ClinVar Miner

Submissions for variant NM_152564.5(VPS13B):c.6302_6303insGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGCGGATCACGAGGTCAGNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAGAAAACATGTGGAG (p.Arg2101_Ala2102insProGlyAlaValAlaHisAlaCysAsnProSerThrLeuGlyGlyArgGlyGlyArgIleThrArgSerXaaXaaXaaXaaLysLysLysLysLysLysLysGluAsnMetTrpArg)

dbSNP: rs2130180694
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001974899 SCV002211382 pathogenic Cohen syndrome 2022-11-01 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 1439245). This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 36 of the VPS13B gene (c.6377_6378ins?), causing a frameshift at codon 2126 (p.Arg2126fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with VPS13B-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in VPS13B are known to be pathogenic (PMID: 15141358, 16648375, 20461111). For these reasons, this variant has been classified as Pathogenic.

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