ClinVar Miner

Submissions for variant NM_016277.5(RAB23):c.82C>T (p.Arg28Ter)

gnomAD frequency: 0.00001  dbSNP: rs765443042
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000305521 SCV000330809 pathogenic not provided 2023-06-06 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Reported previously in two siblings with Carpenter syndrome who harbored a maternally inherited R28X; L145X complex allele in trans with a paternally inherited L145X variant (Jenkins et al., 2011); This variant is associated with the following publications: (PMID: 23599695, 21412941, 33368989)
Invitae RCV001034654 SCV000637233 pathogenic Carpenter syndrome 2023-08-31 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg28*) in the RAB23 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RAB23 are known to be pathogenic (PMID: 17503333, 21412941). This variant is present in population databases (rs765443042, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with Carpenter syndrome, although in one family this variant was shown to be on the same chromosome (in cis) with another pathogenic variant (p.Leu145*) (PMID: 21412941, 23599695). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 280858). For these reasons, this variant has been classified as Pathogenic.
Illumina Laboratory Services, Illumina RCV000546008 SCV000915176 uncertain significance RAB23-related Carpenter syndrome 2017-06-20 criteria provided, single submitter clinical testing The RAB23 c.82C>T (p.Arg28Ter) stop-gained variant has been reported in one study and is found in two brothers with Carpenter syndrome with the p.Arg28Ter and p.Leu145Ter variants on a complex allele. These variants are on the maternal allele and are in trans with p.Leu145Ter on the paternal allele (Jenkins et al. 2011). The clinically unaffected mother was confirmed to be a carrier of the complex allele. Control data are unavailable for this variant, which is reported at a frequency of 0.000025 in the Total population in the Exome Aggregation Consortium. Due to the potential impact of stop-gained variants, the p.Arg28Ter variant is classified as a variant of unknown significance but suspicious for pathogenicity for Carpenter syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Genetics and Molecular Pathology, SA Pathology RCV000546008 SCV002761662 likely pathogenic RAB23-related Carpenter syndrome 2022-03-02 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003930036 SCV004741156 pathogenic RAB23-related disorder 2024-01-17 criteria provided, single submitter clinical testing The RAB23 c.82C>T variant is predicted to result in premature protein termination (p.Arg28*). This variant has been reported in six individuals from three families with Carpenter syndrome (Jenkins et al. 2011. PubMed ID: 21412941; Ben-Salem et al. 2013. PubMed ID: 23599695; Lodhia et al. 2021. PubMed ID: 33368989). In two of those individuals from one family, the c.434T>A and c.82C>T variant were reported to be on the same allele (cis orientation) with a nonsense variant on the other allele (Jenkins et al. 2011. PubMed ID: 21412941). In another family, both parents were heterozygous for the c.82C>T variant and the child with Carpenter syndrome was homozygous for the c.82C>T variant (Lodhia et al. 2021. PubMed ID: 33368989). Chain-terminating variants in RAB23 are expected to be pathogenic. Taken together, this variant is interpreted as pathogenic.
Natera, Inc. RCV000546008 SCV001453296 pathogenic RAB23-related Carpenter syndrome 2020-09-16 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.