dbSNP rs758007075: PRKDC:p.Asn867Asp (chr8-47915346-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_006904.7(PRKDC):c.2599A>G(p.Asn867Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N867H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PRKDC
NM_006904.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.25

Publications

1 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: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30678287).

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.2599A>G	p.Asn867Asp	missense	Exon 23 of 86	NP_008835.5
	PRKDC	NM_001081640.2		c.2599A>G	p.Asn867Asp	missense	Exon 23 of 85	NP_001075109.1	P78527-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRKDC	ENST00000314191.7	TSL:1 MANE Select	c.2599A>G	p.Asn867Asp	missense	Exon 23 of 86	ENSP00000313420.3	P78527-1
PRKDC	ENST00000338368.7	TSL:1	c.2599A>G	p.Asn867Asp	missense	Exon 23 of 85	ENSP00000345182.4	P78527-2
PRKDC	ENST00000911724.1		c.2599A>G	p.Asn867Asp	missense	Exon 23 of 86	ENSP00000581783.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1398902

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

693614

African (AFR)

AF:

0.00

AC:

AN:

31656

American (AMR)

AF:

0.00

AC:

AN:

36232

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25142

East Asian (EAS)

AF:

0.00

AC:

AN:

38688

South Asian (SAS)

AF:

0.00

AC:

AN:

77976

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5484

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1074196

Other (OTH)

AF:

0.00

AC:

AN:

58126

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.016

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.49

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.31

MetaSVM

Uncertain

-0.22

PhyloP100

6.3

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.16

Sift

Uncertain

0.0070

Sift4G

Pathogenic

0.0

Polyphen

0.94

Vest4

0.35

MutPred

0.34

Loss of MoRF binding (P = 0.0558)

MVP

0.62

MPC

0.66

ClinPred

0.99

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.64

gMVP

0.56

Mutation Taster

=76/24

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over