Submissions for variant NM_006904.7(PRKDC):c.9601C>T (p.Pro3201Ser)

gnomAD frequency: 0.00825  dbSNP: rs8178216

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001703568	SCV000517124	likely benign	not provided	2018-09-07	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 24476948)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000548341	SCV000655404	benign	Severe combined immunodeficiency due to DNA-PKcs deficiency	2024-01-29	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000445133	SCV002500355	benign	not specified	2022-03-13	criteria provided, single submitter	clinical testing	Variant summary: PRKDC c.9598C>T (p.Pro3200Ser) (refseq HGVS c.9601C>T, p.Pro3201Ser) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0065 in 243262 control chromosomes in the gnomAD database, including 11 homozygotes. The observed variant frequency is approximately 18 fold of the estimated maximal expected allele frequency for a pathogenic variant in PRKDC causing Severe Combined Immunodeficiency phenotype (0.00035), strongly suggesting that the variant is benign. To our knowledge, no penetrant association or occurrence of c.9598C>T in individuals affected with Severe Combined Immunodeficiency (specifically Immunodeficiency 26, with or without neurologic abnormalities, OMIM 60089) and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
CeGaT Center for Human Genetics Tuebingen	RCV001703568	SCV004157593	benign	not provided	2023-08-01	criteria provided, single submitter	clinical testing	PRKDC: BP4, BS1, BS2
Breakthrough Genomics, Breakthrough Genomics	RCV001703568	SCV005223525	likely benign	not provided		criteria provided, single submitter	not provided
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000445133	SCV001931637	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000445133	SCV001972714	benign	not specified		no assertion criteria provided	clinical testing