ClinVar Miner

Submissions for variant NM_001013838.3(CARMIL2):c.1937G>A (p.Arg646Gln)

gnomAD frequency: 0.00014  dbSNP: rs781084120
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001997165 SCV002230849 uncertain significance not provided 2024-01-02 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 646 of the CARMIL2 protein (p.Arg646Gln). This variant is present in population databases (rs781084120, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with CARMIL2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1448554). 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 CARMIL2 protein function with a positive predictive value of 80%. 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV002077348 SCV002496046 uncertain significance Severe combined immunodeficiency due to CARMIL2 deficiency 2021-06-21 criteria provided, single submitter clinical testing CARMIL2 NM_001013838.2 exon 21 p.Arg646Gln (c.1937G>A): This variant has not been reported in the literature but is present in 0.09% (14/15290) of Latino alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/16-67649823-G-A?dataset=gnomad_r3). Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

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