16-81854547-A-G

Variant names:

Variant summary

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

The NM_002661.5(PLCG2):c.297A>G(p.Leu99Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 1,612,678 control chromosomes in the GnomAD database, including 74,765 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5652 hom., cov: 32)

Exomes 𝑓: 0.30 ( 69113 hom. )

Consequence

PLCG2
NM_002661.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.462

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=-0.79).

BP6

Variant 16-81854547-A-G is Benign according to our data. Variant chr16-81854547-A-G is described in ClinVar as [Benign]. Clinvar id is 403317.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-81854547-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.462 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCG2	NM_002661.5 link	c.297A>G	p.Leu99Leu	synonymous_variant	Exon 3 of 33	ENST00000564138.6	NP_002652.2	P16885
PLCG2	NM_001425749.1 link	c.297A>G	p.Leu99Leu	synonymous_variant	Exon 4 of 34		NP_001412678.1
PLCG2	NM_001425750.1 link	c.297A>G	p.Leu99Leu	synonymous_variant	Exon 3 of 33		NP_001412679.1
PLCG2	NM_001425751.1 link	c.297A>G	p.Leu99Leu	synonymous_variant	Exon 4 of 34		NP_001412680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCG2	ENST00000564138.6 link	c.297A>G	p.Leu99Leu	synonymous_variant	Exon 3 of 33	1	NM_002661.5	ENSP00000482457.1		P16885

Frequencies

GnomAD3 genomes

AF:

0.261

AC:

39632

AN:

152000

Hom.:

5649

Cov.:

show subpopulations

Gnomad AFR

AF:

0.157

Gnomad AMI

AF:

0.348

Gnomad AMR

AF:

0.274

Gnomad ASJ

AF:

0.320

Gnomad EAS

AF:

0.0851

Gnomad SAS

AF:

0.281

Gnomad FIN

AF:

0.321

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.318

Gnomad OTH

AF:

0.280

GnomAD3 exomes

AF:

0.277

AC:

69001

AN:

249418

Hom.:

10229

AF XY:

0.281

AC XY:

37995

AN XY:

135302

show subpopulations

Gnomad AFR exome

AF:

0.154

Gnomad AMR exome

AF:

0.267

Gnomad ASJ exome

AF:

0.327

Gnomad EAS exome

AF:

0.0670

Gnomad SAS exome

AF:

0.268

Gnomad FIN exome

AF:

0.318

Gnomad NFE exome

AF:

0.319

Gnomad OTH exome

AF:

0.292

GnomAD4 exome

AF:

0.303

AC:

442480

AN:

1460560

Hom.:

69113

Cov.:

AF XY:

0.302

AC XY:

219647

AN XY:

726622

show subpopulations

Gnomad4 AFR exome

AF:

0.148

Gnomad4 AMR exome

AF:

0.268

Gnomad4 ASJ exome

AF:

0.326

Gnomad4 EAS exome

AF:

0.0891

Gnomad4 SAS exome

AF:

0.269

Gnomad4 FIN exome

AF:

0.322

Gnomad4 NFE exome

AF:

0.319

Gnomad4 OTH exome

AF:

0.284

GnomAD4 genome

AF:

0.261

AC:

39632

AN:

152118

Hom.:

5652

Cov.:

AF XY:

0.260

AC XY:

19352

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.157

Gnomad4 AMR

AF:

0.274

Gnomad4 ASJ

AF:

0.320

Gnomad4 EAS

AF:

0.0847

Gnomad4 SAS

AF:

0.281

Gnomad4 FIN

AF:

0.321

Gnomad4 NFE

AF:

0.318

Gnomad4 OTH

AF:

0.276

Alfa

AF:

0.284

Hom.:

4822

Bravo

AF:

0.249

Asia WGS

AF:

0.174

AC:

606

AN:

3478

EpiCase

AF:

0.314

EpiControl

AF:

0.320

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 48% of patients studied by a panel of primary immunodeficiencies. Number of patients: 46. Only high quality variants are reported. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Familial cold autoinflammatory syndrome 3

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.48

DANN

Benign

0.38

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