rs1590931704

Description

This variant affects the canonical splice acceptor site of intron 10 and is therefore predicted to alter splicing and exert a loss-of-function effect. A different canonical splice donor site variant in RELA has been reported in an individual with recurrent mucocutaneous ulcers, fever, and elevated inflammatory markers (PMID: 28600438). Family members of the described patient were genotyped and the RELA variant was found to segregate with disease in an autosomal dominant fashion (PMID: 28600438). A separate publication has reported a de novo nonsense variant in a patient with lymphoproliferative disease and autoimmune cytopenias (PMID: 29305315), indicating that the phenotype associated with loss-of-function mutations in RELA may be variable. The c.1034-2A>C variant is absent from the gnomAD population database and is thus presumed to be rare. Analysis of the parental samples was negative for the variant, indicating this variant likely occurred as a de novo event. Based on the available evidence, this variant is classified as a likely pathogenic change.