rs56123237

Positions:

• chr8-47776888-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_006904.7(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 NM_006904.7 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.306

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 -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	UniProt
PRKDC	NM_006904.7	c.12138C>T	p.Tyr4046=	synonymous_variant	85/86	ENST00000314191.7
PRKDC	NM_001081640.2	c.12045C>T	p.Tyr4015=	synonymous_variant	84/85

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKDC	ENST00000314191.7	c.12138C>T	p.Tyr4046=	synonymous_variant	85/86	1	NM_006904.7	P1

Frequencies

GnomAD3 genomes AF: 0.00188 AC: 286 AN: 152078 Hom.: 1 Cov.: 32

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.: 1 AF XY: 0.00116 AC XY: 157 AN XY: 135162

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.: 3 Cov.: 31 AF XY: 0.00132 AC XY: 959 AN XY: 727080

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.: 1 Cov.: 32 AF XY: 0.00177 AC XY: 132 AN XY: 74422

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.: 2

Bravo AF: 0.00215

Asia WGS AF: 0.000577 AC: 2 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

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

Invitae

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

Other links and lift over

dbSNP: rs56123237; hg19: chr8-48689449; COSMIC: COSV104628472; COSMIC: COSV104628472;