ClinVar Miner

Submissions for variant NM_006904.7(PRKDC):c.2873T>C (p.Met958Thr)

gnomAD frequency: 0.00001  dbSNP: rs1270327485
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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 RCV004062484 SCV002747080 uncertain significance not specified 2021-06-23 criteria provided, single submitter clinical testing The p.M958T variant (also known as c.2873T>C), located in coding exon 25 of the PRKDC gene, results from a T to C substitution at nucleotide position 2873. The methionine at codon 958 is replaced by threonine, an amino acid with 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 RCV003748447 SCV004453941 uncertain significance Severe combined immunodeficiency due to DNA-PKcs deficiency 2024-04-04 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 958 of the PRKDC protein (p.Met958Thr). This variant is present in population databases (no rsID available, gnomAD 0.007%). 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: 1797074). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PRKDC 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.

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