Variant rs56123237 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 ENST00000314191.7(PRKDC):c.12138C>T(p.Tyr4046=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 1,613,806 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 3 hom. )

Consequence

PRKDC
ENST00000314191.7 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.306

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=-0.57).

BP6

Variant 8-47776888-G-A is Benign according to our data. Variant chr8-47776888-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 542026.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.306 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKDC	NM_006904.7 linkuse as main transcript	c.12138C>T	p.Tyr4046=	synonymous_variant	85/86	ENST00000314191.7	NP_008835.5
PRKDC	NM_001081640.2 linkuse as main transcript	c.12045C>T	p.Tyr4015=	synonymous_variant	84/85		NP_001075109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKDC	ENST00000314191.7 linkuse as main transcript	c.12138C>T	p.Tyr4046=	synonymous_variant	85/86	1	NM_006904.7	ENSP00000313420	P1	P78527-1

Frequencies

GnomAD3 genomes

AF:

0.00188

AC:

286

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00403

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00151

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00112

AC:

278

AN:

249100

Hom.:

AF XY:

0.00116

AC XY:

157

AN XY:

135162

show subpopulations

Gnomad AFR exome

AF:

0.00472

Gnomad AMR exome

AF:

0.000551

Gnomad ASJ exome

AF:

0.000497

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000719

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.00126

Gnomad OTH exome

AF:

0.00182

GnomAD4 exome

AF:

0.00134

AC:

1962

AN:

1461610

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

959

AN XY:

727080

show subpopulations

Gnomad4 AFR exome

AF:

0.00478

Gnomad4 AMR exome

AF:

0.000514

Gnomad4 ASJ exome

AF:

0.00107

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000846

Gnomad4 FIN exome

AF:

0.000187

Gnomad4 NFE exome

AF:

0.00135

Gnomad4 OTH exome

AF:

0.00244

GnomAD4 genome

AF:

0.00188

AC:

286

AN:

152196

Hom.:

Cov.:

AF XY:

0.00177

AC XY:

132

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.00402

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00151

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00157

Hom.:

Bravo

AF:

0.00215

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00180

EpiControl

AF:

0.00160

ClinVar

Significance: Benign/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

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

-0.57

CADD

Benign

0.60

DANN

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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