ClinVar Miner

Submissions for variant NM_032415.7(CARD11):c.2395G>A (p.Asp799Asn)

dbSNP: rs587778152
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002515826 SCV003471526 uncertain significance Severe combined immunodeficiency due to CARD11 deficiency; BENTA disease 2023-12-21 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 799 of the CARD11 protein (p.Asp799Asn). 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. ClinVar contains an entry for this variant (Variation ID: 133798). 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.
ITMI RCV000120449 SCV000084601 not provided not specified 2013-09-19 no assertion provided reference population
Genetic Services Laboratory, University of Chicago RCV000120449 SCV003839310 uncertain significance not specified 2022-08-22 no assertion criteria provided clinical testing DNA sequence analysis of the CARD11 gene demonstrated a sequence change, c.2395G>A, in exon 18 that results in an amino acid change, p.Asp799Asn. This sequence change does not appear to have been previously described in individuals with CARD11-related disorders. This sequence change has been described in the gnomAD database in one individual in the East Asian subpopulation which corresponds to a population frequency of 0.0005% (dbSNP rs587778152). The p.Asp799Asn change affects a moderately conserved amino acid residue located in a domain of the CARD11 protein that is not known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Asp799Asn substitution. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Asp799Asn change remains unknown at this time.

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