Variant 1-2479811-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014638.4(PLCH2):c.349G>A(p.Asp117Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000405 in 1,598,326 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00041 ( 1 hom. )

Consequence

PLCH2
NM_014638.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.51

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22072646).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCH2	NM_014638.4 linkuse as main transcript	c.349G>A	p.Asp117Asn	missense_variant	3/22	ENST00000378486.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCH2	ENST00000378486.8 linkuse as main transcript	c.349G>A	p.Asp117Asn	missense_variant	3/22	1	NM_014638.4	P2	O75038-1

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

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:

0.000426

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000189

AC:

AN:

216594

Hom.:

AF XY:

0.000176

AC XY:

AN XY:

119568

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000409

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:

0.000285

Gnomad OTH exome

AF:

0.000184

GnomAD4 exome

AF:

0.000414

AC:

599

AN:

1446082

Hom.:

Cov.:

AF XY:

0.000413

AC XY:

297

AN XY:

718424

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000400

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000508

Gnomad4 OTH exome

AF:

0.000334

GnomAD4 genome

AF:

0.000322

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000314

Hom.:

Bravo

AF:

0.000397

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000473

AC:

ExAC

AF:

0.000167

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

Sep 01, 2021

The c.349G>A (p.D117N) alteration is located in exon 3 (coding exon 3) of the PLCH2 gene. This alteration results from a G to A substitution at nucleotide position 349, causing the aspartic acid (D) at amino acid position 117 to be replaced by an asparagine (N). 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

0.21

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.39

Cadd

Pathogenic

Dann

Uncertain

0.99

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.97

M_CAP

Pathogenic

0.37

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Uncertain

0.025

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.7

D;.;D

REVEL

Uncertain

0.39

Sift

Uncertain

0.0070

D;.;D

Sift4G

Uncertain

0.031

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.54

MVP

0.82

MPC

0.64

ClinPred

0.40

GERP RS

4.8

Varity_R

0.42

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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