Submissions for variant NM_001039803.3(CDK20):c.564G>A (p.Trp188Ter)

dbSNP: rs1057519438

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004586702	SCV005076294	uncertain significance	not specified	2024-04-12	criteria provided, single submitter	clinical testing	Variant summary: CDK20 c.564G>A (p.Trp188X) 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, however the molecular mechanism of disease attributed to CDK20 is currently unknown. In addition, this variant disrupts the first nucleotide of exon 6, and therefore can affect splicing. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 205392 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.564G>A has been reported in the literature as a de novo variant in at least one individual affected with seizures, unilateral hearing loss, dysmorphic features, attention deficit hyperactivity disorder, and obsessive-compulsive disorder (e.g., Eldomery_2017), however a co-occurring, de novo HIVEP1 variant was also identified in the same individual. This report therefore does not provide unequivocal conclusions about association of the variant with CDK20-Related Disorders. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication was ascertained in the context of this evaluation (PMID: 28327206). ClinVar contains an entry for this variant (Variation ID: 375376). Based on the evidence outlined above, the variant was classified as uncertain significance.
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000416444	SCV000494162	pathogenic	Seizure; Hearing impairment; Compulsive behaviors; Attention deficit hyperactivity disorder		no assertion criteria provided	research	This variant has been identified in an individual with seizures, hearing loss, dysmorphic features, attention deficit hyperactivity disorder, and obsessive compulsive disorder.