16-81907714-C-T

Position:

chr16-81907714-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.1497C>T(p.Ala499Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.764 in 1,612,556 control chromosomes in the GnomAD database, including 474,023 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 42012 hom., cov: 32)

Exomes 𝑓: 0.77 ( 432011 hom. )

Consequence

PLCG2
NM_002661.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10O:1

Conservation

PhyloP100: -3.15

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:

PLCG2 (HGNC:):

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=-0.69).

BP6

Variant 16-81907714-C-T is Benign according to our data. Variant chr16-81907714-C-T is described in ClinVar as [Benign]. Clinvar id is 403322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-81907714-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.15 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCG2	NM_002661.5 linkuse as main transcript	c.1497C>T	p.Ala499Ala	synonymous_variant	16/33	ENST00000564138.6	NP_002652.2	P16885

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCG2	ENST00000564138.6 linkuse as main transcript	c.1497C>T	p.Ala499Ala	synonymous_variant	16/33	1	NM_002661.5	ENSP00000482457.1		P16885

Frequencies

GnomAD3 genomes

AF:

0.736

AC:

111910

AN:

151968

Hom.:

41981

Cov.:

show subpopulations

Gnomad AFR

AF:

0.603

Gnomad AMI

AF:

0.761

Gnomad AMR

AF:

0.844

Gnomad ASJ

AF:

0.771

Gnomad EAS

AF:

0.969

Gnomad SAS

AF:

0.805

Gnomad FIN

AF:

0.743

Gnomad MID

AF:

0.801

Gnomad NFE

AF:

0.766

Gnomad OTH

AF:

0.778

GnomAD3 exomes

AF:

0.789

AC:

196783

AN:

249382

Hom.:

78609

AF XY:

0.788

AC XY:

106602

AN XY:

135300

show subpopulations

Gnomad AFR exome

AF:

0.597

Gnomad AMR exome

AF:

0.893

Gnomad ASJ exome

AF:

0.779

Gnomad EAS exome

AF:

0.971

Gnomad SAS exome

AF:

0.788

Gnomad FIN exome

AF:

0.743

Gnomad NFE exome

AF:

0.765

Gnomad OTH exome

AF:

0.792

GnomAD4 exome

AF:

0.767

AC:

1120409

AN:

1460470

Hom.:

432011

Cov.:

AF XY:

0.768

AC XY:

558089

AN XY:

726592

show subpopulations

Gnomad4 AFR exome

AF:

0.601

Gnomad4 AMR exome

AF:

0.886

Gnomad4 ASJ exome

AF:

0.782

Gnomad4 EAS exome

AF:

0.968

Gnomad4 SAS exome

AF:

0.788

Gnomad4 FIN exome

AF:

0.746

Gnomad4 NFE exome

AF:

0.759

Gnomad4 OTH exome

AF:

0.769

GnomAD4 genome

AF:

0.736

AC:

111993

AN:

152086

Hom.:

42012

Cov.:

AF XY:

0.740

AC XY:

55007

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.603

Gnomad4 AMR

AF:

0.844

Gnomad4 ASJ

AF:

0.771

Gnomad4 EAS

AF:

0.969

Gnomad4 SAS

AF:

0.805

Gnomad4 FIN

AF:

0.743

Gnomad4 NFE

AF:

0.766

Gnomad4 OTH

AF:

0.780

Alfa

AF:

0.764

Hom.:

67853

Bravo

AF:

0.738

EpiCase

AF:

0.766

EpiControl

AF:

0.771

ClinVar

Significance: Benign

Submissions summary: Benign:10Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
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	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
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 96% of patients studied by a panel of primary immunodeficiencies. Number of patients: 92. Only high quality variants are reported. -

not provided

Benign:2Other:1

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 26, 2018	- -
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. -

Familial cold autoinflammatory syndrome 3

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	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

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.13

DANN

Benign

0.68

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