rs3813009

Variant names:

• chr16-81927353-G-C
• rs3813009
• NM_002661.5:c.2514+175G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-81927353-G-C
• chr16-81927353-G-A
• chr16-81927353-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002661.5(PLCG2):​c.2514+175G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,136 control chromosomes in the GnomAD database, including 2,457 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.16 (2457 hom., cov: 31)
• Consequence: PLCG2 NM_002661.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.554
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 16-81927353-G-C is Benign according to our data. Variant chr16-81927353-G-C is described in ClinVar as Benign. ClinVar VariationId is 1183021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.221 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.2514+175G>C		intron	N/A	NP_002652.2	P16885
	PLCG2	NM_001425749.1		c.2514+175G>C		intron	N/A	NP_001412678.1	P16885
	PLCG2	NM_001425750.1		c.2514+175G>C		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.2514+175G>C		intron	N/A	ENSP00000482457.1	P16885
	PLCG2	ENST00000902427.1		c.2667+175G>C		intron	N/A	ENSP00000572486.1
	PLCG2	ENST00000565054.7	TSL:5	c.2514+175G>C		intron	N/A	ENSP00000520638.1	P16885

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24173 AN: 152018 Hom.: 2458 Cov.: 31

Gnomad AFR AF: 0.0570

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.0281

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.159 AC: 24171 AN: 152136 Hom.: 2457 Cov.: 31 AF XY: 0.157 AC XY: 11642 AN XY: 74388

African (AFR) AF: 0.0568 AC: 2359 AN: 41516

American (AMR) AF: 0.132 AC: 2013 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 803 AN: 3470

East Asian (EAS) AF: 0.0281 AC: 146 AN: 5192

South Asian (SAS) AF: 0.102 AC: 490 AN: 4814

European-Finnish (FIN) AF: 0.233 AC: 2461 AN: 10576

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15248 AN: 67978

Other (OTH) AF: 0.156 AC: 330 AN: 2112

Alfa AF: 0.191 Hom.: 395

Bravo AF: 0.147

Asia WGS AF: 0.0810 AC: 283 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.3
DANN	Benign	0.53
PhyloP100		0.55
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3813009; hg19: chr16-81960958;