rs764247701

Variant names:

• chr20-63488347-GCGC-G
• rs764247701
• NM_001958.5:c.1340_1342delGCG

Your query was ambiguous. Multiple possible variants found:

• chr20-63488347-GCGC-G
• chr20-63488347-GCGC-GCGCCGCCGC

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PM4_Supporting BS2

The NM_001958.5(EEF1A2):​c.1340_1342delGCG​(p.Gly447del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000607 in 1,318,160 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G447G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000061 (0 hom.)
• Consequence: EEF1A2 NM_001958.5 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.33
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001958.5. Strenght limited to Supporting due to length of the change: 1aa.
• BS2: High AC in GnomAdExome4 at 8 AD gene.

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.1340_1342delGCG	p.Gly447del	disruptive_inframe_deletion	Exon 8 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.1340_1342delGCG	p.Gly447del	disruptive_inframe_deletion	Exon 8 of 8	ENSP00000217182.3	Q05639
	EEF1A2	ENST00000298049.13	TSL:1	c.1340_1342delGCG	p.Gly447del	disruptive_inframe_deletion	Exon 8 of 9	ENSP00000298049.9	A0A2U3TZH3
	EEF1A2	ENST00000706949.1		c.1340_1342delGCG	p.Gly447del	disruptive_inframe_deletion	Exon 8 of 9	ENSP00000516669.1	A0A9L9PYI8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000607 AC: 8 AN: 1318160 Hom.: 0 AF XY: 0.00000769 AC XY: 5 AN XY: 649972

African (AFR) AF: 0.00 AC: 0 AN: 26594

American (AMR) AF: 0.00 AC: 0 AN: 26164

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23092

East Asian (EAS) AF: 0.00 AC: 0 AN: 27864

South Asian (SAS) AF: 0.00 AC: 0 AN: 72474

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5050

European-Non Finnish (NFE) AF: 0.00000767 AC: 8 AN: 1043468

Other (OTH) AF: 0.00 AC: 0 AN: 54062

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Developmental and epileptic encephalopathy, 33 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3

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: rs764247701; hg19: chr20-62119700;