rs310609

Variant names:

• chr20-63490877-A-G
• rs310609
• NM_001958.5:c.773-142T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001958.5(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 NM_001958.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.971
• Publications: 1 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 -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 VariationId 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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEF1A2	NM_001958.5	MANE Select	c.773-142T>C		intron	N/A	NP_001949.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEF1A2	ENST00000217182.6	TSL:1 MANE Select	c.773-142T>C		intron	N/A	ENSP00000217182.3
	EEF1A2	ENST00000298049.13	TSL:1	c.773-142T>C		intron	N/A	ENSP00000298049.9
	EEF1A2	ENST00000706949.1		c.773-142T>C		intron	N/A	ENSP00000516669.1

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

African (AFR) AF: 0.334 AC: 6802 AN: 20370

American (AMR) AF: 0.206 AC: 5401 AN: 26250

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 1994 AN: 17122

East Asian (EAS) AF: 0.153 AC: 4983 AN: 32628

South Asian (SAS) AF: 0.116 AC: 6723 AN: 57744

European-Finnish (FIN) AF: 0.264 AC: 7957 AN: 30158

Middle Eastern (MID) AF: 0.124 AC: 348 AN: 2802

European-Non Finnish (NFE) AF: 0.212 AC: 128762 AN: 607472

Other (OTH) AF: 0.198 AC: 7694 AN: 38874

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

African (AFR) AF: 0.333 AC: 13789 AN: 41376

American (AMR) AF: 0.232 AC: 3493 AN: 15088

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 391 AN: 3426

East Asian (EAS) AF: 0.127 AC: 635 AN: 4984

South Asian (SAS) AF: 0.119 AC: 545 AN: 4586

European-Finnish (FIN) AF: 0.270 AC: 2775 AN: 10274

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14428 AN: 67232

Other (OTH) AF: 0.236 AC: 491 AN: 2084

Alfa AF: 0.225 Hom.: 810

Bravo AF: 0.245

Asia WGS AF: 0.169 AC: 588 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.70
DANN	Benign	0.63
PhyloP100		-0.97
Mutation Taster		=100/0	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: rs310609; hg19: chr20-62122230;