Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV002272960 | SCV002557456 | likely pathogenic | Meester-Loeys syndrome | 2022-02-02 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as likely pathogenic. The following criteria are met: 0102 - Loss of function is mechanism of disease in this gene and is associated with Meester-Loeys syndrome (MIM#300989) and X-linked spondyloepimetaphyseal dysplasia (MIM#300106). (I) 0109 - This gene is associated with X-linked recessive disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (v3) (1 heterozygote, 0 homozygotes, 0 hemizygotes). (SP) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 0702 - Other NMD-predicted variants comparable to the one identified in this case have strong previous evidence for pathogenicity. At least three other premature termination codon variants have previously been reported as disease causing, in addition to two copy number variants (CNV) affecting all the coding exons of the gene (exon 2-8) (ClinVar; PMID: 27632686). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Labcorp Genetics |
RCV003096143 | SCV003260002 | pathogenic | not provided | 2023-07-21 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln75*) in the BGN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BGN are known to be pathogenic (PMID: 17502576, 27632686). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1699103). This variant has not been reported in the literature in individuals affected with BGN-related conditions. This variant is not present in population databases (gnomAD no frequency). |
| Centre of Medical Genetics, |
RCV002272960 | SCV004170964 | likely pathogenic | Meester-Loeys syndrome | 2023-10-20 | criteria provided, single submitter | research |