NM_002661.5:c.61G>T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_002661.5(PLCG2):c.61G>T(p.Ala21Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,614,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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.61G>T | p.Ala21Ser | missense_variant | Exon 2 of 33 | ENST00000564138.6 | NP_002652.2 | |
PLCG2 | NM_001425749.1 | c.61G>T | p.Ala21Ser | missense_variant | Exon 3 of 34 | NP_001412678.1 | ||
PLCG2 | NM_001425750.1 | c.61G>T | p.Ala21Ser | missense_variant | Exon 2 of 33 | NP_001412679.1 | ||
PLCG2 | NM_001425751.1 | c.61G>T | p.Ala21Ser | missense_variant | Exon 3 of 34 | NP_001412680.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152240Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461874Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 727240
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152240Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74376
ClinVar
Submissions by phenotype
Familial cold autoinflammatory syndrome 3 Uncertain:1
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: 1520957). This variant is not present in population databases (gnomAD no frequency). 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. This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 21 of the PLCG2 protein (p.Ala21Ser). 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