Submissions for variant NM_152564.5(VPS13B):c.5927del (p.Pro1976fs)

dbSNP: rs755125969

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000299010	SCV000329304	pathogenic	not provided	2024-08-20	criteria provided, single submitter	clinical testing	Reported in a patient in the CAUSES study who also harbors an additional loss of function variant in the VPS13B gene (PMID: 35599849); 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 significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 35599849)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000673645	SCV001235328	pathogenic	Cohen syndrome	2024-09-28	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Pro2001Leufs*18) in the VPS13B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in VPS13B are known to be pathogenic (PMID: 15141358, 16648375, 20461111). This variant is present in population databases (rs755125969, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with VPS13B-related conditions. ClinVar contains an entry for this variant (Variation ID: 279779). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV004678656	SCV005174717	pathogenic	Inborn genetic diseases	2024-04-09	criteria provided, single submitter	clinical testing	The c.6002delC (p.P2001Lfs*18) alteration, located in exon 35 (coding exon 34) of the VPS13B gene, consists of a deletion of one nucleotide at position 6002, causing a translational frameshift with a predicted alternate stop codon after 18 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from gnomAD, this allele has an overall frequency of 0.001% (3/282576) total alleles studied. The highest observed frequency was 0.002% (3/129028) of European (non-Finnish) alleles. Based on the available evidence, this alteration is classified as pathogenic.
Athena Diagnostics	RCV000299010	SCV005621190	pathogenic	not provided	2023-09-26	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. The frequency of this variant in the general population is consistent with pathogenicity. (http://gnomad.broadinstitute.org) This variant has been identified in at least one individual with clinical features associated with this gene. In some published literature, this variant is referred to as c.5927del (p.Pro1976LeufsTer18).
Counsyl	RCV000673645	SCV000798872	likely pathogenic	Cohen syndrome	2018-03-27	no assertion criteria provided	clinical testing
Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals	RCV000673645	SCV000803697	pathogenic	Cohen syndrome	2017-12-11	no assertion criteria provided	clinical testing