ClinVar Miner

Submissions for variant NM_020320.5(RARS2):c.1564G>A (p.Val522Ile)

gnomAD frequency: 0.00006  dbSNP: rs201386427
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Kids Research, The Children's Hospital at Westmead RCV001089498 SCV001244743 uncertain significance Pontocerebellar hypoplasia type 6 criteria provided, single submitter research
Invitae RCV001862656 SCV002240520 pathogenic not provided 2024-01-16 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 522 of the RARS2 protein (p.Val522Ile). This variant is present in population databases (rs201386427, gnomAD 0.03%). This missense change has been observed in individual(s) with pontocerebellar hypoplasia (PMID: 32313153, 33972171, 34247374). 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: 869402). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RARS2 protein function. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV001089498 SCV004206145 likely pathogenic Pontocerebellar hypoplasia type 6 2023-10-04 criteria provided, single submitter clinical testing

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