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

dbSNP: rs755125969

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000299010	SCV000329304	pathogenic	not provided	2018-02-14	criteria provided, single submitter	clinical testing	The c.6002delC variant in the VPS13B gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.6002delC variant causes a frameshift starting with codon Proline 2001, changes this amino acid to a Leucine residue, and creates a premature Stop codon at position 18 of the new reading frame, denoted p.Pro2001LeufsX18. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.6002delC variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret c.6002delC as a pathogenic variant.
Invitae	RCV000673645	SCV001235328	pathogenic	Cohen syndrome	2023-09-08	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.
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