chr8-47927785-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006904.7(PRKDC):āc.2245G>Cā(p.Val749Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000283 in 1,412,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V749A) 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.2245G>C | p.Val749Leu | missense_variant | 20/86 | ENST00000314191.7 | |
PRKDC | NM_001081640.2 | c.2245G>C | p.Val749Leu | missense_variant | 20/85 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKDC | ENST00000314191.7 | c.2245G>C | p.Val749Leu | missense_variant | 20/86 | 1 | NM_006904.7 | P1 | |
PRKDC | ENST00000338368.7 | c.2245G>C | p.Val749Leu | missense_variant | 20/85 | 1 | |||
PRKDC | ENST00000541488.1 | n.184G>C | non_coding_transcript_exon_variant | 2/3 | 3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.0000144 AC: 3AN: 207762Hom.: 0 AF XY: 0.0000178 AC XY: 2AN XY: 112608
GnomAD4 exome AF: 0.00000283 AC: 4AN: 1412212Hom.: 0 Cov.: 30 AF XY: 0.00000286 AC XY: 2AN XY: 699956
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Severe combined immunodeficiency due to DNA-PKcs deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2022 | This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 749 of the PRKDC protein (p.Val749Leu). This variant is present in population databases (rs771482106, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with PRKDC-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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