16-81859103-T-A

Position:

chr16-81859103-T-A

Variant summary

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

The NM_002661.5(PLCG2):c.432-13T>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 1,517,952 control chromosomes in the GnomAD database, including 228,594 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 23448 hom., cov: 33)

Exomes 𝑓: 0.55 ( 205146 hom. )

Consequence

PLCG2
NM_002661.5 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.0710

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=-0.78).

BP6

Variant 16-81859103-T-A is Benign according to our data. Variant chr16-81859103-T-A is described in ClinVar as [Benign]. Clinvar id is 403318.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-81859103-T-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCG2	NM_002661.5 linkuse as main transcript	c.432-13T>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000564138.6	NP_002652.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCG2	ENST00000564138.6 linkuse as main transcript	c.432-13T>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002661.5	ENSP00000482457	P1

Frequencies

GnomAD3 genomes

AF:

0.553

AC:

84062

AN:

152026

Hom.:

23445

Cov.:

show subpopulations

Gnomad AFR

AF:

0.522

Gnomad AMI

AF:

0.693

Gnomad AMR

AF:

0.583

Gnomad ASJ

AF:

0.586

Gnomad EAS

AF:

0.611

Gnomad SAS

AF:

0.447

Gnomad FIN

AF:

0.609

Gnomad MID

AF:

0.573

Gnomad NFE

AF:

0.555

Gnomad OTH

AF:

0.569

GnomAD3 exomes

AF:

0.554

AC:

137831

AN:

248668

Hom.:

38483

AF XY:

0.549

AC XY:

74075

AN XY:

134924

show subpopulations

Gnomad AFR exome

AF:

0.526

Gnomad AMR exome

AF:

0.552

Gnomad ASJ exome

AF:

0.604

Gnomad EAS exome

AF:

0.635

Gnomad SAS exome

AF:

0.448

Gnomad FIN exome

AF:

0.610

Gnomad NFE exome

AF:

0.559

Gnomad OTH exome

AF:

0.564

GnomAD4 exome

AF:

0.546

AC:

745245

AN:

1365808

Hom.:

205146

Cov.:

AF XY:

0.544

AC XY:

372498

AN XY:

685244

show subpopulations

Gnomad4 AFR exome

AF:

0.519

Gnomad4 AMR exome

AF:

0.557

Gnomad4 ASJ exome

AF:

0.604

Gnomad4 EAS exome

AF:

0.577

Gnomad4 SAS exome

AF:

0.454

Gnomad4 FIN exome

AF:

0.605

Gnomad4 NFE exome

AF:

0.547

Gnomad4 OTH exome

AF:

0.559

GnomAD4 genome

AF:

0.553

AC:

84106

AN:

152144

Hom.:

23448

Cov.:

AF XY:

0.554

AC XY:

41185

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.521

Gnomad4 AMR

AF:

0.583

Gnomad4 ASJ

AF:

0.586

Gnomad4 EAS

AF:

0.610

Gnomad4 SAS

AF:

0.447

Gnomad4 FIN

AF:

0.609

Gnomad4 NFE

AF:

0.555

Gnomad4 OTH

AF:

0.567

Alfa

AF:

0.559

Hom.:

4316

Bravo

AF:

0.552

Asia WGS

AF:

0.512

AC:

1779

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	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 -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 12, 2023	This variant is classified as Benign based on local population frequency. This variant was detected in 78% of patients studied by a panel of primary immunodeficiencies. Number of patients: 75. Only high quality variants are reported. -

Familial cold autoinflammatory syndrome 3

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Oct 25, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Autoinflammation-PLCG2-associated antibody deficiency-immune dysregulation

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

5.1

DANN

Benign

0.73

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