chr8-47821644-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_006904.7(PRKDC):c.9071C>T(p.Pro3024Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000544 in 1,602,494 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 (★).
Frequency
Genomes: 𝑓 0.00034 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00056 ( 0 hom. )
Consequence
PRKDC
NM_006904.7 missense
NM_006904.7 missense
Scores
1
8
10
Clinical Significance
Conservation
PhyloP100: 7.36
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 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.34479523).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PRKDC | NM_006904.7 | c.9071C>T | p.Pro3024Leu | missense_variant | 65/86 | ENST00000314191.7 | NP_008835.5 | |
PRKDC | NM_001081640.2 | c.9071C>T | p.Pro3024Leu | missense_variant | 65/85 | NP_001075109.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRKDC | ENST00000314191.7 | c.9071C>T | p.Pro3024Leu | missense_variant | 65/86 | 1 | NM_006904.7 | ENSP00000313420.3 | ||
PRKDC | ENST00000338368.7 | c.9071C>T | p.Pro3024Leu | missense_variant | 65/85 | 1 | ENSP00000345182.4 | |||
PRKDC | ENST00000697603.1 | c.1748C>T | p.Pro583Leu | missense_variant | 12/33 | ENSP00000513358.1 |
Frequencies
GnomAD3 genomes AF: 0.000342 AC: 52AN: 151988Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000340 AC: 79AN: 232088Hom.: 0 AF XY: 0.000279 AC XY: 35AN XY: 125408
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GnomAD4 exome AF: 0.000565 AC: 819AN: 1450506Hom.: 0 Cov.: 31 AF XY: 0.000545 AC XY: 393AN XY: 720454
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GnomAD4 genome AF: 0.000342 AC: 52AN: 151988Hom.: 0 Cov.: 32 AF XY: 0.000216 AC XY: 16AN XY: 74218
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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 | Labcorp Genetics (formerly Invitae), Labcorp | Aug 23, 2022 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 3024 of the PRKDC protein (p.Pro3024Leu). This variant is present in population databases (rs201186757, gnomAD 0.07%). 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: 581140). 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
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
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