Variant chr3-17014786-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001144382.2(PLCL2):c.2893C>T(p.Pro965Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00142 in 1,614,116 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0074 ( 15 hom., cov: 32)

Exomes 𝑓: 0.00079 ( 17 hom. )

Consequence

PLCL2
NM_001144382.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.73

Variant links:

Genes affected

PLCL2 (HGNC:9064): (phospholipase C like 2) Enables GABA receptor binding activity. Predicted to be involved in negative regulation of cold-induced thermogenesis and phosphatidylinositol-mediated signaling. Predicted to act upstream of or within several processes, including B cell activation; gamma-aminobutyric acid signaling pathway; and negative regulation of B cell receptor signaling pathway. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PLCL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003397882).

BP6

Variant 3-17014786-C-T is Benign according to our data. Variant chr3-17014786-C-T is described in ClinVar as [Benign]. Clinvar id is 775850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00745 (1134/152298) while in subpopulation AFR AF= 0.0256 (1062/41556). AF 95% confidence interval is 0.0243. There are 15 homozygotes in gnomad4. There are 534 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1134 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCL2	NM_001144382.2 linkuse as main transcript	c.2893C>T	p.Pro965Ser	missense_variant	3/6	ENST00000615277.5	NP_001137854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCL2	ENST00000615277.5 linkuse as main transcript	c.2893C>T	p.Pro965Ser	missense_variant	3/6	1	NM_001144382.2	ENSP00000478458		Q9UPR0-1
PLCL2	ENST00000432376.5 linkuse as main transcript	c.2515C>T	p.Pro839Ser	missense_variant	3/6	1		ENSP00000412836	P1	Q9UPR0-3
PLCL2	ENST00000419842.1 linkuse as main transcript	c.1747C>T	p.Pro583Ser	missense_variant	2/5	2		ENSP00000404433

Frequencies

GnomAD3 genomes

AF:

0.00744

AC:

1132

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0256

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00187

AC:

469

AN:

251322

Hom.:

AF XY:

0.00127

AC XY:

172

AN XY:

135822

show subpopulations

Gnomad AFR exome

AF:

0.0249

Gnomad AMR exome

AF:

0.00119

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.000790

AC:

1155

AN:

1461818

Hom.:

Cov.:

AF XY:

0.000679

AC XY:

494

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.0260

Gnomad4 AMR exome

AF:

0.00114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000989

Gnomad4 OTH exome

AF:

0.00182

GnomAD4 genome

AF:

0.00745

AC:

1134

AN:

152298

Hom.:

Cov.:

AF XY:

0.00717

AC XY:

534

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0256

Gnomad4 AMR

AF:

0.00320

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00102

Hom.:

Bravo

AF:

0.00799

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0288

AC:

127

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00224

AC:

272

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.28

DEOGEN2

Benign

0.077

T;.

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.69

MetaRNN

Benign

0.0034

T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

0.75

N;N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

1.4

.;N

REVEL

Benign

0.097

Sift

Benign

1.0

.;T

Sift4G

Benign

0.83

T;T

Polyphen

0.0

B;.

Vest4

0.18

MVP

0.22

ClinPred

0.0073

GERP RS

2.2

Varity_R

0.064

gMVP

0.26

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over