20-63493283-G-C

Variant names:

• chr20-63493283-G-C
• rs768753735
• NM_001958.5:c.626C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001958.5(EEF1A2):​c.626C>G​(p.Pro209Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000733 in 1,365,042 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P209L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: EEF1A2 NM_001958.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.13
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.626C>G	p.Pro209Arg	missense	Exon 5 of 8	NP_001949.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEF1A2	ENST00000217182.6	TSL:1 MANE Select	c.626C>G	p.Pro209Arg	missense	Exon 5 of 8	ENSP00000217182.3
	EEF1A2	ENST00000298049.13	TSL:1	c.626C>G	p.Pro209Arg	missense	Exon 5 of 9	ENSP00000298049.9
	EEF1A2	ENST00000706949.1		c.626C>G	p.Pro209Arg	missense	Exon 5 of 9	ENSP00000516669.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000746 AC: 1 AN: 134128 AF XY: 0.0000143

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000195

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.33e-7 AC: 1 AN: 1365042 Hom.: 0 Cov.: 32 AF XY: 0.00000150 AC XY: 1 AN XY: 668684

African (AFR) AF: 0.00 AC: 0 AN: 30748

American (AMR) AF: 0.00 AC: 0 AN: 32876

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23214

East Asian (EAS) AF: 0.00 AC: 0 AN: 34804

South Asian (SAS) AF: 0.00 AC: 0 AN: 75314

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47222

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5554

European-Non Finnish (NFE) AF: 9.44e-7 AC: 1 AN: 1058798

Other (OTH) AF: 0.00 AC: 0 AN: 56512

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.82	D
Eigen	Benign	0.19
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.090	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.65	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		5.1
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.14
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.92	P
Vest4		0.48
MutPred		0.59		Gain of MoRF binding (P = 0.0031)
MVP		0.29
MPC		2.3
ClinPred		0.99	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.89
gMVP		0.94
Mutation Taster		=53/47	polymorphism

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: rs768753735; hg19: chr20-62124636;