rs7185362

chr16-81855300-G-Achr16-81855300-G-Cchr16-81855300-G-T

Variant summary

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

The NM_002661.5(PLCG2):c.337+713G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 151,810 control chromosomes in the GnomAD database, including 5,741 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 0.26 (5741 hom., cov: 31)
• Consequence: PLCG2 NM_002661.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.613

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 = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCG2	NM_002661.5	c.337+713G>A		intron_variant		ENST00000564138.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCG2	ENST00000564138.6	c.337+713G>A		intron_variant		1	NM_002661.5	P1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40196 AN: 151708 Hom.: 5738 Cov.: 31

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.0845

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.265 AC: 40196 AN: 151810 Hom.: 5741 Cov.: 31 AF XY: 0.264 AC XY: 19587 AN XY: 74174

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.0841

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.277

Alfa AF: 0.302 Hom.: 9481

Bravo AF: 0.254

Asia WGS AF: 0.173 AC: 605 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	1.1
Dann	Benign	0.64

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: rs7185362; hg19: chr16-81888905;