rs8178060

Variant names:

• chr8-47912405-C-G
• rs8178060
• NM_006904.7:c.2934+5G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-47912405-C-G
• chr8-47912405-C-T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_006904.7(PRKDC):​c.2934+5G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,567,014 control chromosomes in the GnomAD database, including 1,323 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.052 (705 hom., cov: 32)
  • Exomes 𝑓: 0.0057 (618 hom.)
• Consequence: PRKDC NM_006904.7 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.800
• 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: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 8-47912405-C-G is Benign according to our data. Variant chr8-47912405-C-G is described in ClinVar as Benign. ClinVar VariationId is 379644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

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.2934+5G>C		splice_region intron	N/A	NP_008835.5
	PRKDC	NM_001081640.2		c.2934+5G>C		splice_region intron	N/A	NP_001075109.1	P78527-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKDC	ENST00000314191.7	TSL:1 MANE Select	c.2934+5G>C		splice_region intron	N/A	ENSP00000313420.3	P78527-1
	PRKDC	ENST00000338368.7	TSL:1	c.2934+5G>C		splice_region intron	N/A	ENSP00000345182.4	P78527-2
	PRKDC	ENST00000911724.1		c.2934+5G>C		splice_region intron	N/A	ENSP00000581783.1

Frequencies

GnomAD3 genomes AF: 0.0524 AC: 7967 AN: 152142 Hom.: 704 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0203

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000485

Gnomad OTH AF: 0.0415

GnomAD2 exomes AF: 0.0140 AC: 3091 AN: 220860 AF XY: 0.0107

Gnomad AFR exome AF: 0.186

Gnomad AMR exome AF: 0.00856

Gnomad ASJ exome AF: 0.00206

Gnomad EAS exome AF: 0.0000627

Gnomad FIN exome AF: 0.0000483

Gnomad NFE exome AF: 0.000338

Gnomad OTH exome AF: 0.00757

GnomAD4 exome AF: 0.00567 AC: 8027 AN: 1414754 Hom.: 618 Cov.: 30 AF XY: 0.00513 AC XY: 3594 AN XY: 700128

African (AFR) AF: 0.192 AC: 6028 AN: 31416

American (AMR) AF: 0.00977 AC: 373 AN: 38168

Ashkenazi Jewish (ASJ) AF: 0.00193 AC: 47 AN: 24354

East Asian (EAS) AF: 0.0000526 AC: 2 AN: 38010

South Asian (SAS) AF: 0.00513 AC: 408 AN: 79604

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52562

Middle Eastern (MID) AF: 0.0116 AC: 65 AN: 5594

European-Non Finnish (NFE) AF: 0.000329 AC: 358 AN: 1086800

Other (OTH) AF: 0.0128 AC: 745 AN: 58246

GnomAD4 genome AF: 0.0524 AC: 7977 AN: 152260 Hom.: 705 Cov.: 32 AF XY: 0.0507 AC XY: 3777 AN XY: 74462

African (AFR) AF: 0.181 AC: 7512 AN: 41516

American (AMR) AF: 0.0202 AC: 309 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00580 AC: 28 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000485 AC: 33 AN: 68028

Other (OTH) AF: 0.0406 AC: 86 AN: 2116

Alfa AF: 0.00334 Hom.: 11

Bravo AF: 0.0599

Asia WGS AF: 0.0170 AC: 59 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	PRKDC-related disorder (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	-0.33
CADD	Benign	17
DANN	Benign	0.82
PhyloP100		0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Mutation Taster		=95/5	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: rs8178060; hg19: chr8-48824965;