Variant 3-17089910-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4BP6_ModerateBS1BS2

The NM_001144382.2(PLCL2):c.3382T>G(p.Ter1128GlyextTer5) variant causes a stop lost change. The variant allele was found at a frequency of 0.00141 in 1,611,642 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0073 ( 16 hom., cov: 33)

Exomes 𝑓: 0.00079 ( 15 hom. )

Consequence

PLCL2
NM_001144382.2 stop_lost

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.31

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 -8 ACMG points.

PM4

Stoplost variant in NM_001144382.2 Downstream stopcodon found after 1155 codons.

BP6

Variant 3-17089910-T-G is Benign according to our data. Variant chr3-17089910-T-G is described in ClinVar as [Benign]. Clinvar id is 767888.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00728 (1109/152300) while in subpopulation AFR AF= 0.0249 (1034/41570). AF 95% confidence interval is 0.0236. There are 16 homozygotes in gnomad4. There are 505 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1109 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCL2	NM_001144382.2 linkuse as main transcript	c.3382T>G	p.Ter1128GlyextTer5	stop_lost	6/6	ENST00000615277.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCL2	ENST00000615277.5 linkuse as main transcript	c.3382T>G	p.Ter1128GlyextTer5	stop_lost	6/6	1	NM_001144382.2		Q9UPR0-1
PLCL2	ENST00000432376.5 linkuse as main transcript	c.3004T>G	p.Ter1002GlyextTer5	stop_lost	6/6	1		P1	Q9UPR0-3

Frequencies

GnomAD3 genomes

AF:

0.00725

AC:

1104

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0248

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00575

GnomAD3 exomes

AF:

0.00205

AC:

509

AN:

248252

Hom.:

AF XY:

0.00152

AC XY:

204

AN XY:

134152

show subpopulations

Gnomad AFR exome

AF:

0.0271

Gnomad AMR exome

AF:

0.00154

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000670

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.000332

GnomAD4 exome

AF:

0.000794

AC:

1159

AN:

1459342

Hom.:

Cov.:

AF XY:

0.000690

AC XY:

501

AN XY:

725990

show subpopulations

Gnomad4 AFR exome

AF:

0.0271

Gnomad4 AMR exome

AF:

0.00157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000817

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000675

Gnomad4 OTH exome

AF:

0.00163

GnomAD4 genome

AF:

0.00728

AC:

1109

AN:

152300

Hom.:

Cov.:

AF XY:

0.00678

AC XY:

505

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0249

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00569

Alfa

AF:

0.00127

Hom.:

Bravo

AF:

0.00846

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0227

AC:

100

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00247

AC:

300

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000297

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.67

Eigen

Pathogenic

0.78

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.84

MutationTaster

Benign

1.0

N;N

Vest4

0.057

GERP RS

5.9

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