Submissions for variant NM_020320.5(RARS2):c.1442A>G (p.Tyr481Cys)

gnomAD frequency: 0.00002  dbSNP: rs775657290

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000487313	SCV000574420	uncertain significance	not provided	2017-03-30	criteria provided, single submitter	clinical testing	The Y481C variant in the RARS2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The Y481C variant is observed in 1/66734 (0.0015%) alleles from individuals of non-Finnish European background in the ExAC dataset (Lek et al., 2016). The Y481C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved across species, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, we interpret Y481C as a variant of uncertain significance.
Breakthrough Genomics, Breakthrough Genomics	RCV000487313	SCV005189154	uncertain significance	not provided		criteria provided, single submitter	not provided
Natera, Inc.	RCV001829392	SCV002079895	uncertain significance	Pontocerebellar hypoplasia type 6	2019-11-11	no assertion criteria provided	clinical testing