16-81930013-G-T

Variant names:

• chr16-81930013-G-T
• rs4888190
• NM_002661.5:c.2581+1389G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002661.5(PLCG2):​c.2581+1389G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 151,962 control chromosomes in the GnomAD database, including 40,964 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 0.73 (40964 hom., cov: 31)
• Consequence: PLCG2 NM_002661.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0110
• Publications: 3 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.755 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCG2	NM_002661.5	MANE Select	c.2581+1389G>T		intron	N/A	NP_002652.2	P16885
	PLCG2	NM_001425749.1		c.2581+1389G>T		intron	N/A	NP_001412678.1	P16885
	PLCG2	NM_001425750.1		c.2581+1389G>T		intron	N/A	NP_001412679.1	P16885

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCG2	ENST00000564138.6	TSL:1 MANE Select	c.2581+1389G>T		intron	N/A	ENSP00000482457.1	P16885
	PLCG2	ENST00000902427.1		c.2734+1389G>T		intron	N/A	ENSP00000572486.1
	PLCG2	ENST00000565054.7	TSL:5	c.2581+1389G>T		intron	N/A	ENSP00000520638.1	P16885

Frequencies

GnomAD3 genomes AF: 0.734 AC: 111393 AN: 151844 Hom.: 40935 Cov.: 31

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.729

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.742

Gnomad OTH AF: 0.740

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.734 AC: 111469 AN: 151962 Hom.: 40964 Cov.: 31 AF XY: 0.737 AC XY: 54755 AN XY: 74298

African (AFR) AF: 0.702 AC: 29108 AN: 41444

American (AMR) AF: 0.766 AC: 11699 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.729 AC: 2532 AN: 3472

East Asian (EAS) AF: 0.749 AC: 3861 AN: 5156

South Asian (SAS) AF: 0.722 AC: 3469 AN: 4808

European-Finnish (FIN) AF: 0.750 AC: 7911 AN: 10542

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.742 AC: 50452 AN: 67958

Other (OTH) AF: 0.737 AC: 1557 AN: 2112

Alfa AF: 0.744 Hom.: 54304

Bravo AF: 0.736

Asia WGS AF: 0.746 AC: 2596 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.75
DANN	Benign	0.18
PhyloP100		-0.011
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

Other links and lift over

dbSNP: rs4888190; hg19: chr16-81963618;