ClinVar Miner

Submissions for variant NM_017890.4(VPS13B):c.6491A>G (p.Asn2164Ser) (rs142248228)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics 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 uncertain significance Cohen syndrome 2020-01-08 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 2164 of the VPS13B protein (p.Asn2164Ser). The asparagine residue is weakly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs142248228, ExAC 0.1%). This variant has not been reported in the literature in individuals with VPS13B-related disease. ClinVar contains an entry for this variant (Variation ID: 196985). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Athena Diagnostics Inc RCV000711300 SCV000841640 uncertain significance not provided 2018-05-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV000718314 SCV000849176 likely benign History of neurodevelopmental disorder 2017-04-14 criteria provided, single submitter clinical testing In silico models in agreement (benign) ;Other data supporting benign classification
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000515269 SCV001190426 uncertain significance Cohen syndrome 2019-09-03 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 ( 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 Clinical Services Laboratory,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.
Nilou-Genome 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
Natera, Inc. RCV000515269 SCV001460395 likely benign Cohen syndrome 2020-01-02 no assertion criteria provided clinical testing

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