16-81895883-C-T

Position:

chr16-81895883-C-T

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -1.31

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=-0.71).

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
PLCG2	NM_002661.5 link	c.1149C>T	p.Asp383Asp	synonymous_variant	13/33	ENST00000564138.6	NP_002652.2	P16885
PLCG2	NM_001425749.1 link	c.1149C>T	p.Asp383Asp	synonymous_variant	14/34		NP_001412678.1
PLCG2	NM_001425750.1 link	c.1149C>T	p.Asp383Asp	synonymous_variant	13/33		NP_001412679.1
PLCG2	NM_001425751.1 link	c.1149C>T	p.Asp383Asp	synonymous_variant	14/34		NP_001412680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCG2	ENST00000564138.6 link	c.1149C>T	p.Asp383Asp	synonymous_variant	13/33	1	NM_002661.5	ENSP00000482457.1		P16885

Frequencies

GnomAD3 genomes

AF:

0.344

AC:

52187

AN:

151818

Hom.:

10711

Cov.:

show subpopulations

Gnomad AFR

AF:

0.145

Gnomad AMI

AF:

0.340

Gnomad AMR

AF:

0.531

Gnomad ASJ

AF:

0.348

Gnomad EAS

AF:

0.719

Gnomad SAS

AF:

0.399

Gnomad FIN

AF:

0.443

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.374

Gnomad OTH

AF:

0.377

GnomAD3 exomes

AF:

0.429

AC:

107092

AN:

249514

Hom.:

25811

AF XY:

0.422

AC XY:

57112

AN XY:

135368

show subpopulations

Gnomad AFR exome

AF:

0.142

Gnomad AMR exome

AF:

0.659

Gnomad ASJ exome

AF:

0.344

Gnomad EAS exome

AF:

0.709

Gnomad SAS exome

AF:

0.382

Gnomad FIN exome

AF:

0.429

Gnomad NFE exome

AF:

0.375

Gnomad OTH exome

AF:

0.416

GnomAD4 exome

AF:

0.384

AC:

560548

AN:

1461500

Hom.:

113422

Cov.:

AF XY:

0.383

AC XY:

278242

AN XY:

727078

show subpopulations

Gnomad4 AFR exome

AF:

0.131

Gnomad4 AMR exome

AF:

0.641

Gnomad4 ASJ exome

AF:

0.342

Gnomad4 EAS exome

AF:

0.702

Gnomad4 SAS exome

AF:

0.385

Gnomad4 FIN exome

AF:

0.434

Gnomad4 NFE exome

AF:

0.368

Gnomad4 OTH exome

AF:

0.382

GnomAD4 genome

AF:

0.344

AC:

52202

AN:

151936

Hom.:

10718

Cov.:

AF XY:

0.356

AC XY:

26401

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.145

Gnomad4 AMR

AF:

0.531

Gnomad4 ASJ

AF:

0.348

Gnomad4 EAS

AF:

0.720

Gnomad4 SAS

AF:

0.399

Gnomad4 FIN

AF:

0.443

Gnomad4 NFE

AF:

0.374

Gnomad4 OTH

AF:

0.376

Alfa

AF:

0.347

Hom.:

4932

Bravo

AF:

0.342

Asia WGS

AF:

0.534

AC:

1855

AN:

3478

EpiCase

AF:

0.364

EpiControl

AF:

0.368

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

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.49

DANN

Benign

0.92

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