ClinVar Miner

Submissions for variant NM_006904.7(PRKDC):c.2160G>C (p.Gln720His)

dbSNP: rs772649454
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV004061072 SCV002728479 uncertain significance not specified 2022-09-08 criteria provided, single submitter clinical testing The p.Q720H variant (also known as c.2160G>C), located in coding exon 20 of the PRKDC gene, results from a G to C substitution at nucleotide position 2160. The glutamine at codon 720 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV005097983 SCV005776877 uncertain significance Severe combined immunodeficiency due to DNA-PKcs deficiency 2025-01-01 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 720 of the PRKDC protein (p.Gln720His). This variant is present in population databases (rs772649454, gnomAD 0.001%). This variant has not been reported in the literature in individuals affected with PRKDC-related conditions. ClinVar contains an entry for this variant (Variation ID: 1786909). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt PRKDC 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.

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