20-63488355-G-A

Position:

chr20-63488355-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001958.5(EEF1A2):c.1335C>T(p.Ser445Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00423 in 1,470,598 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0044 ( 40 hom. )

Consequence

EEF1A2
NM_001958.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0140

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

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

BP6

Variant 20-63488355-G-A is Benign according to our data. Variant chr20-63488355-G-A is described in ClinVar as [Benign]. Clinvar id is 383879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.014 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00287 (436/151814) while in subpopulation SAS AF= 0.0281 (135/4812). AF 95% confidence interval is 0.0242. There are 5 homozygotes in gnomad4. There are 241 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 436 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EEF1A2	NM_001958.5 linkuse as main transcript	c.1335C>T	p.Ser445Ser	synonymous_variant	8/8	ENST00000217182.6	NP_001949.1	Q05639

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EEF1A2	ENST00000217182.6 linkuse as main transcript	c.1335C>T	p.Ser445Ser	synonymous_variant	8/8	1	NM_001958.5	ENSP00000217182.3		Q05639

Frequencies

GnomAD3 genomes

AF:

0.00289

AC:

438

AN:

151706

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0282

Gnomad FIN

AF:

0.000858

Gnomad MID

AF:

0.0128

Gnomad NFE

AF:

0.00359

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00655

AC:

612

AN:

93442

Hom.:

AF XY:

0.00855

AC XY:

446

AN XY:

52176

show subpopulations

Gnomad AFR exome

AF:

0.000377

Gnomad AMR exome

AF:

0.000386

Gnomad ASJ exome

AF:

0.000435

Gnomad EAS exome

AF:

0.000311

Gnomad SAS exome

AF:

0.0252

Gnomad FIN exome

AF:

0.00118

Gnomad NFE exome

AF:

0.00426

Gnomad OTH exome

AF:

0.00358

GnomAD4 exome

AF:

0.00439

AC:

5783

AN:

1318784

Hom.:

Cov.:

AF XY:

0.00493

AC XY:

3204

AN XY:

650464

show subpopulations

Gnomad4 AFR exome

AF:

0.000489

Gnomad4 AMR exome

AF:

0.000495

Gnomad4 ASJ exome

AF:

0.000174

Gnomad4 EAS exome

AF:

0.000108

Gnomad4 SAS exome

AF:

0.0255

Gnomad4 FIN exome

AF:

0.00177

Gnomad4 NFE exome

AF:

0.00346

Gnomad4 OTH exome

AF:

0.00374

GnomAD4 genome

AF:

0.00287

AC:

436

AN:

151814

Hom.:

Cov.:

AF XY:

0.00325

AC XY:

241

AN XY:

74232

show subpopulations

Gnomad4 AFR

AF:

0.000483

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0281

Gnomad4 FIN

AF:

0.000858

Gnomad4 NFE

AF:

0.00359

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00241

Hom.:

Bravo

AF:

0.00207

Asia WGS

AF:

0.0140

AC:

AN:

3424

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 04, 2016

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 15, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

EEF1A2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 29, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.98

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over