Variant 1-2476671-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_014638.4(PLCH2):c.83G>C(p.Gly28Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00227 in 1,610,838 control chromosomes in the GnomAD database, including 147 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 15 hom., cov: 34)

Exomes 𝑓: 0.0023 ( 132 hom. )

Consequence

PLCH2
NM_014638.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.53

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002139032).

BP6

Variant 1-2476671-G-C is Benign according to our data. Variant chr1-2476671-G-C is described in ClinVar as [Benign]. Clinvar id is 779852.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCH2	NM_014638.4 linkuse as main transcript	c.83G>C	p.Gly28Ala	missense_variant	1/22	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.83G>C	p.Gly28Ala	missense_variant	1/22	1	NM_014638.4	ENSP00000367747.3	O75038-1
PLCH2	ENST00000419816.6 linkuse as main transcript	c.83G>C	p.Gly28Ala	missense_variant	1/22	5		ENSP00000389803.2	O75038-1
PLCH2	ENST00000449969.5 linkuse as main transcript	c.44-1805G>C		intron_variant		5		ENSP00000397289.1	O75038-2
PLCH2	ENST00000609981.5 linkuse as main transcript	c.116-1805G>C		intron_variant		5		ENSP00000476436.1	V9GY64

Frequencies

GnomAD3 genomes

AF:

0.00231

AC:

352

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0632

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00468

AC:

1136

AN:

242944

Hom.:

AF XY:

0.00429

AC XY:

569

AN XY:

132528

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0622

Gnomad SAS exome

AF:

0.000594

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000364

Gnomad OTH exome

AF:

0.00238

GnomAD4 exome

AF:

0.00227

AC:

3312

AN:

1458520

Hom.:

132

Cov.:

AF XY:

0.00220

AC XY:

1599

AN XY:

725442

show subpopulations

Gnomad4 AFR exome

AF:

0.0000898

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0765

Gnomad4 SAS exome

AF:

0.000570

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000396

Gnomad4 OTH exome

AF:

0.00309

GnomAD4 genome

AF:

0.00230

AC:

350

AN:

152318

Hom.:

Cov.:

AF XY:

0.00248

AC XY:

185

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0630

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.0000716

Hom.:

Bravo

AF:

0.00235

ExAC

AF:

0.00468

AC:

562

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000596

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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.13

T;T

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.35

FATHMM_MKL

Uncertain

0.85

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.75

N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.6

.;N

REVEL

Benign

0.036

Sift

Benign

0.081

.;T

Sift4G

Benign

0.12

T;T

Polyphen

0.058

B;B

Vest4

0.23

MVP

0.38

ClinPred

0.040

GERP RS

2.7

Varity_R

0.069

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