Submissions for variant NM_152564.5(VPS13B):c.2515+16591C>G

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV002471325	SCV002767221	uncertain significance	Cohen syndrome	2019-08-28	criteria provided, single submitter	clinical testing	A heterozygous missense variant was identified, NM_015243.2(VPS13B):c.2572C>G in exon 18 of 18 of the VPS13B gene (NB: This variant is non-coding in alternative transcripts, including the predominant transcript, NM_017890.4). This substitution is predicted to create a minor amino acid change from proline to alanine at position 858 of the protein, NP_056058.2(VPS13B):p.(Pro858Ala). The proline at this position is conserved, but only present, in mammals (100 vertebrates, UCSC), but is not situated in a known functional domain. In silico software predicts this variant to be benign (Polyphen, SIFT, CADD, Mutation Taster). The variant is present in the gnomAD population database at a frequency of 0.024% (15 heterozygotes, 0 homozygotes). The variant has not been previously reported in a clinical testing setting. Based on information available at the time of curation, this variant has been classified as a VARIANT of UNCERTAIN SIGNIFICANCE (VUS) with LOW CLINICAL RELEVANCE.
CeGaT Center for Human Genetics Tuebingen	RCV003427488	SCV004158253	likely benign	not provided	2023-01-01	criteria provided, single submitter	clinical testing	VPS13B: BP4
PreventionGenetics, part of Exact Sciences	RCV003933797	SCV004751811	likely benign	VPS13B-related disorder	2021-09-30	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).