19-3978116-G-T

Variant names:

• chr19-3978116-G-T
• rs145540039
• NM_001961.4:c.1770C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001961.4(EEF2):​c.1770C>A​(p.Leu590Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000738 in 1,355,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L590L) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: EEF2 NM_001961.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.755
• Publications: 0 publications found

Genes affected

EEF2 (HGNC:3214): (eukaryotic translation elongation factor 2) This gene encodes a member of the GTP-binding translation elongation factor family. This protein is an essential factor for protein synthesis. It promotes the GTP-dependent translocation of the nascent protein chain from the A-site to the P-site of the ribosome. This protein is completely inactivated by EF-2 kinase phosporylation. [provided by RefSeq, Jul 2008]

EEF2 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia type 26

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: G2P, Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=0.755 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EEF2	NM_001961.4	c.1770C>A	p.Leu590Leu	synonymous_variant	Exon 12 of 15	ENST00000309311.7	NP_001952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EEF2	ENST00000309311.7	c.1770C>A	p.Leu590Leu	synonymous_variant	Exon 12 of 15	5	NM_001961.4	ENSP00000307940.5
EEF2	ENST00000600794.1	c.18C>A	p.Leu6Leu	synonymous_variant	Exon 1 of 2	3		ENSP00000471265.1
EEF2	ENST00000596417.1	n.188C>A		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.38e-7 AC: 1 AN: 1355686 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 661316

African (AFR) AF: 0.0000324 AC: 1 AN: 30904

American (AMR) AF: 0.00 AC: 0 AN: 32926

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21952

East Asian (EAS) AF: 0.00 AC: 0 AN: 36088

South Asian (SAS) AF: 0.00 AC: 0 AN: 72078

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48224

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5446

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1051980

Other (OTH) AF: 0.00 AC: 0 AN: 56088

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	4.0
DANN	Benign	0.91
PhyloP100		0.76
PromoterAI		-0.023	Neutral

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: rs145540039; hg19: chr19-3978114;