Submissions for variant NM_001366385.1(CARD14):c.1356+4C>T

gnomAD frequency: 0.00031  dbSNP: rs373428751

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000632908	SCV000754113	uncertain significance	Pityriasis rubra pilaris; Psoriasis 2	2024-01-26	criteria provided, single submitter	clinical testing	This sequence change falls in intron 9 of the CARD14 gene. It does not directly change the encoded amino acid sequence of the CARD14 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs373428751, gnomAD 0.07%), and has an allele count higher than expected for a pathogenic variant. This variant has been observed in individual(s) with generalized pustular psoriasis (PMID: 30387497). ClinVar contains an entry for this variant (Variation ID: 527885). 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 is not likely to affect RNA splicing. 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.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002263861	SCV002543218	likely benign	Autoinflammatory syndrome	2021-04-12	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003905695	SCV004718891	likely benign	CARD14-related disorder	2019-07-02	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).