8-47930750-G-C

Position:

chr8-47930750-G-C

Variant summary

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

The ENST00000314191.7(PRKDC):c.1814C>G(p.Thr605Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0045 in 1,590,022 control chromosomes in the GnomAD database, including 270 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T605A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.023 ( 144 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 126 hom. )

Consequence

PRKDC
ENST00000314191.7 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 9.32

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=0.0019198656).

BP6

Variant 8-47930750-G-C is Benign according to our data. Variant chr8-47930750-G-C is described in ClinVar as [Benign]. Clinvar id is 475221.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0777 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.1814C>G	p.Thr605Ser	missense_variant	17/86	ENST00000314191.7	NP_008835.5
PRKDC	NM_001081640.2 linkuse as main transcript	c.1814C>G	p.Thr605Ser	missense_variant	17/85		NP_001075109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKDC	ENST00000314191.7 linkuse as main transcript	c.1814C>G	p.Thr605Ser	missense_variant	17/86	1	NM_006904.7	ENSP00000313420	P1	P78527-1
PRKDC	ENST00000338368.7 linkuse as main transcript	c.1814C>G	p.Thr605Ser	missense_variant	17/85	1		ENSP00000345182		P78527-2

Frequencies

GnomAD3 genomes

AF:

0.0233

AC:

3547

AN:

152146

Hom.:

145

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0803

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0103

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.00623

AC:

1319

AN:

211630

Hom.:

AF XY:

0.00466

AC XY:

530

AN XY:

113678

show subpopulations

Gnomad AFR exome

AF:

0.0850

Gnomad AMR exome

AF:

0.00617

Gnomad ASJ exome

AF:

0.000108

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000390

Gnomad FIN exome

AF:

0.000152

Gnomad NFE exome

AF:

0.000483

Gnomad OTH exome

AF:

0.00315

GnomAD4 exome

AF:

0.00251

AC:

3611

AN:

1437758

Hom.:

126

Cov.:

AF XY:

0.00213

AC XY:

1520

AN XY:

712640

show subpopulations

Gnomad4 AFR exome

AF:

0.0816

Gnomad4 AMR exome

AF:

0.00661

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000159

Gnomad4 FIN exome

AF:

0.0000576

Gnomad4 NFE exome

AF:

0.000255

Gnomad4 OTH exome

AF:

0.00557

GnomAD4 genome

AF:

0.0233

AC:

3543

AN:

152264

Hom.:

144

Cov.:

AF XY:

0.0221

AC XY:

1649

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0800

Gnomad4 AMR

AF:

0.0103

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000412

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.00411

Hom.:

Bravo

AF:

0.0262

ESP6500AA

AF:

0.0815

AC:

303

ESP6500EA

AF:

0.000610

AC:

ExAC

AF:

0.00663

AC:

799

Asia WGS

AF:

0.00433

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

Jan 16, 2017

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 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

T;.

Eigen

Benign

0.13

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.68

T;T

MetaRNN

Benign

0.0019

T;T

MetaSVM

Benign

-0.62

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.18

Sift

Benign

0.36

T;T

Sift4G

Benign

0.60

T;T

Polyphen

0.29

B;B

Vest4

0.17

MutPred

0.22

Loss of glycosylation at T605 (P = 0.0401);Loss of glycosylation at T605 (P = 0.0401);

MVP

0.36

MPC

0.21

ClinPred

0.055

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.29

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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