dbSNP rs1071644: PLCG2:p.Asn1031Asn (chr16-81937798-T-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002661.5(PLCG2):c.3093T>C(p.Asn1031Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 1,613,270 control chromosomes in the GnomAD database, including 200,986 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 14051 hom., cov: 32)

Exomes 𝑓: 0.50 ( 186935 hom. )

Consequence

PLCG2
NM_002661.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10O:1

Conservation

PhyloP100: -0.489

Publications

26 publications found

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 Gene-Disease associations (from GenCC):

autoinflammation-PLCG2-associated antibody deficiency-immune dysregulation
Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet
familial cold autoinflammatory syndrome 3
Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet

PLCG2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 16-81937798-T-C is Benign according to our data. Variant chr16-81937798-T-C is described in ClinVar as Benign. ClinVar VariationId is 403324.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.489 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002661.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLCG2	NM_002661.5	MANE Select	c.3093T>C	p.Asn1031Asn	synonymous	Exon 28 of 33	NP_002652.2	P16885
PLCG2	NM_001425749.1		c.3093T>C	p.Asn1031Asn	synonymous	Exon 29 of 34	NP_001412678.1	P16885
PLCG2	NM_001425750.1		c.3093T>C	p.Asn1031Asn	synonymous	Exon 28 of 33	NP_001412679.1	P16885

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLCG2	ENST00000564138.6	TSL:1 MANE Select	c.3093T>C	p.Asn1031Asn	synonymous	Exon 28 of 33	ENSP00000482457.1	P16885
PLCG2	ENST00000902427.1		c.3246T>C	p.Asn1082Asn	synonymous	Exon 29 of 34	ENSP00000572486.1
PLCG2	ENST00000565054.7	TSL:5	c.3093T>C	p.Asn1031Asn	synonymous	Exon 29 of 34	ENSP00000520638.1	P16885

Frequencies

GnomAD3 genomes

AF:

0.394

AC:

59920

AN:

151988

Hom.:

14054

Cov.:

show subpopulations

Gnomad AFR

AF:

0.141

Gnomad AMI

AF:

0.469

Gnomad AMR

AF:

0.339

Gnomad ASJ

AF:

0.554

Gnomad EAS

AF:

0.369

Gnomad SAS

AF:

0.412

Gnomad FIN

AF:

0.524

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.531

Gnomad OTH

AF:

0.413

GnomAD2 exomes

AF:

0.445

AC:

110907

AN:

249252

AF XY:

0.458

show subpopulations

Gnomad AFR exome

AF:

0.137

Gnomad AMR exome

AF:

0.281

Gnomad ASJ exome

AF:

0.563

Gnomad EAS exome

AF:

0.354

Gnomad FIN exome

AF:

0.521

Gnomad NFE exome

AF:

0.528

Gnomad OTH exome

AF:

0.470

GnomAD4 exome

AF:

0.499

AC:

728819

AN:

1461164

Hom.:

186935

Cov.:

AF XY:

0.499

AC XY:

363069

AN XY:

726914

show subpopulations

African (AFR)

AF:

0.129

AC:

4305

AN:

33474

American (AMR)

AF:

0.289

AC:

12907

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.564

AC:

14728

AN:

26128

East Asian (EAS)

AF:

0.388

AC:

15417

AN:

39690

South Asian (SAS)

AF:

0.432

AC:

37268

AN:

86218

European-Finnish (FIN)

AF:

0.517

AC:

27579

AN:

53394

Middle Eastern (MID)

AF:

0.488

AC:

2812

AN:

5768

European-Non Finnish (NFE)

AF:

0.526

AC:

585121

AN:

1111418

Other (OTH)

AF:

0.475

AC:

28682

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

18205

36410

54616

72821

91026

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16446

32892

49338

65784

82230

<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:

0.394

AC:

59912

AN:

152106

Hom.:

14051

Cov.:

AF XY:

0.392

AC XY:

29119

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.141

AC:

5851

AN:

41508

American (AMR)

AF:

0.338

AC:

5175

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.554

AC:

1925

AN:

3472

East Asian (EAS)

AF:

0.369

AC:

1906

AN:

5160

South Asian (SAS)

AF:

0.413

AC:

1990

AN:

4820

European-Finnish (FIN)

AF:

0.524

AC:

5534

AN:

10566

Middle Eastern (MID)

AF:

0.452

AC:

133

AN:

294

European-Non Finnish (NFE)

AF:

0.531

AC:

36103

AN:

67968

Other (OTH)

AF:

0.410

AC:

867

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1687

3375

5062

6750

8437

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.465

Hom.:

41773

Bravo

AF:

0.372

Asia WGS

AF:

0.327

AC:

1136

AN:

3478

EpiCase

AF:

0.528

EpiControl

AF:

0.530

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

Familial cold autoinflammatory syndrome 3 (2)

not provided (3)

Autoinflammation-PLCG2-associated antibody deficiency-immune dysregulation (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

1.1

(source)

DANN

Benign

0.57

PhyloP100

-0.49

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over