rs1016837424
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002661.5(PLCG2):āc.2931C>Gā(p.Tyr977Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,158 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 ). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_002661.5 stop_gained
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 |
---|---|---|---|---|---|---|---|
PLCG2 | NM_002661.5 | c.2931C>G | p.Tyr977Ter | stop_gained | 27/33 | ENST00000564138.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLCG2 | ENST00000564138.6 | c.2931C>G | p.Tyr977Ter | stop_gained | 27/33 | 1 | NM_002661.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152158Hom.: 0 Cov.: 32
GnomAD4 exome Cov.: 33
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152158Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74344
ClinVar
Submissions by phenotype
Familial cold autoinflammatory syndrome 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 26, 2018 | This sequence change creates a premature translational stop signal (p.Tyr977*) in the PLCG2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PLCG2-related disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in PLCG2 cause disease. 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