Variant chr8-47820838-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_006904.7(PRKDC):c.9217C>T(p.Leu3073Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000543 in 1,613,354 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L3073L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0027 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 2 hom. )

Consequence

PRKDC
NM_006904.7 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.48

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0069336295).

BP6

Variant 8-47820838-G-A is Benign according to our data. Variant chr8-47820838-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 507237.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKDC	NM_006904.7 linkuse as main transcript	c.9217C>T	p.Leu3073Phe	missense_variant	66/86	ENST00000314191.7
PRKDC	NM_001081640.2 linkuse as main transcript	c.9217C>T	p.Leu3073Phe	missense_variant	66/85

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKDC	ENST00000314191.7 linkuse as main transcript	c.9217C>T	p.Leu3073Phe	missense_variant	66/86	1	NM_006904.7	P1	P78527-1
PRKDC	ENST00000338368.7 linkuse as main transcript	c.9217C>T	p.Leu3073Phe	missense_variant	66/85	1			P78527-2
PRKDC	ENST00000697603.1 linkuse as main transcript	c.1894C>T	p.Leu632Phe	missense_variant	13/33

Frequencies

GnomAD3 genomes

AF:

0.00268

AC:

407

AN:

152018

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00947

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000853

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000738

AC:

184

AN:

249276

Hom.:

AF XY:

0.000436

AC XY:

AN XY:

135242

show subpopulations

Gnomad AFR exome

AF:

0.00969

Gnomad AMR exome

AF:

0.000637

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000796

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.000320

AC:

468

AN:

1461218

Hom.:

Cov.:

AF XY:

0.000270

AC XY:

196

AN XY:

726912

show subpopulations

Gnomad4 AFR exome

AF:

0.0108

Gnomad4 AMR exome

AF:

0.000648

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.000828

GnomAD4 genome

AF:

0.00268

AC:

408

AN:

152136

Hom.:

Cov.:

AF XY:

0.00239

AC XY:

178

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.00947

Gnomad4 AMR

AF:

0.000852

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00139

Hom.:

Bravo

AF:

0.00292

ESP6500AA

AF:

0.00990

AC:

ESP6500EA

AF:

0.000121

AC:

ExAC

AF:

0.000927

AC:

112

Asia WGS

AF:

0.000578

AC:

AN:

3474

EpiCase

AF:

0.0000548

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 31, 2018

- -

Severe combined immunodeficiency due to DNA-PKcs deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 04, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.078

T;.

Eigen

Benign

0.10

Eigen_PC

Benign

-0.047

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.76

T;T

MetaRNN

Benign

0.0069

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

M;M

MutationTaster

Benign

0.95

N;N

PrimateAI

Benign

0.38

REVEL

Benign

0.13

Sift4G

Uncertain

0.031

D;D

Polyphen

0.98

D;.

Vest4

0.20

MVP

0.67

MPC

0.38

ClinPred

0.020

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.091

gMVP

0.085

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