rs12432184

Positions:

• chr14-56216743-G-A

Variant summary

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

The ENST00000267460.9(PELI2):​c.207+38279G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 152,042 control chromosomes in the GnomAD database, including 13,036 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 0.40 (13036 hom., cov: 33)
• Consequence: PELI2 ENST00000267460.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.293

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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PELI2	NM_021255.3	c.207+38279G>A		intron_variant		ENST00000267460.9	NP_067078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PELI2	ENST00000267460.9	c.207+38279G>A		intron_variant		1	NM_021255.3	ENSP00000267460	P1
PELI2	ENST00000559044.5	c.-94+38279G>A		intron_variant		4		ENSP00000452666
PELI2	ENST00000561019.1	c.-94+38279G>A		intron_variant		5		ENSP00000453988
PELI2	ENST00000705193.1	c.378+38279G>A		intron_variant				ENSP00000516089

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60844 AN: 151924 Hom.: 13033 Cov.: 33

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.400 AC: 60869 AN: 152042 Hom.: 13036 Cov.: 33 AF XY: 0.406 AC XY: 30204 AN XY: 74314

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.479

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.534

Gnomad4 FIN AF: 0.491

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.432

Alfa AF: 0.431 Hom.: 2511

Bravo AF: 0.393

Asia WGS AF: 0.448 AC: 1559 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.5
DANN	Benign	0.59

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: rs12432184; hg19: chr14-56683461;