Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV000032181 | SCV000807287 | uncertain significance | Koolen-de Vries syndrome | 2017-09-01 | criteria provided, single submitter | clinical testing | Likely pathogenicity based on finding it twice in our laboratory: in a 7-year-old male with intellectual disability, dysmorphisms, short stature, strabismus, asymmetric prominent ventricles, possible undermylination, amygdala/hippocampal dysgenesis; in a 3-year-old feale with global delays, hypotonia, dysmorphisms, short stature, microcephaly, congenital heart disease, brain & eye anomalies. However, inheritance was not determined, and of note, the promoter and 5' exons of KANSL1 can be partially duplicated in some individuals. Exome and Sanger data could not distinguish if this change is located in the real KANSL1 gene or the duplicated copy of the gene |
| Mendelics | RCV000032181 | SCV002516587 | pathogenic | Koolen-de Vries syndrome | 2022-05-04 | criteria provided, single submitter | clinical testing | |
| Genomic Medicine, |
RCV000032181 | SCV005061832 | benign | Koolen-de Vries syndrome | 2024-06-25 | criteria provided, single submitter | clinical testing | Inherited from healthy father. Patient lacking Koolen-de Vries syndrome (KdVS) phenotype. By cDNA analysis, it has been demonstrated that the variant involves a non-functional KANSL1 pseudogene that can be found in some structural haplotypes (PMID: 22751100, PMID: 22751096, PMID: 33050294). IMPORTANT: this variant has been classified as benign in this case because it affects neither functional allele of the KANSL1 gene. it, instead, involves a duplicated genomic region that includes the first two (or three) exons of the KANSL1 transcript NM_015443.4. On the contrary, it should have been considered pathogenic if it was mapped within either functional copy of the KANSL1 gene (PMID: 26306646). It is not possible to define if the variant affects the duplicated region or the functional KANSL1 gene sequence solely on the basis of genomic DNA sequencing results. This variant is reported in the gnomAD database v4.1.0 with a frequency of 0.000005085 in non-Finnish European population (6 out of 1180044 alleles) and of 0.0002702 (8 out of 29606 alleles) in Ashkenazi Jewish population. We expect it is mismapped in those subjects (who are supposed not to be affected by KdVS) and involves the polymorphic duplication of KANSL1 exon 2. |
| Gene |
RCV000032181 | SCV000055765 | not provided | Koolen-de Vries syndrome | no assertion provided | literature only | ||
| OMIM | RCV000032181 | SCV000677104 | pathogenic | Koolen-de Vries syndrome | 2024-10-02 | no assertion criteria provided | literature only |