16-81786039-A-G
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_002661.5(PLCG2):c.50A>G(p.Gln17Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000142 in 1,614,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_002661.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLCG2 | NM_002661.5 | c.50A>G | p.Gln17Arg | missense_variant | Exon 2 of 33 | ENST00000564138.6 | NP_002652.2 | |
PLCG2 | NM_001425749.1 | c.50A>G | p.Gln17Arg | missense_variant | Exon 3 of 34 | NP_001412678.1 | ||
PLCG2 | NM_001425750.1 | c.50A>G | p.Gln17Arg | missense_variant | Exon 2 of 33 | NP_001412679.1 | ||
PLCG2 | NM_001425751.1 | c.50A>G | p.Gln17Arg | missense_variant | Exon 3 of 34 | NP_001412680.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152228Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249496Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135368
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461886Hom.: 0 Cov.: 30 AF XY: 0.0000151 AC XY: 11AN XY: 727246
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74366
ClinVar
Submissions by phenotype
Familial cold autoinflammatory syndrome 3 Uncertain:1
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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 1982820). This variant has not been reported in the literature in individuals affected with PLCG2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 17 of the PLCG2 protein (p.Gln17Arg). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at