Variant 8-47888479-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKDC	NM_006904.7 linkuse as main transcript	c.4413+39T>C		intron_variant		ENST00000314191.7	NP_008835.5	P78527-1
PRKDC	NM_001081640.2 linkuse as main transcript	c.4413+39T>C		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.4413+39T>C		intron_variant		1	NM_006904.7	ENSP00000313420.3		P78527-1
PRKDC	ENST00000338368.7 linkuse as main transcript	c.4413+39T>C		intron_variant		1		ENSP00000345182.4		P78527-2

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

GnomAD3 exomes

AF:

0.0412

AC:

5198

AN:

126280

Hom.:

142

AF XY:

0.0426

AC XY:

2840

AN XY:

66630

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 SAS exome

AF:

0.0411

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

Gnomad4 AFR exome

AF:

0.00856

Gnomad4 AMR exome

AF:

0.0335

Gnomad4 ASJ exome

AF:

0.0834

Gnomad4 EAS exome

AF:

0.000263

Gnomad4 SAS exome

AF:

0.0413

Gnomad4 FIN exome

AF:

0.0305

Gnomad4 NFE exome

AF:

0.0486

Gnomad4 OTH exome

AF:

0.0462

GnomAD4 genome

AF:

0.0345

AC:

5261

AN:

152338

Hom.:

123

Cov.:

AF XY:

0.0339

AC XY:

2522

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00911

Gnomad4 AMR

AF:

0.0404

Gnomad4 ASJ

AF:

0.0824

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0402

Gnomad4 FIN

AF:

0.0234

Gnomad4 NFE

AF:

0.0477

Gnomad4 OTH

AF:

0.0445

Alfa

AF:

0.0465

Hom.:

Bravo

AF:

0.0357

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 16, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.1

DANN

Benign

0.55

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