ClinVar Miner

Submissions for variant NM_016277.5(RAB23):c.82C>T (p.Arg28Ter) (rs765443042)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000305521 SCV000330809 pathogenic not provided 2016-09-19 criteria provided, single submitter clinical testing The R28X pathogenic variant in the RAB23 gene has been 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 variants is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. This variant was not observed at any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret the R28X as a pathogenic variant.
Invitae RCV001034654 SCV000637233 pathogenic Carpenter syndrome 2019-07-05 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. This variant is present in population databases (rs765443042, ExAC 0.01%). This variant has been reported in individuals affected with Carpenter syndrome (PMID: 21412941, 23599695). In one family, this variant was shown to be on the same chromosome (in cis) with another variant (p.Leu145*) (PMID: 21412941). ClinVar contains an entry for this variant (Variation ID: 280858). Loss-of-function variants in RAB23 are known to be pathogenic (PMID: 21412941). For these reasons, this variant has been classified as Pathogenic.
Illumina Clinical Services Laboratory,Illumina RCV000546008 SCV000915176 uncertain significance Carpenter syndrome 1 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.

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