rs587777685
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_ModeratePP5_Moderate
The NM_006904.7(PRKDC):c.9185T>G(p.Leu3062Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_006904.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRKDC | ENST00000314191.7 | c.9185T>G | p.Leu3062Arg | missense_variant | Exon 66 of 86 | 1 | NM_006904.7 | ENSP00000313420.3 | ||
PRKDC | ENST00000338368.7 | c.9185T>G | p.Leu3062Arg | missense_variant | Exon 66 of 85 | 1 | ENSP00000345182.4 | |||
PRKDC | ENST00000697603.1 | c.1862T>G | p.Leu621Arg | missense_variant | Exon 13 of 33 | ENSP00000513358.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 30
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Immunodeficiency 26 without neurologic abnormalities Pathogenic:1
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Severe combined immunodeficiency due to DNA-PKcs deficiency Pathogenic:1
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 154322). This variant is also known as c.9239T>G (p.Leu3061Arg). This missense change has been observed in individual(s) with severe combined immunodeficiency (PMID: 19075392, 25842288, 30121298). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 3062 of the PRKDC protein (p.Leu3062Arg). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at