rs7830743

Positions:

chr8-47798394-A-G

Variant summary

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

The NM_006904.7(PRKDC):c.10301T>C(p.Ile3434Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0775 in 1,593,232 control chromosomes in the GnomAD database, including 8,905 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 0.13 ( 2189 hom., cov: 32)

Exomes 𝑓: 0.072 ( 6716 hom. )

Consequence

PRKDC
NM_006904.7 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.231

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=0.0017988086).

BP6

Variant 8-47798394-A-G is Benign according to our data. Variant chr8-47798394-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 379415.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.267 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.10301T>C	p.Ile3434Thr	missense_variant	73/86	ENST00000314191.7	NP_008835.5	P78527-1
PRKDC	NM_001081640.2 linkuse as main transcript	c.10301T>C	p.Ile3434Thr	missense_variant	73/85		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.10301T>C	p.Ile3434Thr	missense_variant	73/86	1	NM_006904.7	ENSP00000313420.3	P78527-1
PRKDC	ENST00000338368.7 linkuse as main transcript	c.10301T>C	p.Ile3434Thr	missense_variant	73/85	1		ENSP00000345182.4	P78527-2
PRKDC	ENST00000697603.1 linkuse as main transcript	c.2978T>C	p.Ile993Thr	missense_variant	20/33			ENSP00000513358.1	A0A8V8TMR1
PRKDC	ENST00000697602.1 linkuse as main transcript	n.874T>C		non_coding_transcript_exon_variant	5/18

Frequencies

GnomAD3 genomes

AF:

0.133

AC:

20257

AN:

152122

Hom.:

2188

Cov.:

show subpopulations

Gnomad AFR

AF:

0.272

Gnomad AMI

AF:

0.192

Gnomad AMR

AF:

0.213

Gnomad ASJ

AF:

0.0910

Gnomad EAS

AF:

0.0838

Gnomad SAS

AF:

0.165

Gnomad FIN

AF:

0.0322

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0496

Gnomad OTH

AF:

0.135

GnomAD3 exomes

AF:

0.119

AC:

27068

AN:

226646

Hom.:

3007

AF XY:

0.112

AC XY:

13704

AN XY:

122680

show subpopulations

Gnomad AFR exome

AF:

0.281

Gnomad AMR exome

AF:

0.325

Gnomad ASJ exome

AF:

0.0935

Gnomad EAS exome

AF:

0.0689

Gnomad SAS exome

AF:

0.165

Gnomad FIN exome

AF:

0.0388

Gnomad NFE exome

AF:

0.0542

Gnomad OTH exome

AF:

0.0990

GnomAD4 exome

AF:

0.0716

AC:

103208

AN:

1440992

Hom.:

6716

Cov.:

AF XY:

0.0728

AC XY:

52116

AN XY:

715512

show subpopulations

Gnomad4 AFR exome

AF:

0.289

Gnomad4 AMR exome

AF:

0.306

Gnomad4 ASJ exome

AF:

0.0923

Gnomad4 EAS exome

AF:

0.0884

Gnomad4 SAS exome

AF:

0.156

Gnomad4 FIN exome

AF:

0.0387

Gnomad4 NFE exome

AF:

0.0500

Gnomad4 OTH exome

AF:

0.0861

GnomAD4 genome

AF:

0.133

AC:

20284

AN:

152240

Hom.:

2189

Cov.:

AF XY:

0.133

AC XY:

9914

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.272

Gnomad4 AMR

AF:

0.213

Gnomad4 ASJ

AF:

0.0910

Gnomad4 EAS

AF:

0.0840

Gnomad4 SAS

AF:

0.164

Gnomad4 FIN

AF:

0.0322

Gnomad4 NFE

AF:

0.0496

Gnomad4 OTH

AF:

0.137

Alfa

AF:

0.0776

Hom.:

1334

Bravo

AF:

0.158

TwinsUK

AF:

0.0520

AC:

193

ALSPAC

AF:

0.0496

AC:

191

ESP6500AA

AF:

0.261

AC:

975

ESP6500EA

AF:

0.0568

AC:

467

ExAC

AF:

0.115

AC:

13833

Asia WGS

AF:

0.144

AC:

501

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 03, 2021	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 05, 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. -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 42% of patients studied by a panel of primary immunodeficiencies. Number of patients: 40. Only high quality variants are reported. -

not provided

Benign:1

Likely 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

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.045

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.042

DANN

Benign

0.23

DEOGEN2

Benign

0.040

T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.34

T;T

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.40

N;N

PrimateAI

Benign

0.27

REVEL

Benign

0.075

Sift4G

Benign

0.50

T;T

Polyphen

0.0

B;.

Vest4

0.0070

MPC

0.21

ClinPred

0.0021

GERP RS

-7.7

Varity_R

0.039

gMVP

0.048

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