Submissions for variant NM_032415.7(CARD11):c.2703G>A (p.Gln901=)

dbSNP: rs1242710789

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002023313	SCV002305369	uncertain significance	Severe combined immunodeficiency due to CARD11 deficiency; BENTA disease	2022-07-19	criteria provided, single submitter	clinical testing	This sequence change affects codon 901 of the CARD11 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the CARD11 protein. This variant also falls at the last nucleotide of exon 20, which is part of the consensus splice site for this exon. This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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: 1513008). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.