Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001212531 | SCV001384118 | pathogenic | Immunodeficiency, common variable, 2 | 2023-11-14 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 1 of the TNFRSF13B gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in TNFRSF13B are known to be pathogenic (PMID: 16007087, 27123465). This variant is present in population databases (rs760885614, gnomAD 0.006%). Disruption of this splice site has been observed in individual(s) with common variable immunodeficiency (PMID: 19629655). ClinVar contains an entry for this variant (Variation ID: 942527). Studies have shown that disruption of this splice site alters TNFRSF13B gene expression (PMID: 19629655). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Pediatric Infectious Diseases and Immunodeficiencies Unit |
RCV003493823 | SCV004023246 | likely pathogenic | Common variable immunodeficiency | no assertion criteria provided | clinical testing | We found the c.61+2T>A variant in an adult female patient with common variable immunodeficiency (CVID). The variant has a very low frequency in the reference population databases (gnomad v2.1.1 MAF:0.00001). It affects the intron 1 donor splice site causing an aberrantly spliced transcript that lacks exon 2 (exon 2 skipping). We consider the variant Likely Pathogenic. |