ClinVar Miner

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

gnomAD frequency: 0.00001  dbSNP: rs765443042
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Total submissions: 6
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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)
Labcorp Genetics (formerly Invitae), Labcorp RCV001034654 SCV000637233 pathogenic Carpenter syndrome 2024-02-17 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.
Genetics and Molecular Pathology, SA Pathology RCV000546008 SCV002761662 likely pathogenic RAB23-related Carpenter syndrome 2022-03-02 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000546008 SCV005673217 pathogenic RAB23-related Carpenter syndrome 2024-03-13 criteria provided, single submitter clinical testing
Natera, Inc. RCV000546008 SCV001453296 pathogenic RAB23-related Carpenter syndrome 2020-09-16 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV003930036 SCV004741156 pathogenic RAB23-related disorder 2024-01-17 no assertion criteria provided 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.

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