rs8178225

Positions:

chr8-47799296-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006904.7(PRKDC):c.10211G>A(p.Gly3404Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0146 in 1,613,624 control chromosomes in the GnomAD database, including 230 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

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

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 links:

PRKDC (HGNC:):

PRKDC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0056900084).

BP6

Variant 8-47799296-C-T is Benign according to our data. Variant chr8-47799296-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 379650.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.012 (1821/152284) while in subpopulation NFE AF= 0.0198 (1348/68026). AF 95% confidence interval is 0.0189. There are 20 homozygotes in gnomad4. There are 916 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKDC	NM_006904.7 linkuse as main transcript	c.10211G>A	p.Gly3404Glu	missense_variant	72/86	ENST00000314191.7	NP_008835.5	P78527-1
PRKDC	NM_001081640.2 linkuse as main transcript	c.10211G>A	p.Gly3404Glu	missense_variant	72/85		NP_001075109.1	P78527-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKDC	ENST00000314191.7 linkuse as main transcript	c.10211G>A	p.Gly3404Glu	missense_variant	72/86	1	NM_006904.7	ENSP00000313420.3		P78527-1

Frequencies

GnomAD3 genomes

AF:

0.0120

AC:

1822

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00263

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00589

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.0233

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0198

Gnomad OTH

AF:

0.00716

GnomAD3 exomes

AF:

0.0115

AC:

2866

AN:

248590

Hom.:

AF XY:

0.0111

AC XY:

1494

AN XY:

134872

show subpopulations

Gnomad AFR exome

AF:

0.00258

Gnomad AMR exome

AF:

0.00527

Gnomad ASJ exome

AF:

0.00249

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000948

Gnomad FIN exome

AF:

0.0238

Gnomad NFE exome

AF:

0.0180

Gnomad OTH exome

AF:

0.00927

GnomAD4 exome

AF:

0.0149

AC:

21794

AN:

1461340

Hom.:

210

Cov.:

AF XY:

0.0144

AC XY:

10492

AN XY:

726952

show subpopulations

Gnomad4 AFR exome

AF:

0.00233

Gnomad4 AMR exome

AF:

0.00572

Gnomad4 ASJ exome

AF:

0.00230

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00110

Gnomad4 FIN exome

AF:

0.0257

Gnomad4 NFE exome

AF:

0.0172

Gnomad4 OTH exome

AF:

0.0137

GnomAD4 genome

AF:

0.0120

AC:

1821

AN:

152284

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

916

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00262

Gnomad4 AMR

AF:

0.00589

Gnomad4 ASJ

AF:

0.00260

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.0233

Gnomad4 NFE

AF:

0.0198

Gnomad4 OTH

AF:

0.00709

Alfa

AF:

0.0160

Hom.:

Bravo

AF:

0.00980

TwinsUK

AF:

0.0183

AC:

ALSPAC

AF:

0.0161

AC:

ESP6500AA

AF:

0.00299

AC:

ESP6500EA

AF:

0.0194

AC:

162

ExAC

AF:

0.0117

AC:

1412

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0150

EpiControl

AF:

0.0161

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Severe combined immunodeficiency due to DNA-PKcs deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Feb 05, 2021	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 12, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.51

CADD

Benign

1.0

DANN

Benign

0.26

DEOGEN2

Benign

0.043

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.54

T;T

MetaRNN

Benign

0.0057

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;L

PrimateAI

Benign

0.20

REVEL

Benign

0.18

Sift4G

Benign

1.0

T;T

Polyphen

0.0010

B;.

Vest4

0.056

MPC

0.21

ClinPred

0.0024

GERP RS

-2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.059

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over