rs8178231

chr8-47794334-G-A

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.10626C>T(p.Phe3542=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000977 in 1,613,486 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0053 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00052 (6 hom.)
• Consequence: PRKDC NM_006904.7 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.25

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=-0.67).
• BP6: Variant 8-47794334-G-A is Benign according to our data. Variant chr8-47794334-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 380474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-47794334-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=2.25 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00535 (814/152268) while in subpopulation AFR AF= 0.018 (746/41542). AF 95% confidence interval is 0.0169. There are 5 homozygotes in gnomad4. There are 380 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKDC	NM_006904.7	c.10626C>T	p.Phe3542=	synonymous_variant	74/86	ENST00000314191.7
PRKDC	NM_001081640.2	c.10626C>T	p.Phe3542=	synonymous_variant	74/85

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKDC	ENST00000314191.7	c.10626C>T	p.Phe3542=	synonymous_variant	74/86	1	NM_006904.7	P1
PRKDC	ENST00000338368.7	c.10626C>T	p.Phe3542=	synonymous_variant	74/85	1
PRKDC	ENST00000697603.1	c.3303C>T	p.Phe1101=	synonymous_variant	21/33
PRKDC	ENST00000697602.1	n.1199C>T		non_coding_transcript_exon_variant	6/18

Frequencies

GnomAD3 genomes AF: 0.00535 AC: 814 AN: 152150 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0180

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

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: 0.00623

GnomAD3 exomes AF: 0.00117 AC: 290 AN: 248192 Hom.: 2 AF XY: 0.000914 AC XY: 123 AN XY: 134640

Gnomad AFR exome AF: 0.0162

Gnomad AMR exome AF: 0.000901

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000266

Gnomad OTH exome AF: 0.00133

GnomAD4 exome AF: 0.000521 AC: 762 AN: 1461218 Hom.: 6 Cov.: 30 AF XY: 0.000477 AC XY: 347 AN XY: 726816

Gnomad4 AFR exome AF: 0.0186

Gnomad4 AMR exome AF: 0.00119

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000990

Gnomad4 OTH exome AF: 0.00119

GnomAD4 genome AF: 0.00535 AC: 814 AN: 152268 Hom.: 5 Cov.: 32 AF XY: 0.00510 AC XY: 380 AN XY: 74446

Gnomad4 AFR AF: 0.0180

Gnomad4 AMR AF: 0.00346

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: 0.00616

Alfa AF: 0.00111 Hom.: 2

Bravo AF: 0.00618

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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

GeneDx

Apr 23, 2018

- -

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	-0.67
Cadd	Benign	7.1
Dann	Benign	0.73

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: rs8178231; hg19: chr8-48706895;