8-47849499-A-T

Variant names:

• chr8-47849499-A-T
• NM_006904.7:c.7010T>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006904.7(PRKDC):​c.7010T>A​(p.Leu2337Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000618 in 1,457,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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: 0.0000062 (0 hom.)
• Consequence: PRKDC NM_006904.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.08

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKDC	NM_006904.7	c.7010T>A	p.Leu2337Gln	missense_variant	Exon 53 of 86	ENST00000314191.7	NP_008835.5
PRKDC	NM_001081640.2	c.7010T>A	p.Leu2337Gln	missense_variant	Exon 53 of 85		NP_001075109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKDC	ENST00000314191.7	c.7010T>A	p.Leu2337Gln	missense_variant	Exon 53 of 86	1	NM_006904.7	ENSP00000313420.3
PRKDC	ENST00000338368.7	c.7010T>A	p.Leu2337Gln	missense_variant	Exon 53 of 85	1		ENSP00000345182.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000618 AC: 9 AN: 1457132 Hom.: 0 Cov.: 30 AF XY: 0.00000828 AC XY: 6 AN XY: 724700

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000810

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	0.10
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	20
DANN	Benign	0.31
DEOGEN2	Benign	0.13	T;.
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Benign	0.36	T
REVEL	Benign	0.16
Sift4G	Benign	0.078	T;T
Polyphen		0.41	B;.
Vest4		0.26
MutPred		0.38		Gain of disorder (P = 0.0223);Gain of disorder (P = 0.0223);
MVP		0.66
MPC		0.22
ClinPred		0.24	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.36		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.36		Position offset: -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: chr8-48762060;