rs4278157

Positions:

chr8-47826744-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006904.7(PRKDC):c.8695C>T(p.Arg2899Cys) variant causes a missense change. The variant allele was found at a frequency of 0.044 in 1,612,892 control chromosomes in the GnomAD database, including 1,811 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 105 hom., cov: 33)

Exomes 𝑓: 0.045 ( 1706 hom. )

Consequence

PRKDC
NM_006904.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.22

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:

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=0.002094835).

BP6

Variant 8-47826744-G-A is Benign according to our data. Variant chr8-47826744-G-A is described in ClinVar as [Benign]. Clinvar id is 379649.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-47826744-G-A is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.05 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKDC	NM_006904.7 linkuse as main transcript	c.8695C>T	p.Arg2899Cys	missense_variant	63/86	ENST00000314191.7	NP_008835.5	P78527-1
PRKDC	NM_001081640.2 linkuse as main transcript	c.8695C>T	p.Arg2899Cys	missense_variant	63/85		NP_001075109.1	P78527-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PRKDC	ENST00000314191.7 linkuse as main transcript	c.8695C>T	p.Arg2899Cys	missense_variant	63/86	1	NM_006904.7	ENSP00000313420.3	P78527-1
PRKDC	ENST00000338368.7 linkuse as main transcript	c.8695C>T	p.Arg2899Cys	missense_variant	63/85	1		ENSP00000345182.4	P78527-2
PRKDC	ENST00000697603.1 linkuse as main transcript	c.1372C>T	p.Arg458Cys	missense_variant	10/33			ENSP00000513358.1	A0A8V8TMR1

Frequencies

GnomAD3 genomes

AF:

0.0345

AC:

5248

AN:

152168

Hom.:

105

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00864

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0376

Gnomad ASJ

AF:

0.0855

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00786

Gnomad FIN

AF:

0.0461

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0498

Gnomad OTH

AF:

0.0402

GnomAD3 exomes

AF:

0.0383

AC:

9421

AN:

245970

Hom.:

266

AF XY:

0.0381

AC XY:

5099

AN XY:

133944

show subpopulations

Gnomad AFR exome

AF:

0.00765

Gnomad AMR exome

AF:

0.0256

Gnomad ASJ exome

AF:

0.0896

Gnomad EAS exome

AF:

0.000448

Gnomad SAS exome

AF:

0.00550

Gnomad FIN exome

AF:

0.0472

Gnomad NFE exome

AF:

0.0547

Gnomad OTH exome

AF:

0.0449

GnomAD4 exome

AF:

0.0450

AC:

65714

AN:

1460606

Hom.:

1706

Cov.:

AF XY:

0.0437

AC XY:

31775

AN XY:

726558

show subpopulations

Gnomad4 AFR exome

AF:

0.00828

Gnomad4 AMR exome

AF:

0.0266

Gnomad4 ASJ exome

AF:

0.0920

Gnomad4 EAS exome

AF:

0.000302

Gnomad4 SAS exome

AF:

0.00579

Gnomad4 FIN exome

AF:

0.0484

Gnomad4 NFE exome

AF:

0.0504

Gnomad4 OTH exome

AF:

0.0417

GnomAD4 genome

AF:

0.0344

AC:

5242

AN:

152286

Hom.:

105

Cov.:

AF XY:

0.0334

AC XY:

2485

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00861

Gnomad4 AMR

AF:

0.0375

Gnomad4 ASJ

AF:

0.0855

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00766

Gnomad4 FIN

AF:

0.0461

Gnomad4 NFE

AF:

0.0498

Gnomad4 OTH

AF:

0.0398

Alfa

AF:

0.0470

Hom.:

101

Bravo

AF:

0.0340

TwinsUK

AF:

0.0542

AC:

201

ALSPAC

AF:

0.0516

AC:

199

ESP6500AA

AF:

0.00757

AC:

ESP6500EA

AF:

0.0489

AC:

411

ExAC

AF:

0.0389

AC:

4709

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 22, 2016

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Severe combined immunodeficiency due to DNA-PKcs deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

T;.

Eigen

Benign

0.12

Eigen_PC

Benign

0.082

FATHMM_MKL

Benign

0.70

LIST_S2

Uncertain

0.89

D;D

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.2

L;L

PrimateAI

Benign

0.23

REVEL

Benign

0.11

Sift4G

Uncertain

0.013

D;D

Polyphen

0.93

P;.

Vest4

0.065

MPC

0.23

ClinPred

0.019

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.3

Varity_R

0.097

gMVP

0.19

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