Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV001270830 | SCV001451597 | likely pathogenic | Schinzel-Giedion syndrome | 2019-08-12 | criteria provided, single submitter | clinical testing | The SETBP1 c.2561C>A (p.Ser854Tyr) variant is a missense variant. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. This variant is not found in the Genome Aggregation Database in a region of good sequencing coverage, so the variant is presumed to be rare. The variant is located in exon 4, in the SKI homologous region, a domain that has been identified as a mutational hotspot associated with Schinzel-Giedion syndrome (Carvalho et al. 2015). Based on the identification of the variant in a de novo state, its location in a mutational hotspot, and its absence from the population databases, the p.Ser854Tyr variant is classified as likely pathogenic for Schinzel-Giedion syndrome. |
Ambry Genetics | RCV003353268 | SCV004072571 | uncertain significance | Inborn genetic diseases | 2023-07-17 | criteria provided, single submitter | clinical testing | The c.2561C>A (p.S854Y) alteration is located in exon 4 (coding exon 3) of the SETBP1 gene. This alteration results from a C to A substitution at nucleotide position 2561, causing the serine (S) at amino acid position 854 to be replaced by a tyrosine (Y). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Another alteration at the same codon, c.2561C>G (p.S854C), has been detected in at least one individual with nephrocalcinosis, velopharyngeal insufficiency, joint hypermobility, widely spaced teeth, developmental delays/intellectual disability (Deciphering Developmental Disorders, 2015). This amino acid position is highly conserved in available vertebrate species. This alteration is predicted to be deleterious by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |