rs765339827
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_006904.7(PRKDC):āc.2801T>Cā(p.Leu934Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,459,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L934V) has been classified as Uncertain significance.
Frequency
Consequence
NM_006904.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKDC | NM_006904.7 | c.2801T>C | p.Leu934Ser | missense_variant | 25/86 | ENST00000314191.7 | |
PRKDC | NM_001081640.2 | c.2801T>C | p.Leu934Ser | missense_variant | 25/85 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKDC | ENST00000314191.7 | c.2801T>C | p.Leu934Ser | missense_variant | 25/86 | 1 | NM_006904.7 | P1 | |
PRKDC | ENST00000338368.7 | c.2801T>C | p.Leu934Ser | missense_variant | 25/85 | 1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000405 AC: 1AN: 247174Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134184
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1459486Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 725956
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 05, 2023 | The p.L934S variant (also known as c.2801T>C), located in coding exon 25 of the PRKDC gene, results from a T to C substitution at nucleotide position 2801. The leucine at codon 934 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Severe combined immunodeficiency due to DNA-PKcs deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2018 | Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This sequence change replaces leucine with serine at codon 934 of the PRKDC protein (p.Leu934Ser). The leucine residue is highly conserved and there is a large physicochemical difference between leucine and serine. This variant is present in population databases (rs765339827, ExAC 0.002%). This variant has not been reported in the literature in individuals with PRKDC-related disease. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at