Submissions for variant NM_015443.4(KANSL1):c.868C>T (p.Arg290Ter)

gnomAD frequency: 0.00006  dbSNP: rs149830411

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000486096	SCV000570441	pathogenic	not provided	2022-11-28	criteria provided, single submitter	clinical testing	Identified in an individual from a developmental delay cohort in the published literature (Wang et al., 2020); 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; This variant is associated with the following publications: (PMID: 33004838)
Ambry Genetics	RCV000623046	SCV000742976	likely pathogenic	Inborn genetic diseases	2017-11-17	criteria provided, single submitter	clinical testing
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678306	SCV000804365	pathogenic	Koolen-de Vries syndrome	2018-03-19	criteria provided, single submitter	provider interpretation	This variant was identified in a 12 year old female with a history of intellectual disability, hypotonia, short stature, atrial septal defect, patent ductus arteriosus, multicystic dysplastic left kidney, congenital valgus foot deformity, constipation, and dysphagia. Dysmorphic facial features include coarse facies, hypertelorism, epicanthal folds, broad nasal tip, and wide spaced teeth. The variant is present in the gnomAD Finnish population at 0.058% but is absent from all other populations with sufficient data. The presence of an inversion polymorphism at 17q21.31 which overlaps KANSL1 complicates the interpretation of this variant. The proband is adopted and parental samples were not available. However, there was very strong clinical correlation between this patient's clinical features and Koolen-DeVries syndrome. In addition, whole exome sequencing identified an additional VUS in a gene of uncertain significance.
Mendelics	RCV002248704	SCV002517222	uncertain significance	not specified	2022-05-04	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000486096	SCV004042003	likely pathogenic	not provided	2023-06-01	criteria provided, single submitter	clinical testing	KANSL1: PVS1, PS2, BS2
Daryl Scott Lab, Baylor College of Medicine	RCV000678306	SCV004102698	pathogenic	Koolen-de Vries syndrome	2023-11-10	criteria provided, single submitter	clinical testing