Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV002471069 | SCV002769455 | likely pathogenic | Congenital disorder of deglycosylation 1 | 2022-02-02 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.3, this variant is classified as Likely Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with congenital disorder of deglycosylation (MIM#615273). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from arginine to cysteine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0309 - Alternative amino acid changes at the same position have been observed in gnomAD, p.(Arg328Ser) in gnomAD v2 (2 heterozygote(s), 0 homozygotes) and p.(Arg328His) in gnomAD v3 (1 heterozygote, 0 homozygotes). (I) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0600 - Variant is located in the annotated Transglutaminase-like superfamily domain (Pfam). (I) 0704 - Another missense variant comparable to the one identified in this case has limited previous evidence for pathogenicity. The alternative amino acid change p.(Arg328Gly) has been reported homozygous in an individual with NGLY1-CDDG (PMID: 31965062). (SP) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1006 - Clinical laboratory assay shows abnormal function not specific to the gene. Tandem mass spectrometry (MSMS) performed by the Pathology Queensland laboratory on a sample from this patient revealed a biomarker pattern only previously observed in patients with NGLY1-congenital disorder of deglycosylation or aspartylglucosaminuria (PMID: 29550355). (SP) 1102 - Strong phenotype match for this individual. (SP) 1206 - This variant has been shown to be paternally inherited. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Department of Genetics, |
RCV001264673 | SCV001442872 | likely pathogenic | Neurodevelopmental abnormality | 2020-06-04 | no assertion criteria provided | clinical testing |