rs549230210
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006904.7(PRKDC):c.1535G>T(p.Gly512Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,613,588 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. G512G) has been classified as Likely benign.
Frequency
Consequence
NM_006904.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKDC | NM_006904.7 | c.1535G>T | p.Gly512Val | missense_variant | 15/86 | ENST00000314191.7 | |
PRKDC | NM_001081640.2 | c.1535G>T | p.Gly512Val | missense_variant | 15/85 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKDC | ENST00000314191.7 | c.1535G>T | p.Gly512Val | missense_variant | 15/86 | 1 | NM_006904.7 | P1 | |
PRKDC | ENST00000338368.7 | c.1535G>T | p.Gly512Val | missense_variant | 15/85 | 1 | |||
PRKDC | ENST00000697591.1 | n.1576G>T | non_coding_transcript_exon_variant | 15/15 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152136Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000281 AC: 7AN: 249174Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135182
GnomAD4 exome AF: 0.0000335 AC: 49AN: 1461452Hom.: 0 Cov.: 33 AF XY: 0.0000303 AC XY: 22AN XY: 727014
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152136Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74308
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 27, 2023 | The c.1535G>T (p.G512V) alteration is located in exon 15 (coding exon 15) of the PRKDC gene. This alteration results from a G to T substitution at nucleotide position 1535, causing the glycine (G) at amino acid position 512 to be replaced by a valine (V). Based on insufficient or conflicting evidence, 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 | Dec 03, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 512 of the PRKDC protein (p.Gly512Val). This variant is present in population databases (rs549230210, gnomAD 0.006%). 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: 542007). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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