rs8178249

Positions:

chr8-47778507-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_006904.7(PRKDC):c.11805C>T(p.Gly3935=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00537 in 1,613,570 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0056 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0053 ( 49 hom. )

Consequence

PRKDC
NM_006904.7 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -4.33

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 8-47778507-G-A is Benign according to our data. Variant chr8-47778507-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 379753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-47778507-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-4.33 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00534 (7805/1461262) while in subpopulation MID AF= 0.0323 (186/5766). AF 95% confidence interval is 0.0285. There are 49 homozygotes in gnomad4_exome. There are 3825 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKDC	NM_006904.7 linkuse as main transcript	c.11805C>T	p.Gly3935=	synonymous_variant	83/86	ENST00000314191.7
PRKDC	NM_001081640.2 linkuse as main transcript	c.11712C>T	p.Gly3904=	synonymous_variant	82/85

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKDC	ENST00000314191.7 linkuse as main transcript	c.11805C>T	p.Gly3935=	synonymous_variant	83/86	1	NM_006904.7	P1	P78527-1

Frequencies

GnomAD3 genomes

AF:

0.00561

AC:

854

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00818

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.0151

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00664

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00533

AC:

1323

AN:

248176

Hom.:

AF XY:

0.00524

AC XY:

706

AN XY:

134644

show subpopulations

Gnomad AFR exome

AF:

0.00124

Gnomad AMR exome

AF:

0.00384

Gnomad ASJ exome

AF:

0.0101

Gnomad EAS exome

AF:

0.0000558

Gnomad SAS exome

AF:

0.000854

Gnomad FIN exome

AF:

0.0156

Gnomad NFE exome

AF:

0.00599

Gnomad OTH exome

AF:

0.00580

GnomAD4 exome

AF:

0.00534

AC:

7805

AN:

1461262

Hom.:

Cov.:

AF XY:

0.00526

AC XY:

3825

AN XY:

726852

show subpopulations

Gnomad4 AFR exome

AF:

0.00173

Gnomad4 AMR exome

AF:

0.00403

Gnomad4 ASJ exome

AF:

0.00900

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000987

Gnomad4 FIN exome

AF:

0.0153

Gnomad4 NFE exome

AF:

0.00527

Gnomad4 OTH exome

AF:

0.00631

GnomAD4 genome

AF:

0.00560

AC:

853

AN:

152308

Hom.:

Cov.:

AF XY:

0.00600

AC XY:

447

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00144

Gnomad4 AMR

AF:

0.00817

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.0151

Gnomad4 NFE

AF:

0.00663

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00599

Hom.:

Bravo

AF:

0.00483

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2024	PRKDC: BP4, BP7, BS2 -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Severe combined immunodeficiency due to DNA-PKcs deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 28, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Nov 10, 2021	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 02, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.23

DANN

Benign

0.46

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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