rs8177999

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_006904.7(PRKDC):c.16G>T(p.Ala6Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0058 in 1,504,624 control chromosomes in the GnomAD database, including 352 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 216 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 136 hom. )

Consequence

PRKDC
NM_006904.7 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.301

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=0.0014592409).

BP6

Variant 8-47960111-C-A is Benign according to our data. Variant chr8-47960111-C-A is described in ClinVar as [Benign]. Clinvar id is 379772.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKDC	NM_006904.7 link	c.16G>T	p.Ala6Ser	missense_variant	Exon 1 of 86	ENST00000314191.7	NP_008835.5	P78527-1
PRKDC	NM_001081640.2 link	c.16G>T	p.Ala6Ser	missense_variant	Exon 1 of 85		NP_001075109.1	P78527-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PRKDC	ENST00000314191.7 link	c.16G>T	p.Ala6Ser	missense_variant	Exon 1 of 86	1	NM_006904.7	ENSP00000313420.3	P78527-1
PRKDC	ENST00000338368.7 link	c.16G>T	p.Ala6Ser	missense_variant	Exon 1 of 85	1		ENSP00000345182.4	P78527-2
PRKDC	ENST00000697591.1 link	n.57G>T		non_coding_transcript_exon_variant	Exon 1 of 15

Frequencies

GnomAD3 genomes

AF:

0.0284

AC:

4328

AN:

152168

Hom.:

216

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0972

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00857

Gnomad ASJ

AF:

0.0202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.0272

GnomAD3 exomes

AF:

0.00550

AC:

585

AN:

106398

Hom.:

AF XY:

0.00463

AC XY:

274

AN XY:

59214

show subpopulations

Gnomad AFR exome

AF:

0.131

Gnomad AMR exome

AF:

0.00399

Gnomad ASJ exome

AF:

0.0208

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000350

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000738

Gnomad OTH exome

AF:

0.00576

GnomAD4 exome

AF:

0.00324

AC:

4379

AN:

1352344

Hom.:

136

Cov.:

AF XY:

0.00299

AC XY:

1991

AN XY:

664850

show subpopulations

Gnomad4 AFR exome

AF:

0.0961

Gnomad4 AMR exome

AF:

0.00574

Gnomad4 ASJ exome

AF:

0.0233

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000261

Gnomad4 FIN exome

AF:

0.0000301

Gnomad4 NFE exome

AF:

0.000401

Gnomad4 OTH exome

AF:

0.00778

GnomAD4 genome

AF:

0.0285

AC:

4341

AN:

152280

Hom.:

216

Cov.:

AF XY:

0.0274

AC XY:

2041

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0972

Gnomad4 AMR

AF:

0.00856

Gnomad4 ASJ

AF:

0.0202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000529

Gnomad4 OTH

AF:

0.0270

Alfa

AF:

0.00451

Hom.:

Bravo

AF:

0.0318

ESP6500AA

AF:

0.0575

AC:

146

ESP6500EA

AF:

0.00155

AC:

ExAC

AF:

0.00437

AC:

268

Asia WGS

AF:

0.00694

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 03, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Severe combined immunodeficiency due to DNA-PKcs deficiency

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.7

DANN

Benign

0.82

DEOGEN2

Benign

0.058

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.64

T;T

MetaRNN

Benign

0.0015

T;T

MetaSVM

Benign

-0.93

PrimateAI

Benign

0.42

PROVEAN

Benign

0.20

N;N

REVEL

Benign

0.020

Sift

Benign

0.54

T;T

Sift4G

Benign

0.68

T;T

Polyphen

0.0030

B;B

Vest4

0.042

MVP

0.13

MPC

0.15

ClinPred

0.0054

GERP RS

-8.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.024

gMVP

0.16

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