rs79703138

Positions:

• chr8-47858853-TCTC-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PM4_Supporting BP6_Moderate BS2

The NM_006904.7(PRKDC):​c.6338_6340del​(p.Gly2113del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00316 in 1,613,134 control chromosomes in the GnomAD database, including 116 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0058 (27 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (89 hom.)
• Consequence: PRKDC NM_006904.7 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.96

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 Likely_benign. Variant got -5 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_006904.7. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 8-47858853-TCTC-T is Benign according to our data. Variant chr8-47858853-TCTC-T is described in ClinVar as [Benign]. Clinvar id is 542029.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKDC	NM_006904.7	c.6338_6340del	p.Gly2113del	inframe_deletion	47/86	ENST00000314191.7	NP_008835.5
PRKDC	NM_001081640.2	c.6338_6340del	p.Gly2113del	inframe_deletion	47/85		NP_001075109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKDC	ENST00000314191.7	c.6338_6340del	p.Gly2113del	inframe_deletion	47/86	1	NM_006904.7	ENSP00000313420	P1
PRKDC	ENST00000338368.7	c.6338_6340del	p.Gly2113del	inframe_deletion	47/85	1		ENSP00000345182
PRKDC	ENST00000697609.1	n.499_501del		non_coding_transcript_exon_variant	1/4
PRKDC	ENST00000697610.1	n.139_141del		non_coding_transcript_exon_variant	2/4

Frequencies

GnomAD3 genomes AF: 0.00578 AC: 880 AN: 152136 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0116

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0675

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00143

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00712 AC: 1770 AN: 248556 Hom.: 42 AF XY: 0.00716 AC XY: 966 AN XY: 134830

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0110

Gnomad SAS exome AF: 0.000491

Gnomad FIN exome AF: 0.0588

Gnomad NFE exome AF: 0.00217

Gnomad OTH exome AF: 0.00763

GnomAD4 exome AF: 0.00289 AC: 4219 AN: 1460880 Hom.: 89 AF XY: 0.00287 AC XY: 2082 AN XY: 726592

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.0000895

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0115

Gnomad4 SAS exome AF: 0.000487

Gnomad4 FIN exome AF: 0.0540

Gnomad4 NFE exome AF: 0.000588

Gnomad4 OTH exome AF: 0.00295

GnomAD4 genome AF: 0.00578 AC: 880 AN: 152254 Hom.: 27 Cov.: 32 AF XY: 0.00887 AC XY: 660 AN XY: 74424

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0116

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0675

Gnomad4 NFE AF: 0.00143

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00294 Hom.: 0

Bravo AF: 0.000876

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Severe combined immunodeficiency due to DNA-PKcs deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 25, 2023

- -

Computational scores

Source: dbNSFP v4.3

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: rs79703138; hg19: chr8-48771414;