chr15-40291866-G-A

Variant names:

• chr15-40291866-G-A
• rs779256250
• NM_004573.3:c.2585C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004573.3(PLCB2):​c.2585C>T​(p.Thr862Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T862K) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: PLCB2 NM_004573.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.746
• Publications: 1 publications found

Genes affected

PLCB2 (HGNC:9055): (phospholipase C beta 2) The protein encoded by this gene is a phosphodiesterase that catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate to the second messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol. The encoded protein is activated by G proteins and has been shown to be involved in the type 2 taste receptor signal transduction pathway. In addition, nuclear factor kappa B can regulate the transcription of this gene, whose protein product is also an important regulator of platelet responses. [provided by RefSeq, Jan 2017]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06113243).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004573.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCB2	NM_004573.3	MANE Select	c.2585C>T	p.Thr862Met	missense	Exon 24 of 32	NP_004564.2
	PLCB2	NM_001284297.2		c.2573C>T	p.Thr858Met	missense	Exon 24 of 32	NP_001271226.1
	PLCB2	NM_001284298.2		c.2585C>T	p.Thr862Met	missense	Exon 24 of 31	NP_001271227.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCB2	ENST00000260402.8	TSL:2 MANE Select	c.2585C>T	p.Thr862Met	missense	Exon 24 of 32	ENSP00000260402.3
	PLCB2	ENST00000557821.5	TSL:1	c.2573C>T	p.Thr858Met	missense	Exon 24 of 32	ENSP00000453975.1
	PLCB2	ENST00000456256.6	TSL:1	c.2585C>T	p.Thr862Met	missense	Exon 24 of 31	ENSP00000411991.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249274 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461756 Hom.: 0 Cov.: 35 AF XY: 0.00000825 AC XY: 6 AN XY: 727182

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111928

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000826 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.2
DANN	Benign	0.94
DEOGEN2	Benign	0.31	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.75
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.053
Sift	Benign	0.11	T
Sift4G	Uncertain	0.045	D
Polyphen		0.76	P
Vest4		0.19
MutPred		0.24		Loss of glycosylation at T862 (P = 0.0112)
MVP		0.29
MPC		0.32
ClinPred		0.14	T
GERP RS		-6.3
Varity_R		0.015
gMVP		0.23
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs779256250; hg19: chr15-40584067;