Submissions for variant NM_032415.7(CARD11):c.2564G>A (p.Arg855Gln)

gnomAD frequency: 0.00001  dbSNP: rs928782717

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002048379	SCV002306053	uncertain significance	Severe combined immunodeficiency due to CARD11 deficiency; BENTA disease	2024-01-20	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 855 of the CARD11 protein (p.Arg855Gln). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with CARD11-related conditions. ClinVar contains an entry for this variant (Variation ID: 1514913). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CARD11 protein function. 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.
Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn	RCV004793706	SCV005414376	uncertain significance	BENTA disease; Immunodeficiency 11b with atopic dermatitis	2022-08-16	criteria provided, single submitter	clinical testing