NM_002661.5:c.398C>G
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_002661.5(PLCG2):c.398C>G(p.Ala133Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A133V) has been classified as Likely benign.
Frequency
Consequence
NM_002661.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLCG2 | NM_002661.5 | c.398C>G | p.Ala133Gly | missense_variant | Exon 4 of 33 | ENST00000564138.6 | NP_002652.2 | |
PLCG2 | NM_001425749.1 | c.398C>G | p.Ala133Gly | missense_variant | Exon 5 of 34 | NP_001412678.1 | ||
PLCG2 | NM_001425750.1 | c.398C>G | p.Ala133Gly | missense_variant | Exon 4 of 33 | NP_001412679.1 | ||
PLCG2 | NM_001425751.1 | c.398C>G | p.Ala133Gly | missense_variant | Exon 5 of 34 | NP_001412680.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152206Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 249580Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135408
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461556Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 10AN XY: 727118
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152206Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74356
ClinVar
Submissions by phenotype
Familial cold autoinflammatory syndrome 3 Uncertain:1
This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 133 of the PLCG2 protein (p.Ala133Gly). This variant is present in population databases (rs61755444, gnomAD 0.004%). This missense change has been observed in individual(s) with clinical features of PLCG2-related conditions (PMID: 32185379). 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