rs138740003
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006904.7(PRKDC):c.7856G>A(p.Arg2619His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,612,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2619C) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKDC | NM_006904.7 | c.7856G>A | p.Arg2619His | missense_variant | 58/86 | ENST00000314191.7 | |
PRKDC | NM_001081640.2 | c.7856G>A | p.Arg2619His | missense_variant | 58/85 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKDC | ENST00000314191.7 | c.7856G>A | p.Arg2619His | missense_variant | 58/86 | 1 | NM_006904.7 | P1 | |
PRKDC | ENST00000338368.7 | c.7856G>A | p.Arg2619His | missense_variant | 58/85 | 1 | |||
PRKDC | ENST00000697603.1 | c.533G>A | p.Arg178His | missense_variant | 5/33 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152150Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000811 AC: 2AN: 246616Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 133862
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1460340Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 8AN XY: 726356
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152268Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74462
ClinVar
Submissions by phenotype
Severe combined immunodeficiency due to DNA-PKcs deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2023 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 2619 of the PRKDC protein (p.Arg2619His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 575018). 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. 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