8-47858141-C-G

Variant names:

• chr8-47858141-C-G
• rs7003908
• NM_006904.7:c.6465+375G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006904.7(PRKDC):​c.6465+375G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
• Consequence: PRKDC NM_006904.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.839
• Publications: 63 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: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKDC	NM_006904.7	c.6465+375G>C		intron_variant	Intron 48 of 85	ENST00000314191.7	NP_008835.5
PRKDC	NM_001081640.2	c.6465+375G>C		intron_variant	Intron 48 of 84		NP_001075109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKDC	ENST00000314191.7	c.6465+375G>C		intron_variant	Intron 48 of 85	1	NM_006904.7	ENSP00000313420.3
PRKDC	ENST00000338368.7	c.6465+375G>C		intron_variant	Intron 48 of 84	1		ENSP00000345182.4
PRKDC	ENST00000697609.1	n.626+375G>C		intron_variant	Intron 2 of 3
PRKDC	ENST00000697610.1	n.266+375G>C		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes Cov.: 30

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

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.066
DANN	Benign	0.17
PhyloP100		-0.84

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: rs7003908; hg19: chr8-48770702;