ClinVar Miner

Submissions for variant NM_032415.7(CARD11):c.220+1G>A

dbSNP: rs1554276623
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000579340 SCV000681265 pathogenic not provided 2017-12-19 criteria provided, single submitter clinical testing The c.220+1G>A variant in the CARD11 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This splice site variant destroys the canonical splice donor site in intron 3. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.220+1G>Avariant is not observed in large population cohorts (Lek et al., 2016). We interpret c.220+1G>A as a pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV003767257 SCV004585928 uncertain significance Severe combined immunodeficiency due to CARD11 deficiency; BENTA disease 2023-04-22 criteria provided, single submitter clinical testing Studies have shown that disruption of this splice site is associated with altered splicing resulting in in-frame exon 3 skipping (PMID: 33202260). ClinVar contains an entry for this variant (Variation ID: 489270). Disruption of this splice site has been observed in individual(s) with clinical features of CARD11-associated atopy with dominant interference of NF-kB signaling (PMID: 33202260). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 3 of the CARD11 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CARD11 are known to be pathogenic (PMID: 23374270, 23561803, 26289640). 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.
University of Washington Center for Mendelian Genomics, University of Washington RCV001543392 SCV001761950 likely pathogenic Immunodeficiency 11b with atopic dermatitis no assertion criteria provided research

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