Genetic Variant PLCG2:c.-47-2815C>T (chr16-81783128-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002661.5(PLCG2):c.-47-2815C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 489,572 control chromosomes in the GnomAD database, including 50,431 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.42 ( 13640 hom., cov: 30)

Exomes 𝑓: 0.46 ( 36791 hom. )

Consequence

PLCG2
NM_002661.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.440

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PLCG2	NM_002661.5 link	c.-47-2815C>T	intron_variant	Intron 1 of 32	ENST00000564138.6	NP_002652.2	P16885
PLCG2	NM_001425749.1 link	c.-47-2815C>T	intron_variant	Intron 2 of 33		NP_001412678.1
PLCG2	NM_001425750.1 link	c.-47-2815C>T	intron_variant	Intron 1 of 32		NP_001412679.1
PLCG2	NM_001425751.1 link	c.-47-2815C>T	intron_variant	Intron 2 of 33		NP_001412680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCG2	ENST00000564138.6 link	c.-47-2815C>T		intron_variant	Intron 1 of 32	1	NM_002661.5	ENSP00000482457.1		P16885

Frequencies

GnomAD3 genomes

AF:

0.421

AC:

63791

AN:

151652

Hom.:

13632

Cov.:

show subpopulations

Gnomad AFR

AF:

0.412

Gnomad AMI

AF:

0.238

Gnomad AMR

AF:

0.366

Gnomad ASJ

AF:

0.397

Gnomad EAS

AF:

0.284

Gnomad SAS

AF:

0.633

Gnomad FIN

AF:

0.460

Gnomad MID

AF:

0.383

Gnomad NFE

AF:

0.432

Gnomad OTH

AF:

0.389

GnomAD2 exomes

AF:

0.428

AC:

78888

AN:

184232

AF XY:

0.442

show subpopulations

Gnomad AFR exome

AF:

0.392

Gnomad AMR exome

AF:

0.366

Gnomad ASJ exome

AF:

0.382

Gnomad EAS exome

AF:

0.279

Gnomad FIN exome

AF:

0.468

Gnomad NFE exome

AF:

0.422

Gnomad OTH exome

AF:

0.400

GnomAD4 exome

AF:

0.456

AC:

154110

AN:

337802

Hom.:

36791

Cov.:

AF XY:

0.472

AC XY:

91091

AN XY:

192886

show subpopulations

Gnomad4 AFR exome

AF:

0.405

AC:

4075

AN:

10054

Gnomad4 AMR exome

AF:

0.366

AC:

11588

AN:

31650

Gnomad4 ASJ exome

AF:

0.384

AC:

4295

AN:

11188

Gnomad4 EAS exome

AF:

0.290

AC:

3560

AN:

12264

Gnomad4 SAS exome

AF:

0.633

AC:

39351

AN:

62140

Gnomad4 FIN exome

AF:

0.463

AC:

7012

AN:

15138

Gnomad4 NFE exome

AF:

0.433

AC:

76617

AN:

177116

Gnomad4 Remaining exome

AF:

0.423

AC:

6580

AN:

15556

Heterozygous variant carriers

4206

8412

12618

16824

21030

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

572

1144

1716

2288

2860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.421

AC:

63833

AN:

151770

Hom.:

13640

Cov.:

AF XY:

0.425

AC XY:

31545

AN XY:

74150

show subpopulations

Gnomad4 AFR

AF:

0.412

AC:

0.411615

AN:

0.411615

Gnomad4 AMR

AF:

0.366

AC:

0.365735

AN:

0.365735

Gnomad4 ASJ

AF:

0.397

AC:

0.39694

AN:

0.39694

Gnomad4 EAS

AF:

0.284

AC:

0.283605

AN:

0.283605

Gnomad4 SAS

AF:

0.634

AC:

0.633943

AN:

0.633943

Gnomad4 FIN

AF:

0.460

AC:

0.459562

AN:

0.459562

Gnomad4 NFE

AF:

0.432

AC:

0.432366

AN:

0.432366

Gnomad4 OTH

AF:

0.390

AC:

0.390417

AN:

0.390417

Heterozygous variant carriers

1859

3718

5576

7435

9294

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

620

1240

1860

2480

3100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.419

Hom.:

4086

Bravo

AF:

0.404

Asia WGS

AF:

0.429

AC:

1491

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.5

DANN

Benign

0.55

Mutation Taster

=100/0

polymorphism (auto)

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over