Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
St. |
RCV005055287 | SCV005689117 | likely pathogenic | Radioulnar synostosis with amegakaryocytic thrombocytopenia 2 | 2024-07-03 | criteria provided, single submitter | clinical testing | The MECOM c.2467G>A (p.Glu823Lys) missense change is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge, functional studies have not been performed. This variant is located in the zinc finger domain/region where other MECOM deleterious variants have been reported (PMID: 29519864; 26581901, 29146883, 29540340). In one family, this variant was found to segregate in multiple affected individuals with radioulnar synostosis, including one individual who presented with thrombocytopenia (PMID: 29519864). The variant is also known as NM_001105078.4:c.2272G>A (p.Glu758Lys). In summary, this variant meets criteria to be classified as likely pathogenic. |