ClinVar Miner

Submissions for variant NM_018122.5(DARS2):c.536G>A (p.Arg179His)

gnomAD frequency: 0.00004  dbSNP: rs121918210
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001268501 SCV001447478 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001268501 SCV003523357 pathogenic not provided 2022-08-31 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (PMID: 17384640, 24030952, 24566671, 32571458, 33977142). ClinVar contains an entry for this variant (Variation ID: 1064). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt DARS2 protein function. This variant disrupts the p.Arg179 amino acid residue in DARS2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 33977142). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. This variant is present in population databases (rs121918210, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 179 of the DARS2 protein (p.Arg179His).
GeneDx RCV001268501 SCV003921140 likely pathogenic not provided 2023-03-17 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24566671, 17384640, 33977142, 32571458, 35598585, 34405109)
Genome-Nilou Lab RCV000001119 SCV004048883 likely pathogenic Leukoencephalopathy with brain stem and spinal cord involvement-high lactate syndrome 2023-04-11 criteria provided, single submitter clinical testing
OMIM RCV000001119 SCV000021269 pathogenic Leukoencephalopathy with brain stem and spinal cord involvement-high lactate syndrome 2007-04-01 no assertion criteria provided literature only

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