chr15-40298224-T-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM2PP3_ModerateBP6

The NM_004573.3(PLCB2):c.1154A>G(p.Lys385Arg) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000194 in 1,550,220 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PLCB2
NM_004573.3 missense, splice_region

Scores

Splicing: ADA: 0.9999

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 7.83

Publications

1 publications found

Variant links:

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]

PLCB2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

BP6

Variant 15-40298224-T-C is Benign according to our data. Variant chr15-40298224-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 254112.Status of the report is no_assertion_criteria_provided, 0 stars.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PLCB2	NM_004573.3	MANE Select	c.1154A>G	p.Lys385Arg	missense splice_region	Exon 11 of 32	NP_004564.2
PLCB2	NM_001284297.2		c.1154A>G	p.Lys385Arg	missense splice_region	Exon 11 of 32	NP_001271226.1
PLCB2	NM_001284298.2		c.1154A>G	p.Lys385Arg	missense splice_region	Exon 11 of 31	NP_001271227.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PLCB2	ENST00000260402.8	TSL:2 MANE Select	c.1154A>G	p.Lys385Arg	missense splice_region	Exon 11 of 32	ENSP00000260402.3
PLCB2	ENST00000557821.5	TSL:1	c.1154A>G	p.Lys385Arg	missense splice_region	Exon 11 of 32	ENSP00000453975.1
PLCB2	ENST00000456256.6	TSL:1	c.1154A>G	p.Lys385Arg	missense splice_region	Exon 11 of 31	ENSP00000411991.2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000492

AC:

AN:

203424

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000105

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1398008

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

687612

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31538

American (AMR)

AF:

0.00

AC:

AN:

36696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22168

East Asian (EAS)

AF:

0.00

AC:

AN:

39018

South Asian (SAS)

AF:

0.00

AC:

AN:

76258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51436

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5480

European-Non Finnish (NFE)

AF:

0.00000186

AC:

AN:

1077870

Other (OTH)

AF:

0.00

AC:

AN:

57544

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41458

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Oromandibular-limb hypogenesis spectrum

Benign:1

Aug 12, 2016

CHU Sainte-Justine Research Center, University of Montreal

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:research

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Uncertain

0.020

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.73

MetaSVM

Benign

-0.75

MutationAssessor

Benign

0.21

PhyloP100

7.8

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.6

REVEL

Benign

0.23

Sift

Benign

0.42

Sift4G

Benign

0.29

Polyphen

0.75

Vest4

0.75

MutPred

0.50

Loss of methylation at K385 (P = 0.0124)

MVP

0.87

MPC

0.94

ClinPred

0.91

GERP RS

5.0

Varity_R

0.29

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

1.0

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over