8-47881938-G-A
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_006904.7(PRKDC):c.4936C>T(p.Leu1646Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,072 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 Likely benign (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
PRKDC
NM_006904.7 synonymous
NM_006904.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.26
Publications
0 publications found
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]
PRKDC Gene-Disease associations (from GenCC):
- severe combined immunodeficiency due to DNA-PKcs deficiencyInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
Variant 8-47881938-G-A is Benign according to our data. Variant chr8-47881938-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 542028.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=3.26 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_006904.7. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PRKDC | NM_006904.7 | MANE Select | c.4936C>T | p.Leu1646Leu | synonymous | Exon 37 of 86 | NP_008835.5 | ||
| PRKDC | NM_001081640.2 | c.4936C>T | p.Leu1646Leu | synonymous | Exon 37 of 85 | NP_001075109.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PRKDC | ENST00000314191.7 | TSL:1 MANE Select | c.4936C>T | p.Leu1646Leu | synonymous | Exon 37 of 86 | ENSP00000313420.3 | ||
| PRKDC | ENST00000338368.7 | TSL:1 | c.4936C>T | p.Leu1646Leu | synonymous | Exon 37 of 85 | ENSP00000345182.4 | ||
| PRKDC | ENST00000697611.1 | n.1040C>T | non_coding_transcript_exon | Exon 1 of 2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461072Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726728 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461072
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
726728
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33462
American (AMR)
AF:
AC:
0
AN:
44652
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26120
East Asian (EAS)
AF:
AC:
0
AN:
39674
South Asian (SAS)
AF:
AC:
0
AN:
86158
European-Finnish (FIN)
AF:
AC:
0
AN:
53394
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111490
Other (OTH)
AF:
AC:
0
AN:
60356
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
33
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Severe combined immunodeficiency due to DNA-PKcs deficiency Benign:1
Mar 07, 2021
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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