

AF XY:

0.0000379

AC XY:

AN XY:

607454

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25104

American (AMR)

AF:

0.00

AC:

AN:

22328

Ashkenazi Jewish (ASJ)

AF:

0.0000479

AC:

AN:

20880

East Asian (EAS)

AF:

0.00

AC:

AN:

25384

South Asian (SAS)

AF:

0.0000309

AC:

AN:

64758

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30526

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3920

European-Non Finnish (NFE)

AF:

0.0000433

AC:

AN:

993412

Other (OTH)

AF:

0.0000204

AC:

AN:

48986

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.427

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000266

AC:

AN:

150630

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73522

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41248

American (AMR)

AF:

0.00

AC:

AN:

15168

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000198

AC:

AN:

5054

South Asian (SAS)

AF:

0.00

AC:

AN:

4804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9992

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.0000296

AC:

AN:

67602

Other (OTH)

AF:

0.00

AC:

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 19, 2015

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Developmental and epileptic encephalopathy, 33

Uncertain:1

Jan 11, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant, c.1375_1383del, results in the deletion of 3 amino acid(s) of the EEF1A2 protein (p.Gln459_Ala461del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has been observed in individual(s) with intellectual disability and/or epilepsy (PMID: 29784605, 36403551). ClinVar contains an entry for this variant (Variation ID: 252597). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

not provided

Uncertain:1

Jul 23, 2025

GeneDx

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Reported previously in a patient with intellectual disability, anxiety, and course facial features who also harbored variants in other genes (PMID: 29784605); In-frame deletion of 3 amino acids in a non-repeat region; In silico analysis suggests that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 36403551, 29784605) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

5.1

Mutation Taster

=86/114

disease causing

(source)

Splicing

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.

chr20-63488306-CCGCCTTCTG-C

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