dbSNP rs8178097: PRKDC:c.4413+39T>C (chr8-47888479-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006904.7(PRKDC):c.4413+39T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0445 in 1,463,154 control chromosomes in the GnomAD database, including 1,658 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 123 hom., cov: 33)

Exomes 𝑓: 0.046 ( 1535 hom. )

Consequence

PRKDC
NM_006904.7 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.151

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: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

PRKDC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 8-47888479-A-G is Benign according to our data. Variant chr8-47888479-A-G is described in ClinVar as Benign. ClinVar VariationId is 1266899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0574 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006904.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKDC	NM_006904.7	MANE Select	c.4413+39T>C		intron	N/A	NP_008835.5
	PRKDC	NM_001081640.2		c.4413+39T>C		intron	N/A	NP_001075109.1	P78527-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PRKDC	ENST00000314191.7	TSL:1 MANE Select	c.4413+39T>C	intron	N/A	ENSP00000313420.3	P78527-1
PRKDC	ENST00000338368.7	TSL:1	c.4413+39T>C	intron	N/A	ENSP00000345182.4	P78527-2
PRKDC	ENST00000911724.1		c.4413+39T>C	intron	N/A	ENSP00000581783.1

Frequencies

GnomAD3 genomes

AF:

0.0346

AC:

5266

AN:

152220

Hom.:

123

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00914

Gnomad AMI

AF:

0.192

Gnomad AMR

AF:

0.0405

Gnomad ASJ

AF:

0.0824

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0408

Gnomad FIN

AF:

0.0234

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0477

Gnomad OTH

AF:

0.0449

GnomAD2 exomes

AF:

0.0412

AC:

5198

AN:

126280

AF XY:

0.0426

show subpopulations

Gnomad AFR exome

AF:

0.00775

Gnomad AMR exome

AF:

0.0332

Gnomad ASJ exome

AF:

0.0818

Gnomad EAS exome

AF:

0.000457

Gnomad FIN exome

AF:

0.0288

Gnomad NFE exome

AF:

0.0532

Gnomad OTH exome

AF:

0.0509

GnomAD4 exome

AF:

0.0457

AC:

59915

AN:

1310816

Hom.:

1535

Cov.:

AF XY:

0.0461

AC XY:

29456

AN XY:

639060

show subpopulations

African (AFR)

AF:

0.00856

AC:

246

AN:

28736

American (AMR)

AF:

0.0335

AC:

843

AN:

25170

Ashkenazi Jewish (ASJ)

AF:

0.0834

AC:

1890

AN:

22654

East Asian (EAS)

AF:

0.000263

AC:

AN:

34272

South Asian (SAS)

AF:

0.0413

AC:

2672

AN:

64668

European-Finnish (FIN)

AF:

0.0305

AC:

1439

AN:

47224

Middle Eastern (MID)

AF:

0.0630

AC:

333

AN:

5284

European-Non Finnish (NFE)

AF:

0.0486

AC:

49985

AN:

1028774

Other (OTH)

AF:

0.0462

AC:

2498

AN:

54034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

2748

5497

8245

10994

13742

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1948

3896

5844

7792

9740

<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:

0.0345

AC:

5261

AN:

152338

Hom.:

123

Cov.:

AF XY:

0.0339

AC XY:

2522

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.00911

AC:

379

AN:

41586

American (AMR)

AF:

0.0404

AC:

617

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0824

AC:

286

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.0402

AC:

194

AN:

4826

European-Finnish (FIN)

AF:

0.0234

AC:

248

AN:

10618

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0477

AC:

3248

AN:

68040

Other (OTH)

AF:

0.0445

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

273

546

818

1091

1364

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<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:

0.0435

Hom.:

Bravo

AF:

0.0357

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.1

(source)

DANN

Benign

0.55

PhyloP100

-0.15

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over