ClinVar Miner

Submissions for variant NM_016628.5(WAC):c.1470_1477del (p.Gln492fs) (rs1589247025)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001001096 SCV001158231 pathogenic Desanto-shinawi syndrome 2019-02-12 criteria provided, single submitter clinical testing The WAC c.1470_1477del; p.Gln492fs variant is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. This variant, located in exon 11 out of 14, creates a frame shift starting at codon Gln492 resulting in a new reading frame and a premature STOP codon. All previously reported patients with Desanto-Shinawi syndrome had nonsense, framesfift, deletion or splice variants in the WAC gene (Varvagiannis 2017, Uehara 2018, Vanegas 2018), with several of these variants located after p.Gln492fs variant, in exons 12 and 13 of the WAC gene. Uehara et al. (2018) suggested haploinsufficiency as a likely pathogenic molecular mechanism. References: Uehara T et al. Three patients with DeSanto-Shinawi syndrome: Further phenotypic delineation. Am J Med Genet A. 2018 Jun;176(6):1335-1340. PMID: 29663678. Vanegas S et al. DeSanto-Shinawi Syndrome: First Case in South America. Mol Syndromol. 2018 May;9(3):154-158. PMID:29928181. Varvagiannis K et al. WAC-Related Intellectual Disability. 2017 Nov 30. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews (Internet). Seattle (WA): University of Washington, Seattle; 1993-2019. Available from http://www.ncbi.nlm.nih.gov/books/NBK465012/PMID: 29190062.

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