Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000665110 | SCV000789176 | likely pathogenic | Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency | 2017-01-16 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000665110 | SCV001576764 | likely pathogenic | Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency | 2020-03-18 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ADA are known to be pathogenic (PMID: 26255240, 26376800). Disruption of this splice site has been observed in an individual affected with clinical features of severe combined immunodeficiency (Invitae). ClinVar contains an entry for this variant (Variation ID: 550379). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 3 of the ADA gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |