ClinVar Miner

Submissions for variant NM_152564.5(VPS13B):c.7051-1G>A

gnomAD frequency: 0.00001  dbSNP: rs930144563
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000666273 SCV000790535 likely pathogenic Cohen syndrome 2017-03-29 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000666273 SCV000915239 uncertain significance Cohen syndrome 2018-11-26 criteria provided, single submitter clinical testing The VPS13B c.7126-1G>A variant occurs in a canonical splice site (acceptor) and is therefore predicted to disrupt or distort the normal gene product. A literature search was performed for the gene and cDNA change. No publications were found based on this search. The c.7126-1G>A variant is reported at a frequency of 0.000009 in the European (non-Finnish) population of the Genome Aggregation Database, but this is based on one allele only in a region of good sequence coverage so the variant is presumed to be rare. Due to the potential impact of splice acceptor variants and lack of clarifying evidence, the c.7126-1G>A variant is classified as a variant of unknown significance but suspicious for pathogenicity for Cohen syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000666273 SCV003257559 likely pathogenic Cohen syndrome 2023-06-25 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 551263). This variant has not been reported in the literature in individuals affected with VPS13B-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change affects an acceptor splice site in intron 39 of the VPS13B gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in VPS13B are known to be pathogenic (PMID: 15141358, 16648375, 20461111).

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