ClinVar Miner

Submissions for variant NM_002872.5(RAC2):c.184G>A (p.Glu62Lys)

dbSNP: rs1555908409
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Total submissions: 6
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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, Children's Hospital Los Angeles 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
CeGaT Center for Human Genetics Tuebingen 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, Children's Hospital Los Angeles RCV003156104 SCV003845217 likely pathogenic See cases 2022-12-21 criteria provided, single submitter clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago 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

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