rs573302015
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006904.7(PRKDC):āc.6397C>Gā(p.Leu2133Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000231 in 1,560,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00014 ( 0 hom., cov: 33)
Exomes š: 0.0000099 ( 0 hom. )
Consequence
PRKDC
NM_006904.7 missense
NM_006904.7 missense
Scores
1
8
8
Clinical Significance
Conservation
PhyloP100: 1.93
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=0.24011052).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKDC | NM_006904.7 | c.6397C>G | p.Leu2133Val | missense_variant | 48/86 | ENST00000314191.7 | |
PRKDC | NM_001081640.2 | c.6397C>G | p.Leu2133Val | missense_variant | 48/85 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKDC | ENST00000314191.7 | c.6397C>G | p.Leu2133Val | missense_variant | 48/86 | 1 | NM_006904.7 | P1 | |
PRKDC | ENST00000338368.7 | c.6397C>G | p.Leu2133Val | missense_variant | 48/85 | 1 | |||
PRKDC | ENST00000697609.1 | n.558C>G | non_coding_transcript_exon_variant | 2/4 | |||||
PRKDC | ENST00000697610.1 | n.198C>G | non_coding_transcript_exon_variant | 3/4 |
Frequencies
GnomAD3 genomes ? AF: 0.000145 AC: 22AN: 152170Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000208 AC: 4AN: 192284Hom.: 0 AF XY: 0.0000193 AC XY: 2AN XY: 103360
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GnomAD4 exome AF: 0.00000994 AC: 14AN: 1408414Hom.: 0 Cov.: 30 AF XY: 0.00000860 AC XY: 6AN XY: 697838
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GnomAD4 genome ? AF: 0.000144 AC: 22AN: 152288Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74462
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Severe combined immunodeficiency due to DNA-PKcs deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 19, 2023 | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2133 of the PRKDC protein (p.Leu2133Val). This variant is present in population databases (rs573302015, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with PRKDC-related conditions. ClinVar contains an entry for this variant (Variation ID: 576325). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PRKDC protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
REVEL
Uncertain
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MutPred
Gain of methylation at K2132 (P = 0.0322);Gain of methylation at K2132 (P = 0.0322);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at