Submissions for variant NM_152564.5(VPS13B):c.5734_5735del (p.Ile1912fs)

dbSNP: rs386834098

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000050091	SCV000220757	likely pathogenic	Cohen syndrome	2014-09-30	criteria provided, single submitter	literature only
Labcorp Genetics (formerly Invitae), Labcorp	RCV000050091	SCV001589945	pathogenic	Cohen syndrome	2023-09-22	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 56678). This premature translational stop signal has been observed in individual(s) with VPS13B-related conditions (PMID: 15691367). This variant is present in population databases (rs779987157, gnomAD 0.02%). This sequence change creates a premature translational stop signal (p.Ile1937Cysfs*11) 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).
3billion	RCV000050091	SCV002318746	pathogenic	Cohen syndrome	2023-06-22	criteria provided, single submitter	clinical testing	The variant is not observed in the gnomAD v2.1.1 dataset. Predicted Consequence/Location: Missense variant In silico tool predictions suggest damaging effect of the variant on gene or gene product [REVEL: 0.95 (>=0.6, sensitivity 0.68 and specificity 0.92); 3Cnet: 0.73 (>=0.6, sensitivity 0.72 and precision 0.9)]. Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000017366 /PMID: 8325895 /3billion dataset). The variant has been observed in multiple (>3) similarly affected unrelated individuals (PMID: 21924244, 25735649, 8325895). The variant has been reported to co-segregate with the disease in at least 3 similarly affected relatives/individuals in the same family or similarly affected unrelated families (PMID: 21924244). A different missense change at the same codon (p.Arg989Gly) has been reported to be associated with COL2A1 related disorder (PMID: 33908178). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
Fulgent Genetics, Fulgent Genetics	RCV000050091	SCV005667373	pathogenic	Cohen syndrome	2024-05-06	criteria provided, single submitter	clinical testing
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)	RCV000050091	SCV000082500	probable-pathogenic	Cohen syndrome		no assertion criteria provided	not provided	Converted during submission to Likely pathogenic.
Natera, Inc.	RCV000050091	SCV002082590	pathogenic	Cohen syndrome	2020-10-09	no assertion criteria provided	clinical testing
Department of Rehabilitation Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea	RCV000050091	SCV004023311	pathogenic	Cohen syndrome		no assertion criteria provided	clinical testing