rs150276286

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_002661.5(PLCG2):c.540C>G(p.Ala180Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00906 in 1,613,054 control chromosomes in the GnomAD database, including 83 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0064 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0093 ( 79 hom. )

Consequence

PLCG2
NM_002661.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.46

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 made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 16-81869274-C-G is Benign according to our data. Variant chr16-81869274-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 540126.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-81869274-C-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.46 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00637 (970/152286) while in subpopulation NFE AF= 0.0104 (705/68020). AF 95% confidence interval is 0.00973. There are 4 homozygotes in gnomad4. There are 435 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 970 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCG2	NM_002661.5 link	c.540C>G	p.Ala180Ala	synonymous_variant	Exon 6 of 33	ENST00000564138.6	NP_002652.2	P16885
PLCG2	NM_001425749.1 link	c.540C>G	p.Ala180Ala	synonymous_variant	Exon 7 of 34		NP_001412678.1
PLCG2	NM_001425750.1 link	c.540C>G	p.Ala180Ala	synonymous_variant	Exon 6 of 33		NP_001412679.1
PLCG2	NM_001425751.1 link	c.540C>G	p.Ala180Ala	synonymous_variant	Exon 7 of 34		NP_001412680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCG2	ENST00000564138.6 link	c.540C>G	p.Ala180Ala	synonymous_variant	Exon 6 of 33	1	NM_002661.5	ENSP00000482457.1		P16885

Frequencies

GnomAD3 genomes

AF:

0.00637

AC:

970

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00203

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00792

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.000848

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0104

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00604

AC:

1507

AN:

249528

Hom.:

AF XY:

0.00628

AC XY:

850

AN XY:

135378

show subpopulations

Gnomad AFR exome

AF:

0.00168

Gnomad AMR exome

AF:

0.00423

Gnomad ASJ exome

AF:

0.00328

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00480

Gnomad FIN exome

AF:

0.00186

Gnomad NFE exome

AF:

0.00949

Gnomad OTH exome

AF:

0.00660

GnomAD4 exome

AF:

0.00935

AC:

13651

AN:

1460768

Hom.:

Cov.:

AF XY:

0.00926

AC XY:

6729

AN XY:

726776

show subpopulations

Gnomad4 AFR exome

AF:

0.00149

Gnomad4 AMR exome

AF:

0.00423

Gnomad4 ASJ exome

AF:

0.00386

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00472

Gnomad4 FIN exome

AF:

0.00189

Gnomad4 NFE exome

AF:

0.0110

Gnomad4 OTH exome

AF:

0.00843

GnomAD4 genome

AF:

0.00637

AC:

970

AN:

152286

Hom.:

Cov.:

AF XY:

0.00584

AC XY:

435

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00202

Gnomad4 AMR

AF:

0.00791

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00477

Gnomad4 FIN

AF:

0.000848

Gnomad4 NFE

AF:

0.0104

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00653

Hom.:

Bravo

AF:

0.00647

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0125

EpiControl

AF:

0.0122

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Sep 04, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

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

- -

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PLCG2: BP4, BP7, BS1, BS2 -

PLCG2-related disorder

Benign:1

Jan 28, 2024

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Familial cold autoinflammatory syndrome 3;C3553961:Autoinflammation-PLCG2-associated antibody deficiency-immune dysregulation

Benign:1

Nov 04, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Familial cold autoinflammatory syndrome 3

Benign:1

Jan 29, 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

-0.46

CADD

Benign

DANN

Benign

0.71

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