rs760400114

Variant names:

• chr20-63488427-T-TGGGGGGC
• rs760400114
• NM_001958.5:c.1265-9_1265-3dupGCCCCCC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_001958.5(EEF1A2):​c.1265-9_1265-3dupGCCCCCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00026 (5 hom.)
  • Failed GnomAD Quality Control
• Consequence: EEF1A2 NM_001958.5 splice_region, intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.58
• 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 -8 ACMG points.

• BP6: Variant 20-63488427-T-TGGGGGGC is Benign according to our data. Variant chr20-63488427-T-TGGGGGGC is described in ClinVar as [Likely_benign]. Clinvar id is 421074.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EEF1A2	NM_001958.5	c.1265-9_1265-3dupGCCCCCC		splice_region_variant, intron_variant	Intron 7 of 7	ENST00000217182.6	NP_001949.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EEF1A2	ENST00000217182.6	c.1265-3_1265-2insGCCCCCC		splice_region_variant, intron_variant	Intron 7 of 7	1	NM_001958.5	ENSP00000217182.3

Frequencies

GnomAD3 genomes AF: 0.000238 AC: 34 AN: 142590 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: 0.00

Gnomad SAS AF: 0.00740

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000155

Gnomad OTH AF: 0.000512

GnomAD2 exomes AF: 0.000387 AC: 29 AN: 74884 AF XY: 0.000482

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000256 AC: 329 AN: 1287478 Hom.: 5 Cov.: 33 AF XY: 0.000357 AC XY: 226 AN XY: 633836

African (AFR) AF: 0.00 AC: 0 AN: 25528

American (AMR) AF: 0.00 AC: 0 AN: 21752

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21982

East Asian (EAS) AF: 0.00 AC: 0 AN: 27512

South Asian (SAS) AF: 0.00439 AC: 301 AN: 68548

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36504

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4256

European-Non Finnish (NFE) AF: 0.0000136 AC: 14 AN: 1028818

Other (OTH) AF: 0.000266 AC: 14 AN: 52578

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000238 AC: 34 AN: 142696 Hom.: 0 Cov.: 33 AF XY: 0.000372 AC XY: 26 AN XY: 69980

African (AFR) AF: 0.00 AC: 0 AN: 38464

American (AMR) AF: 0.00 AC: 0 AN: 14668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3354

East Asian (EAS) AF: 0.00 AC: 0 AN: 4490

South Asian (SAS) AF: 0.00741 AC: 32 AN: 4316

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10022

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 222

European-Non Finnish (NFE) AF: 0.0000155 AC: 1 AN: 64358

Other (OTH) AF: 0.000507 AC: 1 AN: 1974

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Developmental and epileptic encephalopathy, 33 Benign:1

Jan 17, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

May 19, 2023

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

See Variant Classification Assertion Criteria. -

Congenital heart disease Benign:1

Dec 13, 2019

Cambridge Genomics Laboratory, East Genomic Laboratory Hub, NHS Genomic Medicine Service

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6
Mutation Taster		=80/20	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs760400114; hg19: chr20-62119780;