rs376156239

chr8-47858540-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_006904.7(PRKDC):c.6441C>G(p.Ala2147=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000491 in 1,526,380 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 (★★).

• Frequency:
  • Genomes: 𝑓 0.00033 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00051 (9 hom.)
• Consequence: PRKDC NM_006904.7 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.710

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 8-47858540-G-C is Benign according to our data. Variant chr8-47858540-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 475234.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-47858540-G-C is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.71 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKDC	NM_006904.7	c.6441C>G	p.Ala2147=	synonymous_variant	48/86	ENST00000314191.7
PRKDC	NM_001081640.2	c.6441C>G	p.Ala2147=	synonymous_variant	48/85

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKDC	ENST00000314191.7	c.6441C>G	p.Ala2147=	synonymous_variant	48/86	1	NM_006904.7	P1
PRKDC	ENST00000338368.7	c.6441C>G	p.Ala2147=	synonymous_variant	48/85	1
PRKDC	ENST00000697609.1	n.602C>G		non_coding_transcript_exon_variant	2/4
PRKDC	ENST00000697610.1	n.242C>G		non_coding_transcript_exon_variant	3/4

Frequencies

GnomAD3 genomes AF: 0.000335 AC: 51 AN: 152134 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00106 AC: 187 AN: 175876 Hom.: 3 AF XY: 0.00136 AC XY: 128 AN XY: 93950

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000447

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000715

Gnomad SAS exome AF: 0.00891

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000892

GnomAD4 exome AF: 0.000509 AC: 699 AN: 1374128 Hom.: 9 Cov.: 29 AF XY: 0.000720 AC XY: 490 AN XY: 681006

Gnomad4 AFR exome AF: 0.0000646

Gnomad4 AMR exome AF: 0.0000304

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00863

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000189

Gnomad4 OTH exome AF: 0.000596

GnomAD4 genome AF: 0.000335 AC: 51 AN: 152252 Hom.: 3 Cov.: 32 AF XY: 0.000510 AC XY: 38 AN XY: 74440

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000427 Hom.: 0

Bravo AF: 0.0000491

Asia WGS AF: 0.00578 AC: 20 AN: 3472

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

PRKDC: BP4, BP7, BS2 -

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
Cadd	Benign	8.3
Dann	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs376156239; hg19: chr8-48771101;