8-47931496-GTT-GT

Variant names:

• chr8-47931496-GT-G
• rs546905091
• NM_006904.7:c.1777-710delA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_006904.7(PRKDC):​c.1777-710delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00406 in 144,012 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0041 (2 hom., cov: 32)
• Consequence: PRKDC NM_006904.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.559
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 2 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.1777-710delA		intron	N/A	NP_008835.5
	PRKDC	NM_001081640.2		c.1777-710delA		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.1777-710delA		intron	N/A	ENSP00000313420.3	P78527-1
	PRKDC	ENST00000338368.7	TSL:1	c.1777-710delA		intron	N/A	ENSP00000345182.4	P78527-2
	PRKDC	ENST00000911724.1		c.1777-710delA		intron	N/A	ENSP00000581783.1

Frequencies

GnomAD3 genomes AF: 0.00405 AC: 583 AN: 143972 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00600

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00342

Gnomad ASJ AF: 0.0116

Gnomad EAS AF: 0.00344

Gnomad SAS AF: 0.00646

Gnomad FIN AF: 0.00386

Gnomad MID AF: 0.0133

Gnomad NFE AF: 0.00255

Gnomad OTH AF: 0.00359

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

GnomAD4 genome AF: 0.00406 AC: 584 AN: 144012 Hom.: 2 Cov.: 32 AF XY: 0.00403 AC XY: 282 AN XY: 70030

African (AFR) AF: 0.00601 AC: 238 AN: 39570

American (AMR) AF: 0.00342 AC: 49 AN: 14320

Ashkenazi Jewish (ASJ) AF: 0.0116 AC: 39 AN: 3348

East Asian (EAS) AF: 0.00365 AC: 18 AN: 4936

South Asian (SAS) AF: 0.00627 AC: 28 AN: 4468

European-Finnish (FIN) AF: 0.00386 AC: 35 AN: 9062

Middle Eastern (MID) AF: 0.0108 AC: 3 AN: 278

European-Non Finnish (NFE) AF: 0.00256 AC: 167 AN: 65166

Other (OTH) AF: 0.00356 AC: 7 AN: 1964

Alfa AF: 0.000217 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.56
Mutation Taster		=99/1	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: rs546905091; hg19: chr8-48844056;