rs1042796

chr20-63488364-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001958.5(EEF1A2):c.1326G>A(p.Glu442=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.015 in 1,477,194 control chromosomes in the GnomAD database, including 1,651 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (474 hom., cov: 33)
  • Exomes 𝑓: 0.012 (1177 hom.)
• Consequence: EEF1A2 NM_001958.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.00

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=-0.36).
• BP6: Variant 20-63488364-C-T is Benign according to our data. Variant chr20-63488364-C-T is described in ClinVar as [Benign]. Clinvar id is 380904.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EEF1A2	NM_001958.5	c.1326G>A	p.Glu442=	synonymous_variant	8/8	ENST00000217182.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EEF1A2	ENST00000217182.6	c.1326G>A	p.Glu442=	synonymous_variant	8/8	1	NM_001958.5	P1

Frequencies

GnomAD3 genomes AF: 0.0446 AC: 6771 AN: 151692 Hom.: 471 Cov.: 33

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0163

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000390

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.0336

GnomAD3 exomes AF: 0.0288 AC: 2761 AN: 95750 Hom.: 210 AF XY: 0.0367 AC XY: 1957 AN XY: 53380

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.00445

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000865

Gnomad SAS exome AF: 0.136

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000742

Gnomad OTH exome AF: 0.00859

GnomAD4 exome AF: 0.0116 AC: 15402 AN: 1325394 Hom.: 1177 Cov.: 33 AF XY: 0.0149 AC XY: 9758 AN XY: 653674

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.00750

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000142

Gnomad4 SAS exome AF: 0.139

Gnomad4 FIN exome AF: 0.000147

Gnomad4 NFE exome AF: 0.000297

Gnomad4 OTH exome AF: 0.0195

GnomAD4 genome AF: 0.0448 AC: 6805 AN: 151800 Hom.: 474 Cov.: 33 AF XY: 0.0462 AC XY: 3431 AN XY: 74190

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.0162

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000392

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000368

Gnomad4 OTH AF: 0.0332

Alfa AF: 0.0107 Hom.: 34

Bravo AF: 0.0456

Asia WGS AF: 0.0840 AC: 286 AN: 3422

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

Feb 01, 2024

- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 26, 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

Mar 18, 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

clinical testing

Athena Diagnostics

Oct 25, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
Cadd	Benign	14
Dann	Uncertain	0.98

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: rs1042796; hg19: chr20-62119717;