rs4888183
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_002661.5(PLCG2):c.432-13T>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 1,517,952 control chromosomes in the GnomAD database, including 228,594 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.55 ( 23448 hom., cov: 33)
Exomes 𝑓: 0.55 ( 205146 hom. )
Consequence
PLCG2
NM_002661.5 splice_polypyrimidine_tract, intron
NM_002661.5 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0710
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
Variant 16-81859103-T-A is Benign according to our data. Variant chr16-81859103-T-A is described in ClinVar as [Benign]. Clinvar id is 403318.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-81859103-T-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLCG2 | NM_002661.5 | c.432-13T>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000564138.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLCG2 | ENST00000564138.6 | c.432-13T>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_002661.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.553 AC: 84062AN: 152026Hom.: 23445 Cov.: 33
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GnomAD3 exomes AF: 0.554 AC: 137831AN: 248668Hom.: 38483 AF XY: 0.549 AC XY: 74075AN XY: 134924
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GnomAD4 exome AF: 0.546 AC: 745245AN: 1365808Hom.: 205146 Cov.: 22 AF XY: 0.544 AC XY: 372498AN XY: 685244
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GnomAD4 genome ? AF: 0.553 AC: 84106AN: 152144Hom.: 23448 Cov.: 33 AF XY: 0.554 AC XY: 41185AN XY: 74366
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ClinVar
Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
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 | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
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 12, 2023 | This variant is classified as Benign based on local population frequency. This variant was detected in 78% of patients studied by a panel of primary immunodeficiencies. Number of patients: 75. Only high quality variants are reported. - |
Familial cold autoinflammatory syndrome 3 Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
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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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at