Submissions for variant NM_001958.5(EEF1A2):c.1366CAGAAGGCG[1] (p.456QKA[1])

dbSNP: rs879255373

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000239113	SCV000297111	uncertain significance	not specified	2015-11-19	criteria provided, single submitter	clinical testing
GeneDx	RCV000487209	SCV000569803	likely pathogenic	not provided	2017-04-18	criteria provided, single submitter	clinical testing	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.
Invitae	RCV001057493	SCV001221990	uncertain significance	Developmental and epileptic encephalopathy, 33	2023-12-27	criteria provided, single submitter	clinical testing	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.