8-47799296-C-T

Variant names:

Variant summary

Our verdict is The variant received -5 classification points (ACGS-UK Somatic Oncogenicity v2025). B1_StrongB3_Supporting

The NM_006904.7(PRKDC):c.10211G>A (p.Gly3404Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The gene PRKDC is a tumor suppressor gene (CancerMine: 3 TSG, 11 oncogene, 7 driver citations). The gene PRKDC is a known oncogene (CancerMine: 3 TSG, 11 oncogene, 7 driver citations). The gene PRKDC is a cancer driver gene (CancerMine: 3 TSG, 11 oncogene, 7 driver citations). The variant allele was found at a cumulative frequency of 0.0146 (AC=23,615) in the gnomAD database across 1,613,624 control chromosomes, including 230 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.0189. In-silico predictor (REVEL) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign/Likely Benign (★★). The variant has been observed in cBioPortal in 4 samples across 2 studies and 2 cancer types; somatic enrichment level: SUPPORTING_LOW (Observed in a small number of cBioPortal cases.). This exact variant is curated in the UniProt human variants database as Uncertain Significance; it is also listed as a COSMIC curated somatic variant.

Frequency

Genomes: 𝑓 0.012 ( 20 hom., cov: 32)

Exomes 𝑓: 0.015 ( 210 hom. )

Consequence

PRKDC
NM_006904.7 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.02

Publications

11 publications found

Variant links:

Genes affected

PRKDC (HGNC:9413): (protein kinase, DNA-activated, catalytic subunit) This gene encodes the catalytic subunit of the DNA-dependent protein kinase (DNA-PK). It functions with the Ku70/Ku80 heterodimer protein in DNA double strand break repair and recombination. The protein encoded is a member of the PI3/PI4-kinase family.[provided by RefSeq, Jul 2010]

PRKDC Gene-Disease associations (from GenCC):

severe combined immunodeficiency due to DNA-PKcs deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

PRKDC links:

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new If you want to explore the variant's impact on the transcript NM_006904.7, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 points.

GnomAD effective popmax AF >1% — B1 stand-alone benign; GnomAD effective popmax AF = 0.0189 — exceeds 1% threshold (B1 applied)

Computational evidence does not support a deleterious effect; Missense variant — primary computational scorer does not support an oncogenic/deleterious effect; supports B3

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_006904.7. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKDC	NM_006904.7	MANE Select	c.10211G>A	p.Gly3404Glu	missense	Exon 72 of 86	NP_008835.5
	PRKDC	NM_001081640.2		c.10211G>A	p.Gly3404Glu	missense	Exon 72 of 85	NP_001075109.1	P78527-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRKDC	ENST00000314191.7	TSL:1 MANE Select	c.10211G>A	p.Gly3404Glu	missense	Exon 72 of 86	ENSP00000313420.3	P78527-1
PRKDC	ENST00000338368.7	TSL:1	c.10211G>A	p.Gly3404Glu	missense	Exon 72 of 85	ENSP00000345182.4	P78527-2
PRKDC	ENST00000911724.1		c.10220G>A	p.Gly3407Glu	missense	Exon 72 of 86	ENSP00000581783.1	A0ACI8SJX4

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 6 sources Large-scale international reference populations
GnomAD3 genomes	0.0120	1822	20	152166	32
GnomAD2 exomes	0.0115	2866		248590
GnomAD4 exome	0.0149	21794	210	1461340	30
GnomAD4 genome	0.0120	1821	20	152284	32
TOPMed (Bravo)	0.00980
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	0.0151	4949	56	327150
Local & regional cohorts 7 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	0.0137	32	1	2342
Denmark Genome	0.0367	11		300
ESP6500 (Exome Variant Server)	0.0141	174		12374
GenomeAsia100K	0.00115	4		3478
ToMMo 61KJPN (+60KJPN MNV)	0.00	0	0	122790
Turkish Variome	0.00463	31	0	6702
UK10K	0.0172	130		7562

Showing 13 sources

Case/control cohorts

Cohort	Cases			Controls
Cohort	AF	AC	AN	AF	AC	AN
ASC (Autism)	0.0190 *	207	10906	0.0167 *	290	17390
BipEx (Bipolar disorder (including schizoaffective))	0.0182	517	28418	0.0187	540	28844
Epi25 (Epilepsy)	0.0145	610	41958	0.0148	988	66888
SCHEMA (Schizophrenia)	0.0114	1386	122036	0.0140	2696	192394

Showing 4 cohortsAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Severe combined immunodeficiency due to DNA-PKcs deficiency (2)

not specified (1)

Computational Scores

Algorithm	Calibrated prediction	Prediction	Score
AlphaGenome AVI	Benign	-	7.7
AlphaMissense	Benign	-	0.091
BayesDel_addAF	Benign	T	-0.53
BayesDel_noAF	Benign	-	-0.51
CADD	Benign	-	1.0
DANN	Benign	-	0.26
DEOGEN2	Benign	T	0.043
Eigen	Benign	-	-1.2
Eigen_PC	Benign	-	-1.2
FATHMM_MKL	Benign	N	0.12
FuncVEP CTI	Benign	-	0.00061
GPN-Star LLR	N/A	-	-0.69
GPN-Star score	N/A	-	0.69
LIST_S2	Benign	T	0.54
MetaRNN	Benign	T	0.0057
MetaSVM	Benign	T	-1.1
Mutation Taster	N/A	polymorphism	94/6
MutationAssessor	Benign	L	1.1
PhyloP100	Benign	-	1.0
PrimateAI	Benign	T	0.20
RBP_binding_hub_radar	N/A	-	0.0
RBP_regulation_power_radar	N/A	-	1.8
REVEL	Benign	-	0.18
Sift4G	Benign	T	1.0
Varity_R	N/A	-	0.059
VESM-3B	Benign	-	-5.5

Showing 26 of 26 scores

Splicing Scores

Algorithm	Calibrated prediction	Prediction	Score
Pangolin (max)	Benign	-	0.0
SpliceAI score (max)	Benign	- Details are displayed if max score is > 0.2	0.0

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACGS-UK Somatic Oncogenicity v2025

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Case/control cohorts

ClinVar

Computational Scores

Splicing Scores

Publications

Other links and lift over