rs1231202

Variant names:

• chr8-47933959-T-C
• rs1231202
• NM_006904.7:c.1623+6A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-47933959-T-C
• chr8-47933959-T-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006904.7(PRKDC):​c.1623+6A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.954 in 1,607,496 control chromosomes in the GnomAD database, including 732,409 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.96 (70905 hom., cov: 33)
  • Exomes 𝑓: 0.95 (661504 hom.)
• Consequence: PRKDC NM_006904.7 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5 O:1
• Conservation: PhyloP100: -0.607
• Publications: 15 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 8-47933959-T-C is Benign according to our data. Variant chr8-47933959-T-C is described in ClinVar as Benign. ClinVar VariationId is 379395.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.983 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+6A>G		splice_region intron	N/A	NP_008835.5
	PRKDC	NM_001081640.2		c.1623+6A>G		splice_region 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+6A>G		splice_region intron	N/A	ENSP00000313420.3	P78527-1
	PRKDC	ENST00000338368.7	TSL:1	c.1623+6A>G		splice_region intron	N/A	ENSP00000345182.4	P78527-2
	PRKDC	ENST00000911724.1		c.1623+6A>G		splice_region intron	N/A	ENSP00000581783.1

Frequencies

GnomAD3 genomes AF: 0.965 AC: 146844 AN: 152234 Hom.: 70839 Cov.: 33

Gnomad AFR AF: 0.991

Gnomad AMI AF: 0.997

Gnomad AMR AF: 0.962

Gnomad ASJ AF: 0.914

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.991

Gnomad FIN AF: 0.954

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.949

Gnomad OTH AF: 0.959

GnomAD2 exomes AF: 0.961 AC: 238227 AN: 247968 AF XY: 0.961

Gnomad AFR exome AF: 0.992

Gnomad AMR exome AF: 0.975

Gnomad ASJ exome AF: 0.910

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.953

Gnomad NFE exome AF: 0.944

Gnomad OTH exome AF: 0.954

GnomAD4 exome AF: 0.953 AC: 1387255 AN: 1455144 Hom.: 661504 Cov.: 41 AF XY: 0.955 AC XY: 690910 AN XY: 723764

African (AFR) AF: 0.992 AC: 33092 AN: 33374

American (AMR) AF: 0.974 AC: 43335 AN: 44502

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 23603 AN: 26002

East Asian (EAS) AF: 1.00 AC: 39601 AN: 39608

South Asian (SAS) AF: 0.993 AC: 84821 AN: 85392

European-Finnish (FIN) AF: 0.951 AC: 50610 AN: 53196

Middle Eastern (MID) AF: 0.958 AC: 4419 AN: 4614

European-Non Finnish (NFE) AF: 0.948 AC: 1050351 AN: 1108460

Other (OTH) AF: 0.957 AC: 57423 AN: 59996

GnomAD4 genome AF: 0.965 AC: 146969 AN: 152352 Hom.: 70905 Cov.: 33 AF XY: 0.966 AC XY: 71948 AN XY: 74494

African (AFR) AF: 0.991 AC: 41204 AN: 41582

American (AMR) AF: 0.962 AC: 14730 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.914 AC: 3175 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5186 AN: 5188

South Asian (SAS) AF: 0.992 AC: 4789 AN: 4830

European-Finnish (FIN) AF: 0.954 AC: 10129 AN: 10618

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.949 AC: 64539 AN: 68038

Other (OTH) AF: 0.959 AC: 2026 AN: 2112

Alfa AF: 0.953 Hom.: 79447

Bravo AF: 0.965

Asia WGS AF: 0.996 AC: 3464 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	2	Severe combined immunodeficiency due to DNA-PKcs deficiency (2)
-	-	1	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.15
DANN	Benign	0.51
PhyloP100		-0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs1231202; hg19: chr8-48846519;