Submissions for variant NM_020745.4(AARS2):c.2683-1G>T

gnomAD frequency: 0.00001  dbSNP: rs374185049

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000779507	SCV000916145	uncertain significance	Combined oxidative phosphorylation defect type 8	2018-12-13	criteria provided, single submitter	clinical testing	The AARS2 c.2683-1G>T variant occurs in a canonical splice site (acceptor) and is therefore predicted to disrupt or distort the normal gene product. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. The variant is reported at a frequency of 0.000016 in the European (non-Finnish) population from the Genome Aggregation Database though this is based on two alleles in a region of good sequencing coverage so the variant is presumed to be rare. Based on the variant frequency, disease prevalence, disease penetrance, and inheritance mode, this variant could not be ruled out of causing disease. Due to the potential impact of splice acceptor variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for combined oxidative phosphorylation deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.