rs2477686

Positions:

• chr1-2461209-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000609981.5(PLCH2):​c.116-17267G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 152,206 control chromosomes in the GnomAD database, including 33,125 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.64 (33125 hom., cov: 36)
• Consequence: PLCH2 ENST00000609981.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.698

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCH2	XM_047435023.1	c.386-17267G>C		intron_variant			XP_047290979.1
PLCH2	XM_047435024.1	c.386-17267G>C		intron_variant			XP_047290980.1
PLCH2	XM_047435028.1	c.116-17267G>C		intron_variant			XP_047290984.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCH2	ENST00000609981.5	c.116-17267G>C		intron_variant		5		ENSP00000476436.1

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96809 AN: 152088 Hom.: 33062 Cov.: 36

Gnomad AFR AF: 0.867

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.875

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.569

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.637 AC: 96930 AN: 152206 Hom.: 33125 Cov.: 36 AF XY: 0.642 AC XY: 47773 AN XY: 74410

Gnomad4 AFR AF: 0.868

Gnomad4 AMR AF: 0.662

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.875

Gnomad4 SAS AF: 0.656

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.571

Alfa AF: 0.580 Hom.: 3331

Bravo AF: 0.653

Asia WGS AF: 0.754 AC: 2617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	17
DANN	Benign	0.59

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2477686; hg19: chr1-2392648;