Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
SIB Swiss Institute of Bioinformatics | RCV000722132 | SCV000899137 | pathogenic | Immunodeficiency 15a | 2018-12-13 | criteria provided, single submitter | curation | This variant is interpreted as a Pathogenic for Immunodeficiency 15A, autosomal dominant. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PS3 => Well-established functional studies show a deleterious effect (PMID:30337470). PP1 => Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PMID:30337470). PM6-Strong => PM6 upgraded in strength to Strong (PMID:30337470). |
Labcorp Genetics |
RCV003744629 | SCV004551626 | pathogenic | Severe combined immunodeficiency due to IKK2 deficiency | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 203 of the IKBKB protein (p.Val203Ile). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of anhidrotic ectodermodysplasia with immunodeficiency (PMID: 30337470). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 590941). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects IKBKB function (PMID: 30337470). For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV000722132 | SCV000853307 | pathogenic | Immunodeficiency 15a | 2018-11-28 | no assertion criteria provided | literature only |