Genetic Variant EEF1A2:p.Lys460Arg (chr20-63488311-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001958.5(EEF1A2):c.1379A>G(p.Lys460Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. K460K) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EEF1A2
NM_001958.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.22

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2166901).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EEF1A2	NM_001958.5 link	c.1379A>G	p.Lys460Arg	missense_variant	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.1379A>G	p.Lys460Arg	missense_variant	Exon 8 of 8	1	NM_001958.5	ENSP00000217182.3		Q05639

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1253344

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

617388

African (AFR)

AF:

0.00

AC:

AN:

25168

American (AMR)

AF:

0.00

AC:

AN:

23032

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21032

East Asian (EAS)

AF:

0.00

AC:

AN:

25190

South Asian (SAS)

AF:

0.00

AC:

AN:

68034

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31926

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4104

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1004880

Other (OTH)

AF:

0.00

AC:

AN:

49978

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Intellectual disability, autosomal dominant 38

Uncertain:1

Nov 11, 2021

MGZ Medical Genetics Center

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.27

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.86

M_CAP

Pathogenic

0.69

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.90

MutationAssessor

Pathogenic

3.0

PhyloP100

3.2

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-0.37

REVEL

Benign

0.12

Sift

Uncertain

0.029

Sift4G

Benign

0.081

Polyphen

0.0040

Vest4

0.16

MutPred

0.17

Loss of methylation at K460 (P = 0.0777);

MVP

0.37

MPC

1.4

ClinPred

0.94

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.32

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over