rs8178085

Variant names:

• chr8-47898144-T-G
• rs8178085
• NM_006904.7:c.3464+326A>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.3464+326A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0234 in 152,334 control chromosomes in the GnomAD database, including 107 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 0.023 (107 hom., cov: 33)
• Consequence: PRKDC NM_006904.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490
• Publications: 5 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKDC	NM_006904.7	c.3464+326A>C		intron_variant	Intron 29 of 85	ENST00000314191.7	NP_008835.5
PRKDC	NM_001081640.2	c.3464+326A>C		intron_variant	Intron 29 of 84		NP_001075109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKDC	ENST00000314191.7	c.3464+326A>C		intron_variant	Intron 29 of 85	1	NM_006904.7	ENSP00000313420.3
PRKDC	ENST00000338368.7	c.3464+326A>C		intron_variant	Intron 29 of 84	1		ENSP00000345182.4

Frequencies

GnomAD3 genomes AF: 0.0234 AC: 3555 AN: 152216 Hom.: 108 Cov.: 33

Gnomad AFR AF: 0.0632

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00700

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0848

Gnomad SAS AF: 0.0161

Gnomad FIN AF: 0.0134

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00190

Gnomad OTH AF: 0.0182

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

GnomAD4 genome AF: 0.0233 AC: 3557 AN: 152334 Hom.: 107 Cov.: 33 AF XY: 0.0239 AC XY: 1783 AN XY: 74502

African (AFR) AF: 0.0632 AC: 2625 AN: 41556

American (AMR) AF: 0.00699 AC: 107 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0840 AC: 436 AN: 5188

South Asian (SAS) AF: 0.0164 AC: 79 AN: 4826

European-Finnish (FIN) AF: 0.0134 AC: 142 AN: 10624

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00190 AC: 129 AN: 68042

Other (OTH) AF: 0.0175 AC: 37 AN: 2114

Alfa AF: 0.00810 Hom.: 34

Bravo AF: 0.0254

Asia WGS AF: 0.0560 AC: 194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.66
PhyloP100		0.049
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: rs8178085; hg19: chr8-48810704;