rs756865019

Variant names:

• chr14-56118686-A-G
• rs756865019
• NM_021255.3:c.26A>G

Your query was ambiguous. Multiple possible variants found:

• chr14-56118686-A-G
• chr14-56118686-A-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021255.3(PELI2):​c.26A>G​(p.His9Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000198 in 1,514,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: PELI2 NM_021255.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.565
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06466153).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021255.3. 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
	PELI2	NM_021255.3	MANE Select	c.26A>G	p.His9Arg	missense	Exon 1 of 6	NP_067078.1	Q9HAT8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PELI2	ENST00000267460.9	TSL:1 MANE Select	c.26A>G	p.His9Arg	missense	Exon 1 of 6	ENSP00000267460.4	Q9HAT8
	PELI2	ENST00000705193.1		c.197A>G	p.His66Arg	missense	Exon 1 of 6	ENSP00000516089.1	A0A994J4T1
	PELI2	ENST00000559044.5	TSL:4	c.-224+606A>G		intron	N/A	ENSP00000452666.1	H0YK56

Frequencies

GnomAD3 genomes AF: 0.00000662 AC: 1 AN: 151012 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000655 AC: 1 AN: 152762 AF XY: 0.0000119

Gnomad AFR exome AF: 0.000147

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000147 AC: 2 AN: 1363918 Hom.: 0 Cov.: 30 AF XY: 0.00000296 AC XY: 2 AN XY: 676298

African (AFR) AF: 0.0000707 AC: 2 AN: 28276

American (AMR) AF: 0.00 AC: 0 AN: 32796

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23280

East Asian (EAS) AF: 0.00 AC: 0 AN: 31136

South Asian (SAS) AF: 0.00 AC: 0 AN: 76604

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4460

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1063416

Other (OTH) AF: 0.00 AC: 0 AN: 55322

GnomAD4 genome AF: 0.00000662 AC: 1 AN: 151012 Hom.: 0 Cov.: 32 AF XY: 0.0000136 AC XY: 1 AN XY: 73714

African (AFR) AF: 0.0000243 AC: 1 AN: 41200

American (AMR) AF: 0.00 AC: 0 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5112

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67694

Other (OTH) AF: 0.00 AC: 0 AN: 2074

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.00000850 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	16
DANN	Benign	0.76
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.57	T
M_CAP	Pathogenic	0.36	D
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.56
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.039
Sift	Benign	0.55	T
Sift4G	Benign	0.54	T
Polyphen		0.25	B
Vest4		0.081
MutPred		0.32		Gain of solvent accessibility (P = 0.039)
MVP		0.23
MPC		0.72
ClinPred		0.051	T
GERP RS		-3.5
PromoterAI		-0.032	Neutral
Varity_R		0.061
gMVP		0.23
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

dbSNP: rs756865019; hg19: chr14-56585404;