Variant rs201300612 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_006904.7(PRKDC):c.6342A>G(p.Glu2114=) 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

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 -11 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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/exons	MANE	UniProt
PRKDC	NM_006904.7 linkuse as main transcript	c.6342A>G	p.Glu2114=	synonymous_variant	47/86	ENST00000314191.7
PRKDC	NM_001081640.2 linkuse as main transcript	c.6342A>G	p.Glu2114=	synonymous_variant	47/85

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKDC	ENST00000314191.7 linkuse as main transcript	c.6342A>G	p.Glu2114=	synonymous_variant	47/86	1	NM_006904.7	P1	P78527-1
PRKDC	ENST00000338368.7 linkuse as main transcript	c.6342A>G	p.Glu2114=	synonymous_variant	47/85	1			P78527-2
PRKDC	ENST00000697609.1 linkuse as main transcript	n.503A>G		non_coding_transcript_exon_variant	1/4
PRKDC	ENST00000697610.1 linkuse as main transcript	n.143A>G		non_coding_transcript_exon_variant	2/4

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

GnomAD3 exomes

AF:

0.000692

AC:

172

AN:

248404

Hom.:

AF XY:

0.000853

AC XY:

115

AN XY:

134748

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 SAS exome

AF:

0.000785

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

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000905

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.00126

Gnomad4 OTH exome

AF:

0.00182

GnomAD4 genome

AF:

0.000716

AC:

109

AN:

152180

Hom.:

Cov.:

AF XY:

0.000699

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00103

Gnomad4 FIN

AF:

0.000286

Gnomad4 NFE

AF:

0.00132

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000910

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

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2022

PRKDC: BP4, BP7 -

Severe combined immunodeficiency due to DNA-PKcs deficiency

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.93

DANN

Benign

0.38

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

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