Submissions for variant NM_032415.7(CARD11):c.139C>A (p.Arg47Ser)

dbSNP: rs1780507453

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002029274	SCV002303960	uncertain significance	Severe combined immunodeficiency due to CARD11 deficiency; BENTA disease	2022-04-06	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 47 of the CARD11 protein (p.Arg47Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CARD11-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant disrupts the p.Arg47 amino acid residue in CARD11. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 30170123; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.