rs56387546
Positions:
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong
The NM_006904.7(PRKDC):c.4594C>T(p.Leu1532Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00041 in 1,609,424 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0021 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00023 ( 0 hom. )
Consequence
PRKDC
NM_006904.7 missense
NM_006904.7 missense
Scores
1
9
9
Clinical Significance
Conservation
PhyloP100: 4.11
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 Benign. Variant got -10 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.01166302).
BP6
?
Variant 8-47886126-G-A is Benign according to our data. Variant chr8-47886126-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 475227.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKDC | NM_006904.7 | c.4594C>T | p.Leu1532Phe | missense_variant | 36/86 | ENST00000314191.7 | |
PRKDC | NM_001081640.2 | c.4594C>T | p.Leu1532Phe | missense_variant | 36/85 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKDC | ENST00000314191.7 | c.4594C>T | p.Leu1532Phe | missense_variant | 36/86 | 1 | NM_006904.7 | P1 | |
PRKDC | ENST00000338368.7 | c.4594C>T | p.Leu1532Phe | missense_variant | 36/85 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00212 AC: 322AN: 152196Hom.: 1 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000538 AC: 129AN: 239770Hom.: 1 AF XY: 0.000391 AC XY: 51AN XY: 130590
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GnomAD4 exome AF: 0.000232 AC: 338AN: 1457110Hom.: 0 Cov.: 31 AF XY: 0.000222 AC XY: 161AN XY: 724532
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GnomAD4 genome ? AF: 0.00211 AC: 322AN: 152314Hom.: 1 Cov.: 32 AF XY: 0.00204 AC XY: 152AN XY: 74476
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 13, 2018 | - - |
Severe combined immunodeficiency due to DNA-PKcs deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 12, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
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
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
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