chr8-47879481-A-T

Variant names:

• chr8-47879481-A-T
• rs8178111
• NM_006904.7:c.5235+10T>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_006904.7(PRKDC):​c.5235+10T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000563 in 1,557,436 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00068 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00055 (10 hom.)
• Consequence: PRKDC NM_006904.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00100
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 8-47879481-A-T is Benign according to our data. Variant chr8-47879481-A-T is described in ClinVar as Benign. ClinVar VariationId is 475230.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000683 (104/152356) while in subpopulation EAS AF = 0.0191 (99/5184). AF 95% confidence interval is 0.0161. There are 3 homozygotes in GnomAd4. There are 59 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKDC	NM_006904.7	MANE Select	c.5235+10T>A		intron	N/A	NP_008835.5
	PRKDC	NM_001081640.2		c.5235+10T>A		intron	N/A	NP_001075109.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKDC	ENST00000314191.7	TSL:1 MANE Select	c.5235+10T>A		intron	N/A	ENSP00000313420.3
	PRKDC	ENST00000338368.7	TSL:1	c.5235+10T>A		intron	N/A	ENSP00000345182.4

Frequencies

GnomAD3 genomes AF: 0.000683 AC: 104 AN: 152238 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0191

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00152 AC: 288 AN: 189844 AF XY: 0.00134

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000394

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0199

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000119

Gnomad OTH exome AF: 0.000416

GnomAD4 exome AF: 0.000550 AC: 773 AN: 1405080 Hom.: 10 Cov.: 31 AF XY: 0.000526 AC XY: 364 AN XY: 692632

African (AFR) AF: 0.0000313 AC: 1 AN: 31912

American (AMR) AF: 0.0000548 AC: 2 AN: 36522

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25132

East Asian (EAS) AF: 0.0188 AC: 711 AN: 37760

South Asian (SAS) AF: 0.000285 AC: 22 AN: 77182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51610

Middle Eastern (MID) AF: 0.000386 AC: 2 AN: 5182

European-Non Finnish (NFE) AF: 0.00000647 AC: 7 AN: 1081528

Other (OTH) AF: 0.000481 AC: 28 AN: 58252

GnomAD4 genome AF: 0.000683 AC: 104 AN: 152356 Hom.: 3 Cov.: 32 AF XY: 0.000792 AC XY: 59 AN XY: 74518

African (AFR) AF: 0.00 AC: 0 AN: 41588

American (AMR) AF: 0.0000653 AC: 1 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0191 AC: 99 AN: 5184

South Asian (SAS) AF: 0.000827 AC: 4 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000171 Hom.: 0

Bravo AF: 0.000790

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	12
DANN	Benign	0.61
PhyloP100		-0.0010
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs8178111; hg19: chr8-48792042;