rs1071644

Positions:

chr16-81937798-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002661.5(PLCG2):c.3093T>C(p.Asn1031=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 1,613,270 control chromosomes in the GnomAD database, including 200,986 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 14051 hom., cov: 32)

Exomes 𝑓: 0.50 ( 186935 hom. )

Consequence

PLCG2
NM_002661.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9O:1

Conservation

PhyloP100: -0.489

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]

PLCG2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 16-81937798-T-C is Benign according to our data. Variant chr16-81937798-T-C is described in ClinVar as [Benign]. Clinvar id is 403324.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-81937798-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.489 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCG2	NM_002661.5 linkuse as main transcript	c.3093T>C	p.Asn1031=	synonymous_variant	28/33	ENST00000564138.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCG2	ENST00000564138.6 linkuse as main transcript	c.3093T>C	p.Asn1031=	synonymous_variant	28/33	1	NM_002661.5	P1

Frequencies

GnomAD3 genomes

AF:

0.394

AC:

59920

AN:

151988

Hom.:

14054

Cov.:

show subpopulations

Gnomad AFR

AF:

0.141

Gnomad AMI

AF:

0.469

Gnomad AMR

AF:

0.339

Gnomad ASJ

AF:

0.554

Gnomad EAS

AF:

0.369

Gnomad SAS

AF:

0.412

Gnomad FIN

AF:

0.524

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.531

Gnomad OTH

AF:

0.413

GnomAD3 exomes

AF:

0.445

AC:

110907

AN:

249252

Hom.:

26747

AF XY:

0.458

AC XY:

61990

AN XY:

135216

show subpopulations

Gnomad AFR exome

AF:

0.137

Gnomad AMR exome

AF:

0.281

Gnomad ASJ exome

AF:

0.563

Gnomad EAS exome

AF:

0.354

Gnomad SAS exome

AF:

0.433

Gnomad FIN exome

AF:

0.521

Gnomad NFE exome

AF:

0.528

Gnomad OTH exome

AF:

0.470

GnomAD4 exome

AF:

0.499

AC:

728819

AN:

1461164

Hom.:

186935

Cov.:

AF XY:

0.499

AC XY:

363069

AN XY:

726914

show subpopulations

Gnomad4 AFR exome

AF:

0.129

Gnomad4 AMR exome

AF:

0.289

Gnomad4 ASJ exome

AF:

0.564

Gnomad4 EAS exome

AF:

0.388

Gnomad4 SAS exome

AF:

0.432

Gnomad4 FIN exome

AF:

0.517

Gnomad4 NFE exome

AF:

0.526

Gnomad4 OTH exome

AF:

0.475

GnomAD4 genome

AF:

0.394

AC:

59912

AN:

152106

Hom.:

14051

Cov.:

AF XY:

0.392

AC XY:

29119

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.141

Gnomad4 AMR

AF:

0.338

Gnomad4 ASJ

AF:

0.554

Gnomad4 EAS

AF:

0.369

Gnomad4 SAS

AF:

0.413

Gnomad4 FIN

AF:

0.524

Gnomad4 NFE

AF:

0.531

Gnomad4 OTH

AF:

0.410

Alfa

AF:

0.462

Hom.:

13985

Bravo

AF:

0.372

Asia WGS

AF:

0.327

AC:

1136

AN:

3478

EpiCase

AF:

0.528

EpiControl

AF:

0.530

ClinVar

Significance: Benign

Submissions summary: Benign:9Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

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 12, 2023	This variant is classified as Benign based on local population frequency. This variant was detected in 58% of patients studied by a panel of primary immunodeficiencies. Number of patients: 56. Only high quality variants are reported. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

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	- -

not provided

Benign:1Other:1

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Autoinflammation-PLCG2-associated antibody deficiency-immune dysregulation

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

1.1

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over