Submissions for variant NM_020745.4(AARS2):c.2551C>G (p.Leu851Val)

gnomAD frequency: 0.00014  dbSNP: rs376103315

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000199192	SCV000250982	uncertain significance	not provided	2017-07-07	criteria provided, single submitter	clinical testing	A variant of unknown significance has been identified in the AARS2 gene. The L851V missense substitution has not been published as pathogenic, nor has it been reported as a benign polymorphism to our knowledge. The amino acid substitution is conservative in that both Leucine and Valine are uncharged, non-polar amino acid residues. L851V alters a position that is highly conserved in the AARS2 protein. However, in-silico algorithms are not consistent in their predictions of whether L851V is damaging to the AARS2 protein. Therefore, based on the currently available information, it is unclear whether L851V is a pathogenic variant or a rare benign variant.
Illumina Laboratory Services, Illumina	RCV001161730	SCV001323627	uncertain significance	Combined oxidative phosphorylation defect type 8	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Ambry Genetics	RCV003165451	SCV003867352	uncertain significance	Inborn genetic diseases	2023-01-17	criteria provided, single submitter	clinical testing	The c.2551C>G (p.L851V) alteration is located in exon 19 (coding exon 19) of the AARS2 gene. This alteration results from a C to G substitution at nucleotide position 2551, causing the leucine (L) at amino acid position 851 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
CeGaT Center for Human Genetics Tuebingen	RCV000199192	SCV004698898	uncertain significance	not provided	2024-01-01	criteria provided, single submitter	clinical testing	AARS2: PM2, BP4