16-81786002-G-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_002661.5(PLCG2):c.13G>T(p.Val5Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,613,928 control chromosomes in the GnomAD database, including 1 homozygotes. 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.13G>T | p.Val5Phe | missense_variant | Exon 2 of 33 | ENST00000564138.6 | NP_002652.2 | |
PLCG2 | NM_001425749.1 | c.13G>T | p.Val5Phe | missense_variant | Exon 3 of 34 | NP_001412678.1 | ||
PLCG2 | NM_001425750.1 | c.13G>T | p.Val5Phe | missense_variant | Exon 2 of 33 | NP_001412679.1 | ||
PLCG2 | NM_001425751.1 | c.13G>T | p.Val5Phe | missense_variant | Exon 3 of 34 | NP_001412680.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152150Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248960Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135050
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461660Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 727142
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152268Hom.: 1 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74452
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.13G>T (p.V5F) alteration is located in exon 2 (coding exon 1) of the PLCG2 gene. This alteration results from a G to T substitution at nucleotide position 13, causing the valine (V) at amino acid position 5 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Familial cold autoinflammatory syndrome 3 Uncertain:1
This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 5 of the PLCG2 protein (p.Val5Phe). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with PLCG2-related conditions. This variant is present in population databases (rs556174475, gnomAD 0.01%). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at