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rs140123272

chr8-47834344-G-Achr8-47834344-G-Cchr8-47834344-G-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_006904.7(PRKDC):c.8004C>T(p.Val2668=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000413 in 1,613,920 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 (★★). Synonymous variant affecting the same amino acid position (i.e. V2668V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00042 ( 0 hom. )

Consequence

PRKDC
NM_006904.7 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.05
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 Benign. Variant got -11 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-47834344-G-A is Benign according to our data. Variant chr8-47834344-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 475238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.05 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRKDCNM_006904.7 linkuse as main transcriptc.8004C>T p.Val2668= synonymous_variant 59/86 ENST00000314191.7
PRKDCNM_001081640.2 linkuse as main transcriptc.8004C>T p.Val2668= synonymous_variant 59/85

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRKDCENST00000314191.7 linkuse as main transcriptc.8004C>T p.Val2668= synonymous_variant 59/861 NM_006904.7 P1P78527-1
PRKDCENST00000338368.7 linkuse as main transcriptc.8004C>T p.Val2668= synonymous_variant 59/851 P78527-2
PRKDCENST00000697603.1 linkuse as main transcriptc.681C>T p.Val227= synonymous_variant 6/33

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000375
AC:
57
AN:
152166
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000943
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000764
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000313
AC:
78
AN:
249326
Hom.:
0
AF XY:
0.000281
AC XY:
38
AN XY:
135244
show subpopulations
Gnomad AFR exome
AF:
0.000258
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000186
Gnomad NFE exome
AF:
0.000601
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.000417
AC:
610
AN:
1461636
Hom.:
0
Cov.:
31
AF XY:
0.000414
AC XY:
301
AN XY:
727100
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000749
Gnomad4 NFE exome
AF:
0.000531
Gnomad4 OTH exome
AF:
0.000199
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000374
AC:
57
AN:
152284
Hom.:
0
Cov.:
32
AF XY:
0.000322
AC XY:
24
AN XY:
74454
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000943
Gnomad4 NFE
AF:
0.000764
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000464
Hom.:
0
Bravo
AF:
0.000329
EpiCase
AF:
0.000273
EpiControl
AF:
0.000474

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 submitterclinical testingCeGaT Center for Human Genetics TuebingenSep 01, 2023PRKDC: BP4, BP7 -
Severe combined immunodeficiency due to DNA-PKcs deficiency Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeDec 03, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
Cadd
Benign
0.29
Dann
Benign
0.31

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs140123272; hg19: chr8-48746905; API