rs772451566
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002661.5(PLCG2):c.547C>T(p.Leu183Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,446 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLCG2 | NM_002661.5 | c.547C>T | p.Leu183Phe | missense_variant | Exon 6 of 33 | ENST00000564138.6 | NP_002652.2 | |
PLCG2 | NM_001425749.1 | c.547C>T | p.Leu183Phe | missense_variant | Exon 7 of 34 | NP_001412678.1 | ||
PLCG2 | NM_001425750.1 | c.547C>T | p.Leu183Phe | missense_variant | Exon 6 of 33 | NP_001412679.1 | ||
PLCG2 | NM_001425751.1 | c.547C>T | p.Leu183Phe | missense_variant | Exon 7 of 34 | NP_001412680.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249516Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135378
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460446Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 726630
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Familial cold autoinflammatory syndrome 3;C3553961:Autoinflammation-PLCG2-associated antibody deficiency-immune dysregulation Uncertain:1
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Familial cold autoinflammatory syndrome 3 Uncertain:1
This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 183 of the PLCG2 protein (p.Leu183Phe). This variant is present in population databases (rs772451566, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with PLCG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 540096). 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. 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