dbSNP rs201300612: PRKDC:p.Glu2114Glu (chr8-47858852-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_006904.7(PRKDC):c.6342A>G(p.Glu2114Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,613,038 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 1 hom. )

Consequence

PRKDC
NM_006904.7 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.438

Publications

3 publications found

Variant links:

COSMIC-nc: COSV104628474

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 8-47858852-T-C is Benign according to our data. Variant chr8-47858852-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 542034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.438 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKDC	NM_006904.7 link	c.6342A>G	p.Glu2114Glu	synonymous_variant	Exon 47 of 86	ENST00000314191.7	NP_008835.5	P78527-1
PRKDC	NM_001081640.2 link	c.6342A>G	p.Glu2114Glu	synonymous_variant	Exon 47 of 85		NP_001075109.1	P78527-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PRKDC	ENST00000314191.7 link	c.6342A>G	p.Glu2114Glu	synonymous_variant	Exon 47 of 86	1	NM_006904.7	ENSP00000313420.3	P78527-1
PRKDC	ENST00000338368.7 link	c.6342A>G	p.Glu2114Glu	synonymous_variant	Exon 47 of 85	1		ENSP00000345182.4	P78527-2
PRKDC	ENST00000697609.1 link	n.503A>G		non_coding_transcript_exon_variant	Exon 1 of 4
PRKDC	ENST00000697610.1 link	n.143A>G		non_coding_transcript_exon_variant	Exon 2 of 4

Frequencies

GnomAD3 genomes

AF:

0.000717

AC:

109

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.000286

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00132

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000692

AC:

172

AN:

248404

AF XY:

0.000853

show subpopulations

Gnomad AFR exome

AF:

0.000388

Gnomad AMR exome

AF:

0.0000871

Gnomad ASJ exome

AF:

0.0000998

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000281

Gnomad NFE exome

AF:

0.00111

Gnomad OTH exome

AF:

0.00116

GnomAD4 exome

AF:

0.00111

AC:

1620

AN:

1460858

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

828

AN XY:

726584

show subpopulations

African (AFR)

AF:

0.000209

AC:

AN:

33466

American (AMR)

AF:

0.0000895

AC:

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.000115

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.000905

AC:

AN:

86220

European-Finnish (FIN)

AF:

0.000206

AC:

AN:

53280

Middle Eastern (MID)

AF:

0.00208

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00126

AC:

1395

AN:

1111318

Other (OTH)

AF:

0.00182

AC:

110

AN:

60322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

181

271

362

452

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

108

162

216

270

<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:

0.000716

AC:

109

AN:

152180

Hom.:

Cov.:

AF XY:

0.000699

AC XY:

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

41562

American (AMR)

AF:

0.00

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00103

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000286

AC:

AN:

10498

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00132

AC:

AN:

68020

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000899

Hom.:

Bravo

AF:

0.000635

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00175

EpiControl

AF:

0.00148

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PRKDC: BP4, BP7 -

Severe combined immunodeficiency due to DNA-PKcs deficiency

Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.93

(source)

DANN

Benign

0.38

PhyloP100

-0.44

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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