1-2480243-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_014638.4(PLCH2):c.576C>T(p.Gly192=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000204 in 1,612,744 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00035 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00019 (2 hom.)
• Consequence: PLCH2 NM_014638.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.23

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]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 1-2480243-C-T is Benign according to our data. Variant chr1-2480243-C-T is described in ClinVar as [Benign]. Clinvar id is 773104.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.23 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCH2	NM_014638.4	c.576C>T	p.Gly192=	synonymous_variant	4/22	ENST00000378486.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCH2	ENST00000378486.8	c.576C>T	p.Gly192=	synonymous_variant	4/22	1	NM_014638.4	P2

Frequencies

GnomAD3 genomes AF: 0.000355 AC: 54 AN: 152194 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.000410 AC: 102 AN: 248628 Hom.: 1 AF XY: 0.000348 AC XY: 47 AN XY: 135100

Gnomad AFR exome AF: 0.000388

Gnomad AMR exome AF: 0.00174

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: 0.000204

Gnomad OTH exome AF: 0.00215

GnomAD4 exome AF: 0.000188 AC: 275 AN: 1460432 Hom.: 2 Cov.: 33 AF XY: 0.000200 AC XY: 145 AN XY: 726504

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.00172

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.0000191

Gnomad4 NFE exome AF: 0.000131

Gnomad4 OTH exome AF: 0.000630

GnomAD4 genome AF: 0.000355 AC: 54 AN: 152312 Hom.: 0 Cov.: 34 AF XY: 0.000443 AC XY: 33 AN XY: 74472

Gnomad4 AFR AF: 0.000385

Gnomad4 AMR AF: 0.00163

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.000296 Hom.: 0

Bravo AF: 0.000733

EpiCase AF: 0.000218

EpiControl AF: 0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	1.6
Dann	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs373933358; hg19: chr1-2411682; COSMIC: COSV53939089; COSMIC: COSV53939089;