rs780953775
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_006904.7(PRKDC):āc.5818T>Cā(p.Tyr1940His) variant causes a missense change. The variant allele was found at a frequency of 0.0000508 in 1,613,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. Y1940Y) 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 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKDC | NM_006904.7 | c.5818T>C | p.Tyr1940His | missense_variant | 43/86 | ENST00000314191.7 | |
PRKDC | NM_001081640.2 | c.5818T>C | p.Tyr1940His | missense_variant | 43/85 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKDC | ENST00000314191.7 | c.5818T>C | p.Tyr1940His | missense_variant | 43/86 | 1 | NM_006904.7 | P1 | |
PRKDC | ENST00000338368.7 | c.5818T>C | p.Tyr1940His | missense_variant | 43/85 | 1 | |||
PRKDC | ENST00000546304.1 | n.484T>C | non_coding_transcript_exon_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152220Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000321 AC: 8AN: 249016Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135092
GnomAD4 exome AF: 0.0000547 AC: 80AN: 1461658Hom.: 0 Cov.: 31 AF XY: 0.0000578 AC XY: 42AN XY: 727102
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152220Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74370
ClinVar
Submissions by phenotype
Severe combined immunodeficiency due to DNA-PKcs deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 29, 2022 | This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 1940 of the PRKDC protein (p.Tyr1940His). This variant is present in population databases (rs780953775, gnomAD 0.008%). This missense change has been observed in individual(s) with common variable immunodeficiency (PMID: 26122175). ClinVar contains an entry for this variant (Variation ID: 582132). 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