Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000779160 | SCV000915675 | likely pathogenic | Congenital dyserythropoietic anemia, type I | 2018-10-17 | criteria provided, single submitter | clinical testing | The CDAN1 c.2173C>T (p.Asp725Trp) variant is a missense variant has been reported in at least three studies, in which it is found in a compound heterozygous state in a total of five individuals including two siblings, all diagnosed with congenital dyserythropoietic. This variant has also been reported as p.Asp724Trp (Heimpel et al. 2006; Ahmed et al. 2006; Moreno-Carralero et al. 2018). The p.Asp725Trp variant was absent from 58 controls, but is reported at a frequency of 0.000099 in the European (non-Finnish) population of the Genome Aggregation Database. Based on the evidence, the p.Asp725Trp variant is classified as likely pathogenic for congenital dyserythropoietic anemia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Invitae | RCV002536741 | SCV003442855 | pathogenic | not provided | 2024-01-11 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 725 of the CDAN1 protein (p.Arg725Trp). This variant is present in population databases (rs138334226, gnomAD 0.01%). This missense change has been observed in individuals with congenital dyserythropoietic anemia (PMID: 16141353, 16754775, 28102861, 29901818, 33401150). It has also been observed to segregate with disease in related individuals. This variant is also known as R724W. ClinVar contains an entry for this variant (Variation ID: 632233). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic. |