Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
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 |
RCV000727871 | SCV000855363 | uncertain significance | not provided | 2017-06-30 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000765897 | SCV000897317 | uncertain significance | Pontocerebellar hypoplasia type 6 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Ce |
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 | 2024-03-30 | criteria provided, single submitter | clinical testing | |
Greenwood Genetic Center Diagnostic Laboratories, |
RCV000765897 | SCV004244487 | likely pathogenic | Pontocerebellar hypoplasia type 6 | 2023-11-14 | criteria provided, single submitter | clinical testing | PM3_Strong, PM1 |
Natera, |
RCV000765897 | SCV002079904 | uncertain significance | Pontocerebellar hypoplasia type 6 | 2020-01-20 | no assertion criteria provided | clinical testing |