16-81786000-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_002661.5(PLCG2):c.11C>T(p.Thr4Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00012 in 1,613,544 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000098 ( 1 hom. )

Consequence

PLCG2
NM_002661.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.323

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008903146).

BP6

Variant 16-81786000-C-T is Benign according to our data. Variant chr16-81786000-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 732127.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000335 (51/152304) while in subpopulation AFR AF= 0.000866 (36/41556). AF 95% confidence interval is 0.000643. There are 0 homozygotes in gnomad4. There are 26 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 51 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCG2	NM_002661.5 link	c.11C>T	p.Thr4Met	missense_variant	Exon 2 of 33	ENST00000564138.6	NP_002652.2	P16885
PLCG2	NM_001425749.1 link	c.11C>T	p.Thr4Met	missense_variant	Exon 3 of 34		NP_001412678.1
PLCG2	NM_001425750.1 link	c.11C>T	p.Thr4Met	missense_variant	Exon 2 of 33		NP_001412679.1
PLCG2	NM_001425751.1 link	c.11C>T	p.Thr4Met	missense_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.11C>T	p.Thr4Met	missense_variant	Exon 2 of 33	1	NM_002661.5	ENSP00000482457.1		P16885

Frequencies

GnomAD3 genomes

AF:

0.000335

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000233

AC:

AN:

248706

Hom.:

AF XY:

0.000245

AC XY:

AN XY:

134886

show subpopulations

Gnomad AFR exome

AF:

0.000840

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000982

Gnomad FIN exome

AF:

0.00153

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000979

AC:

143

AN:

1461240

Hom.:

Cov.:

AF XY:

0.0000977

AC XY:

AN XY:

726882

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00122

Gnomad4 NFE exome

AF:

0.0000477

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000335

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.000349

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000866

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000952

Hom.:

Bravo

AF:

0.000306

ESP6500AA

AF:

0.00103

AC:

ESP6500EA

AF:

0.000242

AC:

ExAC

AF:

0.000149

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Familial cold autoinflammatory syndrome 3

Benign:1

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.23

T;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.28

T;T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.0089

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.2

.;N;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.13

N;.;N

REVEL

Benign

0.099

Sift

Benign

0.21

T;.;T

Sift4G

Benign

0.21

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.10, 0.10

MVP

0.53

MPC

0.065

ClinPred

0.0048

GERP RS

-0.32

Varity_R

0.011

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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