rs1057519832

Variant names:

• chr16-81928578-A-C
• rs1057519832
• NM_002661.5:c.2535A>C

Your query was ambiguous. Multiple possible variants found:

• chr16-81928578-A-C
• chr16-81928578-A-G
• chr16-81928578-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002661.5(PLCG2):​c.2535A>C​(p.Leu845Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PLCG2 NM_002661.5 missense
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.881

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCG2	NM_002661.5	c.2535A>C	p.Leu845Phe	missense_variant	Exon 24 of 33	ENST00000564138.6	NP_002652.2
PLCG2	NM_001425749.1	c.2535A>C	p.Leu845Phe	missense_variant	Exon 25 of 34		NP_001412678.1
PLCG2	NM_001425750.1	c.2535A>C	p.Leu845Phe	missense_variant	Exon 24 of 33		NP_001412679.1
PLCG2	NM_001425751.1	c.2535A>C	p.Leu845Phe	missense_variant	Exon 25 of 34		NP_001412680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCG2	ENST00000564138.6	c.2535A>C	p.Leu845Phe	missense_variant	Exon 24 of 33	1	NM_002661.5	ENSP00000482457.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

B-cell chronic lymphocytic leukemia Pathogenic:1

Dec 26, 2014

Database of Curated Mutations (DoCM)

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Uncertain	0.082	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.85	D;.
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.68	D;D
MetaSVM	Benign	-0.50	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.3	.;D
REVEL	Uncertain	0.44
Sift	Benign	0.047	.;D
Sift4G	Uncertain	0.023	D;D
Polyphen		1.0	D;.
Vest4		0.70
MutPred		0.46		Loss of catalytic residue at L845 (P = 0.0079);Loss of catalytic residue at L845 (P = 0.0079);
MVP		0.72
MPC		0.99
ClinPred		0.96	D
GERP RS		1.9
Varity_R		0.65
gMVP		0.77

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: rs1057519832; hg19: chr16-81962183;