Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Neuberg Centre For Genomic Medicine, |
RCV000008082 | SCV005439008 | likely pathogenic | Bruck syndrome 2 | 2023-07-22 | criteria provided, single submitter | clinical testing | The missense c.1856G>A p.Arg619His variant in PLOD2 gene has been reported previously in homozygous state in multiple individuals affected with Bruck syndrome Ha-Vinh et al., 2004; Puig-Hervás et al., 2012; Caparros-Martin et al., 2016; Mumm et al., 2020; Wang et al., 2022. This variant has also been previously identified in homozygous state in proband and heterozygous state in parents and sisters Ha-Vinh et al., 2004; Wang et al., 2022. The p.Arg619His variant is present with allele frequency of 0.001% in gnomAD Exomes. This variant has been submitted to the ClinVar database as Uncertain Significance / Pathogenic. Multiple lines of computational evidence Polyphen - Probably Damaging, SIFT - Damaging and MutationTaster - Disease causing predict a damaging effect on protein structure and function for this variant. The reference amino acid at this position in PLOD2 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. TThe amino acid Arg at position 619 is changed to a His changing protein sequence and it might alter its composition and physico-chemical properties. However, additional functional studies will be required to prove the pathogenicity of this variant. For these reasons, this variant has been classified as Likely Pathogenic. |
| OMIM | RCV000008082 | SCV000028287 | pathogenic | Bruck syndrome 2 | 2004-12-01 | no assertion criteria provided | literature only | |
| Department of Traditional Chinese Medicine, |
RCV000008082 | SCV001837654 | uncertain significance | Bruck syndrome 2 | no assertion criteria provided | research |