rs8178179

Variant names:

• chr8-47832566-T-G
• rs8178179
• NM_006904.7:c.8153-640A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006904.7(PRKDC):​c.8153-640A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.035 in 152,022 control chromosomes in the GnomAD database, including 147 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.035 (147 hom., cov: 33)
• Consequence: PRKDC NM_006904.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.769
• Publications: 14 publications found

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]

PRKDC Gene-Disease associations (from GenCC):

• severe combined immunodeficiency due to DNA-PKcs deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKDC	NM_006904.7	c.8153-640A>C		intron_variant	Intron 59 of 85	ENST00000314191.7	NP_008835.5
PRKDC	NM_001081640.2	c.8153-640A>C		intron_variant	Intron 59 of 84		NP_001075109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKDC	ENST00000314191.7	c.8153-640A>C		intron_variant	Intron 59 of 85	1	NM_006904.7	ENSP00000313420.3
PRKDC	ENST00000338368.7	c.8153-640A>C		intron_variant	Intron 59 of 84	1		ENSP00000345182.4
PRKDC	ENST00000697608.1	n.32A>C		non_coding_transcript_exon_variant	Exon 1 of 3
PRKDC	ENST00000697603.1	c.830-640A>C		intron_variant	Intron 6 of 32			ENSP00000513358.1

Frequencies

GnomAD3 genomes AF: 0.0350 AC: 5319 AN: 151904 Hom.: 147 Cov.: 33

Gnomad AFR AF: 0.00837

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0267

Gnomad ASJ AF: 0.0370

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0199

Gnomad FIN AF: 0.0254

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0571

Gnomad OTH AF: 0.0350

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0350 AC: 5314 AN: 152022 Hom.: 147 Cov.: 33 AF XY: 0.0322 AC XY: 2393 AN XY: 74308

African (AFR) AF: 0.00835 AC: 346 AN: 41454

American (AMR) AF: 0.0267 AC: 408 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0370 AC: 128 AN: 3464

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5168

South Asian (SAS) AF: 0.0197 AC: 95 AN: 4812

European-Finnish (FIN) AF: 0.0254 AC: 268 AN: 10542

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0571 AC: 3884 AN: 67980

Other (OTH) AF: 0.0341 AC: 72 AN: 2110

Alfa AF: 0.0485 Hom.: 86

Bravo AF: 0.0342

Asia WGS AF: 0.00982 AC: 34 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.60
DANN	Benign	0.58
PhyloP100		-0.77
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs8178179; hg19: chr8-48745127;