rs372257864

chr20-63488355-G-Achr20-63488355-G-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001958.5(EEF1A2):c.1335C>T(p.Ser445=) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0140

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]

ACMG classification

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. This position pass quality control queck.
• BS2: High AC in GnomAd at 438 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EEF1A2	NM_001958.5	c.1335C>T	p.Ser445=	synonymous_variant	8/8	ENST00000217182.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EEF1A2	ENST00000217182.6	c.1335C>T	p.Ser445=	synonymous_variant	8/8	1	NM_001958.5	P1

Frequencies

GnomAD3 genomes AF: 0.00289 AC: 438 AN: 151706 Hom.: 5 Cov.: 33

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.: 5 AF XY: 0.00855 AC XY: 446 AN XY: 52176

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.: 40 Cov.: 33 AF XY: 0.00493 AC XY: 3204 AN XY: 650464

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.: 5 Cov.: 33 AF XY: 0.00325 AC XY: 241 AN XY: 74232

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.: 2

Bravo AF: 0.00207

Asia WGS AF: 0.0140 AC: 48 AN: 3424

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Developmental and epileptic encephalopathy, 33 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

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. -

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. -

EEF1A2-related disorder Benign:1

Benign, criteria provided, single submitter

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	11
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

Other links and lift over

dbSNP: rs372257864; hg19: chr20-62119708; COSMIC: COSV53205327; COSMIC: COSV53205327;