Submissions for variant NM_016628.5(WAC):c.1537C>T (p.Arg513Ter)

dbSNP: rs1564421528

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Undiagnosed Diseases Network, NIH	RCV000708579	SCV000837703	pathogenic	DeSanto-Shinawi syndrome due to WAC point mutation	2018-03-05	criteria provided, single submitter	clinical testing
Clinical Genetics and Genomics, Karolinska University Hospital	RCV001269613	SCV001449718	pathogenic	not provided	2019-03-28	criteria provided, single submitter	clinical testing
GeneDx	RCV001269613	SCV002762316	pathogenic	not provided	2022-12-05	criteria provided, single submitter	clinical testing	Previously reported as p.Arg468* (Frisk et al., 2022); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 35118825, 33726816)
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV000708579	SCV005086122	pathogenic	DeSanto-Shinawi syndrome due to WAC point mutation	2023-12-21	criteria provided, single submitter	clinical testing	Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Desanto-Shinawi syndrome (MIM#616708). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Many other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (DECIPHER). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been classified as pathogenic by multiple clinical laboratories in ClinVar and LOVD and has been observed in a de novo individual in DECIPHER. (SP) 1007 - No published functional evidence has been identified for this variant. (I) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed) (by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001269613	SCV002034898	pathogenic	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001269613	SCV002035264	pathogenic	not provided		no assertion criteria provided	clinical testing