ClinVar Miner

Submissions for variant NM_020320.5(RARS2):c.773G>A (p.Arg258His)

gnomAD frequency: 0.00044  dbSNP: rs145297855
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000727871 SCV000252183 uncertain significance not provided 2021-01-13 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Reported previously in two siblings with seizures, microcephaly, and cerebral atrophy without pontocerebellar hypoplasia, who were also compound heterozygous for a slice variant in RARS2 (Kastrissianakis et al., 2013); This variant is associated with the following publications: (PMID: 27061686, 24047924, 29431110, 33209735)
Eurofins Ntd Llc (ga) RCV000727871 SCV000855363 uncertain significance not provided 2017-06-30 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000765897 SCV000897317 uncertain significance Pontocerebellar hypoplasia type 6 2018-10-31 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000727871 SCV002497443 likely pathogenic not provided 2023-01-01 criteria provided, single submitter clinical testing RARS2: PM2, PM3, PP1, PP3
Invitae RCV000727871 SCV002975713 likely pathogenic not provided 2024-01-31 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 258 of the RARS2 protein (p.Arg258His). This variant is present in population databases (rs145297855, gnomAD 0.2%). This missense change has been observed in individual(s) with clinical features of RARS2-related conditions (PMID: 24047924, 33209735). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 215080). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Baylor Genetics RCV000765897 SCV004206131 likely pathogenic Pontocerebellar hypoplasia type 6 2023-10-24 criteria provided, single submitter clinical testing
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center RCV000765897 SCV004244487 likely pathogenic Pontocerebellar hypoplasia type 6 2023-11-14 criteria provided, single submitter clinical testing PM3_Strong, PM1
Natera, Inc. RCV000765897 SCV002079904 uncertain significance Pontocerebellar hypoplasia type 6 2020-01-20 no assertion criteria provided clinical testing

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