Variant rs140578467 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_006904.7(PRKDC):c.9557+4A>C variant causes a splice donor region, intron change. The variant allele was found at a frequency of 0.00027 in 1,575,080 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

PRKDC
NM_006904.7 splice_donor_region, intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.68

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 8-47817446-T-G is Benign according to our data. Variant chr8-47817446-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 542003.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKDC	NM_006904.7 linkuse as main transcript	c.9557+4A>C		splice_donor_region_variant, intron_variant		ENST00000314191.7	NP_008835.5
PRKDC	NM_001081640.2 linkuse as main transcript	c.9557+4A>C		splice_donor_region_variant, intron_variant			NP_001075109.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
PRKDC	ENST00000314191.7 linkuse as main transcript	c.9557+4A>C	splice_donor_region_variant, intron_variant	1	NM_006904.7	ENSP00000313420	P1	P78527-1
PRKDC	ENST00000338368.7 linkuse as main transcript	c.9557+4A>C	splice_donor_region_variant, intron_variant	1		ENSP00000345182		P78527-2
PRKDC	ENST00000697603.1 linkuse as main transcript	c.2234+4A>C	splice_donor_region_variant, intron_variant			ENSP00000513358
PRKDC	ENST00000697607.1 linkuse as main transcript	n.1089+4A>C	splice_donor_region_variant, intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00147

AC:

223

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00495

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000419

AC:

AN:

224364

Hom.:

AF XY:

0.000265

AC XY:

AN XY:

120628

show subpopulations

Gnomad AFR exome

AF:

0.00546

Gnomad AMR exome

AF:

0.000323

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000368

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000300

Gnomad OTH exome

AF:

0.000354

GnomAD4 exome

AF:

0.000142

AC:

202

AN:

1422746

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

706372

show subpopulations

Gnomad4 AFR exome

AF:

0.00487

Gnomad4 AMR exome

AF:

0.000506

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000121

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000322

GnomAD4 genome

AF:

0.00146

AC:

223

AN:

152334

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

119

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00493

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000830

Hom.:

Bravo

AF:

0.00173

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Severe combined immunodeficiency due to DNA-PKcs deficiency

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 08, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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