Submissions for variant NM_152564.5(VPS13B):c.467_470del (p.Asn156fs)

dbSNP: rs386834090

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000050081	SCV001586252	pathogenic	Cohen syndrome	2023-07-07	criteria provided, single submitter	clinical testing	This premature translational stop signal has been observed in individual(s) with Cohen syndrome (PMID: 15141358). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 56668). This variant is also known as c.463_466delATAA. This variant is present in population databases (rs386834090, gnomAD 0.002%). This sequence change creates a premature translational stop signal (p.Asn156Ilefs*4) 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).
Ambry Genetics	RCV002336201	SCV002638135	pathogenic	Inborn genetic diseases	2020-06-16	criteria provided, single submitter	clinical testing	The c.467_470delATAA variant, located in coding exon 4 of the VPS13B gene, results from a deletion of 4 nucleotides at nucleotide positions 467 to 470, causing a translational frameshift with a predicted alternate stop codon (p.N156Ifs*4). This alteration was detected in a homozygous state in an individual with Cohen Syndrome (Kolehmainen J et al. Am. J. Hum. Genet., 2004 Jul;75:122-7). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000050081	SCV004807480	uncertain significance	Cohen syndrome	2024-03-29	criteria provided, single submitter	clinical testing
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)	RCV000050081	SCV000082490	probable-pathogenic	Cohen syndrome		no assertion criteria provided	not provided	Converted during submission to Likely pathogenic.