chr20-63488434-C-CG

Variant names:

• chr20-63488434-C-CG
• rs1170731512
• NM_001958.5:c.1265-10dupC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001958.5(EEF1A2):​c.1265-10dupC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000935 in 1,389,694 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: EEF1A2 NM_001958.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.218
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 20-63488434-C-CG is Benign according to our data. Variant chr20-63488434-C-CG is described in ClinVar as Benign. ClinVar VariationId is 542652.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0000401 (6/149740) while in subpopulation EAS AF = 0.00123 (6/4882). AF 95% confidence interval is 0.000534. There are 0 homozygotes in GnomAd4. There are 2 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 6 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEF1A2	NM_001958.5	MANE Select	c.1265-10dupC		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.1265-10_1265-9insC		intron	N/A	ENSP00000217182.3
	EEF1A2	ENST00000298049.13	TSL:1	c.1265-10_1265-9insC		intron	N/A	ENSP00000298049.9
	EEF1A2	ENST00000706949.1		c.1265-10_1265-9insC		intron	N/A	ENSP00000516669.1

Frequencies

GnomAD3 genomes AF: 0.0000401 AC: 6 AN: 149622 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00122

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000159 AC: 1 AN: 62968 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000568

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000565 AC: 7 AN: 1239954 Hom.: 0 Cov.: 33 AF XY: 0.00000819 AC XY: 5 AN XY: 610796

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24610

American (AMR) AF: 0.00 AC: 0 AN: 19334

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20916

East Asian (EAS) AF: 0.000189 AC: 5 AN: 26402

South Asian (SAS) AF: 0.00 AC: 0 AN: 66276

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34164

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3910

European-Non Finnish (NFE) AF: 0.00000201 AC: 2 AN: 993878

Other (OTH) AF: 0.00 AC: 0 AN: 50464

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000624538), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000401 AC: 6 AN: 149740 Hom.: 0 Cov.: 33 AF XY: 0.0000273 AC XY: 2 AN XY: 73156

African (AFR) AF: 0.00 AC: 0 AN: 40830

American (AMR) AF: 0.00 AC: 0 AN: 15102

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3448

East Asian (EAS) AF: 0.00123 AC: 6 AN: 4882

South Asian (SAS) AF: 0.00 AC: 0 AN: 4590

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10336

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67276

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Developmental and epileptic encephalopathy, 33 Benign:1

Dec 28, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.22

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: rs1170731512; hg19: chr20-62119787;