rs879255373
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM4PP5BS2
The NM_001958.5(EEF1A2):c.1375_1383del(p.Gln459_Ala461del) variant causes a 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 inframe_deletion
NM_001958.5 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.14
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PM4
?
Nonframeshift variant in NON repetitive region in NM_001958.5.
PP5
?
Variant 20-63488306-CCGCCTTCTG-C is Pathogenic according to our data. Variant chr20-63488306-CCGCCTTCTG-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 252597.We mark this variant Likely_pathogenic, oryginal submissions are: {Uncertain_significance=2, Likely_pathogenic=1}.
BS2
?
High AC in GnomAdExome4 at 47 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EEF1A2 | NM_001958.5 | c.1375_1383del | p.Gln459_Ala461del | inframe_deletion | 8/8 | ENST00000217182.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EEF1A2 | ENST00000217182.6 | c.1375_1383del | p.Gln459_Ala461del | inframe_deletion | 8/8 | 1 | NM_001958.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000266 AC: 4AN: 150518Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.0000380 AC: 47AN: 1235298Hom.: 0 AF XY: 0.0000379 AC XY: 23AN XY: 607454
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:1Uncertain:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Apr 18, 2017 | A c.1375_1383delCAGAAGGCG variant that is likely pathogenic has been identified in the EEF1A2 gene. The c.1375_1383delCAGAAGGCG variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 5,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The c.1375_1383delCAGAAGGCG variant results in an in-frame deletion of three amino acids, denoted p.Gln459_Ala461del. This deletion occurs at a position that is conserved in mammals. However, the c.1375_1383delCAGAAGGCG variant is not predicted to cause loss of normal protein function through protein truncation or nonsense-mediated mRNA decay. Therefore, based on the currently available information, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia | Nov 19, 2015 | - - |
Developmental and epileptic encephalopathy, 33 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 27, 2023 | This variant, c.1375_1383del, results in the deletion of 3 amino acid(s) of the EEF1A2 protein (p.Gln459_Ala461del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has been observed in individual(s) with intellectual disability (PMID: 29784605). ClinVar contains an entry for this variant (Variation ID: 252597). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at