rs10514519

Positions:

• chr16-81941460-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002661.5(PLCG2):​c.3481+1401G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,054 control chromosomes in the GnomAD database, including 4,364 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 0.22 (4364 hom., cov: 32)
• Consequence: PLCG2 NM_002661.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCG2	NM_002661.5	c.3481+1401G>A		intron_variant		ENST00000564138.6	NP_002652.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCG2	ENST00000564138.6	c.3481+1401G>A		intron_variant		1	NM_002661.5	ENSP00000482457	P1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33184 AN: 151936 Hom.: 4364 Cov.: 32

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.0629

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.218 AC: 33200 AN: 152054 Hom.: 4364 Cov.: 32 AF XY: 0.213 AC XY: 15805 AN XY: 74324

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.0625

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.193

Alfa AF: 0.177 Hom.: 5296

Bravo AF: 0.225

Asia WGS AF: 0.0960 AC: 338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.92
DANN	Benign	0.20

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

Publications

LitVar

Other links and lift over

dbSNP: rs10514519; hg19: chr16-81975065;