rs879255373

Variant names:

• chr20-63488306-CCGCCTTCTG-C
• rs879255373
• NM_001958.5:c.1375_1383delCAGAAGGCG

Your query was ambiguous. Multiple possible variants found:

• chr20-63488306-CCGCCTTCTG-C
• chr20-63488306-CCGCCTTCTG-CCGCCTTCTGCGCCTTCTG

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 2P and 9B. PM4 BP6 BS1 BS2

The NM_001958.5(EEF1A2):​c.1375_1383delCAGAAGGCG​(p.Gln459_Ala461del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.0000368 in 1,385,928 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000038 (0 hom.)
• Consequence: EEF1A2 NM_001958.5 conservative_inframe_deletion
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3 B:1
• Conservation: PhyloP100: 5.14
• 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), G2P, Ambry Genetics
• 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 -7 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001958.5.
• BP6: Variant 20-63488306-CCGCCTTCTG-C is Benign according to our data. Variant chr20-63488306-CCGCCTTCTG-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 252597.
• BS1: Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.000038 (47/1235298) while in subpopulation NFE AF = 0.0000433 (43/993412). AF 95% confidence interval is 0.0000326. There are 0 homozygotes in GnomAdExome4. There are 23 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check.
• BS2: High AC in GnomAdExome4 at 47 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.1375_1383delCAGAAGGCG	p.Gln459_Ala461del	conservative_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.1375_1383delCAGAAGGCG	p.Gln459_Ala461del	conservative_inframe_deletion	Exon 8 of 8	ENSP00000217182.3	Q05639
	EEF1A2	ENST00000298049.13	TSL:1	c.1350+25_1350+33delCAGAAGGCG		intron	N/A	ENSP00000298049.9	A0A2U3TZH3
	EEF1A2	ENST00000961009.1		c.1444_1452delCAGAAGGCG	p.Gln482_Ala484del	conservative_inframe_deletion	Exon 9 of 9	ENSP00000631068.1

Frequencies

GnomAD3 genomes AF: 0.0000266 AC: 4 AN: 150518 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000197

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000296

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000380 AC: 47 AN: 1235298 Hom.: 0 AF XY: 0.0000379 AC XY: 23 AN XY: 607454

African (AFR) AF: 0.00 AC: 0 AN: 25104

American (AMR) AF: 0.00 AC: 0 AN: 22328

Ashkenazi Jewish (ASJ) AF: 0.0000479 AC: 1 AN: 20880

East Asian (EAS) AF: 0.00 AC: 0 AN: 25384

South Asian (SAS) AF: 0.0000309 AC: 2 AN: 64758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3920

European-Non Finnish (NFE) AF: 0.0000433 AC: 43 AN: 993412

Other (OTH) AF: 0.0000204 AC: 1 AN: 48986

GnomAD4 genome AF: 0.0000266 AC: 4 AN: 150630 Hom.: 0 Cov.: 32 AF XY: 0.0000136 AC XY: 1 AN XY: 73522

African (AFR) AF: 0.0000242 AC: 1 AN: 41248

American (AMR) AF: 0.00 AC: 0 AN: 15168

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000198 AC: 1 AN: 5054

South Asian (SAS) AF: 0.00 AC: 0 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9992

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.0000296 AC: 2 AN: 67602

Other (OTH) AF: 0.00 AC: 0 AN: 2096

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	-	Developmental and epileptic encephalopathy, 33 (1)
-	-	1	Inborn genetic diseases (1)
-	1	-	not provided (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.1
Mutation Taster		=86/114	disease causing

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs879255373;

hg19: chr20-62119659;