ClinVar Miner

Submissions for variant NM_000536.4(RAG2):c.133G>A (p.Val45Ile)

gnomAD frequency: 0.00002  dbSNP: rs770312622
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001896453 SCV002158961 uncertain significance Combined immunodeficiency with skin granulomas; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive 2022-09-07 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 45 of the RAG2 protein (p.Val45Ile). This variant is present in population databases (rs770312622, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with RAG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1392902). 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 not expected to disrupt RAG2 protein function. 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.
Ambry Genetics RCV004041465 SCV004936074 uncertain significance Inborn genetic diseases 2024-02-17 criteria provided, single submitter clinical testing The c.133G>A (p.V45I) alteration is located in exon 2 (coding exon 1) of the RAG2 gene. This alteration results from a G to A substitution at nucleotide position 133, causing the valine (V) at amino acid position 45 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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