1-2479840-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_014638.4(PLCH2):c.378C>T(p.His126=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000691 in 1,609,320 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00040 (5 hom.)
• Consequence: PLCH2 NM_014638.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.52

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-2479840-C-T is Benign according to our data. Variant chr1-2479840-C-T is described in ClinVar as [Benign]. Clinvar id is 720201.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCH2	NM_014638.4	c.378C>T	p.His126=	synonymous_variant	3/22	ENST00000378486.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCH2	ENST00000378486.8	c.378C>T	p.His126=	synonymous_variant	3/22	1	NM_014638.4	P2

Frequencies

GnomAD3 genomes AF: 0.00346 AC: 527 AN: 152192 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.0119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000938 AC: 219 AN: 233386 Hom.: 1 AF XY: 0.000760 AC XY: 98 AN XY: 128998

Gnomad AFR exome AF: 0.0135

Gnomad AMR exome AF: 0.000535

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000914

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000962

Gnomad NFE exome AF: 0.0000291

Gnomad OTH exome AF: 0.000526

GnomAD4 exome AF: 0.000402 AC: 585 AN: 1457010 Hom.: 5 Cov.: 30 AF XY: 0.000346 AC XY: 251 AN XY: 724730

Gnomad4 AFR exome AF: 0.0126

Gnomad4 AMR exome AF: 0.000678

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000354

Gnomad4 SAS exome AF: 0.0000233

Gnomad4 FIN exome AF: 0.0000777

Gnomad4 NFE exome AF: 0.0000522

Gnomad4 OTH exome AF: 0.000848

GnomAD4 genome AF: 0.00346 AC: 527 AN: 152310 Hom.: 2 Cov.: 33 AF XY: 0.00346 AC XY: 258 AN XY: 74474

Gnomad4 AFR AF: 0.0119

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00171 Hom.: 1

Bravo AF: 0.00414

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	-0.81
Cadd	Benign	1.6
Dann	Benign	0.56

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

Other links and lift over

dbSNP: rs185066621; hg19: chr1-2411279;