rs758439876
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_002661.5(PLCG2):c.1971G>C(p.Glu657Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,990 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 (★★).
Frequency
Consequence
NM_002661.5 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLCG2 | NM_002661.5 | c.1971G>C | p.Glu657Asp | missense_variant | Exon 19 of 33 | ENST00000564138.6 | NP_002652.2 | |
PLCG2 | NM_001425749.1 | c.1971G>C | p.Glu657Asp | missense_variant | Exon 20 of 34 | NP_001412678.1 | ||
PLCG2 | NM_001425750.1 | c.1971G>C | p.Glu657Asp | missense_variant | Exon 19 of 33 | NP_001412679.1 | ||
PLCG2 | NM_001425751.1 | c.1971G>C | p.Glu657Asp | missense_variant | Exon 20 of 34 | NP_001412680.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000407 AC: 1AN: 245962Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 133430
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460990Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726618
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
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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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C35"). This variant has not been reported in the literature in individuals with PLCG2-related disease. This variant is present in population databases (rs758439876, ExAC 0.002%). This sequence change replaces glutamic acid with aspartic acid at codon 657 of the PLCG2 protein (p.Glu657Asp). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at