8-47946373-A-G

Variant names:

• chr8-47946373-A-G
• rs4873772
• NM_006904.7:c.722-2344T>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.722-2344T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 151,706 control chromosomes in the GnomAD database, including 36,412 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 0.69 (36412 hom., cov: 30)
• Consequence: PRKDC NM_006904.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950
• Publications: 23 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: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006904.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKDC	NM_006904.7	MANE Select	c.722-2344T>C		intron	N/A	NP_008835.5
	PRKDC	NM_001081640.2		c.722-2344T>C		intron	N/A	NP_001075109.1	P78527-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKDC	ENST00000314191.7	TSL:1 MANE Select	c.722-2344T>C		intron	N/A	ENSP00000313420.3	P78527-1
	PRKDC	ENST00000338368.7	TSL:1	c.722-2344T>C		intron	N/A	ENSP00000345182.4	P78527-2
	PRKDC	ENST00000911724.1		c.722-2344T>C		intron	N/A	ENSP00000581783.1

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104585 AN: 151590 Hom.: 36368 Cov.: 30

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.768

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.856

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.684

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

GnomAD4 genome AF: 0.690 AC: 104686 AN: 151706 Hom.: 36412 Cov.: 30 AF XY: 0.689 AC XY: 51065 AN XY: 74114

African (AFR) AF: 0.698 AC: 28850 AN: 41360

American (AMR) AF: 0.768 AC: 11722 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1803 AN: 3462

East Asian (EAS) AF: 0.856 AC: 4380 AN: 5114

South Asian (SAS) AF: 0.559 AC: 2679 AN: 4790

European-Finnish (FIN) AF: 0.665 AC: 7001 AN: 10524

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.678 AC: 46068 AN: 67900

Other (OTH) AF: 0.686 AC: 1441 AN: 2102

Alfa AF: 0.677 Hom.: 64518

Bravo AF: 0.700

Asia WGS AF: 0.710 AC: 2472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.83
PhyloP100		-0.095
Mutation Taster		=100/0	polymorphism (auto)

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: rs4873772; hg19: chr8-48858933; COSMIC: COSV58051849;