rs868303619
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006904.7(PRKDC):āc.2717T>Cā(p.Phe906Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,612,366 control chromosomes in the GnomAD database, with no homozygous occurrence. 11/19 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. F906L) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKDC | NM_006904.7 | c.2717T>C | p.Phe906Ser | missense_variant | 24/86 | ENST00000314191.7 | |
PRKDC | NM_001081640.2 | c.2717T>C | p.Phe906Ser | missense_variant | 24/85 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKDC | ENST00000314191.7 | c.2717T>C | p.Phe906Ser | missense_variant | 24/86 | 1 | NM_006904.7 | P1 | |
PRKDC | ENST00000338368.7 | c.2717T>C | p.Phe906Ser | missense_variant | 24/85 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152208Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 248068Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134600
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1460158Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 726336
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152208Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74360
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 phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 906 of the PRKDC protein (p.Phe906Ser). This variant is present in population databases (no rsID available, 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: 579006). 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