rs1231201

Variant names:

• chr8-47933603-T-A
• rs1231201
• NM_006904.7:c.1623+362A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006904.7(PRKDC):​c.1623+362A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 152,174 control chromosomes in the GnomAD database, including 16,659 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.42 (16659 hom., cov: 33)
• Consequence: PRKDC NM_006904.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.912
• Publications: 4 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.657 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.1623+362A>T		intron	N/A	NP_008835.5
	PRKDC	NM_001081640.2		c.1623+362A>T		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.1623+362A>T		intron	N/A	ENSP00000313420.3	P78527-1
	PRKDC	ENST00000338368.7	TSL:1	c.1623+362A>T		intron	N/A	ENSP00000345182.4	P78527-2
	PRKDC	ENST00000911724.1		c.1623+362A>T		intron	N/A	ENSP00000581783.1

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63758 AN: 152056 Hom.: 16651 Cov.: 33

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.429

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

GnomAD4 genome AF: 0.419 AC: 63778 AN: 152174 Hom.: 16659 Cov.: 33 AF XY: 0.423 AC XY: 31450 AN XY: 74388

African (AFR) AF: 0.106 AC: 4397 AN: 41558

American (AMR) AF: 0.494 AC: 7541 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1202 AN: 3470

East Asian (EAS) AF: 0.676 AC: 3493 AN: 5166

South Asian (SAS) AF: 0.332 AC: 1605 AN: 4832

European-Finnish (FIN) AF: 0.587 AC: 6213 AN: 10578

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.558 AC: 37921 AN: 67980

Other (OTH) AF: 0.431 AC: 910 AN: 2112

Alfa AF: 0.481 Hom.: 2491

Bravo AF: 0.398

Asia WGS AF: 0.456 AC: 1587 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.69
DANN	Benign	0.41
PhyloP100		0.91
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1231201;

hg19: chr8-48846163;