ClinVar Miner

Submissions for variant NM_005026.5(PIK3CD):c.971G>A (p.Arg324His)

gnomAD frequency: 0.00002  dbSNP: rs773473376
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001055228 SCV001219606 uncertain significance Immunodeficiency 14 2023-02-16 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 324 of the PIK3CD protein (p.Arg324His). This variant is present in population databases (rs773473376, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with PIK3CD-related conditions. ClinVar contains an entry for this variant (Variation ID: 850940). 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 PIK3CD 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.
Baylor Genetics RCV001055228 SCV001528327 uncertain significance Immunodeficiency 14 2018-02-27 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Clinical Genomics Laboratory, Washington University in St. Louis RCV001055228 SCV004177082 uncertain significance Immunodeficiency 14 2023-10-12 criteria provided, single submitter clinical testing The PIK3CD c.971G>A (p.Arg324His) variant was identified at a near heterozygous allelic fraction. This variant, to our knowledge, has not been reported in the medical literature. This variant has been reported in the ClinVar database as a germline variant of uncertain significance by two submitters (ClinVar ID: 850940) and in one cancer case as a somatic variant in the cancer database COSMIC (COSMIC ID: COSV63130652). This variant is only observed on 4/152242 alleles in the general population (gnomAD v.3.1.2), indicating it is not a common variant. Computational predictors suggest that the variant does not impact PIK3CD function. Due to limited information, and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of this variant is uncertain at this time.

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