chr16-81910638-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_002661.5(PLCG2):c.1852C>T(p.Arg618Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,886 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R618L) has been classified 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 -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLCG2 | NM_002661.5 | c.1852C>T | p.Arg618Cys | missense_variant | Exon 18 of 33 | ENST00000564138.6 | NP_002652.2 | |
PLCG2 | NM_001425749.1 | c.1852C>T | p.Arg618Cys | missense_variant | Exon 19 of 34 | NP_001412678.1 | ||
PLCG2 | NM_001425750.1 | c.1852C>T | p.Arg618Cys | missense_variant | Exon 18 of 33 | NP_001412679.1 | ||
PLCG2 | NM_001425751.1 | c.1852C>T | p.Arg618Cys | missense_variant | Exon 19 of 34 | NP_001412680.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152250Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000361 AC: 9AN: 249390Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135330
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461636Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 727150
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152250Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74382
ClinVar
Submissions by phenotype
Familial cold autoinflammatory syndrome 3 Uncertain:1
This variant has not been reported in the literature in individuals with PLCG2-related disease. This sequence change replaces arginine with cysteine at codon 618 of the PLCG2 protein (p.Arg618Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs759496244, ExAC 0.06%). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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