rs12448089

chr16-81929022-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.2581+398G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 152,000 control chromosomes in the GnomAD database, including 36,309 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 0.68 (36309 hom., cov: 34)
• Consequence: PLCG2 NM_002661.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.31

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 (EAS) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCG2	NM_002661.5	c.2581+398G>A		intron_variant		ENST00000564138.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCG2	ENST00000564138.6	c.2581+398G>A		intron_variant		1	NM_002661.5	P1

Frequencies

GnomAD3 genomes AF: 0.685 AC: 104008 AN: 151882 Hom.: 36306 Cov.: 34

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.707

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.724

Gnomad FIN AF: 0.731

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.734

Gnomad OTH AF: 0.704

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

GnomAD4 genome AF: 0.684 AC: 104041 AN: 152000 Hom.: 36309 Cov.: 34 AF XY: 0.689 AC XY: 51178 AN XY: 74302

Gnomad4 AFR AF: 0.534

Gnomad4 AMR AF: 0.776

Gnomad4 ASJ AF: 0.707

Gnomad4 EAS AF: 0.809

Gnomad4 SAS AF: 0.723

Gnomad4 FIN AF: 0.731

Gnomad4 NFE AF: 0.734

Gnomad4 OTH AF: 0.705

Alfa AF: 0.702 Hom.: 4715

Bravo AF: 0.686

Asia WGS AF: 0.762 AC: 2649 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	0.0050
Dann	Benign	0.33

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: rs12448089; hg19: chr16-81962627;