16-81930013-G-T

Position:

• chr16-81930013-G-T

Variant summary

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

The ENST00000564138.6(PLCG2):​c.2581+1389G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 151,962 control chromosomes in the GnomAD database, including 40,964 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 0.73 (40964 hom., cov: 31)
• Consequence: PLCG2 ENST00000564138.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0110

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCG2	NM_002661.5	c.2581+1389G>T		intron_variant		ENST00000564138.6	NP_002652.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCG2	ENST00000564138.6	c.2581+1389G>T		intron_variant		1	NM_002661.5	ENSP00000482457	P1

Frequencies

GnomAD3 genomes AF: 0.734 AC: 111393 AN: 151844 Hom.: 40935 Cov.: 31

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.729

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.742

Gnomad OTH AF: 0.740

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

GnomAD4 genome AF: 0.734 AC: 111469 AN: 151962 Hom.: 40964 Cov.: 31 AF XY: 0.737 AC XY: 54755 AN XY: 74298

Gnomad4 AFR AF: 0.702

Gnomad4 AMR AF: 0.766

Gnomad4 ASJ AF: 0.729

Gnomad4 EAS AF: 0.749

Gnomad4 SAS AF: 0.722

Gnomad4 FIN AF: 0.750

Gnomad4 NFE AF: 0.742

Gnomad4 OTH AF: 0.737

Alfa AF: 0.744 Hom.: 41685

Bravo AF: 0.736

Asia WGS AF: 0.746 AC: 2596 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.75
DANN	Benign	0.18

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: rs4888190; hg19: chr16-81963618;