chr8-47776888-G-A

Variant names:

• chr8-47776888-G-A
• rs56123237
• NM_006904.7:c.12138C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_006904.7(PRKDC):​c.12138C>T​(p.Tyr4046Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 1,613,806 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (3 hom.)
• Consequence: PRKDC NM_006904.7 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.306
• Publications: 3 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 8-47776888-G-A is Benign according to our data. Variant chr8-47776888-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 542026.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.306 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 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.12138C>T	p.Tyr4046Tyr	synonymous	Exon 85 of 86	NP_008835.5
	PRKDC	NM_001081640.2		c.12045C>T	p.Tyr4015Tyr	synonymous	Exon 84 of 85	NP_001075109.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKDC	ENST00000314191.7	TSL:1 MANE Select	c.12138C>T	p.Tyr4046Tyr	synonymous	Exon 85 of 86	ENSP00000313420.3
	PRKDC	ENST00000338368.7	TSL:1	c.12045C>T	p.Tyr4015Tyr	synonymous	Exon 84 of 85	ENSP00000345182.4
	PRKDC	ENST00000697603.1		c.4815C>T	p.Tyr1605Tyr	synonymous	Exon 32 of 33	ENSP00000513358.1

Frequencies

GnomAD3 genomes AF: 0.00188 AC: 286 AN: 152078 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00403

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00151

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00112 AC: 278 AN: 249100 AF XY: 0.00116

Gnomad AFR exome AF: 0.00472

Gnomad AMR exome AF: 0.000551

Gnomad ASJ exome AF: 0.000497

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000278

Gnomad NFE exome AF: 0.00126

Gnomad OTH exome AF: 0.00182

GnomAD4 exome AF: 0.00134 AC: 1962 AN: 1461610 Hom.: 3 Cov.: 31 AF XY: 0.00132 AC XY: 959 AN XY: 727080

African (AFR) AF: 0.00478 AC: 160 AN: 33476

American (AMR) AF: 0.000514 AC: 23 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00107 AC: 28 AN: 26132

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39694

South Asian (SAS) AF: 0.000846 AC: 73 AN: 86238

European-Finnish (FIN) AF: 0.000187 AC: 10 AN: 53400

Middle Eastern (MID) AF: 0.00260 AC: 15 AN: 5768

European-Non Finnish (NFE) AF: 0.00135 AC: 1504 AN: 1111828

Other (OTH) AF: 0.00244 AC: 147 AN: 60364

GnomAD4 genome AF: 0.00188 AC: 286 AN: 152196 Hom.: 1 Cov.: 32 AF XY: 0.00177 AC XY: 132 AN XY: 74422

African (AFR) AF: 0.00402 AC: 167 AN: 41514

American (AMR) AF: 0.000392 AC: 6 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

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

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4824

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10582

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

European-Non Finnish (NFE) AF: 0.00151 AC: 103 AN: 68022

Other (OTH) AF: 0.00142 AC: 3 AN: 2108

Alfa AF: 0.00157 Hom.: 2

Bravo AF: 0.00215

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00180

EpiControl AF: 0.00160

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Apr 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PRKDC: BP4, BP7

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	-0.57
CADD	Benign	0.60
DANN	Benign	0.48
PhyloP100		0.31
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	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: rs56123237; hg19: chr8-48689449; COSMIC: COSV104628472;