chr8-47912405-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_006904.7(PRKDC):c.2934+5G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,567,014 control chromosomes in the GnomAD database, including 1,323 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.052 ( 705 hom., cov: 32)

Exomes 𝑓: 0.0057 ( 618 hom. )

Consequence

PRKDC
NM_006904.7 splice_region, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.800

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

severe combined immunodeficiency due to DNA-PKcs deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

PRKDC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 8-47912405-C-G is Benign according to our data. Variant chr8-47912405-C-G is described in ClinVar as Benign. ClinVar VariationId is 379644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKDC	NM_006904.7 link	c.2934+5G>C		splice_region_variant, intron_variant	Intron 25 of 85	ENST00000314191.7	NP_008835.5
PRKDC	NM_001081640.2 link	c.2934+5G>C		splice_region_variant, intron_variant	Intron 25 of 84		NP_001075109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKDC	ENST00000314191.7 link	c.2934+5G>C		splice_region_variant, intron_variant	Intron 25 of 85	1	NM_006904.7	ENSP00000313420.3
PRKDC	ENST00000338368.7 link	c.2934+5G>C		splice_region_variant, intron_variant	Intron 25 of 84	1		ENSP00000345182.4

Frequencies

GnomAD3 genomes

AF:

0.0524

AC:

7967

AN:

152142

Hom.:

704

Cov.:

show subpopulations

Gnomad AFR

AF:

0.181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0203

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.0415

GnomAD2 exomes

AF:

0.0140

AC:

3091

AN:

220860

AF XY:

0.0107

show subpopulations

Gnomad AFR exome

AF:

0.186

Gnomad AMR exome

AF:

0.00856

Gnomad ASJ exome

AF:

0.00206

Gnomad EAS exome

AF:

0.0000627

Gnomad FIN exome

AF:

0.0000483

Gnomad NFE exome

AF:

0.000338

Gnomad OTH exome

AF:

0.00757

GnomAD4 exome

AF:

0.00567

AC:

8027

AN:

1414754

Hom.:

618

Cov.:

AF XY:

0.00513

AC XY:

3594

AN XY:

700128

show subpopulations

African (AFR)

AF:

0.192

AC:

6028

AN:

31416

American (AMR)

AF:

0.00977

AC:

373

AN:

38168

Ashkenazi Jewish (ASJ)

AF:

0.00193

AC:

AN:

24354

East Asian (EAS)

AF:

0.0000526

AC:

AN:

38010

South Asian (SAS)

AF:

0.00513

AC:

408

AN:

79604

European-Finnish (FIN)

AF:

0.0000190

AC:

AN:

52562

Middle Eastern (MID)

AF:

0.0116

AC:

AN:

5594

European-Non Finnish (NFE)

AF:

0.000329

AC:

358

AN:

1086800

Other (OTH)

AF:

0.0128

AC:

745

AN:

58246

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

337

674

1010

1347

1684

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

210

420

630

840

1050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0524

AC:

7977

AN:

152260

Hom.:

705

Cov.:

AF XY:

0.0507

AC XY:

3777

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.181

AC:

7512

AN:

41516

American (AMR)

AF:

0.0202

AC:

309

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00580

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000485

AC:

AN:

68028

Other (OTH)

AF:

0.0406

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

344

687

1031

1374

1718

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

222

296

370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00334

Hom.:

Bravo

AF:

0.0599

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

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

- -

PRKDC-related disorder

Benign:1

Jul 08, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Mutation Taster

=95/5

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over