chr8-47943304-C-A

Position:

• chr8-47943304-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006904.7(PRKDC):​c.871G>T​(p.Val291Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,459,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict 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: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: PRKDC NM_006904.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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]

ENSG00000287959 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.062347293).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKDC	NM_006904.7	c.871G>T	p.Val291Leu	missense_variant	10/86	ENST00000314191.7	NP_008835.5
PRKDC	NM_001081640.2	c.871G>T	p.Val291Leu	missense_variant	10/85		NP_001075109.1
LOC105375818	XR_007060906.1	n.796+540C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKDC	ENST00000314191.7	c.871G>T	p.Val291Leu	missense_variant	10/86	1	NM_006904.7	ENSP00000313420.3
PRKDC	ENST00000338368.7	c.871G>T	p.Val291Leu	missense_variant	10/85	1		ENSP00000345182.4
ENSG00000287959	ENST00000658178.1	n.1336C>A		non_coding_transcript_exon_variant	2/2
PRKDC	ENST00000697591.1	n.912G>T		non_coding_transcript_exon_variant	10/15

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000122 AC: 3 AN: 245284 Hom.: 0 AF XY: 0.0000226 AC XY: 3 AN XY: 132902

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000100

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1459816 Hom.: 0 Cov.: 31 AF XY: 0.00000826 AC XY: 6 AN XY: 725970

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000700

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	5.7
DANN	Benign	0.85
DEOGEN2	Benign	0.10	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.13	N
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.062	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.85	N;N
REVEL	Benign	0.032
Sift	Benign	0.33	T;T
Sift4G	Benign	0.32	T;T
Polyphen		0.0010	B;B
Vest4		0.31
MutPred		0.28		Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);
MVP		0.52
MPC		0.16
ClinPred		0.024	T
GERP RS		-3.6
Varity_R		0.050
gMVP		0.20

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

Publications

LitVar

Other links and lift over

dbSNP: rs372117480; hg19: chr8-48855864;