Submissions for variant NM_001320.7(CSNK2B):c.139C>T (p.Arg47Ter)

dbSNP: rs1085307703

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001281589	SCV000577080	pathogenic	not provided	2024-05-06	criteria provided, single submitter	clinical testing	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: 33057194, 35982159, 33166063, 34041744, 37717460)
Ambry Genetics	RCV001267434	SCV001445615	pathogenic	Inborn genetic diseases	2018-08-01	criteria provided, single submitter	clinical testing
Laboratoire de Génétique Moléculaire, CHU Bordeaux	RCV001281589	SCV001468911	pathogenic	not provided		criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001281589	SCV001502479	pathogenic	not provided	2021-01-01	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV002468581	SCV002765118	pathogenic	Poirier-Bienvenu neurodevelopmental syndrome	2022-12-07	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002468581	SCV002819345	pathogenic	Poirier-Bienvenu neurodevelopmental syndrome	2022-12-08	criteria provided, single submitter	clinical testing	Variant summary: CSNK2B c.139C>T (p.Arg47X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay. Truncations downstream of this position have been reported in HGMD in association with Poirier-Bienvenu neurodevelopmental syndrome, Intellectual disability and Epilepsy. The variant was absent in 220452 control chromosomes. c.139C>T has been reported in the literature in two individuals in the de novo state, one with intellectual disability, seizures and autistic features, and the second with intellectual disability, seizures and postnatal growth retardation (Ernst_2021, Selvam_2021). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
PreventionGenetics, part of Exact Sciences	RCV003942606	SCV004765536	pathogenic	CSNK2B-related disorder	2023-11-27	no assertion criteria provided	clinical testing	The CSNK2B c.139C>T variant is predicted to result in premature protein termination (p.Arg47*). This variant has been reported, with de novo occurrence, in individuals with Intellectual disability, epilepsy and abnormal linear growth (Selvam et al. 2021. PubMed ID: 33166063; Ernst et al. 2021. PubMed ID: 34041744). This variant has not been reported in a large population database, indicating this variant is rare. Nonsense variants in CSNK2B are expected to be pathogenic. This variant is interpreted as pathogenic.