ClinVar Miner

Submissions for variant NM_020320.5(RARS2):c.28G>A (p.Ala10Thr)

gnomAD frequency: 0.00001  dbSNP: rs755340864
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001567474 SCV001791164 uncertain significance not provided 2020-12-17 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002569039 SCV003580299 uncertain significance Inborn genetic diseases 2021-10-20 criteria provided, single submitter clinical testing The c.28G>A (p.A10T) alteration is located in exon 1 (coding exon 1) of the RARS2 gene. This alteration results from a G to A substitution at nucleotide position 28, causing the alanine (A) at amino acid position 10 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001832774 SCV002079911 uncertain significance Pontocerebellar hypoplasia type 6 2020-03-03 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV003931200 SCV004739581 uncertain significance RARS2-related disorder 2024-02-28 no assertion criteria provided clinical testing The RARS2 c.28G>A variant is predicted to result in the amino acid substitution p.Ala10Thr. This variant was reported in the homozygous state in an individual with pontocerebellar hypoplasia, type 6 (Chuan et al. 2022. PubMed ID: 35571021). This variant is reported in 0.0018% of alleles in individuals of European (Non-Finnish) descent in gnomAD. An alternate nucleotide change affecting the same amino acid (p.Ala10Val), has been reported in an individual with early onset epileptic encephalopathy, hypotonia, and psychomotor delay (Roux et al. 2021. PubMed ID: 33972171). Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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