rs8178232

Variant names:

• chr8-47789225-A-C
• NM_006904.7:c.10684T>G

Your query was ambiguous. Multiple possible variants found:

• chr8-47789225-A-C
• chr8-47789225-A-G
• chr8-47789225-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006904.7(PRKDC):​c.10684T>G​(p.Leu3562Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,433,304 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 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: 7.0e-7 (0 hom.)
• Consequence: PRKDC NM_006904.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.727

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34914607).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKDC	NM_006904.7	c.10684T>G	p.Leu3562Val	missense_variant	Exon 75 of 86	ENST00000314191.7	NP_008835.5
PRKDC	NM_001081640.2	c.10684T>G	p.Leu3562Val	missense_variant	Exon 75 of 85		NP_001075109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKDC	ENST00000314191.7	c.10684T>G	p.Leu3562Val	missense_variant	Exon 75 of 86	1	NM_006904.7	ENSP00000313420.3
PRKDC	ENST00000338368.7	c.10684T>G	p.Leu3562Val	missense_variant	Exon 75 of 85	1		ENSP00000345182.4
PRKDC	ENST00000697603.1	c.3361T>G	p.Leu1121Val	missense_variant	Exon 22 of 33			ENSP00000513358.1
PRKDC	ENST00000697602.1	n.1257T>G		non_coding_transcript_exon_variant	Exon 7 of 18

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1433304 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 712088

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000257

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;.
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Pathogenic	3.0	M;M
PrimateAI	Benign	0.48	T
REVEL	Benign	0.085
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.47
MutPred		0.25		Loss of stability (P = 0.0496);Loss of stability (P = 0.0496);
MVP		0.79
MPC		0.69
ClinPred		0.97	D
GERP RS		2.4
Varity_R		0.18
gMVP		0.65

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-48701786;