16-81786172-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_002661.5(PLCG2):āc.183C>Gā(p.Ile61Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,526 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 (ā ). Synonymous variant affecting the same amino acid position (i.e. I61I) has been classified as Likely benign.
Frequency
Consequence
NM_002661.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLCG2 | NM_002661.5 | c.183C>G | p.Ile61Met | missense_variant | 2/33 | ENST00000564138.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLCG2 | ENST00000564138.6 | c.183C>G | p.Ile61Met | missense_variant | 2/33 | 1 | NM_002661.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248610Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 135010
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461526Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1AN XY: 727046
GnomAD4 genome Cov.: 34
ClinVar
Submissions by phenotype
Familial cold autoinflammatory syndrome 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 10, 2023 | 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. 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 1396342). This variant has not been reported in the literature in individuals affected with PLCG2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 61 of the PLCG2 protein (p.Ile61Met). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at