ClinVar Miner

Submissions for variant NM_017890.4(VPS13B):c.10156dup (p.Thr3386fs) (rs386834055)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000050042 SCV000220266 likely pathogenic Cohen syndrome 2014-04-24 criteria provided, single submitter literature only
Center of Genomic medicine, Geneva,University Hospital of Geneva RCV000050042 SCV000268521 pathogenic Cohen syndrome 2016-03-01 criteria provided, single submitter clinical testing This inherited recessive pathogenic mutation in the VPS13B gene in combination with a second recessive pathogenic mutation in the same gene, NM_152564.4:c.10165_10207del, was observed in a patient with Cohen syndrome.
Invitae RCV000050042 SCV000819826 pathogenic Cohen syndrome 2020-09-07 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr3386Asnfs*3) in the VPS13B gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs752215462, ExAC 0.02%). This variant has been reported as in combination with another VPS13B variant in an individual affected with Cohen Syndrome (PMID: 22855652). ClinVar contains an entry for this variant (Variation ID: 56629). 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000050042 SCV000920341 likely pathogenic Cohen syndrome 2019-08-12 criteria provided, single submitter clinical testing Variant summary: VPS13B c.10156dupA (p.Thr3386AsnfsX3) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 3.6e-05 in 251338 control chromosomes. c.10156dupA has been reported in the literature in individuals affected with Cohen Syndrome (Athanasakis_2012) . These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar (after 2014) and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Centre for Genomic Medicine, Manchester,Central Manchester University Hospitals RCV000050042 SCV001156399 pathogenic Cohen syndrome 2019-02-01 criteria provided, single submitter clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV000050042 SCV001737019 pathogenic Cohen syndrome criteria provided, single submitter clinical testing
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000050042 SCV000082451 probable-pathogenic Cohen syndrome no assertion criteria provided not provided Converted during submission to Likely pathogenic.
GeneDx RCV001571767 SCV001796298 pathogenic not provided 2019-10-16 no assertion criteria provided clinical testing Frameshift 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; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 22855652)

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