Variant rs200510022 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.6348T>C(p.Asp2116=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,511,178 control chromosomes in the GnomAD database, including 1 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.00070 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 1 hom. )

Consequence

PRKDC
NM_006904.7 splice_region, synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.178

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=-0.52).

BP6

Variant 8-47858633-A-G is Benign according to our data. Variant chr8-47858633-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 542036.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.178 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKDC	NM_006904.7 linkuse as main transcript	c.6348T>C	p.Asp2116=	splice_region_variant, synonymous_variant	48/86	ENST00000314191.7	NP_008835.5
PRKDC	NM_001081640.2 linkuse as main transcript	c.6348T>C	p.Asp2116=	splice_region_variant, synonymous_variant	48/85		NP_001075109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKDC	ENST00000314191.7 linkuse as main transcript	c.6348T>C	p.Asp2116=	splice_region_variant, synonymous_variant	48/86	1	NM_006904.7	ENSP00000313420	P1	P78527-1
PRKDC	ENST00000338368.7 linkuse as main transcript	c.6348T>C	p.Asp2116=	splice_region_variant, synonymous_variant	48/85	1		ENSP00000345182		P78527-2
PRKDC	ENST00000697609.1 linkuse as main transcript	n.509T>C		splice_region_variant, non_coding_transcript_exon_variant	2/4
PRKDC	ENST00000697610.1 linkuse as main transcript	n.149T>C		splice_region_variant, non_coding_transcript_exon_variant	3/4

Frequencies

GnomAD3 genomes

AF:

0.000696

AC:

106

AN:

152234

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:

0.000621

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00132

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000738

AC:

102

AN:

138126

Hom.:

AF XY:

0.000895

AC XY:

AN XY:

73782

show subpopulations

Gnomad AFR exome

AF:

0.000490

Gnomad AMR exome

AF:

0.0000709

Gnomad ASJ exome

AF:

0.000182

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000608

Gnomad FIN exome

AF:

0.000319

Gnomad NFE exome

AF:

0.00124

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.00113

AC:

1534

AN:

1358826

Hom.:

Cov.:

AF XY:

0.00116

AC XY:

775

AN XY:

668222

show subpopulations

Gnomad4 AFR exome

AF:

0.000235

Gnomad4 AMR exome

AF:

0.000124

Gnomad4 ASJ exome

AF:

0.000134

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000853

Gnomad4 FIN exome

AF:

0.000204

Gnomad4 NFE exome

AF:

0.00125

Gnomad4 OTH exome

AF:

0.00189

GnomAD4 genome

AF:

0.000696

AC:

106

AN:

152352

Hom.:

Cov.:

AF XY:

0.000671

AC XY:

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.000240

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00132

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000883

Hom.:

Bravo

AF:

0.000635

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

-0.52

CADD

Benign

1.6

DANN

Benign

0.47

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