chr16-81859103-T-A

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

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.0710
Variant links:
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 Protein UniProt
PLCG2NM_002661.5 linkuse as main transcriptc.432-13T>A splice_polypyrimidine_tract_variant, intron_variant ENST00000564138.6 NP_002652.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PLCG2ENST00000564138.6 linkuse as main transcriptc.432-13T>A splice_polypyrimidine_tract_variant, intron_variant 1 NM_002661.5 ENSP00000482457 P1

Frequencies

GnomAD3 genomes
AF:
0.553
AC:
84062
AN:
152026
Hom.:
23445
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.522
Gnomad AMI
AF:
0.693
Gnomad AMR
AF:
0.583
Gnomad ASJ
AF:
0.586
Gnomad EAS
AF:
0.611
Gnomad SAS
AF:
0.447
Gnomad FIN
AF:
0.609
Gnomad MID
AF:
0.573
Gnomad NFE
AF:
0.555
Gnomad OTH
AF:
0.569
GnomAD3 exomes
AF:
0.554
AC:
137831
AN:
248668
Hom.:
38483
AF XY:
0.549
AC XY:
74075
AN XY:
134924
show subpopulations
Gnomad AFR exome
AF:
0.526
Gnomad AMR exome
AF:
0.552
Gnomad ASJ exome
AF:
0.604
Gnomad EAS exome
AF:
0.635
Gnomad SAS exome
AF:
0.448
Gnomad FIN exome
AF:
0.610
Gnomad NFE exome
AF:
0.559
Gnomad OTH exome
AF:
0.564
GnomAD4 exome
AF:
0.546
AC:
745245
AN:
1365808
Hom.:
205146
Cov.:
22
AF XY:
0.544
AC XY:
372498
AN XY:
685244
show subpopulations
Gnomad4 AFR exome
AF:
0.519
Gnomad4 AMR exome
AF:
0.557
Gnomad4 ASJ exome
AF:
0.604
Gnomad4 EAS exome
AF:
0.577
Gnomad4 SAS exome
AF:
0.454
Gnomad4 FIN exome
AF:
0.605
Gnomad4 NFE exome
AF:
0.547
Gnomad4 OTH exome
AF:
0.559
GnomAD4 genome
AF:
0.553
AC:
84106
AN:
152144
Hom.:
23448
Cov.:
33
AF XY:
0.554
AC XY:
41185
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.521
Gnomad4 AMR
AF:
0.583
Gnomad4 ASJ
AF:
0.586
Gnomad4 EAS
AF:
0.610
Gnomad4 SAS
AF:
0.447
Gnomad4 FIN
AF:
0.609
Gnomad4 NFE
AF:
0.555
Gnomad4 OTH
AF:
0.567
Alfa
AF:
0.559
Hom.:
4316
Bravo
AF:
0.552
Asia WGS
AF:
0.512
AC:
1779
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:5
Benign, no assertion criteria providedclinical testingGenome Diagnostics Laboratory, University Medical Center Utrecht-- -
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 28, 2016Variant 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 providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
Benign, no assertion criteria providedclinical testingJoint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+-- -
Benign, criteria provided, single submitterclinical testingUnidad de Genómica Garrahan, Hospital de Pediatría GarrahanNov 12, 2023This 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 submitterclinical testingGenome-Nilou LabOct 25, 2021- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 01, 2024- -
not provided Benign:1
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Autoinflammation-PLCG2-associated antibody deficiency-immune dysregulation Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabOct 25, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
5.1
DANN
Benign
0.73

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs4888183; hg19: chr16-81892708; COSMIC: COSV63878556; API