rs2213178

Positions:

• chr8-47904156-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006904.7(PRKDC):​c.3042+713C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,152 control chromosomes in the GnomAD database, including 4,248 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 0.21 (4248 hom., cov: 32)
• Consequence: PRKDC NM_006904.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKDC	NM_006904.7	c.3042+713C>T		intron_variant		ENST00000314191.7
PRKDC	NM_001081640.2	c.3042+713C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKDC	ENST00000314191.7	c.3042+713C>T		intron_variant		1	NM_006904.7	P1
PRKDC	ENST00000338368.7	c.3042+713C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31332 AN: 152034 Hom.: 4246 Cov.: 32

Gnomad AFR AF: 0.0546

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.206 AC: 31320 AN: 152152 Hom.: 4248 Cov.: 32 AF XY: 0.210 AC XY: 15648 AN XY: 74388

Gnomad4 AFR AF: 0.0543

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.423

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.216

Alfa AF: 0.267 Hom.: 8062

Bravo AF: 0.185

Asia WGS AF: 0.262 AC: 908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.060
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs2213178; hg19: chr8-48816716;