rs746024122
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006904.7(PRKDC):c.8692C>T(p.Leu2898Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000794 in 1,613,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKDC | NM_006904.7 | c.8692C>T | p.Leu2898Phe | missense_variant | 63/86 | ENST00000314191.7 | |
PRKDC | NM_001081640.2 | c.8692C>T | p.Leu2898Phe | missense_variant | 63/85 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKDC | ENST00000314191.7 | c.8692C>T | p.Leu2898Phe | missense_variant | 63/86 | 1 | NM_006904.7 | P1 | |
PRKDC | ENST00000338368.7 | c.8692C>T | p.Leu2898Phe | missense_variant | 63/85 | 1 | |||
PRKDC | ENST00000697603.1 | c.1369C>T | p.Leu457Phe | missense_variant | 10/33 |
Frequencies
GnomAD3 genomes ? AF: 0.0000985 AC: 15AN: 152224Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000569 AC: 14AN: 246020Hom.: 0 AF XY: 0.0000522 AC XY: 7AN XY: 133980
GnomAD4 exome AF: 0.0000780 AC: 114AN: 1460660Hom.: 0 Cov.: 31 AF XY: 0.0000798 AC XY: 58AN XY: 726592
GnomAD4 genome ? AF: 0.0000919 AC: 14AN: 152342Hom.: 0 Cov.: 33 AF XY: 0.0000940 AC XY: 7AN XY: 74498
ClinVar
Submissions by phenotype
Severe combined immunodeficiency due to DNA-PKcs deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2022 | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 2898 of the PRKDC protein (p.Leu2898Phe). This variant is present in population databases (rs746024122, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with PRKDC-related conditions. ClinVar contains an entry for this variant (Variation ID: 565638). 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