rs3936112

chr16-81937333-C-T

Variant summary

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

The NM_002661.5(PLCG2):c.3053-425C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 152,830 control chromosomes in the GnomAD database, including 7,655 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 0.30 (7618 hom., cov: 33)
  • Exomes 𝑓: 0.29 (37 hom.)
• Consequence: PLCG2 NM_002661.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.488

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCG2	NM_002661.5	c.3053-425C>T		intron_variant		ENST00000564138.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCG2	ENST00000564138.6	c.3053-425C>T		intron_variant		1	NM_002661.5	P1

Frequencies

GnomAD3 genomes AF: 0.296 AC: 45026 AN: 152036 Hom.: 7617 Cov.: 33

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.300

GnomAD4 exome AF: 0.288 AC: 195 AN: 676 Hom.: 37 Cov.: 0 AF XY: 0.266 AC XY: 91 AN XY: 342

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.200

Gnomad4 ASJ exome AF: 0.286

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.286

Gnomad4 FIN exome AF: 0.357

Gnomad4 NFE exome AF: 0.312

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.296 AC: 45040 AN: 152154 Hom.: 7618 Cov.: 33 AF XY: 0.296 AC XY: 22012 AN XY: 74378

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.373

Gnomad4 EAS AF: 0.214

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.399

Gnomad4 NFE AF: 0.384

Gnomad4 OTH AF: 0.298

Alfa AF: 0.363 Hom.: 5391

Bravo AF: 0.281

Asia WGS AF: 0.236 AC: 820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.0
Dann	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs3936112; hg19: chr16-81970938;