8-47914053-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006904.7(PRKDC):​c.2629G>A​(p.Asp877Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D877H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

PRKDC
NM_006904.7 missense

Scores

1
3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.58
Variant links:
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]

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ACMG classification

Classification made for transcript

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=0.1503168).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRKDCNM_006904.7 linkc.2629G>A p.Asp877Asn missense_variant Exon 24 of 86 ENST00000314191.7 NP_008835.5 P78527-1
PRKDCNM_001081640.2 linkc.2629G>A p.Asp877Asn missense_variant Exon 24 of 85 NP_001075109.1 P78527-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRKDCENST00000314191.7 linkc.2629G>A p.Asp877Asn missense_variant Exon 24 of 86 1 NM_006904.7 ENSP00000313420.3 P78527-1
PRKDCENST00000338368.7 linkc.2629G>A p.Asp877Asn missense_variant Exon 24 of 85 1 ENSP00000345182.4 P78527-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 24, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The p.D877N variant (also known as c.2629G>A), located in coding exon 24 of the PRKDC gene, results from a G to A substitution at nucleotide position 2629. The aspartic acid at codon 877 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.075
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.74
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.15
T;.
Eigen
Benign
-0.032
Eigen_PC
Benign
0.026
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.94
D;D
M_CAP
Benign
0.0096
T
MetaRNN
Benign
0.15
T;T
MetaSVM
Benign
-0.91
T
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-1.1
N;N
REVEL
Benign
0.059
Sift
Benign
0.073
T;T
Sift4G
Uncertain
0.014
D;D
Polyphen
0.027
B;P
Vest4
0.21
MutPred
0.16
Gain of MoRF binding (P = 0.0663);Gain of MoRF binding (P = 0.0663);
MVP
0.41
MPC
0.16
ClinPred
0.92
D
GERP RS
4.7
Varity_R
0.14
gMVP
0.099

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: chr8-48826613; API