Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001280623 | SCV001467851 | likely pathogenic | X-linked severe congenital neutropenia | 2020-12-24 | criteria provided, single submitter | clinical testing | Variant summary: WAS c.869T>C (p.Ile290Thr) results in a non-conservative amino acid change located in the CRIB domain (IPR000095) also reported as the GTPase-binding domain (GBD) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 181214 control chromosomes. c.869T>C has been reported in the literature in individuals affected with features of X-Linked Neutropenia (example, Kobayashi_2018, Arwani_2018, Xia_2019). These data indicate that the variant is likely to be associated with disease. Although X-linked neutropenia is considered a very rare type of severe congenital neutropenia caused by gain of function mutations in the WAS gene, to our knowledge, no variant specific experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Mayo Clinic Laboratories, |
RCV001509118 | SCV001715656 | likely pathogenic | not provided | 2020-10-06 | criteria provided, single submitter | clinical testing | PM2, PS4_moderate, PP1, PP3 |