Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000481952 | SCV000564546 | likely pathogenic | not provided | 2013-09-20 | criteria provided, single submitter | clinical testing | The L107P missense variant in the ADA gene has been reported previously in association with ADA-SCID (Hirschhorn et al., 1990). This variant was also shown to abolish normal protein function. To our knowledge, the c.362+(5_8)delGTGA splice site variant has neither been published as a pathogenic variant, nor reported as a benign polymorphism. This variant was not observed in approximately 6,500 individuals of European and African American ancestry in the an external variant database, indicating it is not a common benign variant in these populations. Multiple in silico splice algorithms predict that this variant abolishes the normal splice donor site in intron 4, which would cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. Therefore, c.362+(5_8)delGTGA is a strong candidate for a pathogenic variant, however the possibility that it is a benign variant cannot be excluded. |
| Baylor Genetics | RCV003476147 | SCV004213500 | likely pathogenic | Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency | 2023-04-04 | criteria provided, single submitter | clinical testing |