Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV005094492 | SCV001561019 | uncertain significance | not provided | 2024-08-04 | criteria provided, single submitter | clinical testing | This sequence change affects the initiator methionine of the DOCK8 mRNA. The next in-frame methionine is located at codon 69. This variant is present in population databases (rs760902978, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with DOCK8-related conditions. ClinVar contains an entry for this variant (Variation ID: 1056064). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001824958 | SCV002074271 | uncertain significance | not specified | 2022-01-14 | criteria provided, single submitter | clinical testing | Variant summary: DOCK8 c.2T>C (p.Met1?) alters the initiation codon and is predicted to result either in absence of the protein or truncation of the encoded protein due to translation initiation at a downstream codon. The next in-frame methionine is located in exon 3 at codon 69. The gnomAD GTEx v7 dataset shows that the first two exons of the longest transcript (NM_203447.3) are not expressed in several tissues including whole blood and spleen. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.3e-05 in 217964 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2T>C in individuals affected with Severe Combined Immunodeficiency and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter has assessed the variant since 2014, and classified it as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Fulgent Genetics, |
RCV001364837 | SCV002779652 | uncertain significance | Combined immunodeficiency due to DOCK8 deficiency | 2022-04-25 | criteria provided, single submitter | clinical testing |