Submissions for variant NM_020745.4(AARS2):c.2728_2755del (p.Thr910fs)

dbSNP: rs780343109

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000598759	SCV000701730	uncertain significance	not provided	2016-10-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000598759	SCV000710760	likely pathogenic	not provided	2019-03-28	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Frameshift variant in the C-terminus predicted to result in protein truncation, as the last 76 amino acids are lost and replaced with 57 incorrect amino acids (Stenson et al., 2014)
Invitae	RCV000598759	SCV002149925	uncertain significance	not provided	2022-08-23	criteria provided, single submitter	clinical testing	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. This variant disrupts a region of the AARS2 protein in which other variant(s) (p.Gly965Arg) have been observed in individuals with AARS2-related conditions (PMID: 24808023). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 497299). This variant has not been reported in the literature in individuals affected with AARS2-related conditions. This variant is present in population databases (rs780343109, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Thr910Profs*58) in the AARS2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 76 amino acid(s) of the AARS2 protein.