rs310609

Positions:

• chr20-63490877-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000217182.6(EEF1A2):​c.773-142T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 983,666 control chromosomes in the GnomAD database, including 23,748 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4753 hom., cov: 34)
  • Exomes 𝑓: 0.20 (18995 hom.)
• Consequence: EEF1A2 ENST00000217182.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.971

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 20-63490877-A-G is Benign according to our data. Variant chr20-63490877-A-G is described in ClinVar as [Benign]. Clinvar id is 681614.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EEF1A2	NM_001958.5	c.773-142T>C		intron_variant		ENST00000217182.6	NP_001949.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EEF1A2	ENST00000217182.6	c.773-142T>C		intron_variant		1	NM_001958.5	ENSP00000217182	P1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 36772 AN: 150124 Hom.: 4747 Cov.: 34

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.125

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.230

GnomAD4 exome AF: 0.205 AC: 170664 AN: 833420 Hom.: 18995 AF XY: 0.202 AC XY: 84228 AN XY: 417844

Gnomad4 AFR exome AF: 0.334

Gnomad4 AMR exome AF: 0.206

Gnomad4 ASJ exome AF: 0.116

Gnomad4 EAS exome AF: 0.153

Gnomad4 SAS exome AF: 0.116

Gnomad4 FIN exome AF: 0.264

Gnomad4 NFE exome AF: 0.212

Gnomad4 OTH exome AF: 0.198

GnomAD4 genome AF: 0.245 AC: 36802 AN: 150246 Hom.: 4753 Cov.: 34 AF XY: 0.245 AC XY: 17915 AN XY: 73262

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.236

Alfa AF: 0.225 Hom.: 810

Bravo AF: 0.245

Asia WGS AF: 0.169 AC: 588 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.70
DANN	Benign	0.63

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: rs310609; hg19: chr20-62122230;