ClinVar Miner

Submissions for variant NM_020320.5(RARS2):c.1544A>G (p.Asp515Gly)

gnomAD frequency: 0.00005  dbSNP: rs765088174
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München RCV000578317 SCV000680355 likely pathogenic Pontocerebellar hypoplasia type 6 2017-12-07 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001312080 SCV001502521 likely pathogenic not provided 2024-02-01 criteria provided, single submitter clinical testing RARS2: PM3:Strong, PM2
Invitae RCV001312080 SCV002273129 pathogenic not provided 2024-01-25 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 515 of the RARS2 protein (p.Asp515Gly). This variant is present in population databases (rs765088174, gnomAD 0.007%). This missense change has been observed in individual(s) with RARS2-related conditions (PMID: 27683254, 34490615). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 488585). 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 not expected to disrupt RARS2 protein function with a negative predictive value of 80%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV000578317 SCV003813869 likely pathogenic Pontocerebellar hypoplasia type 6 2022-05-09 criteria provided, single submitter clinical testing
GeneDx RCV001312080 SCV004031821 likely pathogenic not provided 2023-08-31 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27683254, 35707589, 34717047, 34490615, 35468344)
Baylor Genetics RCV000578317 SCV004208431 pathogenic Pontocerebellar hypoplasia type 6 2023-07-31 criteria provided, single submitter clinical testing

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