Submissions for variant NM_014516.4(CNOT3):c.1865G>A (p.Trp622Ter)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV002470305	SCV002767051	pathogenic	Intellectual developmental disorder with speech delay, autism, and dysmorphic facies	2020-05-26	criteria provided, single submitter	clinical testing	Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0107 - This gene is known to be associated with autosomal dominant disease. (N) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (exon 15 of 18). (P) 0251 - Variant is heterozygous. (N) 0301 - Variant is absent from gnomAD. (P) 0702 - Comparable variants have strong previous evidence for pathogenicity. Other variants predicted to cause NMD have been reported as pathogenic in multiple individuals (ClinVar, PMID: 31201375). (P) 0803 - Low previous evidence of pathogenicity in unrelated individuals. The variant has been previously reported in one de novo patient with ID (PMID: 31201375). (P) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign