chr16-81937333-C-T

Variant names:

• chr16-81937333-C-T
• rs3936112
• NM_002661.5:c.3053-425C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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]

PLCG2 Gene-Disease associations (from GenCC):

• autoinflammation-PLCG2-associated antibody deficiency-immune dysregulation

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P
• familial cold autoinflammatory syndrome 3

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PLCG2	NM_002661.5	c.3053-425C>T		intron_variant	Intron 27 of 32	ENST00000564138.6	NP_002652.2
PLCG2	NM_001425749.1	c.3053-425C>T		intron_variant	Intron 28 of 33		NP_001412678.1
PLCG2	NM_001425750.1	c.3053-425C>T		intron_variant	Intron 27 of 32		NP_001412679.1
PLCG2	NM_001425751.1	c.3053-425C>T		intron_variant	Intron 28 of 33		NP_001412680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCG2	ENST00000564138.6	c.3053-425C>T		intron_variant	Intron 27 of 32	1	NM_002661.5	ENSP00000482457.1

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

African (AFR) AF: 0.00 AC: 0 AN: 26

American (AMR) AF: 0.200 AC: 10 AN: 50

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 4 AN: 14

East Asian (EAS) AF: 0.333 AC: 6 AN: 18

South Asian (SAS) AF: 0.286 AC: 4 AN: 14

European-Finnish (FIN) AF: 0.357 AC: 5 AN: 14

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.312 AC: 156 AN: 500

Other (OTH) AF: 0.250 AC: 10 AN: 40

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

African (AFR) AF: 0.138 AC: 5736 AN: 41498

American (AMR) AF: 0.253 AC: 3870 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 1294 AN: 3466

East Asian (EAS) AF: 0.214 AC: 1109 AN: 5180

South Asian (SAS) AF: 0.335 AC: 1616 AN: 4820

European-Finnish (FIN) AF: 0.399 AC: 4216 AN: 10566

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.384 AC: 26104 AN: 68010

Other (OTH) AF: 0.298 AC: 630 AN: 2114

Alfa AF: 0.361 Hom.: 5926

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
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3936112; hg19: chr16-81970938;