Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001084351 | SCV000411109 | uncertain significance | T-B+ severe combined immunodeficiency due to JAK3 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000589741 | SCV000695980 | likely benign | not provided | 2016-07-18 | criteria provided, single submitter | clinical testing | Variant summary: The JAK3 c.1929G>A (p.Leu643Leu) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. 4/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE site of SRp40 and SC35. However, these predictions have yet to be confirmed by functional studies. This variant was found in 115/118248 control chromosomes, predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.0016161 (105/64972). This frequency is about 1.5 times greater than the estimated maximal expected allele frequency of a pathogenic JAK3 variant (0.0010801), suggesting this is likely a benign polymorphism found primarily in the populations of European (Non-Finnish) origin. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories. Taken together, this variant is classified as Probable Normal Variant (or Likely Benign). |
| Labcorp Genetics |
RCV001084351 | SCV001013420 | likely benign | T-B+ severe combined immunodeficiency due to JAK3 deficiency | 2025-01-13 | criteria provided, single submitter | clinical testing |