rs56053523

Variant names:

• chr8-47820910-G-A
• rs56053523
• NM_006904.7:c.9145C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-47820910-G-A
• chr8-47820910-G-C

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_006904.7(PRKDC):​c.9145C>T​(p.Leu3049Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00831 in 1,606,574 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0064 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0085 (67 hom.)
• Consequence: PRKDC NM_006904.7 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.538
• Publications: 7 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 8-47820910-G-A is Benign according to our data. Variant chr8-47820910-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 380484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.538 with no splicing effect.
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKDC	NM_006904.7	MANE Select	c.9145C>T	p.Leu3049Leu	synonymous	Exon 66 of 86	NP_008835.5
	PRKDC	NM_001081640.2		c.9145C>T	p.Leu3049Leu	synonymous	Exon 66 of 85	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.9145C>T	p.Leu3049Leu	synonymous	Exon 66 of 86	ENSP00000313420.3	P78527-1
	PRKDC	ENST00000338368.7	TSL:1	c.9145C>T	p.Leu3049Leu	synonymous	Exon 66 of 85	ENSP00000345182.4	P78527-2
	PRKDC	ENST00000911724.1		c.9154C>T	p.Leu3052Leu	synonymous	Exon 66 of 86	ENSP00000581783.1

Frequencies

GnomAD3 genomes AF: 0.00645 AC: 980 AN: 152046 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00400

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.0152

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00957

Gnomad OTH AF: 0.00528

GnomAD2 exomes AF: 0.00645 AC: 1602 AN: 248532 AF XY: 0.00613

Gnomad AFR exome AF: 0.00175

Gnomad AMR exome AF: 0.00210

Gnomad ASJ exome AF: 0.00807

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0171

Gnomad NFE exome AF: 0.00887

Gnomad OTH exome AF: 0.00464

GnomAD4 exome AF: 0.00850 AC: 12364 AN: 1454410 Hom.: 67 Cov.: 30 AF XY: 0.00813 AC XY: 5884 AN XY: 723444

African (AFR) AF: 0.00147 AC: 49 AN: 33412

American (AMR) AF: 0.00233 AC: 104 AN: 44614

Ashkenazi Jewish (ASJ) AF: 0.00902 AC: 234 AN: 25936

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39654

South Asian (SAS) AF: 0.000848 AC: 72 AN: 84878

European-Finnish (FIN) AF: 0.0148 AC: 781 AN: 52928

Middle Eastern (MID) AF: 0.000349 AC: 2 AN: 5736

European-Non Finnish (NFE) AF: 0.00958 AC: 10606 AN: 1107262

Other (OTH) AF: 0.00858 AC: 515 AN: 59990

GnomAD4 genome AF: 0.00645 AC: 981 AN: 152164 Hom.: 3 Cov.: 32 AF XY: 0.00639 AC XY: 475 AN XY: 74392

African (AFR) AF: 0.00147 AC: 61 AN: 41538

American (AMR) AF: 0.00399 AC: 61 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00922 AC: 32 AN: 3470

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

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4820

European-Finnish (FIN) AF: 0.0152 AC: 160 AN: 10558

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

European-Non Finnish (NFE) AF: 0.00959 AC: 652 AN: 68000

Other (OTH) AF: 0.00522 AC: 11 AN: 2106

Alfa AF: 0.00772 Hom.: 5

Bravo AF: 0.00526

Asia WGS AF: 0.00115 AC: 5 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (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	-0.39
CADD	Benign	6.2
DANN	Benign	0.54
PhyloP100		0.54
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: rs56053523; hg19: chr8-48733471; COSMIC: COSV58058155;