Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001043041 | SCV001206752 | pathogenic | Immunodeficiency, common variable, 2 | 2024-12-05 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Cys66*) in the TNFRSF13B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TNFRSF13B are known to be pathogenic (PMID: 16007087, 27123465). This variant is present in population databases (rs144718007, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with TNFRSF13B-related conditions. ClinVar contains an entry for this variant (Variation ID: 840923). For these reasons, this variant has been classified as Pathogenic. |
| Institute of Human Genetics Munich, |
RCV001254048 | SCV001429954 | pathogenic | Immunoglobulin A deficiency 2 | 2020-03-02 | criteria provided, single submitter | clinical testing | |
| 3billion, |
RCV001043041 | SCV002573177 | pathogenic | Immunodeficiency, common variable, 2 | 2022-09-01 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.003%). Stop-gained (nonsense) is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic without evidence for the classification (ClinVar ID: VCV000840923). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. |
| Victorian Clinical Genetics Services, |
RCV001043041 | SCV005398060 | pathogenic | Immunodeficiency, common variable, 2 | 2024-09-21 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with common variable immunodeficiency 2 (MIM#240500) and immunoglobulin A deficiency 2 (MIM#609529). (I) 0108 - This gene is associated with both recessive and dominant disease (OMIM). (I) 0112 - The condition associated with this gene has incomplete penetrance. Asymptomatic individuals with monoallelic or biallelic variants have been reported (PMIDs: 34210994, 34441032). (I) 0115 - Variants in this gene are known to have variable expressivity (PMID: 34210994). (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 (v3: 7 heterozygotes, 0 homozygotes). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. Many NMD-predicted variants have previously been reported as pathogenic in patients with TNFRSF13B-related features (DECIPHER). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported in six individuals (four heterozygotes, one homozygote and one unspecified) with TNFRSF13B-related features (ClinVar, PMIDs: 27123465, 33046446, 34787773). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |