Submissions for variant NM_152564.5(VPS13B):c.11195G>A (p.Arg3732Gln)

gnomAD frequency: 0.00178  dbSNP: rs149318176

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000179212	SCV000231422	likely benign	not specified	2015-02-11	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000355552	SCV000470862	likely benign	Cohen syndrome	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000355552	SCV000630859	benign	Cohen syndrome	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002314659	SCV000849381	likely benign	Inborn genetic diseases	2023-01-10	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Mendelics	RCV000355552	SCV001137690	likely benign	Cohen syndrome	2019-05-28	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000859448	SCV001143638	likely benign	not provided	2019-04-23	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000859448	SCV001155465	likely benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	VPS13B: BS2
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000355552	SCV001190481	uncertain significance	Cohen syndrome	2021-03-30	criteria provided, single submitter	clinical testing	VPS13B NM_017890.4 exon 58 p.Arg3757Gln (c.11270G>A): This variant has not been reported in the literature but is present in 0.4% (108/26824) of South Asian alleles, including 2 homozygotes in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/8-100874154-G-A). This variant is present in ClinVar (Variation ID:198013). Evolutionary conservation suggests that this variant may impact the protein; computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Genome-Nilou Lab	RCV000355552	SCV001653455	likely benign	Cohen syndrome	2021-05-18	criteria provided, single submitter	clinical testing
GeneDx	RCV000859448	SCV001819811	likely benign	not provided	2019-12-16	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000179212	SCV002071436	uncertain significance	not specified	2019-01-22	criteria provided, single submitter	clinical testing
New York Genome Center	RCV000355552	SCV002764408	uncertain significance	Cohen syndrome	2021-10-19	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000355552	SCV001454482	benign	Cohen syndrome	2019-12-25	no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000859448	SCV001799678	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000859448	SCV001922103	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000859448	SCV001927022	likely benign	not provided		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000859448	SCV001963579	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003977475	SCV004798078	likely benign	VPS13B-related disorder	2019-11-25	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).