Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000914387 | SCV001059561 | benign | X-linked agammaglobulinemia with growth hormone deficiency | 2024-01-23 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000990917 | SCV001141970 | likely benign | X-linked agammaglobulinemia | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV001818852 | SCV002069409 | benign | not specified | 2021-09-13 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003902932 | SCV004722903 | likely benign | BTK-related condition | 2023-03-20 | criteria provided, single submitter | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |
Pediatric Infectious Diseases and Immunodeficiencies Unit |
RCV003768811 | SCV004022316 | likely risk allele | Common variable immunodeficiency | no assertion criteria provided | clinical testing | This variant has been reported to be a minimally hypomorphic mutation in BTK resulting in reduced B cell numbers but no clinical disease (PMID: 18241230). In a patient with XLA carrying the p.Tyr418His variant, BTK expression has been studied showing a reduced expression compared to healthy controls (PMID: 11472359). We found the variant in an adult female patient with a clinical diagnosis of common variable immunodeficiency (CVID). The patient had skewed X chromosome inactivation in which the His418 allele (alternative allele) was predominantly expressed. The allele frequency of the variant is 0.0002685 (gnomad v3.2.1), greater than expected to be causing X-linked Agammaglobulinemia (OMIM: 300755). That's the reason why this variant may be considered Likely Benign for XLA. However, based on the reported functional evidence of this variant it can be considered as a risk allele for CVID and eventually for XLA. |