Submissions for variant NM_006904.7(PRKDC):c.5107A>G (p.Thr1703Ala)

gnomAD frequency: 0.00009  dbSNP: rs376188635

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001306611	SCV001495991	uncertain significance	Severe combined immunodeficiency due to DNA-PKcs deficiency	2022-10-05	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 1703 of the PRKDC protein (p.Thr1703Ala). This variant is present in population databases (rs376188635, gnomAD 0.2%). 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: 1009162). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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	RCV001306611	SCV003920355	uncertain significance	Severe combined immunodeficiency due to DNA-PKcs deficiency	2022-07-12	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF 0.01% (3/15262) (https://gnomad.broadinstitute.org/variant/8-47879619-T-C?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:1009162). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.