Submissions for variant NM_152564.5(VPS13B):c.983A>G (p.His328Arg)

gnomAD frequency: 0.00053  dbSNP: rs181625846

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000710112	SCV000232757	uncertain significance	not provided	2015-10-26	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000710112	SCV000616281	uncertain significance	not provided	2018-06-18	criteria provided, single submitter	clinical testing
Invitae	RCV000634098	SCV000755376	likely benign	Cohen syndrome	2024-01-27	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002314673	SCV000847694	uncertain significance	Inborn genetic diseases	2020-11-13	criteria provided, single submitter	clinical testing	The c.983A>G (p.H328R) alteration is located in exon 8 (coding exon 7) of the VPS13B gene. This alteration results from a A to G substitution at nucleotide position 983, causing the histidine (H) at amino acid position 328 to be replaced by an arginine (R). Based on data from the Genome Aggregation Database (gnomAD) database, the VPS13B c.983A>G alteration was observed in 0.05% (151/282442) of total alleles studied, with a frequency of 0.11% (39/35364) in the Latino subpopulation. This amino acid position is well conserved in available vertebrate species. The p.H328R alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV000634098	SCV000897403	uncertain significance	Cohen syndrome	2018-10-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000634098	SCV001323816	uncertain significance	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Knight Diagnostic Laboratories, Oregon Health and Sciences University	RCV000634098	SCV001448763	uncertain significance	Cohen syndrome	2019-06-19	criteria provided, single submitter	clinical testing
GeneDx	RCV000710112	SCV001778594	likely benign	not provided	2021-03-23	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV001818444	SCV002071430	uncertain significance	not specified	2021-04-20	criteria provided, single submitter	clinical testing
New York Genome Center	RCV000634098	SCV003925412	uncertain significance	Cohen syndrome	2022-02-11	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003982931	SCV004797026	likely benign	VPS13B-related disorder	2023-01-04	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).
Clinical Genetics, Academic Medical Center	RCV000710112	SCV001917660	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000710112	SCV001932941	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000710112	SCV001972223	likely benign	not provided		no assertion criteria provided	clinical testing
GenomeConnect - Invitae Patient Insights Network	RCV000634098	SCV004228694	not provided	Cohen syndrome		no assertion provided	phenotyping only	Variant interpreted as Uncertain significance and reported on 02-06-2020 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.