rs879255373
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 3P and 5B. PM4PP5BS1_SupportingBS2
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
Consequence
NM_001958.5 conservative_inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000266 AC: 4AN: 150518Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000380 AC: 47AN: 1235298Hom.: 0 AF XY: 0.0000379 AC XY: 23AN XY: 607454
GnomAD4 genome AF: 0.0000266 AC: 4AN: 150630Hom.: 0 Cov.: 32 AF XY: 0.0000136 AC XY: 1AN XY: 73522
ClinVar
Submissions by phenotype
not provided Pathogenic:1
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. -
Developmental and epileptic encephalopathy, 33 Uncertain:1
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 and/or epilepsy (PMID: 29784605, 36403551). 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. -
not specified Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at