8-47891114-T-C

Variant names:

• chr8-47891114-T-C
• rs10109984
• NM_006904.7:c.3848-634A>G

Variant summary

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

The NM_006904.7(PRKDC):​c.3848-634A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 151,906 control chromosomes in the GnomAD database, including 24,530 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 0.53 (24530 hom., cov: 31)
• Consequence: PRKDC NM_006904.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.700
• Publications: 18 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.828 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.3848-634A>G		intron	N/A	NP_008835.5
	PRKDC	NM_001081640.2		c.3848-634A>G		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.3848-634A>G		intron	N/A	ENSP00000313420.3	P78527-1
	PRKDC	ENST00000338368.7	TSL:1	c.3848-634A>G		intron	N/A	ENSP00000345182.4	P78527-2
	PRKDC	ENST00000911724.1		c.3848-634A>G		intron	N/A	ENSP00000581783.1

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80606 AN: 151786 Hom.: 24484 Cov.: 31

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.531 AC: 80702 AN: 151906 Hom.: 24530 Cov.: 31 AF XY: 0.530 AC XY: 39345 AN XY: 74238

African (AFR) AF: 0.836 AC: 34623 AN: 41438

American (AMR) AF: 0.473 AC: 7220 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 2092 AN: 3468

East Asian (EAS) AF: 0.322 AC: 1660 AN: 5150

South Asian (SAS) AF: 0.650 AC: 3120 AN: 4802

European-Finnish (FIN) AF: 0.387 AC: 4082 AN: 10538

Middle Eastern (MID) AF: 0.589 AC: 172 AN: 292

European-Non Finnish (NFE) AF: 0.386 AC: 26201 AN: 67940

Other (OTH) AF: 0.525 AC: 1107 AN: 2108

Alfa AF: 0.442 Hom.: 27164

Bravo AF: 0.551

Asia WGS AF: 0.529 AC: 1837 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.4
DANN	Benign	0.35
PhyloP100		-0.70
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: rs10109984; hg19: chr8-48803675;