rs140578467

chr8-47817446-T-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.68

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 -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 GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKDC	NM_006904.7	c.9557+4A>C		splice_donor_region_variant, intron_variant		ENST00000314191.7
PRKDC	NM_001081640.2	c.9557+4A>C		splice_donor_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKDC	ENST00000314191.7	c.9557+4A>C		splice_donor_region_variant, intron_variant		1	NM_006904.7	P1
PRKDC	ENST00000338368.7	c.9557+4A>C		splice_donor_region_variant, intron_variant		1
PRKDC	ENST00000697603.1	c.2234+4A>C		splice_donor_region_variant, intron_variant
PRKDC	ENST00000697607.1	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.: 2 Cov.: 32

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: 94 AN: 224364 Hom.: 0 AF XY: 0.000265 AC XY: 32 AN XY: 120628

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.: 0 Cov.: 27 AF XY: 0.000116 AC XY: 82 AN XY: 706372

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.: 2 Cov.: 32 AF XY: 0.00160 AC XY: 119 AN XY: 74490

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.: 1

Bravo AF: 0.00173

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 08, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
Cadd	Benign	17
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

Other links and lift over

dbSNP: rs140578467; hg19: chr8-48730007;