rs375706148
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_006904.7(PRKDC):āc.7010T>Cā(p.Leu2337Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000808 in 1,609,512 control chromosomes in the GnomAD database, including 2 homozygotes. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. L2337L) has been classified as Likely benign.
Frequency
Consequence
NM_006904.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKDC | NM_006904.7 | c.7010T>C | p.Leu2337Pro | missense_variant | 53/86 | ENST00000314191.7 | |
PRKDC | NM_001081640.2 | c.7010T>C | p.Leu2337Pro | missense_variant | 53/85 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKDC | ENST00000314191.7 | c.7010T>C | p.Leu2337Pro | missense_variant | 53/86 | 1 | NM_006904.7 | P1 | |
PRKDC | ENST00000338368.7 | c.7010T>C | p.Leu2337Pro | missense_variant | 53/85 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000919 AC: 14AN: 152262Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000820 AC: 20AN: 243940Hom.: 0 AF XY: 0.0000982 AC XY: 13AN XY: 132366
GnomAD4 exome AF: 0.0000796 AC: 116AN: 1457132Hom.: 2 Cov.: 30 AF XY: 0.0000773 AC XY: 56AN XY: 724700
GnomAD4 genome ? AF: 0.0000919 AC: 14AN: 152380Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8AN XY: 74512
ClinVar
Submissions by phenotype
Severe combined immunodeficiency due to DNA-PKcs deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2023 | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 2337 of the PRKDC protein (p.Leu2337Pro). This variant is present in population databases (rs375706148, gnomAD 0.04%). 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: 541988). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PRKDC protein function with a negative predictive value of 80%. 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