Variant 8-47857285-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_006904.7(PRKDC):c.6480C>T(p.Tyr2160=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00604 in 1,611,100 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0042 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0062 ( 38 hom. )

Consequence

PRKDC
NM_006904.7 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0970

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 8-47857285-G-A is Benign according to our data. Variant chr8-47857285-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 380483.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-47857285-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.097 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKDC	NM_006904.7 linkuse as main transcript	c.6480C>T	p.Tyr2160=	synonymous_variant	49/86	ENST00000314191.7
PRKDC	NM_001081640.2 linkuse as main transcript	c.6480C>T	p.Tyr2160=	synonymous_variant	49/85

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKDC	ENST00000314191.7 linkuse as main transcript	c.6480C>T	p.Tyr2160=	synonymous_variant	49/86	1	NM_006904.7	P1	P78527-1
PRKDC	ENST00000338368.7 linkuse as main transcript	c.6480C>T	p.Tyr2160=	synonymous_variant	49/85	1			P78527-2
PRKDC	ENST00000697609.1 linkuse as main transcript	n.641C>T		non_coding_transcript_exon_variant	3/4
PRKDC	ENST00000697610.1 linkuse as main transcript	n.281C>T		non_coding_transcript_exon_variant	4/4

Frequencies

GnomAD3 genomes

AF:

0.00418

AC:

637

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0108

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.00254

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00695

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00451

AC:

1105

AN:

245140

Hom.:

AF XY:

0.00433

AC XY:

577

AN XY:

133170

show subpopulations

Gnomad AFR exome

AF:

0.00156

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.000102

Gnomad EAS exome

AF:

0.0109

Gnomad SAS exome

AF:

0.000605

Gnomad FIN exome

AF:

0.00368

Gnomad NFE exome

AF:

0.00662

Gnomad OTH exome

AF:

0.00454

GnomAD4 exome

AF:

0.00624

AC:

9097

AN:

1458750

Hom.:

Cov.:

AF XY:

0.00597

AC XY:

4333

AN XY:

725680

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.000981

Gnomad4 ASJ exome

AF:

0.0000385

Gnomad4 EAS exome

AF:

0.00663

Gnomad4 SAS exome

AF:

0.000724

Gnomad4 FIN exome

AF:

0.00348

Gnomad4 NFE exome

AF:

0.00730

Gnomad4 OTH exome

AF:

0.00662

GnomAD4 genome

AF:

0.00417

AC:

635

AN:

152350

Hom.:

Cov.:

AF XY:

0.00385

AC XY:

287

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00108

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0104

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00254

Gnomad4 NFE

AF:

0.00695

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00563

Hom.:

Bravo

AF:

0.00381

Asia WGS

AF:

0.00837

AC:

AN:

3478

EpiCase

AF:

0.00580

EpiControl

AF:

0.00553

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 12, 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

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

PRKDC: BP4, BP7, BS1, BS2 -

Severe combined immunodeficiency due to DNA-PKcs deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.18

DANN

Benign

0.28

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.8

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