Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001097794 | SCV001254108 | uncertain significance | MHC class II deficiency | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Labcorp Genetics |
RCV001097794 | SCV001377864 | uncertain significance | MHC class II deficiency | 2022-08-16 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 145 of the RFX5 protein (p.Asp145His). This variant is present in population databases (no rsID available, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with RFX5-related conditions. ClinVar contains an entry for this variant (Variation ID: 874651). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Genome- |
RCV001097794 | SCV004049766 | uncertain significance | MHC class II deficiency | 2023-04-11 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004782649 | SCV005395443 | uncertain significance | not specified | 2024-09-18 | criteria provided, single submitter | clinical testing | Variant summary: RFX5 c.433G>C (p.Asp145His) results in a non-conservative amino acid change located in the DNA-binding RFX-type winged-helix domain (IPR003150) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.2e-05 in 251452 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.433G>C has been reported in the literature in individuals affected with Bare Lymphocyte Syndrome 2 - RFX5 Related. These report(s) do not provide unequivocal conclusions about association of the variant with Bare Lymphocyte Syndrome 2 - RFX5 Related. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. ClinVar contains an entry for this variant (Variation ID: 874651). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| OMIM | RCV004564580 | SCV005045503 | pathogenic | MHC class II deficiency 3 | 2024-05-23 | no assertion criteria provided | literature only |