Submissions for variant NM_000536.4(RAG2):c.539C>A (p.Pro180His)

dbSNP: rs1064793251

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000481067	SCV000565479	likely pathogenic	not provided	2014-01-02	criteria provided, single submitter	clinical testing	A novel P180H missense change likely associated with RAG2 deficiency was identified. To our knowledge, this variant has neither been published as pathogenic, nor reported as a benign polymorphism. This missense change was not observed in approximately 6,500 individuals of European and African American ancestry in an external variant database, indicating it is not a common benign variant in these populations. P180H represents a non-conservative amino acid substitution as a non-polar Proline reside that contains a unique ring structure is replaced with a large, positively-charged Histidine residue. This substitution occurs at a position in the RAG2 protein that is highly conserved among species. Therefore, P180H is a strong candidate for a pathogenic variant; however, the possibility that it is a benign variant cannot be excluded.
Pediatric Immunology Service, The Chaim Sheba Medical Center at Tel HaShomer	RCV000681583	SCV000693931	pathogenic	Atypical severe combined immunodeficiency due to complete RAG1/2 deficiency; Recombinase activating gene 2 deficiency; Inborn error of immunity	2018-03-06	criteria provided, single submitter	research