chr16-81786163-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002661.5(PLCG2):c.174T>C(p.Ala58Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 1,613,708 control chromosomes in the GnomAD database, including 394,472 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.69 ( 36283 hom., cov: 33)

Exomes 𝑓: 0.70 ( 358189 hom. )

Consequence

PLCG2
NM_002661.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7O:1

Conservation

PhyloP100: -3.07

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 16-81786163-T-C is Benign according to our data. Variant chr16-81786163-T-C is described in ClinVar as [Benign]. Clinvar id is 403316.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-81786163-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.07 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCG2	NM_002661.5 link	c.174T>C	p.Ala58Ala	synonymous_variant	Exon 2 of 33	ENST00000564138.6	NP_002652.2	P16885
PLCG2	NM_001425749.1 link	c.174T>C	p.Ala58Ala	synonymous_variant	Exon 3 of 34		NP_001412678.1
PLCG2	NM_001425750.1 link	c.174T>C	p.Ala58Ala	synonymous_variant	Exon 2 of 33		NP_001412679.1
PLCG2	NM_001425751.1 link	c.174T>C	p.Ala58Ala	synonymous_variant	Exon 3 of 34		NP_001412680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCG2	ENST00000564138.6 link	c.174T>C	p.Ala58Ala	synonymous_variant	Exon 2 of 33	1	NM_002661.5	ENSP00000482457.1		P16885

Frequencies

GnomAD3 genomes

AF:

0.689

AC:

104674

AN:

152006

Hom.:

36262

Cov.:

show subpopulations

Gnomad AFR

AF:

0.644

Gnomad AMI

AF:

0.513

Gnomad AMR

AF:

0.730

Gnomad ASJ

AF:

0.669

Gnomad EAS

AF:

0.874

Gnomad SAS

AF:

0.768

Gnomad FIN

AF:

0.748

Gnomad MID

AF:

0.687

Gnomad NFE

AF:

0.682

Gnomad OTH

AF:

0.668

GnomAD2 exomes

AF:

0.727

AC:

180856

AN:

248772

AF XY:

0.727

show subpopulations

Gnomad AFR exome

AF:

0.641

Gnomad AMR exome

AF:

0.779

Gnomad ASJ exome

AF:

0.684

Gnomad EAS exome

AF:

0.876

Gnomad FIN exome

AF:

0.752

Gnomad NFE exome

AF:

0.689

Gnomad OTH exome

AF:

0.703

GnomAD4 exome

AF:

0.699

AC:

1020982

AN:

1461586

Hom.:

358189

Cov.:

AF XY:

0.700

AC XY:

509115

AN XY:

727082

show subpopulations

African (AFR)

AF:

0.643

AC:

21536

AN:

33476

American (AMR)

AF:

0.774

AC:

34584

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.679

AC:

17732

AN:

26134

East Asian (EAS)

AF:

0.891

AC:

35361

AN:

39700

South Asian (SAS)

AF:

0.768

AC:

66261

AN:

86238

European-Finnish (FIN)

AF:

0.744

AC:

39712

AN:

53400

Middle Eastern (MID)

AF:

0.710

AC:

4069

AN:

5730

European-Non Finnish (NFE)

AF:

0.683

AC:

759881

AN:

1111828

Other (OTH)

AF:

0.693

AC:

41846

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

15929

31858

47786

63715

79644

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.689

AC:

104736

AN:

152122

Hom.:

36283

Cov.:

AF XY:

0.696

AC XY:

51787

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.643

AC:

26698

AN:

41490

American (AMR)

AF:

0.730

AC:

11165

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.669

AC:

2324

AN:

3472

East Asian (EAS)

AF:

0.874

AC:

4516

AN:

5168

South Asian (SAS)

AF:

0.768

AC:

3697

AN:

4814

European-Finnish (FIN)

AF:

0.748

AC:

7918

AN:

10582

Middle Eastern (MID)

AF:

0.695

AC:

203

AN:

292

European-Non Finnish (NFE)

AF:

0.682

AC:

46339

AN:

67986

Other (OTH)

AF:

0.665

AC:

1408

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1722

3444

5165

6887

8609

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.686

Hom.:

53264

Bravo

AF:

0.686

Asia WGS

AF:

0.747

AC:

2598

AN:

3478

EpiCase

AF:

0.683

EpiControl

AF:

0.683

ClinVar

Significance: Benign

Submissions summary: Benign:7Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

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. -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:2

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 95% of patients studied by a panel of primary immunodeficiencies. Number of patients: 91. Only high quality variants are reported. -

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 -

Familial cold autoinflammatory syndrome 3

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 25, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autoinflammation-PLCG2-associated antibody deficiency-immune dysregulation

Benign:1

Oct 25, 2021

Genome-Nilou Lab

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

-0.66

CADD

Benign

0.25

(source)

DANN

Benign

0.76

PhyloP100

-3.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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chr16-81786163-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over