Variant 8-47912405-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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/exons	MANE	Protein	UniProt
PRKDC	NM_006904.7 linkuse as main transcript	c.2934+5G>C		splice_region_variant, intron_variant		ENST00000314191.7	NP_008835.5	P78527-1
PRKDC	NM_001081640.2 linkuse as main transcript	c.2934+5G>C		splice_region_variant, intron_variant			NP_001075109.1	P78527-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKDC	ENST00000314191.7 linkuse as main transcript	c.2934+5G>C		splice_region_variant, intron_variant		1	NM_006904.7	ENSP00000313420.3		P78527-1
PRKDC	ENST00000338368.7 linkuse as main transcript	c.2934+5G>C		splice_region_variant, intron_variant		1		ENSP00000345182.4		P78527-2

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

GnomAD3 exomes

AF:

0.0140

AC:

3091

AN:

220860

Hom.:

257

AF XY:

0.0107

AC XY:

1289

AN XY:

120330

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 SAS exome

AF:

0.00515

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

Gnomad4 AFR exome

AF:

0.192

Gnomad4 AMR exome

AF:

0.00977

Gnomad4 ASJ exome

AF:

0.00193

Gnomad4 EAS exome

AF:

0.0000526

Gnomad4 SAS exome

AF:

0.00513

Gnomad4 FIN exome

AF:

0.0000190

Gnomad4 NFE exome

AF:

0.000329

Gnomad4 OTH exome

AF:

0.0128

GnomAD4 genome

AF:

0.0524

AC:

7977

AN:

152260

Hom.:

705

Cov.:

AF XY:

0.0507

AC XY:

3777

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.181

Gnomad4 AMR

AF:

0.0202

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00580

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.0406

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2016

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Severe combined immunodeficiency due to DNA-PKcs deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

PRKDC-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 08, 2019

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

DANN

Benign

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

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

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