Submissions for variant NM_152564.5(VPS13B):c.11750_11752dup (p.Asp3917dup)

dbSNP: rs386834068

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000081876	SCV000113811	uncertain significance	not provided	2013-10-04	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002313737	SCV000848670	uncertain significance	Inborn genetic diseases	2018-12-07	criteria provided, single submitter	clinical testing	The c.11825_11827dupATG variant (also known as p.D3942dup), located in coding exon 61 of the VPS13B gene, results from an in-frame duplication of ATG at nucleotide positions 11825 to 11827. This results in the duplication of an aspartate residue between codons 3942 and 3943. This duplication (reported as p.D3942_G3943insD) was detected in compound heterozygous state with a gross deletion encompassing exons 1 to 17 of VPS13B and exon 4 of ORS2 in a patient with developmental delay and cardiac defect (Rivera-Brugués N et al. J. Med. Genet., 2011 Feb;48:136-40). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by PROVEAN in silico analysis (Choi Y et al., PLoS ONE 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000050055	SCV000899088	uncertain significance	Cohen syndrome	2021-09-17	criteria provided, single submitter	clinical testing	VPS13B NM_017890.4 exon 62 p.Asp3942_dup (c.11825_11827dupATG): This variant has been reported in the literature as a compound heterozygote (in trans with a multi-exon deletion of this gene) in 1 individual with a diagnosis of Cohen syndrome (Rivera-Brugues 2011 PMID:20921020, gene identified as alternate name COH1). However, this variant is present in 0.4% (100/24024) of African alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs558633643). This variant is present in ClinVar (Variation ID:56642). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant represents a duplication of 1 amino acid at position 3942 and is not predicted to alter the reading frame. However, the effect of this variant on the protein is unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000050055	SCV000963968	likely benign	Cohen syndrome	2024-01-31	criteria provided, single submitter	clinical testing
Mendelics	RCV000050055	SCV001137692	uncertain significance	Cohen syndrome	2019-05-28	criteria provided, single submitter	clinical testing
GeneDx	RCV000081876	SCV001819828	likely benign	not provided	2021-02-26	criteria provided, single submitter	clinical testing	In-frame insertion of one amino acid in a non-repeat region; Reported previously using alternate nomenclature (c.1827_11828insATG) in an individual with developmental delay, cardiac defects, and dysmorphic features who harbored a partial gene deletion on the opposite allele (in trans) (Rivera-Brugues et al., 2011); This variant is associated with the following publications: (PMID: 20921020)
Revvity Omics, Revvity	RCV000050055	SCV003820436	uncertain significance	Cohen syndrome	2019-08-06	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003982870	SCV004799517	likely benign	VPS13B-related disorder	2022-03-18	criteria provided, single submitter	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).
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)	RCV000050055	SCV000082464	probable-pathogenic	Cohen syndrome		no assertion criteria provided	not provided	Converted during submission to Likely pathogenic.