rs8178232
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_006904.7(PRKDC):c.10684T>A(p.Leu3562Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00223 in 1,585,258 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L3562F) has been classified as Uncertain significance.
Frequency
Consequence
NM_006904.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKDC | NM_006904.7 | c.10684T>A | p.Leu3562Met | missense_variant | 75/86 | ENST00000314191.7 | |
PRKDC | NM_001081640.2 | c.10684T>A | p.Leu3562Met | missense_variant | 75/85 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKDC | ENST00000314191.7 | c.10684T>A | p.Leu3562Met | missense_variant | 75/86 | 1 | NM_006904.7 | P1 | |
PRKDC | ENST00000338368.7 | c.10684T>A | p.Leu3562Met | missense_variant | 75/85 | 1 | |||
PRKDC | ENST00000697603.1 | c.3361T>A | p.Leu1121Met | missense_variant | 22/33 | ||||
PRKDC | ENST00000697602.1 | n.1257T>A | non_coding_transcript_exon_variant | 7/18 |
Frequencies
GnomAD3 genomes AF: 0.00479 AC: 727AN: 151864Hom.: 16 Cov.: 33
GnomAD3 exomes AF: 0.00746 AC: 1697AN: 227604Hom.: 39 AF XY: 0.00594 AC XY: 736AN XY: 123854
GnomAD4 exome AF: 0.00196 AC: 2813AN: 1433288Hom.: 59 Cov.: 31 AF XY: 0.00178 AC XY: 1268AN XY: 712080
GnomAD4 genome AF: 0.00478 AC: 727AN: 151970Hom.: 16 Cov.: 33 AF XY: 0.00596 AC XY: 443AN XY: 74268
ClinVar
Submissions by phenotype
Severe combined immunodeficiency due to DNA-PKcs deficiency Benign:2
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 06, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 27, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at