rs78163867

chr8-47826778-G-Achr8-47826778-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_006904.7(PRKDC):c.8661C>T(p.Pro2887=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000973 in 1,611,454 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P2887P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0048 (8 hom., cov: 33)
  • Exomes 𝑓: 0.00057 (4 hom.)
• Consequence: PRKDC NM_006904.7 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.19

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 8-47826778-G-A is Benign according to our data. Variant chr8-47826778-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 475240.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-47826778-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-4.19 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00482 (734/152338) while in subpopulation AFR AF= 0.0167 (695/41572). AF 95% confidence interval is 0.0157. There are 8 homozygotes in gnomad4. There are 335 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKDC	NM_006904.7	c.8661C>T	p.Pro2887=	synonymous_variant	63/86	ENST00000314191.7
PRKDC	NM_001081640.2	c.8661C>T	p.Pro2887=	synonymous_variant	63/85

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKDC	ENST00000314191.7	c.8661C>T	p.Pro2887=	synonymous_variant	63/86	1	NM_006904.7	P1
PRKDC	ENST00000338368.7	c.8661C>T	p.Pro2887=	synonymous_variant	63/85	1
PRKDC	ENST00000697603.1	c.1338C>T	p.Pro446=	synonymous_variant	10/33

Frequencies

GnomAD3 genomes AF: 0.00484 AC: 736 AN: 152220 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.0168

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

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: 0.000176

Gnomad OTH AF: 0.00383

GnomAD3 exomes AF: 0.00133 AC: 322 AN: 241704 Hom.: 1 AF XY: 0.000940 AC XY: 124 AN XY: 131872

Gnomad AFR exome AF: 0.0195

Gnomad AMR exome AF: 0.000708

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000567

Gnomad SAS exome AF: 0.0000334

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000165

Gnomad OTH exome AF: 0.000341

GnomAD4 exome AF: 0.000572 AC: 834 AN: 1459116 Hom.: 4 Cov.: 31 AF XY: 0.000462 AC XY: 335 AN XY: 725626

Gnomad4 AFR exome AF: 0.0194

Gnomad4 AMR exome AF: 0.000698

Gnomad4 ASJ exome AF: 0.0000385

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000233

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000945

Gnomad4 OTH exome AF: 0.000648

GnomAD4 genome AF: 0.00482 AC: 734 AN: 152338 Hom.: 8 Cov.: 33 AF XY: 0.00450 AC XY: 335 AN XY: 74486

Gnomad4 AFR AF: 0.0167

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.000968 Hom.: 1

Bravo AF: 0.00547

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 24, 2017

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. -

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	-0.62
Cadd	Benign	0.86
Dann	Benign	0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

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

Other links and lift over

dbSNP: rs78163867; hg19: chr8-48739339;