rs3818681

Variant names:

• chr20-63495973-G-A
• rs3818681
• NM_001958.5:c.207C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-63495973-G-A
• chr20-63495973-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001958.5(EEF1A2):​c.207C>T​(p.Arg69Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0442 in 1,613,086 control chromosomes in the GnomAD database, including 3,717 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. R69R) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.042 (289 hom., cov: 33)
  • Exomes 𝑓: 0.044 (3428 hom.)
• Consequence: EEF1A2 NM_001958.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -3.56
• Publications: 5 publications found

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 20-63495973-G-A is Benign according to our data. Variant chr20-63495973-G-A is described in ClinVar as Benign. ClinVar VariationId is 380903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.57 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EEF1A2	NM_001958.5	c.207C>T	p.Arg69Arg	synonymous_variant	Exon 3 of 8	ENST00000217182.6	NP_001949.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EEF1A2	ENST00000217182.6	c.207C>T	p.Arg69Arg	synonymous_variant	Exon 3 of 8	1	NM_001958.5	ENSP00000217182.3

Frequencies

GnomAD3 genomes AF: 0.0419 AC: 6367 AN: 152130 Hom.: 285 Cov.: 33

Gnomad AFR AF: 0.0165

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0993

Gnomad ASJ AF: 0.0309

Gnomad EAS AF: 0.0912

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.0310

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0301

Gnomad OTH AF: 0.0344

GnomAD2 exomes AF: 0.0678 AC: 16982 AN: 250516 AF XY: 0.0724

Gnomad AFR exome AF: 0.0144

Gnomad AMR exome AF: 0.108

Gnomad ASJ exome AF: 0.0358

Gnomad EAS exome AF: 0.0985

Gnomad FIN exome AF: 0.0324

Gnomad NFE exome AF: 0.0270

Gnomad OTH exome AF: 0.0525

GnomAD4 exome AF: 0.0444 AC: 64864 AN: 1460838 Hom.: 3428 Cov.: 32 AF XY: 0.0490 AC XY: 35593 AN XY: 726726

African (AFR) AF: 0.0148 AC: 495 AN: 33480

American (AMR) AF: 0.107 AC: 4768 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0335 AC: 876 AN: 26132

East Asian (EAS) AF: 0.116 AC: 4603 AN: 39700

South Asian (SAS) AF: 0.210 AC: 18151 AN: 86254

European-Finnish (FIN) AF: 0.0346 AC: 1815 AN: 52480

Middle Eastern (MID) AF: 0.0199 AC: 115 AN: 5766

European-Non Finnish (NFE) AF: 0.0280 AC: 31161 AN: 1111932

Other (OTH) AF: 0.0477 AC: 2880 AN: 60380

GnomAD4 genome AF: 0.0419 AC: 6377 AN: 152248 Hom.: 289 Cov.: 33 AF XY: 0.0482 AC XY: 3587 AN XY: 74448

African (AFR) AF: 0.0165 AC: 684 AN: 41544

American (AMR) AF: 0.0991 AC: 1516 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0309 AC: 107 AN: 3468

East Asian (EAS) AF: 0.0916 AC: 474 AN: 5174

South Asian (SAS) AF: 0.226 AC: 1089 AN: 4820

European-Finnish (FIN) AF: 0.0310 AC: 329 AN: 10618

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0301 AC: 2044 AN: 68012

Other (OTH) AF: 0.0360 AC: 76 AN: 2112

Alfa AF: 0.0241 Hom.: 26

Bravo AF: 0.0401

Asia WGS AF: 0.149 AC: 518 AN: 3478

EpiCase AF: 0.0256

EpiControl AF: 0.0241

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Jan 14, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Jun 28, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Developmental and epileptic encephalopathy, 33 Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases Benign:1

Mar 21, 2016

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.0090
DANN	Benign	0.93
PhyloP100		-3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3818681; hg19: chr20-62127326; COSMIC: COSV53205265; COSMIC: COSV53205265;