ClinVar Miner

Submissions for variant NM_203447.4(DOCK8):c.2594T>C (p.Val865Ala)

gnomAD frequency: 0.00010  dbSNP: rs373018701
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000818083 SCV000958678 uncertain significance Combined immunodeficiency due to DOCK8 deficiency 2022-10-05 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 865 of the DOCK8 protein (p.Val865Ala). This variant is present in population databases (rs373018701, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with DOCK8-related conditions. ClinVar contains an entry for this variant (Variation ID: 660804). 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 DOCK8 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000818083 SCV002496100 uncertain significance Combined immunodeficiency due to DOCK8 deficiency 2021-03-18 criteria provided, single submitter clinical testing DOCK8 NM_203447.3 exon 21 p.Val865Ala (c.2594T>C): This variant has not been reported in the literature but is present in 0.04% (7/15286) of Latino alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/9-379924-T-C?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:660804). This variant amino acid Alanine (Ala) is present in 7 mammals and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Fulgent Genetics, Fulgent Genetics RCV000818083 SCV005677337 uncertain significance Combined immunodeficiency due to DOCK8 deficiency 2024-03-12 criteria provided, single submitter clinical testing

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