Submissions for variant NM_024537.4(CARS2):c.38del (p.Pro13fs)

dbSNP: rs1412483498

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001008175	SCV001167941	likely pathogenic	not provided	2018-05-14	criteria provided, single submitter	clinical testing	The c.38delC variant in the CARS2 gene causes a frameshift starting with codon Proline 13, changes this amino acid to an Arginine residue and creates a premature Stop codon at position 53 of the new reading frame, denoted p.Pro13ArgfsX53. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.38delC variant is not observed in large population cohorts (Lek et al., 2016). Although this variant has not been previously reported to our knowledge, it is likely a pathogenic variant.
Invitae	RCV001371593	SCV001568164	uncertain significance	Combined oxidative phosphorylation defect type 27	2020-09-20	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Pro13Argfs*53) in the CARS2 gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals with CARS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 817082). The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in CARS2 cause disease. 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.