Submissions for variant NM_024537.4(CARS2):c.1068dup (p.Asp357Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003002558	SCV003298598	uncertain significance	Combined oxidative phosphorylation defect type 27	2022-01-15	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 has not been reported in the literature in individuals affected with CARS2-related conditions. This variant is present in population databases (rs749680674, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Asp357*) in the CARS2 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in CARS2 cause disease.
Ambry Genetics	RCV003002559	SCV003651639	pathogenic	Inborn genetic diseases	2022-11-11	criteria provided, single submitter	clinical testing	The c.1068dupT (p.D357*) alteration, located in exon 11 (coding exon 11) of the CARS2 gene, consists of a duplication of T at position 1068. This changes the amino acid from an aspartic acid (D) to a stop codon at amino acid position 357. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This allele was reported in one heterozygous individual in population-based cohorts in the Genome Aggregation Database (gnomAD). Based on the available evidence, this alteration is classified as pathogenic.