Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000541785 | SCV000639579 | pathogenic | Neutrophil immunodeficiency syndrome | 2022-05-31 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects RAC2 function (PMID: 30723080). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt RAC2 protein function. ClinVar contains an entry for this variant (Variation ID: 464885). This missense change has been observed in individual(s) with autosomal dominant combined immunodeficiency (PMID: 30723080; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 62 of the RAC2 protein (p.Glu62Lys). |
Center for Personalized Medicine, |
RCV000735310 | SCV000854463 | likely pathogenic | Severe combined immunodeficiency disease; Immunodeficiency; Lymphopenia; Abnormal cellular immune system morphology; Abnormality of T cell physiology; Combined immunodeficiency | criteria provided, single submitter | clinical testing | ||
Ce |
RCV001092009 | SCV001248337 | pathogenic | not provided | 2023-06-01 | criteria provided, single submitter | clinical testing | RAC2: PS2:Very Strong, PM2, PS4:Moderate, PP3, PS3:Supporting |
Center for Personalized Medicine, |
RCV003156104 | SCV003845217 | likely pathogenic | See cases | 2022-12-21 | criteria provided, single submitter | clinical testing | |
Center for Genomics, |
RCV003224325 | SCV003920373 | pathogenic | Neutrophil immunodeficiency syndrome; Immunodeficiency 73b with defective neutrophil chemotaxis and lymphopenia; Immunodeficiency 73c with defective neutrophil chemotaxis and hypogammaglobulinemia | 2021-11-23 | criteria provided, single submitter | clinical testing | RAC2:NM_002872:exon3, p.Glu62Lys (c.184G>A): This variant has been reported in 1 individual with suspected Combined Immune Deficiency (CID) as de novo (Hsu 2016) and is not present in large control databases. Furthermore, it is a de novo variant in this child, and evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is highly suspicious for disease, but requires further evidence for pathogenicity. Therefore, this variant classified as likely pathogenic. |
OMIM | RCV001254813 | SCV001430922 | pathogenic | Immunodeficiency 73b with defective neutrophil chemotaxis and lymphopenia | 2020-08-24 | no assertion criteria provided | literature only |