8-47946373-A-G

Position:

• chr8-47946373-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKDC	NM_006904.7	c.722-2344T>C		intron_variant		ENST00000314191.7	NP_008835.5
PRKDC	NM_001081640.2	c.722-2344T>C		intron_variant			NP_001075109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKDC	ENST00000314191.7	c.722-2344T>C		intron_variant		1	NM_006904.7	ENSP00000313420.3
PRKDC	ENST00000338368.7	c.722-2344T>C		intron_variant		1		ENSP00000345182.4
PRKDC	ENST00000697591.1	n.763-2344T>C		intron_variant

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

Gnomad4 AFR AF: 0.698

Gnomad4 AMR AF: 0.768

Gnomad4 ASJ AF: 0.521

Gnomad4 EAS AF: 0.856

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.665

Gnomad4 NFE AF: 0.678

Gnomad4 OTH AF: 0.686

Alfa AF: 0.673 Hom.: 45421

Bravo AF: 0.700

Asia WGS AF: 0.710 AC: 2472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.83

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