Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000796674 | SCV000936197 | likely pathogenic | MHC class II deficiency | 2024-09-19 | criteria provided, single submitter | clinical testing | This variant results in the deletion of part of exon 6 (c.419_438+38del) of the RFXANK 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 RFXANK are known to be pathogenic (PMID: 10803838, 16166641, 21908431). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has been observed in individual(s) with MHC class II deficiency (PMID: 9806546). ClinVar contains an entry for this variant (Variation ID: 643059). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
OMIM | RCV004576969 | SCV000027173 | pathogenic | MHC class II deficiency 2 | 1998-11-01 | no assertion criteria provided | literature only | |
Prevention |
RCV003411751 | SCV004106334 | likely pathogenic | RFXANK-related disorder | 2023-12-08 | no assertion criteria provided | clinical testing | The RFXANK c.419_438+38del58 variant is predicted to result in a deletion affecting a canonical splice site. This variant has been reported in individuals with major histocompatibility class II deficiency, also referred to as bare lymphocyte syndrome, complementation group B (Masternak et al. 1998. PubMed ID: 9806546; Supplemental Table 3, Farwell et al. 2014. PubMed ID: 25356970). This variant is reported in 0.0023% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Frameshift variants in RFXANK are expected to be pathogenic. This variant is interpreted as likely pathogenic. |