1-2459813-A-C

Position:

• chr1-2459813-A-C

Variant summary

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

The ENST00000609981.5(PLCH2):​c.116-18663A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 152,104 control chromosomes in the GnomAD database, including 25,743 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 0.57 (25743 hom., cov: 35)
• Consequence: PLCH2 ENST00000609981.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.28

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCH2	XM_047435023.1	c.386-18663A>C		intron_variant			XP_047290979.1
PLCH2	XM_047435024.1	c.386-18663A>C		intron_variant			XP_047290980.1
PLCH2	XM_047435025.1	c.386-18663A>C		intron_variant			XP_047290981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCH2	ENST00000609981.5	c.116-18663A>C		intron_variant		5		ENSP00000476436

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87056 AN: 151988 Hom.: 25714 Cov.: 35

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.875

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.529

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

GnomAD4 genome AF: 0.573 AC: 87134 AN: 152104 Hom.: 25743 Cov.: 35 AF XY: 0.580 AC XY: 43154 AN XY: 74358

Gnomad4 AFR AF: 0.635

Gnomad4 AMR AF: 0.640

Gnomad4 ASJ AF: 0.404

Gnomad4 EAS AF: 0.875

Gnomad4 SAS AF: 0.657

Gnomad4 FIN AF: 0.570

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.531

Alfa AF: 0.543 Hom.: 2813

Bravo AF: 0.579

Asia WGS AF: 0.735 AC: 2552 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16824398; hg19: chr1-2391252;