Submissions for variant NM_152564.5(VPS13B):c.6416A>G (p.Asn2139Ser)

gnomAD frequency: 0.00070  dbSNP: rs142248228

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000711300	SCV000229838	uncertain significance	not provided	2015-03-11	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000194104	SCV000249415	uncertain significance	not specified	2015-04-02	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000515269	SCV000611531	uncertain significance	Cohen syndrome	2017-05-23	criteria provided, single submitter	clinical testing
Invitae	RCV000515269	SCV000755395	likely benign	Cohen syndrome	2024-01-31	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000711300	SCV000841640	uncertain significance	not provided	2018-05-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002314637	SCV000849176	likely benign	Inborn genetic diseases	2021-11-03	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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000515269	SCV001190426	uncertain significance	Cohen syndrome	2021-03-30	criteria provided, single submitter	clinical testing	VPS13B NM_017890.4 exon39 p.Asn2164Ser (c.6491A>G): This variant has not been reported in the literature but is present in 0.1% (48/30532) of South Asian alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/8-100712122-A-G). This variant is also present in ClinVar (Variation ID: 196985). This variant amino acid Serine (Ser) is present in 40 species including multiple mammals, and it is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Illumina Laboratory Services, Illumina	RCV000515269	SCV001326106	uncertain significance	Cohen syndrome	2018-03-02	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.
Genome-Nilou Lab	RCV000515269	SCV001653495	uncertain significance	Cohen syndrome	2021-05-18	criteria provided, single submitter	clinical testing
GeneDx	RCV000711300	SCV001823468	likely benign	not provided	2020-07-29	criteria provided, single submitter	clinical testing
New York Genome Center	RCV000515269	SCV004046485	uncertain significance	Cohen syndrome	2023-01-13	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University Hospital of Duesseldorf	RCV000515269	SCV004046667	uncertain significance	Cohen syndrome		criteria provided, single submitter	not provided
PreventionGenetics, part of Exact Sciences	RCV003982929	SCV004797038	likely benign	VPS13B-related disorder	2022-02-01	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).
CeGaT Center for Human Genetics Tuebingen	RCV000711300	SCV004811028	likely benign	not provided	2024-04-01	criteria provided, single submitter	clinical testing	VPS13B: BP4
Natera, Inc.	RCV000515269	SCV001460395	likely benign	Cohen syndrome	2020-01-02	no assertion criteria provided	clinical testing