8-47929148-G-T

Variant names:

• chr8-47929148-G-T
• rs8178046
• NM_006904.7:c.2083C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006904.7(PRKDC):​c.2083C>A​(p.Pro695Thr) variant causes a missense 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. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P695S) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRKDC NM_006904.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.962

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.070953935).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKDC	NM_006904.7	c.2083C>A	p.Pro695Thr	missense_variant	Exon 19 of 86	ENST00000314191.7	NP_008835.5
PRKDC	NM_001081640.2	c.2083C>A	p.Pro695Thr	missense_variant	Exon 19 of 85		NP_001075109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKDC	ENST00000314191.7	c.2083C>A	p.Pro695Thr	missense_variant	Exon 19 of 86	1	NM_006904.7	ENSP00000313420.3
PRKDC	ENST00000338368.7	c.2083C>A	p.Pro695Thr	missense_variant	Exon 19 of 85	1		ENSP00000345182.4
PRKDC	ENST00000541488.1	n.22C>A		non_coding_transcript_exon_variant	Exon 1 of 3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000501 AC: 1 AN: 199624 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 106480

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: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000118

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1427158 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 706408

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000167 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	15
DANN	Benign	0.31
DEOGEN2	Benign	0.16	T;.
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.55
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.071	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.012
Sift	Benign	0.43	T;T
Sift4G	Benign	0.67	T;T
Polyphen		0.0090	B;B
Vest4		0.084
MutPred		0.14		Gain of phosphorylation at P695 (P = 0.0293);Gain of phosphorylation at P695 (P = 0.0293);
MVP		0.59
MPC		0.20
ClinPred		0.030	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.048
gMVP		0.27

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: rs8178046; hg19: chr8-48841708;