chr16-81895883-C-T
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_002661.5(PLCG2):c.1149C>T(p.Asp383Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 1,613,436 control chromosomes in the GnomAD database, including 124,140 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.34 ( 10718 hom., cov: 31)
Exomes 𝑓: 0.38 ( 113422 hom. )
Consequence
PLCG2
NM_002661.5 synonymous
NM_002661.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.31
Genes affected
PLCG2 (HGNC:9066): (phospholipase C gamma 2) The protein encoded by this gene is a transmembrane signaling enzyme that catalyzes the conversion of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to 1D-myo-inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) using calcium as a cofactor. IP3 and DAG are second messenger molecules important for transmitting signals from growth factor receptors and immune system receptors across the cell membrane. Mutations in this gene have been found in autoinflammation, antibody deficiency, and immune dysregulation syndrome and familial cold autoinflammatory syndrome 3. [provided by RefSeq, Mar 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
Variant 16-81895883-C-T is Benign according to our data. Variant chr16-81895883-C-T is described in ClinVar as [Benign]. Clinvar id is 403320.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-81895883-C-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-1.31 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
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PLCG2 | NM_002661.5 | c.1149C>T | p.Asp383Asp | synonymous_variant | 13/33 | ENST00000564138.6 | NP_002652.2 | |
PLCG2 | NM_001425749.1 | c.1149C>T | p.Asp383Asp | synonymous_variant | 14/34 | NP_001412678.1 | ||
PLCG2 | NM_001425750.1 | c.1149C>T | p.Asp383Asp | synonymous_variant | 13/33 | NP_001412679.1 | ||
PLCG2 | NM_001425751.1 | c.1149C>T | p.Asp383Asp | synonymous_variant | 14/34 | NP_001412680.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.344 AC: 52187AN: 151818Hom.: 10711 Cov.: 31
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GnomAD3 exomes AF: 0.429 AC: 107092AN: 249514Hom.: 25811 AF XY: 0.422 AC XY: 57112AN XY: 135368
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GnomAD4 exome AF: 0.384 AC: 560548AN: 1461500Hom.: 113422 Cov.: 43 AF XY: 0.383 AC XY: 278242AN XY: 727078
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GnomAD4 genome AF: 0.344 AC: 52202AN: 151936Hom.: 10718 Cov.: 31 AF XY: 0.356 AC XY: 26401AN XY: 74242
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ClinVar
Significance: Benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Nov 14, 2023 | This variant is classified as Benign based on local population frequency. This variant was detected in 82% of patients studied by a panel of primary immunodeficiencies. Number of patients: 79. Only high quality variants are reported. - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 23, 2024 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 04, 2021 | - - |
Familial cold autoinflammatory syndrome 3 Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 03, 2025 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Oct 25, 2021 | - - |
Autoinflammation-PLCG2-associated antibody deficiency-immune dysregulation Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Oct 25, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at