Variant rs13333716 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002661.5(PLCG2):c.1188C>G(p.Thr396=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0696 in 1,613,924 control chromosomes in the GnomAD database, including 4,395 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.065 ( 375 hom., cov: 31)

Exomes 𝑓: 0.070 ( 4020 hom. )

Consequence

PLCG2
NM_002661.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.194

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=-0.57).

BP6

Variant 16-81895922-C-G is Benign according to our data. Variant chr16-81895922-C-G is described in ClinVar as [Benign]. Clinvar id is 403321.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-81895922-C-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.194 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0789 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.1188C>G	p.Thr396=	synonymous_variant	13/33	ENST00000564138.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCG2	ENST00000564138.6 linkuse as main transcript	c.1188C>G	p.Thr396=	synonymous_variant	13/33	1	NM_002661.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0651

AC:

9901

AN:

152010

Hom.:

372

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0809

Gnomad AMI

AF:

0.0855

Gnomad AMR

AF:

0.0443

Gnomad ASJ

AF:

0.0392

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0254

Gnomad FIN

AF:

0.0479

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0724

Gnomad OTH

AF:

0.0484

GnomAD3 exomes

AF:

0.0525

AC:

13089

AN:

249510

Hom.:

405

AF XY:

0.0518

AC XY:

7016

AN XY:

135374

show subpopulations

Gnomad AFR exome

AF:

0.0789

Gnomad AMR exome

AF:

0.0358

Gnomad ASJ exome

AF:

0.0394

Gnomad EAS exome

AF:

0.000222

Gnomad SAS exome

AF:

0.0278

Gnomad FIN exome

AF:

0.0517

Gnomad NFE exome

AF:

0.0701

Gnomad OTH exome

AF:

0.0540

GnomAD4 exome

AF:

0.0700

AC:

102330

AN:

1461796

Hom.:

4020

Cov.:

AF XY:

0.0684

AC XY:

49743

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.0824

Gnomad4 AMR exome

AF:

0.0364

Gnomad4 ASJ exome

AF:

0.0389

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0274

Gnomad4 FIN exome

AF:

0.0514

Gnomad4 NFE exome

AF:

0.0788

Gnomad4 OTH exome

AF:

0.0661

GnomAD4 genome

AF:

0.0652

AC:

9920

AN:

152128

Hom.:

375

Cov.:

AF XY:

0.0629

AC XY:

4674

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0812

Gnomad4 AMR

AF:

0.0442

Gnomad4 ASJ

AF:

0.0392

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0256

Gnomad4 FIN

AF:

0.0479

Gnomad4 NFE

AF:

0.0724

Gnomad4 OTH

AF:

0.0479

Alfa

AF:

0.0673

Hom.:

134

Bravo

AF:

0.0661

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.0715

EpiControl

AF:

0.0722

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
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 -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

Familial cold autoinflammatory syndrome 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

5.5

DANN

Benign

0.54

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.

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