rs754314

Positions:

• chr14-56285879-G-A

Variant summary

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

The NM_021255.3(PELI2):​c.310-2558G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0737 in 152,148 control chromosomes in the GnomAD database, including 564 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 0.074 (564 hom., cov: 32)
• Consequence: PELI2 NM_021255.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155

Genes affected

PELI2 (HGNC:8828): (pellino E3 ubiquitin protein ligase family member 2) Predicted to enable protein-macromolecule adaptor activity and ubiquitin protein ligase activity. Acts upstream of or within positive regulation of MAPK cascade and positive regulation of protein phosphorylation. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PELI2	NM_021255.3	c.310-2558G>A		intron_variant		ENST00000267460.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PELI2	ENST00000267460.9	c.310-2558G>A		intron_variant		1	NM_021255.3	P1
PELI2	ENST00000559044.5	c.10-2558G>A		intron_variant		4
PELI2	ENST00000561019.1	c.10-2558G>A		intron_variant		5
PELI2	ENST00000705193.1	c.481-2558G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0737 AC: 11201 AN: 152030 Hom.: 565 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.0352

Gnomad ASJ AF: 0.0412

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.0933

Gnomad FIN AF: 0.0339

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0521

Gnomad OTH AF: 0.0542

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

GnomAD4 genome AF: 0.0737 AC: 11217 AN: 152148 Hom.: 564 Cov.: 32 AF XY: 0.0735 AC XY: 5470 AN XY: 74376

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.0355

Gnomad4 ASJ AF: 0.0412

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.0934

Gnomad4 FIN AF: 0.0339

Gnomad4 NFE AF: 0.0521

Gnomad4 OTH AF: 0.0579

Alfa AF: 0.0625 Hom.: 42

Bravo AF: 0.0754

Asia WGS AF: 0.130 AC: 451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.45

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: rs754314; hg19: chr14-56752597;