Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
SIB Swiss Institute of Bioinformatics | RCV000684758 | SCV000930068 | likely pathogenic | Severe combined immunodeficiency due to CARMIL2 deficiency | 2019-01-08 | criteria provided, single submitter | curation | This variant is interpreted as a Likely pathogenic for Immunodeficiency 58, autosomal recessive. 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. PP3 : Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PP1 : Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PMID:27896283). PM1 : Located in a mutational hot spot and/or critical and well-established functional domain (e.g., active site of an enzyme) without benign variation. |
Invitae | RCV001861900 | SCV002130452 | uncertain significance | not provided | 2021-11-29 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 565281). This missense change has been observed in individual(s) with clinical features of primary immunodeficiency (PMID: 27896283). This variant is present in population databases (rs775061512, gnomAD 0.01%). This sequence change replaces leucine, which is neutral and non-polar, with histidine, which is basic and polar, at codon 639 of the CARMIL2 protein (p.Leu639His). |
OMIM | RCV000684758 | SCV000812275 | pathogenic | Severe combined immunodeficiency due to CARMIL2 deficiency | 2018-09-28 | no assertion criteria provided | literature only |