Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory of Inherited Metabolic Diseases, |
RCV001787270 | SCV002029102 | uncertain significance | Spondyloepiphyseal dysplasia congenita | 2021-12-04 | criteria provided, single submitter | clinical testing | We decided to re-evaluate clinical significance of the variant. Clinical phenotype of the patient is highly specific to the type 2 collagenopathies group of diseases. However, this variant localized in C-propeptide domain. Various predictive programs put a criterion PM1, believing that this is a well-studied domain. However, studies published to date indicate that further research is required, because pathogenic variants in this domain occur much less frequently than in the triple helix domain. Therefore, we removed the criteria PM1 and PP2, due to insufficient knowledge of this domain. Also, the variant was found in one of the parents with same clinical phenotype and this is not a strong criterion (PP1). Our updated criteria: PM2, PP1, PP3, PP4 according to ACMG it is interpreted like "Uncertain Significance" |