chr8-47960111-C-A

Position:

• chr8-47960111-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006904.7(PRKDC):​c.16G>T​(p.Ala6Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0058 in 1,504,624 control chromosomes in the GnomAD database, including 352 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (216 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (136 hom.)
• Consequence: PRKDC NM_006904.7 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.301

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014592409).
• BP6: Variant 8-47960111-C-A is Benign according to our data. Variant chr8-47960111-C-A is described in ClinVar as [Benign]. Clinvar id is 379772.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKDC	NM_006904.7	c.16G>T	p.Ala6Ser	missense_variant	1/86	ENST00000314191.7	NP_008835.5
PRKDC	NM_001081640.2	c.16G>T	p.Ala6Ser	missense_variant	1/85		NP_001075109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKDC	ENST00000314191.7	c.16G>T	p.Ala6Ser	missense_variant	1/86	1	NM_006904.7	ENSP00000313420.3
PRKDC	ENST00000338368.7	c.16G>T	p.Ala6Ser	missense_variant	1/85	1		ENSP00000345182.4
PRKDC	ENST00000697591.1	n.57G>T		non_coding_transcript_exon_variant	1/15

Frequencies

GnomAD3 genomes AF: 0.0284 AC: 4328 AN: 152168 Hom.: 216 Cov.: 32

Gnomad AFR AF: 0.0972

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00857

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.0272

GnomAD3 exomes AF: 0.00550 AC: 585 AN: 106398 Hom.: 19 AF XY: 0.00463 AC XY: 274 AN XY: 59214

Gnomad AFR exome AF: 0.131

Gnomad AMR exome AF: 0.00399

Gnomad ASJ exome AF: 0.0208

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000350

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000738

Gnomad OTH exome AF: 0.00576

GnomAD4 exome AF: 0.00324 AC: 4379 AN: 1352344 Hom.: 136 Cov.: 31 AF XY: 0.00299 AC XY: 1991 AN XY: 664850

Gnomad4 AFR exome AF: 0.0961

Gnomad4 AMR exome AF: 0.00574

Gnomad4 ASJ exome AF: 0.0233

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000261

Gnomad4 FIN exome AF: 0.0000301

Gnomad4 NFE exome AF: 0.000401

Gnomad4 OTH exome AF: 0.00778

GnomAD4 genome AF: 0.0285 AC: 4341 AN: 152280 Hom.: 216 Cov.: 32 AF XY: 0.0274 AC XY: 2041 AN XY: 74456

Gnomad4 AFR AF: 0.0972

Gnomad4 AMR AF: 0.00856

Gnomad4 ASJ AF: 0.0202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000529

Gnomad4 OTH AF: 0.0270

Alfa AF: 0.00451 Hom.: 3

Bravo AF: 0.0318

ESP6500AA AF: 0.0575 AC: 146

ESP6500EA AF: 0.00155 AC: 9

ExAC AF: 0.00437 AC: 268

Asia WGS AF: 0.00694 AC: 24 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Severe combined immunodeficiency due to DNA-PKcs deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.7
DANN	Benign	0.82
DEOGEN2	Benign	0.058	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.64	T;T
MetaRNN	Benign	0.0015	T;T
MetaSVM	Benign	-0.93	T
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.20	N;N
REVEL	Benign	0.020
Sift	Benign	0.54	T;T
Sift4G	Benign	0.68	T;T
Polyphen		0.0030	B;B
Vest4		0.042
MVP		0.13
MPC		0.15
ClinPred		0.0054	T
GERP RS		-8.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.024
gMVP		0.16

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: rs8177999; hg19: chr8-48872671;