ClinVar Miner

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

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000718314 SCV000849176 likely benign History of neurodevelopmental disorder 2017-04-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign) ,Other data supporting benign classification
Athena Diagnostics Inc RCV000711300 SCV000841640 uncertain significance not provided 2018-05-15 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000711300 SCV000229838 uncertain significance not provided 2015-03-11 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
Genetic Services Laboratory, University of Chicago RCV000194104 SCV000249415 uncertain significance not specified 2015-04-02 criteria provided, single submitter clinical testing
Invitae RCV000515269 SCV000755395 uncertain significance Cohen syndrome 2018-11-09 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.

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