rs2274860

Variant names:

• chr20-63494946-C-T
• rs2274860
• NM_001958.5:c.480G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-63494946-C-T
• chr20-63494946-C-A
• chr20-63494946-C-G

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.480G>A​(p.Pro160Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,612,748 control chromosomes in the GnomAD database, including 17,013 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1555 hom., cov: 34)
  • Exomes 𝑓: 0.13 (15458 hom.)
• Consequence: EEF1A2 NM_001958.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -3.78
• Publications: 22 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=-0.57).
• BP6: Variant 20-63494946-C-T is Benign according to our data. Variant chr20-63494946-C-T is described in ClinVar as Benign. ClinVar VariationId is 380779.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.78 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001958.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEF1A2	NM_001958.5	MANE Select	c.480G>A	p.Pro160Pro	synonymous	Exon 4 of 8	NP_001949.1	Q05639

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEF1A2	ENST00000217182.6	TSL:1 MANE Select	c.480G>A	p.Pro160Pro	synonymous	Exon 4 of 8	ENSP00000217182.3	Q05639
	EEF1A2	ENST00000298049.13	TSL:1	c.480G>A	p.Pro160Pro	synonymous	Exon 4 of 9	ENSP00000298049.9	A0A2U3TZH3
	EEF1A2	ENST00000706949.1		c.480G>A	p.Pro160Pro	synonymous	Exon 4 of 9	ENSP00000516669.1	A0A9L9PYI8

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17245 AN: 152172 Hom.: 1554 Cov.: 34

Gnomad AFR AF: 0.0256

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0895

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.0695

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.116

GnomAD2 exomes AF: 0.139 AC: 34691 AN: 250166 AF XY: 0.136

Gnomad AFR exome AF: 0.0226

Gnomad AMR exome AF: 0.0810

Gnomad ASJ exome AF: 0.123

Gnomad EAS exome AF: 0.425

Gnomad FIN exome AF: 0.224

Gnomad NFE exome AF: 0.133

Gnomad OTH exome AF: 0.132

GnomAD4 exome AF: 0.131 AC: 191988 AN: 1460458 Hom.: 15458 Cov.: 37 AF XY: 0.129 AC XY: 93916 AN XY: 726520

African (AFR) AF: 0.0201 AC: 673 AN: 33480

American (AMR) AF: 0.0807 AC: 3607 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 3014 AN: 26132

East Asian (EAS) AF: 0.436 AC: 17293 AN: 39692

South Asian (SAS) AF: 0.0585 AC: 5043 AN: 86258

European-Finnish (FIN) AF: 0.219 AC: 11416 AN: 52090

Middle Eastern (MID) AF: 0.0986 AC: 569 AN: 5768

European-Non Finnish (NFE) AF: 0.128 AC: 142273 AN: 1111948

Other (OTH) AF: 0.134 AC: 8100 AN: 60370

GnomAD4 genome AF: 0.113 AC: 17242 AN: 152290 Hom.: 1555 Cov.: 34 AF XY: 0.119 AC XY: 8843 AN XY: 74454

African (AFR) AF: 0.0256 AC: 1063 AN: 41572

American (AMR) AF: 0.0896 AC: 1371 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 424 AN: 3472

East Asian (EAS) AF: 0.442 AC: 2283 AN: 5168

South Asian (SAS) AF: 0.0686 AC: 331 AN: 4828

European-Finnish (FIN) AF: 0.224 AC: 2374 AN: 10618

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9087 AN: 68004

Other (OTH) AF: 0.115 AC: 243 AN: 2116

Alfa AF: 0.121 Hom.: 3238

Bravo AF: 0.101

Asia WGS AF: 0.206 AC: 714 AN: 3478

EpiCase AF: 0.125

EpiControl AF: 0.128

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Developmental and epileptic encephalopathy, 33 (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.41
DANN	Benign	0.89
PhyloP100		-3.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2274860; hg19: chr20-62126299; COSMIC: COSV53206642; COSMIC: COSV53206642;