rs2477686

Variant names:

• chr1-2461209-G-C
• rs2477686
• ENST00000609981.5:c.116-17267G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 29 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000609981.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCH2	ENST00000609981.5	TSL:5	c.116-17267G>C		intron	N/A	ENSP00000476436.1	V9GY64

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

African (AFR) AF: 0.868 AC: 36023 AN: 41520

American (AMR) AF: 0.662 AC: 10131 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1413 AN: 3472

East Asian (EAS) AF: 0.875 AC: 4523 AN: 5168

South Asian (SAS) AF: 0.656 AC: 3171 AN: 4832

European-Finnish (FIN) AF: 0.569 AC: 6040 AN: 10616

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.498 AC: 33845 AN: 67976

Other (OTH) AF: 0.571 AC: 1206 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	17
DANN	Benign	0.59
PhyloP100		-0.70

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2477686;

hg19: chr1-2392648;