Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
3billion | RCV003153166 | SCV003842015 | likely pathogenic | Pseudoachondroplastic spondyloepiphyseal dysplasia syndrome | 2023-02-23 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.88; 3Cnet: 0.93). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with COMP related disorder (PMID: 26377240). However, the evidence of pathogenicity is insufficient at this time. Different missense changes at the same codon (p.Asp439Asn, p.Asp439Glu, p.Asp439Tyr) have been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000692028, VCV000803548, VCV001066197). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. |