rs183986754
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7
The NM_006904.7(PRKDC):c.3222G>A(p.Lys1074=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000158 in 1,608,732 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: 𝑓 0.00099 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000071 ( 0 hom. )
Consequence
PRKDC
NM_006904.7 synonymous
NM_006904.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.47
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 -9 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
?
Variant 8-47902616-C-T is Benign according to our data. Variant chr8-47902616-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 542017.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.47 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKDC | NM_006904.7 | c.3222G>A | p.Lys1074= | synonymous_variant | 27/86 | ENST00000314191.7 | |
PRKDC | NM_001081640.2 | c.3222G>A | p.Lys1074= | synonymous_variant | 27/85 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKDC | ENST00000314191.7 | c.3222G>A | p.Lys1074= | synonymous_variant | 27/86 | 1 | NM_006904.7 | P1 | |
PRKDC | ENST00000338368.7 | c.3222G>A | p.Lys1074= | synonymous_variant | 27/85 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000979 AC: 149AN: 152166Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000256 AC: 63AN: 245914Hom.: 0 AF XY: 0.000270 AC XY: 36AN XY: 133468
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GnomAD4 exome AF: 0.0000714 AC: 104AN: 1456448Hom.: 0 Cov.: 30 AF XY: 0.0000787 AC XY: 57AN XY: 724230
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GnomAD4 genome ? AF: 0.000985 AC: 150AN: 152284Hom.: 0 Cov.: 32 AF XY: 0.000940 AC XY: 70AN XY: 74468
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 12, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Severe combined immunodeficiency due to DNA-PKcs deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 14, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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