Variant 1-2479850-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014638.4(PLCH2):c.388C>T(p.Arg130Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,610,582 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

PLCH2
NM_014638.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.98

Variant links:

Genes affected

PLCH2 (HGNC:29037): (phospholipase C eta 2) PLCH2 is a member of the PLC-eta family of the phosphoinositide-specific phospholipase C (PLC) superfamily of enzymes that cleave PtdIns(4,5) P2 to generate second messengers inositol 1,4,5-trisphosphate and diacylglycerol (Zhou et al., 2005 [PubMed 16107206]).[supplied by OMIM, Jun 2009]

PLCH2 links:

PLCH2 (HGNC:):

PLCH2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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/exons	MANE	Protein	UniProt
PLCH2	NM_014638.4 linkuse as main transcript	c.388C>T	p.Arg130Cys	missense_variant	3/22	ENST00000378486.8	NP_055453.2	O75038-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PLCH2	ENST00000378486.8 linkuse as main transcript	c.388C>T	p.Arg130Cys	missense_variant	3/22	1	NM_014638.4	ENSP00000367747.3	O75038-1
PLCH2	ENST00000419816.6 linkuse as main transcript	c.388C>T	p.Arg130Cys	missense_variant	3/22	5		ENSP00000389803.2	O75038-1
PLCH2	ENST00000449969.5 linkuse as main transcript	c.307C>T	p.Arg103Cys	missense_variant	3/22	5		ENSP00000397289.1	O75038-2
PLCH2	ENST00000278878.6 linkuse as main transcript	c.-39C>T		upstream_gene_variant		5		ENSP00000278878.6	B9DI82

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152188

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000340

AC:

AN:

235606

Hom.:

AF XY:

0.0000384

AC XY:

AN XY:

130118

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000295

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000133

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000192

Gnomad OTH exome

AF:

0.000174

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1458276

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

725400

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000930

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000567

ExAC

AF:

0.0000333

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2024

The c.388C>T (p.R130C) alteration is located in exon 3 (coding exon 3) of the PLCH2 gene. This alteration results from a C to T substitution at nucleotide position 388, causing the arginine (R) at amino acid position 130 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.14

.;T;T

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.77

M_CAP

Uncertain

0.23

MetaRNN

Uncertain

0.43

T;T;T

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.6

.;M;M

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.98

N;.;N

REVEL

Benign

0.18

Sift

Benign

0.12

T;.;T

Sift4G

Benign

0.17

T;T;T

Polyphen

0.0090

.;B;B

Vest4

0.55

MutPred

0.57

.;Loss of disorder (P = 0.0334);Loss of disorder (P = 0.0334);

MVP

0.78

MPC

0.84

ClinPred

0.12

GERP RS

2.7

Varity_R

0.078

gMVP

0.50

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