1-2476606-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_014638.4(PLCH2):c.18C>T(p.Pro6=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000849 in 1,580,426 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0048 (6 hom., cov: 34)
  • Exomes 𝑓: 0.00043 (5 hom.)
• Consequence: PLCH2 NM_014638.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.75

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 1-2476606-C-T is Benign according to our data. Variant chr1-2476606-C-T is described in ClinVar as [Benign]. Clinvar id is 791770.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.75 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00479 (730/152354) while in subpopulation AFR AF= 0.0167 (696/41582). AF 95% confidence interval is 0.0157. There are 6 homozygotes in gnomad4. There are 358 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCH2	NM_014638.4	c.18C>T	p.Pro6=	synonymous_variant	1/22	ENST00000378486.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCH2	ENST00000378486.8	c.18C>T	p.Pro6=	synonymous_variant	1/22	1	NM_014638.4	P2
PLCH2	ENST00000419816.6	c.18C>T	p.Pro6=	synonymous_variant	1/22	5		P2
PLCH2	ENST00000449969.5	c.44-1870C>T		intron_variant		5		A2
PLCH2	ENST00000609981.5	c.116-1870C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00479 AC: 729 AN: 152236 Hom.: 6 Cov.: 34

Gnomad AFR AF: 0.0168

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

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: 0.00431

GnomAD3 exomes AF: 0.000908 AC: 180 AN: 198346 Hom.: 2 AF XY: 0.000712 AC XY: 77 AN XY: 108208

Gnomad AFR exome AF: 0.0140

Gnomad AMR exome AF: 0.000554

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000382

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000226

Gnomad OTH exome AF: 0.000197

GnomAD4 exome AF: 0.000428 AC: 611 AN: 1428072 Hom.: 5 Cov.: 31 AF XY: 0.000368 AC XY: 261 AN XY: 708432

Gnomad4 AFR exome AF: 0.0165

Gnomad4 AMR exome AF: 0.000579

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000243

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000728

Gnomad4 OTH exome AF: 0.000608

GnomAD4 genome AF: 0.00479 AC: 730 AN: 152354 Hom.: 6 Cov.: 34 AF XY: 0.00481 AC XY: 358 AN XY: 74498

Gnomad4 AFR AF: 0.0167

Gnomad4 AMR AF: 0.00131

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: 0.00426

Alfa AF: 0.00292 Hom.: 2

Bravo AF: 0.00509

Asia WGS AF: 0.000866 AC: 3 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

Jul 31, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.13
Dann	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs370278142; hg19: chr1-2408045;