chr8-47854957-C-G

Variant names:

• chr8-47854957-C-G
• rs8178158
• NM_006904.7:c.6761+265G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006904.7(PRKDC):​c.6761+265G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0789 in 152,220 control chromosomes in the GnomAD database, including 693 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.079 (693 hom., cov: 33)
• Consequence: PRKDC NM_006904.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.276
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 8-47854957-C-G is Benign according to our data. Variant chr8-47854957-C-G is described in ClinVar as Benign. ClinVar VariationId is 1270550.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.186 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.6761+265G>C		intron	N/A	NP_008835.5
	PRKDC	NM_001081640.2		c.6761+265G>C		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.6761+265G>C		intron	N/A	ENSP00000313420.3	P78527-1
	PRKDC	ENST00000338368.7	TSL:1	c.6761+265G>C		intron	N/A	ENSP00000345182.4	P78527-2
	PRKDC	ENST00000911724.1		c.6761+265G>C		intron	N/A	ENSP00000581783.1

Frequencies

GnomAD3 genomes AF: 0.0789 AC: 12003 AN: 152102 Hom.: 695 Cov.: 33

Gnomad AFR AF: 0.0853

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.0897

Gnomad EAS AF: 0.0826

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.0325

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0488

Gnomad OTH AF: 0.0939

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

GnomAD4 genome AF: 0.0789 AC: 12013 AN: 152220 Hom.: 693 Cov.: 33 AF XY: 0.0805 AC XY: 5990 AN XY: 74428

African (AFR) AF: 0.0851 AC: 3536 AN: 41532

American (AMR) AF: 0.192 AC: 2930 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0897 AC: 311 AN: 3466

East Asian (EAS) AF: 0.0828 AC: 428 AN: 5172

South Asian (SAS) AF: 0.155 AC: 745 AN: 4818

European-Finnish (FIN) AF: 0.0325 AC: 345 AN: 10612

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0488 AC: 3319 AN: 68014

Other (OTH) AF: 0.0948 AC: 200 AN: 2110

Alfa AF: 0.0206 Hom.: 9

Bravo AF: 0.0966

Asia WGS AF: 0.113 AC: 391 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.69
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs8178158; hg19: chr8-48767518;