Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Neuberg Centre For Genomic Medicine, |
RCV004577225 | SCV005061144 | uncertain significance | Abdominal obesity-metabolic syndrome 3 | criteria provided, single submitter | clinical testing | The missense variant c.1811C>T(p.Pro604Leu) in DYRK1B gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The observed variant has allele frequency of 0.007% in gnomAD exomes database. This variant has not been reported to the ClinVar database. The amino acid change p.Pro604Leu in DYRK1B is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. Multiple lines of computational evidence (Polyphen- benign, SIFT- damaging and MutationTaster- disease causing) predicts a conflicting evidences on protein structure and function for this variant. The amino acid Pro at position 604 is changed to a Leu changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Uncertain Significance (VUS). | |
Ambry Genetics | RCV004621957 | SCV005112219 | uncertain significance | Inborn genetic diseases | 2024-03-15 | criteria provided, single submitter | clinical testing | The c.1811C>T (p.P604L) alteration is located in exon 11 (coding exon 10) of the DYRK1B gene. This alteration results from a C to T substitution at nucleotide position 1811, causing the proline (P) at amino acid position 604 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Prevention |
RCV004747438 | SCV005350683 | uncertain significance | DYRK1B-related disorder | 2024-08-07 | no assertion criteria provided | clinical testing | The DYRK1B c.1811C>T variant is predicted to result in the amino acid substitution p.Pro604Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.047% of alleles in individuals of East Asian descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |