Variant 16-81891389-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002661.5(PLCG2):c.868-83C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 818,028 control chromosomes in the GnomAD database, including 5,275 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.085 ( 709 hom., cov: 33)

Exomes 𝑓: 0.11 ( 4566 hom. )

Consequence

PLCG2
NM_002661.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.12

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 16-81891389-C-T is Benign according to our data. Variant chr16-81891389-C-T is described in ClinVar as [Benign]. Clinvar id is 1273765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCG2	NM_002661.5 linkuse as main transcript	c.868-83C>T		intron_variant		ENST00000564138.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCG2	ENST00000564138.6 linkuse as main transcript	c.868-83C>T		intron_variant		1	NM_002661.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0850

AC:

12923

AN:

152082

Hom.:

709

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0189

Gnomad AMI

AF:

0.0702

Gnomad AMR

AF:

0.0687

Gnomad ASJ

AF:

0.150

Gnomad EAS

AF:

0.0278

Gnomad SAS

AF:

0.155

Gnomad FIN

AF:

0.127

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.119

Gnomad OTH

AF:

0.0851

GnomAD4 exome

AF:

0.110

AC:

73226

AN:

665828

Hom.:

4566

AF XY:

0.114

AC XY:

40834

AN XY:

356752

show subpopulations

Gnomad4 AFR exome

AF:

0.0195

Gnomad4 AMR exome

AF:

0.0525

Gnomad4 ASJ exome

AF:

0.152

Gnomad4 EAS exome

AF:

0.0246

Gnomad4 SAS exome

AF:

0.156

Gnomad4 FIN exome

AF:

0.127

Gnomad4 NFE exome

AF:

0.116

Gnomad4 OTH exome

AF:

0.109

GnomAD4 genome

AF:

0.0849

AC:

12918

AN:

152200

Hom.:

709

Cov.:

AF XY:

0.0859

AC XY:

6387

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0188

Gnomad4 AMR

AF:

0.0686

Gnomad4 ASJ

AF:

0.150

Gnomad4 EAS

AF:

0.0277

Gnomad4 SAS

AF:

0.155

Gnomad4 FIN

AF:

0.127

Gnomad4 NFE

AF:

0.119

Gnomad4 OTH

AF:

0.0842

Alfa

AF:

0.0984

Hom.:

525

Bravo

AF:

0.0770

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.6

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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