Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV001126490 | SCV004102772 | uncertain significance | T-B+ severe combined immunodeficiency due to JAK3 deficiency | 2023-11-14 | reviewed by expert panel | curation | The c.896T>C (NM_000215.4) variant in JAK3 is a missense variant predicted to cause the substitution of Valine by Alanine at amino acid 299 (p.Val299Ala). The filtering allele frequency (the upper threshold of the 95% CI of 7/24876) of the c.896T>C variant in JAK3 is 0.00002138 for African/African American chromosomes by gnomAD v2.1.1, which is lower than the ClinGen SCID VCEP threshold (<0.000115) for PM2_Supporting, and therefore meets this criterion (PM2_Supporting). To our knowledge, this variant has not been reported in the literature in individuals affected with JAK3-related conditions. In summary, this variant meets the criteria to be classified as Variant of Uncertain Significance for autosomal recessive SCID based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP. Criteria applied: PM2_supporting. ( (VCEP specifications version 1.0). |
| Illumina Laboratory Services, |
RCV001126490 | SCV001285697 | uncertain significance | T-B+ severe combined immunodeficiency due to JAK3 deficiency | 2018-01-13 | 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 |
RCV001126490 | SCV002113857 | likely benign | T-B+ severe combined immunodeficiency due to JAK3 deficiency | 2024-10-29 | criteria provided, single submitter | clinical testing |