rs7185362

Variant names:

• chr16-81855300-G-A
• rs7185362
• NM_002661.5:c.337+713G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-81855300-G-A
• chr16-81855300-G-C
• chr16-81855300-G-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.337+713G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 151,810 control chromosomes in the GnomAD database, including 5,741 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 0.26 (5741 hom., cov: 31)
• Consequence: PLCG2 NM_002661.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.613
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.315 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.337+713G>A		intron	N/A	NP_002652.2	P16885
	PLCG2	NM_001425749.1		c.337+713G>A		intron	N/A	NP_001412678.1	P16885
	PLCG2	NM_001425750.1		c.337+713G>A		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.337+713G>A		intron	N/A	ENSP00000482457.1	P16885
	PLCG2	ENST00000567980.5	TSL:1	n.581+713G>A		intron	N/A
	PLCG2	ENST00000902427.1		c.337+713G>A		intron	N/A	ENSP00000572486.1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40196 AN: 151708 Hom.: 5738 Cov.: 31

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.0845

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.265 AC: 40196 AN: 151810 Hom.: 5741 Cov.: 31 AF XY: 0.264 AC XY: 19587 AN XY: 74174

African (AFR) AF: 0.173 AC: 7157 AN: 41376

American (AMR) AF: 0.274 AC: 4183 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1109 AN: 3464

East Asian (EAS) AF: 0.0841 AC: 436 AN: 5184

South Asian (SAS) AF: 0.280 AC: 1346 AN: 4800

European-Finnish (FIN) AF: 0.322 AC: 3365 AN: 10464

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21624 AN: 67958

Other (OTH) AF: 0.277 AC: 583 AN: 2104

Alfa AF: 0.298 Hom.: 11765

Bravo AF: 0.254

Asia WGS AF: 0.173 AC: 605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.64
PhyloP100		-0.61
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: rs7185362; hg19: chr16-81888905;