rs78163867

Variant names:

• chr8-47826778-G-A
• rs78163867
• NM_006904.7:c.8661C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-47826778-G-A
• chr8-47826778-G-C
• chr8-47826778-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_006904.7(PRKDC):​c.8661C>T​(p.Pro2887Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000973 in 1,611,454 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P2887P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0048 (8 hom., cov: 33)
  • Exomes 𝑓: 0.00057 (4 hom.)
• Consequence: PRKDC NM_006904.7 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.19
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 8-47826778-G-A is Benign according to our data. Variant chr8-47826778-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 475240.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.19 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00482 (734/152338) while in subpopulation AFR AF = 0.0167 (695/41572). AF 95% confidence interval is 0.0157. There are 8 homozygotes in GnomAd4. There are 335 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

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.8661C>T	p.Pro2887Pro	synonymous	Exon 63 of 86	NP_008835.5
	PRKDC	NM_001081640.2		c.8661C>T	p.Pro2887Pro	synonymous	Exon 63 of 85	NP_001075109.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKDC	ENST00000314191.7	TSL:1 MANE Select	c.8661C>T	p.Pro2887Pro	synonymous	Exon 63 of 86	ENSP00000313420.3
	PRKDC	ENST00000338368.7	TSL:1	c.8661C>T	p.Pro2887Pro	synonymous	Exon 63 of 85	ENSP00000345182.4
	PRKDC	ENST00000911724.1		c.8670C>T	p.Pro2890Pro	synonymous	Exon 63 of 86	ENSP00000581783.1

Frequencies

GnomAD3 genomes AF: 0.00484 AC: 736 AN: 152220 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.0168

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.00133 AC: 322 AN: 241704 AF XY: 0.000940

Gnomad AFR exome AF: 0.0195

Gnomad AMR exome AF: 0.000708

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000567

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000165

Gnomad OTH exome AF: 0.000341

GnomAD4 exome AF: 0.000572 AC: 834 AN: 1459116 Hom.: 4 Cov.: 31 AF XY: 0.000462 AC XY: 335 AN XY: 725626

African (AFR) AF: 0.0194 AC: 650 AN: 33430

American (AMR) AF: 0.000698 AC: 31 AN: 44416

Ashkenazi Jewish (ASJ) AF: 0.0000385 AC: 1 AN: 26006

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39638

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85716

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52996

Middle Eastern (MID) AF: 0.000875 AC: 5 AN: 5712

European-Non Finnish (NFE) AF: 0.0000945 AC: 105 AN: 1110976

Other (OTH) AF: 0.000648 AC: 39 AN: 60226

GnomAD4 genome AF: 0.00482 AC: 734 AN: 152338 Hom.: 8 Cov.: 33 AF XY: 0.00450 AC XY: 335 AN XY: 74486

African (AFR) AF: 0.0167 AC: 695 AN: 41572

American (AMR) AF: 0.00124 AC: 19 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68034

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00211 Hom.: 3

Bravo AF: 0.00547

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)
-	-	1	Severe combined immunodeficiency due to DNA-PKcs deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.86
DANN	Benign	0.89
PhyloP100		-4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=90/10	polymorphism

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: rs78163867; hg19: chr8-48739339;