NM_002661.5:c.2417+1099C>G

Variant names:

• chr16-81924693-C-G
• rs7192724
• NM_002661.5:c.2417+1099C>G

Variant summary

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

The NM_002661.5(PLCG2):​c.2417+1099C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,174 control chromosomes in the GnomAD database, including 4,522 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 0.24 (4522 hom., cov: 33)
• Consequence: PLCG2 NM_002661.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.262
• Publications: 6 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P
• familial cold autoinflammatory syndrome 3

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCG2	NM_002661.5	c.2417+1099C>G		intron_variant	Intron 22 of 32	ENST00000564138.6	NP_002652.2
PLCG2	NM_001425749.1	c.2417+1099C>G		intron_variant	Intron 23 of 33		NP_001412678.1
PLCG2	NM_001425750.1	c.2417+1099C>G		intron_variant	Intron 22 of 32		NP_001412679.1
PLCG2	NM_001425751.1	c.2417+1099C>G		intron_variant	Intron 23 of 33		NP_001412680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCG2	ENST00000564138.6	c.2417+1099C>G		intron_variant	Intron 22 of 32	1	NM_002661.5	ENSP00000482457.1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36962 AN: 152056 Hom.: 4514 Cov.: 33

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.243 AC: 37009 AN: 152174 Hom.: 4522 Cov.: 33 AF XY: 0.241 AC XY: 17965 AN XY: 74402

African (AFR) AF: 0.270 AC: 11218 AN: 41522

American (AMR) AF: 0.190 AC: 2904 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 783 AN: 3466

East Asian (EAS) AF: 0.185 AC: 961 AN: 5184

South Asian (SAS) AF: 0.307 AC: 1480 AN: 4826

European-Finnish (FIN) AF: 0.249 AC: 2632 AN: 10588

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16324 AN: 67982

Other (OTH) AF: 0.236 AC: 498 AN: 2112

Alfa AF: 0.144 Hom.: 257

Bravo AF: 0.235

Asia WGS AF: 0.239 AC: 831 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.3
DANN	Benign	0.67
PhyloP100		-0.26
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: rs7192724; hg19: chr16-81958298;